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

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.