Slight changes in PSA warrant closer attention in nonmetastatic CRPC

Men with nonmetastatic castration-resistant prostate cancer (nmCRPC) who have rapidly rising levels of prostate-specific antigen (PSA) see radiographic progression of their malignancy even without meeting the criteria set by the Prostate Cancer Working Group 2 (PCWG2), a recent study has shown.

Such radiographic evidence of cancer progression may indicate that any increase in PSA is worth further evaluation and closer monitoring.

Researchers conducted a posthoc, retrospective analysis of nmCRPC patients who had previously been randomized to receive enzalutamide or placebo. All participants were on antigen deprivation therapy (ADT). A total of 208 enzalutamide-treated patients showed PCWG2-defined PSA progression while 725 did not. In the placebo arm, 324 had PSA progression and 144 had no progression.

In both the enzalutamide and placebo arms, the metastasis-free survival (MFS) was shorter among patients who showed evidence of PSA progression; in men who had no such progression, median MFS was not reached. The risk of metastasis or death was likewise significantly aggravated among patients with PSA progression, but only in the enzalutamide arm (p<0.0001) and not among placebo controls.

However, even among participants who had no PSA progression, as defined by the PCWG2, some signals of radiographic progression were observed. Of the 725 enzalutamide-treated men without PSA progression, 10 percent (n=75) showed evidence of radiographic progression. This proportion was higher among placebo-treated patients at 26 percent (n=38).

Radiographic progression was nevertheless more prevalent among patients with PSA progression, reaching rates of over 50 percent in both the enzalutamide and placebo arms.