OBJECTIVE: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. PATIENTS AND METHODS: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. RESULTS: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses. CONCLUSION: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

CNRS Inserm CHU Lille Institut Pasteur de Lille UMR9020 U1277 CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies University of Lille Lille France

Department of Cancer Medicine Gustave Roussy Université Paris Saclay Villejuif France

Department of Genitourinary Oncology H Lee Moffitt Cancer Center and Research Institute Tampa FL USA

Department of Maternal Infant and Urologic Sciences Policlinico Umberto 1 Hospital Sapienza University of Rome Rome Italy

Department of Neurosciences Reproductive Sciences and Odontostomatology University of Naples Federico 2 Naples Italy

Department of Urologic Sciences University of British Columbia Vancouver BC Canada

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology and Neurourology Marien Hospital Herne Ruhr University Bochum Herne Germany

Department of Urology CHU Lille Claude Huriez Hospital Lille France

Department of Urology Comprehensive Cancer Center Innsbruck Medical University of Innsbruck Innsbruck Austria

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology Eberhard Karls University Tübingen Tübingen Germany

Department of Urology Fundació Puigvert Autonomous University of Barcelona Barcelona Spain

Department of Urology Marienkrankenhaus Hamburg Germany

Department of Urology Mayo Clinic Rochester MN USA

Department of Urology Solothurner Spitäler AG Kantonsspital Olten and Bürgerspital Solothurn Switzerland

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology The Netherlands Cancer Institute Amsterdam The Netherlands

Department of Urology University Hospital of Bern University of Bern Bern Switzerland

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology Urological Research Institute Vita Salute San Raffaele Milan Italy

Department of Urology Urosud La Croix Du Sud Hospital Quint Fonsegrives France

Department of Urology Weill Cornell Medical College New York NY USA

Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman Jordan

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Service d'Urologie Hôpital Erasme Université Libre de Bruxelles Bruxelles Belgium

Unit of Oncologic Minimally Invasive Urology and Andrology Department of Experimental and Clinical Medicine Careggi Hospital University of Florence Florence Italy

Urology Unit Department of Surgical Sciences Tor Vergata University Hospital University of Rome Tor Vergata Rome Italy

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