Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy

Prostate. 2020 Mar;80(4):336-344. doi: 10.1002/pros.23948. Epub 2020 Jan 3.

Abstract

Background: Immunosuppressive cytokines have the potential to promote prostate cancer progression. Assessing their longitudinal changes may implicate mechanisms of progression, treatment resistance, and suggest new therapeutic targets.

Methods: Thirty-seven men with biochemically recurrent (BCR) prostate cancer who received 6 months of androgen deprivation therapy (ADT) and were monitored until the time to prostate-specific antigen progression (TTPP) were identified from a completed phase III trial (NCT00020085). Serum samples were archived at baseline, 3 months after ADT, and at TTPP. Cytokine concentrations were quantified using a 36-parameter electrochemiluminescence assay. The Wilcoxon signed-rank sum test was used to compare observations between time points. Kaplan-Meier analysis was used to calculate TTPP dichotomized by cytokine values above or below the median. Pearson's rank correlation coefficient was used to compare continuous variables.

Results: Median TTPP was 399 days (range, 114-1641). Median prostate-specific antigen (PSA) at baseline and progression were 8.5 and 5.3 ng/mL, respectively. Twenty-three patients (62%) achieved undetectable PSA with ADT. Castrate levels of testosterone (<50 ng/dL) after 3 months of ADT occurred in 35 patients (95%). TNF-α (P = .002), IL-23 (P = .002), and CXCL10 (P = .001) significantly increased from baseline to post ADT. Certain cytokines correlated longitudinally: TNF-α correlated with IL-23 (r = .72; P < .001) and IL-8 (r = .59; P < .001) from baseline to post ADT and to PSA progression. Neutrophil-to-lymphocyte ratio correlated with IL-27 (r = .57; P < .001) and MIP-3α (r = .56; P < .001). Patients with a detectable PSA after ADT had elevated levels of IL-6 (P = .049) and IL-8 (P = .013) at PSA progression as compared with those with an undetectable PSA. There was a trend toward shorter TTPP in patients with TNF-α levels above the median (P = .042).

Conclusions: Several innate cytokines were associated with biochemically recurrent prostate cancer.

Keywords: IL-23; IL-8; TNF-α; biochemical recurrence.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Biomarkers, Tumor / blood
  • Cohort Studies
  • Cytokines / blood
  • Cytokines / immunology*
  • Disease Progression
  • Double-Blind Method
  • Goserelin / administration & dosage
  • Humans
  • Immune Tolerance
  • Immunity, Innate
  • Immunosuppressive Agents / administration & dosage
  • Kallikreins / blood*
  • Leuprolide / administration & dosage
  • Longitudinal Studies
  • Male
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / immunology*
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / immunology*
  • Thalidomide / administration & dosage

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Cytokines
  • Immunosuppressive Agents
  • Goserelin
  • Thalidomide
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen
  • Leuprolide

Associated data

  • ClinicalTrials.gov/NCT00020085