Variant histology or divergent differentiation (VH/DD) of urothelial carcinoma (UC) may impact outcomes after neoadjuvant chemotherapy (NAC) in muscle invasive bladder cancer. Our aim was to assess the pathological response and progression free survival (PFS) of patients with VH/DD in the prospective VESPER clinical trial.
This post-hoc study included 300 NAC-treated patients with available transurethral diagnostic slides. Presence and percentage of VH/DD was reviewed. For pathological response, logistic regression models were computed to measure association with VH/DD. For PFS, the associations were estimated in Cox proportional hazard regression model. All models were adjusted for randomization arm.
VH/DD was identified in 177/300 patients (59%), and was predominant (≥ 50%) in 85/177. Compared to pure UC, VH/DD (≥ 10% or ≥ 50%), was not associated with a difference in proportion of complete pathological response (pCR) (ypT0N0) (OR adjusted: 0.79, 95% CI 0.49-1.29), downstaging (≤ ypT1N0) (OR adjusted: 0.62, 95% CI 0.37-1.02), or with an increased hazard of PFS (HR adjusted: 1.24, 95% CI 0.83-1.85). However, comparing specific VH/DD to pure UC, nested subtype was associated with decreased odds of pCR (OR adjusted: 0.33, 95% CI 0.12-0.88) and downstaging (OR adjusted: 0.30, 95% CI 0.13-0.74), and an increased hazard of PFS was observed for UC with ≥ 50% squamous differentiation (HR adjusted: 2.11 95% CI 1.01-4.38) or micropapillary subtype (HR adjusted: 2.03 95% CI 0.98-4.22).
In the VESPER trial, we did not observe evidence for association of VH/DD with outcomes after NAC, but the specific presence of a predominant squamous differentiation or micropapillary subtype may be associated with shorter PFS.
The Journal of urology. 2023 Dec 28 [Epub ahead of print]
Yves Allory, Stephane Culine, Clémentine Krucker, Jacqueline Fontugne, Valentin Harter, Christian Pfister
Université Paris-Saclay, UVSQ, Institut Curie, Department of Pathology, Saint-Cloud, France., Université de Paris Cité, AP-HP, Hôpital Saint-Louis, Department of Medical Oncology, Paris, France., Institut Curie, PSL Research University, CNRS, UMR144, Equipe Labellisée Ligue Contre le Cancer, Paris, France., Centre François Baclesse, North-West Canceropole Data Center, Caen, France., Université de Rouen Normandie, Inserm, CIC Inserm 1404, Onco-Urology, Hôpital Universitaire Charles Nicolle, Department of Urology, Rouen, France.