Bobek, Olivia

INTRODUCTION: The goal of this study was to identify nationwide access to transient elastography (TE), magnetic resonance elastography (MRE), and gastroenterologists. METHODS: We used public data from each test's manufacturer's website to identify the number of TE and MRE units in the United States. We used public data from the Health Resources and Services Administration to identify the number of gastroenterologists in the United States. RESULTS: Overall, 82.4% of US counties do not contain TE or MRE, and 69.2% do not contain a gastroenterologist. Two-thirds (67.4%) of US counties do not contain either elastography or a gastroenterologist. DISCUSSION: There is limited access to TE, MRE, and gastroenterologists in the United States.

Background The optimal management of biochemical recurrence (BCR) after radical prostatectomy (RP) remains controversial, particularly in the absence of clinical or radiographic evidence of disease. Salvage radiotherapy (SRT) remains standard of care, but it is unclear whether SRT benefits patients when modern imaging with a multiparametric magnetic resonance imaging (mpMRI) and prostate‐specific membrane antigen‐positron emission tomography/computed tomography (PSMA‐PET/CT) are negative for local recurrence. Retrospective data comparing SRT to observation for such patients is fraught with selection bias, underscoring the need for a prospective randomised controlled trial. Study Design and Methods The Biochemical Recurrence Irradiation or Observation (BRIO) is a randomised study under the DIVINE trial framework (NCT06378866) enrolling men with BCR (prostate‐specific antigen [PSA] level ≥0.2, up to 1.5 ng/mL) after RP with no radiographic evidence of recurrence on mpMRI and PSMA‐PET/CT. Major inclusion criteria include age ≥18 years, biochemically recurrent prostate cancer after RP with a PSA level between 0.2 and 1.5 ng/mL, and no local or metastatic recurrence on imaging. A total of 312 patients will be enrolled. Participants are randomised 1:1 to standard‐of‐care SRT followed by surveillance (Group A), or initial observation with subsequent image‐guided therapy at radiographic progression (Group B). Based on historical analysis, a total of 30 metastasis events provides 80% power to detect a significant improvement (hazard ratio 0.5 corresponding to a 5‐year metastasis‐free proportion of 80.7% in the control group and 89.8% in the experimental group with one‐sided type I error rate of 0.15). All participants undergo baseline blood collection to measure prostate cancer‐extracellular vesicles and cell‐free DNA for biomarker development. Participants are followed in a 16‐week cycle with serial PSA measurements, repeat imaging if PSA doubles, safety assessment, and patient‐reported outcomes. Endpoints The primary endpoint is distant recurrence‐free survival at 5‐years using a 12‐month landmark to mitigate bias arising from differing assessment schedules for patients receiving optional 6 months of androgen deprivation therapy. Key secondary outcomes include time to hormone therapy, quality of life measures, adverse effects, and novel blood and urine biomarkers. Conclusion The BRIO study will clarify the clinical benefit of immediate SRT vs observation with image‐guided intervention in mpMRI and PET‐negative BCR after RP.

Abstract Purpose: Mutations in hematopoietic progenitor cells accumulate with age leading to clonal expansion, termed clonal hematopoiesis (CH). CH in the general population is associated with hematopoietic neoplasms and reduced overall survival (OS), predominantly through cardiovascular adverse events (CVAE). Because androgen receptor pathway inhibitors (ARPI) used in metastatic castration-resistant prostate cancer (mCRPC) are also associated with CVAEs and because CH negatively impacted survival in an advanced solid tumor cohort, we hypothesized that CH in mCRPC may be associated with increased CVAEs and inferior survival. Experimental Design: A targeted DNA sequencing panel captured common CH mutations in pretreatment blood samples from 957 patients enrolled in Alliance A031201: a randomized trial of enzalutamide ± abiraterone/prednisone in the first-line mCRPC setting. The primary outcome was the impact of CH on OS; the secondary outcomes were progression-free survival (PFS) and CVAEs. Results: Baseline comorbidities were similar by CH status. No differences in OS/progression-free survival were detected regardless of treatment arm or the variant allele frequency threshold used to define CH [primary: 2% (normal-CH, N-CH); exploratory: 0.5% (low-CH) and 10% (high-CH, H-CH)]. Patients with H-CH (7.2%) and TET2-mutated N-CH (6.0%) had greater odds of any CVAE (14.5% vs. 4.0%; P = 0.0004 and 12.3% vs. 4.2%; P = 0.010, respectively). More major CVAEs were observed in patients with H-CH (5.8% vs. 1.9%; P = 0.042) and N-CH (3.4% vs. 1.8%; P = 0.147). Conclusions: CH did not affect survival in patients with mCRPC treated with ARPIs in A031201. H-CH and TET2-mutated CH were associated with more CVAEs. These findings inform the risk/benefit discussion about ARPIs in mCRPC.

PURPOSE Enzalutamide and abiraterone both target androgen receptor signaling but via different mechanisms. The mechanism of action of one drug may counteract the resistance pathways of the other. We sought to determine whether the addition of abiraterone acetate and prednisone (AAP) to enzalutamide prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) in the first-line setting. PATIENTS AND METHODS Men with untreated mCRPC were randomly assigned (1:1) to receive first-line enzalutamide with or without AAP. The primary end point was OS. Toxicity, prostate-specific antigen declines, pharmacokinetics, and radiographic progression-free survival (rPFS) were also examined. Data were analyzed using an intent-to-treat approach. The Kaplan-Meier estimate and the stratified log-rank statistic were used to compare OS between treatments. RESULTS In total, 1,311 patients were randomly assigned: 657 to enzalutamide and 654 to enzalutamide plus AAP. OS was not statistically different between the two arms (median, 32.7 [95% CI, 30.5 to 35.4] months for enzalutamide v 34.2 [95% CI, 31.4 to 37.3] months for enzalutamide and AAP; hazard ratio [HR], 0.89; one-sided P = .03; boundary nominal significance level = .02). rPFS was longer in the combination arm (median rPFS, 21.3 [95% CI, 19.4 to 22.9] months for enzalutamide v 24.3 [95% CI, 22.3 to 26.7] months for enzalutamide and AAP; HR, 0.86; two-sided P = .02). However, pharmacokinetic clearance of abiraterone was 2.2- to 2.9-fold higher when administered with enzalutamide, compared with clearance values for abiraterone alone. CONCLUSION The addition of AAP to enzalutamide for first-line treatment of mCRPC was not associated with a statistically significant benefit in OS. Drug-drug interactions between the two agents resulting in increased abiraterone clearance may partly account for this result, although these interactions did not prevent the combination regimen from having more nonhematologic toxicity.