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Purpose: Whole pelvis radiation therapy (WPRT) may improve clinical outcomes over prostate-only radiation therapy (PORT) in high-risk prostate cancer patients by sterilization of micrometastatic nodal disease, provided there is optimal control of the primary site.Methods and Materials: A prospective multicenter cohort study of eligible patients (stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) treated between 2009 and 2013 were enrolled in a United Kingdom national protocol delivering combined external beam radiation therapy and high-dose-rate brachytherapy. Centers elected to deliver WPRT, 46 Gy in 23 fractions or PORT 37.5 Gy in 15 fractions with 15 Gy single dose high-dose-rate brachytherapy. The primary endpoint was biochemical progression-free survival (bPFS). Secondary endpoints were overall survival, genitourinary, and gastrointestinal toxicity. This was not a randomized comparison and was subject to bias; the findings are therefore hypothesis generating, but not conclusive.Results: Eight hundred and twelve patients were entered; 401 received WPRT and 411 received PORT. With a median follow-up of 4.7 years, 5-year bPFS rates for WPRT versus PORT arms were 89% versus 81% (P = .007) for all patients and 84% versus 77% (P = .001) for high-risk patients. Differences in bPFS remained significant after accounting for Gleason score, presenting prostate-specific antigen, T stage, and androgen deprivation therapy duration as covariates. There was no difference in overall survival. The overall post treatment toxicities across both cohorts were low with no greater than 1.5% of ≥grade 3 toxicities at any follow-up time point. WPRT increased both prevalence and cumulative incidence of acute genitourinary toxicity (P = .004) and acute gastrointestinal toxicity (P = .003). No difference in late radiation toxicity was observed.Conclusions: A significant improvement in 5-year bPFS was seen in intermediate and high-risk prostate cancer treated with WPRT compared with PORT in a combined external beam radiation therapy and brachytherapy schedule with no increase in late radiation toxicity. [ABSTRACT FROM AUTHOR]

Purpose: CHHiP is a randomized trial evaluating moderately hypofractionated radiation therapy for treatment of localized prostate cancer. Of all participants, 97% of them had concurrent short-course hormone therapy (HT), either luteinizing hormone-releasing hormone analog (LHRHa) or 150 mg of bicalutamide daily. This exploratory analysis compares efficacy and side effects in a nonrandomized comparison.Methods and Materials: In our study, 2700 patients received LHRHa and 403 received bicalutamide. The primary endpoint was biochemical/clinical failure. Groups were compared with Cox regression adjusted for various prognostic factors and stratified by radiation therapy dose. A key secondary endpoint was erectile dysfunction (ED) assessed by clinicians (using scores from Late Effects on Normal Tissues: Subjective/Objective/Management [LENT-SOM] subjective erectile function for vaginal penetration) and patients (single items within the University of California-Los Angeles Prostate Cancer Index [UCLA PCI] and Expanded Prostate Cancer Index Composite [EPIC]-50 questionnaires) at 2 years and compared between HT regimens by χ2 trend test.Results: Bicalutamide patients were significantly younger (median 67 vs 69 years LHRHa). Median follow-up was 9.3 years. There was no difference in biochemical or clinical failure with an adjusted hazard ratio or 0.97 (95% confidence interval, 0.77-1.23; P = .8). At 2 years, grade ≥2 LENT-SOM ED was reported in significantly more LHRHa patients (313 out of 590; 53%) versus bicalutamide (17 out of 68; 25%) (P < .0001). There were no differences in ED seen with UCLA-PCI and EPIC-50 questionnaires.Conclusions: In this nonrandomized comparison, there was no evidence of a difference in efficacy according to type of HT received. Bicalutamide preserved clinician assessed (LENT-SOM) erectile function at 2 years but patient-reported outcomes were similar between groups. [ABSTRACT FROM AUTHOR]

Background: Elevated lipoprotein(a) [Lp(a)] and coronary artery calcium (CAC) score are individually associated with increased atherosclerotic cardiovascular disease (ASCVD) risk but have not been studied in combination.Objectives: This study sought to investigate the independent and joint association of Lp(a) and CAC with ASCVD risk.Methods: Plasma Lp(a) and CAC were measured at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 4,512) and DHS (Dallas Heart Study) (n = 2,078) cohorts. Elevated Lp(a) was defined as the highest race-specific quintile, and 3 CAC score categories were studied (0, 1-99, and ≥100). Associations of Lp(a) and CAC with ASCVD risk were evaluated using risk factor-adjusted Cox regression models.Results: Among MESA participants (61.9 years of age, 52.5% women, 36.8% White, 29.3% Black, 22.2% Hispanic, and 11.7% Chinese), 476 incident ASCVD events were observed during 13.2 years of follow-up. Elevated Lp(a) and CAC score (1-99 and ≥100) were independently associated with ASCVD risk (HR: 1.29; 95% CI: 1.04-1.61; HR: 1.68; 95% CI: 1.30-2.16; and HR: 2.66; 95% CI: 2.07-3.43, respectively), and Lp(a)-by-CAC interaction was not noted. Compared with participants with nonelevated Lp(a) and CAC = 0, those with elevated Lp(a) and CAC ≥100 were at the highest risk (HR: 4.71; 95% CI: 3.01-7.40), and those with elevated Lp(a) and CAC = 0 were at a similar risk (HR: 1.31; 95% CI: 0.73-2.35). Similar findings were observed when guideline-recommended Lp(a) and CAC thresholds were considered, and findings were replicated in the DHS.Conclusions: Lp(a) and CAC are independently associated with ASCVD risk and may be useful concurrently for guiding primary prevention therapy decisions. [ABSTRACT FROM AUTHOR]

Purpose: Many muscle-invasive bladder cancers are hypoxic, which limits the efficacy of radiation therapy. Hypoxia modification using carbogen and nicotinamide has been tested in a phase 3 trial, Bladder Carbogen Nicotinamide. We present mature follow-up data with biomarker predictions of outcomes.Methods and Materials: Bladder Carbogen Nicotinamide is a prospective, phase 3, multicenter, randomized, 2-arm, nonblinded clinical trial. Participants were randomized to receive radical radiation therapy (RT; control arm) alone or with the addition of carbogen (98% O2; 2% CO2) and nicotinamide (CON). Patients with muscle-invasive or high-grade non-muscle invasive bladder cancer were included. Tumor tissue was collected at entry and was analyzed for tumor necrosis, hypoxia (24-gene signature), and basal and luminal tumor molecular subtypes. Overall survival (OS) and disease-free survival and relationships with biomarker status outcomes are analyzed using multivariable Cox regression and log-rank analysis.Results: We analyzed 333 patients with a median follow-up of 10.3 years. The 10-year OS rates were 30% (95% confidence interval [CI], 0.23-0.39) in RT + CON patients and 24% (95% CI, 0.18-0.33) in the RT-alone patients (hazard ratio [HR], 0.80; 95% CI, 0.61-1.04; P = .08). The greatest benefit from CON was seen in patients with tumor necrosis (n = 79; 5-year OS, 53% vs. 33% in patients without tumor necrosis; HR, 0.59; 95% CI, 0.36-0.99; P = .04). Cases with a high hypoxia gene score (n = 75) had a 5-year OS rate of 51%, compared to 34% for a low score (HR, 0.64; 95% CI, 0.38-1.08; P = .09); those with the basal molecular subtype (n = 70) had a 5-year OS rate of 58%, compared to 38% for those with the luminal subtype (HR, 0.58; 95% CI, 0.32-1.06; P = .08).Conclusions: Although the improvement in long-term OS in the whole population is not statistically significant, patients selected by necrosis and high hypoxia gene score benefitted from hypoxia modification. [ABSTRACT FROM AUTHOR]

Purpose: Outcome data on radiation therapy for prostate cancer in an elderly population are sparse. The CHHiP (Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer) trial provides a large, prospectively collected, contemporary dataset in which to explore outcomes by age.Methods and Materials: CHHiP participants received 3 to 6 months of androgen deprivation therapy and were randomly assigned (1:1:1) to receive 74 Gy in 37 fractions (conventional fractionation), 60 Gy in 20 fractions, or 57 Gy in 19 fractions. Toxicity was assessed using clinician-reported outcome (CRO) and patient-reported outcome questionnaires. Participants were categorized as aged < 75 years or ≥ 75 years. Outcomes were compared by age group.Results: Of 3216 patients, 491 (15%) were aged ≥ 75 years. There was no difference in biochemical or clinical failure rates between the groups aged < 75 years and ≥ 75 years for any of the fractionation schedules. In the group aged ≥ 75 years, biochemical or clinical failure-free rates favored hypofractionation, and at 5 years, they were 84.7% for 74 Gy, 91% for 60 Gy, and 87.7% for 57 Gy. The incidence of CRO (grade 3) acute bowel toxicity was 2% in both age groups. The incidence of grade 3 acute bladder toxicity was 8% in patients aged < 75 years and 7% in those aged ≥ 75 years. The 5-year cumulative incidence of CRO grade ≥ 2 late bowel side effects was similar in both age groups. However, in the group aged ≥ 75 years, there was a suggestion of a higher cumulative incidence of bowel bother (small or greater) with 60 Gy compared with 74 Gy and 57 Gy. Patient-reported bladder bother was slightly higher in the group aged ≥ 75 years than the group aged < 75 years, and there was a suggestion of a lower cumulative incidence of bladder bother with 57 Gy compared with 74 Gy and 60 Gy in patients aged ≥ 75 years, which was not evident in those aged < 75 years.Conclusions: Hypofractionated radiation therapy appears to be well tolerated and effective in men aged ≥ 75 years. The 57-Gy schedule has potential advantages in that it may moderate long-term side effects without compromising treatment efficacy in this group. [ABSTRACT FROM AUTHOR]