Urologic Oncology Fellow University of Texas Southwestern Medical Center
Introduction: Intravesical bacillus Calmette Guerin (BCG) is the standard of care adjuvant therapy for high risk non-muscle invasive bladder cancer (NMIBC), yet many patients experience recurrence or disease progression. The mechanism of BCG is thought to be related to stimulation of immune surveillance. Relatedly, systemic immune checkpoint inhibition is being utilized in advanced bladder cancer and approved for BCG unresponsive NMIBC. We sought to determine the association between PD-L1 expression and BCG treatment.
Methods: We identified 102 BCG-naïve patients with high grade (HG) NMIBC treated with BCG. All patients underwent initial transurethral resection (TUR). Dako 22c3 assay was used to determine PD-L1 expression. Patients were defined as PD-L1 positive if the combined positive score > 0. BCG unresponsiveness was defined by presence of HG disease at 6 months following adequate BCG (one induction and maintenance cycle or two induction cycles) for pT1 or 12 months for CIS or presence of pT1 at 3 months after induction. HG relapse was defined as HG disease after being followed for 6 months after BCG.
Results: The median follow-up was 57 months. Median number of BCG maintenance cycles was 1, and 17 (16.7%) patients underwent immediate reinduction BCG. PD-L1 expression was observed in 5.9% of pTa, 30.0% of pT1, and 3.6% of CIS. BCG unresponsiveness and HG relapse were observed in 32 (35.6%) and 29 (34.5%), respectively. On univariate analysis, PD-L1 expression was inversely associated with BCG unresponsiveness (OR = 0.11; 95% CI 0.01-0.90) but not HG relapse (OR = 0.30; 95% CI 0.06-1.44). The sensitivity, specificity, positive predictive value, and negative predictive value of PD-L1 expression for BCG responsiveness were 22%, 97%, 93%, and 41%, respectively. PD-L1 positive patients had a post-test probability of BCG responsiveness of 93%. On multivariate regression, pT1 (OR = 0.16; 95% CI 0.05-0.60), CIS (OR = 0.25; 95% CI 0.07-0.86), and PD-L1 expression (OR = 15.63; 95% CI 1.78-142.86) were associated with BCG responsiveness.
Conclusions: PD-L1 expression in HG NMIBC was low, and those with PD-L1 expression at initial TUR were more likely to harbor invasive disease. Patients with PD-L1 expression were more likely to demonstrate BCG responsiveness. These findings suggest a role of PD-L1 in the immune surveillance mechanism of BCG at initial diagnosis and may assist in predicting response to BCG in patients with HG NMIBC. Further investigation is needed to determine if additional immune checkpoint markers have strong correlation with BCG response, particularly among patients without PD-L1 expression.
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