The effect of PSA frequency and duration on PSA doubling time (PSADT) calculations in men with biochemically recurrent prostate cancer (BRPC) after definitive local therapy.

Abstract

4559 Background: The prognostic nature of PSADT in men with BRPC makes it an attractive intermediate endpoint for assessing novel therapies in these patients. Although a number of investigational agents appear to favorably modulate PSADT, slowing in PSADT has also been observed in placebo-treated men. We aimed to determine whether PSADT calculations could be influenced by the frequency and duration of PSA measurements. Methods: We performed a retrospective analysis of men with BRPC who chose to defer hormonal therapy. Eligible men were those with PSA values ≥0.2 ng/mL and at least 6 values taken on average 3 mo apart, and whose local prostate cancer therapy was completed ≥1 year prior. To examine the influence of PSA frequency and duration on PSADT, we calculated median PSADT using different subsets of available PSA values (e.g. each vs every other; and first 3 vs. remaining PSA values). Results: After a median follow-up of 58 mo (range, 6-185 mo), 213 men with BRPC had ≥6 PSA values and 127 men had ≥9 PSA values for analysis. Men (77% white, 23% black/other) had a median age of 61 y with Gleason score distribution as follows (≤6: 30%; 7: 40%; ≥8: 18%; NOS: 12%). For men with ≥6 data points: PSADT calculated using earlier values ranged from 13.2 to 16.6 mo, compared to 16.6 to 17.8 mo, respectively, for the remaining values (within-patient change range: 0.6-1.2 mo). For men with ≥9 data points: PSADT calculated using earlier values ranged from 15.3 to 19.9 mo compared to 22.1 to 22.3 mo, respectively, for the remaining values (within-patient change range: 3.5 to 4.5 mo). When we examined the frequency of PSADT by using every other value, we found little difference (22.3 vs 22.1 mo). Conclusions: These data show that PSADT appears to increase even in the absence of therapy, and may be influenced by duration of PSA follow up. This finding explains PSADT slowing on placebo arms and calls into question the utility of PSADT as a surrogate endpoint. Placebo-controlled trials and the use of standard clinical endpoints are recommended to screen novel agents in men with BRPC to mitigate bias because of natural PSADT variability.