Immunohistochemistry-Based Molecular Subtyping in Muscle-Invasive Bladder Cancer: Predicting Response to Neoadjuvant Chemotherapy.

Abstract

Background: Muscle-invasive bladder cancer (MIBC) presents a heterogeneous response to perioperative chemotherapy. Although several molecular classifications of MIBC have been proposed, two main subtypes, namely, luminal and basal, are widely recognised. This study aims to explore the relationship between the molecular subtypes of MIBC, as characterised by GATA binding protein 3 (GATA3) and cytokeratin 5/6 (CK5/6) immunohistochemistry, and treatment response to neoadjuvant chemotherapy.

Methods: Patients with nonmetastatic MIBC who were treated with cisplatin-based neoadjuvant chemotherapy at the Reina Sofía University Hospital between 2014 and 2023 were retrospectively analysed. Tumours were classified into luminal (GATA3+, CK5/6-), basal (GATA3-, CK5/6+), double-positive (GATA3+, CK5/6+), or double-negative (GATA3-, CK5/6-) subtypes. Clinical and pathological data, including overall survival (OS), disease-free survival (DFS) and pathological response, were analysed by using Kaplan-Meier curves, log-rank tests and chi-squared tests.

Results: Amongst the 69 patients included, 13 were classified as luminal, five as basal, 50 as double positive and one as double negative. Patients with luminal tumours had significantly higher five-year DFS (91.7% vs. 50.7%, p = 0.021) and OS (100% vs. 60.5%, p = 0.016) than those with double-positive tumours. Pathological complete response (ypT0) was observed in 7/13 (53.8%) luminal tumours and in 15/50 (30.0%) double-positive tumours (p = 0.190). Additionally, 9/13 (69.2%) luminal tumours achieved tumour downstaging (p = 0.060) achieved tumour downstaging. Basal and double-negative subtypes were excluded from analysis because of their low representation in the sample.

Conclusions: The luminal subtype showed superior outcomes in terms of DFS and OS compared with double-positive tumours. Higher rates of pathological complete response and tumour downstaging were observed in luminal tumours than in other tumour types. However, these differences did not reach statistical significance.