Salvage radiotherapy for biochemical and clinical failures following radical prostatectomy

The proportion of prostate cancer patients undergoing radical prostatectomy has increased over the past 10 to 15 years. It is conceivable that a corresponding increase in local tumor recurrences after prostatectomies will be observed. The role of salvage radiotherapy is presently unclear. In this study, the results of salvage radiotherapy for patients with biochemical evidence of local recurrence, as evidenced from rising prostate-specific antigen (PSA) levels, after radical prostatectomy at UCLA Medical Center and the West Los Angeles Veterans Administration Medical Center are described.

Between 1990 and 1997, 69 patients were diagnosed with presumed local tumor recurrence after radical prostatectomy. Of these patients, 60 patients were referred to radiotherapy for salvage treatments. Tumor recurrence was detected biochemically, with or without a palpable nodule on digital rectal examination, and a metastatic workup revealing no evidence of extrapelvic disease. Biochemical failure after salvage radiotherapy was defined as two consecutive rises in serum PSA level after a PSA nadir or an absence of a PSA nadir after radiation treatments, as was earlier defined at the ASTRO Consensus Panel on PSA Guidelines. Patients referred for adjuvant postoperative radiation treatment and patients with metastatic disease at presentation were excluded from the study. Patients were treated with a four-field approach (anteroposterior/posteroanterior and opposing laterals) to a median dose of 64.8 Gy in 1.8-Gy fractions. Follow-up evaluations included serum PSA level and digital rectal examination every 3 to 6 months.

At last follow-up (mean follow-up, 36 months after salvage radiotherapy), 40 of 60 patients (67%) were biochemically free of disease. Thirty of 60 patients (50%) had undetectable PSA levels, and 55 of 60 (92%) had achieved some initial decrease after salvage radiation treatments. Three-year and 5-year actuarial biochemical disease-free survival was 63% and 55%, respectively. Of the 20 patients with biochemical failure after salvage radiation therapy, 10 patients (50%) developed distant metastases, and two (10%) patients were found to have persistent local disease. The mean time to biochemical relapse after salvage radiotherapy was 10 months, and the mean time to distant metastasis after salvage radiotherapy was 20 months. Evaluation of the remaining eight biochemical failures (43%) revealed no evidence of local disease progression or distant metastasis to date. Univariate and multivariate analyses revealed that both PSA > 1.0 ng/mL at the time of salvage radiotherapy and perineural invasion significant prognosticators for biochemical relapse after salvage radiotherapy. Likewise, both univariate and multivariate analyses revealed that prognosticators for distant metastasis included seminal vesicle invasion and perineural invasion.

Salvage radiation therapy is a viable option for post prostatectomy local tumor recurrences. Of the patients who fail biochemically after salvage radiotherapy, 50% were eventually found to have distant metastases. In addition, biopsy-proven local recurrence after-prostatectomy was found not to confer an adverse outcome after salvage radiotherapy.