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

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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.

Original languageEnglish (US)
Pages (from-to)336-344
Number of pages9
JournalProstate
Volume80
Issue number4
DOIs
StatePublished - Mar 1 2020

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Prostate-Specific Antigen
Immunosuppressive Agents
Prostatic Neoplasms
Cytokines
Androgens
Therapeutics
Interleukin-23
Interleukin-8
Interleukin-27
Kaplan-Meier Estimate
Nonparametric Statistics
Testosterone
Interleukin-6
Neutrophils
Lymphocytes

All Science Journal Classification (ASJC) codes

  • Urology
  • Oncology

Keywords

  • biochemical recurrence
  • IL-23
  • IL-8
  • TNF-α

Cite this

@article{c4af731a48f34cc5a28957fa85d3d483,
title = "Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy",
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 = "biochemical recurrence, IL-23, IL-8, TNF-α",
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TY - JOUR

T1 - Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy

AU - Stein, Mark N.

PY - 2020/3/1

Y1 - 2020/3/1

N2 - 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.

AB - 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.

KW - biochemical recurrence

KW - IL-23

KW - IL-8

KW - TNF-α

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VL - 80

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SN - 0270-4137

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