Prostate-specific Antigen Progression in Enzalutamide-treated Men with Nonmetastatic Castration-resistant Prostate Cancer: Any Rise in Prostate-specific Antigen May Require Closer Monitoring

Abstract

Background: There is no universally accepted definition for prostate-specific antigen (PSA) progression. However, changes in PSA in patients with castration-resistant prostate cancer (CRPC) are used to inform treatment decisions.

Objective: To determine whether the Prostate Cancer Working Group 2 (PCWG2) definition of PSA progression is adequate to predict radiographic or clinical progression in enzalutamide-treated men with nonmetastatic CRPC (nmCRPC).

Design, setting, and participants: A post hoc, retrospective analysis of men with nmCRPC from PROSPER (NCT02003924) was performed.

Intervention: Continued androgen deprivation therapy; patients randomized 2:1 to enzalutamide 160 mg/d or placebo.

Outcome measurements and statistical analysis: Metastasis-free survival (MFS) in men with and without PSA progression, defined by PCWG2, and PSA at the time of radiographic progression were assessed.

Results and limitations: As of June 28, 2017, in enzalutamide-treated patients, the risk of metastasis or death was increased significantly in those with PSA progression versus those without (hazard ratio [HR] 3.99; 95% confidence interval [CI], 2.95-5.41; p < 0.0001). Median MFS was not reached (NR; 95% CI, NR-NR) in patients without PSA progression and was 22.6 mo (95% CI, 21.9-29.0) in those with PSA progression. In placebo-treated patients, PSA progression was not significantly associated with MFS (HR 1.72; 95% CI, 0.86-3.45; p = 0.1). Median MFS was NR (95% CI, 25.6-NR) in patients without PSA progression and 18.3 mo (95% CI, 14.9-19.4) in those with PSA progression. The median PSA increase from nadir at the time of radiographic progression was 1.4 ng/mL in enzalutamide-treated men and 25.6 ng/mL for the placebo arm.

Conclusions: In men with nmCRPC and rapidly rising PSA, radiographic progression often occurred without PCWG2-defined PSA progression, suggesting that any increase in PSA may warrant closer monitoring. While PCWG2-defined PSA progression was associated with radiographic progression in enzalutamide-treated men, our findings argue for prospective re-evaluation of this threshold.

Patient summary: In this report, we looked at changes in prostate-specific antigen (PSA) in enzalutamide-treated men with nonmetastatic castration-resistant prostate cancer who no longer respond to testosterone-lowering treatment. We found that even very small changes in PSA while on treatment could be an early indication of disease progression and should trigger closer monitoring.

Keywords: Enzalutamide; Nonmetastatic castration-resistant prostate cancer; Prostate Cancer Working Group 2; Prostate-specific antigen progression.