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

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

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Free PMC article

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

Heng Li et al. J Cancer. .
Free PMC article

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Representative hematoxylin-eosin (H&E) and immunohistochemical (IHC) staining of PDL1 and PD1. (A, D, G and J) are hematoxylin-eosin staining, (B, E, H and K) are immunohistochemical staining for programmed death ligand 1 (PDL1) and (C, F, I and L) are immunohistochemical staining for PD1 in four consecutive tissue sections. The first and second rows are PDL1-high expression and the third and fourth rows are PDL1-low expression; the first and third rows are considered as PD1 positive while the second and fourth rows are PD1 negative. Original magnification: 200×.
Figure 2
Figure 2
(A) The time to biochemistry recurrence (BCR) after adjuvant hormonal therapy in the PDL1-high and PDL1-low expression groups. Black crosshairs denote the mean time to BCR with 95% CI. (B) The time to PSA nadir (TTN) after adjuvant hormonal therapy in the PDL1-high and PDL1-low expression groups. Black crosshairs denote the mean TTN with 95% CI. p values are for Student's t tests.
Figure 3
Figure 3
Kaplan-Meier analysis of biochemical recurrence free survival according to PDL1/PD1 status in patients stratified by localized or metastatic disease (A, B, C, D, E and F). (A) The hazard ratio for BCR progression with PDL1-high-expression in localized disease was 6.087 (95% CI: 3.028-11.73; p<0.0001 by the log-rank test). (B) The hazard ratio for BCR progression with PD1 positivity in localized disease was 0.317 (95% CI: 0.186-1.134; p=0.094 by the log-rank test). (C) The hazard ratio for BCR progression with the panel of PDL1-high/PD1-negative status expression in localized disease was 6.330 (95% CI: 2.843-14.095; p<0.0001 by the log-rank test) (D) .The hazard ratio for BCR progression with PDL1-high-expression in metastatic disease was 2.746 (95% CI: 0.733-10.33; p=0.135 by the log-rank test). (E) The hazard ratio for BCR progression with PD1 positivity in metastatic disease was 2.253 (95% CI: 0.593-11.580; p=0.2085 by the log-rank test). (F) The hazard ratio for BCR progression with the panel of PDL1-high/PD1-negative status expression in metastatic disease was 0.761 (95% CI: 0.158-3.668; p=0.753 by the log-rank test)
Figure 4
Figure 4
Kaplan-Meier analysis of biochemical recurrence free survival in all enrolled patients according to different PDL1/PD1 status (A, B, C and D). (A) The hazard ratio for BCR progression with PDL1-high expression in PD1-positive patients was 6.799 (95% CI: 1.365-33.85; p=0.0193 by the log-rank test). (B) The hazard ratio for BCR progression with PDL1-high expression in PD1-negative patients was 4.344 (95% CI: 2.333-8.583; p<0.0001 by the log-rank test). (C) The hazard ratio for BCR progression with PD1-positive expression in PDL1-high expression patients was 0.917 (95% CI: 0.389-2.162; p=0.8446 by the log-rank test). (D) The hazard ratio for BCR progression with PD1-positive expression in PDL1-low expression patients was 0.2865 (95% CI: 0.055-1.486; p=0.1367 by the log-rank test)

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References

    1. Ferlay J, Soerjomataram I, Dikshit R. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer Journal international du cancer. 2015;136:E359–386. - PubMed
    1. Siegel R, DeSantis C, Virgo K. et al. Cancer treatment and survivorship statistics, 2012. CA: a cancer journal for clinicians. 2012;62:220–241. - PubMed
    1. Heidenreich A, Bastian PJ, Bellmunt J. et al. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. European urology. 2014;65:124–137. - PubMed
    1. See WA, Wirth MP, McLeod DG. et al. Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program. The Journal of urology. 2002;168:429–435. - PubMed
    1. Messing EM, Manola J, Sarosdy M. et al. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. The New England journal of medicine. 1999;341:1781–1788. - PubMed
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