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Carboplatin versus Cisplatin Based Chemotherapy for Lymph Node Positive Bladder Cancer - Expert Commentary

Up to a third of patients with muscle-invasive bladder cancer (MIBC) present with clinically lymph node-positive disease (cN+), associated with poor prognosis. Eligible patients can be treated with cisplatin-based induction chemotherapy (IC) followed by radical cystectomy if they exhibit a clinical response. Although cisplatin-ineligible patients comprise up to 50% of patients, little is known about optimal treatment modalities for this patient subgroup. von Deimling et al. conducted a retrospective study to compare the efficacy of gemcitabine/carboplatin IC versus cisplatin-based combination IC in patients with cN+ bladder cancer.

A total of 369 patients were included in the study, of whom 315 received cisplatin-based treatment and 54 received gemcitabine/carboplatin. The authors used propensity score matching to adjust for the difference in sample sizes of the two groups, resulting in a smaller cohort of 216 patients. Nodal status and other clinicopathological features were similar between the cisplatin-based and gemcitabine/carboplatin groups. At radical cystectomy, 25% of all patients had a pathological objective response (pOR), and 17% had pathological complete response (pCR). Pathological nodal status of ypN0 was present in 48% of cisplatin-treated patients and 46% of gemcitabine/carboplatin-treated patients (p = 0.5).

Median follow-up after radical cystectomy was 23.4 months, with 50.9% of patients developing recurrence and 43.1% dying of bladder cancer. In patients who were treated with cisplatin, the median overall survival (OS) was 37 months (95% CI, 27.4 – 78.0), and the median cancer-specific survival (CSS) was 39.2 months (28.0 – not reached). In patients who received carboplatin, the median OS was 15 months (10.0 – 24.8), and the median CSS was 17 months (11.0 – not reached). The 2-year OS rate was 58.1% (50.2 – 67.2) in the cisplatin group and 34.1% (22.3 – 52.2) in the carboplatin group. The 2-year CSS was 59.8% (51.9 – 69.0) in the cisplatin group and 38.8% (26.0 – 57.9) in the carboplatin group. Univariate Cox regression analysis revealed that gemcitabine/carboplatin treatment was significantly associated with shorter OS (p = 0.002) and CSS (p = 0.011). Multivariate Cox regression analyses adjusted for confounding variables showed that the following variables were significantly associated with shorter OS and CSS: gemcitabine/carboplatin treatment (p = 0.003), ypT3 status (p = 0.003), ypT4 status (p = 0.014), ypN2 status (p < 0.001), ypN3 status (p < 0.001), and positive surgical margins (p < 0.001). In an analysis of patient subgroups, there was no association between gemcitabine/carboplatin treatment and survival in the cN1 subgroup (p = 0.2), whereas this treatment was associated with shorter OS (p < 0.001) and CSS (p = 0.001) in the cN2/3 subgroup.

Patients who received cisplatin-based treatment exhibited significant survival benefits compared to those who received gemcitabine/carboplatin. Nevertheless, carboplatin-based treatment is a reasonable alternative for patients before radical cystectomy, even for patients with cN1 disease unable to receive cisplatin.

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

Reference:

  1. von Deimling M, Mertens LS, Van Rhijn BWG, et al. Carboplatin induction chemotherapy in clinically lymph node-positive bladder cancer. European urology. 2023;83:S781-S782. doi:10.1016/j.euros.2023.02.014