Carboplatin Induction Chemotherapy in Clinically Lymph Node-positive Bladder Cancer.

There are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node-positive (cN+) bladder cancer (BCa).

To investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa.

This was an observational study of 369 patients with cT2-4 N1-3 M0 BCa.

IC followed by consolidative radical cystectomy (RC).

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.

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.

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.

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.

European urology open science. 2023 Mar 25*** epublish ***

Markus von Deimling, Laura S Mertens, Bas W G van Rhijn, Yair Lotan, Philippe E Spiess, Siamak Daneshmand, Peter C Black, Maximilian Pallauf, David D'Andrea, Marco Moschini, Francesco Soria, Francesco Del Giudice, Luca Afferi, Ekaterina Laukhtina, Takafumi Yanagisawa, Tatsushi Kawada, Jeremy Y-C Teoh, Mohammad Abufaraj, Guillaume Ploussard, Mathieu RoumiguiƩ, Pierre I Karakiewicz, Marko Babjuk, Paolo Gontero, Evanguelos Xylinas, Michael Rink, Shahrokh F Shariat, Benjamin Pradere

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Department of Urology, University of Texas Southwestern, Dallas, TX, USA., Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA., 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., Department of Urology, Urological Research Institute, Vita-Salute San Raffaele, Milan, Italy., Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy., Department of Maternal Infant and Urologic Sciences, Sapienza University of Rome, Policlinico Umberto I Hospital, Rome, Italy., Department of Urology, Luzerner Kantonsspital, Luzern, Switzerland., S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China., Department of Urology, La Croix Du Sud Hospital, Quint-Fonsegrives, France., Department of Urology, CHU Toulouse-IUCT Oncopole, Toulouse, France., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Canada., Department of Urology, Hospital Motol, Second Faculty of Medicine, Charles University, Prague, Czechia., Division of Urology, Molinette Hospital, University of Studies of Torino, Torino, Italy., Department of Urology, Bichat-Claude Bernard Hospital, AP-HP, Paris University, Paris, France., Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.