4-Year Outcomes of Hypofractionated Image-Guide Radiotherapy (55 Gy/16 fractions/4 weeks) for Low and Intermediate Risk Prostate Cancer: A Multicenter Study

Purpose/Objective(s)Modeling of the fractionation sensitivity of prostate cancer has suggested a therapeutic advantage of hypofractionated radiotherapy (RT) based on estimates of a low alpha/beta ratio. This study was conducted to evaluate gastrointestinal (GI) and genitourinary (GU) toxicities of a dose-schedule using 3.44 Gy/fraction to a total dose of 55 Gy/16 fractions/4 weeks (4 fractions per week).Materials/MethodsSeventy-three patients with low (18/73) or intermediate risk (55/73) prostate cancer were accrued in a phase I/II clinical trial between Sep 2004 and May 2006 from four regional cancer centers (local REB approved). Median baseline PSA was 6.4 ng/mL (max. 19.4). Up to 6 months of neoadjuvant LHRH was given in 11/73 patients. Image-guided RT using implanted fiducial (gold) markers was delivered via 3D conformal, IMRT, dynamic conformal arcs, or tomotherapy techniques depending on institutional preference. PTV = prostate with or without proximal seminal vesicles plus 1 cm margin (except posterior margin 0.5 cm over rectum). Rectal dose-constraints were D50 = 37 Gy, D35 = 45 Gy, D25 = 51 Gy, D15 = 55 Gy. Patient reported outcomes including bladder, bowel and sexual function were evaluated using Prostate Cancer Index. Toxicity scoring by RTOG grading.ResultsMedian follow-up of all patients has reached 48 months from first day of RT; 7/73 dropped out before 36-month visit due to unrelated reasons. Acute grade 3 toxicity was ≤ 5% for GU (4/73) and GI (3/73) symptoms. By 36 months, max. grade 3 GI and GU toxicity was observed in 2/73 and 1/73 patients respectively (total late grade 3 toxicity = 4%). Mean patient-reported bladder and bowel function scores were 91 and 84 respectively at baseline, and 87 and 85 at 36 months. Sexual function score dropped significantly for all patients. Biochemical (PSA nadir+2) and/or biopsy-proven failure was observed in 4/73 patients.ConclusionsHypofractionated IGRT (55 Gy/16 fractions/4 weeks) for low to intermediate risk prostate cancer was well tolerated with no excessive acute or late toxicities. Tumor control has been satisfactory on long term follow-up. A Canadian multicenter randomized controlled trial of conventional- vs. hypo-fractionated IGRT for intermediate risk prostate cancer is on-going. Purpose/Objective(s)Modeling of the fractionation sensitivity of prostate cancer has suggested a therapeutic advantage of hypofractionated radiotherapy (RT) based on estimates of a low alpha/beta ratio. This study was conducted to evaluate gastrointestinal (GI) and genitourinary (GU) toxicities of a dose-schedule using 3.44 Gy/fraction to a total dose of 55 Gy/16 fractions/4 weeks (4 fractions per week). Modeling of the fractionation sensitivity of prostate cancer has suggested a therapeutic advantage of hypofractionated radiotherapy (RT) based on estimates of a low alpha/beta ratio. This study was conducted to evaluate gastrointestinal (GI) and genitourinary (GU) toxicities of a dose-schedule using 3.44 Gy/fraction to a total dose of 55 Gy/16 fractions/4 weeks (4 fractions per week). Materials/MethodsSeventy-three patients with low (18/73) or intermediate risk (55/73) prostate cancer were accrued in a phase I/II clinical trial between Sep 2004 and May 2006 from four regional cancer centers (local REB approved). Median baseline PSA was 6.4 ng/mL (max. 19.4). Up to 6 months of neoadjuvant LHRH was given in 11/73 patients. Image-guided RT using implanted fiducial (gold) markers was delivered via 3D conformal, IMRT, dynamic conformal arcs, or tomotherapy techniques depending on institutional preference. PTV = prostate with or without proximal seminal vesicles plus 1 cm margin (except posterior margin 0.5 cm over rectum). Rectal dose-constraints were D50 = 37 Gy, D35 = 45 Gy, D25 = 51 Gy, D15 = 55 Gy. Patient reported outcomes including bladder, bowel and sexual function were evaluated using Prostate Cancer Index. Toxicity scoring by RTOG grading. Seventy-three patients with low (18/73) or intermediate risk (55/73) prostate cancer were accrued in a phase I/II clinical trial between Sep 2004 and May 2006 from four regional cancer centers (local REB approved). Median baseline PSA was 6.4 ng/mL (max. 19.4). Up to 6 months of neoadjuvant LHRH was given in 11/73 patients. Image-guided RT using implanted fiducial (gold) markers was delivered via 3D conformal, IMRT, dynamic conformal arcs, or tomotherapy techniques depending on institutional preference. PTV = prostate with or without proximal seminal vesicles plus 1 cm margin (except posterior margin 0.5 cm over rectum). Rectal dose-constraints were D50 = 37 Gy, D35 = 45 Gy, D25 = 51 Gy, D15 = 55 Gy. Patient reported outcomes including bladder, bowel and sexual function were evaluated using Prostate Cancer Index. Toxicity scoring by RTOG grading. ResultsMedian follow-up of all patients has reached 48 months from first day of RT; 7/73 dropped out before 36-month visit due to unrelated reasons. Acute grade 3 toxicity was ≤ 5% for GU (4/73) and GI (3/73) symptoms. By 36 months, max. grade 3 GI and GU toxicity was observed in 2/73 and 1/73 patients respectively (total late grade 3 toxicity = 4%). Mean patient-reported bladder and bowel function scores were 91 and 84 respectively at baseline, and 87 and 85 at 36 months. Sexual function score dropped significantly for all patients. Biochemical (PSA nadir+2) and/or biopsy-proven failure was observed in 4/73 patients. Median follow-up of all patients has reached 48 months from first day of RT; 7/73 dropped out before 36-month visit due to unrelated reasons. Acute grade 3 toxicity was ≤ 5% for GU (4/73) and GI (3/73) symptoms. By 36 months, max. grade 3 GI and GU toxicity was observed in 2/73 and 1/73 patients respectively (total late grade 3 toxicity = 4%). Mean patient-reported bladder and bowel function scores were 91 and 84 respectively at baseline, and 87 and 85 at 36 months. Sexual function score dropped significantly for all patients. Biochemical (PSA nadir+2) and/or biopsy-proven failure was observed in 4/73 patients. ConclusionsHypofractionated IGRT (55 Gy/16 fractions/4 weeks) for low to intermediate risk prostate cancer was well tolerated with no excessive acute or late toxicities. Tumor control has been satisfactory on long term follow-up. A Canadian multicenter randomized controlled trial of conventional- vs. hypo-fractionated IGRT for intermediate risk prostate cancer is on-going. Hypofractionated IGRT (55 Gy/16 fractions/4 weeks) for low to intermediate risk prostate cancer was well tolerated with no excessive acute or late toxicities. Tumor control has been satisfactory on long term follow-up. A Canadian multicenter randomized controlled trial of conventional- vs. hypo-fractionated IGRT for intermediate risk prostate cancer is on-going.