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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-? (P?=?.002), IL-23 (P?=?.002), and CXCL10 (P?=?.001) significantly increased from baseline to post ADT. Certain cytokines correlated longitudinally: TNF-? correlated with IL-23 (r?=?.72; P?

SUBMITTER: Hawley JE

PROVIDER: S-EPMC6980998 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Hawley Jessica E JE Pan Samuel S Figg William D WD Lopez-Bujanda Zoila A ZA Strope Jonathan D JD Aggen David H DH Dallos Matthew C MC Lim Emerson A EA Stein Mark N MN Hu Jianhua J Drake Charles G CG

The Prostate 20200103 4

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 31899823

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Project description:Based on in vitro studies, it is known that androgen deprivation therapy (ADT) increases prostate-specific membrane antigen (PSMA) expression on prostate cancer (PCa) cells. However, ADT also has cytoreductive effects which can decrease lesion size. The present evaluation was conducted to further analyze the influence of ongoing ADT on [18F]DCFPyL positron emission tomography/computed tomography (PET/CT) performance in the setting of biochemically recurrent PCa. We retrospectively evaluated two groups of PCa patients, previously treated with radical intent, who had undergone [18F]DCFPyL PET/CT because of biochemical relapse with a minimum PSA level of 0.4 ng/mL. One group consisted of 95 patients under ADT at the time of the PET examination, and the other consisted of 445 patients not receiving ADT at the time of PET/CT. The uptake characteristics of the cardiac blood pool, liver, parotid glands, and five most active lesions were measured and compared between these two groups. The overall detection rate of [18F]DCFPyL PET/CT in patients under ADT at the time of imaging was significantly higher than patients not under ADT (91.6% vs. 80.4%, p-value = 0.007). However, the PSA-stratified differences in detection rates between patients with and without ADT did not reach statistical significance. Except for the maximal standardized uptake values corrected for lean body mass (SULmax) in the PSA range of 1 to <2 ng/mL, the intensity and volume of [18F]DCFPyL accumulation were higher in patients with ADT compared to the patients without. Statistical significance was attained for the SULmax in PSA range of 0.5 to <1 ng/mL (p-value = 0.0004) and metabolic tumor volume (MTV) in all PSA ranges (p-values of 0.0005 to 0.03). No significant difference was observed for radiotracer uptake in normal organs between the two groups with and without ADT. In this study population with biochemical recurrence of PCa and measurable PSA, ongoing ADT at the time of [18F]DCFPyL PET/CT imaging was associated with higher radiotracer uptake and overall lesion detection rate. This could be due in part to the more aggressive disease phenotype in patients with ongoing ADT.

Dataset Information

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

Publications

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

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