EAU 2017: Is neoadjuvant chemotherapy beneficial before radical cystectomy? Examining the external validity of the SWOG-8710 trial

London, England (UroToday.com) Neoadjuvant cisplatin based chemotherapy (NAC) prior to radical cystectomy (RC) is a recognized standard of care for the management of muscle invasive bladder cancer (MIBC) based on Level 1 evidence, including RCTs such as SWOG-8710 trial. However, those studies are limited to well selected patients for clinical trial purposes. The authors herein externally validate the use of NAC on a large population-level dataset, the National Cancer Database (NCDB).

Patients with non-metastatic MIBC diagnosed between 2004 and 2012 were identified, and stratified based on receipt of NAC – all patients were cT2N0M0 to cT4aN0M0 to match the SWOG study. All 8732 patients underwent RC, though only 19% received NAC – consistent with prior studies demonstrating underutilization. Importantly, the cohort was older, more commonly female, and had higher clinical stage – the older age and higher clinical stage is likely a better representation of the typical patient population. To account for comorbidities and confounding factors, the authors used a propensity score adjustment to compare the NAC+RC cohort to the RC alone cohort.

The primary endpoint was overall survival (OS) - receipt of NAC was associated with an OS benefit (HR 0.88, p=0.017). It was also associated with higher downstaging rates (13.3% in NAC+RC cohort vs. 2.3% in RC alone) and lower 90-day postoperative mortality.

Limitations / Discussion Points:
1. They only included patients with Charlson Comorbidity Index = 0 (healthy patients). In my mind, they negated any benefit of looking at the general population by excluding patients with worse comorbidities. While a subset analysis of this group would have been ok, but not looking at all patients, it becomes less generalizable.
2. The authors, and the moderators, attribute the 90-day mortality benefit to selection bias – despite being older and more female, they were also patients who were likely closely followed at an academic institution and had more pre-operative clearance prior to undergoing surgery.
3. While confirming the importance of the studies in a more “typical”patient population, this study doesn’t change clinical practice.
4. The underutilization of NAC remains a significant issue that needs to be addressed.

Presented by: N. Hanna

Co-Authors: Trinh Q.-D., Sammon J., Seisen T., Vetterlein M., Moreira R., Preston M., Lipsitz S., Bellmunt J., Menon M., Choueiri T., Abdollah F.

1. Brigham and Women's Hospital, Harvard Medical School, Dept. of Urology, Boston, United States of America
2. Henry Ford Hospital, Dept. of Urology, Detroit, United States of America
3. Dana-Farber Cancer Institute, Dept. of Medical Oncology, Boston, United States of America

Written by: Thenappan Chandrasekar, Clinical Fellow, University of Toronto

Twitter: @tchandra_uromd

at the #EAU17 -March 24-28, 2017- London, England