The Immunoscore in Localized Urothelial Carcinoma Treated with Neoadjuvant Chemotherapy: Clinical Significance for Pathologic Responses and Overall Survival.

Bernhard Mlecnik,Xavier Barthere ,Aristotelis Bamias,Constance Thibault,Virginie Verkarre,Jérôme Galon,Marine Martel,Isabelle Boquet,Stéphane Oudard,Marie Auvray,B D'acremont ,Daniela Bruni,Elise F. Nassif,François Audenet ,A. Colau ,Marine Lefèvre ,Philippe Camparo,P. Colin ,Arnaud Méjean ,Gabriela Bindea,Mostefa Bennamoun,Aurélie Fugon,Roubini Zakopoulou,Aurélie Catteau,Éva Compérat

doi:10.3390/cancers13030494

Abstract

Simple SummaryThe prognosis of localized muscle-invasive bladder cancer is poor and the prognostic and predictive biomarkers of the response to treatment are lacking. We retrospectively investigated the role of the Immunoscore in the neoadjuvant setting, where the Immunoscore is a standardized quantitative assay of lymphocytes in the tumor microenvironment. We found it allowed for the stratification of patient prognoses and the prediction of response to neoadjuvant chemotherapy.(1) Background—The five-year overall survival (OS) of muscle-invasive bladder cancer (MIBC) with neoadjuvant chemotherapy and cystectomy is around 50%. There is no validated biomarker to guide the treatment decision. We investigated whether the Immunoscore (IS) could predict the pathologic response to neoadjuvant chemotherapy and survival outcomes. (2) Methods—This retrospective study evaluated the IS in 117 patients treated using neoadjuvant chemotherapy for localized MIBC from six centers (France and Greece). Pre-treatment tumor samples were immunostained for CD3+ and CD8+ T cells and quantified to determine the IS. The results were associated with the response to neoadjuvant chemotherapy, time to recurrence (TTR), and OS. (3) Results—Low (IS-0), intermediate (IS-1–2), and high (IS-3–4) ISs were observed in 36.5, 43.7, and 19.8% of the cohort, respectively. IS was positively associated with a pathologic complete response (pCR; p-value = 0.0096). A high IS was found in 35.7% of patients with a pCR, whereas it was found in 11.3% of patients without a pCR. A low IS was observed in 48.4% of patients with no pCR and in 21.4% of patients with a pCR. Low-, intermediate-, and high-IS patients had five-year recurrence-free rates of 37.2%, 36.5%, and 72.6%, respectively. In the multivariable analysis, a high IS was associated with a prolonged TTR (high vs. low: p = 0.0134) and OS (high vs. low: p = 0.011). (4) Conclusions—This study showed the significant prognostic and predictive roles of IS regarding localized MIBC.

Highlights

Bladder cancer is the fourth and eighth most common cancer in men and women respectively, in Western countries [1]
Recurrence was defined as either metastatic disease on the radiological assessment if seen within the first year of follow-up or histologically confirmed if recurrence was seen after 12 months following surgery, or local relapse, which was defined as histologically confirmed muscle-invasive urothelial carcinoma
A total of 117 patients treated with neoadjuvant platinum-based chemotherapy for invasive urothelial carcinoma were included in the final analysis (Figure S1)

Summary

Introduction

Bladder cancer is the fourth and eighth most common cancer in men and women respectively, in Western countries [1]. 30% of patients will present with muscle-invasive bladder cancer (MIBC). The standard-of-care treatment for patients with localized MIBC is neoadjuvant chemotherapy before a radical cystectomy [2,3]. The fiveyear overall survival (OS) rate after this initial treatment is around 50% [4]. Major clinical prognostic factors are the tumor T stage and nodal status [5]. The pathologic complete response (pCR) to neoadjuvant chemotherapy is associated with an improved OS [6]. There is no tumor biomarker that is validated for the prediction of the response to chemotherapy or prognosis in this context

Methods

Results

Conclusion