J Cancer 2019; 10(14):3102-3111. doi:10.7150/jca.30384

Research Paper

The Immune Checkpoint Regulator PDL1 is an Independent Prognostic Biomarker for Biochemical Recurrence in Prostate Cancer Patients Following Adjuvant Hormonal Therapy

Heng Li1,2*, Zhize Wang1,3*, Yucong Zhang1,2, Guoliang Sun1,2, Beichen Ding1,2, Libin Yan1,2, Haoran Liu1,2, Wei Guan1,2, Zhiquan Hu1,2, Shaogang Wang1,2, Fei Cheng5, Hua Xu1,2✉, Xu Zhang4, Zhangqun Ye1,2

1. Hubei Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
2. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
3. Department of Urology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
4. Department of Urology/State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/PLA Medical School, Beijing 100000, China.
5. Department of Pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
*These authors contributed equally to this work.

Abstract

Background: The programmed death 1 (PD1)/programmed death ligand 1 (PDL1) targeted therapies have gained positive outcomes in several tumors, but the evidence of the expression and prognosis value of PD1/PDL1 in high risk prostate cancer was rare.

Methods: Immunohistochemical analysis of PDL1/PD1 expression by a validated antibody was performed in a retrospectively collected high risk prostate cancer cohort who received adjuvant hormonal therapy (AHT) after radical prostatectomy (RP). The association between PDL1/PD1 expression and prognosis was determined.

Results: In total, 127 patients were enrolled. 49.6% patients were considered PDL1-high expression while the PD1-positive expression proportion was 24.4%. High PDL1 and negative PD1 expression were significantly associated with lower prostate specific antigen (PSA) density (p=0.010 and p=0.033, respectively). Compared with the PDL1-low expression patients, the PDL1-high expression patients had significantly shorter time to PSA nadir (TTN) (P=0.001) and biochemical recurrence (BCR) (P=0.004). In Kaplan-Meier analysis, the PDL1-high expression group (p<0.0001) and the PDL1-high/PD1-negative expression group (p<0.0001) showed markedly lower BCR-free survival in localized disease. Univariate cause-specific Cox proportional hazard regression model concluded total PSA (p=0.047), PDL1-high-expression (p<0.001), PDL1-high/PD1-negative expression (p<0.001) were significant risk factors of shorter progression time to BCR in localized disease. PDL1-high-expression was the independent predictor of time to BCR in multiple Cox regression of all patients (Hazard ratio [HR]: 3.901; 95% Confidence interval [CI]: 1.287-11.824; p=0.016).

Conclusions: PDL1 expression is not only highly prevalent in high-risk prostate cancer, but is also an independent biomarker in the prognosis of high-risk prostate cancer received AHT after RP. PDL1/PD1 targeted therapy might be a potentially adjuvant treatment option for high-risk prostate cancer after RP.

Keywords: PDL1, PD1, prostate cancer, adjuvant hormonal therapy, biomarker

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How to cite this article:
Li H, Wang Z, Zhang Y, Sun G, Ding B, Yan L, Liu H, Guan W, Hu Z, Wang S, Cheng F, Xu H, Zhang X, Ye Z. The Immune Checkpoint Regulator PDL1 is an Independent Prognostic Biomarker for Biochemical Recurrence in Prostate Cancer Patients Following Adjuvant Hormonal Therapy. J Cancer 2019; 10(14):3102-3111. doi:10.7150/jca.30384. Available from http://www.jcancer.org/v10p3102.htm