PQA 08 - PQA 08 Genitourinary Cancer, Patient Safety, and Nursing/Supportive Care Poster Q&A
3244 - A Randomized Phase II Trial of High Dose-Rate (HDR) and Low Dose-Rate (LDR) Brachytherapy as Monotherapy in Localized Prostate Cancer: Analysis of Initial Arms of Canadian Cancer Trials Group PR19 (NC
Sunnybrook Health Sciences Centre Toronto, ON, Canada
G. Morton1, E. Vigneault2, M. Barkati3, J. Helou4, T. M. Niazi5, J. Robinson6, D. A. Loblaw1, C. L. Tseng1, H. T. Chung1, G. Delouya3, D. Taussky3, C. Menard7, A. G. Martin2, P. Chung8, D. Batchelar9, M. D. Brundage10, K. Whelan11, K. Ding11, and W. Parulekar11; 1Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 2CHU de Québec – Université Laval, Radiation Oncology, Québec, Canada, Quebec, QC, Canada, 3Département de radio-oncologie, Centre Hospitalier de lUniversité de Montréal (CHUM), Montréal, QC, Canada, 4Department of Oncology, London Regional Program, London, ON, Canada, 5McGill University, Montreal, QC, Canada, 6University of Calgary, Calgary, AB, Canada, 7Département de radio-oncologie, Centre de Recherche du Centre Hospitalier de lUniversité de Montréal (CRCHUM), Montréal, QC, Canada, 8Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, 9University of British Columbia, Kelowna, BC, Canada, 10Division of Cancer Care and Epidemiology, Queens University, Kingston, ON, Canada, 11Canadian Cancer Trials Group, Queens University, Kingston, ON, Canada
Purpose/Objective(s): Low Dose-Rate Brachytherapy (LDR) and High Dose-Rate Brachytherapy (HDR) are established treatment options for men with favorable risk prostate cancer.We hypothesized that HDR provides comparable disease control with less urinary toxicity.Our primary objective was to determine prostate cancer control at 48 months, defined as a PSA < 0.4 ng/ml.Secondary objectives included biochemical and disease-free survival, toxicity, quality of life.For disease control rate: <83% was unacceptable (H0) ; >90% acceptable (Ha) . Planned sample size was 232.
Materials/
Methods: Eligible patients had T1-T2 adenocarcinoma of prostate with Grade Group 1 and PSA < 20 ng/ml, or Grade Group 2 and PSA < 15 ng/ml with =50% cores positive.Randomization (1:1) was to Arm 1 LDR using I-125 seeds to 144 Gy, or Arm 2 HDR with single fraction 19 Gy + intraprostatic boost of 150% (28.5 Gy) to the MR-defined GTV.Allocation stratified by Grade Group and centre. Follow-up included PSA, toxicity (CTCAE v 4.0), and Quality of Life (EPIC 26).With emerging data on sub-optimal outcomes with single fraction HDR, Arm 2 was closed to accrual in May 2019 and a third arm (HDR 13.5 Gy x 2) was opened.We report outcome of Arms 1 and 2 prior to May 2019 study closure and amendment.
Results: Between 2016 and 2019, 103 patients were randomized: 51 to Arm 1 and 52 to Arm 2.Median age was 65 years; 76% had Grade Group 2, 90% PSA <10, and 80% stage T1c.Median follow-up was 53 months.Prostate Cancer control at 4 years was 78.4% (80% CI 69.3% to 85.8%) in Arm 1, and 21.2% (80% CI 13.9% to 30.2%) in Arm 2.On sensitivity analysis excluding ineligible, untreated, and those missing 48 month PSA values, Prostate Cancer control rates were 88.9% (CI 80.4% to 94.5%) and 22.4% (CI 14.8% to 31.9%) for Arms 1 and 2, respectively.The estimated 4-year PSA progression rate (nadir + 2 ng/ml) was 0% in Arm 1 and 7.8% (80% CI 3.9% to 13.6%) in Arm 2.Rates of local progression were 3.5% (CI 0.7% to 10.1%) in Arm 1 and 12.1% (CI 6.9% to 18.9%) Arm 2.No nodal or distant progression occurred, and 4-year overall survival was 98% and 100% in Arm 1 and 2, respectively. Treatment related Grade 3 adverse events occurred in 6 patients in Arm 1 (all erectile dysfunction) and 2 patients in Arm 2 (1 erectile dysfunction, 1 hematuria).EPIC-26 urinary irritative symptoms at 6 months were clinically meaningfully worse in arm 1 (mean change -8.4 vs -1.2; p=.006) as were bowel function scores (mean change -6.2 vs -2.0, p=.047).
Conclusion: LDR brachytherapy is associated with a high prostate cancer disease control rate at 4 years, although with greater negative impact on urinary and bowel quality of life in the first 6 months.The single fraction HDR arm was discontinued early, and was associated with an unacceptable prostate cancer control rate based on the early primary endpoint used in the trial.
