Lymphovascular Invasion is Predictive for Adjuvant Platinum Therapy Benefit in Urothelial Bladder Cancer

Perioperative platinum-based chemotherapy remains the standard systemic treatment for nonmetastatic muscle-invasive bladder cancer (MIBC). Adjuvant chemotherapy (AC) is recommended for patients with pT3/4 (stage IIIA) or lymph node-positive (LN+, stage IIIB) disease following radical cystectomy (RC). However, not all patients benefit equally, highlighting the need for predictive biomarkers. Lymphovascular invasion (LVI) is a known risk-factor in several cancers, including MIBC, but its predictive value for AC benefit remains unclear. Therefore, we aimed to assess whether LVI can predict response to platinum-based AC in MIBC.

We conducted a retrospective cohort study involving MIBC patients who underwent RC between 2005 and 2023 at two academic centers. Inclusion criteria were pT3/T4M0 or LN+ disease, with available LVI status and survival data. Patients were divided into a treatment (AC) and a control group (RC without AC). Overall survival (OS) was the primary endpoint; cancer-specific survival (CSS) was secondary. Statistical analysis was performed using Kaplan-Meier estimates, Cox proportional hazards models, and propensity score matching (PSM) to adjust for potential confounders.

A total of 345 patients fulfilled the inclusion criteria of whom 92 (27%) received and 253 (73%) did not receive AC. LVI-positive patients demonstrated significantly improved OS and CSS when treated with AC (both P < .001), while no significant OS or CSS benefit was observed for AC-treated LVI-negative patients (P = .146 for OS, P = .975 for CSS). Results remained similar after PSM correction revealing survival benefit for AC treatment in LVI-positive but not in LVI-negative patients.

This study demonstrates, for the first time, LVI status as a predictor of treatment benefit from platinum-based AC. Our results suggest that LVI status is an easily assessable biomarker to identify those patients who derive greater benefit from the treatment, while LVI-negative patients might be spared unnecessary chemotherapy and its associated toxicity.