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Neoadjuvant Gemcitabine-Carboplatin Versus Gemcitabine-Cisplatin in Patients with Muscle-Invasive Bladder Cancer - Expert Commentary

Patients with muscle-invasive bladder cancer (MIBC) typically receive cisplatin-based chemotherapy prior to radical cystectomy. However, around half of MIBC patients may be ineligible for cisplatin, therefore necessitating alternative treatment modalities. A recent study by Einerhand et al. evaluated response and survival among MIBC patients receiving gemcitabine and carboplatin (gem-carbo) compared to gemcitabine and cisplatin (gem-cis).


Researchers identified 747 patients with MIBC, of whom 80.3% received preoperative gem-cis and 19.7% received preoperative gem-carbo. Patients in the gem-carbo group were significantly older than those in the gem-cis group and were more likely to have hydronephrosis, a cT4 tumor, and node-positive disease.

Complete pathological response rates were not significantly different between the two treatment groups (20.7% for gem-carbo and 22.1% for gem-cis), while partial pathological response rates were significantly higher for gem-cis (32% for gem-carbo and 43% for gem-cis). Lower cT stage was associated with higher rates of complete and partial pathological responses, while lower age was significantly associated with partial response. Overall median follow-up was 14.3 months. Median overall survival was 28.6 months for those treated with gem-carbo and 45.1 months for those treated with gem-cis. Median cancer-specific survival was 28.8 months for gem-carbo and 71 months for gem-cis. However, in Cox proportional hazards regression analyses, chemotherapy type was not significantly associated with survival. High cT stage was a predictive factor for reaching a complete pathological response and was associated with survival.

In this retrospective non-randomized study, the response rates were comparable between pre-operative gem-carbo and gem-cis treatment. However, non-response was more common among those treated with gem-carbo, which may be related to the presence of comorbidities. This is supported by a multivariable analysis that revealed patient and tumor characteristics significantly affected response to treatment and survival. Emerging options including immunotherapy and targeted therapy in the neoadjuvant setting may address a significant need for cisplatin-ineligible MIBC patients.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

References:

  1. Einerhand SMH, Black AJ, Zargar H, et al. Multicenter evaluation of neoadjuvant and induction gemcitabine-carboplatin versus gemcitabine-cisplatin followed by radical cystectomy for muscle-invasive bladder cancer. World J Urol. 2022;40(11):2707-2715. doi:10.1007/s00345-022-04160-7
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