Abstract
For many years EAU guidelines have recommended the use of cisplatin-based regimens over carboplatin for treatment of advanced urothelial cell carcinoma (UCC) in eligible patients. The claim of an overall survival (OS) benefit is based on (a meta-analysis of) 2 RCTs totalling 190 patients, of which one study has methodological flaws. These studies warrant secondary analysis to substantiate the evidence for an OS benefit of cisplatin- versus carboplatin-based regimens. Individual patient data (IPD) were reconstructed from the 2 RCTs, assessing OS in both treatment arms. IPD of both studies were then jointly reanalysed to assess an OS estimate with Kaplan-Meier methods, with, and without an alternative censoring scenario to assess the impact of the original biased censoring approach. Kaplan-Meier curves were compared by calculating restricted mean survival time (RMST) differences. In each study individually, and in both studies combined, the survival benefit of cisplatin versus carboplatin was less than 1 month and not significant in a follow-up window of 12 months. This was also the case when an alternative censoring scenario was applied. Careful scrutiny of the data on which guidelines base the recommendation of cisplatin-based chemotherapy for the treatment of advanced UCC does not uphold the finding that cisplatin leads to an OS benefit when compared to carboplatin. This conclusion, combined with higher toxicity in cisplatin-based regimens warrants a reconsideration of this guideline recommendation.
Highlights
Platinum-based chemotherapy has been the long-established standard of care for treatment of advanced and metastatic urothelial carcinoma, which can be categorized into cisplatin-based, and carboplatin-based combination regimens
In the meta-analysis referred to by the EAU guidelines, the overall survival (OS) benefit was summarized as the relative risk of being alive at 12 months after treatment with cisplatin compared to treatment with carboplatin.[5]
Careful scrutiny of the data on which guidelines base the recommendation of cisplatin-based chemotherapy for the treatment of advanced urothelial carcinoma does not uphold the finding that cisplatin yields a survival benefit when compared to carboplatin
Summary
Platinum-based chemotherapy has been the long-established standard of care for treatment of advanced and metastatic urothelial carcinoma, which can be categorized into cisplatin-based, and carboplatin-based combination regimens. In 2004, a phase III RCT was published on the efficacy of cisplatin-based chemotherapy versus carboplatin-based chemotherapy for the treatment of advanced/metastatic urothelial cancer.[1] In 2007, a phase II trial comparing cisplatin and carboplatin regimens was published, including an overall survival (OS) analysis.[2] The phase III trial did not report a difference in OS, but was terminated prematurely because of low patient accrual, and was underpowered. The phase II trial intended to compare safety profiles and so did Clinical Genitourinary Cancer 2022 1.
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