Does hormonal manipulation in conjunction with permanent interstitial brachytherapy, with or without supplemental external beam irradiation, improve the biochemical outcome for men with intermediate or high-risk prostate cancer?

Abstract

OBJECTIVE To determine whether hormonal manipulation improves the biochemical outcome for men with intermediate or high‐risk prostate cancer and undergoing permanent brachytherapy with or without supplemental external beam radiation therapy. PATIENTS AND METHODS From April 1995 to August 2000, 350 patients with intermediate‐risk (225 men; a Gleason score of ≥ 7 or a prostate specific antigen, PSA, level of ≥ 10 ng/mL or clinical stage ≥ T2b) or high‐risk features (125 men; two or three of a Gleason score of ≥ 7 or PSA ≥ 10 ng/mL or clinical stage ≥ T2b) underwent transperineal ultrasonography‐guided permanent brachytherapy. No patient underwent pathological lymph node staging. Of these patients, 293 received supplemental external beam radiation therapy (EBRT), 141 received hormonal manipulation, with 82 having hormonal therapy for ≤ 4 months (median 4) for cytoreduction, while 59 had neoadjuvant and adjuvant hormonal manipulation (median 8 and 12 months for intermediate‐ and high‐risk, respectively). The median patient age was 68.5 years. No patient was lost to follow‐up. The mean (sd) and median follow‐up was 50 (18) and 49 months (calculated from the day of implantation). Biochemical disease‐free (BDF) survival was defined using a consensus definition. The clinical variables evaluated for BDF survival included risk group, Gleason score, patient age, clinical T‐stage and pretreatment PSA. Treatment variables included use of hormonal manipulation stratified into cytoreductive (≤ 4 months) vs adjuvant (> 4 months) regimens, supplemental EBRT, isotope and dosimetric variables. RESULTS For intermediate‐risk patients, the 6‐year actuarial BDF survival rates were 98%, 96% and 100% for hormone naïve, cytoreductive and adjuvant treatment, respectively (P = 0.693); for high‐risk patients the respective values were 79%, 94% and 92% (P = 0.046). When stratified by pretreatment PSA, hormonal manipulation improved the outcome for patients with a PSA of ≥ 10 ng/mL (P = 0.019), but not for those with < 10 ng/mL (P = 0.661). Hormonal status was not statistically significant in predicting biochemical outcome when stratified by Gleason score. The follow‐up in hormone‐naïve patients was significantly longer than that in hormonally manipulated patients, at 55 (20) vs 43 (15) months (P < 0.001). In a multivariate analysis only the Gleason score predicted failure in intermediate‐risk patients, while pretreatment PSA, the use of hormonal manipulation and Gleason score predicted the outcome in high‐risk patients (P = 0.035). For both hormone‐naïve and hormonally manipulated BDF patients, the median PSA level after implantation was < 0.1 ng/mL. CONCLUSION In patients treated by permanent prostate brachytherapy, hormonal manipulation improved the biochemical outcome for those at high‐risk and those with an initial PSA of ≥ 10 ng/mL, but not for those with intermediate‐risk features. The use of hormonal therapy for> 4 months conferred no additional biochemical advantage over short‐course regimens. Because the follow‐up in hormone‐naïve patients was longer than that for those receiving hormonal manipulation, additional follow‐up will be mandatory to confirm the durability of these findings.