Carboplatin Induction Chemotherapy in Clinically Lymph Node–positive Bladder Cancer

• Published in: European urology open science (Online) 2023-05, Vol.51, p.39-46
• Main Authors: von Deimling, Markus, Mertens, Laura S., van Rhijn, Bas W.G., Lotan, Yair, Spiess, Philippe E., Daneshmand, Siamak, Black, Peter C., Pallauf, Maximilian, D'Andrea, David, Moschini, Marco, Soria, Francesco, Del Giudice, Francesco, Afferi, Luca, Laukhtina, Ekaterina, Yanagisawa, Takafumi, Kawada, Tatsushi, Teoh, Jeremy Y.-C., Abufaraj, Mohammad, Ploussard, Guillaume, Roumiguié, Mathieu, Karakiewicz, Pierre I., Babjuk, Marko, Gontero, Paolo, Xylinas, Evanguelos, Rink, Michael, Shariat, Shahrokh F., Pradere, Benjamin
• Format: Article
• Language: English
• Subjects: Bladder Cancer; Carboplatin; Induction chemotherapy; Oligometastatic; Survival; Urinary bladder neoplasms
• ISSN: 2666-1683; 2666-1691; 2666-1683
• DOI: 10.1016/j.euros.2023.02.014

No guideline recommendations exist for the treatment of cisplatin-ineligible patients with clinically lymph node–positive (cN+) bladder cancer. In this study, carboplatin-based induction chemotherapy appeared to be an attractive alternative before radical cystectomy for this population. In particular, patients with cN1 disease who are not eligible for cisplatin may benefit from gemcitabine/carboplatin induction chemotherapy. 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 clini