PD-L1 expression may assist in predicting responses to bacillus Calmette-Guérin (BCG) therapy among patients with high-grade nonmuscle-invasive bladder cancer (NMIBC), investigators reported at the ASCO Genitourinary Cancers Symposium 2022.
In a cohort of 102 BCG-naïve patients, PD-L1 expression was generally low (15%), but higher with increasing invasiveness: cTis (3.7%), cTa (5.8%), and cT1 disease (30%). All patients underwent initial transurethral resection followed by BCG (median 1 maintenance cycle). A total of 17 patients (16.7%) underwent immediate reinduction BCG.
Investigators observed BCG unresponsiveness in 32 patients (35.6%) and high-grade relapse in 29 (34.5%) patients.
On univariate analysis, higher PD-L1 expression was significantly associated with 89% decreased odds of BCG unresponsiveness, but not high-grade relapse, Solomon L. Woldu, MD, of UT Southwestern Medical Center, Dallas, Texas, reported on behalf of his team. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PD-L1 expression for BCG responsiveness were 22%, 97%, 93%, and 41%, respectively. The investigators found that the post-test probability of BCG responsiveness was 93% in patients positive for PD-L1 based on a positive likelihood ratio of 7.33 for PD-L1 expression.
On multivariate regression, PD-L1 expression was significantly associated with 15.1-fold increased odds of response to BCG. In contrast, pT1 and CIS were significantly associated with 84% and 75% decreased odds of BCG responsiveness.
“BCG’s mechanism of action is believed to be stimulation of the immune system, and systemic immune checkpoint inhibition is approved for BCG-unresponsive NMIBC,” Dr Woldu said in an interview. “PD-L1 expression was strongly associated with BCG responsiveness. Lack of PD-L1 expression, however, was not strongly associated with lack of response to BCG. Therefore upfront management should remain standard of care BCG induction – regardless of PD-L1 expression. Routine PD-L1 expression testing is not warranted.”
The team is currently investigating expression of other immune checkpoint proteins to determine if these might function as markers of BCG response, particularly among patients without PD-L1 expression.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Woldu SL, Gerald T, Margulis V, et al. PD-L1 expression and BCG response in nonmuscle invasive bladder cancer. Paper presented at: ASCO GU 2022; February 17-19, 2022. Abstract 545.