ASCO GU 2022: PD-L1 Expression and BCG Response in Nonmuscle Invasive Bladder Cancer (NMIBC)

(UroToday.com) The 2022 GU ASCO Annual meeting included a urothelial carcinoma session featuring work from Dr. Solomon L. Woldu and colleagues presenting results assessing PD-L1 expression and BCG response in nonmuscle invasive bladder cancer (NMIBC). Intravesical BCG is the standard of care adjuvant therapy for high risk NMIBC, yet many patients experience recurrence or disease progression. The mechanism of action of BCG is believed to be related to the stimulation of immune surveillance. Relatedly, systemic immune checkpoint inhibition is currently being utilized in advanced bladder cancer and approved for BCG unresponsive NMIBC. This study sought to determine the association between PD-L1 expression and BCG treatment. This study identified 102 BCG-naïve patients with high grade NMIBC treated with BCG. All patients underwent initial transurethral resection (TUR) for pathologic diagnosis. Dako 22c3 assay was used to determine PD-L1 expression. Patients were defined as PD-L1 positive if the combined positive score (CPS) > 0. BCG unresponsiveness was defined by the presence of high grade 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 following induction. High grade relapse was defined as the presence of any high grade disease after being followed for 6 months after BCG.

The median follow-up time was 57 months. The median number of BCG maintenance cycles was 1, and 17 (16.7%) patients underwent immediate re-induction BCG. PD-L1 expression was observed 5.9% of pTa, 30.0% of pT1, and 3.6% of CIS (p = 0.002):

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BCG unresponsiveness and high grade relapse were observed in 32 (35.6%) and 29 (34.5%) patients, respectively. On univariate analysis, PD-L1 expression was inversely associated with BCG unresponsiveness (OR = 0.112; 95% CI 0.014-0.898) but not high grade relapse (OR = 0.296; 95% CI 0.061-1.440). 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:

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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, pT1 (OR 0.159, 95% CI 0.045-0.600), CIS (OR 0.247, 95% CI 0.071-0.857), and PD-L1 expression (OR 15.625, 95% CI 1.779-142.857) were independently associated with BCG responsiveness.

Dr. Woldu concluded his presentation assessing PD-L1 expression and BCG response in NMIBC with the following take-home messages:

PD-L1 expression in high grade NMIBC was low, and patients with PD-L1 expression at initial TUR were more likely to harbor invasive disease
Patients showing 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 pathologic diagnosis and may assist in predicting responses to BCG among patients with high grade NMIBC
Further investigation is required to determine if additional immune checkpoint markers have strong correlation with BCG response, particularly among patients without PD-L1 expression

Presented by: Solomon L. Woldu, MD, University of Texas Southwestern Medical Center, Dallas, TX

Co-Authors: Thomas Gerald, Vitaly Margulis, Daniel Halstuch, Yaara Ber, Karin Lifshitz, David Margel, Yair Lotan, Liwei Jia

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022

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