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Ji J, Wang C, Goel A, Melstrom K, Zerhouni Y, Lai L, Melstrom L, Raoof M, Fong Y, Kaiser A, Fakih M. Circulating Tumor DNA Testing in Curatively Resected Colorectal Cancer and Salvage Resection. JAMA Netw Open 2024; 7:e2452661. [PMID: 39729315 PMCID: PMC11681374 DOI: 10.1001/jamanetworkopen.2024.52661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 10/31/2024] [Indexed: 12/28/2024] Open
Abstract
Importance Serial circulating tumor DNA (ctDNA) has emerged as a routine surveillance strategy for patients with resected colorectal cancer, but how serial ctDNA monitoring is associated with potential curative outcomes has not been formally assessed. Objective To examine whether there is a benefit of adding serial ctDNA assays to standard-of-care imaging surveillance for potential curative outcomes in patients with resected colorectal cancer. Design, Setting, and Participants In this single-center (City of Hope Comprehensive Cancer Center, Duarte, California), retrospective, case cohort study, patients with stage II to IV colorectal cancer underwent curative resection and were monitored with serial ctDNA assay and National Cancer Center Network (NCCN)-guided imaging surveillance from September 20, 2019, to April 3, 2024. The median duration of follow-up was 26 months (range, 2-54 months). Interventions Serial ctDNA assays were performed every 3 months for 2 years and every 6 months for the 3 following years in conjunction with NCCN-guided radiographic surveillance. Main Outcomes and Measures The primary outcome was the proportion of patients with clinical benefit from ctDNA testing, defined as the proportion of patients with a newly positive ctDNA assay and negative scheduled imaging (most recent or concurrent) that subsequently led to early imaging confirmation of recurrence, followed by curative-intent intervention with no evidence of recurrence at the time of data cutoff. Recurrence was categorized by ctDNA recurrence, radiographic recurrence, or concurrent ctDNA and imaging recurrence. Salvage resections and associated durable remissions were described within each of the 3 categories. Descriptive statistics were used to characterize the patient population. Results In total, 184 patients (median age, 59 years [range, 32-88 years]; 97 female [52.7%]) were included in this study, and 129 (70.1%) had stage II to III disease. Forty-five patients (24.5%) had ctDNA or imaging-confirmed recurrence. Of these 45 patients, 14 had radiographic recurrence with negative ctDNA, and 11 had concurrent ctDNA and imaging recurrence. Twenty of 45 patients had ctDNA positivity with negative imaging at first ctDNA positivity; 6 had reflex imaging that was positive for recurrence, and 14 continued with serial imaging and ctDNA monitoring. Ten of 14 patients had subsequent recurrent disease, 3 patients had a spontaneous clearance of ctDNA, and 1 patient remained imaging negative 7 months after positive ctDNA, after which she was lost to follow-up. Altogether, 11 of 20 patients with ctDNA recurrence without initial concurrent imaging recurrence had subsequent metastasectomy, and only 3 were disease-free at the cutoff date in April 2024, representing 1.6% of the surveilled population. Conclusions and Relevance In this cohort study of patients with stage II to IV colorectal cancer who underwent curative-intent resection, the addition of serial tumor-informed ctDNA assay to the standard NCCN-recommended surveillance had limited clinical benefits. Additional prospective research is needed to clarify the value of ctDNA testing in the surveillance setting.
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Affiliation(s)
- Jingran Ji
- Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Chongkai Wang
- Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Kurt Melstrom
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Yasmin Zerhouni
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Lily Lai
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Laleh Melstrom
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Mustafa Raoof
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Yuman Fong
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Andreas Kaiser
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Marwan Fakih
- Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California
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Coco C, Rizzo G, Amodio LE, Pafundi DP, Marzi F, Tondolo V. Current Management of Locally Recurrent Rectal Cancer. Cancers (Basel) 2024; 16:3906. [PMID: 39682094 DOI: 10.3390/cancers16233906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 11/13/2024] [Accepted: 11/20/2024] [Indexed: 12/18/2024] Open
Abstract
Locally recurrent rectal cancer (LRRC), which occurs in 6-12% of patients previously treated with surgery, with or without pre-operative chemoradiation therapy, represents a complex and heterogeneous disease profoundly affecting the patient's quality of life (QoL) and long-term survival. Its management usually requires a multidisciplinary approach, to evaluate the several aspects of a LRRC, such as resectability or the best approach to reduce symptoms. Surgical treatment is more complex and usually needs high-volume centers to obtain a higher rate of radical (R0) resections and to reduce the rate of postoperative complications. Multiple factors related to the patient, to the primary tumor, and to the surgery for the primary tumor contribute to the development of local recurrence. Accurate pre-treatment staging of the recurrence is essential, and several classification systems are currently used for this purpose. Achieving an R0 resection through radical surgery remains the most critical factor for a favorable oncologic outcome, although both chemotherapy and radiotherapy play a significant role in facilitating this goal. If a R0 resection of a LRRC is not feasible, palliative treatment is mandatory to reduce the LRRC-related symptoms, especially pain, minimizing the effect of the recurrence on the QoL of the patients. The aim of this manuscript is to provide a comprehensive narrative review of the literature regarding the management of LRRC.
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Affiliation(s)
- Claudio Coco
- UOC Chirurgia Generale 2, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Gianluca Rizzo
- UOC Chirurgia Digestiva e del Colon-Retto, Ospedale Isola Tiberina Gemelli Isola, 00186 Rome, Italy
| | - Luca Emanuele Amodio
- UOC Chirurgia Digestiva e del Colon-Retto, Ospedale Isola Tiberina Gemelli Isola, 00186 Rome, Italy
| | - Donato Paolo Pafundi
- UOC Chirurgia Generale 2, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Federica Marzi
- UOC Chirurgia Digestiva e del Colon-Retto, Ospedale Isola Tiberina Gemelli Isola, 00186 Rome, Italy
| | - Vincenzo Tondolo
- UOC Chirurgia Digestiva e del Colon-Retto, Ospedale Isola Tiberina Gemelli Isola, 00186 Rome, Italy
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He D, Chen J, Jiang X, Chen H, Huang J, Chen Z. Risk factors for synchronous high-risk polyps in patients with colorectal cancer. Front Surg 2024; 11:1424809. [PMID: 38978992 PMCID: PMC11228258 DOI: 10.3389/fsurg.2024.1424809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Accepted: 06/11/2024] [Indexed: 07/10/2024] Open
Abstract
Purpose Colorectal cancer (CRC) patients may experience inadequate preoperative colonoscopy due to bowel obstruction or inadequate bowel preparation, leading to potential oversight of other polyps. We aimed to identify risk factors for CRC complicated with synchronous high-risk polyps. Methods A retrospective analysis of 6,674 CRC patients from December 2014 to September 2018 was conducted. High-risk polyps were defined as adenomas or serrated polyps that were ≥10 mm, or with tubulovillous/villous components or high-grade dysplasia. All other polyps were defined as low-risk polyps. Patients with complete pathological and clinical information were categorized into three groups: the no polyp group, the low-risk polyp group, and the high-risk polyp group. Univariate and multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for all potential risk factors. Results Among the 4,659 eligible patients, 848 (18.2%) were found to have low-risk polyps, while 675 (14.5%) were diagnosed with high-risk polyps. In a multivariate logistic regression model, compared to patients without polyps, those with synchronous high-risk polyps were more likely to be male (OR = 2.07), aged 50 or older (OR = 2.77), have early-stage tumors (OR = 1.46), colon tumors (OR = 1.53), NRAS mutant tumors (OR = 1.66), and BRAF wild-type tumors (OR = 2.43). Conclusion Our study has identified several risk factors associated with the presence of synchronous high-risk polyps in CRC patients. Based on these findings, we recommend that patients who exhibit these high-risk factors undergo early follow-up of colonoscopy to detect synchronous polyps early.
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Affiliation(s)
- Degao He
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Anorectal Surgery, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong, China
| | - Junguo Chen
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xuefei Jiang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hao Chen
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Juanni Huang
- Department of Geriatrics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zexian Chen
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
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Cui LL, Cui SQ, Qu Z, Ren ZQ. Intensive follow-up vs conventional follow-up for patients with non-metastatic colorectal cancer treated with curative intent: A meta-analysis. World J Gastrointest Oncol 2023; 15:2197-2211. [PMID: 38173431 PMCID: PMC10758651 DOI: 10.4251/wjgo.v15.i12.2197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 09/22/2023] [Accepted: 10/30/2023] [Indexed: 12/14/2023] Open
Abstract
BACKGROUND The frequency and content of follow-up strategies remain controversial for colorectal cancer (CRC), and scheduled follow-ups have limited value. AIM To compare intensive and conventional follow-up strategies for the prognosis of non-metastatic CRC treated with curative intent using a meta-analysis. METHODS PubMed, Embase, and the Cochrane Library databases were systematically searched for potentially eligible randomized controlled trials (RCTs) from inception until April 2023. The Cochrane risk of bias was used to assess the methodological quality of the included studies. The hazard ratio, relative risk, and 95% confidence interval were used to calculate survival and categorical data, and pooled analyses were performed using the random-effects model. Additional exploratory analyses were performed for sensitivity, subgroups, and publication bias. RESULTS Eighteen RCTs involving 8533 patients with CRC were selected for the final analysis. Intensive follow-up may be superior to conventional follow-up in improving overall survival, but this difference was not statistically significant. Moreover, intensive follow-up was associated with an increased incidence of salvage surgery compared to conventional follow-up. In addition, there was no significant difference in the risk of recurrence between intensive and conventional follow-up strategies, whereas intensive follow-up was associated with a reduced risk of interval recurrence compared to conventional follow-up. Finally, the effects of intensive and conventional follow-up strategies differed when stratified by tumor location and follow-up duration. CONCLUSION Intensive follow-up may have a beneficial effect on the overall survival of patients with non-metastatic CRC treated with curative intent.
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Affiliation(s)
- Li-Li Cui
- Department of Operating Room, Jiangsu Taizhou People’s Hospital, Taizhou 225300, Jiangsu Province, China
| | - Shi-Qi Cui
- Department of Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, Zhejiang Province, China
| | - Zhong Qu
- Department of Endoscopy Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, Zhejiang Province, China
| | - Zhen-Qing Ren
- Department of Nursing, Jiangsu Taizhou People’s Hospital, Taizhou 225300, Jiangsu Province, China
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Frazzoni L, La Marca M, DI Giorgio V, Laterza L, Bazzoli F, Hassan C, Fuccio L. Endoscopic surveillance after surgery for colorectal cancer. Minerva Med 2023; 114:224-236. [PMID: 32573518 DOI: 10.23736/s0026-4806.20.06732-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide and its global incidence is rapidly increasing among adults younger than 50 years, especially in the 20-39 age group. Once a curative resection is achieved, surveillance is mandatory. Colonoscopy has a pivotal role aimed at resecting premalignant neoplasms and detecting cancer at a curable stage. In the current review, an update on the role of surveillance colonoscopy after CRC is provided, considered the most recent international guidelines and evidence published on this issue. In particular, several questions have been answered, why, how and how often colonoscopy should be performed, whether intensive surveillance is more effective than standard surveillance, how endoscopically resected T1 cancer should be followed, the different management existing between colon and rectal cancer, and, finally, how to improve the endoscopic surveillance. In a period of resource constraints, appropriateness will be mandatory, thus understanding how to optimize the role of colonoscopy in the surveillance of patients with a history of CRC is of crucial importance. Improving the quality of colonoscopy and identifying risk factors for recurrent and new-onset CRC, will allow us to individualize the surveillance program while sparing health care cost.
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Affiliation(s)
- Leonardo Frazzoni
- Unit of Gastroenterology, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy
| | - Marina La Marca
- Unit of Gastroenterology, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy
| | - Valentina DI Giorgio
- Unit of Gastroenterology, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy
| | - Liboria Laterza
- Unit of Gastroenterology, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy
| | - Franco Bazzoli
- Unit of Gastroenterology, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy
| | - Cesare Hassan
- Unit of Endoscopy, Nuovo Regina Margherita Hospital, Rome, Italy
| | - Lorenzo Fuccio
- Unit of Gastroenterology, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy -
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Lauretta A, Montori G, Guerrini GP. Surveillance strategies following curative resection and non-operative approach of rectal cancer: How and how long? Review of current recommendations. World J Gastrointest Surg 2023; 15:177-192. [PMID: 36896297 PMCID: PMC9988648 DOI: 10.4240/wjgs.v15.i2.177] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/30/2022] [Accepted: 01/18/2023] [Indexed: 02/27/2023] Open
Abstract
Different follow-up strategies are available for patients with rectal cancer following curative treatment. A combination of biochemical testing and imaging investigation, associated with physical examination are commonly used. However, there is currently no consensus about the types of tests to perform, the timing of the testing, and even the need for follow-up at all has been questioned. The aim of this study was to review the evidence of the impact of different follow-up tests and programs in patients with non-metastatic disease after definitive treatment of the primary. A literature review was performed of studies published on MEDLINE, EMBASE, the Cochrane Library and Web of Science up to November 2022. Current published guidelines from the most authoritative specialty societies were also reviewed. According to the follow-up strategies available, the office visit is not efficient but represents the only way to maintain direct contact with the patient and is recommended by all authoritative specialty societies. In colorectal cancer surveillance, carcinoembryonic antigen represents the only established tumor marker. Abdominal and chest computed tomography scan is recommended considering that the liver and lungs are the most common sites of recurrence. Since local relapse in rectal cancer is higher than in colon cancer, endoscopic surveillance is mandatory. Different follow-up regimens have been published but randomized comparisons and meta-analyses do not allow to determine whether intensive or less intensive follow-up had any significant influence on survival and recurrence detection rate. The available data do not allow the drawing of final conclusions on the ideal surveillance methods and the frequency with which they should be applied. It is very useful and urgent for clinicians to identify a cost-effective strategy that allows early identification of recurrence with a special focus for high-risk patients and patients undergoing a “watch and wait” approach.
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Affiliation(s)
- Andrea Lauretta
- Department of Surgical Oncology, Centro di Riferimento Oncologico di Aviano IRCCS, Aviano 33081, Italy
| | - Giulia Montori
- Department of General Surgery, Vittorio Veneto Hospital, ULSS 2 Marca Trevigiana, Vittorio Veneto 31029, Italy
| | - Gian Piero Guerrini
- Hepato-Pancreato-Biliary Surgical Oncology and Liver Transplantation Unit, Policlinico-AUO Modena, Modena 41124, Italy
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Galjart B, Höppener DJ, Aerts JGJV, Bangma CH, Verhoef C, Grünhagen DJ. Follow-up strategy and survival for five common cancers: A meta-analysis. Eur J Cancer 2022; 174:185-199. [PMID: 36037595 DOI: 10.1016/j.ejca.2022.07.025] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 07/19/2022] [Accepted: 07/21/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND This meta-analysis aimed to evaluate the effectiveness of intensive follow-up after curative intent treatment for five common solid tumours, in terms of survival and treatment of recurrences. METHODS A systematic literature search was conducted, identifying comparative studies on follow-up for colorectal, lung, breast, upper gastro-intestinal and prostate cancer. Outcomes of interest were overall survival (OS), cancer specific survival (CSS), and treatment of recurrences. Random effects meta-analyses were conducted, with particular focus on studies at low risk of bias. RESULTS Fourteen out of 63 studies were considered to be at low risk of bias (8 colorectal, 4 breast, 0 lung, 1 upper gastro-intestinal, 1 prostate). These studies showed no significant impact of intensive follow-up on OS (hazard ratio, 95% confidence interval) for colorectal (0.99; 0.92-1.06), breast 1.06 (0.92-1.23), upper gastro-intestinal (0.78; 0.51-1.19) and prostate cancer (1.00; 0.86-1.16). No impact on CSS (hazard ratio, 95% confidence interval) was found for colorectal cancer (0.94; 0.77-1.16). CSS was not reported for other cancer types. Intensive follow-up increased the rate of curative treatment (relative risk; 95% confidence interval) for colorectal cancer recurrences (1.30; 1.05-1.61), but not for upper gastro-intestinal cancer recurrences (0.92; 0.47-1.81). For the other cancer types, no data on treatment of recurrences was available in low risk studies. CONCLUSION For colorectal and breast cancer, high quality studies do not suggest an impact of intensive follow-up strategies on survival. Colorectal cancer recurrences are more often treated locally after intensive follow-up. For other cancer types evaluated, limited high quality research on follow-up is available.
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Affiliation(s)
- Boris Galjart
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Diederik J Höppener
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Joachim G J V Aerts
- Department of Pulmonology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Christiaan H Bangma
- Department of Urology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Dirk J Grünhagen
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
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Design and verification of individualized follow-up strategy of colonoscopy for postoperative patients with colorectal cancer. Eur J Gastroenterol Hepatol 2022; 34:48-55. [PMID: 33560683 DOI: 10.1097/meg.0000000000002073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Current guidelines do not establish an individual scheme for surveillance colonoscopy in postoperative colorectal cancer (CRC) patients. AIMS The purpose of the study was to screen possible risk factors for the development of metachronous adenoma in postoperative CRC patients and to develop a risk prediction model and verify it. METHODS Consecutive postoperative patients with CRC were enrolled from April 2007 to December 2013 as the derivation group. Baseline data of patients and clinicopathological features of the tumor were collected, logistic regression analysis was performed, and clinical model was established and was verified internally. The model was externally validated in an independent cohort (validation group) from January 2014 to October 2017 in the same hospital. RESULTS A total of 734 patients were included, with average (64.6 ± 11.5) years old. The overall incidence of metachronous adenoma was 35.4%. There was no significant difference in the incidence of metachronous adenoma between the derivation group and validation group (P > 0.05). Age, diabetes mellitus, right colon cancer, moderately to poorly differentiated adenocarcinoma and synchronous adenoma were independent risk factors for metachronous adenoma. The C-index of the metachronous adenoma line chart model was 0.932, and the index decreased by 0.022 after internal verification. The C-index of external validation was 0.910. The Hosmer-Lemeshow test showed that the P value of metachronous adenoma risk prediction model was 0.247. CONCLUSIONS Individual surveillance strategies should be designed for postoperative patients with CRC. For high-risk patients, it is appropriate to undergo more than two colonoscopies in 36 months after operation.
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Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer. Cancers (Basel) 2021; 13:cancers13153892. [PMID: 34359796 PMCID: PMC8345682 DOI: 10.3390/cancers13153892] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/23/2021] [Accepted: 07/26/2021] [Indexed: 12/24/2022] Open
Abstract
In colorectal cancer (CRC), 20-50% of patients relapse after curative-intent surgery with or without adjuvant therapy. We investigated the lead times and prognostic value of post-adjuvant (8 months from randomisation to adjuvant treatment) serum CEA, CA19-9, IL-6, CRP, and YKL-40. We included 147 radically resected stage II-IV CRC treated with 24 weeks of adjuvant 5-fluorouracil-based chemotherapy in the phase III LIPSYT-study (ISRCTN98405441). All 147 were included in lead time analysis, but 12 relapsing during adjuvant therapy were excluded from post-adjuvant analysis. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired disease-free survival (DFS) with hazard ratio (HR) 5.21 (95% confidence interval 2.32-11.69); 3.72 (1.99-6.95); 2.58 (1.18-5.61), respectively, and elevated IL-6 and CRP with impaired overall survival (OS) HR 3.06 (1.64-5.73); 3.41 (1.55-7.49), respectively. Elevated post-adjuvant IL-6 in CEA-normal patients identified a subgroup with impaired DFS. HR 3.12 (1.38-7.04) and OS, HR 3.20 (1.39-7.37). The lead times between the elevated biomarker and radiological relapse were 7.8 months for CEA and 10.0-53.1 months for CA19-9, IL-6, CRP, and YKL-40, and the lead time for the five combined was 27.3 months. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired DFS. The lead time was shortest for CEA.
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Park MY, Park IJ, Ryu HS, Jung J, Kim MS, Lim SB, Yu CS, Kim JC. Optimal Postoperative Surveillance Strategies for Colorectal Cancer: A Retrospective Observational Study. Cancers (Basel) 2021; 13:3502. [PMID: 34298715 PMCID: PMC8306168 DOI: 10.3390/cancers13143502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 07/12/2021] [Accepted: 07/12/2021] [Indexed: 11/25/2022] Open
Abstract
This study aimed to assess whether surveillance intensity is associated with recurrence and survival in colorectal cancer (CRC) patients. Overall, 3794 patients with pathologic stage I-III CRC who underwent radical surgery between January 2012 and December 2014 were examined. Surveillance comprised abdominopelvic computed tomography (CT) every 6 months and chest CT annually for 5 years. Patients who underwent more than and less than an average of three imaging examinations annually were assigned to the high-intensity (HI) and low-intensity (LI) groups, respectively. Demographics were similar in both groups. T and N stages were higher and perineural and lymphovascular invasion were more frequent in the HI group (p < 0.001 each). The mean overall survival (OS) was similar for both groups; however, recurrence-free survival (RFS) was longer (p < 0.001) and post-recurrence survival (PRS) was shorter (p = 0.024) in the LI group. In the multivariate analysis, surveillance intensity was associated with RFS (p < 0.001) in contrast to PRS (p = 0.731). In patients with high recurrence risk predicted using the nomogram, OS was longer in the HI group (p < 0.001). A higher imaging frequency in patients at high risk of recurrence could be expected to lead to a slight increase in PRS but does not improve OS. Therefore, rather than increasing the number of CT scans in high-risk patients, other imaging modalities or innovative approaches, such as liquid biopsy, are required.
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Affiliation(s)
| | - In-Ja Park
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (M.-Y.P.); (H.-S.R.); (J.J.); (M.-S.K.); (S.-B.L.); (C.-S.Y.); (J.-C.K.)
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The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Surveillance and Survivorship Care of Patients After Curative Treatment of Colon and Rectal Cancer. Dis Colon Rectum 2021; 64:517-533. [PMID: 33591043 DOI: 10.1097/dcr.0000000000001984] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Giglio V, Schneider P, Madden K, Lin B, Multani I, Baldawi H, Thornley P, Naji L, Levin M, Wang P, Bozzo A, Wilson D, Ghert M. Published randomized controlled trials of surveillance in cancer patients - a systematic review. Oncol Rev 2021; 15:522. [PMID: 34267889 PMCID: PMC8256375 DOI: 10.4081/oncol.2021.522] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 04/09/2021] [Indexed: 01/14/2023] Open
Abstract
With solid tumor cancer survivorship increasing, the number of patients requiring post-treatment surveillance also continues to increase. This highlights the need for evidence-based cancer surveillance guidelines. Ideally, these guidelines would be based on combined high-quality data from randomized controlled trials (RCTs). We present a systematic review of published cancer surveillance RCTs in which we sought to determine the feasibility of data pooling for guideline development. We carried out a systematic search of medical databases for RCTs in which adult patients with solid tumors that had undergone surgical resection with curative intent and had no metastatic disease at presentation, were randomized to different surveillance regimens that assessed effectiveness on overall survival (OS). We extracted study characteristics and primary and secondary outcomes, and assessed risk of bias and validity of evidence with standardized checklist tools. Our search yielded 32,216 articles for review and 18 distinct RCTs were included in the systematic review. The 18 trials resulted in 23 comparisons of surveillance regimens. There was a highlevel of variation between RCTs, including the study populations evaluated, interventions assessed and follow-up periods for the primary outcome. Most studies evaluated colorectal cancer patients (11/18, [61%]). The risk of bias and validity of evidence were variable and inconsistent across studies. This review demonstrated that there is tremendous heterogeneity among RCTs that evaluate effectiveness of different postoperative surveillance regimens in cancer patients, rendering the consolidation of data to inform high-quality cancer surveillance guidelines unfeasible. Future RCTs in the field should focus on consistent methodology and primary outcome definition.
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Affiliation(s)
- Victoria Giglio
- Division of Orthopedic Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | - Patricia Schneider
- Division of Orthopedic Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | - Kim Madden
- Division of Orthopedic Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | - Bill Lin
- Division of Orthopedic Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | | | - Hassan Baldawi
- Division of Orthopedic Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | - Patrick Thornley
- Division of Orthopedic Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | - Leen Naji
- Department of Family Medicine, McMaster University, Hamilton, ON, Canada
| | - Marc Levin
- Michael DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
| | - Peiyao Wang
- Division of Orthopedic Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | - Anthony Bozzo
- Division of Orthopedic Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | - David Wilson
- Hamilton Health Sciences, Juravinski Hospital and Cancer Center, Hamilton, ON, Canada
| | - Michelle Ghert
- Hamilton Health Sciences, Juravinski Hospital and Cancer Center, Hamilton, ON, Canada
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Monteil J, Le Brun-Ly V, Cachin F, Zasadny X, Seitz JF, Mundler O, Selvy M, Smith D, Rullier E, Lavau-Denes S, Lades G, Labrunie A, Lecaille C, Valli N, Leobon S, Terrebonne E, Deluche E, Tubiana-Mathieu N. Comparison of 18FDG-PET/CT and conventional follow-up methods in colorectal cancer: A randomised prospective study. Dig Liver Dis 2021; 53:231-237. [PMID: 33153929 DOI: 10.1016/j.dld.2020.10.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 10/02/2020] [Accepted: 10/06/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND A surveillance program was performed in colorectal cancer (CRC) patients after surgery, to diagnose asymptomatic recurrence. AIMS To assess whether 18-FDG positron emission tomography/CT (PET/CT) improved the detection of recurrence during a 3-year follow-up. METHODS A multicentre, two-arm randomised prospective trial comparing different 36-month follow-up strategies. Complete colonoscopy was performed at baseline and after 3 years and clinical exams with imaging every 3 months. The conventional arm (A) received carcinoembryonic antigen, liver echography, and alternated between lung radiography and computed tomography (CT) scans. The experimental arm (B) received PET/CT. RESULTS A total of 365 patients with colon (79.4%) or rectal cancer (20.6%), stages II (48.2%) or III (50.8%), were enroled in this study. At 36 months, intention-to-treat analysis revealed recurrence in 31 (17.2%) patients in arm A and 47 (25.4%) in arm B (p = 0.063). At 3 years, 7 of 31 relapses (22.5%) in arm A were surgically treated with curative intent, compared to 17 of 47 (36.2%) in arm B (p = 0.25). The rates of recurrence and new cancers were higher in arm B than arm A (p = 0.038). CONCLUSIONS PET/CT follow-up every 6 months did not increase the rate of recurrence at 3 years or the rate of surgically treated recurrence compared with conventional follow-up.
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Affiliation(s)
- Jacques Monteil
- Department of Nuclear Medicine, University Hospital, Limoges, France
| | | | - Florent Cachin
- Department of Nuclear Medicine, Jean Perrin Cancer Institute, Clermont-Ferrand, France
| | - Xavier Zasadny
- Department of Radiotherapy, François Chénieux Clinic, Limoges, France
| | - Jean-François Seitz
- Department of Oncology and Hepato-Gastroenterology, University Hospital La Timone, Marseille, France
| | - Olivier Mundler
- Department of Nuclear Medicine, University Hospital La Timone, Marseille, France
| | - Marie Selvy
- Department of Digestive Surgery and Oncology, Estaing Hospital, Clermont-Ferrand, France
| | - Denis Smith
- Department of Digestive Oncology, University Hospital Saint André, Bordeaux, France
| | - Eric Rullier
- Department of Digestive Surgery, University Hospital Saint André, Bordeaux, France
| | | | - Guillaume Lades
- Department of Nuclear Medicine, University Hospital, Limoges, France
| | - Anais Labrunie
- Department of Biostatistics and Clinical Research, University Hospital, Limoges, France
| | - Cedric Lecaille
- Department of Gastroenterology and Digestive Oncology, Bordeaux Nord Polyclinic, Bordeaux, France
| | - Nathalie Valli
- Department of Nuclear Medicine, Bordeaux Nord Polyclinic, Bordeaux, France
| | - Sophie Leobon
- Department of Medical Oncology, University Hospital, Limoges, France
| | - Eric Terrebonne
- Department of Gastroenterology and Digestive Oncology, University Hospital Haut-Lévêque, Bordeaux, France
| | - Elise Deluche
- Department of Medical Oncology, University Hospital, Limoges, France.
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Hines RB, Jiban MJH, Lee E, Odahowski CL, Wallace AS, Adams SJE, Rahman SMM, Zhang S. Characteristics Associated With Nonreceipt of Surveillance Testing and the Relationship With Survival in Stage II and III Colon Cancer. Am J Epidemiol 2021; 190:239-250. [PMID: 32902633 DOI: 10.1093/aje/kwaa195] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 08/30/2020] [Accepted: 09/03/2020] [Indexed: 12/13/2022] Open
Abstract
We investigated characteristics of patients with colon cancer that predicted nonreceipt of posttreatment surveillance testing and the subsequent associations between surveillance status and survival outcomes. This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Patients diagnosed between 2002 and 2009 with disease stages II and III and who were between 66 and 84 years of age were eligible. A minimum of 3 years' follow-up was required, and patients were categorized as having received any surveillance testing (any testing) versus none (no testing). Poisson regression was used to obtain risk ratios with 95% confidence intervals for the relative likelihood of No Testing. Cox models were used to obtain subdistribution hazard ratios with 95% confidence intervals for 5- and 10-year cancer-specific and noncancer deaths. There were 16,009 colon cancer cases analyzed. Patient characteristics that predicted No Testing included older age, Black race, stage III disease, and chemotherapy. Patients in the No Testing group had an increased rate of 10-year cancer death that was greater for patients with stage III disease (subdistribution hazard ratio = 1.79, 95% confidence interval: 1.48, 2.17) than those with stage II disease (subdistribution hazard ratio = 1.41, 95% confidence interval: 1.19, 1.66). Greater efforts are needed to ensure all patients receive the highest quality medical care after diagnosis of colon cancer.
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Recurrence Risk after Radical Colorectal Cancer Surgery-Less Than before, But How High Is It? Cancers (Basel) 2020; 12:cancers12113308. [PMID: 33182510 PMCID: PMC7696064 DOI: 10.3390/cancers12113308] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/27/2020] [Accepted: 11/06/2020] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Evidence indicates that recurrence risk after colon cancer today is less than it was when trials performed decades ago showed that adjuvant chemotherapy reduces the risk and prolong disease-free and overall survival. After rectal cancer surgery, local recurrence rates have decreased but it is unclear if systemic recurrences have. After a systematic review of available literature reporting recurrence risks after curative colorectal cancer surgery we report that the risks are lower today than they were in the past and that this risk reduction is not solely ascribed to the use of adjuvant therapy. Adjuvant therapy always means overtreatment of many patients, already cured by the surgery. Fewer recurrences mean that progress in the care of these patients has happened but also that the present guidelines giving recommendations based upon old data must be adjusted. The relative gains from adding chemotherapy are not altered, but the absolute number of patients gaining is less. Abstract Adjuvant chemotherapy aims at eradicating tumour cells sometimes present after radical surgery for a colorectal cancer (CRC) and thereby diminish the recurrence rate and prolong time to recurrence (TTR). Remaining tumour cells will lead to recurrent disease that is usually fatal. Adjuvant therapy is administered based upon the estimated recurrence risk, which in turn defines the need for this treatment. This systematic overview aims at describing whether the need has decreased since trials showing that adjuvant chemotherapy provides benefits in colon cancer were performed decades ago. Thanks to other improvements than the administration of adjuvant chemotherapy, such as better staging, improved surgery, the use of radiotherapy and more careful pathology, recurrence risks have decreased. Methodological difficulties including intertrial comparisons decades apart and the present selective use of adjuvant therapy prevent an accurate estimate of the magnitude of the decreased need. Furthermore, most trials do not report recurrence rates or TTR, only disease-free and overall survival (DFS/OS). Fewer colon cancer patients, particularly in stage II but also in stage III, today display a sufficient need for adjuvant treatment considering the burden of treatment, especially when oxaliplatin is added. In rectal cancer, neo-adjuvant treatment will be increasingly used, diminishing the need for adjuvant treatment.
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Skelton WP, Franke AJ, Iqbal A, George TJ. Comprehensive literature review of randomized clinical trials examining novel treatment advances in patients with colon cancer. J Gastrointest Oncol 2020; 11:790-802. [PMID: 32953161 PMCID: PMC7475336 DOI: 10.21037/jgo-20-184] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 07/20/2020] [Indexed: 12/18/2022] Open
Abstract
The treatment of colon cancer has had numerous recent advances, in terms of surgical approach, adjuvant therapies, and more. In this review, the authors examine randomized clinical trials comparing open surgery to laparoscopic surgery (including total mesocolic excision), and also examine the role of robotic surgery. Novel surgical techniques including the no-touch technique, side-to-side anastomosis, suture technique, complete mesocolic excision (CME) with central vascular ligation (CVL), and natural orifice transluminal endoscopic surgery (NOTES) are outlined. The role of placing endoscopic self-expandable metal stents (SEMS) for colonic obstruction is compared and contrasted with the surgical approach, and the effect that the anti-VEGF inhibitor bevacizumab may have on this side effect profile is further explored. The role of the resection of the primary tumor in the setting of metastatic disease is examined with respect to survival benefit. Pathways of perioperative care which can accelerate post-surgical recovery, including enhanced recovery after surgery (ERAS) are examined. The role of adjuvant chemotherapy in patients with high-risk stage II and patients with stage III disease is examined, along with the role on circulating tumor DNA (ctDNA) as well as with the biologic targeted agents cetuximab and bevacizumab. Lastly, the authors detail the postoperative surveillance schedules after surgical resection with respect to survival outcomes.
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Affiliation(s)
- William Paul Skelton
- Division of Medical Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Florida, USA
| | - Aaron J. Franke
- Division of Medical Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Florida, USA
| | - Atif Iqbal
- Section of Colorectal Surgery, Baylor College of Medicine, Houston, USA
| | - Thomas J. George
- Division of Hematology & Oncology, Department of Medicine, University of Florida College of Medicine, Florida, USA
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Hall C, Clarke L, Pal A, Buchwald P, Eglinton T, Wakeman C, Frizelle F. A Review of the Role of Carcinoembryonic Antigen in Clinical Practice. Ann Coloproctol 2019; 35:294-305. [PMID: 31937069 PMCID: PMC6968721 DOI: 10.3393/ac.2019.11.13] [Citation(s) in RCA: 122] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 11/13/2019] [Indexed: 12/11/2022] Open
Abstract
Carcinoembryonic antigen (CEA) is not normally produced in significant quantities after birth but is elevated in colorectal cancer. The aim of this review was to define the current role of CEA and how best to investigate patients with elevated CEA levels. A systematic review of CEA was performed, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were identified from PubMed, Cochrane library, and controlled trials registers. We identified 2,712 papers of which 34 were relevant. Analysis of these papers found higher preoperative CEA levels were associated with advanced or metastatic disease and thus poorer prognosis. Postoperatively, failure of CEA to return to normal was found to be indicative of residual or recurrent disease. However, measurement of CEA levels alone was not sufficient to improve survival rates. Two algorithms are proposed to guide investigation of patients with elevated CEA: one for patients with elevated CEA after CRC resection, and another for patients with de novo elevated CEA. CEA measurement has an important role in the investigation, management and follow-up of patients with colorectal cancer.
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Affiliation(s)
- Claire Hall
- Colorectal Unit, Department of Surgery, University of Otago, Christchurch, New Zealand
| | - Louise Clarke
- Colorectal Unit, Department of Surgery, University of Otago, Christchurch, New Zealand
| | - Atanu Pal
- Colorectal Unit, Department of Surgery, University of Otago, Christchurch, New Zealand
- Norfolk & Norwich University Hospital, Norwich, UK
| | - Pamela Buchwald
- Colorectal Unit, Department of Surgery, University of Otago, Christchurch, New Zealand
| | - Tim Eglinton
- Colorectal Unit, Department of Surgery, University of Otago, Christchurch, New Zealand
| | - Chris Wakeman
- Colorectal Unit, Department of Surgery, University of Otago, Christchurch, New Zealand
| | - Frank Frizelle
- Colorectal Unit, Department of Surgery, University of Otago, Christchurch, New Zealand
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18
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Høeg BL, Bidstrup PE, Karlsen RV, Friberg AS, Albieri V, Dalton SO, Saltbæk L, Andersen KK, Horsboel TA, Johansen C. Follow-up strategies following completion of primary cancer treatment in adult cancer survivors. Cochrane Database Syst Rev 2019; 2019:CD012425. [PMID: 31750936 PMCID: PMC6870787 DOI: 10.1002/14651858.cd012425.pub2] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Most cancer survivors receive follow-up care after completion of treatment with the primary aim of detecting recurrence. Traditional follow-up consisting of fixed visits to a cancer specialist for examinations and tests are expensive and may be burdensome for the patient. Follow-up strategies involving non-specialist care providers, different intensity of procedures, or addition of survivorship care packages have been developed and tested, however their effectiveness remains unclear. OBJECTIVES The objective of this review is to compare the effect of different follow-up strategies in adult cancer survivors, following completion of primary cancer treatment, on the primary outcomes of overall survival and time to detection of recurrence. Secondary outcomes are health-related quality of life, anxiety (including fear of recurrence), depression and cost. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, four other databases and two trials registries on 11 December 2018 together with reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA We included all randomised trials comparing different follow-up strategies for adult cancer survivors following completion of curatively-intended primary cancer treatment, which included at least one of the outcomes listed above. We compared the effectiveness of: 1) non-specialist-led follow-up (i.e. general practitioner (GP)-led, nurse-led, patient-initiated or shared care) versus specialist-led follow-up; 2) less intensive versus more intensive follow-up (based on clinical visits, examinations and diagnostic procedures) and 3) follow-up integrating additional care components relevant for detection of recurrence (e.g. patient symptom education or monitoring, or survivorship care plans) versus usual care. DATA COLLECTION AND ANALYSIS We used the standard methodological guidelines by Cochrane and Cochrane Effective Practice and Organisation of Care (EPOC). We assessed the certainty of the evidence using the GRADE approach. For each comparison, we present synthesised findings for overall survival and time to detection of recurrence as hazard ratios (HR) and for health-related quality of life, anxiety and depression as mean differences (MD), with 95% confidence intervals (CI). When meta-analysis was not possible, we reported the results from individual studies. For survival and recurrence, we used meta-regression analysis where possible to investigate whether the effects varied with regards to cancer site, publication year and study quality. MAIN RESULTS We included 53 trials involving 20,832 participants across 12 cancer sites and 15 countries, mainly in Europe, North America and Australia. All the studies were carried out in either a hospital or general practice setting. Seventeen studies compared non-specialist-led follow-up with specialist-led follow-up, 24 studies compared intensity of follow-up and 12 studies compared patient symptom education or monitoring, or survivorship care plans with usual care. Risk of bias was generally low or unclear in most of the studies, with a higher risk of bias in the smaller trials. Non-specialist-led follow-up compared with specialist-led follow-up It is uncertain how this strategy affects overall survival (HR 1.21, 95% CI 0.68 to 2.15; 2 studies; 603 participants), time to detection of recurrence (4 studies, 1691 participants) or cost (8 studies, 1756 participants) because the certainty of the evidence is very low. Non-specialist- versus specialist-led follow up may make little or no difference to health-related quality of life at 12 months (MD 1.06, 95% CI -1.83 to 3.95; 4 studies; 605 participants; low-certainty evidence); and probably makes little or no difference to anxiety at 12 months (MD -0.03, 95% CI -0.73 to 0.67; 5 studies; 1266 participants; moderate-certainty evidence). We are more certain that it has little or no effect on depression at 12 months (MD 0.03, 95% CI -0.35 to 0.42; 5 studies; 1266 participants; high-certainty evidence). Less intensive follow-up compared with more intensive follow-up Less intensive versus more intensive follow-up may make little or no difference to overall survival (HR 1.05, 95% CI 0.96 to 1.14; 13 studies; 10,726 participants; low-certainty evidence) and probably increases time to detection of recurrence (HR 0.85, 95% CI 0.79 to 0.92; 12 studies; 11,276 participants; moderate-certainty evidence). Meta-regression analysis showed little or no difference in the intervention effects by cancer site, publication year or study quality. It is uncertain whether this strategy has an effect on health-related quality of life (3 studies, 2742 participants), anxiety (1 study, 180 participants) or cost (6 studies, 1412 participants) because the certainty of evidence is very low. None of the studies reported on depression. Follow-up strategies integrating additional patient symptom education or monitoring, or survivorship care plans compared with usual care: None of the studies reported on overall survival or time to detection of recurrence. It is uncertain whether this strategy makes a difference to health-related quality of life (12 studies, 2846 participants), anxiety (1 study, 470 participants), depression (8 studies, 2351 participants) or cost (1 studies, 408 participants), as the certainty of evidence is very low. AUTHORS' CONCLUSIONS Evidence regarding the effectiveness of the different follow-up strategies varies substantially. Less intensive follow-up may make little or no difference to overall survival but probably delays detection of recurrence. However, as we did not analyse the two outcomes together, we cannot make direct conclusions about the effect of interventions on survival after detection of recurrence. The effects of non-specialist-led follow-up on survival and detection of recurrence, and how intensity of follow-up affects health-related quality of life, anxiety and depression, are uncertain. There was little evidence for the effects of follow-up integrating additional patient symptom education/monitoring and survivorship care plans.
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Affiliation(s)
- Beverley L Høeg
- Danish Cancer Society Research CenterSurvivorship UnitStrandboulevarden 49CopenhagenCentral Denmark RegionDenmark2100
| | - Pernille E Bidstrup
- Danish Cancer Society Research CenterSurvivorship UnitStrandboulevarden 49CopenhagenCentral Denmark RegionDenmark2100
| | - Randi V Karlsen
- Danish Cancer Society Research CenterSurvivorship UnitStrandboulevarden 49CopenhagenCentral Denmark RegionDenmark2100
| | - Anne Sofie Friberg
- Danish Cancer Society Research CenterSurvivorship UnitStrandboulevarden 49CopenhagenCentral Denmark RegionDenmark2100
- Rigshospitalet, Copenhagen University HospitalDepartment of OncologyCopenhagenDenmark
| | - Vanna Albieri
- Danish Cancer Society Research CenterStatistics and Pharmaco‐Epidemiology UnitStrandboulevarden 49CopenhagenDenmark
| | - Susanne O Dalton
- Danish Cancer Society Research CenterSurvivorship UnitStrandboulevarden 49CopenhagenCentral Denmark RegionDenmark2100
- Zealand University HospitalDepartment of OncologyNæstvedDenmark
| | - Lena Saltbæk
- Danish Cancer Society Research CenterSurvivorship UnitStrandboulevarden 49CopenhagenCentral Denmark RegionDenmark2100
- Zealand University HospitalDepartment of OncologyNæstvedDenmark
| | - Klaus Kaae Andersen
- Danish Cancer Society Research CenterStatistics and Pharmaco‐Epidemiology UnitStrandboulevarden 49CopenhagenDenmark
| | - Trine Allerslev Horsboel
- Danish Cancer Society Research CenterSurvivorship UnitStrandboulevarden 49CopenhagenCentral Denmark RegionDenmark2100
| | - Christoffer Johansen
- Danish Cancer Society Research CenterSurvivorship UnitStrandboulevarden 49CopenhagenCentral Denmark RegionDenmark2100
- Rigshospitalet, Copenhagen University HospitalDepartment of OncologyCopenhagenDenmark
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Pöhler GH, Ringe KI. [Computed tomography and/or magnetic resonance imaging of the liver : How, why, what for?]. Radiologe 2019; 59:804-811. [PMID: 31414150 DOI: 10.1007/s00117-019-00583-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
CLINICAL PROBLEM Colorectal metastases are the most common malignant liver lesions. Imaging of the liver in patients with colorectal carcinoma is performed for early detection of liver metastases (CRLM) at the time of initial tumor diagnosis, for monitoring and follow-up in order to exclude or diagnose metachronous metastases. STANDARD RADIOLOGICAL METHODS Radiological imaging includes primarily multislice computed tomography (CT) and magnetic resonance imaging (MRI), which play an important role regarding therapeutic management and assessment of prognosis. PERFORMANCE, ACHIEVEMENTS Contrast-enhanced CT is broadly available and allows for rapid image acquisition including the possibility for complete tumor staging. MRI, on the other hand, is characterized by very good soft tissue contrast and has-especially with the use of diffusion-weighted imaging and administration of liver-specific contrast agents-the highest sensitivity for detection of metastases smaller than 1 cm. PRACTICAL RECOMMENDATIONS The choice of imaging in daily routine is often dependent on availability and clinical question. Frequently, e.g. for assessment of resectability (extent of metastases, anatomic relation of lesions to critical structures), both modalities may be implemented in combination.
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Affiliation(s)
- G H Pöhler
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover, Hannover, Deutschland
| | - K I Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover, Hannover, Deutschland.
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20
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Juchems MS, Wessling J. [Rational staging and follow-up of colorectal cancer : Do guidelines provide further help?]. Radiologe 2019; 59:820-827. [PMID: 31455978 DOI: 10.1007/s00117-019-0578-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
CLINICAL/METHODICAL ISSUE Colorectal cancer is one of the most common malignant tumors. Preoperative imaging is crucial in rectal cancer as patients can only receive optimal treatment when accurate staging is performed. The N‑staging is often difficult with the available options and must be called into question as a staging parameter. STANDARD RADIOLOGICAL METHODS Endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) are particularly suitable for local staging. Multiparametric MRI with diffusion imaging is indispensable for tumor follow-up. METHODICAL INNOVATIONS The assessment of infiltration of the mesorectal fascia is best accomplished using high-resolution MRI. In addition, extramural vascular infiltration (EMVI) has become established as another important prognostic factor. After neoadjuvant therapy and restaging of locally advanced rectal cancer, the identification and validation of prognostically relevant image parameters are prioritized. Multiparametric MRI of the rectum including diffusion imaging as well as the application of radiological and pathological scores (MR-TRG) are becoming increasingly more important in this context. ASSESSMENT For the radiologist it is important to become familiar with indicators of the resectability of rectal cancer and to be able to reliably read prognostically relevant imaging parameters in the tumor follow-up. PRACTICAL RECOMMENDATIONS For the practical application, the establishment of a fixed MRI protocol is essential. In addition to a guideline-compliant TNM classification, the radiologist must provide the clinician with information on infiltration of the mesorectal fascia and extramural vascular infiltration. The MR-TRGs are becoming increasingly more important in tumor follow-up.
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Affiliation(s)
- M S Juchems
- Diagnostische und Interventionelle Radiologie, Klinikum Konstanz, Mainaustr. 35, 78464, Konstanz, Deutschland.
| | - J Wessling
- Zentrum für Radiologie, Neuroradiologie und Nuklearmedizin, Clemenshospital Münster, Münster, Deutschland
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Jeffery M, Hickey BE, Hider PN. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev 2019; 9:CD002200. [PMID: 31483854 PMCID: PMC6726414 DOI: 10.1002/14651858.cd002200.pub4] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND This is the fourth update of a Cochrane Review first published in 2002 and last updated in 2016.It is common clinical practice to follow patients with colorectal cancer for several years following their curative surgery or adjuvant therapy, or both. Despite this widespread practice, there is considerable controversy about how often patients should be seen, what tests should be performed, and whether these varying strategies have any significant impact on patient outcomes. OBJECTIVES To assess the effect of follow-up programmes (follow-up versus no follow-up, follow-up strategies of varying intensity, and follow-up in different healthcare settings) on overall survival for patients with colorectal cancer treated with curative intent. Secondary objectives are to assess relapse-free survival, salvage surgery, interval recurrences, quality of life, and the harms and costs of surveillance and investigations. SEARCH METHODS For this update, on 5 April 2109 we searched CENTRAL, MEDLINE, Embase, CINAHL, and Science Citation Index. We also searched reference lists of articles, and handsearched the Proceedings of the American Society for Radiation Oncology. In addition, we searched the following trials registries: ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We contacted study authors. We applied no language or publication restrictions to the search strategies. SELECTION CRITERIA We included only randomised controlled trials comparing different follow-up strategies for participants with non-metastatic colorectal cancer treated with curative intent. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. Two review authors independently determined study eligibility, performed data extraction, and assessed risk of bias and methodological quality. We used GRADE to assess evidence quality. MAIN RESULTS We identified 19 studies, which enrolled 13,216 participants (we included four new studies in this second update). Sixteen out of the 19 studies were eligible for quantitative synthesis. Although the studies varied in setting (general practitioner (GP)-led, nurse-led, or surgeon-led) and 'intensity' of follow-up, there was very little inconsistency in the results.Overall survival: we found intensive follow-up made little or no difference (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.80 to 1.04: I² = 18%; high-quality evidence). There were 1453 deaths among 12,528 participants in 15 studies. In absolute terms, the average effect of intensive follow-up on overall survival was 24 fewer deaths per 1000 patients, but the true effect could lie between 60 fewer to 9 more per 1000 patients.Colorectal cancer-specific survival: we found intensive follow-up probably made little or no difference (HR 0.93, 95% CI 0.81 to 1.07: I² = 0%; moderate-quality evidence). There were 925 colorectal cancer deaths among 11,771 participants enrolled in 11 studies. In absolute terms, the average effect of intensive follow-up on colorectal cancer-specific survival was 15 fewer colorectal cancer-specific survival deaths per 1000 patients, but the true effect could lie between 47 fewer to 12 more per 1000 patients.Relapse-free survival: we found intensive follow-up made little or no difference (HR 1.05, 95% CI 0.92 to 1.21; I² = 41%; high-quality evidence). There were 2254 relapses among 8047 participants enrolled in 16 studies. The average effect of intensive follow-up on relapse-free survival was 17 more relapses per 1000 patients, but the true effect could lie between 30 fewer and 66 more per 1000 patients.Salvage surgery with curative intent: this was more frequent with intensive follow-up (risk ratio (RR) 1.98, 95% CI 1.53 to 2.56; I² = 31%; high-quality evidence). There were 457 episodes of salvage surgery in 5157 participants enrolled in 13 studies. In absolute terms, the effect of intensive follow-up on salvage surgery was 60 more episodes of salvage surgery per 1000 patients, but the true effect could lie between 33 to 96 more episodes per 1000 patients.Interval (symptomatic) recurrences: these were less frequent with intensive follow-up (RR 0.59, 95% CI 0.41 to 0.86; I² = 66%; moderate-quality evidence). There were 376 interval recurrences reported in 3933 participants enrolled in seven studies. Intensive follow-up was associated with fewer interval recurrences (52 fewer per 1000 patients); the true effect is between 18 and 75 fewer per 1000 patients.Intensive follow-up probably makes little or no difference to quality of life, anxiety, or depression (reported in 7 studies; moderate-quality evidence). The data were not available in a form that allowed analysis.Intensive follow-up may increase the complications (perforation or haemorrhage) from colonoscopies (OR 7.30, 95% CI 0.75 to 70.69; 1 study, 326 participants; very low-quality evidence). Two studies reported seven colonoscopic complications in 2292 colonoscopies, three perforations and four gastrointestinal haemorrhages requiring transfusion. We could not combine the data, as they were not reported by study arm in one study.The limited data on costs suggests that the cost of more intensive follow-up may be increased in comparison with less intense follow-up (low-quality evidence). The data were not available in a form that allowed analysis. AUTHORS' CONCLUSIONS The results of our review suggest that there is no overall survival benefit for intensifying the follow-up of patients after curative surgery for colorectal cancer. Although more participants were treated with salvage surgery with curative intent in the intensive follow-up groups, this was not associated with improved survival. Harms related to intensive follow-up and salvage therapy were not well reported.
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Affiliation(s)
- Mark Jeffery
- Christchurch HospitalCanterbury Regional Cancer and Haematology ServicePrivate Bag 4710ChristchurchNew Zealand8140
| | - Brigid E Hickey
- Princess Alexandra HospitalRadiation Oncology Mater Service31 Raymond TerraceBrisbaneQueenslandAustralia4101
- The University of QueenslandSchool of MedicineBrisbaneAustralia
| | - Phillip N Hider
- University of Otago, ChristchurchDepartment of Population HealthPO Box 4345ChristchurchNew Zealand8140
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Intensive follow-up strategies after radical surgery for nonmetastatic colorectal cancer: A systematic review and meta-analysis of randomized controlled trials. PLoS One 2019; 14:e0220533. [PMID: 31361784 PMCID: PMC6667274 DOI: 10.1371/journal.pone.0220533] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Accepted: 07/14/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Intensive follow-up after surgery for colorectal cancers is common in clinical practice, but evidence of a survival benefit is limited. OBJECTIVE To conduct a systematic review and meta-analysis on the effects of follow-up strategies for nonmetastatic colorectal cancer. DATA SOURCES We searched Medline, Embase, and CENTRAL databases through May 30, 2018. STUDY SELECTION We included randomized clinical trials evaluating intensive follow-up versus less follow-up in patients with nonmetastatic colorectal cancer. INTERVENTIONS Intensive follow-up. MAIN OUTCOMES MEASURES Overall survival. RESULTS The analyses included 17 trials with a total of 8039 patients. Compared with less follow-up, intensive follow-up significantly improved overall survival in patients with nonmetastatic colorectal cancer after radical surgery (HR 0.85, 95% CI 0.74-0.97, P = 0.01; I2 = 30%; high quality). Subgroup analyses showed that differences between intensive-frequency and intensive-test follow-up (P = 0.04) and between short interval and long interval of follow-up (P = 0.02) in favor of the former one. LIMITATIONS Clinical heterogeneity of interventions. CONCLUSIONS For patients with nonmetastatic colorectal cancer after curative resection, intensive follow-up strategy was associated with an improvement in overall survival compared with less follow-up strategy. Intensive-frequency follow-up strategy was associated with a greater reduction in mortality compared with intensive-test follow-up strategy.
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Ramphal W, Boeding JRE, Schreinemakers JMJ, Gobardhan PD, Rutten HJT, Crolla RMPH. Colonoscopy Surveillance After Colorectal Cancer: the Optimal Interval for Follow-Up. J Gastrointest Cancer 2019; 51:469-477. [PMID: 31155695 DOI: 10.1007/s12029-019-00254-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
PURPOSE Patients who have undergone curative surgery for colorectal cancer are at risk of developing a metachronous colorectal tumour or anastomotic recurrence. The aim of this study was to determine the incidence of recurrent colorectal cancer in a cohort of patients who participated in a colonoscopy surveillance programme. METHODS This single-centre retrospective observational cohort study included patients who underwent curative surgery for colorectal cancer between 2005 and 2015. All reports of postoperative colonoscopies were retrieved to calculate the incidence rates of recurrence and metachronous colorectal cancer. RESULTS Of 2420 patients, 1644 (67.9%) underwent at least one postoperative colonoscopy and 776 (32.1%) did not. In 1087 patients, colonoscopy was performed in the first 18 months after surgery, which detected 34 (3.1%) instances of metachronous colorectal tumours or anastomotic recurrence. Thirty-three additional patients were also diagnosed with recurrent colorectal cancer, but the tumours were detected by other diagnostic modalities or detected perioperatively, rather than by colonoscopy. CONCLUSIONS Patients with a history of colorectal cancer have an increased risk for a second colorectal tumour. Therefore, we recommend a colonoscopic surveillance programme with the first colonoscopy performed 1 year after curative surgery, which is in accordance with national guidelines.
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Affiliation(s)
- Winesh Ramphal
- Department of Surgery, Amphia Hospital Breda, Molengracht 21, 4818 CK, Breda, The Netherlands.
| | - Jeske R E Boeding
- Department of Surgery, Amphia Hospital Breda, Molengracht 21, 4818 CK, Breda, The Netherlands
| | | | - Paul D Gobardhan
- Department of Surgery, Amphia Hospital Breda, Molengracht 21, 4818 CK, Breda, The Netherlands
| | - Harm J T Rutten
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.,GROW: School of Oncology and Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Rogier M P H Crolla
- Department of Surgery, Amphia Hospital Breda, Molengracht 21, 4818 CK, Breda, The Netherlands
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Rose J, Homa L, Kong CY, Cooper GS, Kattan MW, Ermlich BO, Meyers JP, Primrose JN, Pugh SA, Shinkins B, Kim U, Meropol NJ. Development and validation of a model to predict outcomes of colon cancer surveillance. Cancer Causes Control 2019; 30:767-778. [DOI: 10.1007/s10552-019-01187-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Accepted: 05/17/2019] [Indexed: 11/28/2022]
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Teke ME, Emuakhagbon VS. Trends in Colorectal Cancer Surveillance: Current Strategies and Future Innovations-. CURRENT COLORECTAL CANCER REPORTS 2019. [DOI: 10.1007/s11888-019-00433-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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26
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Guraya SY. Pattern, Stage, and Time of Recurrent Colorectal Cancer After Curative Surgery. Clin Colorectal Cancer 2019; 18:e223-e228. [PMID: 30792036 DOI: 10.1016/j.clcc.2019.01.003] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 01/09/2019] [Accepted: 01/17/2019] [Indexed: 02/07/2023]
Abstract
Surgery remains the mainstay of curative treatment for colorectal cancer (CRC). Despite curative surgery, some patients experience cancer recurrence. However, the pattern, stage, and time of recurrent disease (RD) remain unknown. We aimed to determine the pattern and stage of RD after curative open and laparoscopic surgery for CRC. Databases were searched using selected keywords for clinical studies that analyzed the pattern, stage, and time of RD from CRC. A systematic protocol was used for data extraction, data synthesis, and interpretation of results. Of 455 publications retrieved from databases, 9 clinical studies were selected for this systematic review. There is substantial evidence that pulmonary recurrence is most commonly associated with rectal tumors, and multisite RD appears more frequently with right-sided CRC. RD from colon cancers predominantly appears early in liver, while recurrences from rectal cancer appear late in lungs. Approximately 30% to 50% of RD after curative resection of CRC occurs within the first 2 years; however, median time to recurrence is gradually increasing, particularly for patients with rectal cancers. Advanced primary CRC is significantly correlated with more locoregional and distant RD, with worse disease-free survival. There is a decrease in the 5-year incidence of RD that is associated with prolongation of time of RD for both locoregional and metastatic disease. The duration and design of postoperative follow-up protocols for recurrences from CRC should be tailored to site and stage of primary tumor, as rectal cancers demand longer surveillance times than colon cancer.
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Affiliation(s)
- Salman Yousuf Guraya
- Head Surgery Unit, Clinical Sciences Department, College of Medicine University of Sharjah, Sharjah, United Arab Emirates.
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27
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Smith JC, Sheltzer JM. Systematic identification of mutations and copy number alterations associated with cancer patient prognosis. eLife 2018; 7:e39217. [PMID: 30526857 PMCID: PMC6289580 DOI: 10.7554/elife.39217] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 11/12/2018] [Indexed: 02/06/2023] Open
Abstract
Successful treatment decisions in cancer depend on the accurate assessment of patient risk. To improve our understanding of the molecular alterations that underlie deadly malignancies, we analyzed the genomic profiles of 17,879 tumors from patients with known outcomes. We find that mutations in almost all cancer driver genes contain remarkably little information on patient prognosis. However, CNAs in these same driver genes harbor significant prognostic power. Focal CNAs are associated with worse outcomes than broad alterations, and CNAs in many driver genes remain prognostic when controlling for stage, grade, TP53 status, and total aneuploidy. By performing a meta-analysis across independent patient cohorts, we identify robust prognostic biomarkers in specific cancer types, and we demonstrate that a subset of these alterations also confer specific therapeutic vulnerabilities. In total, our analysis establishes a comprehensive resource for cancer biomarker identification and underscores the importance of gene copy number profiling in assessing clinical risk.
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Kupfer SS, Lubner S, Coronel E, Pickhardt PJ, Tipping M, Graffy P, Keenan E, Ross E, Li T, Weinberg DS. Adherence to postresection colorectal cancer surveillance at National Cancer Institute-designated Comprehensive Cancer Centers. Cancer Med 2018; 7:5351-5358. [PMID: 30338661 PMCID: PMC6247039 DOI: 10.1002/cam4.1678] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 05/13/2018] [Accepted: 05/18/2018] [Indexed: 01/12/2023] Open
Abstract
Guidelines recommend surveillance after resection of colorectal cancer (CRC), but rates of adherence to surveillance are variable and have not been studied at National Cancer Institute (NCI)‐designated Comprehensive Cancer Centers. The aim of this study was to determine rates of adherence to standard postresection CRC surveillance recommendations including physician visits, carcinoembryonic antigen (CEA), computed tomography (CT), and colonoscopy after CRC resection at three NCI‐designated centers. Data on patients with resected CRC from 2010 to 2017 were reviewed. Adherence to physician visits was defined as having at least two visits within 14 months after surgical resection. CEA adherence was defined as having at least four CEA levels drawn within 14 months. CT and colonoscopy adherence were defined as completing each between 10 and 14 months from surgical resection. Chi‐square test and logistic regression analyses were performed for overall adherence and adherence to individual components. A total of 241 CRC patients were included. Overall adherence was 23%. While adherence to physician visits was over 98%, adherence to CEA levels, CT, and colonoscopy were each less than 50%. Center was an independent predictor of adherence to CEA, CT, and/or colonoscopy. Stage III disease predicted CT adherence, while distance traveled of 40 miles or less predicted colonoscopy adherence. Overall adherence to postresection CRC guideline‐recommended care is low at NCI‐designated centers. Adherence rates to surveillance vary by center, stage, and distance traveled for care. Understanding factors associated with adherence is critical to ensure CRC patients benefit from postresection surveillance.
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Affiliation(s)
- Sonia S Kupfer
- Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, Illinois
| | - Sam Lubner
- University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin
| | - Emmanuel Coronel
- Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, Illinois
| | - Perry J Pickhardt
- University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin
| | - Matthew Tipping
- University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin
| | - Peter Graffy
- University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin
| | | | - Eric Ross
- Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Tianyu Li
- Fox Chase Cancer Center, Philadelphia, Pennsylvania
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Gunawardene A, Dennett E, Larsen P. Prognostic value of multiple cytokine analysis in colorectal cancer: a systematic review. J Gastrointest Oncol 2018; 10:134-143. [PMID: 30788169 DOI: 10.21037/jgo.2018.07.11] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The link between inflammation and outcome has been established in colorectal cancer through experimental evidence demonstrating an influential role of pro-inflammatory cytokines on tumour growth and progression. Furthermore, prognostic scores based on overall markers of systemic inflammation such as C-reactive protein and neutrophil count have been validated. Over recent years, an increasing number of inflammatory cytokines have been identified as prognostic predictors in colorectal cancer and the aim of this review was to evaluate the literature on the prognostic value of multiple cytokine measurement. The English language literature published since the year 2000 was searched using terms including, 'colorectal cancer', 'cytokines' and 'prognosis' through Medline, Embase and Scopus databases. Reports were screened by two independent reviewers and studies evaluating fewer than three cytokines were excluded. Quality assessments were performed in six domains before data extraction was undertaken in duplicate. Seven studies were found to evaluate multiple cytokines after 570 records were screened. The quality of these studies ranged from poor to moderate and were heterogeneous in terms of the patient population and the number and selection of cytokines tested. Four studies combined multiple cytokine levels into a single score and found them to be predictive of prognosis whereas the association between individual cytokines and outcome was not demonstrated consistently. The combination of multiple cytokine markers into a single prognostic score shows promise in colorectal cancer and further research is required to establish and validate such a score.
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Affiliation(s)
- Ashok Gunawardene
- Department of Surgery & Anaesthesia, University of Otago, Wellington, New Zealand
| | - Elizabeth Dennett
- Department of Surgery & Anaesthesia, University of Otago, Wellington, New Zealand.,Capital & Coast District Health Board, Wellington, New Zealand
| | - Peter Larsen
- Department of Surgery & Anaesthesia, University of Otago, Wellington, New Zealand
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Mäkelä JT, Klintrup KH, Rautio TT. Mortality and Survival after Surgical Treatment of Colorectal Cancer in Patients Aged over 80 Years. Gastrointest Tumors 2017; 4:36-44. [PMID: 29071263 DOI: 10.1159/000477721] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 05/08/2017] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVE The purpose of this study was to identify the clinical factors and tumor characteristics that predict the outcome of colorectal cancer patients aged >80 years. MATERIALS AND METHODS The data of 186 patients aged >80 years with colorectal cancer were collected from a computer database, and the variables were analyzed by both uni- and multivariate analyses. RESULTS The 30-day mortality was 4% and the 90-day mortality 10%. The 1-year survival was 76%, and 27 (61%) of the 44 deaths were unrelated to cancer. The overall 5-year survival was 36%, the median survival 38 months, and the cancer-specific survival 40%. The recurrence rate after radical surgery was 22% and it was not affected by age. Kaplan-Meier estimates indicated that age, number of underlying diseases, radical operation, Union for International Cancer Control stage of the tumor, tumor size, number of lymph nodes involved, venous invasion, and recurrent disease were significant predictors of survival, but in the Cox regression model, only radical operation and venous invasion were independent prognostic factors for survival. CONCLUSIONS After good surgical selection, low early mortality and acceptable long-term survival can be achieved even in the oldest old patients with colorectal cancer. However, low early mortality seems to underestimate the effects of surgery during the first postoperative year.
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Affiliation(s)
- Jyrki Tapani Mäkelä
- Department of Surgery, Surgical Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Kai Hans Klintrup
- Department of Surgery, Surgical Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Tero Tapani Rautio
- Department of Surgery, Surgical Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
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Colorectal Cancer Surveillance: What Is the Optimal Frequency of Follow-up and Which Tools Best Predict Recurrence? CURRENT COLORECTAL CANCER REPORTS 2017. [DOI: 10.1007/s11888-017-0382-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Mant D, Gray A, Pugh S, Campbell H, George S, Fuller A, Shinkins B, Corkhill A, Mellor J, Dixon E, Little L, Perera-Salazar R, Primrose J. A randomised controlled trial to assess the cost-effectiveness of intensive versus no scheduled follow-up in patients who have undergone resection for colorectal cancer with curative intent. Health Technol Assess 2017; 21:1-86. [PMID: 28641703 PMCID: PMC5494506 DOI: 10.3310/hta21320] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Intensive follow-up after surgery for colorectal cancer is common practice but lacks a firm evidence base. OBJECTIVE To assess whether or not augmenting symptomatic follow-up in primary care with two intensive methods of follow-up [monitoring of blood carcinoembryonic antigen (CEA) levels and scheduled imaging] is effective and cost-effective in detecting the recurrence of colorectal cancer treatable surgically with curative intent. DESIGN Randomised controlled open-label trial. Participants were randomly assigned to one of four groups: (1) minimum follow-up (n = 301), (2) CEA testing only (n = 300), (3) computerised tomography (CT) only (n = 299) or (4) CEA testing and CT (n = 302). Blood CEA was measured every 3 months for 2 years and then every 6 months for 3 years; CT scans of the chest, abdomen and pelvis were performed every 6 months for 2 years and then annually for 3 years. Those in the minimum and CEA testing-only arms had a single CT scan at 12-18 months. The groups were minimised on adjuvant chemotherapy, gender and age group (three strata). SETTING Thirty-nine NHS hospitals in England with access to high-volume services offering surgical treatment of metastatic recurrence. PARTICIPANTS A total of 1202 participants who had undergone curative treatment for Dukes' stage A to C colorectal cancer with no residual disease. Adjuvant treatment was completed if indicated. There was no evidence of metastatic disease on axial imaging and the post-operative blood CEA level was ≤ 10 µg/l. MAIN OUTCOME MEASURES Primary outcome Surgical treatment of recurrence with curative intent. Secondary outcomes Time to detection of recurrence, survival after treatment of recurrence, overall survival and quality-adjusted life-years (QALYs) gained. RESULTS Detection of recurrence During 5 years of scheduled follow-up, cancer recurrence was detected in 203 (16.9%) participants. The proportion of participants with recurrence surgically treated with curative intent was 6.3% (76/1202), with little difference according to Dukes' staging (stage A, 5.1%; stage B, 7.4%; stage C, 5.6%; p = 0.56). The proportion was two to three times higher in each of the three more intensive arms (7.5% overall) than in the minimum follow-up arm (2.7%) (difference 4.8%; p = 0.003). Surgical treatment of recurrence with curative intent was 2.7% (8/301) in the minimum follow-up group, 6.3% (19/300) in the CEA testing group, 9.4% (28/299) in the CT group and 7.0% (21/302) in the CEA testing and CT group. Surgical treatment of recurrence with curative intent was two to three times higher in each of the three more intensive follow-up groups than in the minimum follow-up group; adjusted odds ratios (ORs) compared with minimum follow-up were as follows: CEA testing group, OR 2.40, 95% confidence interval (CI) 1.02 to 5.65; CT group, OR 3.69, 95% CI 1.63 to 8.38; and CEA testing and CT group, OR 2.78, 95% CI 1.19 to 6.49. Survival A Kaplan-Meier survival analysis confirmed no significant difference between arms (log-rank p = 0.45). The baseline-adjusted Cox proportional hazards ratio comparing the minimum and intensive arms was 0.87 (95% CI 0.67 to 1.15). These CIs suggest a maximum survival benefit from intensive follow-up of 3.8%. Cost-effectiveness The incremental cost per patient treated surgically with curative intent compared with minimum follow-up was £40,131 with CEA testing, £43,392 with CT and £85,151 with CEA testing and CT. The lack of differential impact on survival resulted in little difference in QALYs saved between arms. The additional cost per QALY gained of moving from minimum follow-up to CEA testing was £25,951 and for CT was £246,107. When compared with minimum follow-up, combined CEA testing and CT was more costly and generated fewer QALYs, resulting in a negative incremental cost-effectiveness ratio (-£208,347) and a dominated policy. LIMITATIONS Although this is the largest trial undertaken at the time of writing, it has insufficient power to assess whether or not the improvement in detecting treatable recurrence achieved by intensive follow-up leads to a reduction in overall mortality. CONCLUSIONS Rigorous staging to detect residual disease is important before embarking on follow-up. The benefit of intensive follow-up in detecting surgically treatable recurrence is independent of stage. The survival benefit from intensive follow-up is unlikely to exceed 4% in absolute terms and harm cannot be absolutely excluded. A longer time horizon is required to ascertain whether or not intensive follow-up is an efficient use of scarce health-care resources. Translational analyses are under way, utilising tumour tissue collected from Follow-up After Colorectal Surgery trial participants, with the aim of identifying potentially prognostic biomarkers that may guide follow-up in the future. TRIAL REGISTRATION Current Controlled Trials ISRCTN41458548. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 32. See the NIHR Journals Library website for further project information.
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Affiliation(s)
- David Mant
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Alastair Gray
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Siân Pugh
- University Surgery, University of Southampton, Southampton, UK
| | - Helen Campbell
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Stephen George
- Faculty of Medicine, University of Southampton, Southampton, UK
| | - Alice Fuller
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Bethany Shinkins
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - Andrea Corkhill
- Southampton Clinical Trials Unit, University of Southampton, Southampton, UK
| | - Jane Mellor
- Southampton Clinical Trials Unit, University of Southampton, Southampton, UK
| | - Elizabeth Dixon
- Southampton Clinical Trials Unit, University of Southampton, Southampton, UK
| | - Louisa Little
- Southampton Clinical Trials Unit, University of Southampton, Southampton, UK
| | - Rafael Perera-Salazar
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - John Primrose
- University Surgery, University of Southampton, Southampton, UK
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Godhi S, Godhi A, Bhat R, Saluja S. Colorectal Cancer: Postoperative Follow-up and Surveillance. Indian J Surg 2017; 79:234-237. [PMID: 28659677 DOI: 10.1007/s12262-017-1610-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Accepted: 02/24/2017] [Indexed: 12/28/2022] Open
Abstract
Follow-up and surveillance form an important aspect of care in patients with colorectal cancers (CRC). Most recurrences will occur within 2 years of surgery and 90% by 5 years. Follow up protocols have not been well defined in stage I disease and the approach should be individualized. As 40% of patients with stages II and III will develop recurrences, intensive postoperative follow-up strategy is recommended for them. It includes visit to the clinician for clinical examination, serum carcinoembryonic antigen (CEA), computed tomography (CT) of the chest and abdomen, colonoscopy, and flexible proctosigmoidoscopy in rectal cancers. Surveillance should be undertaken in those who are medically fit for repeat surgical procedures or for chemoradiotherapy. The concept of intensive post operative surveillance is based on the fact that some of these patients can have resectable/curable recurrence.
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Affiliation(s)
- Satyajit Godhi
- Surgical Gastroenterology, Apollo Hospitals, Bangalore, Karnataka India
| | - Ashok Godhi
- Surgery, Jawaharlal Nehru Medical College, Belgaum, Karnataka India
| | - Ravishankar Bhat
- Surgical Gastroenterology, Apollo Hospitals, Bangalore, Karnataka India
| | - Sundeep Saluja
- Surgical Gastroenterology , G.B. Panth Institute of Post Graduate Medical Education and Research, New Delhi, India
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Sehdev A, Sherer EA, Hui SL, Wu J, Haggstrom DA. Patterns of computed tomography surveillance in survivors of colorectal cancer at Veterans Health Administration facilities. Cancer 2017; 123:2338-2351. [PMID: 28211937 DOI: 10.1002/cncr.30569] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2016] [Revised: 11/21/2016] [Accepted: 12/26/2016] [Indexed: 01/21/2023]
Abstract
BACKGROUND Annual computed tomography (CT) scans are a component of the current standard of care for the posttreatment surveillance of survivors of colorectal cancer (CRC) after curative-intent resection. The authors conducted a retrospective study with the primary aim of assessing patient, physician, and organizational characteristics associated with the receipt of CT surveillance among veterans. METHODS The Department of Veterans Affairs Central Cancer Registry was used to identify patients diagnosed with AJCC collaborative stage I to III CRC between 2001 and 2009. Patient sociodemographic and clinical (ie, CRC stage and comorbidity) characteristics, provider specialty, and organizational characteristics were measured. Hierarchical multivariable logistic regression models were used to assess the association between patient, provider, and organizational characteristics on receipt of 1) consistently guideline-concordant care (at least 1 CT every 12 months for both of the first 2 years of CRC surveillance) versus no CT receipt and 2) potential overuse (>1 CT every 12 months during the first 2 years of CRC surveillance) of CRC surveillance using CT. The authors also analyzed the impact of the 2005 American Society of Clinical Oncology update in CRC surveillance guidelines on care received over time. RESULTS For 2263 survivors of stage II/III CRC who were diagnosed after 2005, 19.4% of patients received no surveillance CT, whereas potential overuse occurred in both surveillance years for 14.9% of patients. Guideline-concordant care was associated with younger age, higher stage of disease (stage III vs stage II), and geographic region. In adjusted analyses, younger age and higher stage of disease (stage III vs stage II) were found to be associated with overuse. There was no significant difference in the annual rate of CT scanning noted across time periods (year ≤ 2005 vs year > 2005). CONCLUSIONS Among a minority of veteran survivors of CRC, both underuse and potential overuse of CT surveillance were present. Patient factors, but no provider or organizational characteristics, were found to be significantly associated with patterns of care. The 2005 change in American Society of Clinical Oncology guidelines did not appear to have an impact on rates of surveillance CT. Cancer 2017;123:2338-2351. © 2017 American Cancer Society.
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Affiliation(s)
- Amikar Sehdev
- Division of Hematology and Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.,Center for Health Services Research, Regenstrief Institute, Indianapolis, Indiana.,Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana
| | - Eric A Sherer
- Department of Chemical Engineering, Louisiana Tech University, Ruston, Louisiana.,Center for Health Information and Communication, Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, Indianapolis, Indiana
| | - Siu L Hui
- Center for Health Services Research, Regenstrief Institute, Indianapolis, Indiana
| | - Jingwei Wu
- Department of Epidemiology and Biostatistics, College of Public Health, Temple University, Philadelphia, Pennsylvania
| | - David A Haggstrom
- Center for Health Services Research, Regenstrief Institute, Indianapolis, Indiana.,Center for Health Information and Communication, Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, Indianapolis, Indiana.,Division of General Internal Medicine and Geriatrics, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
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35
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van der Stok EP, Spaander MCW, Grünhagen DJ, Verhoef C, Kuipers EJ. Surveillance after curative treatment for colorectal cancer. Nat Rev Clin Oncol 2016; 14:297-315. [DOI: 10.1038/nrclinonc.2016.199] [Citation(s) in RCA: 118] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Sekiguchi M, Matsuda T, Saito Y. Surveillance after endoscopic and surgical resection of colorectal cancer. Best Pract Res Clin Gastroenterol 2016; 30:959-970. [PMID: 27938790 DOI: 10.1016/j.bpg.2016.09.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Revised: 08/05/2016] [Accepted: 09/06/2016] [Indexed: 01/31/2023]
Abstract
With the increase in colorectal cancer burden, surveillance following endoscopic and surgical resection is an essential issue. The aim of surveillance programs is improvement of patient survival by early detection of residual tumor tissue or local recurrence, metachronous colorectal tumors, and metastases. Appropriate surveillance should be determined according to this risk of factors. In current guidelines, only surveillance colonoscopy is recommended after endoscopic resection of polyps with high-grade dysplasia, whereas intensive, multimodality surveillance using colonoscopy, radiological imaging and tumor marker measurements is recommended following surgical resection of invasive colorectal cancer. Detailed recommendations, including the timing of surveillance, are described based on high-quality evidence. However, there are still many unresolved issues for which more high-quality evidence is required.
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Affiliation(s)
- Masau Sekiguchi
- Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan; Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan; Division of Screening Technology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Takahisa Matsuda
- Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan; Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan; Division of Screening Technology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
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Khan K, Athauda A, Aitken K, Cunningham D, Watkins D, Starling N, Cook GJ, Kalaitzaki E, Chau I, Rao S. Survival Outcomes in Asymptomatic Patients With Normal Conventional Imaging but Raised Carcinoembryonic Antigen Levels in Colorectal Cancer Following Positron Emission Tomography-Computed Tomography Imaging. Oncologist 2016; 21:1502-1508. [PMID: 27742904 PMCID: PMC5153343 DOI: 10.1634/theoncologist.2016-0222] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Accepted: 07/21/2016] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND This study had two aims: (a) to evaluate the utility of fluorine 18-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) in detecting occult disease recurrence with raised carcinoembryonic antigen (CEA) and (b) to establish the prognostic effects of early detection of disease recurrence in patients with colorectal cancer (CRC). PATIENTS AND METHODS Clinico-pathological data were obtained from all consecutive patients undergoing CRC surveillance from 2004 to 2010 who had an elevated CEA level (>3 ng/mL in nonsmokers, >5 ng/mL in smokers) but normal or equivocal conventional investigations. Histopathological confirmation or a minimum of 12 months' clinical and radiological follow-up were required to ascertain disease relapse. RESULTS A total of 1,200 patients were screened; of those, 88 (59% men; mean age, 66 years [SD, 9.6]) eligible patients (67 with normal and 21 with equivocal results on conventional investigations) were identified. Recurrent disease was detected in 56 of 88 patients (64%). The sensitivity of FDG PET-CT to detect recurrence was 49 of 56 (88%; 95% confidence interval [CI], 76%-95%) and specificity was 28 of 32 (88%; 95% CI, 71%-97%). Twenty-seven of 49 (55%) patients with PET-CT-detected relapsed disease were deemed eligible for further curative therapy; 19 (70%) went on to receive potentially curative therapy. The median time to progression (8.8 months [interquartile range (IQR), 4.5-19.1 months] vs. 2.2 months [IQR, 0.7-5.6]), median overall survival (39.9 months [IQR, 23.6-65.4 months] vs. 15.6 months [IQR, 7.3-25.7 months]), and 5-year survival (36.8% [95% CI, 16.5%-57.5%] vs. 6.1% [95% CI, 1.1%-17.6%]; p ≤ .001) were higher in patients who received potentially curative therapy than in those who received noncurative therapy. CONCLUSION FDG PET-CT is a highly sensitive and specific tool for the detection of occult CRC recurrence. In >50% of patients, recurrent disease may still be potentially amenable to curative therapy. Long-term survival can be achieved in such patients. IMPLICATIONS FOR PRACTICE Colorectal cancer (CRC) patients who, on follow-up, have normal or equivocal results on clinical investigations but raised carcinoembryonic antigen (CEA) levels pose a significant challenge to treating physicians. This study supported the notion that the early use of fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) may have predictive and prognostic value in management of such patients. Long-term disease control and cure can be achieved in a subgroup of this patient population with low-volume disease relapse who are amenable to potentially curative treatment strategies. Reassuringly, the sensitivity and specificity for recurrence did not significantly vary as a function of the CEA level, suggesting that even with a minimal CEA rise, benefit can be attained by conducting FDG PET-CT in a timely manner.
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Affiliation(s)
- Khurum Khan
- GI and Lymphoma Unit, Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Avani Athauda
- GI and Lymphoma Unit, Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Katharine Aitken
- GI and Lymphoma Unit, Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - David Cunningham
- GI and Lymphoma Unit, Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - David Watkins
- GI and Lymphoma Unit, Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Naureen Starling
- GI and Lymphoma Unit, Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Gary J Cook
- Department of Nuclear Medicine, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Eleftheria Kalaitzaki
- Department of Statistics, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Ian Chau
- GI and Lymphoma Unit, Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Sheela Rao
- GI and Lymphoma Unit, Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
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Jeffery M, Hickey BE, Hider PN, See AM. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev 2016; 11:CD002200. [PMID: 27884041 PMCID: PMC6464536 DOI: 10.1002/14651858.cd002200.pub3] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND It is common clinical practice to follow patients with colorectal cancer (CRC) for several years following their curative surgery or adjuvant therapy, or both. Despite this widespread practice, there is considerable controversy about how often patients should be seen, what tests should be performed, and whether these varying strategies have any significant impact on patient outcomes. This is the second update of a Cochrane Review first published in 2002 and first updated in 2007. OBJECTIVES To assess the effects of intensive follow-up for patients with non-metastatic colorectal cancer treated with curative intent. SEARCH METHODS For this update, we searched CENTRAL (2016, Issue 3), MEDLINE (1950 to May 20th, 2016), Embase (1974 to May 20th, 2016), CINAHL (1981 to May 20th, 2016), and Science Citation Index (1900 to May 20th, 2016). We also searched reference lists of articles, and handsearched the Proceedings of the American Society for Radiation Oncology (2011 to 2014). In addition, we searched the following trials registries (May 20th, 2016): ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We further contacted study authors. No language or publication restrictions were applied to the search strategies. SELECTION CRITERIA We included only randomised controlled trials comparing different follow-up strategies for participants with non-metastatic CRC treated with curative intent. DATA COLLECTION AND ANALYSIS Two authors independently determined trial eligibility, performed data extraction, and assessed methodological quality. MAIN RESULTS We studied 5403 participants enrolled in 15 studies. (We included two new studies in this second update.) Although the studies varied in setting (general practitioner (GP)-led, nurse-led, or surgeon-led) and "intensity" of follow-up, there was very little inconsistency in the results.Overall survival: we found no evidence of a statistical effect with intensive follow-up (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.78 to 1.02; I² = 4%; P = 0.41; high-quality evidence). There were 1098 deaths among 4786 participants enrolled in 12 studies.Colorectal cancer-specific survival: this did not differ with intensive follow-up (HR 0.93, 95% CI 0.78 to 1.12; I² = 0%; P = 0.45; moderate-quality evidence). There were 432 colorectal cancer deaths among 3769 participants enrolled in seven studies.Relapse-free survival: we found no statistical evidence of effect with intensive follow-up (HR 1.03, 95% CI 0.90 to 1.18; I² = 5%; P = 0.39; moderate-quality evidence). There were 1416 relapses among 5253 participants enrolled in 14 studies.Salvage surgery with curative intent: this was more frequent with intensive follow-up (risk ratio (RR) 1.98, 95% CI 1.53 to 2.56; I² = 31%; P = 0.14; high-quality evidence). There were 457 episodes of salvage surgery in 5157 participants enrolled in 13 studies.Interval (symptomatic) recurrences: these were less frequent with intensive follow-up (RR 0.59, 95% CI 0.41 to 0.86; I² = 66%; P = 0.007; moderate-quality evidence). Three hundred and seventy-six interval recurrences were reported in 3933 participants enrolled in seven studies.Intensive follow-up did not appear to affect quality of life, anxiety, nor depression (reported in three studies).Harms from colonoscopies did not differ with intensive follow-up (RR 2.08, 95% CI 0.11 to 40.17; moderate-quality evidence). In two studies, there were seven colonoscopic complications in 2112 colonoscopies. AUTHORS' CONCLUSIONS The results of our review suggest that there is no overall survival benefit for intensifying the follow-up of patients after curative surgery for colorectal cancer. Although more participants were treated with salvage surgery with curative intent in the intensive follow-up group, this was not associated with improved survival. Harms related to intensive follow-up and salvage therapy were not well reported.
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Affiliation(s)
- Mark Jeffery
- Christchurch HospitalCanterbury Regional Cancer and Haematology ServicePrivate Bag 4710ChristchurchNew Zealand8140
| | | | - Phil N Hider
- University of Otago, ChristchurchDepartment of Population HealthPO Box 4345ChristchurchNew Zealand8140
| | - Adrienne M See
- Princess Alexandra HospitalRadiation Oncology Mater Service31 Raymond TerraceBrisbaneAustralia4101
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Lopez NE, Peterson CY. Advances in Biomarkers: Going Beyond the Carcinoembryonic Antigen. Clin Colon Rectal Surg 2016; 29:196-204. [PMID: 27582644 DOI: 10.1055/s-0036-1584289] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Using biologically available markers to guide treatment decisions in colorectal cancer care is becoming increasingly common, though our understanding of these biomarkers is in its infancy. In this article, we will discuss how this area is rapidly changing, review important biomarkers being used currently, and explain how the results influence clinical decision-making. We will also briefly discuss the possibility of a liquid biopsy and explore several exciting and new options.
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Affiliation(s)
- Nicole E Lopez
- Division of Surgical Oncology, University of North Carolina, Chapel Hill, North Carolina
| | - Carrie Y Peterson
- Division of Colorectal Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
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Mokhles S, Macbeth F, Farewell V, Fiorentino F, Williams NR, Younes RN, Takkenberg JJM, Treasure T. Meta-analysis of colorectal cancer follow-up after potentially curative resection. Br J Surg 2016; 103:1259-68. [PMID: 27488593 PMCID: PMC5031212 DOI: 10.1002/bjs.10233] [Citation(s) in RCA: 82] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 05/15/2016] [Accepted: 05/17/2016] [Indexed: 12/24/2022]
Abstract
Background After potentially curative resection of primary colorectal cancer, patients may be monitored by measurement of carcinoembryonic antigen and/or CT to detect asymptomatic metastatic disease earlier. Methods A systematic review and meta-analysis was conducted to find evidence for the clinical effectiveness of monitoring in advancing the diagnosis of recurrence and its effect on survival. MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science and other databases were searched for randomized comparisons of increased intensity monitoring compared with a contemporary standard policy after resection of primary colorectal cancer. Results There were 16 randomized comparisons, 11 with published survival data. More intensive monitoring advanced the diagnosis of recurrence by a median of 10 (i.q.r. 5–24) months. In ten of 11 studies the authors reported no demonstrable difference in overall survival. Seven RCTs, published from 1995 to 2016, randomly assigned 3325 patients to a monitoring protocol made more intensive by introducing new methods or increasing the frequency of existing follow-up protocols versus less invasive monitoring. No detectable difference in overall survival was associated with more intensive monitoring protocols (hazard ratio 0·98, 95 per cent c.i. 0·87 to 1·11). Conclusion Based on pooled data from randomized trials published from 1995 to 2016, the anticipated survival benefit from surgical treatment resulting from earlier detection of metastases has not been achieved.
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Affiliation(s)
- S Mokhles
- Department of Cardio-Thoracic Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - F Macbeth
- Wales Cancer Trials Unit, Cardiff University, Cardiff, UK
| | - V Farewell
- Medical Research Council Biostatistics Unit, Institute of Public Health, University of Cambridge, Cambridge, UK
| | - F Fiorentino
- Division of Surgery and Cancer, and Imperial College Trials Unit, Imperial College London, London, UK
| | - N R Williams
- Surgical and Interventional Trials Unit, Division of Surgery and Interventional Science, Faculty of Medical Sciences, University College London, London, UK
| | - R N Younes
- Oncology Centre, Hospital Alemão Oswaldo Cruz, Sao Paulo, Brazil
| | - J J M Takkenberg
- Department of Cardio-Thoracic Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - T Treasure
- Clinical Operational Research Unit, University College London, London, UK
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Abstract
BACKGROUND Radiological imaging plays an important role in the setting of staging, follow-up, and imaging-guided treatment of colorectal carcinoma (CRC). METHODS This review aims to summarize the current state of the art of the different radiological imaging procedures in CRC including an overview over recently published national and European guidelines and consensus statements concerning the imaging of CRC patients. RESULTS AND CONCLUSION Radiological imaging is widely embedded in national and international guidelines, and structured reporting is recommended.
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Affiliation(s)
- Bettina Baeßler
- Department of Radiology, University Hospital of Cologne, Cologne, Germany
| | - David Maintz
- Department of Radiology, University Hospital of Cologne, Cologne, Germany
| | - Thorsten Persigehl
- Department of Radiology, University Hospital of Cologne, Cologne, Germany
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Ouchi A, Asano M, Aono K, Watanabe T, Oya S. Staple-line recurrence arising 10 years after functional end-to-end anastomosis for colon cancer: a case report. Surg Case Rep 2016; 1:7. [PMID: 26943375 PMCID: PMC4747930 DOI: 10.1186/s40792-014-0011-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Accepted: 12/22/2014] [Indexed: 02/05/2023] Open
Abstract
We report a rare case of late staple-line recurrence arising 10 years after functional end-to-end anastomosis for splenic flexure colon cancer. An 80-year-old man, who underwent partial colectomy with functional end-to-end anastomosis for splenic flexure colon cancer 10 years earlier, presented with a chief complaint of anorexia. Complete blood count showed anemia, and the fecal occult blood test was positive. Lower gastrointestinal series showed an irregular defect of the splenic flexure, and colonoscopy showed an ulcerated tumor on the staple line of the primary surgery. Partial colectomy was performed, and the tumor was pathologically diagnosed as moderately differentiated tubular adenocarcinoma, resembling the pathology of primary colon cancer. This case suggests the importance of considering staple-line recurrence after functional end-to-end anastomosis for colon cancer even more than 5 years after primary surgery.
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Affiliation(s)
- Akira Ouchi
- Department of Surgery, Chita City Hospital, 2-1 Nagai, Shinchi, Chita, Aichi, 478-8640, Japan.
| | - Masahiko Asano
- Department of Surgery, Chita City Hospital, 2-1 Nagai, Shinchi, Chita, Aichi, 478-8640, Japan.
| | - Keiya Aono
- Department of Surgery, Chita City Hospital, 2-1 Nagai, Shinchi, Chita, Aichi, 478-8640, Japan.
| | - Tetsuya Watanabe
- Department of Surgery, Chita City Hospital, 2-1 Nagai, Shinchi, Chita, Aichi, 478-8640, Japan.
| | - Shingo Oya
- Department of Surgery, Chita City Hospital, 2-1 Nagai, Shinchi, Chita, Aichi, 478-8640, Japan.
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Kahi CJ, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T, Lieberman D, Levin TR, Robertson DJ, Rex DK. Colonoscopy surveillance after colorectal cancer resection: recommendations of the US multi-society task force on colorectal cancer. Gastrointest Endosc 2016; 83:489-98.e10. [PMID: 26802191 DOI: 10.1016/j.gie.2016.01.020] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Charles J Kahi
- Richard L. Roudebush VA Medical Center, Indianapolis, IN; Indiana University School of Medicine, Indianapolis, Indiana.
| | | | - Jason A Dominitz
- VA Puget Sound Health Care System, Seattle, Washington; University of Washington School of Medicine, Seattle, Washington
| | | | | | - Tonya Kaltenbach
- Veterans Affairs Palo Alto, Palo Alto, California; Stanford University School of Medicine, Palo Alto, California
| | | | | | - Douglas J Robertson
- VA Medical Center, White River Junction, Vermont; Geisel School of Medicine at Dartmouth, Hanover, NH
| | - Douglas K Rex
- Indiana University School of Medicine, Indianapolis, Indiana
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Kahi CJ, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T, Lieberman D, Levin TR, Robertson DJ, Rex DK. Colonoscopy Surveillance After Colorectal Cancer Resection: Recommendations of the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2016; 150:758-768.e11. [PMID: 26892199 DOI: 10.1053/j.gastro.2016.01.001] [Citation(s) in RCA: 139] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The US Multi-Society Task Force has developed updated recommendations to guide health care providers with the surveillance of patients after colorectal cancer (CRC) resection with curative intent. This document is based on a critical review of the literature regarding the role of colonoscopy, flexible sigmoidoscopy, endoscopic ultrasound, fecal testing and CT colonography in this setting. The document addresses the effect of surveillance, with focus on colonoscopy, on patient survival after CRC resection, the appropriate use and timing of colonoscopy for perioperative clearing and for postoperative prevention of metachronous CRC, specific considerations for the detection of local recurrence in the case of rectal cancer, as well as the place of CT colonography and fecal tests in post-CRC surveillance.
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Affiliation(s)
- Charles J Kahi
- Richard L. Roudebush VA Medical Center, Indianapolis, IN; Indiana University School of Medicine, Indianapolis, Indiana.
| | | | - Jason A Dominitz
- VA Puget Sound Health Care System, Seattle, Washington; University of Washington School of Medicine, Seattle, Washington
| | | | | | - Tonya Kaltenbach
- Veterans Affairs Palo Alto, Palo Alto, California; Stanford University School of Medicine, Palo Alto, California
| | | | | | - Douglas J Robertson
- VA Medical Center, White River Junction, Vermont; Geisel School of Medicine at Dartmouth, Hanover, NH
| | - Douglas K Rex
- Indiana University School of Medicine, Indianapolis, Indiana
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Kahi CJ, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T, Lieberman D, Levin TR, Robertson DJ, Rex DK. Colonoscopy Surveillance after Colorectal Cancer Resection: Recommendations of the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2016; 111:337-46; quiz 347. [PMID: 26871541 DOI: 10.1038/ajg.2016.22] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 12/07/2015] [Indexed: 12/11/2022]
Abstract
The US Multi-Society Task Force has developed updated recommendations to guide health care providers with the surveillance of patients after colorectal cancer (CRC) resection with curative intent. This document is based on a critical review of the literature regarding the role of colonoscopy, flexible sigmoidoscopy, endoscopic ultrasound, fecal testing and CT colonography in this setting. The document addresses the effect of surveillance, with focus on colonoscopy, on patient survival after CRC resection, the appropriate use and timing of colonoscopy for perioperative clearing and for postoperative prevention of metachronous CRC, specific considerations for the detection of local recurrence in the case of rectal cancer, as well as the place of CT colonography and fecal tests in post-CRC surveillance.
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Affiliation(s)
- Charles J Kahi
- Richard L. Roudebush VA Medical Center, Indianapolis, IN.,Indiana University School of Medicine, Indianapolis, Indiana
| | | | - Jason A Dominitz
- VA Puget Sound Health Care System, Seattle, Washington.,University of Washington School of Medicine, Seattle, Washington
| | | | | | - Tonya Kaltenbach
- Veterans Affairs Palo Alto, Palo Alto, California.,Stanford University School of Medicine, Palo Alto, California
| | | | | | - Douglas J Robertson
- VA Medical Center, White River Junction, Vermont.,Geisel School of Medicine at Dartmouth, Hanover, NH
| | - Douglas K Rex
- Indiana University School of Medicine, Indianapolis, Indiana
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Hansdotter Andersson P, Wille-Jørgensen P, Horváth-Puhó E, Petersen SH, Martling A, Sørensen HT, Syk I. The COLOFOL trial: study design and comparison of the study population with the source cancer population. Clin Epidemiol 2016; 8:15-21. [PMID: 26869813 PMCID: PMC4734721 DOI: 10.2147/clep.s92661] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Introduction The COLOFOL trial, a prospective randomized multicenter trial comparing two follow-up regimes after curative surgical treatment for colorectal cancer, focuses on detection of asymptomatic recurrences. This paper aims to describe the design and recruitment procedure in the COLOFOL trial, comparing demographic characteristics between randomized patients and eligible patients not included in the study. Materials and methods COLOFOL was designed as a pragmatic trial with wide inclusion criteria and few exclusion criteria, in order to obtain a sample reflecting the general patient population. To be eligible, patients had to be 75 years or younger and curatively resected for stage II or III colorectal cancer. Exclusion criteria were hereditary colorectal cancer, no signed consent, other malignancy, and life expectancy less than 2 years due to concomitant disease. In four of the 24 participating centers, we scrutinized hospital inpatient data to identify all colorectal cancer patients who underwent surgery, in order to ascertain all eligible patients who were not included in the study and to compare them with enrolled patients. Results Of a total of 4,445 eligible patients, 2,509 patients were randomized (56.4% inclusion rate). A total of 1,221 eligible patients were identified in the scrutinized hospitals, of which 684 (56%) were randomized. No difference in age or sex distribution was observed between randomized and nonrandomized eligible patients. However, a difference was noted in tumor location and stage distribution, with 5.6% more patients in the randomized group having colon cancer and 6.7% more patients having stage II disease. Conclusion Patients in the two study arms were not only demographically similar, but also similar to nonincluded eligible patients, apart from stage and localization. The analyses will be stratified by these variables. Taken together, we conclude that our trial results will be robust and possible to extrapolate to the target population.
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Affiliation(s)
| | | | | | | | - Anna Martling
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden
| | - Henrik Toft Sørensen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Ingvar Syk
- Department of Surgery, Skåne University Hospital, Malmö, Sweden
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Petrillo A, Fusco R, Catalano O. Imaging Modalities. Updates Surg 2016. [DOI: 10.1007/978-88-470-5767-8_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Follow-Up Strategy After Primary and Early Diagnosis. Updates Surg 2016. [DOI: 10.1007/978-88-470-5767-8_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Nicholson BD, Shinkins B, Pathiraja I, Roberts NW, James TJ, Mallett S, Perera R, Primrose JN, Mant D. Blood CEA levels for detecting recurrent colorectal cancer. Cochrane Database Syst Rev 2015; 2015:CD011134. [PMID: 26661580 PMCID: PMC7092609 DOI: 10.1002/14651858.cd011134.pub2] [Citation(s) in RCA: 104] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND Testing for carcino-embryonic antigen (CEA) in the blood is a recommended part of follow-up to detect recurrence of colorectal cancer following primary curative treatment. There is substantial clinical variation in the cut-off level applied to trigger further investigation. OBJECTIVES To determine the diagnostic performance of different blood CEA levels in identifying people with colorectal cancer recurrence in order to inform clinical practice. SEARCH METHODS We conducted all searches to January 29 2014. We applied no language limits to the searches, and translated non-English manuscripts. We searched for relevant reviews in the MEDLINE, EMBASE, MEDION and DARE databases. We searched for primary studies (including conference abstracts) in the Cochrane Central Register of Controlled Trials (CENTRAL), in MEDLINE, EMBASE, and the Science Citation Index & Conference Proceedings Citation Index - Science. We identified ongoing studies by searching WHO ICTRP and the ASCO meeting library. SELECTION CRITERIA We included cross-sectional diagnostic test accuracy studies, cohort studies, and randomised controlled trials (RCTs) of post-resection colorectal cancer follow-up that compared CEA to a reference standard. We included studies only if we could extract 2 x 2 accuracy data. We excluded case-control studies, as the ratio of cases to controls is determined by the study design, making the data unsuitable for assessing test accuracy. DATA COLLECTION AND ANALYSIS Two review authors (BDN, IP) assessed the quality of all articles independently, discussing any disagreements. Where we could not reach consensus, a third author (BS) acted as moderator. We assessed methodological quality against QUADAS-2 criteria. We extracted binary diagnostic accuracy data from all included studies as 2 x 2 tables. We conducted a bivariate meta-analysis. We used the xtmelogit command in Stata to produce the pooled estimates of sensitivity and specificity and we also produced hierarchical summary ROC plots. MAIN RESULTS In the 52 included studies, sensitivity ranged from 41% to 97% and specificity from 52% to 100%. In the seven studies reporting the impact of applying a threshold of 2.5 µg/L, pooled sensitivity was 82% (95% confidence interval (CI) 78% to 86%) and pooled specificity 80% (95% CI 59% to 92%). In the 23 studies reporting the impact of applying a threshold of 5 µg/L, pooled sensitivity was 71% (95% CI 64% to 76%) and pooled specificity 88% (95% CI 84% to 92%). In the seven studies reporting the impact of applying a threshold of 10 µg/L, pooled sensitivity was 68% (95% CI 53% to 79%) and pooled specificity 97% (95% CI 90% to 99%). AUTHORS' CONCLUSIONS CEA is insufficiently sensitive to be used alone, even with a low threshold. It is therefore essential to augment CEA monitoring with another diagnostic modality in order to avoid missed cases. Trying to improve sensitivity by adopting a low threshold is a poor strategy because of the high numbers of false alarms generated. We therefore recommend monitoring for colorectal cancer recurrence with more than one diagnostic modality but applying the highest CEA cut-off assessed (10 µg/L).
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Affiliation(s)
- Brian D Nicholson
- University of OxfordNuffield Department of Primary Care Health SciencesOxfordUK
| | - Bethany Shinkins
- University of LeedsAcademic Unit of Health Economics101 Clarendon RoadLeedsUKLS29LJ
| | - Indika Pathiraja
- University of OxfordNuffield Department of Primary Care Health SciencesOxfordUK
| | - Nia W Roberts
- University of OxfordBodleian Health Care LibrariesKnowledge Centre, ORC Research Building, Old Road CampusOxfordOxfordshireUKOX3 7DQ
| | - Tim J James
- Oxford University Hospitals NHS TrustClinical BiochemistryHeadingtonOxfordUK
| | - Susan Mallett
- University of BirminghamPublic Health, Epidemiology and BiostatisticsEdgbastonBirminghamUKB15 2TT
| | - Rafael Perera
- University of OxfordNuffield Department of Primary Care Health SciencesOxfordUK
| | - John N Primrose
- University of SouthamptonDepartment of SurgerySouthampton General HospitalTremona RoadSouthamptonUKS0322AB
| | - David Mant
- University of OxfordNuffield Department of Primary Care Health SciencesOxfordUK
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Makhoul R, Alva S, Wilkins KB. Surveillance and Survivorship after Treatment for Colon Cancer. Clin Colon Rectal Surg 2015; 28:262-70. [PMID: 26648797 PMCID: PMC4655110 DOI: 10.1055/s-0035-1564435] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Colorectal cancer is the third most common cancer diagnosed in the United States. Majority of patients have localized disease that is amenable to curative resection. Disease recurrence remains a major concern after resection. In addition, patients are at an increased risk for developing a second or metachronous colon cancer. The principal goal of surveillance following treatment of colon cancer is to improve disease-free and overall survival. Survivorship is a distinct phase following surveillance to help improve quality of life and promote longevity.
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Affiliation(s)
- Rami Makhoul
- Rutger-Robert Wood Johnson University Hospital, New Brunswick, New Jersey
| | - Suraj Alva
- Rutger-Robert Wood Johnson University Hospital, New Brunswick, New Jersey
| | - Kirsten B. Wilkins
- Rutger-Robert Wood Johnson University Hospital, New Brunswick, New Jersey
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