BACKGROUND: There are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node-positive (cN+) bladder cancer (BCa). OBJECTIVE: To investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. DESIGN SETTING AND PARTICIPANTS: This was an observational study of 369 patients with cT2-4 N1-3 M0 BCa. INTERVENTION: IC followed by consolidative radical cystectomy (RC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. RESULTS AND LIMITATIONS: After PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9-69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26-57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. CONCLUSIONS: Cisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. PATIENT SUMMARY: In this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montreal Health Center Montreal Canada

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

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

Department of Urology 2nd Faculty of Medicine Charles University Prague Czechia

Department of Urology Bichat Claude Bernard Hospital AP HP Paris University Paris France

Department of Urology Caritas St Josef Medical Centre University of Regensburg Regensburg Germany

Department of Urology CHU Toulouse IUCT Oncopole Toulouse France

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

Department of Urology Hospital Motol 2nd Faculty of Medicine Charles University Prague Czechia

Department of Urology Jikei University School of Medicine Tokyo Japan

Department of Urology La Croix Du Sud Hospital Quint Fonsegrives France

Department of Urology Luzerner Kantonsspital Luzern Switzerland

Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan

Department of Urology The Netherlands Cancer Institute Amsterdam The Netherlands

Department of Urology University Hospital Salzburg Paracelsus Medical University Salzburg Austria

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 Weill Cornell Medical College New York NY USA

Division of Urology Department of Special Surgery The University of Jordan Amman Jordan

Division of Urology Department of Surgical Sciences San Giovanni Battista Hospital University of Studies of Torino Turin Italy

Division of Urology Molinette Hospital University of Studies of Torino Torino Italy

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

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

S H Ho Urology Centre Department of Surgery The Chinese University of Hong Kong Hong Kong China

USC Norris Comprehensive Cancer Center Institute of Urology University of Southern California Los Angeles CA USA

Vancouver Prostate Centre Department of Urologic Sciences University of British Columbia Vancouver Canada

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