Chemotherapy Options for Metastatic Urothelial Cancer Patients Who Already Received Cisplatin for Localized Disease - Expert Commentary

Cisplatin-based chemotherapy is the preferred first-line for patients with metastatic urothelial cancer if they are cisplatin eligible. However, a significant proportion of these patients already receive cisplatin-based chemotherapy in the perioperative setting for their localized disease. It is unclear if re-challenge with platinum-based chemotherapy (PBC) is a better option compared to non-platinum based (NPBC) chemotherapy. A recent study published by Do et al. in Clinical Genitourinary Cancer investigated the efficacy of PBC versus NPBC first-line chemotherapy for patients with metastatic urothelial cancer who already received prior cisplatin-based chemotherapy for localized disease.

The investigators used the RISC database, which included 3024 patients from 28 international academic centers from 2005 to 2012. A total of 132 patients fulfilled the study's inclusion criteria, which entailed prior receipt of perioperative cisplatin-containing chemotherapy and receipt of cytotoxic chemotherapy in the first-line metastatic setting. Patients who received PBC (n=74) did not show a significant difference in overall survival (OS) and progression-free survival compared to NPBC (n= 58). The baseline characteristics of the two cohorts PBC and NPBC were comparable except for the smoking status.

Limiting the analysis to patients who received chemotherapy more than a year after the initial perioperative chemotherapy showed that PBC was associated with better overall survival (OS) compared to NPBC (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.10-0.92; P = 0.03). The study was conducted in patients treated in the era before immune checkpoint inhibitors, which become an increasingly effective treatment option in maintenance, first, and later lines. However, in those patients who are unable to receive immunotherapy and one year elapsed since their receipt of cisplatin-based chemotherapy, re-challenge with PBC may be superior to NPBC. In view of the positive results from the CheckMate-274 trial of adjuvant nivolumab, it is expected that some patients may receive both neoadjuvant chemotherapy and adjuvant immune checkpoint inhibitors. The Do et al. study results potentially support the return to PBC to these patients in case of progression to metastatic disease.

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


  1. “Opdivo (Nivolumab) Significantly Improves Disease Free-Survival vs. Placebo as Adjuvant Therapy for Patients with High-Risk, Muscle-Invasive Urothelial Carcinoma in Phase 3 CheckMate -274 Trial.” Accessed December 24, 2020.
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