Wojciech Krajewski1, Łukasz Nowak1, Marco Moschini2, Sławomir Poletajew3, Joanna Chorbińska1, Andrea Necchi4, Francesco Montorsi5, Alberto Briganti5, Rafael Sanchez-Salas6, Shahrokh F Shariat7,8,9,10,11,12,13, Juan Palou14, Marek Babjuk13, Jeremy Yc Teoh15, Francesco Soria16, Benjamin Pradere7,17, Paola Irene Ornaghi2, Aleksandra Pawlak18, Janusz Dembowski1, Romuald Zdrojowy1. 1. Department of Urology and Oncologic Urology, Wrocław Medical University, 50-556 Wroclaw, Poland. 2. Klinik für Urologie, Luzerner Kantonsspital, 6004 Lucerne, Switzerland. 3. Second Department of Urology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland. 4. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. 5. Unit of Urology, Urological Research Institute (URI), IRCCS Ospedale San Raffaele, 20132 Milan, Italy. 6. Department of Urology, Institute Mutualiste Montsouris, Université Paris-Descartes, 75014 Paris, France. 7. Department of Urology, Medical University of Vienna, 1090 Vienna, Austria. 8. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 9. Departments of Urology, Weill Cornell Medical College, New York, NY 10065, USA. 10. Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, 119146 Moscow, Russia. 11. Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman 11942, Jordan. 12. European Association of Urology Research Foundation, 6803 AA Arnhem, The Netherlands. 13. Department of Urology, Second Faculty of Medicine and Hospital Motol, Charles University, 15006 Prague, Czech Republic. 14. Fundació Puigvert, Department of Urology, Autonomous University of Barcelona, 08025 Barcelona, Spain. 15. S.H. Ho Urology Centre, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong. 16. Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, 10124 Turin, Italy. 17. Department of Oncology and Urology, University Hospital of Tours, 37000 Tours, France. 18. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wrocław, Poland.
Abstract
BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3-T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3-T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. MATERIALS AND METHODS: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). RESULTS: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75-0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32-0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58-1.35; p = 0.58). CONCLUSIONS: The administration of AC in patients with MIBC and pT3-T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients.
BACKGROUND:Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3-T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3-T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. MATERIALS AND METHODS: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). RESULTS: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75-0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32-0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58-1.35; p = 0.58). CONCLUSIONS: The administration of AC in patients with MIBC and pT3-T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients.
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