Percent free prostate-specific antigen after radiotherapy for prostate cancer

The range of "normal" prostate-specific antigen (PSA) values compatible with cure following radiotherapy (RT) for prostate cancer (PCa) has yet to be established. Various thresholds, ranging from 0.5 to 4.0 ng/mL are used to define biochemical disease-free status. Because the proportion of free PSA is lower in men with PCa, the ratio of free PSA to total PSA could theoretically be useful in determining cancer-free status after RT.

One hundred two men treated with standard external beam RT from October 1988 to October 1994 (median dose, 66 Gy) were chosen for measurement of percent free PSA because they had a routine follow-up visit in November or December of 1996. All patients had undergone systematic transrectal ultrasound-guided biopsies after RT. Biopsies were negative in 66 patients, positive in 21, and indeterminate in 15 (rare, degenerated cancer cells with no evidence of proliferation by immunohistochemical stains). Stage distribution was T1b, 8; T1c, 9; T2a, 25; T2b/c, 40; and T3, 20. Median follow-up is 40 months.

Total serum PSA ranged from 0. 1 to 10.0 ng/mL. Because the mean (+/-SD) percent free PSA for patients with negative (n = 66) and indeterminate (n = 15) biopsies were 29% +/- 18% and 25% +/- 7%, respectively (P = 0.13), these were combined. The mean (+/-SD) percent free PSA for those with positive biopsies (n = 21) was 15% +/- 8% and was significantly different from those with negative or indeterminate biopsies (P < 0.001). Patients with negative or indeterminate biopsies were grouped according to their total PSA as 0.1 to 0.5 ng/mL (n = 33), 0.6 to 1.0 ng/mL (n = 23), 1.1 to 2.0 ng/mL (n = 17), and greater than 2.0 ng/mL (n = 7). The mean percent free PSAs were 34%, 28%, 21%, and 12%, respectively.

Percent free PSA may be a useful adjunct in diagnosing recurrent PCa after RT. The ratio is significantly different in patients of known biopsy status, distinguishing a group with positive biopsies from those with negative. However, there is overlap in individual values, and because patients with negative biopsies after RT may have subclinical distant disease, more follow-up is necessary before percent free PSA can be incorporated into a definition of biochemical disease-free status. Percent free PSA may be most useful for PSA from 0.6 to 2.0 ng/mL, where failure is common, but not universal.