Patients With Muscle-Invasive Bladder Cancer With Lymphovascular Invasion in Transurethral Resection Specimen Benefits Most From Platinum-Based Neoadjuvant Chemotherapy

The identification of patients who would benefit from neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) remains unclear. In this study, we evaluated the survival benefit of NAC prior to RC by comparing it to a similar cohort that underwent RC alone. The results confirmed a substantial survival benefit for patients with lymphovascular invasion in transurethral resection (TUR) specimens (LVI-positive), while no significant benefit of NAC was observed. Purpose: The survival benefit of neoadjuvant chemotherapy (NAC) before definitive radical cystectomy (RC) varied among patients, suggesting proper selection of patients for NAC to maximize the survival benefit. This study aimed to investigate the role of lymphovascular invasion (LVI) in transurethral resection (TUR) specimens in selecting patients with MIBC for NAC. Methods: Two retrospective cohorts of patients with cT2-4aN0 MIBC who underwent RC from 2004 to 2015 provided by Lund University were included. Inverse probability weighting was applied to make the NAC-treated (NAC) and untreated (non-NAC) cohorts comparable. Survival benefits were estimated with Kaplan -Meier curves and Cox proportional hazards models. The primary endpoint was cancer -specific survival (CSS). LVI in TUR specimens and molecular taxonomies (BASE47, UNC, and LundTax) were examined, and bulk RNA-seq datasets were explored for LVI-relevant signatures. Results: A total of 341 patients with cT2-4aN0 MIBC were included. The NAC cohort included 125 patients, whereas the non-NAC cohort included 216 patients. The 3 -year CSS benefit of NAC was 7.1%. For patients with positive LVI in TUR specimens, the 3 -year CSS benefit of NAC was 26.2% (48.1% vs. 74.3%), with a risk reduction of 56% (HR = 0.44, P = .03). A sensitivity analysis confirmed a significant interaction between LVI and NAC. This study failed to identify the molecular subtypes that maximized the survival benefit of NAC. Exploration of LVI-relevant signatures remains inconclusive. Conclusions: LVI in TUR specimens could help identify patients with MIBC who would derive maximal survival benefit from NAC. Further prospective validation is necessary.