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

Heng Li; Zhize Wang; Yucong Zhang; Guoliang Sun; Beichen Ding; Libin Yan; Haoran Liu; Wei Guan; Zhiquan Hu; Shaogang Wang; Fei Cheng; Hua Xu; Xu Zhang; Zhangqun Ye

doi:10.7150/jca.30384

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

J Cancer. 2019 Jun 2;10(14):3102-3111. doi: 10.7150/jca.30384. eCollection 2019.

Authors

Heng Li^{1

2}, Zhize Wang^{1

3}, Yucong Zhang^{1

2}, Guoliang Sun^{1

2}, Beichen Ding^{1

2}, Libin Yan^{1

2}, Haoran Liu^{1

2}, Wei Guan^{1

2}, Zhiquan Hu^{1

2}, Shaogang Wang^{1

2}, Fei Cheng⁴, Hua Xu^{1

2}, Xu Zhang⁵, Zhangqun Ye^{1

2}

Affiliations

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 Pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
⁵ Department of Urology/State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/PLA Medical School, Beijing 100000, China.

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: PD1; PDL1; adjuvant hormonal therapy; biomarker; prostate cancer.