Predictors of androgen independence in metastatic prostate cancer

To assess the factors that influence the onset of androgen independence (AI, which heralds a dismal outcome) in patients with metastatic prostate carcinoma.

The records of 361 consecutive patients with prostate carcinoma diagnosed and treated in the authors' institution from 1 January 1996 to 31 December 1999 were reviewed retrospectively; 92 with metastatic prostate carcinoma were assessed (median age 71.0 years, range 42-93). Patients were included if they developed metastatic disease from prostate cancer at the time of diagnosis. The nadir for prostate specific antigen (PSA) level was defined as the date of the lowest PSA level after hormonal therapy, and AI was defined as the date of the third consecutive PSA increase above the nadir value by any threshold.

The median Gleason sum was 8 and the modal Gleason score 4 + 5. The median (range) pretreatment PSA level was 274.0 (1.3-2179) ng/mL. Of the 92 men, 57 (62%) attained a nadir PSA, including 23 with a nadir of < 2 ng/mL; 32 (35%) progressed to AI within 2 years and 27% reached a nadir PSA but did not develop AI. The mean (sd) time from diagnosis to the nadir PSA was 13.7 (11.8) months, while the mean time from diagnosis to progression to AI was 30.3 (15.6) months. Univariate analysis showed that a nadir PSA level after treatment of >/= 1 ng/mL (P = 0.0128) was an early predictor of progression to AI; a nadir PSA level of >/= 2 ng/mL (P = 0.0216) was a predictor of poor overall survival.

Failure to attain a nadir PSA of < 1 ng/mL after treatment predicts progression to AI and a nadir PSA of > 2 ng/mL predicts poorer overall survival. The development of skeletal events predicts the onset of AI but occurs late in the disease and is unsuitable as an early prognostic marker.