TIME TO 2ND PROSTATE-SPECIFIC ANTIGEN FAILURE IS A SURROGATE END-POINT FOR PROSTATE-CANCER DEATH IN A PROSPECTIVE TRIAL OF THERAPY FOR LOCALIZED DISEASE

Objectives. The most relevant endpoint in comparing the efficacy of cu rative therapies for prostate cancer is cancer-specific death. Prospec tive trials need to mature for at least a decade to yield meaningful c ancer death data due to the long natural history of the disease and th e use of salvage androgen suppression, This delay may be long enough t hat the tested treatments are outdated by the time of reporting; thus, there is a need for reliable early surrogate endpoints for cancer sur vival. Methods. This report evaluates 202 patients entered into a sing le institution prospective randomized study for T3-4 prostate cancer. Patients were accrued between 1982 and 1992 and received radical irrad iation to either a standard dose of 67.2 Gy or a higher dose of 75.6 G y. Median follow-up was 5.4 years. A total of 76 men have received and rogen suppression or orchiectomy for salvage following relapse. Of thi s group, 35 experienced a second relapse heralded by a rise in the ser um prostate-specific antigen (PSA). Results. The median survival from the time of second biochemical relapse (defined as a progression with a rise in serum PSA more than 10% above the nadir after androgen suppr ession) was 27 months. Kaplan-Meier analysis projected a 0% survival f or this group at 4 years, All those dying after second biochemical fai lure died of the prostate cancer. Conclusions. Second PSA failure (or PSA progression on hormonal therapy) has potential as a surrogate for impending cancer death and its use as an endpoint in prospective studi es could allow earlier reporting by 2 to 4 years.