David M. Nudell

Radiotherapy after radical prostatectomy : Treatment outcomes and failure patterns

OBJECTIVES To define the optimal role for radiotherapy (RT) after radical prostatectomy (RP) and to characterize specific patterns of PSA failure in this setting. METHODS The records of 105 patients who underwent RT after RP (69 received therapeutic RT because of an elevated prostate-specific antigen [PSA] level, 36 received immediate adjuvant RT) were reviewed. The median follow-up was 35 months after RT and 57 months after RP. Radiation success was defined as achievement and maintenance of a PSA less than 0.2 ng/mL. Preoperative, pathologic, and postoperative characteristics were examined for their ability to predict success after RT. Patterns of PSA recurrence after RT were also examined by determining the PSA nadir, PSA velocity, and timing of androgen-deprivation therapy. RESULTS Of 105 patients, 47 experienced biochemical failure. Actuarial 3 and 5-year progression-free survival estimates for all patients were 55% and 43%, respectively. Significant favorable predictors of response to RT by multivariate analysis were preoperative PSA less than 20 ng/mL and the use of adjuvant RT. However, patients who received therapeutic RT with a pre-RT PSA less than 1.0 ng/mL demonstrated progression-free outcome equivalent to those who received adjuvant RT. Two distinct patterns of PSA failure were observed on the basis of PSA nadir after RT. Patients whose PSA failed to reach a nadir less than 0.2 ng/mL after RT had progression with a high PSA velocity (1.5 ng/mL/yr). Patients whose PSA reached a nadir less than 0.2 ng/mL but who subsequently had treatment failure progressed later with a lower PSA velocity (0.36 ng/ml/yr). CONCLUSIONS RT is effective in select patients after RP. Given the low PSA velocity consistent with persistent local disease in nearly 50% of patients in whom RT failed, more effective local therapy is needed after RP in high-risk patients.

Is anastomotic biopsy necessary before radiotherapy after radical prostatectomy

PURPOSE External beam radiotherapy may be given after radical prostatectomy as adjuvant (immediate) or therapeutic (delayed) treatment, the latter in response to evidence of disease recurrence. In patients receiving delayed radiotherapy the necessity of a positive anastomotic biopsy before treatment remains unclear. We determined whether a positive anastomotic biopsy predicted the response to radiation in this setting. MATERIALS AND METHODS We reviewed the records of 67 patients who received radiotherapy for biochemical or biopsy proved recurrent prostate cancer after radical prostatectomy. Patients underwent surgery at our institution or its affiliated hospitals, or were referred to our institution for radiotherapy. All patients had a negative metastatic evaluation before receiving radiotherapy. Biochemical failure after radiotherapy was defined as serum prostate specific antigen (PSA) 0.2 ng./dl. or greater on 2 or more consecutive occasions. Biochemical recurrence-free survival was calculated using the Kaplan-Meier method. Independent predictors of PSA failure after radiotherapy were identified using the multivariate Cox proportional hazards model. RESULTS Of the 67 patients evaluated 33 and 34 received radiotherapy for biochemical failure and biopsy proved local recurrence, respectively. The 3-year recurrence-free survival rate was 49% in patients treated for biochemical failure and 39% in those with biopsy proved local recurrence. There was no significant difference in PSA-free survival in these 2 groups. Only pre-radiotherapy PSA 1 ng./dl. or greater (p = 0.02) and seminal vesicle invasion (p = 0.02) were significant independent predictors of biochemical failure. CONCLUSIONS A positive anastomotic biopsy did not predict an improved outcome after radiotherapy following radical prostatectomy. Anastomotic biopsy was associated with a longer time to salvage radiotherapy. However, this delay did not translate into worse disease-free outcomes in patients who underwent anastomotic biopsy. High pre-radiotherapy PSA greater than 1 ng./ml. was the most significant predictor of biochemical failure after therapeutic radiotherapy. Decisions regarding local radiation therapy after radical prostatectomy may be made without documenting recurrent local disease.

MANAGEMENT OF A POSITIVE SURGICAL MARGIN AFTER RADICAL PROSTATECTOMY: DECISION ANALYSIS

PURPOSE We created and tested a decision analysis model to help determine the preferred management of a positive surgical margin(s) after radical prostatectomy. MATERIALS AND METHODS We constructed a decision tree modeling surveillance versus immediate prophylactic adjuvant radiation in patients with a positive surgical margin(s) after radical prostatectomy. Literature and institution based estimates were determined for certain factors, including the probability of undetectable prostate specific antigen (PSA) in patients followed expectantly postoperatively and those treated with immediate adjuvant radiotherapy, complications of radiotherapy after prostatectomy and probability of undetectable PSA in those treated with therapeutic radiation for detectable PSA postoperatively. A panel of experts assigned utilities to the various outcomes. Sensitivity analysis was performed to determine threshold values required to change the model outcome. RESULTS Using average probability estimates from a literature review the decision model recommended initial surveillance. Sensitivity analysis demonstrated that the model depended on the probability of disease recurrence in men followed expectantly after surgery as well as the efficacy of therapeutic radiation. We tested the decision model again for patient groups based on tumor grade, pathological stage, preoperative PSA and number of positive margins. The model recommended initial radiation for patients with low to intermediate grade disease, no evidence of seminal vesicle invasion and multiple positive margins. CONCLUSIONS The results of our decision analysis imply that immediate radiation may be appropriate for patients with a positive surgical margin(s) and a high likelihood of recurrent local rather than distant disease. This model may be useful to physicians and patients who use individual probability estimates and utility values to determine the preferred course of management after surgery.

IMAGING FOR RECURRENT PROSTATE CANCER

Multiple imaging modalities are available to evaluate recurrent prostate cancer following primary treatment with RP, RT, or cryo-surgery. These tests must be used in close conjunction with clinical parameters, such as the characteristics of the tumor itself (grade, stage) as well as specific PSA characteristics that can help predict the sites of probable recurrence. Figure 19 represents an algorithm of how patients can be monitored for recurrence according to their mode of primary treatment. As more treatments become available for recurrent prostate cancer, it will be necessary to monitor disease response with many of the imaging modalities discussed in this article.