SUO 2017: Neoadjuvant Versus Adjuvant Chemotherapy for MIBC: A Propensity Matched Analysis

Washington, DC ( While neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is established in the literature and guidelines based on Level 1 Evidence (meta-analysis demonstrated 7% survival benefit), its utilization has only slowly increased and its uptake is not yet ideal. However, often cited as reasons for not being incorporated into clinical practice includes NAC effect on renal function, perioperative outcomes, and chemotherapy tolerability. Indeed, many individuals feel that a large proportion of patients never make it to RC (radical cystectomy) due to chemotherapy effects or progression, and use this as a reason to avoid NAC. However, those same individuals advocate for adjuvant chemotherapy in patients who successfully underwent RC – despite lack of Level 1 evidence. While the prior adjuvant trials were acknowledged to be flawed, the debate between AC and NAC continues.

In this study, the authors utilized National Cancer Data Base (NCDB) to identify patients with cT2-T4, N0, M0 urothelial cell carcinoma who underwent RC. Patients who received NAC were propensity matched by age, race, ethnicity, sex, insurance type, academic/research program, comorbidity, and clinical stage to patients receiving AC within 90 days of RC. They then compared overall survival (OS), down-staging to non-MIBC (NMIBC), and N upstaging between the groups.

They identified 509 patients treated with NAC and 283 patients treated with AC over a 10-yer period (2004-2013). After propensity matching 283 NAC with the 283 AC patients, NAC patients had better 5 year OS (50.3%, 95% CI: 43.2%-57.0%) compared to patients who received AC (38.0%, 95% CI: 32.0%-44.0%). NAC was a significant predictor of decreased mortality, decreased progression to node positivity, and down-staging to NMIBC (0.68, 0.54-0.86, p=0.001; 0.18, 0.12-0.26, p<0.001; 12.75, 6.06-26.81, p<0.001). 

Based on this, the authors concluded that NAC+RC was associated with better OS compared to RC+AC for patients diagnosed with cT2-T4, N0, M0 bladder cancer, in support of the current literature. They posit that the increased survival benefit associated with NAC compared to AC among patients undergoing RC may be due to its systemic effect on micrometastatic disease prior to surgical consolidation, therefore being associated with decreased progression to node positivity and higher rates of pathologic down-staging.

Limitations / Discussion Points:

1. Immortal time bias – any study comparing the outcomes of adjuvant vs. neoadjuvant therapy is susceptible to immortal time bias. This study, like all those studies, is no different. Patients who underwent RC but never made to adjuvant therapy are not included in the adjuvant arm – though they should be if the intent was adjuvant therapy. By excluding these patients, the results of the adjuvant therapy arm are artificially elevated.

2. National Cancer Database – as previously mentioned many times, the NCDB is severely limited by the lack of cancer-specific survival outcomes. Overall survival is a poor substitute, and assesses completely different outcomes.

Based on the severe limitations, their conclusions are hard to justify.

Presented by: Joshua Jue, BS

Co-Authors: María Velásquez MD, Luís Sávio MD, Mahmoud Alameddine MD, Tulay Koru-Sengul PhD, MHS, Feng Miao MS, Chad Ritch MD, MBA and Mark Gonzalgo MD, PhD - Miami, FL

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC