Serum prostate-specific antigen decline as a marker of clinical outcome in hormone-refractory prostate cancer patients: association with progression-free survival, pain end points, and survival.

PURPOSE

Validated end points are lacking for clinical trials in hormone-refractory prostate cancer (HRPC). Controversy remains regarding the utility of a posttreatment decline of prostate-specific antigen (PSA). The purpose of this study was to determine whether posttreatment declines in PSA were associated with clinical measures of improvement in a randomized phase III trial of suramin plus hydrocortisone versus placebo plus hydrocortisone.

PATIENTS AND METHODS

A total of 460 HRPC patients were randomized to receive suramin plus hydrocortisone (n = 229) or placebo plus hydrocortisone (n = 231). All patients had symptomatic, metastatic HRPC requiring opioid analgesics. Clinical end points evaluated included overall survival, objective progression-free survival (OPFS), and time to pain progression (TTPP). An evaluation of overall survival, OPFS, and TTPP as a function of a PSA decline of > or = 50%, lasting at least 28 days, was undertaken by using a landmark analysis at 6, 9, and 12 weeks. A multivariate analysis of the impact of PSA decline was performed on these clinical end points.

RESULTS

A decline in PSA of > or = 50% lasting > or = 28 days was significantly associated with a prolonged median overall survival, OPFS, and TTPP, both in the entire group and the suramin plus hydrocortisone group at all three landmarks in both univariate and multivariate analysis.

CONCLUSION

In this prospective, randomized trial of suramin plus hydrocortisone versus placebo plus hydrocortisone, a posttherapy decline in PSA of > or = 50%, lasting 28 days, was associated with prolonged median overall survival, improved median progression-free survival, and median TTPP. This analysis suggests that a posttreatment decline in PSA may be a reasonable intermediate end point in HRPC trials and calls into question the clinical utility of preclinical assays evaluating the in vitro effect of given agents on PSA secretion.