Salvage radiotherapy for isolated prostate specific antigen increase after radical prostatectomy: evaluation of prognostic factors and creation of a prognostic scoring system

PURPOSE: This study was performed to evaluate the results and prognostic factors associated with radiotherapy for a detectable serum prostate specific antigen level after radical prostatectomy. MATERIALS AND METHODS: From July 1987 through July 2003, 368 patients received radiotherapy for a detectable prostate specific antigen level (biochemical relapse) as the sole evidence of recurrence after radical prostatectomy for node negative prostate cancer. Estimated survival and relapse-free probabilities were obtained via Kaplan-Meier estimation. Associations of patient factors with survival and biochemical relapse were investigated using Cox proportional hazards models. RESULTS: With a median followup of 5 years the 5 and 8-year freedom from biochemical relapse were an estimated 46% (95% CI 41%-53%) and 35% (95% CI 29%-43%) while survival was 92% (95% CI 89%-95%) and 80% (95% CI 74%-87%), respectively. Patient and treatment variables showing evidence of association with biochemical relapse on multivariate analysis included pathological stage T3a or less vs T3b (seminal vesicle involvement, p = 0.029), pathological Gleason score 7 or less vs 8 or greater (p <0.001) and pre-radiotherapy prostate specific antigen (p <0.001). Four biochemical failure risk groups were created by assigning seminal vesicle involvement, Gleason score and pre-radiotherapy prostate specific antigen each a score of 0 to 2. These individual scores were summed. The freedom from biochemical failure at 5 years for each risk group was 0 to 1-69%, 2-53%, 3-26% and 4 to 5-6%. CONCLUSIONS: The presence of seminal vesicle involvement and high Gleason score in the radical prostatectomy specimen are inherent predictors of adverse outcome. Early referral for salvage radiotherapy can decrease subsequent biochemical relapse.     

Salvage radical prostatectomy for radiorecurrent prostate cancer: morbidity revisited

PURPOSE: With the advent of prostate specific antigen (PSA) testing and transrectal ultrasound guided prostate biopsy there has been stage migration in the diagnosis of prostate cancer, so that more younger men are being diagnosed with organ confined prostate cancer. Many patients elect radiation therapy, while some have recurrent or new prostate cancer with absent systemic disease and life expectancy greater than 10 years. We present our experience with salvage radical prostatectomy in these cases. MATERIALS AND METHODS: Between 1995 and 2000, 6 men treated with curative intent with radiotherapy for prostate cancer were subsequently treated with salvage surgery for clinically localized prostate cancer. All men had biopsy proved recurrent or persistent prostate cancer, increasing serum PSA, no evidence of systemic disease at surgery and life expectancy greater than 10 years. We assessed the morbidity associated with this procedure and compared results to those in the contemporary literature. RESULTS: Six patients underwent salvage radical prostatectomy. Initial pre-radiation PSA was 4.5 to 15.7 ng./ml. Pre-radiation disease was clinical stage T1c in 5 cases and B2 in 1. The interval from radiotherapy to repeat biopsy was 12 to 48 months. A mean of 6.3 months after local recurrence was detected and before salvage radical prostatectomy was performed 4 patients underwent androgen deprivation therapy. Mean operative time was 195 minutes, intraoperative blood loss was 680 cc, and hospital stay and catheterization time were 3.2 and 13.8 days, respectively. There were no rectal injuries. All 6 patients are impotent, 5 are continent and 1 has mild stress incontinence. There was biochemical failure in 1 case 36 months after salvage radical prostatectomy and no evidence of recurrence in the remaining 5 at a mean followup of 27 months. CONCLUSIONS: Salvage radical prostatectomy is a technically challenging procedure. In the past it was associated with a high incidence of rectal injury, urinary incontinence and anastomotic stricture. The results of our relatively small series are encouraging and concur with those of recent studies that the morbidity of salvage radical prostatectomy is lower than previously reported. We believe that salvage radical prostatectomy may be considered a reasonable treatment option in appropriate patients with radiorecurrent prostate cancer.     

Salvage radiotherapy following radical prostatectomy

Recurrent disease following radical prostatectomy will occur in approximately 20% of patients, for whom the therapeutic options include surveillance, salvage radiotherapy, or hormonal therapy. This review will focus on the evidence for salvage radiotherapy. Efficacy results of 30–50% have been reported from multiple retrospective series, with minimal morbidity. Unfortunately there are no randomized or prospective studies in this area. Results of salvage radiotherapy improve when given earlier, ideally with the serum prostate-specific antigen < 1 ng/mL. Other positive prognosticators are positive margins at radical prostatectomy, longer prostate-specific antigen doubling times, lower radical prostatectomy Gleason scores, and the absence of lymph node metastases. Current standard dosage is 64 Gy or slightly higher, although the optimal dosage has yet to be defined with prospective randomized trials. Salvage radiotherapy can provide a durable response when given early, and patients with recurrent disease should be considered for treatment or enrolment in clinical trials.     

Prostate specific antigen recurrence after definitive therapy

PURPOSE: We estimate that approximately 70,000 men yearly have prostate specific antigen-only recurrence after failed definitive therapy. The ideal salvage therapy for these men is not clear. Treatment must be individualized based on the patient risk of progression, the likelihood of success and the risks involved with the therapy. However, to do so the risks and benefits of the various options must be known. Therefore, we provide a comprehensive overview of the natural history and treatment options for men with prostate specific antigen-only recurrence. MATERIALS AND METHODS: A literature review and overview of prostate specific antigen-only recurrence after failed definitive therapy was done. RESULTS: The natural history after prostate specific antigen-only recurrence is long but variable. Median time from prostate specific antigen-only recurrence after radical prostatectomy to prostate cancer death exceeds 16 years, although some men die within 1 year after PSA recurrence. Rapid prostate specific antigen doubling time is the best prognostic factor for poor outcome. Salvage radiation therapy after radical prostatectomy results in a 45% 4-year prostate specific antigen response rate, although long-term outcomes appear poor. To our knowledge the effect on survival is not known. Salvage radical prostatectomy is rarely performed but in the highly selected patient it may provide some benefit. There are no randomized studies of early vs late hormonal therapy for men with prostate specific antigen-only recurrence. A retrospective study suggested delayed metastasis when therapy was begun early but only in men at high risk. This mirrors other data suggesting that men at high risk may derive significant benefits from early hormonal therapy, whereas men at low risk are unlikely to benefit and may be harmed by hormonal therapy. CONCLUSIONS: Prostate specific antigen-only recurrence is the most common form of advanced prostate cancer. Optimal salvage treatments and timing of these treatments remain controversial.     

Salvage radical prostatectomy: quality of life outcomes and long-term oncological control of radiorecurrent prostate cancer

PURPOSE: We review our 20-year experience with salvage radical prostatectomy to determine prognostic variables predictive of oncological control of radiorecurrent prostate cancer. Using a standardized questionnaire we also evaluate outcome data regarding the long-term sexual and urinary effects of salvage radical prostatectomy. MATERIALS AND METHODS: Between 1983 and 2002 salvage radical prostatectomy was performed in 51 patients with locally recurrent prostate cancer following definitive radiotherapy. Clinical information was obtained from a prospective database. Quality of life data were collected using the UCLA Prostate Cancer Index, a validated, patient administered instrument. RESULTS: At 5 years 47% of patients were progression-free without androgen deprivation therapy. Among patients with pT2 disease 100% were progression-free at 5 years, compared with 35% of patients with pT3N0 disease or higher and 0% of patients with node positive (pTxN+) disease (p < 0.001). Preoperative PSA 5.0 ng/ml or less was predictive of organ confined disease, and strongly associated with prolonged progression-free and overall survival (p < 0.001 and 0.01, respectively). Mean urinary function scores for patients with or without an artificial urinary sphincter compared favorably with scores reported after standard, nonsalvage prostatectomy. Sexual dysfunction was nearly uniform in patients undergoing standard salvage radical prostatectomy but implantation of a penile prosthesis was associated with a clinically significant improvement in sexual function. CONCLUSIONS: When initiated early in the course of recurrent disease, salvage radical prostatectomy provides excellent oncological control of radiorecurrent prostate cancer without the need for androgen ablation. Implantation of an artificial urinary sphincter and inflatable penile prosthesis devices in patients with postoperative urinary incontinence or erectile dysfunction results in significantly improved quality of life parameters.     

Salvage surgery for radiorecurrent prostate cancer: contemporary outcomes

PURPOSE: We present a 30-year experience with performing salvage surgery in patients with persistent prostate cancer (PCA) after definitive radiotherapy. MATERIALS AND METHODS: Patients with biopsy proven PCA following definitive radiotherapy who underwent salvage surgery were identified retrospectively (1967 to 2000). Prostate specimens were evaluated by a single pathologist. Progression-free survival (PFS) and cancer specific survival (CSS) estimates were made with multivariate analysis of outcome predictors. Complications were reviewed. RESULTS: Sufficient information was available on 199 patients, including 138 with retropubic prostatectomy (RP) and 61 with cystoprostatectomies (CP). Median followup was 7.0 years. Rectal injury rates (5% for RP and 10% for CP) remained stable, while transfused units of blood decreased. Urinary extravasation (15% of cases) and bladder neck contracture (22%) were the most common complications. Urinary continence (0 pads) improved from 43% to 56% of patients (p = 0.17) with an additional 20% requiring 1 or fewer pad daily. Overall 10-year CSS in all patients undergoing salvage surgery was 65%. Patients undergoing RP fared better than those needing CP (10-year CSS 77% vs 38%, p <0.001 and median PFS 8.7 vs. 4.4 years, p <0.001). Tumor ploidy, percent 4/5 Gleason grade and pathological stage were strong predictors of outcome, while margin status and preoperative prostate specific antigen had minimal predictive strength. CONCLUSIONS: Significant PFS and CSS can be expected following salvage surgery for radioresistant PCA. Several pathological features of the removed prostate are predictive of survival. The surgical risks of salvage surgery are now defined. Morbidity rates, including continence, have moderately improved with time.