CORRELATION OF CLINICAL AND PATHOLOGICAL FACTORS WITH RISING PROSTATE-SPECIFIC ANTIGEN PROFILES AFTER RADICAL PROSTATECTOMY ALONE FOR CLINICALLY LOCALIZED PROSTATE-CANCER

Objectives. To better identify factors affecting prostate-specific ant igen (PSA) level elevation after radical prostatectomy alone in men wi th clinical Stage T1-2 prostate cancer, we have reviewed our experienc e in the PSA era with 337 cases. The identification of these factors p ermits better understanding of the impact of case selection on treatme nt outcome in prostate cancer. Methods. The charts of all patients tre ated with radical prostatectomy alone between 1987 and 1993 were revie wed. Patients with clinical Stage T3 disease, without preoperative Gle ason scores or PSA levels, with synchronous bladder cancer, and who re ceived adjuvant or neoadjuvant therapy were excluded. The distribution of cases by pretreatment PSA levels was as follows: 4 ng/mL or less ( 16%); greater than 4 to 10 ng/mL (48%); greater than 10 to 20 ng/mL (2 2%); and greater than 20 ng/mL (14%). The median pretreatment PSA leve l for the entire group was 8 ng/mL. Only 26 patients (8%) had patholog ically positive pelvic lymph nodes. The overall margin involvement rat e was 43%. Margin involvement rates increased with increasing preopera tive PSA levels. One hundred eighty-two patients (54%) had surgical Gl eason scores of 7 or higher, and 208 (62%) had extracapsular extension . The median follow-up time was 36 months. Results. The 3- and 5-year relapse-free survival (RFS) rates were 74% and 61%, respectively, with relapse being defined as either a clinically detectable recurrence or detectable/rising PSA levels. Among preoperative factors, PSA level w as the only independent factor predicting relapse (P = 0.006); the 5-y ear RFS was 89% in patients with preoperative PSA levels of 4 ng/mL or less; 62% for PSA level of 4 to 10 ng/mL; 56% for PSA level of 10 to 20 ng/mL; and 26% for a PSA level greater than 20 ng/mL. Among patholo gic parameters, margin involvement was the most potent independent fac tor predicting relapse (P < 0.001), followed by Gleason score (P = 0.0 02) and capsular penetration (P = 0.006). The 5-year RFS rates for mar gin-positive versus margin-negative patients were 37% versus 80%, resp ectively (P < 0.001). With pretreatment PSA levels of 10 ng)ml or less , lymph node involvement was seen in 3%, and margin involvement in 36% ; the 5-year RFS rate was 71%. With pretreatment PSA levels of greater than 10 ng/mL, lymph node involvement was seen in 16%, and margin inv olvement in 57%; the 5-year RFS rate was 42%. However, patients with a n initial PSA level greater than 10 ng/mL and positive margins had a 5 -year RFS rate of 22% versus 73% in patients with a PSA level of 10 ng /mL or less or negative margins (P < 0.001). All clinical relapses wer e accompanied by a rise in PSA. In patients manifesting a clinical rec urrence, PSA elevations preceded clinical recurrences by an average of 15 months (range 0 to 71). Only 34 cases (10%) had clinical failures within 5 years. Conclusions. Pretreatment PSA is the most potent clini cal factor independently predicting biochemical relapse. The great ran ge in the relapse-free survival rates predicted by preoperative PSA le vels demonstrates the importance of pretreatment PSA levels in case se lection. Gleason score, extracapsular extension, and surgical margin i nvolvement are also independent predictors of biochemical relapse. Ach ieving negative margins, even in relatively advanced disease, provides excellent long-term local control.