Is Ultrahypofractionated Whole Pelvis Radiation Therapy (WPRT) as Well Tolerated as Conventionally Fractionated WPRT in Patients With Prostate Cancer? Early Results From the HOPE Trial.

OBJECTIVE: The aim of this work was to evaluate the acute toxicity and quality-of-life (QOL) impact of ultrahypofractionated whole pelvis radiation therapy (WPRT) compared with conventional WPRT fractionation after high-dose-rate prostate brachytherapy (HDR-BT). METHODS AND MATERIALS: The HOPE trial is a phase 2, multi-institutional randomized controlled trial of men with prostate-confined disease and National Comprehensive Cancer Network unfavorable intermediate-, high-, or very-high-risk prostate cancer. Patients were randomly assigned to receive conventionally fractionated WPRT (standard arm) or ultrahypofractionated WPRT (experimental arm) in a 1:1 ratio. All patients underwent radiation therapy with 15 Gy HDR-BT boost in a single fraction followed by WPRT delivered with conventional fractionation (45 Gy in 25 daily fractions or 46 Gy in 23 fractions) or ultrahypofractionation (25 Gy in 5 fractions delivered on alternate days). Acute toxicities measured during radiation therapy and at 6 weeks posttreatment were assessed using the clinician-reported Common Terminology Criteria for Adverse Events version 5.0, and QOL was measured using the Expanded Prostate Cancer Index Composite (EPIC-50) and International Prostate Symptom Score (IPSS). RESULTS: A total of 80 patients were enrolled and treated across 3 Canadian institutions, of whom 39 and 41 patients received external radiation therapy with conventionally fractionated and ultrahypofractionated WPRT, respectively. All patients received androgen deprivation therapy except for 2 patients treated in the ultrahypofractionated arm. The baseline clinical characteristics of the 2 arms were similar, with 51 (63.8%) patients having high or very-high-risk prostate cancer disease. Treatment was well tolerated with no significant differences in the rate of acute adverse events between arms. No grade 4 adverse events or treatment-related deaths were reported. Ultrahypofractionated WPRT had a less detrimental impact on the EPIC-50 bowel total, function, and bother domain scores compared with conventional WPRT in the acute setting. By contrast, more patients treated with ultrahypofractionated WPRT reached the minimum clinical important difference on the EPIC-50 urinary domains. No significant QOL differences between arms were noted in the sexual and hormonal domains. CONCLUSIONS: Ultrahypofractionated WPRT after HDR-BT is a well-tolerated treatment strategy in the acute setting that has less detrimental impact on bowel QOL domains compared with conventional WPRT.

An Updated Analysis of the Survival Endpoints of ASCENDE-RT.

PURPOSE: Using the primary endpoint of time to biochemical progression (TTP), Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) randomized National Comprehensive Cancer Network patients with intermediate and high-risk prostate cancer to low-dose-rate brachytherapy boost (LDR-PB) or dose-escalated external beam boost (DE-EBRT). Randomization to the LDR-PB arm resulted in a 2-fold reduction in biochemical progression compared with the DE-EBRT group at a median follow-up of 6.5 years (P < .001). Herein, the primary endpoint and secondary survival endpoints of the ASCENDE-RT trial are updated at a 10-year median follow-up. METHODS: Patients were randomly assigned to either the LDR-PB or the DE-EBRT arm (1:1). All patients received 1 year of androgen deprivation therapy and 46 Gy in 23 fractions of pelvic RT. Patients in the DE-EBRT arm received an additional 32 Gy in 16 fractions, and those in the LDR-PB arm received an 125I implant prescribed to a minimum peripheral dose of 115 Gy. Two hundred patients were randomized to the DE-EBRT arm and 198 to the LDR-PB arm. RESULTS: The 10-year Kaplan-Meier TTP estimate was 85% ± 5% for LDR-PB compared with 67% ± 7% for DE-EBRT (log rank P < .001). Ten-year time to distant metastasis (DM) was 88% ± 5% for the LDR-PB arm and 86% ± 6% for the DE-EBRT arm (P = .56). There were 117 (29%) deaths. Ten-year overall survival (OS) estimates were 80% ± 6% for the LDR-PB arm and 75% ± 7% for the DE-EBRT arm (P = .51). There were 30 (8%) patients who died of prostate cancer: 12 (6%) in the LDR-PB arm, including 2 treatment-related deaths, and 18 (9%) in the DE-EBRT arm. CONCLUSIONS: Men randomized to the LDR-PB boost arm of the ASCENDE-RT trial continue to experience a large advantage in TTP compared with those randomized to the DE-EBRT arm. ASCENDE-RT was not powered to detect differences in its secondary survival endpoints (OS, DM, and time to prostate cancer-specific death) and none are apparent.

Late urinary side effects 10 years after low-dose-rate prostate brachytherapy: population-based results from a multiphysician practice treating with a standardized protocol and uniform dosimetric goals.

PURPOSE: To determine late urinary toxicity (>12 months) in a large cohort of uniformly treated low-dose-rate prostate brachytherapy patients. METHODS AND MATERIALS: From 1998 to 2009, 2709 patients with National Comprehensive Cancer Network-defined low-risk and low-tier intermediate-risk prostate cancer were treated with Iodine 125 ((125)I) low-dose-rate prostate brachytherapy; 2011 patients with a minimum of 25 months of follow-up were included in the study. Baseline patients, treatment, implant factors, and late urinary toxicity (Radiation Therapy Oncology Group [RTOG] grading system and International Prostate Symptom Score [IPSS]) were recorded prospectively. Time to IPSS resolution, late RTOG genitourinary toxicity was examined with Kaplan-Meier and log-rank tests. Cox proportional hazards regression was done for individual covariates and multivariable models. RESULTS: Median follow-up was 54.5 months (range, 2-13 years). Actuarial toxicity rates reached 27% and 10% (RTOG ≥2 and ≥3, respectively) at 9-13 years. Symptoms resolved quickly in the majority of patients (88% in 6-12 months). The prevalence of RTOG 0, 1, 2, 3, and 4 toxicity with a minimum of 7 years' follow-up was 70%, 21%, 6.4%, 2.3%, and 0.08%, respectively. Patients with a larger prostate volume, higher baseline IPSS, higher D90, acute toxicity, and age >70 years had more late RTOG ≥2 toxicity (all P≤.02). The IPSS resolved slower in patients with lower baseline IPSS and larger ultrasound prostate volume, those not receiving androgen deprivation therapy, and those with higher D90. The crude rate of RTOG 3 toxicity was 6%. Overall the rate of transurethral resection of the prostate was 1.9%; strictures, 2%; incontinence, 1.3%; severe symptoms, 1.8%; late catheterization, 1.3%; and hematuria, 0.8%. The majority (80%) resolved their symptoms in 6-12 months. CONCLUSION: Long-term urinary toxicity after brachytherapy is low. Although actuarial rates increase with longer follow-up (27% RTOG 2 and 10% RTOG 3 at 13 years), symptoms resolve relatively quickly; between 5 and 13 years' follow-up, >90% of patients have minimal urinary toxicity. Refining patient selection criteria, planning, and treatment delivery may further reduce toxicity.