Efficacy of Neoadjuvant Chemotherapy in Patients with MIBC Undergoing Radiation - Expert Commentary

Neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is a standard of care in patients with muscle-invasive bladder cancer (MIBC). However, the role of NAC remains controversial for patients undergoing bladder preservation with radiation therapy (RT). Kool et al. recently investigated the effect of NAC on survival outcomes in MIBC patients treated with curative RT.

The study included retrospective data for 586 patients with MIBC, 17% of whom received NAC before RT. Most patients (70%) received definitive RT within 90 days of diagnosis or NAC. Most patients (78%) received gemcitabine/cisplatin NAC regimens. The median RT dose was 50 Gy and 92% of patients underwent at least three complete cycles of NAC. Patients who underwent NAC were more likely to be younger, had higher cT and cN stages, and were more commonly treated with concurrent chemotherapy.

Overall, 77% of patients had a complete response (CR) after RT and there were 143 cancer-related deaths. There was no significant association between NAC and CR (p = 0.3). The median follow-up time was 34 months. NAC was associated with improved cancer-specific survival (HR, 0.28; 95% CI, 0.14 – 0.56; p < 0.001). The median overall survival (OS) was reached at 108 months in the NAC group and at 60 months in the group of patients that did not receive NAC. NAC was associated with improved OS (HR, 0.56; 95% CI, 0.38 – 0.84; p = 0.005).

Overall, patients undergoing RT and receiving NAC treatment had a survival advantage. However, conflicting results from previous clinical trials highlight the complexities of incorporating NAC into MIBC treatment protocols. Limitations of these studies include small sample sizes, heterogeneous treatment protocols, and potential biases in patient selection. It is possible that the survival benefit with systemic NAC is mainly derived from the elimination of disseminated cancer cells or micro-metastatic disease rather than from the improvement of local control rates.

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

References:

  1. Kool R, Dragomir A, Kulkarni GS, et al. Benefit of Neoadjuvant Cisplatin-based Chemotherapy for Invasive Bladder Cancer Patients Treated with Radiation-based Therapy in a Real-world Setting: An Inverse Probability Treatment Weighted Analysis. Eur Urol Oncol. Published online February 6, 2024. doi:10.1016/j.euo.2024.01.014
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