AUA 2019: Role of Adjuvant Cisplatin-based Chemotherapy Following Radical Cystectomy in Muscle-invasive and Locally Advanced Bladder Cancer

Chicago, IL ( Neoadjuvant cisplatin-based chemotherapy (NAC) is currently part of the standard of care prior to radical cystectomy for muscle-invasive bladder cancer (MIBC). However contemporary data shows rates of NAC administration less than 25% which cannot be fully accounted for by rates of cisplatin ineligibility. For these patients, adjuvant chemotherapy remains an option, a meta-analysis of randomized data supports an overall survival benefit over placebo.

During Moderated Poster Session 26 - Bladder Cancer, Invasive I, Dr. Do Kyung Kim presented “Role of adjuvant cisplatin-based chemotherapy following radical cystectomy in muscle-invasive and locally advanced bladder cancer: systematic review and meta-analysis of randomized trials” another meta-analysis of these randomized trials but focused on patients with locally advanced disease, defined as pT3-4M0 with any N stage. Eight total adjuvant trials were identified, four of which contained data on patients with locally advanced disease for a total of 490 patients included. Chemotherapy regimens in each trial were CAP, CMV, MVAC or MVEC, and MVAC or GC. Median follow up ranged from approximately 55 months in the shortest trial to 7 years in the longest. Pooled hazard ratios for progression-free survival (PFS) and overall survival (OS) confirmed a significant benefit of adjuvant therapy over placebo (HR 0.48 p<0.00001 and HR 0.63, p=0.0009 respectively). The absolute increases in PFS and OS were 17% and 10% respectively for locally advanced disease, which compared favorably to the 10% and 5% which were seen in the overall cystectomy population.

The results of this analysis confirm intuition. Patients with known locally advanced disease at the time of solid tumor resection are generally those who benefit most from adjuvant chemotherapy, so it would be very surprising to find a lack of benefit in this cohort given the known benefit of cisplatin for MIBC in both a neoadjuvant setting and an all-comers adjuvant setting. The success of neoadjuvant chemo in the current era also limits the applicability of this data to current practice. As the moderator Dr. Witjes pointed out during the session, none of the patients enrolled in these trials were offered neoadjuvant chemotherapy, so a patient to whom these results apply is one who is cisplatin eligible after cystectomy, who did not receive standard of care cisplatin preoperatively, but who is now being considered for postoperative cisplatin. Knowledge of the effect size of the benefit of cisplatin in this setting is certainly valuable for counseling, but hopefully, the population to whom this data will be relevant will continue to shrink over time as adherence to guidelines increases.

Presented by: Do Kyung Kim, MD, Department of Urology, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
Moderated by:  J.A. Witjes, MD, Raboud University Medical Center, Tracy M Downs, MD, University of Wisconsin, Khurshid A Guru, MD, Roswell Park Comprehensive Cancer Center

Written by: Marshall Strother, MD, Chief Resident, Division of Urology, University of Pennsylvania, Philadelphia PA at the American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois