|
1
|
Sachan A, Nayyar R, Pethe S, Singh P, Seth A. A 3-arm randomized control trial to compare the efficacy of re-circulant hyperthermic intravesical chemotherapy versus conventional intravesical mitomycin C and BCG therapy for intermediate-risk non-muscle invasive bladder cancer. World J Urol 2024; 42:609. [PMID: 39480527 DOI: 10.1007/s00345-024-05338-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Accepted: 10/22/2024] [Indexed: 11/02/2024] Open
Abstract
INTRODUCTION To evaluate the efficacy and side effects of re-circulant hyperthermic intravesical chemotherapy versus conventional treatments for intermediate risk non-muscle invasive bladder cancer (NMIBC). METHODS A randomized 3-arm, parallel group trial was conducted at a single tertiary care centre. 135 patients with low-grade intermediate-risk cancer, having undergone complete resection of bladder tumor were included. Patients were assigned 1:1:1, to receive intra-vesical chemo-hyperthermia (C-HT), mitomycin-C (MMC) or BCG therapy. There was no treatment crossover. Patients were followed up with check cystoscopy every 3 months for histopathological recurrence. RESULTS The three arms were comparable in terms of age, gender, tumor size, number of tumors and clinical stage or grade of tumors. Mean tumor size was 2.58 (± 0.88) cm and the mean number of tumors resected was 2.04 (± 1.02) (Range 1-5). There was no significant difference between the various groups for tumor recurrence (χ2 = 1.96, p = 0.375) or time to recurrence (13.6 vs. 10.8 vs. 9.8 months, p = 0.844) though incidence of non-healing necrotic area was higher with C-HT (22.2% vs. 11.1% and 4.8%, χ2 = 6.093, p = 0.048). Median (IQR) follow up period was 26 (12-52) months. Treatment discontinuation or drug intolerance was significantly higher in BCG arm (p = 0.03). CONCLUSIONS Intravesical C-HT with MMC, conventional MMC and BCG are equally effective and comparable alternatives for intravesical therapy in low-grade intermediate-risk NMIBC. Higher incidence of non-healing resection site with C-HT and higher local symptoms with BCG are a concern.
Collapse
Affiliation(s)
- Ankit Sachan
- Department of Urology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India
| | - Rishi Nayyar
- Department of Urology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
| | - Sahil Pethe
- Department of Urology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India
| | - Prashant Singh
- Department of Urology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India
| | - Amlesh Seth
- Department of Urology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India
| |
Collapse
|
|
2
|
Melgarejo Segura MT, Yáñez Castillo Y, Lozano Lorca M, Morales Martínez A, Arrabal Polo MÁ, Arrabal Martín M. Efficacy of conduction hyperthermia in the treatment of non-muscle invasive bladder cancer: A systematic review. Urol Oncol 2024; 42:251-265. [PMID: 38670818 DOI: 10.1016/j.urolonc.2024.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 03/01/2024] [Accepted: 03/18/2024] [Indexed: 04/28/2024]
Abstract
INTRODUCTION Intravesical treatment for non-muscle invasive bladder cancer (NMIBC) aims to reduce recurrences and stop progression. Hyperthermia-enhanced chemotherapy with devices like COMBAT BRS, Unithermia, and BR-TRG-I is a promising alternative to conventional Bacillus de Calmette Guerin (BCG) therapy. OBJECTIVE To systematically review the efficacy of hyperthermia generated by conduction devices in the treatment of NMIBC. MATERIAL AND METHODS The review followed the preferred reporting items for systematic reviews and meta-analyses guidelines. A search was performed in the PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases. Two reviewers independently assessed the eligibility of candidate studies and abstracted data from studies that met the inclusion criteria. The primary endpoint was assessment of recurrence. Secondary objectives included evaluation of treatment progression and safety. RESULTS Thirty studies meeting inclusion criteria underwent data extraction. In intermediate-risk NMIBC patients, COMBAT versus mitomycin C (MMC) in normothermia revealed no superiority in reducing recurrence or progression. High-risk NMIBC patients using COMBAT achieved similar or superior outcomes to BCG. BR-TRG-I demonstrated superior results over normothermia in intermediate- and high-risk NMIBC patients. Unithermia proved less effective than BCG in high-risk NMIBC. Progression outcomes were promising with COMBAT and BR-TRG-I, but comprehensive analysis was limited due to inconsistent assessment across studies. Adverse events were primarily mild-moderate, with some device-specific differences. CONCLUSIONS Studies on conduction hyperthermia present great variability, which do not allow us to determine the superiority of 1 device over another in terms of recurrence, progression, and/or adverse effects. Further research with consistent administration protocols is crucial for definitive conclusions.
Collapse
Affiliation(s)
| | | | - Macarena Lozano Lorca
- Department of Preventive Medicine and Public Health, University of Granada, Melilla, Spain; Institute of Biosanitary Research ibs. Granada, Granada, Spain
| | | | - Miguel Ángel Arrabal Polo
- Department of Urology, University Hospital San Cecilio, Granada, Spain; Institute of Biosanitary Research ibs. Granada, Granada, Spain
| | | |
Collapse
|
|
3
|
Wang S, Yu Z, Du P, Cao Y, Yang X, Ma J, Tang X, Zhang Q, Yang Y. Combination of hyperthermia and intravesical chemotherapy for the treatment of pT1 stage bladder cancer: A retrospectively clinical study. Asia Pac J Clin Oncol 2024; 20:228-233. [PMID: 36656047 DOI: 10.1111/ajco.13931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 12/27/2022] [Accepted: 01/04/2023] [Indexed: 01/20/2023]
Abstract
PURPOSE To evaluate the efficiency and safety of combined local bladder hyperthermia and intravesical chemotherapy (IVC) for the treatment of patients with pT1 stage bladder cancer. METHOD A total of 189 patients with pT1 who underwent transurethral resection of bladder cancer (TURBT) were retrospectively reviewed. After TURBT, the patients with low-grade urothelial carcinoma (UC) were treated with either an IVC with pirarubicin (THP) protocol or chemo-thermotherapy (CHT) with THP protocol, whereas patients with high-grade UC were treated with either an intravesical immunotherapy (IVI) with bacillus Calmette-Guerin (BCG) protocol or CHT protocol, patients' characteristics, tumor biological features, and follow-up data were analyzed and compared between CHT and IVC group in low-grade UC, CHT, and IVI group in high-grade UC, respectively. RESULTS The median follow-up time was 24 months. In patients with low-grade UC, the median recurrence free survival (RFS) interval and costs of treatment in CHT group were significantly higher than those in IVC group (p = .01, p < .001, respectively), CHT was associated with higher RFS compared with IVC by Kaplan-Meier analysis, and three patients in IVC group upgraded to high grade when tumor recurred, whereas no cases were found upgraded in CHT group, p = .38. In patients with high-grade UC, tumor recurrence rates at 12 (p = .004) and 24 months (p = .004) after TURBT, rate of complications (p = .04)-especially for hematuresis (p = .03) and irritation symptoms (p = .04)-the median costs of treatment (p < .001) in CHT group were significantly lower than those in IVI group, RFS interval, health-related quality of life) at 12 and 24 months after TURBT in CHT group was significantly higher than those in IVI group (p < .001, p = .002, and p < .001, respectively), and CHT was associated with higher RFS compared with IVI by Kaplan-Meier analysis. The rate of patients upstaged to pT2 in CHT group seemed lower than that in IVI group, but there was no significantly statistical difference (14.3% vs. 24%, p = .58). CONCLUSION CHT has a beneficial prophylactic effect in patients with pT1 bladder cancer, especially in patients with high-grade UC, which is much more effective and safer than BCG, meanwhile it costs less compared with BCG.
Collapse
Affiliation(s)
- Shuo Wang
- Key Laboratory of Carcinogenesis and Translational Research (Mninistry of Education), Urological Department, Peking University Cancer Hospital & Institute, Beijing, China
| | - Ziyi Yu
- Key Laboratory of Carcinogenesis and Translational Research (Mninistry of Education), Urological Department, Peking University Cancer Hospital & Institute, Beijing, China
| | - Peng Du
- Key Laboratory of Carcinogenesis and Translational Research (Mninistry of Education), Urological Department, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yudong Cao
- Key Laboratory of Carcinogenesis and Translational Research (Mninistry of Education), Urological Department, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiao Yang
- Key Laboratory of Carcinogenesis and Translational Research (Mninistry of Education), Urological Department, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jinchao Ma
- Key Laboratory of Carcinogenesis and Translational Research (Mninistry of Education), Urological Department, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiaohu Tang
- Urological Department, Western Beijing Cancer Hospital, Beijing, China
| | - Qi Zhang
- Urological Department, Western Beijing Cancer Hospital, Beijing, China
| | - Yong Yang
- Key Laboratory of Carcinogenesis and Translational Research (Mninistry of Education), Urological Department, Peking University Cancer Hospital & Institute, Beijing, China
| |
Collapse
|
|
4
|
Eilender BM, Katims AB, Pfail JL, Sfakianos J. Evolving Treatment in Non-muscle-Invasive Bladder Cancer. Urol Oncol 2022. [DOI: 10.1007/978-3-030-89891-5_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
|
|
5
|
Jeong H, Park W, Kim DH, Na K. Dynamic nanoassemblies of nanomaterials for cancer photomedicine. Adv Drug Deliv Rev 2021; 177:113954. [PMID: 34478780 DOI: 10.1016/j.addr.2021.113954] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 07/09/2021] [Accepted: 08/27/2021] [Indexed: 12/11/2022]
Abstract
Photomedicine has long been used for treating cancerous diseases. With advances in chemical and material sciences, various types of light-activated photosensitizers (PSs) have been developed for effective photodynamic therapy (PDT) and photothermal therapy (PTT). However, conventional organic/inorganic materials-based PSs lack disease recognition capability and show limited therapeutic effects in addition to side effects. Recently, intelligent dynamic nanoassemblies that are activated in a tumor environment have been extensively researched to target diseased tissues more effectively, for increasing therapeutic effectiveness while minimizing side effects. This paper presents the latest dynamic nanoassemblies for effective PDT or PTT and combination phototherapies, including immunotherapy and image-guided therapy. Dynamic self-assembly exhibits great potential for clinical translation in diagnosis and treatment through its integrated versatility. Nanoassemblies based on multidisciplinary technology are a promising technique for treating incurable cancerous diseases in the future.
Collapse
Affiliation(s)
- Hayoon Jeong
- Department of Biomedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Bucheon, Gyeonggi 14662, Republic of Korea; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Bucheon, Gyeonggi 14662, Republic of Korea
| | - Wooram Park
- Department of Biomedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Bucheon, Gyeonggi 14662, Republic of Korea; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Bucheon, Gyeonggi 14662, Republic of Korea
| | - Dong-Hyun Kim
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA; Department of Biomedical Engineering, McCormick School of Engineering, Evanston, IL 60208, USA; Department of Bioengineering, The University of Illinois at Chicago, Chicago, IL 60607, USA.
| | - Kun Na
- Department of Biomedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Bucheon, Gyeonggi 14662, Republic of Korea; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Bucheon, Gyeonggi 14662, Republic of Korea.
| |
Collapse
|
|
6
|
Altintas G, Akduman I, Janjic A, Yilmaz T. A Novel Approach on Microwave Hyperthermia. Diagnostics (Basel) 2021; 11:493. [PMID: 33802130 PMCID: PMC7999730 DOI: 10.3390/diagnostics11030493] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 03/08/2021] [Accepted: 03/08/2021] [Indexed: 11/16/2022] Open
Abstract
Microwave hyperthermia (MH) requires the selective focusing of microwave energy on the targeted region while minimally affecting the healthy tissue. Emerging from the simple nature of the linear antenna arrays, this work demonstrates focusing maps as an application guide for MH focusing by adjusting the antenna phase values. The focusing of the heating potential (HP) on different density breast models is performed via the proposed method using Vivaldi antennas. The effect of the tumor conductivity on the focusing is discussed. As a straightforward approach and utilizing the Vivaldi antennas, the system can be further combined with MH monitoring application.
Collapse
Affiliation(s)
- Gulsah Altintas
- Department of Electronics and Communication Engineering, İstanbul Technical University, 34469 İstanbul, Turkey; (I.A.); (A.J.); (T.Y.)
| | - Ibrahim Akduman
- Department of Electronics and Communication Engineering, İstanbul Technical University, 34469 İstanbul, Turkey; (I.A.); (A.J.); (T.Y.)
- Mitos Medical Technologies, 34469 İstanbul, Turkey
| | - Aleksandar Janjic
- Department of Electronics and Communication Engineering, İstanbul Technical University, 34469 İstanbul, Turkey; (I.A.); (A.J.); (T.Y.)
- Mitos Medical Technologies, 34469 İstanbul, Turkey
| | - Tuba Yilmaz
- Department of Electronics and Communication Engineering, İstanbul Technical University, 34469 İstanbul, Turkey; (I.A.); (A.J.); (T.Y.)
- Mitos Medical Technologies, 34469 İstanbul, Turkey
| |
Collapse
|
|
7
|
Álvarez-Maestro M, Guerrero-Ramos F, Rodríguez-Faba O, Domínguez-Escrig J, Fernández-Gómez J. Current treatments for BCG failure in non-muscle invasive bladder cancer (NMIBC). Actas Urol Esp 2021; 45:93-102. [PMID: 33012593 DOI: 10.1016/j.acuro.2020.08.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 08/22/2020] [Indexed: 12/17/2022]
Abstract
The treatment of choice for high-risk non-muscle invasive bladder cancer (NMIBC) is bacillus Calmette-Guérin (BCG). However, when this fails, the indicated treatment is radical cystectomy. In recent years, trials are being developed with various drugs to avoid this surgery in patients with BCG failure. The aim of this article is to update the treatments under study for bladder preservation in this patient population. Non-systematic review, searching PubMed with the terms "Bladder cancer", "Non-muscle invasive bladder cancer", "NMIBC", "BCG", "BCG-refractory", "Mitomycin C", "MMC", "Hyperthermia", "Electromotive Drug Administration", "EMDA". We used the search engines clinicaltrials.gov and clinicaltrialsregister.eu to find clinical trials. The only intravesical drug approved by the Food and Drug Administration (FDA) for carcinoma in situ (CIS) after failure to BCG is Valrubicin. Recently, the FDA has approved intravenous Pembrolizumab, following the publication of preliminary data from the KEYNOTE-057 study. Atezolizumab has demonstrated similar preliminary efficacy results. Only microwave-induced chemohyperthermia and EMDA-MMC (Electromotive Drug Administration) are recognized as alternatives in European guidelines. Other options under investigation are taxanes and gemcitabine, alone or in combination, recombinant viruses and device-assisted intravesical chemohyperthermia. The results of new drugs are promising, with a large number of trials underway. Knowing the mechanisms of resistance to BCG is essential to explore new therapeutic options.
Collapse
|
|
8
|
Ruan Q, Ding D, Wang B, He C, Ren X, Feng Z, Pang Z, Wang J, Zhang X, Tang H, Wang J, He Q, Lei Z, Liao Q, Luo J, Cui S. A multi-institutional retrospective study of hyperthermic plus intravesical chemotherapy versus intravesical chemotherapy treatment alone in intermediate and high risk nonmuscle-invasive bladder cancer. Cancer Biol Med 2021; 18:308-317. [PMID: 33628603 PMCID: PMC7877165 DOI: 10.20892/j.issn.2095-3941.2020.0125] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 07/10/2020] [Indexed: 11/11/2022] Open
Abstract
Objective: To compare the efficacy and safety of hyperthermic intravesical chemotherapy (HIVEC) and intravesical chemotherapy (IVEC) in patients with intermediate and high risk nonmuscle-invasive bladder cancer (NMIBC) after transurethral resection. Methods: We included 560 patients diagnosed with primary or recurrent NMIBC between April 2009 and December 2015 at 1 of 6 tertiary centers. We matched 364 intermediate or high risk cases and divided them into 2 groups: the HIVEC+IVEC group [chemohyperthermia (CHT) composed of 3 consecutive sessions followed by intravesical instillation without hyperthermia] and the IVEC group (intravesical instillation without hyperthermia). The data were recorded in the database. The primary endpoint was 2-year recurrence-free survival (RFS) in all NMIBC patients (n = 364), whereas the secondary endpoints were the assessment of radical cystectomy (RC) and 5-year overall survival (OS). Results: There was a significant difference in the 2-year RFS between the two groups in all patients (n = 364; HIVEC+IVEC: 82.42% vs. IVEC: 74.18%, P = 0.038). Compared with the IVEC group, the HIVEC+IVEC group had a lower incidence of RC (P = 0.0274). However, the 5-year OS was the same between the 2 groups (P = 0.1434). Adverse events (AEs) occurred in 32.7% of all patients, but none of the events was serious (grades 3–4). No difference in the incidence or severity of AEs between each treatment modality was observed. Conclusions: This retrospective study showed that HIVEC+IVEC had a higher 2-year RFS and a lower incidence of RC than IVEC therapy in intermediate and high risk NMIBC patients. Both treatments were well-tolerated in a similar manner.
Collapse
Affiliation(s)
- Qiang Ruan
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China.,The First Affiliated Hospital of Jinan University, the First Clinical Medical College of Jinan University, Guangzhou 510630, China
| | - Degang Ding
- Department of Urinary Surgery, Henan Provincial People's Hospital, Zhengzhou 450003, China
| | - Bin Wang
- Department of Urinary Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Chaohong He
- Department of Urinary Surgery, Henan Cancer Hospital, Zhengzhou 450008, China
| | - Xuequn Ren
- Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng 475000, China
| | - Zhenhua Feng
- Department of Urinary Surgery, Gaozhou People's Hospital, Maoming 525200, China
| | - Zhigang Pang
- Department of General Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China
| | - Jin Wang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Xiangliang Zhang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Hongsheng Tang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Jiahong Wang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Qingjun He
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Ziying Lei
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Quanxing Liao
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Jiali Luo
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Shuzhong Cui
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| |
Collapse
|
|
9
|
Abstract
PURPOSE OF REVIEW To give an overview of current options for conservative treatment of patients failing intravesical bacillus Calmette-Guerin (BCG) and to discuss emerging approaches with potential future clinical applications. RECENT FINDINGS Radical cystectomy is the standard-of-care for patients failing BCG therapy. In patients unfit or unwilling to undergo surgery, salvage therapy options could be proposed with the aim to offer local cancer control and prevent progression to muscle-invasive disease. Salvage treatments have been conducted using intravesical chemotherapy regimens, chemoradiation or chemohyperthermia. Intravesical agents such as valrubicin, gemcitabine or docetaxel showed response rates varying between 16 and 40%, whereas combination treatments of gemcitabine with docetaxel or mitomycin reported response rates in up to 50% of all patients with durable responses in about one out of three patients. For chemohyperthermia, 2-year recurrence rates between 41 and 56% have been reported. Ongoing clinical trials are evaluating chemoradiation as well as novel approaches such as systemic immunotherapy, viral gene therapy, targeted therapy or vaccination strategies with promising preliminary outcomes. SUMMARY Salvage therapeutic bladder-sparing strategies for BCG failure such as intravesical chemotherapy or chemoradiation should currently only be considered in patients unfit for or refusing surgery. Innovative concepts such as chemohyperthermia, checkpoint inhibitors, targeted therapy or viral gene therapy could lead to major changes in clinical management of BCG failures in the future.
Collapse
|
|
10
|
Liu K, Zhu J, Song YX, Wang X, Zhou KC, Lu Y, Liu XQ. Thermal Intravesical Chemotherapy Reduce Recurrence Rate for Non-muscle Invasive Bladder Cancer Patients: A Meta-Analysis. Front Oncol 2020; 10:29. [PMID: 32117709 PMCID: PMC7015071 DOI: 10.3389/fonc.2020.00029] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 01/09/2020] [Indexed: 12/24/2022] Open
Abstract
Background: Non-muscle invasive bladder cancer accounts for nearly 80% of newly diagnosed bladder cancer cases, which often recur and progress. This meta-analysis was evaluated by the adverse events and recurrence rate of thermal intravesical chemotherapy vs. normal temperature intravesical chemotherapy in the treatment of non-muscle invasive bladder cancer. Methods: A systematic review and cumulative analysis of studies reporting adverse events and recurrence rate of thermal intravesical chemotherapy vs. normal temperature intravesical chemotherapy was performed through a comprehensive search of Pubmed, Embase, Cochranelibrary.com, CNKI, Wanfang Med Online database and VIP database. All analyses were performed using the Revman manager 5. Result: Twelve studies (11 randomized controlled trials and 1 retrospective study) including 888 patients, 445 in the thermal intravesical chemotherapy group, and 443 in the normal temperature intravesical chemotherapy group, met the eligibility criteria. Patients in the thermal intravesical chemotherapy group had a lower risk of disease recurrence than those who had normal temperature intravesical chemotherapy (24 months follow-up group: RR = 0.30, 95% CI: 0.21-0.43, P < 0.00001, I 2 = 0%; 36 months follow-up group: RR = 0.27, 95% CI: 0.14-0.54, P = 0.0002, I 2 = 0%) while no significant difference in adverse events rate (RR = 0.89, 95% CI = 0.53-1.52; P = 0.67, I 2 = 78%). Conclusions: When compared with normal temperature intravesical chemotherapy, thermal intravesical chemotherapy can reduce the recurrence rate without increasing incidence of adverse events in patients with non-muscle invasive bladder cancer.
Collapse
Affiliation(s)
- Kang Liu
- Department of Urology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China
| | - Jun Zhu
- Department of Urology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China
| | - Yu-Xuan Song
- Department of Urology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China
| | - Xiao Wang
- Department of Urology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China
| | - Ke-Chong Zhou
- Department of Urology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China
| | - Yi Lu
- Department of Urology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China
| | - Xiao-Qiang Liu
- Department of Urology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China
| |
Collapse
|
|
11
|
Khaled D, Taylor J, Holzbeierlein J. Salvage Therapy for Non-muscle-invasive Bladder Cancer: Novel Intravesical Agents. Urol Clin North Am 2019; 47:119-128. [PMID: 31757295 DOI: 10.1016/j.ucl.2019.09.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Bacillus Calmette-Guerin (BCG)-refractory high-grade non-muscle-invasive bladder cancer remains a challenging problem. Radical cystectomy is standard of care, but carries significant morbidity. Therefore, there is a need for effective treatments. Previous salvage intravesical therapies have had disappointing results with long-term follow-up; however, a wide array of novel agents is currently under investigation. These include novel combinations of existing intravesical agents, novel modes of delivery such as hyperthermia, viral mediated therapies, and immunotherapy. We review the need for novel treatment with existing agents and their long-term results, and discuss novel intravesical therapies and the data currently available on these therapies.
Collapse
Affiliation(s)
- Dunia Khaled
- Department of Urology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 3016, Kansas City, KS 66160, USA
| | - John Taylor
- Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA
| | - Jeffrey Holzbeierlein
- Department of Urology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 3016, Kansas City, KS 66160, USA.
| |
Collapse
|
|
12
|
Tan WP, Longo TA, Inman BA. Heated Intravesical Chemotherapy: Biology and Clinical Utility. Urol Clin North Am 2019; 47:55-72. [PMID: 31757301 DOI: 10.1016/j.ucl.2019.09.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Non-muscle-invasive bladder cancer can be a challenging disease to manage. In recent years, hyperthermia therapy in conjunction with intravesical therapy has been gaining traction as a treatment option for bladder cancer, especially if Bacillus Calmette-Guerin might not be available. Trials of intravesical chemotherapy with heat are few and there has been considerable heterogeneity between studies. However, multiple new trials have accrued and high-quality data are forthcoming. In this review, we discuss the role of combined intravesical hyperthermia and chemotherapy as a novel approach for the treatment of bladder cancer.
Collapse
Affiliation(s)
- Wei Phin Tan
- Division of Urology, Duke University Medical Center, Durham, NC 27710, USA
| | - Thomas A Longo
- Division of Urology, Duke University Medical Center, Durham, NC 27710, USA
| | - Brant A Inman
- Division of Urology, Duke University Medical Center, Durham, NC 27710, USA.
| |
Collapse
|
|
13
|
Abstract
Non-muscle-invasive bladder cancer (NMIBC), the most prevalent type of bladder cancer, accounts for ~75% of bladder cancer diagnoses. This disease has a 50% risk of recurrence and 20% risk of progression within 5 years, despite the use of intravesical adjuvant treatments (such as BCG or mitomycin C) that are recommended by clinical guidelines. Intravesical device-assisted therapies, such as radiofrequency-induced thermochemotherapeutic effect (RITE), conductive hyperthermic chemotherapy, and electromotive drug administration (EMDA), have shown promising efficacy. These device-assisted treatments are an attractive alternative to BCG, as issues with supply have been a problem in some countries. RITE might be an effective treatment option for some patients who have experienced BCG failure and are not candidates for radical cystectomy. Data from trials using EMDA suggest that it is effective in high-risk disease but requires further validation, and results of randomized trials are eagerly awaited for conductive hyperthermic chemotherapy. Considerable heterogeneity in patient cohorts, treatment sessions, use of maintenance regimens, and single-arm study design makes it difficult to draw solid conclusions, although randomized controlled trials have been reported for RITE and EMDA.
Collapse
|
|
14
|
Dzimitrowicz A, Cyganowski P, Jamroz P, Jermakowicz-Bartkowiak D, Rzegocka M, Cwiklinska A, Pohl P. Tuning Optical and Granulometric Properties of Gold Nanostructures Synthesized with the Aid of Different Types of Honeys for Microwave-Induced Hyperthermia. MATERIALS (BASEL, SWITZERLAND) 2019; 12:E898. [PMID: 30889837 PMCID: PMC6471425 DOI: 10.3390/ma12060898] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 03/01/2019] [Accepted: 03/14/2019] [Indexed: 12/19/2022]
Abstract
Size-controlled gold nanoparticles (AuNPs) were synthesised with solutions of three types of Polish honeys (lime, multiflower, honeydew) and used in microwave-induced hyperthermia cancer treatment. Optical and structural properties of nanostructures were optimized in reference to measurements made by using UV/Vis absorption spectrophotometry (UV/Vis), transmission electron microscopy (TEM) supported by energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and attenuated total reflectance Fourier transformation infrared spectroscopy (ATR FT-IR). In addition, concentrations of reducing sugars and polyphenols of honeys applied were determined to reveal the role of these chemical compounds in green synthesis of AuNPs. It was found that the smallest AuNPs (20.6 ± 23.3 nm) were produced using a 20% (w/v) multiflower aqueous honey solution and 25 mg·L-1 of Au(III) ions. These AuNPs were then employed in microwave-induced hyperthermia in a system simulating metastatic tissues. This research illustrated that AuNPs, as produced with the aid of a multiflower honey solution, could be suitably used for microwave-induced heating of cancer. A fluid containing resultant Au nanostructures, as compared to water, revealed facilitated heating and the ability to maintain a temperature of 45 °C required for hyperthermia treatment.
Collapse
Affiliation(s)
- Anna Dzimitrowicz
- Department of Analytical Chemistry and Chemical Metallurgy, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze St. Wyspianskiego 27, 50-370 Wroclaw, Poland.
| | - Piotr Cyganowski
- Department of Polymer and Carbonaceous Materials, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze St. Wyspianskiego 27, 50-370 Wroclaw, Poland.
| | - Piotr Jamroz
- Department of Analytical Chemistry and Chemical Metallurgy, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze St. Wyspianskiego 27, 50-370 Wroclaw, Poland.
| | - Dorota Jermakowicz-Bartkowiak
- Department of Polymer and Carbonaceous Materials, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze St. Wyspianskiego 27, 50-370 Wroclaw, Poland.
| | - Malgorzata Rzegocka
- Department of Analytical Chemistry and Chemical Metallurgy, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze St. Wyspianskiego 27, 50-370 Wroclaw, Poland.
| | - Agnieszka Cwiklinska
- Department of Analytical Chemistry and Chemical Metallurgy, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze St. Wyspianskiego 27, 50-370 Wroclaw, Poland.
| | - Pawel Pohl
- Department of Analytical Chemistry and Chemical Metallurgy, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze St. Wyspianskiego 27, 50-370 Wroclaw, Poland.
| |
Collapse
|
|
15
|
Moschini M, Zamboni S, Mattei A, Amparore D, Fiori C, De Dominicis C, Esperto F. Bacillus Calmette-Guérin unresponsiveness in non-muscle-invasive bladder cancer patients: what the urologists should know. MINERVA UROL NEFROL 2019; 71:17-30. [DOI: 10.23736/s0393-2249.18.03309-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
|
|
16
|
What to do during Bacillus Calmette–Guérin shortage? Valid strategies based on evidence. Curr Opin Urol 2018; 28:570-576. [DOI: 10.1097/mou.0000000000000544] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
|
|
17
|
Schooneveldt G, Kok HP, Bakker A, Geijsen ED, Rasch CRN, Rosette JJMCHDL, Hulshof MCCM, Reijke TMD, Crezee H. Clinical validation of a novel thermophysical bladder model designed to improve the accuracy of hyperthermia treatment planning in the pelvic region. Int J Hyperthermia 2018; 35:383-397. [PMID: 30381980 DOI: 10.1080/02656736.2018.1506164] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
PURPOSE Hyperthermia treatment planning for deep locoregional hyperthermia treatment may assist in phase and amplitude steering to optimize the temperature distribution. This study aims to incorporate a physically correct description of bladder properties in treatment planning, notably the presence of convection and absence of perfusion within the bladder lumen, and to assess accuracy and clinical implications for non muscle invasive bladder cancer patients treated with locoregional hyperthermia. METHODS We implemented a convective thermophysical fluid model based on the Boussinesq approximation to the Navier-Stokes equations using the (finite element) OpenFOAM toolkit. A clinician delineated the bladder on CT scans obtained from 14 bladder cancer patients. We performed (1) conventional treatment planning with a perfused muscle-like solid bladder, (2) with bladder content properties without and (3) with flow dynamics. Finally, we compared temperature distributions predicted by the three models with temperature measurements obtained during treatment. RESULTS Much higher and more uniform bladder temperatures are predicted with physically accurate fluid modeling compared to previously employed muscle-like models. The differences reflect the homogenizing effect of convection, and the absence of perfusion. Median steady state temperatures simulated with the novel convective model (3) deviated on average -0.6 °C (-12%) from values measured during treatment, compared to -3.7 °C (-71%) and +1.5 °C (+29%) deviation for the muscle-like (1) and static (2) models, respectively. The Grashof number was 3.2 ± 1.5 × 105 (mean ± SD). CONCLUSIONS Incorporating fluid modeling in hyperthermia treatment planning yields significantly improved predictions of the temperature distribution in the bladder lumen during hyperthermia treatment.
Collapse
Affiliation(s)
- Gerben Schooneveldt
- a Department of Radiation Oncology , Academic Medical Center , Amsterdam , the Netherlands
| | - H Petra Kok
- a Department of Radiation Oncology , Academic Medical Center , Amsterdam , the Netherlands
| | - Akke Bakker
- a Department of Radiation Oncology , Academic Medical Center , Amsterdam , the Netherlands
| | - Elisabeth D Geijsen
- a Department of Radiation Oncology , Academic Medical Center , Amsterdam , the Netherlands
| | - Coen R N Rasch
- a Department of Radiation Oncology , Academic Medical Center , Amsterdam , the Netherlands
| | | | - Maarten C C M Hulshof
- a Department of Radiation Oncology , Academic Medical Center , Amsterdam , the Netherlands
| | - Theo M de Reijke
- b Department of Urology , Academic Medical Center , Amsterdam , the Netherlands
| | - Hans Crezee
- a Department of Radiation Oncology , Academic Medical Center , Amsterdam , the Netherlands
| |
Collapse
|
|
18
|
Tan WS, Panchal A, Buckley L, Devall AJ, Loubière LS, Pope AM, Feneley MR, Cresswell J, Issa R, Mostafid H, Madaan S, Bhatt R, McGrath J, Sangar V, Griffiths TRL, Page T, Hodgson D, Datta SN, Billingham LJ, Kelly JD. Radiofrequency-induced Thermo-chemotherapy Effect Versus a Second Course of Bacillus Calmette-Guérin or Institutional Standard in Patients with Recurrence of Non-muscle-invasive Bladder Cancer Following Induction or Maintenance Bacillus Calmette-Guérin Therapy (HYMN): A Phase III, Open-label, Randomised Controlled Trial. Eur Urol 2018; 75:63-71. [PMID: 30274699 DOI: 10.1016/j.eururo.2018.09.005] [Citation(s) in RCA: 95] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 09/04/2018] [Indexed: 11/19/2022]
Abstract
BACKGROUND There is no effective intravesical second-line therapy for non-muscle-invasive bladder cancer (NMIBC) when bacillus Calmette-Guérin (BCG) fails. OBJECTIVE To compare disease-free survival time (DFS) between radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/maintenance BCG. DESIGN, SETTINGS, AND PARTICIPANTS Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 (HYMN [ClinicalTrials.gov: NCT01094964]). INTERVENTION Patients were randomly assigned (1:1) to RITE (60min, 40mg mitomycin-C, 42±2°C) or control following stratification for carcinoma in situ (CIS) status (present/absent), therapy history (failure of previous induction/maintenance BCG), and treatment centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary outcome measures were DFS and complete response (CR) at 3 mo for the CIS at randomisation subgroup. Analysis was based on intention-to-treat. RESULTS AND LIMITATIONS A total of 104 patients were randomised (48 RITE: 56 control). Median follow-up for the 31 patients without a DFS event was 36 mo. There was no significant difference in DFS between treatment arms (hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.84-2.10, p=0.23) or in 3-mo CR rate in CIS patients (n=71; RITE: 30% vs control: 47%, p=0.15). There was no significant difference in DFS between treatment arms in non-CIS patients (n=33; RITE: 53% vs control: 24% at 24 mo, HR 0.50, 95% CI 0.22-1.17, p=0.11). DFS was significantly lower in RITE than in control in CIS with/without papillary patients (n=71; HR 2.06, 95% CI 1.17-3.62, p=0.01; treatment-subgroup interaction p=0.007). Disease progression was observed in four patients in each treatment arm. Adverse events and health-related quality of life between treatment arms were comparable. CONCLUSIONS DFS was similar between RITE and control. RITE may be a second-line therapy for non-CIS recurrence following BCG failure; however, confirmatory trials are needed. RITE patients with CIS with/without papillary had lower DFS than control. HYMN highlights the importance of the control arm when evaluating novel therapies. PATIENT SUMMARY This study did not show a difference in bladder cancer outcomes between microwave-heated chemotherapy and standard of care treatment. Papillary bladder lesions may benefit from microwave-heated chemotherapy treatment; however, more research is needed. Both treatments are similarly well tolerated.
Collapse
Affiliation(s)
- Wei Shen Tan
- Division of Surgery & Interventional Science, University College London, London, UK; Department of Urology, University College London Hospital, London, UK
| | - Anesh Panchal
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Laura Buckley
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Adam J Devall
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Laurence S Loubière
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Ann M Pope
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Mark R Feneley
- Department of Urology, University College London Hospital, London, UK
| | - Jo Cresswell
- Department of Urology, James Cook University Hospital, Middlesbrough, UK
| | - Rami Issa
- Department of Urology, St George's Hospital, London, UK
| | - Hugh Mostafid
- Department of Urology, Royal Surrey County Hospital, Guildford, UK
| | - Sanjeev Madaan
- Department of Urology, Darent Valley Hospital, Dartford, UK
| | - Rupesh Bhatt
- Department of Urology, Queen Elizabeth Hospital, Birmingham, UK
| | - John McGrath
- Department of Urology, Royal Devon and Exeter Hospital, Exeter, UK
| | - Vijay Sangar
- Department of Urology, Withington Hospital, Manchester, UK
| | | | - Toby Page
- Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Dominic Hodgson
- Department of Urology, Queen Alexandra Hospital, Portsmouth, UK
| | | | - Lucinda J Billingham
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - John D Kelly
- Division of Surgery & Interventional Science, University College London, London, UK; Department of Urology, University College London Hospital, London, UK.
| |
Collapse
|
|
19
|
Sommariva ML, Sandri SD, Guerrer CS. Treatment of Acute Iatrogenic Cystitis Secondary to Bladder Chemo-Immuno-Instillation or Pelvic Radiotherapy. Urologia 2018. [DOI: 10.1177/039156031007700305] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The onset of cystitis during intravesical chemo-immunotherapy for the treatment of non-muscle invasive transitional cell bladder tumor, or after pelvic radiotherapy mainly for prostate cancer, is a frequent clinical situation, not easily manageable due to the lack of responsiveness to symptomatic drugs, often resulting in discontinuation of cancer treatment in many cases. The similarity of symptoms with those of the painful bladder syndrome, otherwise called interstitial cystitis, has led us to use the same treatment with intravesical sodium hyaluronate in order to obtain an improvement of symptomatology. We therefore performed a prospective study on 55 consecutive male symptomatic patients, aged from 54 to 81 years: 11 after radiotherapy, 17 after BCG and 27 after Mitomicyn C bladder instillations, 12 of whom in combination with bladder hyperthermia. All subjects underwent bladder instillations with sodium hyaluronate 40 mg in 50 mL weekly for 8 to 24 weeks depending on the time needed to the resolution of the symptoms. During the first 4 weeks 32 mg of dexamethasone were also instilled intravesically, mixed with hyaluronate, in order to obtain a stronger anti-inflammatory activity due also to its higher capacity of penetration in the bladder mucosa. The symptoms intensity was evaluated through a Visual Analogue Score (VAS) of the discomfort and pain perceived from 0 to 10, and bladder capacity was recorded with micturition diary before and after the treatment. After 16 weeks VAS improved in every case of chemical cystitis from an initial mean value of 8.6 to a final mean value of 1(with 3 as a maximum value recorded). The difference was highly significant (p <0.001). Bladder capacity increased in all cases of chemical cystitis from a mean value of 56 to 276 mL with a highly significant improvement (p <0.001) and in all cases of post-actinic cystitis from a mean bladder capacity of 89 to a final mean value of 239 mL, with a significant improvement (p= 0.05). We did not observe any side effect due to our treatment. Therefore, we can conclude that bladder instillation with sodium hyaluronate for at least 8 weeks and dexamethasone in the first 4 weeks can solve the symptoms of iatrogenic cystitis secondary to chemo-immunotherapy or pelvic radiotherapy, without incurring in side effects. To our knowledge this treatment has never been published before in scientific medical literature.
Collapse
Affiliation(s)
- Monica L Sommariva
- Unità Operativa Complessa di Urologia, Unità Spinale Ospedale “G. Fornaroli”, Magenta
| | - Sandro D. Sandri
- Unità Operativa Complessa di Urologia, Unità Spinale Ospedale “G. Fornaroli”, Magenta
| | - Chiara S. Guerrer
- Unità Operativa Complessa di Urologia, Unità Spinale Ospedale “G. Fornaroli”, Magenta
| |
Collapse
|
|
20
|
Buss JH, Begnini KR, Bender CB, Pohlmann AR, Guterres SS, Collares T, Seixas FK. Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer. Front Pharmacol 2018; 8:977. [PMID: 29379438 PMCID: PMC5770893 DOI: 10.3389/fphar.2017.00977] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Accepted: 12/21/2017] [Indexed: 01/06/2023] Open
Abstract
Mycobacterium bovis bacillus Calmette–Guerin (BCG) remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1) controlling drug release for extended time frames, (2) combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3) reducing systemic side effects, (4) increasing bioavailability, (5) and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer.
Collapse
Affiliation(s)
- Julieti Huch Buss
- Laboratory of Cancer Biotechnology, Biotechnology Graduate Program, Technology Development Center, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil
| | - Karine Rech Begnini
- Laboratory of Cancer Biotechnology, Biotechnology Graduate Program, Technology Development Center, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil
| | - Camila Bonemann Bender
- Laboratory of Cancer Biotechnology, Biotechnology Graduate Program, Technology Development Center, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil
| | - Adriana R Pohlmann
- Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Institute of Chemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Silvia S Guterres
- Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Tiago Collares
- Laboratory of Cancer Biotechnology, Biotechnology Graduate Program, Technology Development Center, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil
| | - Fabiana Kömmling Seixas
- Laboratory of Cancer Biotechnology, Biotechnology Graduate Program, Technology Development Center, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil
| |
Collapse
|
|
21
|
Flores-Carbajal J, Sousa-Escandón A, Sousa-Gonzalez D, Rodriguez Gomez S, Lopez Saavedra M, Fernandez Martinez ME. Recirculating chemohyperthermia as a treatment for non-muscle invasive bladder cancer: Current and future perspectives. World J Clin Urol 2017; 6:34-39. [DOI: 10.5410/wjcu.v6.i2.34] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2016] [Revised: 12/19/2016] [Accepted: 03/13/2017] [Indexed: 02/05/2023] Open
Abstract
About 75% of all bladder cancer diagnosed are non-muscle invasive bladder cancer (NMIBC), recurring over 50% of them after transurethral resection of the bladder tumor. In order to prevent recurrences, adjuvant intravesical chemotherapy with mitomycin C and immunotherapy with bacillus Calmette-Guérin (BCG) is traditionally used. Unfortunately, many patients relapse after receiving these treatments and a significant proportion of them require surgery. After a one-to-three years BCG maintenance, the risk for progression at 5 years was 19.3% for T1G3 tumors. Many new treatment approaches are being investigated to increase the effectiveness of adjuvant intravesical therapy. One of the developing treatments for intermediate and high-risk NMIBC is the combination of intravesical chemotherapy and hyperthermia, called chemohyperthermia. This article provides a review of the mechanism of action, current status and indications, results and future perspectives.
Collapse
|
|
22
|
Woldu SL, Şanli Ö, Lotan Y. Tackling non-muscle invasive bladder cancer in the clinic. Expert Rev Anticancer Ther 2017; 17:467-480. [PMID: 28359179 DOI: 10.1080/14737140.2017.1313119] [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] [Indexed: 01/05/2023]
Abstract
INTRODUCTION Non-muscle invasive bladder cancer (NMIBC) is a common disease process with a high propensity for recurrence and risk of progression to muscle-invasive or systemic disease. Optimal management of NMIBC depends on appropriate resection and staging, risk-based use of intravesical therapy and tailored surveillance. Current challenges include compliance with guideline recommendations and cancers which are refractory to standard therapies. Areas covered: This review summarizes the conventional management of NMIBC - which relies on strict cystoscopic surveillance and intravesical therapies with chemotherapy and/or immunotherapy in the form of bacillus Calmette-Guerin (BCG). As many patients will be resistant to conventional treatment, investigational therapies and novel prognostic models will also be discussed. Expert commentary: For decades, the management of NMIBC has been predicated on intravesical therapies, most often through the instillation of BCG which has proven clinical efficacy over transurethral resection alone. Despite this, many patients will recur or progress after BCG therapy. While radical cystectomy remains the standard for such patients, suitable alternatives are being actively investigated. An increased interest in immunotherapy for malignancy has reinvigorated this field and on-going advances in disease prognostication are likely to improve upon the existing treatment paradigms for NMIBC.
Collapse
Affiliation(s)
- Solomon L Woldu
- a Department of Urology , University of Texas Southwestern Medical Center , Dallas , TX , USA
| | - Öner Şanli
- a Department of Urology , University of Texas Southwestern Medical Center , Dallas , TX , USA.,b Department of Urology, Istanbul Faculty of Medicine , Istanbul University , Istanbul , Turkey
| | - Yair Lotan
- a Department of Urology , University of Texas Southwestern Medical Center , Dallas , TX , USA
| |
Collapse
|
|
23
|
Sadee C, Kashdan E. A model of thermotherapy treatment for bladder cancer. MATHEMATICAL BIOSCIENCES AND ENGINEERING : MBE 2016; 13:1169-1183. [PMID: 27775374 DOI: 10.3934/mbe.2016037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
In this work, we investigate chemo- thermotherapy, a recently clinically-approved post-surgery treatment of non muscle invasive urothelial bladder carcinoma. We developed a mathematical model and numerically simulated the physical processes related to this treatment. The model is based on the conductive Maxwell's equations used to simulate the therapy administration and Convection-Diffusion equation for incompressible fluid to study heat propagation through the bladder tissue. The model parameters correspond to the data provided by the thermotherapy device manufacturer. We base our computational domain on a CT image of a human bladder. Our numerical simulations can be applied to further research on the effects of chemo- thermotherapy on bladder and surrounding tissues and for treatment personalization in order to maximize the effect of the therapy while avoiding burning of the bladder.
Collapse
Affiliation(s)
- Christoph Sadee
- School of Mathematics and Statistics, University College Dublin, Belfield, Dublin 4, Ireland.
| | | |
Collapse
|
|
24
|
Schooneveldt G, Kok HP, Balidemaj E, Geijsen ED, van Ommen F, Sijbrands J, Bakker A, de la Rosette JJMCH, Hulshof MCCM, de Reijke TM, Crezee J. Improving hyperthermia treatment planning for the pelvis by accurate fluid modeling. Med Phys 2016; 43:5442. [DOI: 10.1118/1.4961741] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
|
|
25
|
Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guérin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non–Muscle-invasive Bladder Cancer. Eur Urol 2016; 69:1046-52. [DOI: 10.1016/j.eururo.2016.01.006] [Citation(s) in RCA: 140] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Accepted: 01/05/2016] [Indexed: 01/29/2023]
|
|
26
|
Schooneveldt G, Bakker A, Balidemaj E, Chopra R, Crezee J, Geijsen ED, Hartmann J, Hulshof MC, Kok HP, Paulides MM, Sousa-Escandon A, Stauffer PR, Maccarini PF. Thermal dosimetry for bladder hyperthermia treatment. An overview. Int J Hyperthermia 2016; 32:417-33. [DOI: 10.3109/02656736.2016.1156170] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
|
|
27
|
Abstract
PURPOSE OF REVIEW This article reviews the natural biology of noninvasive bladder cancer and its management strategies while summarizing the most recent advances in the field. RECENT FINDINGS Nonmuscle invasive bladder cancer (NMIBC) has a tendency to recur and progress. Risk stratification has helped triage patients but improved tools, including biomarkers, are still needed. Enhanced endoscopy with photodynamic imaging, narrow band imaging, optical coherence tomography and confocal laser endomicroscopy show promise for diagnosis, risk stratification and disease monitoring. Attempts at better treatment, especially in refractory high-risk cases, include the addition of intravesical hyperthermia, combination and sequential therapy with existing agents and the use of novel agents such as mycobacterial cell wall extract. New data are emerging regarding the potential role of active surveillance in low-risk patients. SUMMARY NMIBC represents a variety of disease states and continues to pose management challenges. As our understanding of tumor biology improves and technology advances, achieving better outcomes through individualized care may be possible.
Collapse
|
|
28
|
Abstract
Hyperthermia represents a unique, safe, and advantageous methodology for improving therapeutic strategies in the management of bladder cancer. This modality has shown promise in contributing to treatment regimens for both superficial and muscle-invasive disease. Especially in conjunction with intravesical chemotherapy, systemic therapy, and radiotherapy, hyperthermia shows particular synergistic benefit. As such, it should be explored further through clinical use and clinical trial in conjunction with currently available techniques and emerging technologies. However, to conceptualise the way forward, it is particularly important to understand the current challenges to widespread use of non-invasive, bladder-sparing approaches and the current state of bladder cancer care. As such, in the following article, we have focused on not only the rationale for concurrent radiotherapy and hyperthermia, but also the clinical landscape in bladder cancer as a whole.
Collapse
Affiliation(s)
- James William Snider
- a Department of Radiation Oncology , University of Maryland Medical Center , Baltimore , Maryland , USA
| | - Niloy Ranjan Datta
- b Department of Radiation Oncology, KSA-KSB, Kantonsspital Aarau , Aarau , Switzerland
| | - Zeljko Vujaskovic
- a Department of Radiation Oncology , University of Maryland Medical Center , Baltimore , Maryland , USA
| |
Collapse
|
|
29
|
Liem EIML, Crezee H, de la Rosette JJ, de Reijke TM. Chemohyperthermia in non-muscle-invasive bladder cancer: An overview of the literature and recommendations. Int J Hyperthermia 2016; 32:363-73. [PMID: 27056069 DOI: 10.3109/02656736.2016.1155760] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Non-muscle-invasive bladder cancer (NMIBC) is characterised by a high risk of recurrence for the present standard treatment of transurethral resection of the bladder (TURB) followed by intravesical instillation of Mitomycin-C (MMC) or bacillus Calmette-Guérin (BCG). To decrease this high recurrence rate, alternative treatments are studied. Intravesical MMC combined with hyperthermia could be an interesting alternative active treatment for intermediate- and high-risk NMIBC, and has been investigated in the past years. Hyperthermia, raising tumour temperatures to 40-44 °C, can be achieved with several hyperthermia systems, based on three different techniques: 1) intravesical microwave induced heating, 2) conductive heating, and 3) loco-regional, using external radiofrequency antennas. In this review an overview is given of the available hyperthermia systems and the reported outcomes. Future directions are discussed. Optimal implementation of a combined regimen of MMC and hyperthermia requires further clinical trials to identify patients who will benefit most from this treatment, to optimise treatment schedules and to compare the efficacy of different hyperthermia devices.
Collapse
Affiliation(s)
- Esmee I M L Liem
- a Department of Urology , Academic Medical Centre , Amsterdam , the Netherlands
| | - Hans Crezee
- b Department of Radiation oncology Academic Medical Centre , Amsterdam , the Netherlands
| | | | - Theo M de Reijke
- a Department of Urology , Academic Medical Centre , Amsterdam , the Netherlands
| |
Collapse
|
|
30
|
Stauffer PR, van Rhoon GC. Overview of bladder heating technology: matching capabilities with clinical requirements. Int J Hyperthermia 2016; 32:407-16. [PMID: 26939993 DOI: 10.3109/02656736.2016.1141239] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Moderate temperature hyperthermia (40-45°C for 1 h) is emerging as an effective treatment to enhance best available chemotherapy strategies for bladder cancer. A rapidly increasing number of clinical trials have investigated the feasibility and efficacy of treating bladder cancer with combined intravesical chemotherapy and moderate temperature hyperthermia. To date, most studies have concerned treatment of non-muscle-invasive bladder cancer (NMIBC) limited to the interior wall of the bladder. Following the promising results of initial clinical trials, investigators are now considering protocols for treatment of muscle-invasive bladder cancer (MIBC). This paper provides a brief overview of the devices and techniques used for heating bladder cancer. Systems are described for thermal conduction heating of the bladder wall via circulation of hot fluid, intravesical microwave antenna heating, capacitively coupled radio-frequency current heating, and radiofrequency phased array deep regional heating of the pelvis. Relative heating characteristics of the available technologies are compared based on published feasibility studies, and the systems correlated with clinical requirements for effective treatment of MIBC and NMIBC.
Collapse
Affiliation(s)
- Paul R Stauffer
- a Department of Radiation Oncology , Thomas Jefferson University , Philadelphia , Pennsylvana , USA and
| | - Gerard C van Rhoon
- b Department of Radiation Oncology , Erasmus Medical Centre Cancer Institute , Rotterdam , The Netherlands
| |
Collapse
|
|
31
|
Soria F, Allasia M, Oderda M, Gontero P. Hyperthermia for non-muscle invasive bladder cancer. Expert Rev Anticancer Ther 2016; 16:313-321. [DOI: 10.1586/14737140.2016.1135743] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
|
|
32
|
van Valenberg H, Colombo R, Witjes F. Intravesical radiofrequency-induced hyperthermia combined with chemotherapy for non-muscle-invasive bladder cancer. Int J Hyperthermia 2016; 32:351-62. [PMID: 26905963 DOI: 10.3109/02656736.2016.1140232] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Although many treatment modalities and schedules for non-muscle-invasive bladder cancer (NMIBC) exist, all yet prove to have limitations. Therefore the search for new forms of therapy continues. One of these forms consists of combining intravesical chemotherapy, typically mitomycin C (MMC), with hyperthermia achieved by a microwave-applicator. We aimed to review the current status of intravesical radiofrequency (RF) induced chemohyperthermia (CHT) for NMIBC with regard to efficacy, adverse-events (AEs) and its future perspective. A search for RF-induced CHT in MEDLINE, Embase, Cochrane and ClinicalTrials.gov databases was performed. Relevant conference abstracts were searched for manually. If applicable, experts on the area were consulted. Papers were selected based on abstract and title. A table of newly published clinical trials since 2011 was constructed. No meta-analysis could be performed based on these new papers. Efficacy proved to be better for RF-induced CHT compared to both MMC alone and bacillus Calmette-Guérin (BCG) instillations, with the latter being based on just one abstract of a randomised controlled trial. The AE rate in CHT is higher compared to MMC instillation, but is similar compared to BCG, albeit different in the type of AE. In almost all studies no severe AEs are reported. Although heterogeneity in methodology exists, RF-induced CHT seems promising. However, alternative methods of applying hyperthermia are starting to present their first results, imposing as effective options too. Intravesical RF-induced CHT may become an alternative for BCG instillation, and possibly for cystectomy, although further level 1 evidence is required for both reliable and reproducible data on efficacy and adverse events.
Collapse
Affiliation(s)
- Hans van Valenberg
- a Department of Urology , Radboud University Medical Centre , Nijmegen , Netherlands and
| | - Renzo Colombo
- b Department of Urology , University 'Vita-Salute' San Raffaele , Milan , Italy
| | - Fred Witjes
- a Department of Urology , Radboud University Medical Centre , Nijmegen , Netherlands and
| |
Collapse
|
|
33
|
Radiofrequency-Induced Thermo-Chemotherapy Effect (Rite) for Non Muscle Invasive Bladder Cancer Treatment: Current Role and Perspectives. Urologia 2016; 83:7-17. [DOI: 10.5301/uro.5000197] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2016] [Indexed: 11/20/2022]
Abstract
Although many treatment modalities and schedules for nonmuscle invasive bladder cancer (NMIBC) exist, all yet prove to have limitations and the search for new therapeutic strategies continues. Among these, the combination of intravesical chemotherapy and microwave-induced local hyperthermia has been investigated and clinically tested during more than 15 years. Objective An updated review of intravesical radiofrequency (RF)-induced thermo-chemotherapy effect (RITE) for NMIBC with regard to efficacy, adverse events (AEs) and perspectives. Evidence Acquisition An extensive and sensitive search for RF-induced chemo-hyperthermia in Medline, Embase, Cochrane and ClinicalTrials.gov databases was performed. A table of published clinical trials up to 2016 was constructed. No meta-analysis could be performed on the basis of new papers. Evidence Synthesis Recurrence was seen 59% less after RITE than after mitomycin C (MMC) alone in adjuvant clinical setting with an overall bladder preservation rate after RITE of 85%. The efficacy was proved to be comparable to that of Bacillus Calmette-Guèrin (BCG), based on a single comparative multicentric study. Due to short follow-up, no conclusions can be drawn about time to recurrence and progression. The AE rate in RITE was higher, although not statistically significant, than MMC alone and similar to that of BCG, albeit different in the type of AE. In almost all studies, no severe AEs are reported. Conclusions RITE appears as a promising treatment option for NMIBC, particularly for high-risk patients with recurrent tumors, for those unsuitable for radical cystectomy and when Bacillus Calmette-Guèrin treatment is contraindicated. Further high-level evidence is needed for both reliable and reproducible data on efficacy and adverse events.
Collapse
|
|
34
|
A smart, phase transitional and injectable DOX/PLGA-Fe implant for magnetic-hyperthermia-induced synergistic tumor eradication. Acta Biomater 2016; 29:298-306. [PMID: 26432438 DOI: 10.1016/j.actbio.2015.09.037] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Revised: 09/09/2015] [Accepted: 09/28/2015] [Indexed: 12/15/2022]
Abstract
Magnetic hyperthermia ablation is a new and minimally invasive modality for localized tumor removal. However, an inadequate ablation dosage can leave a residual tumor or cause a variety of complications. In addition, commonly used magnetic nanoparticles can easily escape from the tumor tissue, which present potential safety problems. In this study, a smart phase transitional and injectable implant based on biocompatible poly lactic-co-glycolic acid (PLGA) implant incorporating magnetic material (Fe powder) and anti-cancer drug (doxorubicin (DOX)) was developed. The magnetic-induced hyperthermia and release efficiency of DOX were evaluated in vitro. Drug release can be controlled under external alternating current magnetic field (AMF). The results of the in vivo tumor therapeutic efficacy showed that when exposed to external AMF, this smart injectable DOX/PLGA-Fe implant could converse magnetic energy into heat and accelerate the release of DOX, which leads to increasing the temperature to achieve tumor coagulative necrosis and accelerating the release of DOX to enhance residual tumor apoptosis. Furthermore, there was no leakage of magnetic material, as demonstrated using real-time ultrasound (US) and computerized tomography (CT) imaging, realizing the guidance and monitoring of tumor therapy. In conclusion, this smart phase transitional and injectable implant DOX/PLGA-Fe has the ability to improve the efficiency of this newly developed minimally invasive magnetic ablation of tumor treatment technique, and will provide a new avenue of developing minimally invasive synergistic tumor therapy.
Collapse
|
|
35
|
Tang DH, Chang SS. Management of carcinoma in situ of the bladder: best practice and recent developments. Ther Adv Urol 2015; 7:351-64. [PMID: 26622320 DOI: 10.1177/1756287215599694] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Management of carcinoma in situ of the bladder remains a complex and challenging endeavor due to its high rate of recurrence and progression. Although it is typically grouped with other nonmuscle invasive bladder cancers, its higher grade and aggressiveness make it a unique clinical entity. Intravesical bacillus Calmette-Guérin is the standard first-line treatment given its superiority to other agents. However, high rates of bacillus Calmette-Guérin failure highlight the need for additional therapies. Radical cystectomy has traditional been the standard second-line therapy, but additional intravesical therapies may be more appealing for non-surgical candidates and patients refusing cystectomy. The subject of this review is the treatment strategies and available therapies currently available for carcinoma in situ of the bladder. It discusses alternative intravesical treatment options for patients whose condition has failed to respond to bacillus Calmette-Guérin therapy and who are unfit or unwilling to undergo cystectomy.
Collapse
Affiliation(s)
- Dominic H Tang
- Department of Urologic Surgery, Vanderbilt University Medical Center, MCN A-1302, Nashville, TN 37027, USA
| | - Sam S Chang
- Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| |
Collapse
|
|
36
|
Bahouth Z, Halachmi S, Moskovitz B, Nativ O. The role of hyperthermia as a treatment for non-muscle invasive bladder cancer. Expert Rev Anticancer Ther 2015; 16:189-98. [PMID: 26618756 DOI: 10.1586/14737140.2016.1126515] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Non-muscle invasive bladder cancer (NMIBC) has a high tendency for recurrence and progression. Currently, all known intravesical agents are associated with adverse effects (AEs) and limited efficacy. The combination of hyperthermia (HT) with intravesical Mitomycin C (MMC) chemotherapy has been shown to improve outcomes. The added efficacy of HT to MMC was first shown in preclinical studies. The reports on patients with NMIBC have indicated that the treatment is safe and well tolerated. Several clinical studies reported the efficacy of radiofrequency-induced chemotherapy effect (RITE) in the treatment of patients with NMIBC. This modality was shown to be superior to MMC alone. RITE was effective also in patients with high-risk NMIBC, including those who failed Bacillus Calmette-Guérin (BCG). This study provides an updated review of literature regarding the use of RITE in patients with NMIBC.
Collapse
Affiliation(s)
- Zaher Bahouth
- a Department of Urology, Bnai-Zion Medical Center, Faculty of Medicine , Technion- Institute of Technology , Haifa , Israel
| | - Sarel Halachmi
- a Department of Urology, Bnai-Zion Medical Center, Faculty of Medicine , Technion- Institute of Technology , Haifa , Israel
| | - Boaz Moskovitz
- a Department of Urology, Bnai-Zion Medical Center, Faculty of Medicine , Technion- Institute of Technology , Haifa , Israel
| | - Ofer Nativ
- a Department of Urology, Bnai-Zion Medical Center, Faculty of Medicine , Technion- Institute of Technology , Haifa , Israel
| |
Collapse
|
|
37
|
Geijsen ED, de Reijke TM, Koning CC, Zum Vörde Sive Vörding PJ, de la Rosette JJ, Rasch CR, van Os RM, Crezee J. Combining Mitomycin C and Regional 70 MHz Hyperthermia in Patients with Nonmuscle Invasive Bladder Cancer: A Pilot Study. J Urol 2015; 194:1202-8. [DOI: 10.1016/j.juro.2015.05.102] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/13/2015] [Indexed: 10/23/2022]
Affiliation(s)
- Elisabeth D. Geijsen
- Departments of Radiation Oncology and Urology (TMdR, JJdlR), Academic Medical Center, Amsterdam, The Netherlands
| | - Theo M. de Reijke
- Departments of Radiation Oncology and Urology (TMdR, JJdlR), Academic Medical Center, Amsterdam, The Netherlands
| | - Caro C. Koning
- Departments of Radiation Oncology and Urology (TMdR, JJdlR), Academic Medical Center, Amsterdam, The Netherlands
| | | | - Jean J. de la Rosette
- Departments of Radiation Oncology and Urology (TMdR, JJdlR), Academic Medical Center, Amsterdam, The Netherlands
| | - Coen R. Rasch
- Departments of Radiation Oncology and Urology (TMdR, JJdlR), Academic Medical Center, Amsterdam, The Netherlands
| | - Rob M. van Os
- Departments of Radiation Oncology and Urology (TMdR, JJdlR), Academic Medical Center, Amsterdam, The Netherlands
| | - Johannes Crezee
- Departments of Radiation Oncology and Urology (TMdR, JJdlR), Academic Medical Center, Amsterdam, The Netherlands
| |
Collapse
|
|
38
|
Kassouf W, Traboulsi SL, Kulkarni GS, Breau RH, Zlotta A, Fairey A, So A, Lacombe L, Rendon R, Aprikian AG, Siemens DR, Izawa JI, Black P. CUA guidelines on the management of non-muscle invasive bladder cancer. Can Urol Assoc J 2015; 9:E690-704. [PMID: 26664503 PMCID: PMC4662433 DOI: 10.5489/cuaj.3320] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
| | | | | | | | | | - Andrew Fairey
- Division of Urology, University of Alberta, Edmonton, AB
| | - Alan So
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC
| | | | | | | | | | | | - Peter Black
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC
| |
Collapse
|
|
39
|
|
|
40
|
Sooriakumaran P, Chiocchia V, Dutton S, Pai A, Ayres BE, Le Roux P, Swinn M, Bailey M, Perry MJ, Issa R. Predictive Factors for Time to Progression after Hyperthermic Mitomycin C Treatment for High-Risk Non-Muscle Invasive Urothelial Carcinoma of the Bladder: An Observational Cohort Study of 97 Patients. Urol Int 2015; 96:83-90. [DOI: 10.1159/000435788] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Accepted: 06/05/2015] [Indexed: 11/19/2022]
Abstract
Introduction: Hyperthermic mitomycin (HM) is a novel treatment modality for selected patients with high-risk non-muscle invasive bladder cancer (NMIBC). We sought to determine predictors of response to this therapy. Patients and Methods: A longitudinal, cohort study of 97 patients with high-risk NMIBC treated with ≥4 HM instillations on a prophylactic schedule was conducted. The primary outcome was time-to-progression survival; secondary outcomes were overall survival, cancer-specific survival, and adverse events. Descriptive statistics, Kaplan-Meier survival analyses, Cox proportional hazards modelling, and univariate and multivariable regression were performed. Results: The presence of initial complete response (CR; no evidence of disease at first check video-cystoscopy and urine cytology) post-HM treatment was an independent predictor of good response to HM. Female patients and those without carcinoma in situ (CIS) also appeared to respond better to the intervention. The overall bladder preservation rate at a median of 27 months was 81.4%; 17/97 (17.5%) patients died during the course of the study. Conclusions: High-risk NMIBC patients can be safely treated with HM and have good oncological outcome. However, those without an initial CR have a poor prognosis and should be counselled towards adopting other treatment methodologies such as cystectomy. Female gender and lack of CIS may be good prognostic indicators for response to HM.
Collapse
|
|
41
|
Casey RG, Catto JW, Cheng L, Cookson MS, Herr H, Shariat S, Witjes JA, Black PC. Diagnosis and Management of Urothelial Carcinoma In Situ of the Lower Urinary Tract: A Systematic Review. Eur Urol 2015; 67:876-88. [DOI: 10.1016/j.eururo.2014.10.040] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Accepted: 10/24/2014] [Indexed: 12/28/2022]
|
|
42
|
Abstract
PURPOSE OF REVIEW Radical cystectomy is the standard of care for patients who fail intravesical bacillus Calmette-Guérin (BCG) for nonmuscle invasive bladder cancer (NMIBC). For patients unwilling or unable to undergo cystectomy, numerous local therapies exist, although few are approved by the Food and Drug Administration. This review describes available therapies for this challenging clinical entity. RECENT FINDINGS Combination intravesical chemotherapy, targeted therapy, and drug delivery enhancement have all been under recent investigation and are promising, although none has proven superior as of yet. SUMMARY While BCG is standard treatment for intermediate and high-risk NMIBC, many patients fail therapy with recurrence or progression. Early cystectomy is the standard of care for BCG failure; however, many patients are unwilling or unable to undergo cystectomy. Multiple intravesical therapies have been used in this BCG failure population with moderate success, and, recently, technologies to improve drug delivery or create novel drugs have also been applied. Comparing efficacy of these therapies remain challenging as study cohorts are heterogeneous and study designs are variable. However, there are an increasing number of novel treatment options that can be offered to patients faced with recurrent NMIBC after BCG who seek bladder-sparing therapy.
Collapse
|
|
43
|
Begnini KR, Buss JH, Collares T, Seixas FK. Recombinant Mycobacterium bovis BCG for immunotherapy in nonmuscle invasive bladder cancer. Appl Microbiol Biotechnol 2015; 99:3741-54. [DOI: 10.1007/s00253-015-6495-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2014] [Revised: 02/17/2015] [Accepted: 02/19/2015] [Indexed: 02/07/2023]
|
|
44
|
Arends TJH, Falke J, Lammers RJM, Somford DM, Hendriks JCM, de Weijert MCA, Arentsen HC, van der Heijden AG, Oosterwijk E, Alfred Witjes J. Urinary cytokines in patients treated with intravesical mitomycin-C with and without hyperthermia. World J Urol 2014; 33:1411-7. [DOI: 10.1007/s00345-014-1458-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2014] [Accepted: 11/27/2014] [Indexed: 10/24/2022] Open
|
|
45
|
Wong TW. Electrical, magnetic, photomechanical and cavitational waves to overcome skin barrier for transdermal drug delivery. J Control Release 2014; 193:257-69. [DOI: 10.1016/j.jconrel.2014.04.045] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Revised: 04/21/2014] [Accepted: 04/23/2014] [Indexed: 01/17/2023]
|
|
46
|
Kiss B, Schneider S, Thalmann GN, Roth B. Is thermochemotherapy with the Synergo system a viable treatment option in patients with recurrent non-muscle-invasive bladder cancer? Int J Urol 2014; 22:158-62. [PMID: 25339291 DOI: 10.1111/iju.12639] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Accepted: 09/02/2014] [Indexed: 11/30/2022]
Abstract
OBJECTIVES To prospectively evaluate the outcome of combined microwave-induced bladder wall hyperthermia and intravesical mitomycin C instillation (thermochemotherapy) in patients with recurrent non-muscle-invasive bladder cancer. METHODS Between 2003 and 2009, 21 patients (median age 70 years, range 35-95 years) with recurrent non-muscle-invasive bladder cancer (pTaG1-2 n = 9; pTaG3 n = 3; pT1 n = 9; concurrent pTis n = 8) were prospectively enrolled. Of 21 patients, 15 (71%) had received previous intravesical instillations with bacillus Calmette-Guérin, mitomycin C and/or farmorubicin. Thermochemotherapy using the Synergo system was carried out in 11 of 21 patients (52%) with curative intent, and in 10 of 21 patients (48%) as prophylaxis against recurrence. RESULTS The median number of thermochemotherapy cycles per patient was six (range 1-12). Adverse effects were frequent and severe: urinary urgency/frequency in 11 of 21 patients (52%), pain in eight of 21 patients (38%) and gross hematuria in five of 21 patients (24%). In eight of 21 patients (38%), thermochemotherapy had to be abandoned because of the severity of the adverse effects (pain in 3/8, severe bladder spasms in 2/8, allergic reaction in 2/8, urethral perforation in 1/8). Overall, six of 21 patients (29%) remained free of tumor after a median follow up of 50 months (range 1-120), six of 21 patients (29%) had to undergo cystectomy because of multifocal recurrences or cancer progression and seven of 21 patients (33%) died (2/7 of metastatic disease, 5/7 of non-cancer related causes). CONCLUSIONS Given the high rate of severe side-effects leading to treatment discontinuation, as well as the limited tumor response, thermochemotherapy should be offered only in highly selected cases of recurrent non-muscle-invasive bladder cancer.
Collapse
Affiliation(s)
- Bernhard Kiss
- Department of Urology, University of Bern, Bern, Switzerland
| | | | | | | |
Collapse
|
|
47
|
Arends TJ, van der Heijden AG, Witjes JA. Combined Chemohyperthermia: 10-Year Single Center Experience in 160 Patients with Nonmuscle Invasive Bladder Cancer. J Urol 2014; 192:708-13. [DOI: 10.1016/j.juro.2014.03.101] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2014] [Indexed: 11/17/2022]
Affiliation(s)
- Tom J.H. Arends
- Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | - J. Alfred Witjes
- Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands
| |
Collapse
|
|
48
|
Slater SE, Patel P, Viney R, Foster M, Porfiri E, James ND, Montgomery B, Bryan RT. The effects and effectiveness of electromotive drug administration and chemohyperthermia for treating non-muscle invasive bladder cancer. Ann R Coll Surg Engl 2014; 96:415-9. [PMID: 25198970 PMCID: PMC4474190 DOI: 10.1308/003588414x13946184901001] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/11/2013] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION Preliminary studies show that device assisted intravesical therapies appear more effective than passive diffusion intravesical therapy for the treatment of non-muscle invasive bladder cancer (NMIBC) in specific settings, and phase III studies are now being conducted. Consequently, we have undertaken a non-systematic review with the objective of describing the scientific basis and mechanisms of action of electromotive drug administration (EMDA) and chemohyperthermia (CHT). METHODS PubMed, ClinicalTrials.gov and the Cochrane Library were searched to source evidence for this non-systematic review. Randomised controlled trials, systematic reviews and meta-analyses were evaluated. Publications regarding the scientific basis and mechanisms of action of EMDA and CHT were identified, as well as clinical studies to date. RESULTS EMDA takes advantage of three phenomena: iontophoresis, electro-osmosis and electroporation. It has been found to reduce recurrence rates in NMIBC patients and has been proposed as an addition or alternative to bacillus Calmette-Guérin (BCG) therapy in the treatment of high risk NMIBC. CHT improves the efficacy of mitomycin C by three mechanisms: tumour cell cytotoxicity, altered tumour blood flow and localised immune responses. Fewer studies have been conducted with CHT than with EMDA but they have demonstrated utility for increasing disease-free survival, especially in patients who have previously failed BCG therapy. CONCLUSIONS It is anticipated that EMDA and CHT will play important roles in the management of NMIBC in the future. Techniques of delivery should be standardised, and there is a need for more randomised controlled trials to evaluate the benefits of the treatments alongside quality of life and cost-effectiveness.
Collapse
Affiliation(s)
| | | | | | - M Foster
- Heart of England NHS Foundation Trust, UK
| | - E Porfiri
- University Hospitals Birmingham NHS Foundation Trust, UK
| | | | | | | |
Collapse
|
|
49
|
Sun T, Wang Y, Wang Y, Xu J, Zhao X, Vangveravong S, Mach RH, Xia Y. Using SV119-gold nanocage conjugates to eradicate cancer stem cells through a combination of photothermal and chemo therapies. Adv Healthc Mater 2014; 3:1283-91. [PMID: 24677807 DOI: 10.1002/adhm.201400026] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2014] [Revised: 02/13/2014] [Indexed: 01/01/2023]
Abstract
Cancer stem cells (CSCs) are believed to be responsible for the long-term growth of a tumor, as well as its metastasis and recurrence after conventional therapies. Here, it is demonstrated that the sigma-2 receptor is overexpressed on the surface of breast CSCs, and thus could serve as a biomarker for the purpose of targeting. Breast CSCs are targeted with Au nanocages (AuNCs) by functionalizing their surfaces with SV119, a synthetic small molecule capable of binding to the sigma-2 receptor with high specificity. The interiors of the AuNCs could also be loaded with an anticancer drug to be selectively delivered to breast CSCs and released in a controllable fashion. The results demonstrate that the SV119-AuNC conjugate can serve as a new platform to carry out photothermal and chemo therapies simultaneously, eradicating breast CSCs more effectively through a synergetic effect.
Collapse
Affiliation(s)
- Tianmeng Sun
- The Wallace H. Coulter Department of Biomedical Engineering; Georgia Institute of Technology and Emory University; Atlanta GA 30332 USA
| | - Yi Wang
- The Wallace H. Coulter Department of Biomedical Engineering; Georgia Institute of Technology and Emory University; Atlanta GA 30332 USA
| | - Yucai Wang
- The Wallace H. Coulter Department of Biomedical Engineering; Georgia Institute of Technology and Emory University; Atlanta GA 30332 USA
| | - Jinbin Xu
- Mallinckrodt Institute of Radiology; Washington University School of Medicine; St Louis MO 63110 USA
| | - Xin Zhao
- The Wallace H. Coulter Department of Biomedical Engineering; Georgia Institute of Technology and Emory University; Atlanta GA 30332 USA
| | - Suwanna Vangveravong
- Mallinckrodt Institute of Radiology; Washington University School of Medicine; St Louis MO 63110 USA
| | - Robert H. Mach
- Mallinckrodt Institute of Radiology; Washington University School of Medicine; St Louis MO 63110 USA
- Department of Radiology; University of Pennsylvania; Philadelphia PA 19104 USA
| | - Younan Xia
- The Wallace H. Coulter Department of Biomedical Engineering; Georgia Institute of Technology and Emory University; Atlanta GA 30332 USA
| |
Collapse
|
|
50
|
Maffezzini M, Campodonico F, Canepa G, Manuputty EE, Tamagno S, Puntoni M. Intravesical mitomycin C combined with local microwave hyperthermia in non-muscle-invasive bladder cancer with increased European Organization for Research and Treatment of Cancer (EORTC) score risk of recurrence and progression. Cancer Chemother Pharmacol 2014; 73:925-30. [PMID: 24585046 DOI: 10.1007/s00280-014-2423-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Accepted: 02/20/2014] [Indexed: 11/27/2022]
Abstract
PURPOSE To assess the activity of intravesical chemotherapy and local microwave hyperthermia (ICLMH) in increasing the disease-free interval (DFI) in patients with non-muscle-invasive bladder cancer (NMIBC) and treatment toxicity. METHODS Forty-two patients with a diagnosis of high-risk NMIBC, according to the European Organization for Research and Treatment of Cancer (EORTC) criteria, were treated with an intensive schedule of ICLMH using 40 mg mitomycin C. The treatment consisted of 4 weekly sessions, followed by 6 sessions delivered every 2 weeks, and by 4 monthly sessions, for a total of 14 sessions over 8 months. The DFIs before and after treatment were compared in each patient. RESULTS The schedule was completed as planned by 32 patients (76.2 %). The percentage of disease-free patients the year before study was 14.9 % (95 % CI 5.5-28.8) versus 88.8 % (95 % CI 73.7-94.8) after ICLMH (p < 0.0001). Patient EORTC scores, multifocality, and tumour stage were all associated significantly and independently with a higher risk of recurrence after ICLMH treatment with HR of 41.1 (p = 0.01), 17.7 (p = 0.02), and 8.5 (p = 0.02), respectively. After a median follow-up of 38 months, 24 patients (57.1 %) did not show evidence of disease, whereas 13 patients (30.9 %) underwent disease recurrence and 5 patients (11.9 %) showed also stage progression. Toxicity consisted in grades 1 and 2 frequency, non-infectious cystitis, and haematuria. CONCLUSIONS ICLMH significantly increases the DFI of NMIBC patients with high EORTC score for recurrence and progression. Toxicity of the intensive treatment schedule was generally mild.
Collapse
|