Muscle-invasive bladder cancer (MIBC) remains associated with a poor prognosis: approximately 30% of patients with bladder cancer present with a muscle-invasive form, and five-year overall survival following neoadjuvant chemotherapy and radical cystectomy plateaus at around 50%. Yet, despite the recognized prognostic value of tumor T stage and nodal status, as well as of pathological complete response to chemotherapy, no tumor biomarker has so far been validated to predict treatment response or guide therapeutic decision-making. It is this gap that the authors sought to address by evaluating the Immunoscore, a standardized quantitative assay measuring the density of T lymphocytes (CD3+ and CD8+) within the tumor microenvironment, already established as a robust prognostic tool in colorectal cancer.
This multicenter retrospective study included 117 patients treated with neoadjuvant chemotherapy for localized MIBC, recruited across six centers in France and Greece. Pretreatment tumor specimens were immunostained for CD3+ and CD8+ T lymphocytes and then quantified to derive the Immunoscore, whose results were correlated with chemotherapy response, time to recurrence, and overall survival. Scores were distributed across low (IS-0: 36.5%), intermediate (IS-1-2: 43.7%), and high (IS-3-4: 19.8%) values.
A high Immunoscore was found to be positively associated with pathological complete response (p = 0.0096): a high score was observed in 35.7% of patients achieving a complete response, compared with only 11.3% of those who did not. Five-year recurrence-free survival rates reached 72.6% in the high-score group, versus 37.2% and 36.5% in the low- and intermediate-score groups, respectively. In multivariate analysis stratified by center, a high score remained independently associated with prolonged time to recurrence (p = 0.013) and better overall survival (p = 0.011), with the Immunoscore providing the strongest contribution among all variables studied. CD8+ lymphocyte infiltration of the tumor core was furthermore correlated with overall survival (median of 64.7 months versus 27.4 months for low infiltration).
The authors acknowledge the limitations inherent to the retrospective nature of the study and to certain missing clinical data, notably nodal status, while emphasizing that this is a large cohort drawn from routine clinical practice. They also note variability in the Immunoscore and immune densities across the histological subtypes of urothelial carcinoma. In conclusion, the Immunoscore enables effective risk stratification and prediction of response to neoadjuvant chemotherapy in localized MIBC—findings that warrant further prospective evaluation, already underway, before any implementation in routine clinical practice.