Original Article
PSA Doubling Time as a Predictor of Clinical Progression After Biochemical Failure Following Radical Prostatectomy for Prostate Cancer

https://doi.org/10.4065/76.6.576Get rights and content

Objectives

To characterize the clinical progression of disease in men who have undergone prostatectomy for clinically localized prostate cancer and have postoperative biochemical failure (elevated prostate-specific antigen [PSA] level) and to identify predictors of clinical disease progression, including the possible effect of PSA doubling time (PSADT).

Patients and Methods

Between 1987 and 1993, 2809 patients underwent radical retropubic prostatectomy for clinically localized (≤T2) disease. In our database, all patients with postoperative biochemical failure (PSA level ≥0.4 ng/mL) were identified. The PSADT was estimated using log linear regression on all PSA values (excluding those values determined after administration of hormonal therapy) within 15 months after biochemical failure. All patients had regular PSA measurements from the time of surgery through the follow-up period. Systemic progression (SP) was defined as evidence of metastatic disease on a bone scan. Local recurrence (LR) was defined on the basis of digital rectal examination, transrectal ultrasonography, and biopsy. The SP-free survival and LR/SP-free survival (survival free of both LR and SP) after biochemical failure was estimated with use of the Kaplan-Meier method. Patients with prostate cancer treatment after biochemical failure had their follow-up censored from this study at the time of treatment.

Results

Postoperative biochemical failure occurred in 879 men (31%). The mean follow-up from time of biochemical failure was 4.7 years (range, 0.5–11 years). The mean time to biochemical failure was 2.9 years (median, 2.4 years). The overall mean SP-free survival from time of biochemical failure was 94% and 91% at 5 and 10 years, respectively. The mean LR/SP-free survival was 64% and 53% at 5 and 10 years, respectively. By using univariate analysis on the 587 patients with PSADT data, significant risk factors for SP were PSADT (P<.001) and pathologic Gleason score (P=.005); for LR/SP, significant risk factors included PSADT (P<.001) and pathologic Gleason score (P<.001). In multivariate Cox models analysis, only PSADT remained a significant risk factor for both SP and LR/SP (P<.001). Mean 5-year SP-free survival was 99%, 95%, 93%, and 64% for patients with PSADT of 10 years or longer, 1.0 to 9.9 years, 0.5 to 0.9 year, and less than 0.5 year, respectively; the respective mean LR/SP-free survivals were 87%, 62%, 46%, and 38%. The percentage of patients with PSADT of less than 0.5 year was considerably higher if the type of first clinical event was SP (48%) compared with LR (18%) (P<.001).

Conclusions

For patients who have undergone radical prostatectomy, a rising PSA level suggests evidence of residual or recurrent prostate cancer. Many men remain free of clinical disease for an extended time after biochemical failure following radical prostatectomy for clinically localized prostate cancer. The PSADT appears to be an important predictor of SP and also of any clinical progression (local or systemic). These data may be useful when counseling men regarding the timing of adjuvant therapies.

Section snippets

PATIENTS AND METHODS

A total of 2809 patients were treated with primary bilateral pelvic lymphadenectomy and RRP at Mayo Clinic, Rochester, Minn, for clinically localized (cT½) adenocarcinoma of the prostate between 1987 and 1993. All patients were entered into the Mayo Clinic radical prostatectomy database. Pathologic staging and grading were performed on histopathologic examination of the entire specimen, as previously described.11 Histopathologic grading was performed according to the Gleason grading system.12

RESULTS

Table 1 shows the pathologic stages, Gleason scores, DNA ploidy status, and preoperative PSA in all patients in each cohort. A total of 879 men (31% of the RRP cohort) had biochemical failure during the follow-up period. The mean time from RRP to biochemical failure was 2.9 years (median, 2.4 years). Of those who developed biochemical failure, 84% did so within 5 years of their surgery. In the cohort of 2809 men, the median number of PSA measurements during the follow-up time was 1.03 per man

DISCUSSION

The majority of men undergoing radical prostatectomy for clinically localized (T½) prostate cancer are cured by the procedure; however, in approximately one third of men, a PSA elevation develops during long-term follow-up.2, 3, 4, 5, 6, 7 Data are lacking regarding how best to manage these men with a PSA relapse; no prospective trials have been performed, and until recently, the long-term risk of clinical progression in these patients was unknown.8, 9 In this study it was our intent to

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Dr Roberts is now with Urology Associates, Scottsdale, Ariz.

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