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The aim of this work is to report on the results of a phase 2 randomized trial of moderately hypofractionated (MH) versus conventionally fractionated (CF) radiation therapy to the prostate with elective nodal irradiation. This was a single-center, prospective, phase 2 randomized study. Patients with high-risk disease (cT3, prostate-specific antigen level >20 ng/mL, or Gleason score 8-10) were eligible. Patients were randomized to either MH using a simultaneous integrated boost (68 Gy in 25 fractions to prostate; 48 Gy to pelvis) or CF (46 Gy in 23 fractions with a sequential boost to the prostate of 32 Gy in 16 fractions), with long-term androgen deprivation therapy. The primary endpoint was grade ≥2 acute gastrointestinal (GI) and genitourinary (GU) toxicity (Common Terminology Criteria for Adverse Events version 3.0). Secondary endpoints included late GI and GU toxicity, quality of life, and oncologic outcomes. One-hundred eighty patients were enrolled; 90 were randomized to and received MH and 90 to CF. The median follow-up was 67.4 months. Seventy-five patients (41.7%) experienced a grade ≥2 acute GI and/or GU toxicity, including 34 (37.8%) in the MH and 41 (45.6%) in the CF arms, respectively (P =.29). Late grade ≥2 GI (P =.07) and GU (P =.25) toxicity was not significantly different between arms; however, late grade ≥3 GI toxicity was worse in the MH group (P =.01). There were no statistically significant quality-of-life differences between the 2 treatments. There were no statistically significant differences observed in cumulative incidence of biochemical failure (P =.71) or distant metastasis (P =.31) and overall survival (P =.46). MH to the prostate and pelvis with androgen deprivation therapy for men with high-risk localized prostate cancer was not significantly different than CF with regard to acute toxicity, quality of life, and oncologic efficacy. However, late grade ≥3 GI toxicity was more common in the MH arm. [ABSTRACT FROM AUTHOR]

Purpose: The role of metastasis-directed therapy (MDT) in molecularly defined oligorecurrent prostate cancer (PCa) remains irresolute. We present extended follow-up and an independent validation cohort of a prospective trial.Methods and Materials: This study consists of 2 sequential single-arm phase-2 trials of patients with biochemical recurrence (prostate specific antigen [PSA] 0.4-3.0 ng/mL) and negative conventional imaging after radical prostatectomy and postoperative radiation therapy. All patients underwent [18F]DCFPyL positron emission tomography/computed tomography. Patients with molecularly defined oligorecurrent prostate cancer underwent MDT with stereotactic body radiation therapy or surgery, without androgen deprivation therapy (ADT). The primary end point was biochemical response (≥50% PSA decline from baseline). Secondary end points included PSA progression-free survival and ADT-free survival. The sample size of 37 MDT patients was determined based on a Simon's 2-stage design with biochemical response rate >20%, and this design was also applied for the subsequent independent validation cohort.Results: Seventy-four patients underwent MDT: 37 each in the initial and validation cohorts. Both cohorts met the prespecified biochemical response rate and completed the planned 2-stages of accrual. For the pooled cohort, the median number of prostate specific membrane antigen positron emission tomography avid lesions was 2 and most (87%) recurrences were nodal. Sixty-four (87%) had stereotactic body radiation therapy and 10 (13%) had surgery. Median follow-up (interquartile range [IQR]) for the initial, validation and combined cohorts were 41 (35-46) months, 14 months (7-21), and 24 months (14-41), respectively. The biochemical response rates for the initial, validation and combined cohorts were 59%, 43%, and 51%, respectively. For the combined cohort, median biochemical progression-free survival was 21 months (95% confidence interval, 13-not reached), and median ADT-free survival was 45 months (95% confidence interval, 31-not reached).Conclusions: Half of patients treated with MDT for molecularly defined-only oligorecurrent prostate cancer exhibited a biochemical response. This study provides necessary and validated evidence to support randomized trials aiming to determine whether MDT (alone or with systemic therapy) can affect clinically meaningful end points. [ABSTRACT FROM AUTHOR]

• Long-term results of elective nodal irradiation and hypofractionated prostate boost. • At 10 years, biochemical failure 33%, distant metastasis 17% and survival 76% • Low cumulative incidence of grade ≥3 gastrointestinal and genitourinary toxicity. To report on long-term results of elective pelvic nodal irradiation (EPNI) and a simultaneous hypofractionated prostate boost for high-risk prostate cancer. This was a prospective single-arm study. Patients with high-risk disease (cT3, PSA >20 ng/mL, or Gleason score 8–10) were eligible. Patients received 45 Gy in 25 fractions to the prostate and pelvic lymph nodes with a simultaneous intensity-modulated radiotherapy boost of 22.5 Gy to the prostate (total dose 67.5 Gy in 25 fractions), with androgen deprivation therapy (ADT) for 2–3 years. The primary endpoint was biochemical failure. Secondary endpoints included distant metastases and overall survival. Multivariable analysis was performed to look for predictive factors. Late toxicity was assessed using CTCAE v3.0. 230 patients enrolled. Median follow-up was 11.2 years (IQR 8.1–12.9). At 10 years, cumulative incidence of biochemical failure was 33.4%, distant metastasis was 16.5%, and overall survival was 76.3%. On multivariable analysis, PSA nadir ≥0.05 ng/mL was associated with biochemical failure (HR 6.8, 95% CI 4–11.8, p < 0.001) and distant metastases (HR 7.5, 95% CI 3.9–14.5, p < 0.0001). PSA nadir ≥0.1 ng/mL (HR 5.2, 95% 2.2–12, p = 0.0001) and ADT use ≤12 months (versus >24 months) (HR 2.3, 95% CI 1.3–3.9, p = 0.004) were associated with worse survival. The 5-year cumulative incidence of any late grade ≥3 gastrointestinal and genitourinary toxicity was 2.3% and 7.5%, respectively. EPNI and a simultaneous hypofractionated prostate boost combined with long-term ADT for high-risk prostate cancer resulted in acceptable 10-year biochemical control and survival with low grade ≥3 toxicity. [ABSTRACT FROM AUTHOR]

The use of combination RT and androgen deprivation therapy in many prostate cancer curative-intent treatment scenarios is supported by level 1 evidence. However, in our current clinical paradigm, we have no ability to determine a priori which patients truly benefit from combination therapy and therefore apply the combination RT and androgen deprivation therapy intensification strategy to all patients, which results in overtreatment or undertreatment of the majority of our patients. Genomics has the ability to more deeply and objectively characterize the disease, in turn refining our prognostication capabilities and enabling the individualization of treatments. We review the commercially available prostate cancer genomic tests, focusing on those able to predict patient outcomes following radiotherapy or guide radiotherapy treatment decisions. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of RTOG-9601 and GETUG-AFU-16 on the routine use of combination androgen deprivation therapy (ADT) with postoperative radiotherapy (PORT) for prostate cancer (CaP).Material and Methods: Patients with localized CaP treated with radical prostatectomy (RP) and PORT with or without ADT at a comprehensive cancer center from January 2006 to June 2007 (Period 1 = P1), July 2011 to December 2012 (Period 2 = P2), and January 2017 to June 2018 (Period 3 = P3) were included. Clinicopathologic features and treatment characteristics were analyzed and compared. Multivariable logistic regression was used to assess prognostic factors and association with ADT use. Statistical tests were two-sided and a P value <0.05 was considered significant. To validate the findings, United States National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results (SEER) data were collected to assess rates of combined ADT and PORT from 2004 to 2015.Results: Five hundred and two patients were included: 152 (P1), 185 (P2), and 165 (P3). PORT was most commonly delivered as early SRT (delivered >1 year post-RP with undetectable PSA or PSA >0.05 and ≤0.5 ng/ml) in all periods. The use of combination PORT and ADT increased over time: 14.5% (P1), 32% (P2), and 41% (P3) (P < 0.001). The proportion of patients that met eligibility criteria for either GETUG-AFU-16 or RTOG-9601 decreased from 47% (P1) to 35% (P3) (P = 0.04). International Society of Urological Pathology grade ≥4 (P < 0.002) and pre-PORT PSA >0.5 ng/ml (P < 0.001) were associated with use of ADT. Positive surgical margin status had a negative association (RR 0.5, P < 0.002). The NCDB demonstrated similar trends for use of combined ADT with PORT, increasing from 37% to 49% from 2004 to 2015.Conclusion: The use of combined ADT with PORT increased over time. However, only a third of contemporary patients undergoing PORT are represented in the major trials supporting the evidence for combination treatment, highlighting the need to characterize the modern impact of this intensification strategy. [ABSTRACT FROM AUTHOR]

High dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) is a widely accepted treatment for patients with clinically localized prostate cancer. A significant impact on sexual health related quality of life (sHRQoL) is reported in published series. The etiology is probably multifactorial, including baseline factors, trauma and dose to the neurovascular bundles (NVB). Magnetic resonance imaging (MRI) enables the visualization and proper localization of the NVB. Herein we aim to analyze the long-term sHRQoL after MRI-guided whole gland HDR-BT boost for prostate cancer and to assess the impact of the dose to the NVB and other factors on sHRQoL. Sixty-one patients were treated with a single 15 Gy MRI-guided HDR-BT followed by EBRT as part of a prospective phase II trial approved by the local Research Ethic Board (09-0026-C). For this analysis, patients who received over 12 months of androgen deprivation therapy (ADT) and / or patients with a baseline erectile dysfunction were excluded. The left and right NVB were delineated in retrospect on T2-weighted images. Sexual HRQoL was prospectively collected using the expanded prostate index composite (EPIC) questionnaire at baseline, 1month, 3 months, 6 months, 12 months and Q12 monthly thereafter until 60 months. A minimally important difference (MID) was defined as a deterioration of sHRQoL scores at 3 months ≥ 0.5 standard deviation of baseline score. Linear and logistic regression models were used. Twenty-eight patients met the criteria to be included in this analysis. A short course of ADT was given to 15 patients. the mean baseline sexual HRQOL score was 48.1 (SD=27.1): 41.9 (SD=28.5) for sexual function and 63.8 (SD=37.9) for sexual bother (37.9). At 12, 24, 36 and 60 months the mean sexual score was 37.5 (SD=26.3), 47(SD=24.3), 45.1 (SD=20.4) and 36.8 (SD=29.1), p>0.05. A MID was reported by 50% of patients at 60 months. The mean sHRQoL score at 60 months of patients who had a short course of ADT was 44.1 (SD=27.1) versus 32.2 (SD=31.1), p >0.05.The mean delineated volume of the NVB was 0.35 cc ± 0.12 on the right and 0.36 cc ± 0.13 on the left. The median number of needles used was 18 [interquartile range(IQR):17-19]. The median dose max to the left NVB is 20.9 Gy (17.4-22.8) and to the right NVB is 21.1 Gy (19.0-24.0). the median dose to the penile bulb was 5.4 Gy (4.2-7.8).There was no association found between any of the baseline or dosimetric parameters with the deterioration sHRQoL. Fifty percent of prostate cancer patients treated with MRI-guided HDR-BT followed by EBRT reported a MID in their sHRQoL at 5 years after. The dose received by the NVB bilaterally was consistently higher than 120% of the prescription dose. A short course of ADT was not associated with a worse sHRQoL score at 5 years. Further studies should focus on using MRI to accurately delineate the NVB and assess the feasibility and impact of limiting the dose to the NVB. [ABSTRACT FROM AUTHOR]