Initial results of a randomized phase III trial of high dose image guided radiation with or without androgen deprivation therapy for intermediate-risk prostate cancer.

BACKGROUND: Prior randomized studies have shown a survival benefit using combined androgen deprivation therapy (ADT) and radiation therapy for intermediate-risk prostate cancer. However, these studies either used low doses of radiation (66.6 Gy to isocenter) or imaged guidance was not available. This study reports the initial differences for high dose image guided radiation with or without ADT. METHODS: From 2012 to 2014, 56 patients were treated with and 60 patients without 6 months of ADT (N = 116) in our phase III randomized trial for intermediate-risk prostate cancer. The primary endpoints of the current analysis are Expanded Prostate Cancer Index Composite (EPIC) scores, International Prostate Symptom Score (IPSS) scores, and bowel or urinary adverse events (AEs, graded using CTCAE v4) with and without ADT. Treatment consisted of 81 Gy in 45 treatments (tx) or 100 Gy Pd-103 implant followed by 45 Gy in 25 tx with or without ADT. Cone-beam fiducial-based guidance was done. Statistical analysis included Fisher's exact test, chi-square test, and ANCOVA. RESULTS: Median follow-up for both groups was 2.6 years. Acute or chronic urinary and acute or chronic bowel toxicities were similar with or without ADT (acute urinary: 16 vs 25 G0-1, 39 vs 35 G2 and 1 vs 0 G3, p = 0.17; chronic urinary: 40 vs 45 G1 and 16 vs 15 G2 toxicities, p = 0.68; acute bowel: 56 vs 59 G1 and 0 vs 1 G2 toxicities, p = 0.99; chronic bowel: 56 vs 59 G1 and 0 vs 1 G2 toxicities, p = 0.99). One patient had grade 3 urinary AE (1/116 or 0.8%). No patient had grade 3 bowel AE. With the use of ADT, a temporary decline in the EPIC sexual (p = 0.004) and hormonal scores (p = 0.02) were seen for the first 3 to 6 months after the completion of radiation, but the scores recovered by 12 months. Brachytherapy plus external beam radiation was compared to external beam radiation alone; brachytherapy EPIC urinary irritative scores were temporarily lower at 3 months, 76 vs. 84 (p = 0.006), had higher IPSS scores at 3 months, 15 vs 12 (p = 0.01), and had increased acute urinary AEs (p<0.001). No difference in failures were seen with or without ADT or associated with the use of brachytherapy. SIGNIFICANCE: Low toxicity and minimal temporary bother as measured by EPIC and IPSS were seen in both arms. ADT was well-tolerated and associated with temporary changes.

Salvage brachytherapy for recurrent prostate cancer.

PURPOSE: To evaluate the role of salvage prostate brachytherapy for locally recurrent prostate cancer after external beam radiation alone. METHODS AND MATERIALS: Sixty-nine consecutive patients treated with salvage brachytherapy after a local failure were analyzed. All patients were found to have pathologic proven recurrent prostate cancer at least 2 years after initial therapy and no regional or distant disease on imaging studies. Pd-103 was used with a prescribed pD90 of 100 Gy. In total, 89.9% of patients received androgen suppression (AS) as part of their salvage therapy. Patients whose prostate-specific antigen >5.0 ng/mL while on AS were considered to have castration resistant prostate cancer (CRPC). Patients on AS >6 months before salvage brachytherapy were considered to have delayed therapy. Patients retreated within 5 years after their initial treatment were considered to have early failures. RESULTS: Total median followup after salvage therapy was 5.0 years (0.6-13.7). From the date of salvage, 5-year biochemical control for low-risk patients was 85.6%, intermediate-risk patients 74.8%, and high-risk patients 66%. Five-year biochemical control was 73.8% for non-CRPC and 22% for CRPC cases (<0.001). Including and excluding CRPC cases, early treatment after failure vs. delayed treatment was significantly better (p<0.05). Chronic adverse events were seen in few patients, with genitourinary Grade 3 toxicity of 8.7% and no genitourinary Grade 4 or gastrointestinal Grade 3 or higher toxicities. CONCLUSIONS: A subset of failures after definitive radiation is local in nature, and excellent control is possible with salvage brachytherapy.

Long-term outcomes and prognostic factors in patients treated with intraoperatively planned prostate brachytherapy.

PURPOSE: Evaluate outcomes and prognostic factors in men with localized prostate cancer. METHODS AND MATERIALS: A total of 3760 patients have undergone prostate seed implantation at our institution. This review is of our initial 304 consecutive patients treated before January 30, 2001. A total of 124 patients were treated with (125)I implant monotherapy and 180 with (103)Pd implant combined with 45-Gy external beam radiation therapy. RESULTS: The median followup was 10.3 years. A 10-year biochemical control for low risk (LR) was 98% , intermediate risk (IR) 94%, high risk (HR) 78%, and HR with one HR factor 88% (p < 0.001); cause-specific survival was 99%, 98%, and 84% for LR, IR, and HR, respectively (p < 0.001); No significant difference in outcome was seen for LR and IR patients (p > 0.3). On multivariate analysis, only pretreatment PSA, Gleason score, and T-stage were significant for biochemical control. Most biochemical failures occurred within 5 years (93%). CONCLUSIONS: With a minimum followup of 10 years, results are excellent and do not differ for LR or IR prostate cancer patients. HR patients are a very heterogeneous group, and excellent results can still be achieved for HR patients with only one HR feature.