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

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.

Molecular profiling of radical prostatectomy tissue from patients with no sign of progression identifiesERGas the strongest independent predictor of recurrence

“…They showed, by multivariate analysis, that p65 nuclear localization was an independent predictor for BCR using continuous (Hazard ratio [HR] 1.03; 95% Confidence interval [CI] 1.02–1.04]; p < 0.001) and dichotomized (HR 1.60; 95% CI 1.32–1.94; p < 0.001) p65 expression data in the validation cohort. In another study, Li and colleagues examined the association between expression of Programmed Cell Death Protein 1 (PD1) and (Programmed Cell Death 1 Ligand 1) PD-L1 proteins with BCR in prostate cancer patients following adjuvant hormonal therapy (AHT) [86]. They reported that overexpression of PDL1 in high risk prostate cancer is significantly correlated with a shorter median time to BCR ( p = 0.004) after AHT.…”

“…Furthermore, while the racial or ethnic status of the patient cohort were not defined in these recently published studies, our study is based on a diverse patient cohort, consisting of approximately 70% CA and 30% AA patients. Moreover, in evaluating the predictive value of detecting ERG for BCR, our study we not only used the NanoString platform, but we compared it to IHC and qRT-PCR, whereas only IHC [85, 86] or IHC and FISH [87] were used in the other studies. Lastly, we evaluated a total of 121 genes or gene alteration events for association with progression to BCR while the other studies examined the association of either a single biomarker [85], or two interacting proteins [86], or protein expression and copy number amplification associated with a single gene [87].…”

Assessment of biochemical recurrence of prostate cancer (Review)

“…However, the biochemical relapse rates for high-risk localized disease [PSA>20 ng/ml, GS>7, or cT2c (3)] can increase to 50-80% (252). Males with high-risk tumors can be managed with adjuvant therapy following RP; in a small group of patients (n=127) treated with adjuvant hormone therapy, high level of PDL1 expression is an independent risk factor of BCR (253). The PDL1 expression status could facilitate the diagnosis of BCR following RP.…”

Association between CD8 and PD‐L1 expression and outcomes after radical prostatectomy for localized prostate cancer

“…In contrast, the data on the association between immune checkpoints and outcomes in prostate cancer is more convincing. Several studies have shown that higher PD‐L1 expression correlates with adverse clinicopathologic features and a higher risk of clinical progression, BCR or MFS, 10,21–24 and this has also been confirmed in a meta‐analysis 9 . There has also been work assessing changes in immune marker profiles after hormonal therapy, with a decrease in PD‐L1 expression and CD8+ TILs seen after treatment with neoadjuvant abiraterone and androgen deprivation 25 .…”