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Purpose: Low-dose-rate (LDR) brachytherapy and stereotactic body radiation therapy (SBRT) have both shown acceptable outcomes in the treatment of low- and intermediate-risk prostate cancer. Minimal data have been published directly comparing rates of biochemical control and toxicity with these 2 modalities. We hypothesize that LDR and SBRT will provide similar rates of biochemical control.Methods and Materials: All low- and intermediate-risk patients with prostate cancer treated definitively with SBRT or LDR between 2010 and 2018 were captured. Phoenix definition was used for biochemical failure. Independent t tests were used to compare baseline characteristics, and repeated measure analysis of variance test was used to compare American Urologic Association (AUA) and the Expanded Prostate Cancer Index Composite (EPIC) scores between treatment arms over time. Biochemical control was estimated using the Kaplan-Meier method. Differences in acute and late toxicity were assessed via Pearson χ2.Results: In the study, 219 and 118 patients were treated with LDR and SBRT. Median follow-up was 4.3 years (interquartile range, 3.1-6.1). All patients treated with LDR received 125.0 Gy in a single fraction. SBRT consisted of 42.5 Gy in 5 fractions. Five-year biochemical control for LDR versus SBRT was 91.6% versus 97.6% (P = .108). LDR patients had a larger increase in mean AUA scores at 1 month (17.2 vs 10.3, P < .001) and 3 months posttreatment (14.0 vs 9.7, P < .001), and in mean EPIC scores at 1 month (15.7 vs 13.8, P < .001). There was no significant difference between LDR and SBRT in late grade 3 genitourinary toxicity (0.9% vs 2.5%, P = .238); however, LDR had lower rates of late grade 3 gastrointestinal toxicity (0.0% vs 2.5%, P = .018).Conclusions: Our data show similar biochemical control and genitourinary toxicity rates at 5 years for both SBRT and LDR, with slightly higher gastrointestinal toxicity with SBRT and higher AUA and EPIC scores with LDR. [ABSTRACT FROM AUTHOR]

Purpose: This study presents a prospective phase 1, institutional review board-approved dose-escalated stereotactic body radiation therapy trial for prostate cancer (CaP) to assess the impact of dose level on quality of life, toxicity, and clinical outcomes.Methods and Materials: From 2011 to 2016, 26 patients with low- and intermediate-risk CaP received 40, 45, and 50 Gy in 5 fractions to the prostate in cohorts of 9, 10, and 7 patients. Self-reported quality of life was prospectively measured from the Expanded Prostate Cancer Index Composite and American Urological Association. Common Terminology Criteria for Adverse Events (version 4.03) data were collected to observe acute and late toxicities. The Phoenix definition was used to calculate outcome. No patients received androgen deprivation therapy.Results: Median follow-up was 67.2 months (range, 71-230 months). There was an increase in Expanded Prostate Cancer Index Composite and American Urological Association scores followed by a return to baseline over 2 years for all cohorts. There were no grade 3 or higher toxicities or significant differences in toxicity between treatment arms. The prostate-specific antigen (PSA) nadir was significantly lower in the 45-Gy and 50-Gy cohorts when compared with the 40-Gy cohort (P < .05). Two biochemical failures were observed in the 40-Gy arm after 43 and 62 months, resulting in a freedom from biochemical failure rate of 92%. PSA survival was 100%, and actuarial overall survival was 96%. PSA nadir was 0.6, 0.1, and 0.1 ng/mL, in the 40-Gy, 45-Gy, and 50-Gy cohorts, respectively.Conclusions: This prospective, phase 1 dose-escalation study of stereotactic body radiation therapy for CaP identified acceptable genitourinary and gastrointestinal toxicity for each dose level of 40, 45, and 50 Gy. Although there was no difference in biochemical failure between the groups, we showed that higher doses of 45 and 50 Gy are associated with improved PSA nadir. The results of this study will be used to develop a larger prospective study to confirm the findings. [ABSTRACT FROM AUTHOR]

Background: Irritative voiding symptoms are common in elderly men and following prostate radiotherapy. There is limited clinical data on the impact of hypofractionated treatment on irritative voiding symptoms. This study sought to evaluate urgency, frequency, and nocturia following stereotactic body radiation therapy (SBRT) for prostate cancer. Methods: Patients treated with SBRT monotherapy for localized prostate cancer from August 2007 to July 2011 at Georgetown University Hospital were included in this study. Treatment was delivered using the CyberKnife® with doses of 35-36.25 Gy in five fractions. Patient-reported urinary symptoms were assessed using the International Prostate Symptom Score (IPSS) before treatment and at 1, 3, 6, 9, and 12 months post-treatment and every 6 months thereafter. Results: Two hundred four patients at a median age of 69 years received SBRT with a median follow-up of 4.8 years. Prior to treatment, 50.0% of patients reported moderate to severe lower urinary tract symptoms (LUTS) and 17.7% felt that urinary frequency was a moderate to big problem. The mean prostate volume was 39 cc and 8% had prior procedures for benign prostatic hyperplasia. A mean baseline IPSS-irritative (IPSS-I) score of 4.8 significantly increased to 6.5 at 1 month (p<0.0001), however returned to baseline at 3 months (p=0.73). The IPSS-I score returned to baseline in 91% of patients by 6 months and 96% of patients by 2 years. Transient increases in irritative voiding symptoms were common at 1 year. The mean baseline IPSS-I score decreased to 4.4 at 24 months (p =0.03) and 3.7 at 36 months (p <0.0001). In men with moderate to severe LUTS (IPSS⁄8) at baseline, the mean IPSS-I decreased from a baseline score of 6.8-4.9 at 3 years post-SBRT. This decrease was both statistically (p <0.0001) and clinically significant (minimally important difference D1.45). Only 14.6% of patients felt that urinary frequency was a moderate to big problem at 3 years post-SBRT (p =0.23). Conclusion: Treatment of prostate cancer with SBRT resulted in an acute increase in irritative urinary symptoms that peaked within the first month post-treatment. Irritative voiding symptoms returned to baseline in the majority of patients by 3 months post-SBRT and were actually improved from baseline at 3 years post-SBRT. [ABSTRACT FROM AUTHOR]

We demonstrate that patients with oligometastatic castration-sensitive prostate cancer detected via molecular imaging alone have less aggressive disease, as indicated by fewer high-risk pathogenic DNA mutations, and better overall survival in comparison to patients with oligometastasis detected via conventional imaging. In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel therapy, metastasis-directed therapy, and radiation to the prostate. Although there are multiple definitions of disease volume, they have commonly been studied in the context of metastases detected via conventional imaging (CIM). One such numeric definition of disease volume, termed oligometastasis, is heavily dependent on the sensitivity of the imaging modality. We performed an international multi-institutional retrospective review of men with metachronous oligometastatic CSPC (omCSPC), detected via either advanced molecular imaging alone (AMIM) or CIM. Patients were compared with respect to clinical and genomic features using the Mann-Whitney U test, Pearson's χ2 test, and Kaplan-Meier overall survival (OS) analyses with a log-rank test. A total of 295 patients were included for analysis. Patients with CIM-omCSPC had significantly higher Gleason grade group (p = 0.032), higher prostate-specific antigen at omCSPC diagnosis (8.0 vs 1.7 ng/ml; p < 0.001), more frequent pathogenic TP53 mutations (28% vs 17%; p = 0.030), and worse 10-yr OS (85% vs 100%; p < 0.001). This is the first report of clinical and biological differences between AMIM-detected and CIM-detected omCSPC. Our findings are particularly important for ongoing and planned clinical trials in omCSPC. Metastatic prostate cancer with just a few metastases only detected via newer scanning methods (called molecular imaging) is associated with fewer high-risk DNA mutations and better survival in comparison to metastatic cancer detected via conventional scan methods. [ABSTRACT FROM AUTHOR]

Purpose: Black men in the United States suffer significantly higher incidence of and mortality from prostate cancer (PCa) than non-Black men. The cause of this disparity is multifactorial, though inequitable access to curative radiation modalities, including low-dose-rate (LDR) brachytherapy, may contribute. Despite this, there are few analyses evaluating the potential of different radiation therapies to mitigate outcome disparities. Therefore, we examined the clinical outcomes of Black and non-Black patients treated with definitive LDR brachytherapy for prostate cancer.Methods: Data were collected for all patients treated with definitive LDR brachytherapy between 2005 and 2018 on a retrospective IRB-approved protocol. Pearson Chi-Squared analysis was used to assess demographic and cancer differences between Black and non-Black cohorts. Freedom from biochemical failure (FFBF) was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were used to identify factors predictive of biochemical failure.Results: One hundred and sixty-seven patients were included in the analysis (Black: n=81 [48.5%]) with a median follow-up of 88.4 months. Black patients were from lower income communities (P <0.01), had greater social vulnerability (P <0.01), and had a longer interval between diagnosis and treatment (P = 0.011). Overall cumulative FFBF was 92.3% (95% CI: 87.8% - 96.8%) at 5 years and 87.7% (95% CI: 82.0% - 93.4%) at 7 years. There was no significant difference in FFBF in Black and non-Black patients (P = 0.114) and Black race was not independently predictive of failure (HR 1.51 [95% CI: 0.56 - 4.01]; P = 0.42). Overall survival was comparable between racial groups (P = 0.972). Only nadir PSA was significantly associated with biochemical failure on MVA (HR = 3.57 [95% CI: 02.44 - 5.22]; P <0.001).Conclusions: Black men treated with LDR brachytherapy achieved similar FFBF to their non-Black counterparts despite poorer socioeconomic status. This suggests that PCa treatment with brachytherapy may eliminate some disparities clinical outcomes. [ABSTRACT FROM AUTHOR]

WNT signaling is a cellular pathway that has been implicated in the development and progression of prostate cancer. Oligometastatic castration-sensitive prostate cancer (omCSPC) represents a unique state of disease in which metastasis-directed therapy (MDT) has demonstrated improvement in progression-free survival. Herein, we investigate the clinical implications of genomic alterations in the WNT signaling cascade in men with omCSPC. We performed an international multi-institutional retrospective study of 277 men with metachronous omCSPC who underwent targeted DNA sequencing of their primary/metastatic tumor. Patients were classified by presence or absence of pathogenic WNT pathway mutations (in the genes APC, RNF43, and CTNNB1). Pearson χ2 and Mann-Whitney U tests were used to determine differences in clinical factors between genomic strata. Kaplan-Meier survival curves were generated for radiographic progression-free survival and overall survival, stratified according to WNT pathway mutation status. A pathogenic WNT pathway mutation was detected in 11.2% of patients. Patients with WNT pathway mutations were more likely to have visceral metastases (22.6% vs 2.8%; P <.01) and less likely to have regional lymph node metastases (29.0% vs 50.4%; P =.02). At time of oligometastasis, these patients were treated with MDT alone (33.9%), MDT + limited course of systemic therapy (20.6%), systemic therapy alone (22.4%), or observation (defined as no treatment for ≥6 months after metastatic diagnosis). Multivariable cox regression demonstrated WNT pathway mutations associated with significantly worse overall survival (hazard ratio, 3.87; 95% confidence interval, 1.25-12.00). Somatic WNT pathway alterations are present in approximately 11% of patients with omCSPC and are associated with an increased likelihood of visceral metastases. Although these patients have a worse natural history, they may benefit from MDT. [ABSTRACT FROM AUTHOR]