Long-Term Outcomes and Paired Immune and Genomic Exploratory Analyses After Neoadjuvant Dose-Dense MVAC in Muscle-Invasive Bladder Cancer: A Single-Centre Case Series
Retrospective cohort study reports long-term outcomes and immune depletion after dose-dense MVAC in muscle-invasive bladder cancer, highlighting stable genomics in residual tumors.
Key Points
To describe long-term survival outcomes and evaluate paired pre- and post-treatment immune and genomic alterations in muscle-invasive bladder cancer treated with neoadjuvant dose-dense MVAC.
Retrospective single-centre analysis of 54 consecutive patients with muscle-invasive bladder cancer treated with neoadjuvant dose-dense MVAC between November 2013 and November 2019, of whom 42 underwent radical cystectomy.
Conducted immunohistochemical profiling (CD3, CD8, FOXP3, PD-1, PD-L1, PD-L2, NY-ESO-1) on 31 baseline and 22 paired specimens, alongside paired genomic profiling via whole-exome sequencing (n=10) and TSO-500 (n=7).
Pathologic complete response (pCR) was attained in 11/42 patients (26%, 95% CI 15–41) over a median follow-up of 87 months (IQR 24–104); pCR significantly prolonged recurrence-free survival (log-rank p = 0.017), though overall survival differences were not significant (p = 0.121).
Baseline hydronephrosis was significantly associated with failure to achieve pCR (p = 0.016), whereas baseline immune markers, including PD-L1, showed no association with response.
Neoadjuvant chemotherapy significantly reduced intratumoral FOXP3 (q = 0.001), NY-ESO-1 (q = 0.013), PD-L2 (q = 0.013), and CD3 (q = 0.043), while tumour mutational burden remained unchanged across paired assessments (TSO-500 p = 0.67; WES p = 0.86).