Acute and Late Toxicity in High-risk Prostate Cancer Treated with Androgen Suppression and Hypofractionated Intensity Modulated Radiotherapy

Abstract

Purpose/Objective(s)Standard curative treatment for high-risk prostate cancer includes radical radiotherapy (RT) with androgen suppression therapy (AST). Recent literature supports hypofractionation and dose escalation in the treatment of prostate cancer, due to its unique radiobiology, with acceptable organ at risk toxicities. We report on acute and late toxicity, overall survival and progression free survival using hypofractionated intensity modulated radiation therapy (IMRT) with AST.Materials/MethodsPhase II prospective study enrolled 60 patients with diagnosis of high-risk prostate adenocarcinoma (clinical stage ≥T3a or initial prostate-specific antigen (PSA) ≥20 ng/mL or Gleason score 8-10 or combination of PSA >15 ng/mL plus Gleason score 7). Patients received 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to prostate and proximal seminal vesicles. Pelvic lymph nodes and distal seminal vesicles received 45 Gy in 25 fractions (1.8 Gy/fraction) concurrently. Treatment was delivered with helical TomoTherapy-based IMRT with daily megavoltage CT image-guided verification for positioning. Patients received AST for up to 3 years. Acute toxicities were recorded weekly during RT and 3 months post-RT and late toxicities every 6 months using Radiation Therapy Oncology Group toxicity scores. Primary endpoints included acute and late toxicity scores.ResultsSixty patients completed RT; 59 patients were analyzed for late toxicity data as one patient withdrew from the study before 6 months. Maximum acute toxicity was 35% Grade 2, 6.7% Grade 3 gastrointestinal (GI) toxicities, and 33.3% Grade 2 genitourinary (GU) toxicities. For late toxicity, median follow-up was 53.3 months (15.5-69.9 months). Maximum late toxicity was 8% and 7% Grade 3 GI and GU toxicity, respectively, with 1 patient experiencing Grade 5 GI toxicity. Analysis of toxicity data (day 1-24 months) revealed the odds ratio (OR) of high GU and GI toxicity (≥ Grade 2) decreased with time beyond 12 months. Survival probability was 100%, 96.5%, 94.7%, 94.7%, and 94.7% at 12, 24, 36, 48, and 60 months, respectively. Progression-free survival probability was: 100% at 12, 24 months; 98.3% at 36 months; 94.7% at 48 months; and 88.4% at 60, and 70 months.ConclusionsThis study illustrates the utility of hypofractionation and dose escalation in treatment of high-risk prostate cancer with excellent outcomes in terms of overall and progression free survival. RT was well tolerated acutely and late GI and GU toxicity peaked at 12 months and decreased thereafter. A randomized control trial to compare hypofractionation and dose escalation with standard conventional treatment is needed. Purpose/Objective(s)Standard curative treatment for high-risk prostate cancer includes radical radiotherapy (RT) with androgen suppression therapy (AST). Recent literature supports hypofractionation and dose escalation in the treatment of prostate cancer, due to its unique radiobiology, with acceptable organ at risk toxicities. We report on acute and late toxicity, overall survival and progression free survival using hypofractionated intensity modulated radiation therapy (IMRT) with AST. Standard curative treatment for high-risk prostate cancer includes radical radiotherapy (RT) with androgen suppression therapy (AST). Recent literature supports hypofractionation and dose escalation in the treatment of prostate cancer, due to its unique radiobiology, with acceptable organ at risk toxicities. We report on acute and late toxicity, overall survival and progression free survival using hypofractionated intensity modulated radiation therapy (IMRT) with AST. Materials/MethodsPhase II prospective study enrolled 60 patients with diagnosis of high-risk prostate adenocarcinoma (clinical stage ≥T3a or initial prostate-specific antigen (PSA) ≥20 ng/mL or Gleason score 8-10 or combination of PSA >15 ng/mL plus Gleason score 7). Patients received 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to prostate and proximal seminal vesicles. Pelvic lymph nodes and distal seminal vesicles received 45 Gy in 25 fractions (1.8 Gy/fraction) concurrently. Treatment was delivered with helical TomoTherapy-based IMRT with daily megavoltage CT image-guided verification for positioning. Patients received AST for up to 3 years. Acute toxicities were recorded weekly during RT and 3 months post-RT and late toxicities every 6 months using Radiation Therapy Oncology Group toxicity scores. Primary endpoints included acute and late toxicity scores. Phase II prospective study enrolled 60 patients with diagnosis of high-risk prostate adenocarcinoma (clinical stage ≥T3a or initial prostate-specific antigen (PSA) ≥20 ng/mL or Gleason score 8-10 or combination of PSA >15 ng/mL plus Gleason score 7). Patients received 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to prostate and proximal seminal vesicles. Pelvic lymph nodes and distal seminal vesicles received 45 Gy in 25 fractions (1.8 Gy/fraction) concurrently. Treatment was delivered with helical TomoTherapy-based IMRT with daily megavoltage CT image-guided verification for positioning. Patients received AST for up to 3 years. Acute toxicities were recorded weekly during RT and 3 months post-RT and late toxicities every 6 months using Radiation Therapy Oncology Group toxicity scores. Primary endpoints included acute and late toxicity scores. ResultsSixty patients completed RT; 59 patients were analyzed for late toxicity data as one patient withdrew from the study before 6 months. Maximum acute toxicity was 35% Grade 2, 6.7% Grade 3 gastrointestinal (GI) toxicities, and 33.3% Grade 2 genitourinary (GU) toxicities. For late toxicity, median follow-up was 53.3 months (15.5-69.9 months). Maximum late toxicity was 8% and 7% Grade 3 GI and GU toxicity, respectively, with 1 patient experiencing Grade 5 GI toxicity. Analysis of toxicity data (day 1-24 months) revealed the odds ratio (OR) of high GU and GI toxicity (≥ Grade 2) decreased with time beyond 12 months. Survival probability was 100%, 96.5%, 94.7%, 94.7%, and 94.7% at 12, 24, 36, 48, and 60 months, respectively. Progression-free survival probability was: 100% at 12, 24 months; 98.3% at 36 months; 94.7% at 48 months; and 88.4% at 60, and 70 months. Sixty patients completed RT; 59 patients were analyzed for late toxicity data as one patient withdrew from the study before 6 months. Maximum acute toxicity was 35% Grade 2, 6.7% Grade 3 gastrointestinal (GI) toxicities, and 33.3% Grade 2 genitourinary (GU) toxicities. For late toxicity, median follow-up was 53.3 months (15.5-69.9 months). Maximum late toxicity was 8% and 7% Grade 3 GI and GU toxicity, respectively, with 1 patient experiencing Grade 5 GI toxicity. Analysis of toxicity data (day 1-24 months) revealed the odds ratio (OR) of high GU and GI toxicity (≥ Grade 2) decreased with time beyond 12 months. Survival probability was 100%, 96.5%, 94.7%, 94.7%, and 94.7% at 12, 24, 36, 48, and 60 months, respectively. Progression-free survival probability was: 100% at 12, 24 months; 98.3% at 36 months; 94.7% at 48 months; and 88.4% at 60, and 70 months. ConclusionsThis study illustrates the utility of hypofractionation and dose escalation in treatment of high-risk prostate cancer with excellent outcomes in terms of overall and progression free survival. RT was well tolerated acutely and late GI and GU toxicity peaked at 12 months and decreased thereafter. A randomized control trial to compare hypofractionation and dose escalation with standard conventional treatment is needed. This study illustrates the utility of hypofractionation and dose escalation in treatment of high-risk prostate cancer with excellent outcomes in terms of overall and progression free survival. RT was well tolerated acutely and late GI and GU toxicity peaked at 12 months and decreased thereafter. A randomized control trial to compare hypofractionation and dose escalation with standard conventional treatment is needed.