A Th2-score in the tumor microenvironment as a predictive biomarker of response to BCG in patients with non-muscle invasive bladder carcinoma. A retrospective study.

Abstract

Intravesical BCG is the gold standard therapy for intermediate/high-risk NMIBC. However, the response rate is ~60%, and 50% of non-responders will progress to muscle invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1), and ultimately cytotoxic tumor elimination. We searched for a predictive biomarker of BCG response by analyzing TILs polarization in the TME in pre-treatment biopsies. Materials and Methods: Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillations of BCG (n=32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ (Th2) lymphocyte ratio (G/T), and the density and degranulation of EPX+ eosinophils. In addition, PD-1/PD-L1 staining was quantified. The results correlated with the BCG response. In most nonresponders, Th1/Th2 markers were compared in pre-and post-BCG biopsies.ORR was 65.6% in the study population. BCG responders had a higher G/T ratio and higher number of degranulated EPX+ cells. Variables combined into a Th2-score showed a significant association with higher scores in responders (p=0.027). A Th2-score cut-off value >48.1 allowed discrimination of responders with 91% sensitivity, but with lower specificity. Relapse-free survival was significantly associated with the Th2-score (p=0.007). In post-BCG biopsies from recurring patients, TILs increased Th2-polarization, probably reflecting BCG failure to induce a pro-inflammatory status and, thus, a lack of response. PD-L1/PD-1 expression was not associated with the BCG response.Our results support the hypothesis that a pre-existing Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity.

Efficiency of transurethral en‐bloc resection vs. conventional transurethral resection for non‐muscle‐invasive bladder cancer: An umbrella review

“…15 Simultaneously, obtaining the entire tumor specimen could assist pathologists in making more accurate diagnoses and facilitate the identification of histological variants that had a significant impact on the prognosis of patients with NMIBC. [40][41][42] Moreover, all pooled meta-analyses demonstrated that ERBT was associated with a lower incidence of residual tumor. These two pieces of evidence confirmed the sufficient efficacy of ERBT in managing NMIBC.…”

“…Invasive detrusor muscle is the diagnostic criterion for NMIBC and MIBC 15 . Simultaneously, obtaining the entire tumor specimen could assist pathologists in making more accurate diagnoses and facilitate the identification of histological variants that had a significant impact on the prognosis of patients with NMIBC 40–42 . Moreover, all pooled meta‐analyses demonstrated that ERBT was associated with a lower incidence of residual tumor.…”

Identification and validation of basement membrane-related genes predicting prognosis and immune infiltration associated with bladder cancer

“…[1,2] About 3-quarters of bladder malignancies are non-muscle-invasive. [3] In contrast, 20% to 25% of bladder malignancies are muscle-invasive at the initial onset. [4,5] Patients with localized disease can be cured by surgical resection or radiotherapy, but this treatment is limited if the disease is recurrent or spread over long distances.…”