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Montalti R, Pepe F, Cassese G, Russo G, Malapelle U, Carlomagno C, Giglio MC, Falco G, Alagia M, De Simone G, Geboes K, Troncone G, Troisi RI, Rompianesi G. Prognostic role of postoperative persistence of ctDNA molecular signature after liver resection for colorectal liver metastases: Preliminary results from a prospective study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109706. [PMID: 40009912 DOI: 10.1016/j.ejso.2025.109706] [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: 06/06/2024] [Revised: 02/06/2025] [Accepted: 02/14/2025] [Indexed: 02/28/2025]
Abstract
INTRODUCTION Liver resection represents the cornerstone treatment for Colo-Rectal Liver Metastases (CRLM), but it is still followed by a high recurrence rate. The identification of a valid and reproducible predictor of recurrence can play a key role in correct and timely management of the disease. In this scenario, liquid biopsy may represent an integrative, less invasive, and easily manageable tool to clinically stratify colorectal cancer patients.We aimed to investigate the prognostic role of persistent circulating tumor DNA (ctDNA) signature on CRLM recurrence after liver resection. METHODS A series of 51 consecutive patients undergoing liver resection for CRLM were prospectively enrolled between January 2020 and March 2023. Patients underwent liquid biopsy from peripheral blood samples before and after surgery. Other risk factors for disease recurrence were also investigated. RESULTS Twenty-nine patients were found to be positive for one of the clinically relevant molecular alterations detected by NGS, at preoperative (T0) ctDNA analysis. At univariate analysis, total tumor size bigger than 60 mm (p = 0.046, HR 2.486) and postoperative persistence of ctDNA molecular signature (p = 0.024, HR 2.831) were significantly associated with recurrence. Multivariable Cox Regression analysis showed that only postoperative persistence of ctDNA molecular signature was associated with recurrence (p = 0.027, HR 2.766). Similarly, 1-3 yr DFS was significantly lower in the subgroup with persistence of molecular signature at liquid biopsy (100-49.5 % vs 57.1-21.4 %, p = 0.018). CONCLUSION Postoperative persistence of ctDNA molecular signature could represent a useful tool to predict recurrence after liver resection for CRLM patients.
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Affiliation(s)
- Roberto Montalti
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy; Department of Public Health, Federico II University, 80131, Naples, Italy.
| | - Francesco Pepe
- Department of Public Health, Federico II University, 80131, Naples, Italy
| | - Gianluca Cassese
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy
| | - Gianluca Russo
- Department of Public Health, Federico II University, 80131, Naples, Italy
| | - Umberto Malapelle
- Department of Public Health, Federico II University, 80131, Naples, Italy
| | - Chiara Carlomagno
- Department of Clinical Medicine and Surgery, Division of Oncology, University Federico II, Naples, Italy
| | - Mariano Cesare Giglio
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy
| | - Giacinto Falco
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy
| | - Mariantonietta Alagia
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy
| | - Giuseppe De Simone
- Department of Anesthesiology, Federico II University Hospital, Naples, Italy
| | - Karen Geboes
- Oncology Centrum, Ghent University Hospital, Belgium
| | - Giancarlo Troncone
- Department of Public Health, Federico II University, 80131, Naples, Italy
| | - Roberto Ivan Troisi
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy
| | - Gianluca Rompianesi
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy
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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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Dompé C, Chojnowska A, Ramlau R, Nowicki M, Alix-Panabières C, Budna-Tukan J. Unveiling the dynamics of circulating tumor cells in colorectal cancer: from biology to clinical applications. Front Cell Dev Biol 2024; 12:1498032. [PMID: 39539964 PMCID: PMC11557528 DOI: 10.3389/fcell.2024.1498032] [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: 09/19/2024] [Accepted: 10/18/2024] [Indexed: 11/16/2024] Open
Abstract
This review delves into the pivotal role of circulating tumor cells (CTCs) in colorectal cancer (CRC) metastasis, focusing on their biological properties, interactions with the immune system, advanced detection techniques, and clinical implications. We explored how metastasis-competent CTCs evade immune surveillance and proliferate, utilizing cutting-edge detection and isolation technologies, such as microfluidic devices and immunological assays, to enhance sensitivity and specificity. The review highlights the significant impact of CTC interactions with immune cells on tumor progression and patient outcomes. It discusses the application of these findings in clinical settings, including non-invasive liquid biopsies for early diagnosis, prognosis, and treatment monitoring. Despite advancements, challenges remain, such as the need for standardized methods to consistently capture and analyze CTCs. Addressing these challenges through further molecular and cellular research on CTCs could lead to improved interventions and outcomes for CRC patients, underscoring the importance of unraveling the complex dynamics of CTCs in cancer progression.
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Affiliation(s)
- Claudia Dompé
- Department of Immunology, Poznan University of Medical Sciences, Poznan, Poland
- Doctoral School, Poznan University of Medical Sciences, Poznan, Poland
| | | | - Rodryg Ramlau
- Department of Oncology, Poznan University of Medical Sciences, Poznan, Poland
| | - Michal Nowicki
- Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, Poland
| | - Catherine Alix-Panabières
- Laboratory of Rare Human Circulating Cells and Liquid Biopsy (LCCRH), University Medical Centre of Montpellier, Montpellier, France
- Centre de Recherche en Ecologie et Evolution du Cancer, Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Contrôle, University of Montpellier, Centre National de la Recherche Scientifique, Institut de Recherche Pour le Dévelopement, Montpellier, France
- European Liquid Biopsy Society (ELBS), Hamburg, Germany
| | - Joanna Budna-Tukan
- Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, Poland
- Department of Anatomy and Histology, Collegium Medicum, University of Zielona Gora, Zielona Gora, Poland
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Lee TH, Kim JS, Baek SJ, Kwak JM, Kim J. Diagnostic Accuracy of Carcinoembryonic Antigen (CEA) in Detecting Colorectal Cancer Recurrence Depending on Its Preoperative Level. J Gastrointest Surg 2023; 27:1694-1701. [PMID: 37407895 DOI: 10.1007/s11605-023-05761-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 06/11/2023] [Indexed: 07/07/2023]
Abstract
BACKGROUND Serum carcinoembryonic antigen (CEA) increase in patients with colorectal cancer (CRC) recurrence was observed to vary depending on their initial values. This study aimed to evaluate the diagnostic accuracy of CEA for detecting CRC recurrence in patients with normal and elevated initial CEA levels. METHODS A total of 261 CRC recurrence patients who underwent curative resection were included and divided into two groups, normal and elevated initial CEA. Analysis was performed comparing patient, tumor, and recurrence characteristics retrospectively. RESULTS There were 192 patients with normal and 69 with high initial CEA levels. Patient and tumor characteristics were similar. Eighty-six patients had elevated CEA at the time of recurrence, and the overall sensitivity of CEA for recurrence was 33.0%. In the high initial CEA group, 59.4% exhibited increased CEA level at recurrence, whereas in patients with normal initial CEA levels, only 23.4% showed elevated levels (p < 0.001). Patients with both high CEA preoperatively and at recurrence had more local recurrence, but there was no statistical significance (p = 0.053), and the rate of lung metastasis was higher in patients whose CEA remained normal at recurrence (38.3% vs. 24.4%, p = 0.026). The overall survival of patients with elevated CEA at recurrence was worse than those with normal CEA levels (56.9% vs. 42.4%, p = 0.003). CONCLUSION The diagnostic accuracy of CEA for detecting recurrence depends on initial CEA level. Regardless of the initial CEA level, elevation at recurrence was significantly associated with overall survival in patients with recurrent CRC.
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Affiliation(s)
- Tae-Hoon Lee
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Ji-Seon Kim
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Se-Jin Baek
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea.
| | - Jung-Myun Kwak
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Jin Kim
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea
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Yokota M, Morikawa A, Matsuoka H, Muto J, Hashida K, Nagahisa Y, Masui T, Okabe M, Kitagawa H, Kawamoto K. Is frequent measurement of tumor markers beneficial for postoperative surveillance of colorectal cancer? Int J Colorectal Dis 2023; 38:75. [PMID: 36947196 DOI: 10.1007/s00384-023-04356-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2023] [Indexed: 03/23/2023]
Abstract
PURPOSE To determine whether frequent measurement of tumor markers triggers early detection of colorectal cancer recurrence. METHODS Of 1,651 consecutive patients undergoing colorectal cancer surgery between 2010 and 2016, 1,050 were included. CEA and CA 19-9 were considered to be postoperative tumor markers and were measured every 3 months for 3 years, and then every 6 months for 2 years. Sensitivity analysis of elevated CEA and CA19-9 levels and multivariate analysis of factors associated with elevated CEA and CA19-9 levels were performed. The proportion of triggers for detecting recurrence was determined. RESULTS The median follow-up period was 5.3 years. After applying the exclusion criteria, 1,050 patients were analyzed, 176 (16.8%) of whom were found to have recurrence. After excluding patients with persistently elevated CEA and CA19-9 levels before and after surgery from the 176 patients, 71 (43.6%) of 163 patients had elevated CEA levels and 35 (20.2%) of 173 patients had elevated CA19-9 levels. Sensitivity/positive predictive values for elevated CEA and CA19-9 levels at recurrence were 43.6%/32.3% and 20.2%/32.4%, respectively. Lymph node metastasis was a factor associated with both elevated CEA and CA19-9 levels at recurrence. Of the 176 patients, computed tomography triggered the detection of recurrence in 137 (78%) and elevated tumor marker levels in 13 (7%); the diagnostic lead interval in the latter 13 patients was 1.7 months. CONCLUSION Tumor marker measurements in surveillance after radical colorectal cancer resection contribute little to early detection, and frequent measurements are unnecessary for stage I patients with low risk of recurrence.
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Affiliation(s)
- Mitsuru Yokota
- Department of General Surgery, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan.
| | - Akitaka Morikawa
- Department of General Surgery, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan
| | - Hiroya Matsuoka
- Department of General Surgery, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan
| | - Jun Muto
- Department of General Surgery, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan
| | - Kazuki Hashida
- Department of General Surgery, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan
| | - Yoshio Nagahisa
- Department of General Surgery, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan
| | - Toshihiko Masui
- Department of General Surgery, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan
| | - Michio Okabe
- Department of General Surgery, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan
| | - Hirohisa Kitagawa
- Department of General Surgery, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan
| | - Kazuyuki Kawamoto
- Department of General Surgery, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan
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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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NCK-associated protein 1 regulates metastasis and is a novel prognostic marker for colorectal cancer. Cell Death Dis 2023; 9:7. [PMID: 36639705 PMCID: PMC9839720 DOI: 10.1038/s41420-023-01303-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/21/2022] [Accepted: 01/04/2023] [Indexed: 01/14/2023]
Abstract
Metastatic colorectal cancer (CRC) remains a substantial problem for mortality and requires screening and early detection efforts to increase survival. Epithelial-mesenchymal transition (EMT) and circulation of tumor cells in the blood play important roles in metastasis. To identify a novel target for metastasis of CRC, we conducted a gene microarray analysis using extracted RNA from the blood of preclinical models. We found that NCK-associated protein 1 (NCKAP1) was significantly increased in the blood RNA of patient-derived xenograft (PDX) models of colon cancer. In the NCKAP1 gene knockdown-induced human colon cancer cell lines HCT116 and HT29, there was a reduced wound healing area and significant inhibition of migration and invasion. As the result of marker screening for cytoskeleton and cellular interactions, CRC treated with siRNA of NCKAP1 exhibited significant induction of CDH1 and phalloidin expression, which indicates enhanced adherent cell junctions and cytoskeleton. In HCT116 cells with a mesenchymal state induced by TGFβ1, metastasis was inhibited by NCKAP1 gene knockdown through the inhibition of migration, and there was increased CTNNB1 expression and decreased FN expression. We established metastasis models for colon cancer to liver transition by intrasplenic injection shRNA of NCKAP1-transfected HCT116 cells or by implanting tumor tissue generated with the cells on cecal pouch. In metastasis xenograft models, tumor growth and liver metastasis were markedly reduced. Taken together, these data demonstrate that NCKAP1 is a novel gene regulating EMT that can contribute to developing a diagnostic marker for the progression of metastasis and new therapeutics for metastatic CRC treatment.
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Lindgren M, Rask G, Jonsson J, Berglund A, Lundin C, Jonsson P, Ljuslinder I, Nyström H. Type IV Collagen in Human Colorectal Liver Metastases—Cellular Origin and a Circulating Biomarker. Cancers (Basel) 2022; 14:cancers14143396. [PMID: 35884455 PMCID: PMC9325127 DOI: 10.3390/cancers14143396] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/30/2022] [Accepted: 07/11/2022] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Patients with colorectal liver metastases (CLM) can be cured through surgery if metastases are detected early in disease progression. Today, CLM diagnosis relies heavily on diagnostic imaging, and cheap, non-invasive, and efficiently measurable biomarkers are needed. Circulating type IV collagen (COL IV) is a potential biomarker for detecting CLM. Patients with CLM show elevated circulating levels of COL IV and increased tissue expression of COL IV in CLM tissue, which could result from enhanced production and degradation of COL IV. This study aimed to establish the cellular source behind enhanced COL IV levels, which is helpful in the evaluation of the biomarker potential of COL IV. We show that fibroblasts express COL IV both in vitro and in the stromal tissue of CLM. We also found that CLM tissue expresses COL IV-degrading proteases. Lastly, CLM patients have higher circulating COL IV levels than healthy controls. Abstract Circulating type IV collagen (cCOL IV) is a potential biomarker for patients with colorectal liver metastases (CLM) who present with elevated levels of COL IV in both CLM tissue and circulation. This study aimed to establish the cellular origin of elevated levels of COL IV and analyze circulating COL IV in CLM patients. The cellular source was established through in situ hybridization, immunohistochemical staining, and morphological evaluation. Cellular expression in vitro was assessed by immunofluorescence. Tissue expression of COL IV-degrading matrix metalloproteinases (MMPs)-2, -7, -9, and -13 was studied with immunohistochemical staining. Plasma levels of COL IV in CLM patients and healthy controls were analyzed with ELISA. This study shows that cancer-associated fibroblasts (CAFs) express COL IV in the stroma of CLM and that COL IV is expressed in vitro by fibroblasts but not by tumor cells. MMP-2, -7, -9, and -13 are expressed in CLM tissue, mainly by hepatocytes and immune cells, and circulating COL IV is significantly elevated in CLM patients compared with healthy controls. Our study shows that stromal cells, not tumor cells, produce COL IV in CLM, and that circulating COL IV is elevated in patients with CLM.
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Affiliation(s)
- Moa Lindgren
- Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden; (G.R.); (J.J.); (A.B.); (C.L.); (H.N.)
- Correspondence:
| | - Gunilla Rask
- Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden; (G.R.); (J.J.); (A.B.); (C.L.); (H.N.)
- Department of Medical Biosciences/Pathology, Umeå University, SE-901 87 Umeå, Sweden
| | - Josefin Jonsson
- Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden; (G.R.); (J.J.); (A.B.); (C.L.); (H.N.)
| | - Anette Berglund
- Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden; (G.R.); (J.J.); (A.B.); (C.L.); (H.N.)
| | - Christina Lundin
- Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden; (G.R.); (J.J.); (A.B.); (C.L.); (H.N.)
| | - Pär Jonsson
- Department of Chemistry, Umeå University, SE-907 36 Umeå, Sweden;
| | - Ingrid Ljuslinder
- Department of Radiation Sciences/Oncology, Umeå University, SE-901 87 Umeå, Sweden;
| | - Hanna Nyström
- Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden; (G.R.); (J.J.); (A.B.); (C.L.); (H.N.)
- Wallenberg Centre for Molecular Medicine, Umeå University, SE-901 87 Umeå, Sweden
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Mahmoud NN. Colorectal Cancer. Surg Oncol Clin N Am 2022; 31:127-141. [DOI: 10.1016/j.soc.2021.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Fenqi D, Yupeng L, Qiuju Z, Chao Y, Wenjie S, Tianyi X, Junnan G, Weinan X, Xiufeng J, Junge B, Chenyang J, Hua X, Yien L, Xuefeng B, Yanlong L. Early Postoperative Serum Carcinoembryonic Antigen Is a Stronger Independent Prognostic Factor for Stage II Colorectal Cancer Patients Than T4 Stage and Preoperative CEA. Front Oncol 2022; 11:758509. [PMID: 35087748 PMCID: PMC8786716 DOI: 10.3389/fonc.2021.758509] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 12/20/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Serum carcinoembryonic antigen (CEA) is an important biomarker for diagnosis, prognosis, recurrence, metastasis monitoring, and the evaluation of the effect of chemotherapy in colorectal cancer (CRC). However, few studies have focused on the role of early postoperative CEA in the prognosis of stage II CRC. METHODS Patients with stage II CRC diagnosed between January 2007 and December 2015 were included. Receiver operating characteristic (ROC) curves were used to obtain the cutoff value of early postoperative CEA, CEA ratio and CEA absolute value. The areas under curves (AUCs) were used to estimate the predictive abilities of the CEA and T stage. The stepwise regression method was used to screen the factors included in the Cox regression analysis. Before and after propensity score (PS) - adjusted Cox regression and sensitivity analysis were used to identify the relationship between early postoperative CEA and prognosis. Meta-analysis was performed to verify the results. Kaplan-Meier survival curves were used to estimate the effects of CEA on prognosis. RESULTS We included 1081 eligible patients. ROC curves suggested that the cutoff value of early postoperative CEA was 3.66 ng/ml (P <0.001) and the AUC showed early postoperative CEA was the most significant prognostic marker in stage II CRC (P = 0.0189). The Cox regression and sensitivity analysis before and after adjusting for PS both revealed elevated early postoperative CEA was the strongest independent prognostic factor of OS, DFS, and CSS (P < 0.001). Survival analysis revealed that patients with elevated early postoperative CEA had lower OS (53.62% VS 84.16%), DFS (50.03% VS 86.75%), and CSS (61.77% VS 90.30%) than patients with normal early postoperative CEA (P < 0.001). When the postoperative CEA was positive, the preoperative CEA level showed no significant effect on the patient's prognosis (all P-values were > 0.05). Patients with a CEA ratio ≤0.55 or CEA absolute value ≤-0.98 had a worse prognosis (all P-values were < 0.001). Survival analysis suggested that adjuvant chemotherapy for stage II CRC patients with elevated early postoperative CEA may improve the CSS (P = 0.040). CONCLUSIONS Early postoperative CEA was a better biomarker for prognosis of stage II CRC patients than T stage and preoperative CEA, and has the potential to become a high-risk factor to guide the prognosis and treatment of stage II CRC patients.
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Affiliation(s)
- Du Fenqi
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Liu Yupeng
- Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China
| | - Zhang Qiuju
- Department of Biostatistics, Public Health School of Harbin Medical University, Harbin, China
| | - Yuan Chao
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Song Wenjie
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xia Tianyi
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Guo Junnan
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xue Weinan
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jiang Xiufeng
- Department of Anus and Intestine Surgery, The First Hospital of Qiqihar, Qiqihar, China
| | - Bai Junge
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jia Chenyang
- Department of Epidemiology, Public Health School of Harbin Medical University, Harbin, China
| | - Xi Hua
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Li Yien
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Bai Xuefeng
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Liu Yanlong
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
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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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Mizuno H, Miyake H, Nagai H, Yoshioka Y, Shibata K, Asai S, Takamizawa J, Yuasa N. Optimal cutoff value of preoperative CEA and CA19-9 for prognostic significance in patients with stage II/III colon cancer. Langenbecks Arch Surg 2021; 406:1987-1997. [PMID: 34148158 DOI: 10.1007/s00423-021-02236-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 06/08/2021] [Indexed: 12/15/2022]
Abstract
PURPOSE This unicentric, retrospective cohort study aimed to identify the optimal cutoff values of preoperative serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) for the prognosis in patients with stage II/III colon cancer. METHODS After excluding 43 patients with CA19-9 levels < 0.2 U/mL, 588 were included. Receiver operating characteristic curves were constructed to determine the optimal cutoff values of CEA and CA 19-9 for disease relapse. RESULTS The median CEA and CA19-9 values were 3.6 (interquartile range: 2.1-7.2 ng/mL) and 14.3 (interquartile range: 8.1-30.0) U/mL, respectively. The optimal cutoff values of CEA and CA19-9 were 5.4 ng/mL and 22.4 U/mL, respectively. A multivariate analysis of relapse-free survival (RFS) showed that cancer stage, CEA, and CA19-9 were significant independent factors. The RFS of patients with stages II and III colon cancer was significantly stratified by CEA (< 5.4/ ≥ 5.4 ng/mL) and CA19-9 (< 22.4/ ≥ 22.4 U/mL). Prognostication based on the reference values (< 5.0 ng/mL for CEA and < 37.0 U/mL for CA19-9) was less significant than that based on the optimal cutoff values. Both elevated CEA and CA19-9 had no value dependency on RFS: RFS curves were similar between extremely elevated CEA (≥ 54.0 ng/ml) and intermediate CEA (5.4-54.0 ng/ml) and between extremely elevated CA19-9 (≥ 224.0 U/ml) and intermediate CA19-9 (22.4-224.0 U/ml). CONCLUSION The optimal cutoff values of preoperative CEA and CA19-9 for RFS were 5.4 ng/ml and 22.4 U/mL, respectively, in patients with stages II and III colon cancer. Further relapse risk stratification is possible using these values.
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Affiliation(s)
- Hironori Mizuno
- Department of Gastrointestinal Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan
| | - Hideo Miyake
- Department of Gastrointestinal Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan
| | - Hidemasa Nagai
- Department of Gastrointestinal Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan
| | - Yuichiro Yoshioka
- Department of Gastrointestinal Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan
| | - Koji Shibata
- Department of Gastrointestinal Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan
| | - Soichiro Asai
- Department of Gastrointestinal Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan
| | - Junichi Takamizawa
- Department of Laboratory Medicine, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan
| | - Norihiro Yuasa
- Department of Gastrointestinal Surgery, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan. .,Department of Laboratory Medicine, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan.
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13
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Ramphal W, Boeding JR, van Iwaarden M, Schreinemakers JM, Rutten HJ, Crolla RM, Gobardhan PD. Serum carcinoembryonic antigen to predict recurrence in the follow-up of patients with colorectal cancer. Int J Biol Markers 2019; 34:60-68. [DOI: 10.1177/1724600818820679] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Introduction: Serum carcinoembryonic (CEA) antigen is used as a diagnostic screening tool during follow-up in colorectal cancer patients. However, it remains unclear whether preoperative serum CEA is a reliable marker in the follow-up to predict recurrence. The aim of the study is to determine the value of elevated pre- and postoperative serum carcinoembryonic antigen levels (CEA > 5 µg/L) as an independent prognostic factor for locoregional and distant recurrence in patients who underwent curative surgery for colorectal cancer. Methods: This single center retrospective observational cohort study includes patients who underwent curative surgery for colorectal cancer between 2005 and 2015 and had pre- and postoperative serum CEA measurements. Five-year disease-free survival and multivariate Cox regression analyses were performed to adjust for confounding factors. Results: Preoperative serum CEA level was measured in 2093 patients with colorectal cancer. No significant association was found between an elevated preoperative serum CEA and locoregional recurrence (adjusted hazard ratio (HR) 1.29 (95% confidence interval (CI) 0.91, 1.84; P=0.26)). However, a significant association was found between an elevated preoperative serum CEA and systemic recurrence (adjusted HR 1.58 (95% CI 1.25, 2.00; P<0.01)]. The five-year disease-free survival was lower in patients with elevated preoperative serum CEA levels ( P<0.01). Postoperative serum CEA level was the most sensitive for hepatic metastases during follow-up (73.3%). Conclusions: The preoperative serum CEA level is an independent prognostic factor for systemic metastasis after curative surgery for colorectal cancer in patients with stage I–III disease. The level is the most sensitive for hepatic metastasis compared to metastasis to other anatomic sites.
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Affiliation(s)
- Winesh Ramphal
- Department of Surgery Amphia Hospital 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
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Reece MM, Chapuis PH, Keshava A, Stewart P, Suen M, Rickard MJFX. When does curatively treated colorectal cancer recur? An Australian perspective. ANZ J Surg 2018; 88:1163-1167. [DOI: 10.1111/ans.14870] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Accepted: 08/07/2018] [Indexed: 12/13/2022]
Affiliation(s)
- Mifanwy M. Reece
- Department of Colorectal Surgery; Concord Repatriation General Hospital; Sydney New South Wales Australia
| | - Pierre H. Chapuis
- Department of Colorectal Surgery; Concord Repatriation General Hospital; Sydney New South Wales Australia
- Discipline of Surgery, Sydney Medical School; The University of Sydney; Sydney New South Wales Australia
| | - Anil Keshava
- Department of Colorectal Surgery; Concord Repatriation General Hospital; Sydney New South Wales Australia
- Discipline of Surgery, Sydney Medical School; The University of Sydney; Sydney New South Wales Australia
| | - Peter Stewart
- Department of Colorectal Surgery; Concord Repatriation General Hospital; Sydney New South Wales Australia
| | - Michael Suen
- Department of Colorectal Surgery; Concord Repatriation General Hospital; Sydney New South Wales Australia
| | - Matthew J. F. X. Rickard
- Department of Colorectal Surgery; Concord Repatriation General Hospital; Sydney New South Wales Australia
- Discipline of Surgery, Sydney Medical School; The University of Sydney; Sydney New South Wales Australia
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Tobaruela E, Enriquez JM, Diez M, Camunas J, Muguerza J, Granell J. Evaluation of Serum Carcinoembryonic Antigen Monitoring in the follow-up of Colorectal Cancer Patients with Metastatic Lymph Nodes and a Normal Preoperative Serum Level. Int J Biol Markers 2018; 12:18-21. [PMID: 9176713 DOI: 10.1177/172460089701200104] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The value of serial serum carcinoembryonic antigen (CEA) assay in the follow-up of colorectal cancer patients with metastatic lymph nodes and normal (≤ 5 ng/ml) preoperative CEA levels, was examined in this study. Thirty-eight patients were studied and compared with 22 patients with elevated CEA levels. The overall sensitivity of CEA for the diagnosis of recurrence was 36%. Postoperative CEA was strongly influenced by the site of recurrence. CEA monitoring showed the best results in patients who developed hepatic metastases (sensitivity 60%, specificity 94%, positive predictive value 60%, and negative predictive value 94%), and was ineffective for the detection of locoregional or pulmonary metastases. The results indicate that elevation of CEA in the postoperative course of these patients is an indicator of the presence of hepatic metastases. Postoperative CEA monitoring should not be omitted in Dukes C patients with normal preoperative levels, and is more reliable for the detection of liver metastases.
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Affiliation(s)
- E Tobaruela
- Department of General Surgery, Principe de Asturias University Hospital, Alcalá de Henares, Madrid, Spain
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Carcinoembryonic antigen testing after curative liver resection for synchronous liver metastasis of colorectal cancer: a Japanese multicenter analysis. Surg Today 2017; 47:1223-1229. [PMID: 28439715 DOI: 10.1007/s00595-017-1530-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2016] [Accepted: 02/11/2017] [Indexed: 12/18/2022]
Abstract
PURPOSE To identify the possible roles of carcinoembryonic antigen (CEA) testing after liver resection for synchronous colorectal liver metastasis (CLM). METHODS The subjects of this retrospective study were patients who underwent complete resection of primary tumors and synchronous CLM between 1997 and 2007 at 20 institutions in Japan. We studied the associations between perioperative CEA levels and the characteristics of recurrence. RESULTS Recurrence was detected during the median follow-up time of 52 months in 445 (73.7%) of the total 604 patients analyzed. A postoperative CEA level >5 ng/ml was an independent predictor, with the highest hazard ratio (2.25, 95% confidence interval 1.29-3.91, P = 0.004). A postoperative CEA level >5 ng/ml had a specificity of 86.2% and a positive predictive value of 84.2% for recurrence. Patients with a high postoperative CEA level had a significantly higher recurrence rate, with a shorter time until recurrence and a higher frequency of multiple metastatic sites than those with a low postoperative CEA level. Among the patients with recurrence, 173 (52.7%) had an elevated CEA level (>5 ng/ml) when recurrence was detected. CONCLUSIONS A postoperative CEA level >5 ng/ml was an independent predictor of recurrence; however, CEA testing was not a reliable surveillance tool to identity recurrence after liver resection.
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17
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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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van der Sluis FJ, Zhan Z, Verberne CJ, Muller Kobold AC, Wiggers T, de Bock GH. Predictive performance of TPA testing for recurrent disease during follow-up after curative intent surgery for colorectal carcinoma. Clin Chem Lab Med 2017; 55:269-274. [PMID: 27522097 DOI: 10.1515/cclm-2016-0207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2016] [Accepted: 07/14/2016] [Indexed: 11/15/2022]
Abstract
BACKGROUND The aim of the present study was to investigate the predictive performance of serial tissue polypeptide antigen (TPA) testing after curative intent resection for detection of recurrence of colorectal malignancy. METHODS Serum samples were obtained in 572 patients from three different hospitals during follow-up after surgery. Test characteristics of serial TPA testing were assessed using a cut-off value of 75 U/L. The relation with American Joint Committee on Cancer stage and the potential additive value of tissue polypeptide antigen testing upon standard carcinoembryonic antigen (CEA) testing were investigated. RESULTS The area under the receiver operating characteristic curve of TPA for recurrent disease was 0.70, indicating marginal usefulness as a predictive test. Forty percent of cases that were detected by CEA testing would have been missed by TPA testing alone, whilst most cases missed by CEA were also not detected by TPA testing. In the subpopulation of patients with stage III disease predictive performance was good (area under the curve 0.92 within 30 days of diagnosing recurrent disease). In this group of patients, 86% of cases that were detected by CEA were also detected by TPA. CONCLUSIONS Overall, TPA is a relatively poor predictor for recurrent disease during follow-up. When looking at the specific subpopulation of patients with stage III disease predictive performance of TPA was good. However, TPA testing was not found to be superior to CEA testing in this specific subpopulation.
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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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Chang YT, Huang MY, Yeh YS, Huang CW, Tsai HL, Cheng TL, Wang JY. A Prospective Study of Comparing Multi-Gene Biomarker Chip and Serum Carcinoembryonic Antigen in the Postoperative Surveillance for Patients with Stage I-III Colorectal Cancer. PLoS One 2016; 11:e0163264. [PMID: 27701415 PMCID: PMC5049757 DOI: 10.1371/journal.pone.0163264] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 09/05/2016] [Indexed: 01/08/2023] Open
Abstract
Background Circulating biomarkers can predict clinical outcomes in colorectal cancer patients. The aim of the study was to evaluate the feasibility of our multigene biomarker chip for detecting circulating tumor cells for postoperative surveillance of stage I–III colorectal cancer patients. Materials and Methods In total, 298 stage I–III colorectal cancer patients were analyzed after curative resection between June 2010 and October 2014. During each follow-up, a postoperative surveillance strategy, including ESMO Guidelines Working Group recommendations and the biochip, was used. Results After a 28.4-month median follow-up, 48 (16.1%) patients had postoperative relapse. Univariate analysis revealed that the postoperative relapse risk factors were rectal tumor, perineural invasion, elevated preoperative and postoperative serum carcinoembryonic antigen levels, and positive biochip results (all P < 0.05). Multivariate analyses revealed that postoperative relapse correlated significantly with elevated postoperative serum carcinoembryonic antigen levels (odds ratio = 4.136, P = 0.008) and positive biochip results (odds ratio = 66.878, P < 0.001). However, the sensitivity (P = 0.003), specificity (P = 0.003), positive (P = 0.002) and negative (P = 0.006) predictive values, and accuracy (P < 0.001) of the biochip for predicting postoperative relapse were significantly higher than those of elevated postoperative serum carcinoembryonic antigen levels. Moreover, the median lead time between positive biochip result and postoperative relapse detection was significantly earlier than that between elevated postoperative serum carcinoembryonic antigen level and postoperative relapse detection (10.7 vs. 2.8 months, P < 0.001). Furthermore, positive biochip results correlated strongly with lower disease-free survival and overall survival of colorectal cancer patients (both P < 0.001). Conclusion Compared with conventional serum carcinoembryonic antigen detection, our multigene chip aided more accurate and earlier prediction of postoperative relapse during stage I–III colorectal cancer patient surveillance. In clinical practice, this biochip may facilitate early postoperative relapse diagnosis in colorectal cancer patients.
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Affiliation(s)
- Yu-Tang Chang
- Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Pediatric Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yii Huang
- Department of Radiation Oncology, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yung-Sung Yeh
- Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Trauma and Critical Care, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Wen Huang
- Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsiang-Lin Tsai
- Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of General Surgery Medicine, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Tian-Lu Cheng
- Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jaw-Yuan Wang
- Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Research Center for Environment Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- * E-mail:
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Yang KM, Park IJ, Kim CW, Roh SA, Cho DH, Kim JC. The prognostic significance and treatment modality for elevated pre- and postoperative serum CEA in colorectal cancer patients. Ann Surg Treat Res 2016; 91:165-171. [PMID: 27757393 PMCID: PMC5064226 DOI: 10.4174/astr.2016.91.4.165] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 04/29/2016] [Accepted: 05/16/2016] [Indexed: 01/21/2023] Open
Abstract
Purpose The purpose of this study was to evaluate the prognostic significance of serum CEA (s-CEA) changes in colorectal cancer (CRC) patients with sustained elevated postoperative s-CEA levels. Methods Between January 1999 and December 2008, 9,380 CRC patients underwent surgery. Curative resection was performed in 1,242 CRC patients with high preoperative s-CEA levels (>6 ng/mL). High s-CEA levels were normalized in 924 patients (74.4%) within 2 weeks from surgery, whereas high s-CEA levels were persistent in 318 patients (25.6%). Patients were divided into 2 groups according to their postoperative s-CEA levels: group 1 (37 patients with a 1-year postoperative s-CEA>6 ng/mL) and group 2 (281 patients with a 1-year postoperative s-CEA≤6 ng/mL). Results A postoperative recurrence was identified in 24 patients (64.9%) in group 1 and 65 patients (23.1%) in group 2 (P < 0.001). A curative resection after recurrence was performed in 22 patients (33.8%) from group 2, but no patients from group 1 (P = 0.001). The 5-year overall survival and time to recurrence were significantly lower in patients with recurrent cancer in group 1 (P < 0.001). Conclusion Patients with persistent elevated postoperative s-CEA levels are at high risk for recurrence and a low survival rate. More intensive surveillance of patients with high postoperative s-CEA levels should be mandatory.
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Affiliation(s)
- Kwan Mo Yang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In Ja Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chan Wook Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.; Institute of Innovative Cancer Research, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
| | - Seon Ae Roh
- Institute of Innovative Cancer Research, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
| | - Dong-Hyung Cho
- Institute of Innovative Cancer Research, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.; Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea
| | - Jin Cheon Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.; Institute of Innovative Cancer Research, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
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Huang MY, Tsai HL, Huang JJ, Wang JY. Clinical Implications and Future Perspectives of Circulating Tumor Cells and Biomarkers in Clinical Outcomes of Colorectal Cancer. Transl Oncol 2016; 9:340-7. [PMID: 27567958 PMCID: PMC5006809 DOI: 10.1016/j.tranon.2016.06.006] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2016] [Revised: 06/30/2016] [Accepted: 06/30/2016] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a major public health problem. Early CRC detection, pretherapeutic responsiveness prediction, and postoperative micrometastasis monitoring are the hallmarks for successful CRC treatment. Here, the methodologies used for detecting circulating tumor cells (CTCs) from CRC are reviewed. In addition to the traditional CRC biomarkers, the persistent presence of posttherapeutic CTCs indicates resistance to adjuvant chemotherapy and/or radiotherapy; hence, CTCs also play a decisive role in the subsequent relapse of CRC. Moreover, the genetic and phenotypic profiling of CTCs often differs from that of the primary tumor; this difference can be used to select the most effective targeted therapy. Consequently, studying CTCs can potentially individualize treatment strategies for patients with CRC. Therefore, CTC detection and characterization may be valuable tools for refining prognosis, and CTCs can be used in a real-time tumor biopsy for designing individually tailored therapy against CRC.
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Affiliation(s)
- Ming-Yii Huang
- Department of Radiation Oncology, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Center for Biomarkers and Biotech Drugs, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Hsiang-Lin Tsai
- Division of General Surgery Medicine, Department of Surgery, Kaohsiung Medical University, Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University, Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Joh-Jong Huang
- Department of Family Medicine and Department of Community Medicine, Kaohsiung Medical University, Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
| | - Jaw-Yuan Wang
- Center for Biomarkers and Biotech Drugs, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University, Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Graduate Institute of Clinical Medicine, Department of Surgery, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
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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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24
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Sørensen CG, Karlsson WK, Pommergaard HC, Burcharth J, Rosenberg J. The diagnostic accuracy of carcinoembryonic antigen to detect colorectal cancer recurrence - A systematic review. Int J Surg 2015; 25:134-44. [PMID: 26700203 DOI: 10.1016/j.ijsu.2015.11.065] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 11/29/2015] [Indexed: 01/15/2023]
Abstract
INTRODUCTION Carcinoembryonic Antigen (CEA) has been used as a tumor marker in the follow-up of colorectal cancer for more than 40 years. Controversy exists regarding its diagnostic applicability due to a relatively low sensitivity and a questionable effect on mortality. The aim of this review was to assess the diagnostic accuracy of CEA in detecting recurrence after intended curative surgery for primary colorectal cancer. METHODS Systematic literature searches were performed in PubMed, EMBASE and Cochrane databases, and articles were chosen based on predefined inclusion criteria. Reference lists from included articles were manually searched for additional publications of relevance. RESULTS Forty-two original studies with generally representative populations and long follow-up were included. Data were reported on outcomes from 9,834 CEA tests during follow-up. Reporting on the reference standards used was not optimal. Sensitivity of CEA ranged from 17.4 % to 100 %, specificity ranged from 66.1 % to 98.4 %, positive predictive value ranged from 45.8 % to 95.2% and negative predictive value ranged from 74.5 % to 100 %. CONCLUSION Results point toward a sensitivity of CEA ranging between 50 % and 80 %, and a specificity and negative predictive value above 80 %. Results on positive predictive value showed low reliability. Overall, CEA did not effectively detect treatable recurrences at an early stage, and a clinically relevant effect on patient mortality remains to be proven.
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Affiliation(s)
- Caspar G Sørensen
- Faculty of Health Sciences - University of Copenhagen, Blegdamsvej 3 - 2200 København N, Denmark.
| | - William K Karlsson
- Faculty of Health Sciences - University of Copenhagen, Blegdamsvej 3 - 2200 København N, Denmark
| | - Hans-Christian Pommergaard
- Hvidovre Hospital - University of Copenhagen, Department of Surgery, Kettegård Alle 30 - 2650 Hvidovre, Denmark
| | - Jakob Burcharth
- Herlev Hospital - University of Copenhagen, Centre for Perioperative Optimization, Department of Surgery, Herlev Ringvej 75 - 2730 Herlev, Denmark
| | - Jacob Rosenberg
- Herlev Hospital - University of Copenhagen, Centre for Perioperative Optimization, Department of Surgery, Herlev Ringvej 75 - 2730 Herlev, Denmark
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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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Survival in Resected Stage II Colorectal Cancer Is Dependent on Tumor Depth, Vascular Invasion, Postoperative CEA Level, and The Number of Examined Lymph Nodes. World J Surg 2015; 40:1002-9. [PMID: 26560149 DOI: 10.1007/s00268-015-3331-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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27
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Liu GC, Zhang X, Xie E, An X, Cai PQ, Zhu Y, Tang JH, Kong LH, Lin JZ, Pan ZZ, Ding PR. The Value of Restaging With Chest and Abdominal CT/MRI Scan After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer. Medicine (Baltimore) 2015; 94:e2074. [PMID: 26632714 PMCID: PMC5058983 DOI: 10.1097/md.0000000000002074] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Little was known with regard to the value of preoperative systemic restaging for patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT). This study was designed to evaluate the role of chest and abdominal computed tomography (CT) scan or magnetic resonance imaging (MRI) on preoperative restaging in LARC after neoadjuvant CRT and to assess the impact on treatment strategy.Between January 2007 and April 2013, 386 newly diagnosed consecutive patients with LARC who underwent neoadjuvant CRT and received restaging with chest and abdominal CT/MRI scan were included. Imaging results before and after CRT were analyzed.Twelve patients (3.1%) (6 liver lesions, 2 peritoneal lesions, 2 distant lymph node lesions, 1 lung lesions, 1 liver and lung lesions) were diagnosed as suspicious metastases on the restaging scan after radiotherapy. Seven patients (1.8%) were confirmed as metastases by pathology or long-term follow-up. The treatment strategy was changed in 5 of the 12 patients as a result of restaging CT/MRI findings. Another 10 patients (2.6%) who present with normal restaging imaging findings were diagnosed as metastases intra-operatively. The sensitivity, specificity accuracy, negative predictive value, and positive predictive values of restaging CT/MRI was 41.4%, 98.6%, 58.3%, and 97.3%, respectively.The low incidence of metastases and minimal consequences for the treatment plan question the clinical value of routine restaging of chest and abdomen after neoadjuvant CRT. Based on this study, a routine restaging CT/MRI of chest and abdomen in patients with rectal cancer after neoadjuvant CRT is not advocated, carcino-embryonic antigen (CEA) -guided CT/MRI restaging might be an alternative.
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Affiliation(s)
- Guo-Chen Liu
- From the State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine (G-CL, XZ, EX, XA, P-QC, YZ, J-HT, L-HK, J-ZL, Z-ZP, P-RD); Departments of Colorectal Surgery, Sun Yat-sen University Cancer Center (G-CL, YZ, J-HT, L-HK, J-ZL, Z-ZP, P-RD); Departments of Thoracic Surgery, Sun Yat-sen University Cancer Center (XZ); Departments of Medical Oncology, Sun Yat-sen University Cancer Center (XA); Departments of Medical Imaging & Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China (P-QC); and Departments of Gastrointestinal Surgery, Shantou Central Hospital, Shantou, P. R. China (EX)
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Marks EI, Brennan M, El-Deiry WS. Correlation of CEA but not CA 19-9 as serum biomarkers of disease activity in a case of metastatic rectal adenocarcinoma. Cancer Biol Ther 2015; 16:1136-9. [PMID: 26047368 DOI: 10.1080/15384047.2015.1057360] [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: 10/23/2022] Open
Abstract
We present the case of a 62-year-old-man with moderately differentiated adenocarcinoma of the rectum. This patient underwent neoadjuvant chemoradiation and surgical resection followed by adjuvant chemotherapy. After completing therapy, this patient had 2 instances of CEA elevation, both of which preceded the discovery of recurrent disease. While on treatment for these recurrences, CA 19-9 increased rapidly to 4,405. This CA 19-9 elevation persisted for approximately 4 months in the absence of clinical, radiographic or additional serologic evidence of progressive disease before returning to baseline. Shortly after this tumor marker normalized, a small area of locally recurrent disease was discovered. This case highlights the utility and pitfalls of colorectal cancer disease monitoring with CEA and CA 19-9. The differential diagnosis of CA 19-9 elevation is discussed in this report.
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Affiliation(s)
- Eric I Marks
- a Pennsylvania State College of Medicine ; Pennsylvania State Hershey Cancer Institute ; Hershey , PA USA
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29
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Bhatti I, Patel M, Dennison AR, Thomas MW, Garcea G. Utility of postoperative CEA for surveillance of recurrence after resection of primary colorectal cancer. Int J Surg 2015; 16:123-128. [PMID: 25771102 DOI: 10.1016/j.ijsu.2015.03.002] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2014] [Revised: 02/15/2015] [Accepted: 03/01/2015] [Indexed: 12/16/2022]
Abstract
INTRODUCTION To evaluate the usefulness of postoperative CEA levels in the surveillance of colorectal cancer patients. METHODS Over a 56 month period a total of 569 patients with measured CEA levels underwent curative resection for colorectal cancer. The median follow up was 40 months, during which period recurrence occurred in 149. Serum CEA levels were measured at 6 monthly intervals starting from 3 months post resection. ROC was used to calculate the optimum cut-off of CEA (5 ng/ml). RESULTS Postoperative elevation of CEA levels were more frequent in patients with an aggressive primary colorectal cancer (grade, T stage and nodal disease; p < 0.05). In patients found to have colorectal recurrence, a significantly higher proportion of patients were resectable in the group with a non-elevated CEA (diagnosed by CT with PET imaging p < 0.05). The median interval between CEA elevation and diagnosis of recurrence (diagnostic interval) was 4 weeks. CEA elevation led to a change in the routine surveillance program by bringing imaging forward by 2 months. CEA levels were a significant predictor of survival following resection of colorectal primary (CEA ≤5-38 months, CEA >5-27 months; p < 0.05). CEA (p < 0.05) retained its significance on multivariate analysis along with the T stage (p < 0.05). CONCLUSION CEA is a predictor of recurrence, resectability and survival following resection of colorectal cancer. Furthermore, an elevated CEA has a short diagnostic interval (4 weeks) for detecting recurrent disease and therefore should mandate adjustment of the routine surveillance program with the next planned imaging being brought forward (2 months).
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Affiliation(s)
- Imran Bhatti
- Department of Surgery, Leicester General Hospital, Leicester, UK.
| | - Meera Patel
- Department of Surgery, Leicester General Hospital, Leicester, UK
| | | | - Michael W Thomas
- Department of Surgery, Leicester General Hospital, Leicester, UK
| | - Giuseppe Garcea
- Department of Surgery, Leicester General Hospital, Leicester, UK
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30
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Post-Resection Surveillance in GI Cancers. Indian J Surg 2014; 76:382-91. [PMID: 26396472 PMCID: PMC4571523 DOI: 10.1007/s12262-013-0943-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Accepted: 06/21/2013] [Indexed: 10/26/2022] Open
Abstract
Recurrence after curative resection of gastrointestinal (GI) cancers is common. Early detection of resectable recurrences may result in a curative resection. In un-resectable recurrences, early detection may improve the quality of life by palliation or with the use of newer chemotherapeutic drugs. The guidelines regarding follow-up of patients after curative resection of GI cancers are from the West which is very different from the Indian population in terms of a disease pattern and social milieu. The guidelines which are commonly used are also not strictly followed. We have proposed in this article the protocols which we follow at our centre after curative resection of GI cancer and how these are different from the guidelines proposed by the West.
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31
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Caglar M, Yener C, Karabulut E. Value of CT, FDG PET-CT and serum tumor markers in staging recurrent colorectal cancer. Int J Comput Assist Radiol Surg 2014; 10:993-1002. [PMID: 25213271 DOI: 10.1007/s11548-014-1115-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2014] [Accepted: 08/22/2014] [Indexed: 12/18/2022]
Abstract
BACKGROUND Serum tumor markers and computed tomography (CT) are the most widely accepted monitoring tools for the follow-up patients with colorectal cancer (CRC). Positron emission tomography (PET) with 18[F]-fluorodeoxyglucose (FDG) is a promising modality for the evaluation of recurrent CRC. The purpose of this study was to (1) investigate the sensitivity and specificity of serum tumor marker assay, CT and FDG PET-CT, (2) determine the correlation of these markers with FDG PET-CT quantitative indices such as maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients suspected to have recurrent CRC. PATIENTS FDG PET-CT imaging was performed in 212 patients with possible CRC recurrence. A retrospective study was performed on patients with (1) a history of CRC with complete remission after treatment, (2) pathology of adenocarcinoma and (3) increase in cancer antigen 19-9 (CA 19-9) and/or carcinoembryonic antigen (CEA) or suspicious radiological evaluation during follow-up after complete remission. METHODS All patients underwent integrated FDG PET-CT scan. Serum tumor markers were obtained within 3 months of PET-CT. All enrolled cases showed increase in a tumor marker over the reference value on at least two serial measurements or abnormal CT scan before PET-CT was performed. Results were compared with histopathological findings or clinical follow-up. RESULTS Following exclusion of 57 patients with missing data or lost to follow-up, 155 patients (87 men, mean age: 61 years) remained for final analysis. Serum CEA and CA 19-9 had a sensitivity of 74 and 35% and specificity of 86 and 83% for the detection recurrent CRC, respectively. The sensitivities of CT and FDG PET-CT were 79 and 92% and specificities were 45 and 100%, respectively. At an adaptive threshold of 42%, the median SUVmax, SUVmean, MTV and TLG of these lesions were 8.8, 5.2, 11.3 cm[Formula: see text] and 55.4, respectively. All FDG PET-CT quantitative parameters correlated positively with serum CEA levels, and the correlation coefficients were 0.45, 0.44 and 0.49 for SUVmax, MTV and TLG [Formula: see text]. CONCLUSION PET-CT scan, CEA and CA-19-9 results were correlated. However, both tumor markers had poor sensitivity to detect metastatic disease. PET-CT is more accurate than CT in detecting recurrent CRC in this study. Majority of the recurrences were in the liver and the sensitivity is affected by tumor histology. The correlation between semiquantitative FDG PET parameters and serum tumor marker levels is moderate.
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Affiliation(s)
- Meltem Caglar
- Department of Nuclear Medicine, Hacettepe University Medical Faculty, Siihiye, Ankara, 06100, Turkey,
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32
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Ryuk JP, Choi GS, Park JS, Kim HJ, Park SY, Yoon GS, Jun SH, Kwon YC. Predictive factors and the prognosis of recurrence of colorectal cancer within 2 years after curative resection. Ann Surg Treat Res 2014; 86:143-51. [PMID: 24761423 PMCID: PMC3994626 DOI: 10.4174/astr.2014.86.3.143] [Citation(s) in RCA: 110] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2013] [Revised: 11/08/2013] [Accepted: 11/27/2013] [Indexed: 12/26/2022] Open
Abstract
PURPOSE Because predicting recurrence intervals and patterns would allow for appropriate therapeutic strategies, we evaluated the clinical and pathological characteristics of early and late recurrences of colorectal cancer. METHODS Patients who developed recurrence after undergoing curative resection for colorectal cancer stage I-III between January 2000 and May 2006 were identified. Early recurrence was defined as recurrence within 2 years after primary surgery of colorectal cancer. Analyses were performed to compare the clinicopathological characteristics and overall survival rate between the early and late recurrence groups. RESULTS One hundred fifty-eight patients experienced early recurrence and 64 had late recurrence. Multivariate analysis revealed that the postoperative elevation of carbohydrate antigen 19-9 (CA 19-9), venous invasion, and N stage correlated with the recurrence interval. The liver was the most common site of early recurrence (40.5%), whereas late recurrence was more common locally (28.1%), or in the lung (32.8%). The 5-year overall survival rates for early and late recurrence were significantly different (34.7% vs. 78.8%; P < 0.001). Survival rates after the surgical resection of recurrent lesions were not different between the two groups. CONCLUSION Early recurrence within 2 years after surgery was associated with poor survival outcomes after colorectal cancer recurrence. An elevated postoperative CA 19-9 level, venous invasion, and advanced N stage were found to be significant risk factors for early recurrence of colorectal cancer.
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Affiliation(s)
- Jong Pil Ryuk
- Colorectal Cancer Center, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Korea
| | - Gyu-Seog Choi
- Colorectal Cancer Center, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Korea
| | - Jun Seok Park
- Colorectal Cancer Center, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Korea
| | - Hye Jin Kim
- Colorectal Cancer Center, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Korea
| | - Soo Yeun Park
- Colorectal Cancer Center, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Korea
| | - Ghil Suk Yoon
- Department of Pathology, Kyungpoook National University School of Medicine, Daegu, Korea
| | - Soo Han Jun
- Department of Surgery, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Yong Chul Kwon
- Department of Pathology, Catholic University of Daegu School of Medicine, Daegu, Korea
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Németh Z, Boér K, Kásler M, Borbély K. [Clinical use of 18F-FDG PET/CT in colorectal carcinoma]. Orv Hetil 2013; 154:1447-53. [PMID: 24016751 DOI: 10.1556/oh.2013.29700] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Modern imaging techniques have an important role in the diagnostic procedures of malignancies, and assessing response to therapy. The 18F-FDG PET/CT revolutionized the evaluation of colorectal cancer in terms of preoperative staging and monitoring of recurrence. Conventional imaging techniques have limitations in early assessment of response to therapy. 18F-FDG PET has been shown to allow earlier treatment monitoring, because the metabolic change appears before any anatomic change occurs. The Response Evaluation Criteria in Solid Tumours (RECIST) are widely applied, but they have some limitations. There are new international guidelines for treatment response assessment using PET/CT in solid tumours. The authors review indications and the role of hybrid PET/CT in colorectal cancer.
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Affiliation(s)
- Zsuzsanna Németh
- Szent Margit Kórház Onkológiai Osztály Budapest Bécsi út 132. 1032
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Grossmann I, Doornbos PM, Klaase JM, de Bock GH, Wiggers T. Changing patterns of recurrent disease in colorectal cancer. Eur J Surg Oncol 2013; 40:234-9. [PMID: 24295727 DOI: 10.1016/j.ejso.2013.10.028] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Revised: 10/12/2013] [Accepted: 10/30/2013] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Due to changes in staging, (neo)-adjuvant treatment and surgical techniques for colorectal cancer (CRC), it is expected that the recurrence pattern will change as well. This study aims to report the current incidence of, and time to recurrent disease (RD), further the localization(s) and the eligibility for successive curative treatment. METHODS A consecutive cohort of CRC patients, whom were routinely staged with CT and underwent curative treatment according to the national guidelines, was analyzed (n = 526). RESULTS After a mean and median FU of 39 months, 20% of all patients and 16% of all AJCC stage 0-III patients had developed RD. The annual incidences were the highest in the first two years but tend to retain in the succeeding years for stage 0-III patients. The majority of RD was confined to one organ (58%) and 28% of these patients were again treated with curative intent. CONCLUSIONS In follow-up nowadays, less recurrences are found than reported in historical studies but these can more often be treated with curative intent. A main cause for the decreased incidence of RD, next to improvements in treatment, is probably stage shift elicited by pre-operative staging. The outcomes support continuation of follow-up in colorectal cancer.
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Affiliation(s)
- I Grossmann
- Department of Surgery, Medical Spectrum Twente, Haaksbergerstraat 55, 7513 ER Enschede, The Netherlands.
| | - P M Doornbos
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
| | - J M Klaase
- Department of Surgery, Medical Spectrum Twente, Haaksbergerstraat 55, 7513 ER Enschede, The Netherlands.
| | - G H de Bock
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
| | - T Wiggers
- Department of Surgery, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
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Vargas GM, Sheffield KM, Parmar AD, Han Y, Brown KM, Riall TS. Physician follow-up and observation of guidelines in the post treatment surveillance of colorectal cancer. Surgery 2013; 154:244-55. [PMID: 23889952 DOI: 10.1016/j.surg.2013.04.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2013] [Accepted: 04/04/2013] [Indexed: 01/21/2023]
Abstract
BACKGROUND Guidelines for post resection surveillance of colorectal cancer recommend a collection of the patient's history and physical examination, testing for carcinoembryonic antigen (CEA), and colonoscopy. No consistent guidelines exist for the use of abdominal computed tomography (CT) and position emission tomography (PET)/PET-CT. The goal of our study was to describe current trends, the impact of oncologic follow-up on guideline adherence, and the patterns of use of nonrecommended tests. METHODS We used Texas Cancer Registry-Medicare-linked data (2000-2009) to identify physician visits, CEA testing, colonoscopy, abdominal CT, and PET/PET-CT scans in patients ≥ 66 years old with stage I-III colorectal cancer who underwent curative resection. Compliance with guidelines was assessed with a composite measure of physician visits, CEA tests, and colonoscopy use from start of surveillance. RESULTS In patients who survived 3 years, the overall compliance with guidelines was 25.1%. In patients seen regularly by a medical oncologist, compliance with guidelines increased to 61.5% compared with 8.8% for those not seen by a medical oncologist regularly (P < .0001). The use of abdominal CT and PET/PET-CT increased from 57.5% and 9.5%, respectively, in 2001 to 65.8% and 24.6% (P < .0001) in 2006. Patients who saw a medical oncologist were more likely to get cross-sectional imaging than those who did not (P < .0001). CONCLUSION Compliance with current minimum guidelines for post treatment surveillance of colorectal cancer is low and the use of nonrecommended testing has increased over time. Both compliance and use of nonrecommended tests are markedly increased in patients seen by a medical oncologist. The comparative effectiveness of CT and PET/PET-CT in the surveillance of colorectal cancer patients needs further examination.
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Affiliation(s)
- Gabriela M Vargas
- Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555-0541, USA
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Koo SL, Wen JH, Hillmer A, Cheah PY, Tan P, Tan IB. Current and emerging surveillance strategies to expand the window of opportunity for curative treatment after surgery in colorectal cancer. Expert Rev Anticancer Ther 2013; 13:439-50. [PMID: 23560838 DOI: 10.1586/era.13.14] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Colorectal cancer is the third most common cancer globally. At diagnosis, more than 70% of patients have nonmetastatic disease. Cure rates for early-stage colorectal cancer have improved with primary screening, improvements in surgical techniques and advances in adjuvant chemotherapy. Despite optimal primary treatment, 30-50% of these patients will still relapse. While death will result from widespread metastatic disease, patients with small volume oligometastatic disease are still considered curable with aggressive multimodality therapy. Hence, early detection of relapsed cancer when it is still amenable to resection expands the window of opportunity for cure. Here, the authors review the modalities currently employed in clinical practice and the evidence supporting intensive surveillance strategies. The authors also discuss ongoing clinical trials examining specific surveillance programs and emerging modalities that may be deployed in the future for early detection of metastatic disease.
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Affiliation(s)
- Si Lin Koo
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore
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Peng NJ, Hu C, King TM, Chiu YL, Wang JH, Liu RS. Detection of resectable recurrences in colorectal cancer patients with 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography. Cancer Biother Radiopharm 2013; 28:479-87. [PMID: 23713869 PMCID: PMC3715809 DOI: 10.1089/cbr.2012.1382] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To evaluate the usefulness of 2-[(18)F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the early detection of resectable recurrences of colorectal cancer (CRC) and the impacts on the clinical disease management. METHODS FDG-PET/CT was performed on patients with elevated serum carcinoembryonic antigen (CEA) levels >5 ng/mL (Group 1) or suspicious recurrences without rise in serum CEA levels (Group 2). The results were analyzed on the basis of histological data, disease progression, and/or clinical follow-up. Recurrence was defined as evidence of recurrent lesions within 6 months of the FDG-PET/CT scan. Resectable recurrences and changes in management were calculated based on medical records. RESULTS In our study, 128 consecutive FDG-PET/CT analyses (n=49 in Group 1 and n=79 in Group 2) were performed on 96 recruited patients. Recurrences were proven in 63. The overall sensitivity, specificity, and accuracy of FDG-PET/CT were 98.4%, 89.2%, and 93.8%, respectively, and were 100%, 88.9%, and 95.9% in Group 1 and 96.9% and 89.4% and 92.4% in Group 2, respectively. Surgical resections were performed in 38.7% (12/31) of Group 1 patients and 53.1% (17/32) of Group 2 patients. FDG-PET/CT induced changes in planned management in 48.4% (62/128) of all patients, which included 63.3% (31/49) of Group 1 patients and 39.2% (31/79) of Group 2 patients (p=0.008). After a follow-up, 3.4% (1/29) of patients who underwent surgical resection of recurrent lesions and 34.3% (11/34) patients who did not undergo resection died at the end of study (p=0.004). CONCLUSIONS The surgical resection of limited recurrent disease, as determined by FDG-PET/CT, improves the survival of CRC patients. FDG-PET/CT should be performed not only in patients with elevated serum CEA levels, but also in those in whom recurrences are suspected to improve the early detection of resectable disease.
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Affiliation(s)
- Nan-Jing Peng
- Department of Nuclear Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China.
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Amin A, Reddy A, Wilson R, Jha M, Miranda S, Amin J. Unnecessary surgery can be avoided by judicious use of PET/CT scanning in colorectal cancer patients. J Gastrointest Cancer 2013; 43:594-8. [PMID: 22552946 DOI: 10.1007/s12029-012-9391-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
AIM This study aims to determine the role of positron emission tomography (PET)/computed tomography (CT) in changing the management plan in patients with metastatic or recurrent colorectal cancer (CRC) and to evaluate the role of PET/CT in patients with an unexplained rise in carcinoembryonic antigen (CEA). MATERIALS AND METHODS A total of 60 consecutive patients with CRC, who had PET/CT, were identified between 2008 and 2010. All patients had CT scans prior to the PET/CT. Data were collected from clinic letters, CT and PET CT reports and pathology results and cross-checked with the patient's notes. RESULTS Patients were aged between 43 and 85 years [33 males, 27 females]. CEA was raised in 37 patients and normal in 23. Results of PET/CT were compared with that of CT scan and 33 out of the 60 patients (55%) had PET/CT results which were different to that of CT scan and 27 patients (45%) had similar PET/CT and CT results. PET scan appropriately altered the management in 23/60 patients (38%) and avoided unnecessary surgery in 14 patients. PET/CT had a sensitivity of 86% and specificity of 84%. In patients with an unexplained rise in CEA, PET/CT was positive in only one out of ten (10%) patients. CONCLUSION PET/CT is valuable in deciding the management outcome in patients with metastatic or recurrent colorectal cancer. Unnecessary surgery might be avoided by careful use of PET/CT scanning in colorectal cancer patients. PET/CT might not be of value in patients with an unexplained rise in CEA.
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Lu CY, Tsai HL, Uen YH, Hu HM, Chen CW, Cheng TL, Lin SR, Wang JY. Circulating tumor cells as a surrogate marker for determining clinical outcome to mFOLFOX chemotherapy in patients with stage III colon cancer. Br J Cancer 2013; 108:791-7. [PMID: 23422758 PMCID: PMC3590657 DOI: 10.1038/bjc.2012.595] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND This study was aimed to detect post-chemotherapeutic circulating tumour cells (CTCs) in stage III colon cancer patients and identify those who were at high risk of relapse. METHODS We used human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen (CEA) as the biomarkers to detect CTCs in 90 stage III colon cancer patients undergoing curative resection followed by mFOLFOX chemotherapy. RESULTS Post-chemotherapeutic relapse occurred in 30 (33.3%) patients. By univariate analysis and multivariate proportional hazards regression analysis, perineural invasion (hazard ratio (HR): 2.752; 95% confidence interval (CI): 1.026-7.381), high post-chemotherapeutic serum CEA levels (HR: 2.895; 95% CI: 1.143-7.333) and persistent presence of post-chemotherapeutic CTCs (HR: 6.273; 95% CI: 2.442-16.117) were independent predictors of post-chemotherapeutic relapse. In addition, the persistent presence of post-chemotherapeutic CTCs strongly correlated with reduced disease-free survival and overall survival. Accuracy of detecting relapse in post-chemotherapeutic stage III colon cancer patients by analysing the persistent presence of post-chemotherapeutic CTCs was higher than that by post-chemotherapeutic CEA levels (odds ratio: 50.091 vs 5.211). CONCLUSION The persistent presence of post-chemotherapeutic CTCs is a potential powerful surrogate marker for determining clinical outcome in stage III colon cancer patients receiving adjuvant mFOLFOX chemotherapy.
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Affiliation(s)
- C-Y Lu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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Clinical Implications of Circulating Tumor Cells in Advanced Colorectal Cancer. CURRENT COLORECTAL CANCER REPORTS 2012. [DOI: 10.1007/s11888-012-0138-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Pulmonary recurrence predominates after combined modality therapy for rectal cancer: an original retrospective study. Ann Surg 2012; 256:111-6. [PMID: 22664562 DOI: 10.1097/sla.0b013e31825b3a2b] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To characterize patterns of recurrence in locally advanced rectal cancer treated with combined modality therapy (CMT): neoadjuvant chemoradiation + total mesorectal excision + adjuvant chemotherapy. METHODS A total of 593 consecutive rectal cancer patients (1998 to 2007) with locally advanced (stage II/III) disease (noted on endorectal ultrasound or magnetic resonance imaging) who received CMT were analyzed for patterns of recurrence. RESULTS After median 44-month follow-up (interquartile range, 25 to 64 months), 119 patients (20%) recurred: 105 distant, 7 local, 7 local and distant, and 112 distant-only recurrence. Ninety-three (78%) had single-organ recurrence, and 26 (22%) had multiple-organ recurrence. The most common site of distant recurrence was lung (69% of all patients with distant relapse); 20% had liver recurrence. Fourteen patients (2.4%) recurred locally. Pulmonary metastases were most commonly identified by computed tomographic scan versus abnormal positron emission tomographic (PET) scan or carcinoembryonic antigen (CEA). Risk factors associated with pulmonary recurrence were the following: pathologic stage, tumor distance from anal verge, lymphovascular or perineural invasion. Five-year freedom from pulmonary recurrence for patients with 0, 1, 2, or 3 risk factors was 99%, 90%, 61%, and 42%, respectively. Thirty of 59 patents with pulmonary recurrence underwent lung metastasectomy; 3-year freedom from recurrence was 37%. CONCLUSIONS Unlike colon cancer, which most frequently recurs in the liver, locally advanced rectal cancer treated with CMT relapses most frequently in the lung. Pulmonary metastasis was associated with advanced pathologic stage, low-lying tumor, lymphovascular invasion, or perineural invasion. Confirmation of pulmonary metastasis usually requires serial imaging because metastases are often small when initially detected, well below the resolution of PET, and not necessarily associated with elevated CEA. Individualized risk-based surveillance strategies are recommended in this patient population.
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The role of 18F-FDG PET/CT in detecting colorectal cancer recurrence in patients with elevated CEA levels. Nucl Med Commun 2012; 33:395-402. [PMID: 22367859 DOI: 10.1097/mnm.0b013e32834f7dbe] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION In this study we aimed to define the success of fluorine-18 (18F) fluorodeoxyglucose (FDG) PET/computed tomography (PET/CT) in detecting recurrent disease in our patient group with colorectal cancer (CRC) and elevated carcinoembryonic antigen (CEA) levels. MATERIAL AND METHOD Patients who had a previous diagnosis of CRC were searched retrospectively in our PET center database. Seventy-six 18F-FDG PET/CT studies between October 2006 and December 2010 of 69 patients (25 women, 44 men; mean age: 61.61 ± 4.1 years) with elevated CEA levels were evaluated. 18F-FDG PET/CT findings and concurrent abdominopelvic contrast-enhanced computed tomography (ceCT) findings were compared with histopathological findings and/or clinical follow-up data as the 'gold standard'. RESULTS In the patient-based analysis, the sensitivity and specificity of 18F-FDG PET/CT in the detection of disease recurrence were calculated as 97 and 61%, respectively. A statistically significant difference was found in frequencies of positive and negative 18F-FDG PET/CT findings between patients with or without recurrent disease by gold standard (P<0.05). There was no correlation between patients' serum CEA levels and lesions' maximum standardized uptake values (P=0.85). The sensitivity and specificity of ceCT were computed as 51 and 60%, respectively. In the evaluation of separate patient groups, although the sensitivity and specificity of 18F-FDG PET/CT were calculated as 100 and 60% in the group whose CEA level elevation was less than two-fold (5-9.9 ng/ml), these were 100 and 75% in the group with CEA elevation less than three-fold (10-14.9 ng/ml) and 95 and 62% in the group with elevation more than three-fold (≥ 15 ng/ml). The sensitivity and specificity of 18F-FDG PET/CT were computed as 98 and 85% in the lesion-based evaluation. The sensitivity and specificity of ceCT were 73 and 86%, respectively. CONCLUSION 18F-FDG PET/CT is a safe imaging method that can be used in the determination of CRC recurrence in patients with elevated CEA levels, regardless of the CEA level.
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Sanli Y, Kuyumcu S, Ozkan ZG, Kilic L, Balik E, Turkmen C, Has D, Isik G, Asoglu O, Kapran Y, Adalet I. The utility of FDG-PET/CT as an effective tool for detecting recurrent colorectal cancer regardless of serum CEA levels. Ann Nucl Med 2012; 26:551-8. [PMID: 22644560 DOI: 10.1007/s12149-012-0609-0] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2012] [Accepted: 05/01/2012] [Indexed: 12/11/2022]
Abstract
PURPOSE Tumor recurrence of colorectal cancers (CRC) is generally followed up by analyses of the serum carcinoembryonic antigen (CEA) levels. However, recent evidence suggests that tumor recurrence can also be visualized by 18F-fluoro-deoxyglucose emission tomography/computed tomography (FDG-PET/CT) in patients with normal CEA levels. We retrospectively evaluated the diagnostic performance of FDG-PET/CT in patients with suspected recurrence of CRC by comparing PET/CT performance in patients with normal CEA levels with PET/CT performance in patients with elevated CEA levels. METHODS A total of 235 patients with CRC who had been treated with surgery and/or chemotherapy/radiotherapy underwent PET/CT for the detection of tumor recurrence. The patients [96 females and 139 males; age (mean ± SD) 59.9 ± 12.6 years; range 18-85] were divided into 2 groups based on whether their CEA levels were normal (<5 ng/ml) (Group 1, n = 118) or elevated (>5 ng/ml) (Group 2, n = 117). All of the patients had suspected recurrence based on raised CEA levels, clinical symptoms, and/or tumor detection using other imaging modalities. RESULTS Of the 235 patients, 172 (73.1 %) had disease recurrence confirmed by a pathological examination (either biopsy or surgical exploration) or clinical follow-up studies. The FDG-PET/CT study yielded a true positive in detecting recurrence in 169 (71.9 %) patients, a true negative in 53 (22.5 %) patients, a false negative in 3 (1.2 %) patients and a false positive in 10 (4.2 %) patients. CRC recurrence was detected in 64.4 % (76/118) and 88 % (103/117) patients in Group 1 and Group 2 with FDG-PET/CT, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the FDG-PET/CT study for establishing recurrence were 100, 84, 89.4, 100 and 93.2 %, respectively, for Group 1; by contrast, these parameters were 97.1, 84.6, 98, 78.5 and 95.7 %, respectively, for Group 2. The number of patients with hepatic and extra-hepatic metastases, such as lung and abdominal lymph node metastasis, detected with FDG-PET/CT was significantly different in Group 1 than in Group 2; however, the number of patients with local recurrence and peritoneal implants detected with FDG-PET/CT was not different between the two groups. CONCLUSIONS FDG-PET/CT can accurately detect tumor recurrence in patients with suspected recurrent CRC, even for patients with normal CEA levels.
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Affiliation(s)
- Yasemin Sanli
- Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
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Su BB, Shi H, Wan J. Role of serum carcinoembryonic antigen in the detection of colorectal cancer before and after surgical resection. World J Gastroenterol 2012; 18:2121-6. [PMID: 22563201 PMCID: PMC3342612 DOI: 10.3748/wjg.v18.i17.2121] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2011] [Revised: 12/19/2011] [Accepted: 03/09/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine whether serum levels of carcinoembryonic antigen (CEA) correlate with the presence of primary colorectal cancer (CRC), and/or recurrent CRC following radical resection.
METHODS: A total of 413 patients with CRC underwent radical surgery between January 1998 and December 2002 in our department and were enrolled in this study. The median follow-up period was 69 mo (range, 3-118 mo), and CRC recurrence was experienced by 90/413 (21.8%) patients. Serum levels of CEA were assayed preoperatively, and using a cutoff value of 5 ng/mL, patients were divided into two groups, those with normal serum CEA levels (e.g., ≤ 5 ng/mL) and those with elevated CEA levels (> 5 ng/mL).
RESULTS: The overall sensitivity of CEA for the detection of primary CRC was 37.0%. The sensitivity of CEA according to stage, was 21.4%, 38.9%, and 41.7% for stages I-III, respectively. Moreover, for stage II and stage III cases, the 5-year disease-free survival rates were reduced for patients with elevated preoperative serum CEA levels (P < 0.05). The overall sensitivity of CEA for detecting recurrent CRC was 54.4%, and sensitivity rates of 36.6%, 66.7%, and 75.0% were associated with cases of local recurrence, single metastasis, and multiple metastases, respectively. In patients with normal serum levels of CEA preoperatively, the sensitivity of CEA for detecting recurrence was reduced compared with patients having a history of elevated CEA prior to radical resection (32.6% vs 77.3%, respectively, P < 0.05).
CONCLUSION: CRC patients with normal serum CEA levels prior to resection maintained these levels during CRC recurrence, especially in cases of local recurrence vs cases of metastasis.
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Ladd JJ, Busald T, Johnson MM, Zhang Q, Pitteri SJ, Wang H, Brenner DE, Lampe PD, Kucherlapati R, Feng Z, Prentice RL, Hanash SM. Increased plasma levels of the APC-interacting protein MAPRE1, LRG1, and IGFBP2 preceding a diagnosis of colorectal cancer in women. Cancer Prev Res (Phila) 2012; 5:655-64. [PMID: 22277732 DOI: 10.1158/1940-6207.capr-11-0412] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Longitudinal blood collections from cohort studies provide the means to search for proteins associated with disease before clinical diagnosis. We investigated plasma samples from the Women's Health Initiative (WHI) cohort to determine quantitative differences in plasma proteins between subjects subsequently diagnosed with colorectal cancer (CRC) and matched controls that remained cancer-free during the period of follow-up. Proteomic analysis of WHI samples collected before diagnosis of CRC resulted in the identification of six proteins with significantly (P < 0.05) elevated concentrations in cases compared with controls. Proteomic analysis of two CRC cell lines showed that five of the six proteins were produced by cancer cells. Microtubule-associated protein RP/EB family member 1 (MAPRE1), insulin-like growth factor-binding protein 2 (IGFBP2), leucine-rich alpha-2-glycoprotein (LRG1), and carcinoembryonic antigen (CEA) were individually assayed by enzyme linked immunosorbent assay (ELISA) in 58 pairs of newly diagnosed CRC samples and controls and yielded significant elevations (P < 0.05) among cases relative to controls. A combination of these four markers resulted in a receiver operating characteristics curve with an area under the curve value of 0.841 and 57% sensitivity at 95% specificity. This combination rule was tested in an independent set of WHI samples collected within 7 months before diagnosis from cases and matched controls resulting in 41% sensitivity at 95% specificity. A panel consisting of CEA, MAPRE1, IGFBP2, and LRG1 has predictive value in prediagnostic CRC plasmas.
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Affiliation(s)
- Jon J Ladd
- Molecular Diagnostics Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
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Lee SY, Min KS, Chung JK, Jung IM, Ahn YJ, Hwang KT, Ahn HS, Heo SC. Carcinoembryonic antigen level of draining venous blood as a predictor of recurrence in colorectal cancer patient. JOURNAL OF THE KOREAN SURGICAL SOCIETY 2011; 81:387-93. [PMID: 22200039 PMCID: PMC3243855 DOI: 10.4174/jkss.2011.81.6.387] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/29/2011] [Revised: 07/08/2011] [Accepted: 10/06/2011] [Indexed: 01/28/2023]
Abstract
PURPOSE We designed this study to evaluate the efficacy of carcinoembryonic antigen in draining venous blood (vCEA) as a predictor of recurrence. METHODS Draining venous and supplying arterial bloods were collected separately during the operation of 82 colorectal cancer patients without distant metastasis from September 2004 to December 2006. Carcinoembryonic antigen was measured and assessed for the efficacy as a prognostic factor of recurrence using receiver operating characteristic (ROC) and Kaplan-Meier curves. RESULTS vCEA is a statistically significant factor that predicts recurrence (P = 0.032) and the optimal cut-off value for vCEA from ROC curve is 8.0 ng/mL. The recurrence-free survival between patients with vCEA levels >8 ng/mL and ≤8 ng/mL significantly differed (P < 0.001). The significance of vCEA as a predictor of recurrence gets higher when limited to patients without lymph node metastasis. The proper cut-off value for vCEA is 4.0 ng/mL if confined to patients without lymph node metastasis. The recurrence-free survival between the patients of vCEA levels >4 ng/mL and ≤4 ng/mL significantly differed (P < 0.001). Multivariate analysis revealed vCEA is an independent prognostic factor in patients without lymph node metastasis. CONCLUSION vCEA is an independent prognostic factor of recurrence in colorectal cancer patients especially in patients without lymph node metastases.
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Affiliation(s)
- Soo Young Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Department of Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Kyung Sun Min
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea
| | - Jung Kee Chung
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Department of Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - In Mok Jung
- Department of Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Young Joon Ahn
- Department of Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Ki-Tae Hwang
- Department of Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Hye Seong Ahn
- Department of Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Seung Chul Heo
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Department of Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
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Tsai MH, Wu CC, Peng PH, Liang Y, Hsiao YC, Chien KY, Chen JT, Lin SJ, Tang RP, Hsieh LL, Yu JS. Identification of secretory gelsolin as a plasma biomarker associated with distant organ metastasis of colorectal cancer. J Mol Med (Berl) 2011; 90:187-200. [DOI: 10.1007/s00109-011-0817-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2011] [Revised: 07/28/2011] [Accepted: 09/05/2011] [Indexed: 02/03/2023]
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Accuracy of monitoring serum carcinoembryonic antigen levels in postoperative stage III colorectal cancer patients is limited to only the first postoperative year. Surg Today 2011; 41:1357-62. [PMID: 21922357 DOI: 10.1007/s00595-010-4519-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2010] [Accepted: 07/07/2010] [Indexed: 02/07/2023]
Abstract
PURPOSE The aim of the present study was to determine the accuracy of yearly postoperative monitoring of serum tumor markers to either detect or rule out recurrence in colorectal cancer patients. METHODS A total of 127 colorectal cancer patients who underwent curative surgery were enrolled. The serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were assayed, and radiological examinations were performed routinely for 5 years after surgery or until recurrence was detected. Yearly recurrence rates (number of recurrences/number of patients assessed in a given year), sensitivities, specificities, and likelihood ratios were calculated. Post-test probabilities were calculated from these values. RESULTS Recurrences tended to show almost the same frequencies in the first and second year after surgery (20 of 127 patients and 18 of 107 patients, respectively). However, the post-test probability of recurrence in patients with positive and negative serum CEA levels was significantly lower in the second year than in the first year (test positive: 40.0% and 76.0%; test negative: 9.3% and 0.5%, respectively). CONCLUSIONS Measuring CEA can help to identify patients likely to demonstrate recurrence with high accuracy only within the first year after surgery. Another examination, such as imaging, is therefore necessary for monitoring patients at 2 or more years after surgery.
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The Role of High Frequency Dynamic Threshold (HiDT) Serum Carcinoembryonic Antigen (CEA) Measurements in Colorectal Cancer Surveillance: A (Revisited) Hypothesis Paper. Cancers (Basel) 2011; 3:2302-15. [PMID: 24212811 PMCID: PMC3757419 DOI: 10.3390/cancers3022302] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2011] [Revised: 04/22/2011] [Accepted: 05/04/2011] [Indexed: 12/20/2022] Open
Abstract
Following curative treatment for colorectal cancer (CRC), 30% to 50% of patients will develop recurrent disease. For CRC there are several lines of evidence supporting the hypothesis that early detection of metachronous disease offers a second opportunity for cure. This paper revisits the potential role of serum carcinoembryonic antigen (CEA) in follow-up. A comprehensive review of the literature (1978–2008) demonstrates that the initial promise of serum CEA as an effective surveillance tool has been tarnished through perpetuation of poorly designed studies. Specific limitations included: testing CEA as only an ‘add-on’ diagnostic tool; lack of standardization of threshold values; use of static thresholds; too low measurement frequency. Major changes in localizing imaging techniques and treatment of metastatic CRC further cause a decrease of clinical applicability of past trial outcomes. In 1982, Staab hypothesized that the optimal benefit of serum CEA as a surveillance tool is through high-frequency triage using a dynamic threshold (HiDT). Evidence supporting this hypothesis was found in the biochemical characteristics of serum CEA and retrospective studies showing the superior predictive value of a dynamic threshold. A multi-centred randomized phase III study optimizing the usage of HiDT against resectability of recurrent disease is commencing recruitment in the Netherlands.
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Lu CY, Uen YH, Tsai HL, Chuang SC, Hou MF, Wu DC, Juo SHH, Lin SR, Wang JY. Molecular detection of persistent postoperative circulating tumour cells in stages II and III colon cancer patients via multiple blood sampling: prognostic significance of detection for early relapse. Br J Cancer 2011; 104:1178-84. [PMID: 21343933 PMCID: PMC3068492 DOI: 10.1038/bjc.2011.40] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Background: The purpose of this study was to detect postoperative persistent circulating tumour cells (CTCs) in stages II and III colon cancer patients undergoing curative resection and so identify a subgroup of patients who are at high risk for early relapse. Methods: Four mRNA molecular markers including human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen (CEA) mRNA were used to detect CTCs in 141 stages II and III colon cancer patients undergoing curative resection to determine the significance of CTCs in postoperative early relapse. Results: Out of 141 patients, postoperative early relapse and non-early relapse/no relapse was found in 48 (34.0%) patients and 93 (66.0%) patients, respectively. Univariately, postoperative early relapse was significantly correlated with lymph node metastasis (P=0.025), vascular invasion (P=0.002), perineural invasion (P=0.001), laparoscopic surgery (P=0.019), high postoperative serum CEA levels (P=0.001), and presence of persistent postoperative CTCs (P<0.001). Using a multivariate proportional hazards regression analysis, the presence of perineural invasion (P=0.034; HR, 1.974; 95% CI: 1.290–3.861), high postoperative serum CEA levels (P=0.020; HR, 2.377; 95% CI: 1.273–4.255), and the presence of persistent postoperative CTCs (P<0.001; HR, 11.035; 95% CI: 4.396–32.190), were demonstrated to be independent predictors for postoperative early relapse. Furthermore, the presence of persistent postoperative CTCs was strongly correlated with a poorer disease-free and overall survival (both P<0.001). Conclusions: This study suggests that molecular detection of persistent postoperative CTCs is a prognostic predictor of early relapse in UICC stage II/III colon cancer patients, and thus could help to define patients with this tumour entity for an enhanced follow-up and therapeutic program.
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Affiliation(s)
- C-Y Lu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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