PL02  Presentation Time: 1:45 PM: HDR Monotherapy for Low and Intermediate Risk Prostate Cancer: Update of a Randomized Trial

Introduction High dose-rate brachytherapy is increasingly being used as monotherapy for low and intermediate risk prostate cancer. A dose of 27 Gy in 2 fractions is endorsed by the NCCN Guidelines, although with limited data on long-term efficacy. Our objective is to determine long-term efficacy of HDR monotherapy delivered as either a single fraction of 19 Gy or as two fractions of 13.5 Gy from a prospective randomized trial. Materials and Methods Eligible patients had low and intermediate risk prostate cancer, and 170 patients were randomized to receive either 19 Gy x 1 or 13.5 Gy x 2. The latter was delivered as two separate implants 1-2 weeks apart. No androgen deprivation was allowed. Median age was 65 years, and 19%, 51% and 30% had low-risk, favourable intermediate, and unfavourable intermediate-risk disease, respectively. Median baseline PSA was 6.4 (IQR 4.7, 8.9) and 6.3 (IQR 4.6, 8.7) ng/ml, in the single and 2-fraction arms, respectively. Patients with a rising PSA were investigated with prostate MRI, PSMA PET and biopsy where indicated. Toxicity was assessed using CTCAE v4. Results Median follow-up was 91 months. A total of 7 patients (4%) had died, none from prostate cancer. Median PSA at 5-years was 0.57 ng/ml and 0.18 ng/ml in the single and 2-fraction arms, respectively. Biochemical failure occurred in 37% in the single fraction arm and 18% in the 2-fraction arm. The 8-year biochemical disease-free survival probability (bDFS) was 58% and 80% (p=0.003), Figure 1, and cumulative incidence of local failure 36% and 12% (p=0.008), respectively. The respective cumulative incidence of distant failure was 2.6% and 3.8% (p=0.92). In the single-fraction arm, bDFS was 80%, 55% and 46% in the low, favourable and unfavourable- intermediate risk groups, respectively. In the 2-fraction arm, respective bDFS by risk groups was 88%, 81% and 73%. On multivariable analysis, biochemical disease-free survival was associated with treatment arm, baseline PSA, and percentage pattern 4. Local failure was associated with treatment arm, baseline PSA, and clinical stage (T2 vs. T1c). Distant failure was associated with baseline PSA and presence of perineural invasion. Late urinary toxicity was more common in the single-fraction arm, with a cumulative incidence of 64% Grade 2 and 2% Grade 3 (retention), compared with 46% and 0% in the 2-fraction arm (p=.03). The cumulative incidence of any Grade 2 late GI toxicity was 12% and 9%, respectively (p=0.61). Conclusions Longer follow-up continues to show inferior disease control and worse toxicity in patients treated with single 19 Gy. Patients treated with 13.5 Gy x 2 are at increasing risk of biochemical failure and local recurrence beyond 5 years. It remains important to compare HDR with permanent seed LDR monotherapy in randomized trials, and to continue to explore methods to improve HDR outcomes through further dose escalation and addition of androgen deprivation in selected patients.