Justin R. Gregg

Active surveillance (AS) is an increasingly utilized strategy for managing localized prostate cancer, yet reliable biomarkers for predicting disease progression remain limited. Low testosterone has been associated with aggressive prostate cancer features at diagnosis, but its role in grade group progression during AS remains unclear. To evaluate the association between baseline serum testosterone levels and grade group progression in men undergoing AS for localized prostate cancer. We conducted a retrospective cohort study of 924 men enrolled in an AS program between 2001 and 2024, with a median follow-up of 46.1 months among those who did not progress. Serum testosterone levels were categorized as low if they met a threshold of ≤ 300 ng/dl based on guideline recommendations. Primary outcomes were biopsy progression to grade group 2 (GG2) or "extreme" progression to grade group 3 or higher (GG3) disease. Multivariable Cox proportional hazards models were used to assess associations between testosterone levels and progression, adjusting for age, PSA density and biopsy tumor volume. Potential clinically significant confounding by BMI, smoking status, and ethnicity was also considered. Among 924 men, the mean age was 63.6 years (SD 8.1), and the mean PSA density was 0.13 ng/mL² (SD 0.14). The average baseline testosterone was 394 ng/dL (SD 160.4), with 29.4% (n=272) of men having a testosterone level ≤ 300 ng/dL. Low testosterone was associated with a statistically significant increased risk of GG3 progression (HR 1.61, 95% CI 1.03-2.51, p=0.04). Further, evidence suggested that low testosterone was not associated with risk of GG2 progression (HR 1.23, 95% CI 0.93-1.64, P=0.15). Findings were consistent when employing alternative cut-points for testosterone and when considering other potential confounders. These findings suggest that while low testosterone is not clearly associated with moderate progression (GG2), it may increase the risk of higher-grade "extreme" progression to GG3 or higher. Future studies should focus on prospective validation of our findings to elucidate the biological relationship between androgens and prostate cancer progression.

Prostate cancer (PCa) disproportionately affects Black men and men of low socioeconomic status, who are more likely to experience higher incidence, disease progression, and mortality. Despite this, cardiovascular disease remains a leading cause of death among men with localized disease. Therefore, lifestyle interventions, particularly diet-based, provide an opportunity to drastically improve outcomes. Little is known about how underserved men with PCa and their families perceive barriers to dietary change, including adaptation of the cardioprotective Mediterranean diet (MD). This qualitative study explored dietary knowledge, cultural influences, and willingness to participate in dietary interventions among Black and Hispanic men with localized PCa at a county hospital. Six focus groups were conducted in English or Spanish with 31 total participants (men and their partners) recruited from a safety-net county hospital. Thematic analysis was guided by the health belief model and theory of planned behavior. Four themes emerged: First, the attitudes toward healthy diet and physician advice; second, the positive and negative influence of family, friends, and culture; third, the emotional and spiritual influences on dietary behavior; and finally, structural barriers and their impact on self-efficacy. Findings underscore the critical role of buy-in from family, the importance of education and instruction, and the value of maintaining space for emotion and spirituality. These results support the development of partner-engaged, culturally tailored dietary interventions for medically underserved populations with PCa.

Background: Prostate cancer is the most common noncutaneous malignancy among men and disproportionately affects those with low socioeconomic status, particularly men from racial and ethnic minority populations. Purpose: This study describes the development of a culturally tailored Mediterranean diet intervention for medically underserved Black and Hispanic men with prostate cancer, using the Intervention Mapping Adaptation (IM ADAPT) framework. Methods: Conducted at a county safety-net hospital in a large urban area, which serves a population with high medical needs and low socioeconomic status, the project aimed to ensure the intervention was culturally relevant and evidence-based. A collaborative process was used, involving community scientists and patient stakeholders to identify dietary barriers and preferences, while existing interventions were reviewed for cultural fit. Guided by the six steps of the IM ADAPT framework, stakeholder feedback was incorporated throughout the adaptation process. The result was a culturally adapted intervention that included tailored dietary modifications, food provision strategies, and educational materials specifically designed for Black and Hispanic men. Results: Completion of the IM ADAPT steps yielded a culturally adapted Mediterranean diet intervention incorporating tailored dietary recommendations, provision of food, and distribution of educational materials designed to meet the specific needs of Black and Hispanic men. Conclusions: The IM ADAPT framework enabled the development of a culturally tailored, evidence-based dietary intervention ready for pilot testing among medically underserved men with prostate cancer. This approach may serve as a replicable model for designing interventions for other racial and ethnic minority populations affected by cancer.

PURPOSE: Men with prostate cancer face considerable cardiovascular (CV) comorbidity. Androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs) elevate this risk, yet no prostate-specific CV monitoring tools exist. Clinicians rely on general calculators such as the American Heart Association (AHA)/American College of Cardiology (ACC) atherosclerotic cardiovascular disease (ASCVD) score, which remain unvalidated in this setting. The purpose of this study is to evaluate changes in the estimated CV risk of men with prostate cancer after 6 months of hormone therapy using clinical tools established for the general population. METHODS: This was a post hoc analysis of sixty-three men with localized high-risk prostate cancer treated with 6 months of preoperative ADT plus apalutamide with or without abiraterone on a trial (ClinicalTrials.gov identifier: NCT03279250 ). ASCVD risk and metabolic syndrome (MetS) Z scores were calculated at baseline and the end of treatment using AHA/ACC and MetS calculators. RESULTS: After 6 months of ADT plus ARPI, the median ASCVD risk score increased modestly (+0.95), with 21% exhibiting a clinically significant increase (≥2.5%). This was primarily driven by increases in total cholesterol (median, 182-211) and low-density lipoprotein (median, 101-122), whereas blood pressure did not have a clinically significant change. Five patients experienced a major adverse CV event, yet only one had a clinically significant increase in ASCVD risk score. Only 28% of patients experienced an increase in MetS risk. CONCLUSION: After 6 months of ADT plus ARPI, men with prostate cancer showed worsening lipid profiles and 21% had worsening of their CV risk based on general population tools. These findings highlight the unmet need to develop prostate cancer–specific CV risk assessment tools.

Purpose: To determine the association of grade group (GG) 1 core positivity with rates of adverse pathology in intermediate-risk prostate cancer, hypothesizing that inclusion of GG1 core positivity in National Comprehensive Cancer Network (NCCN)–based stratification is not associated with rates of adverse pathology at the time of surgery. We additionally explored use of targeted biopsy results from MRI-detected lesions in improving risk stratification. Methods: We included 307 fusion biopsy patients with intermediate risk disease who underwent radical prostatectomy. Modified intermediate-risk disease, as determined by biopsy, was defined using the same criteria as NCCN stratification, with the exception that GG1 positive cores were not counted as part of the core-positivity equation. We additionally evaluated a novel classification scheme based on MRI-visible presence of GG3 disease using data from targeted fusion biopsy. Results: Using current criteria, 144 patients (46.9%) had favorable risk disease, while 175 (57%) did with modified criteria, representing a change in 31 patients (19%). AUC for prediction of adverse pathology using traditional criteria was 0.552 and 0.551 using modified criteria (P = .97). AUC for predicting adverse pathology when stratifying those men with GG3 disease and/or a total MRI-visible GG2 or GG3 tumor volume of 11.5 mm or higher as unfavorable had an AUC of 0.611 (P = .048). Conclusions: Inclusion of GG1 core positivity in the determination of unfavorable disease stratification is not associated with rate of adverse pathology. Inclusion of MRI-visible tumor grade and volume data may improve risk stratification.

Active surveillance (AS) is widely accepted for select patients with low-risk or favorable intermediate-risk prostate cancer. A confirmatory biopsy, commonly performed with MRI-ultrasound fusion (MRGBx) that combines targeted (TBx) and systematic (SBx) sampling, is recommended by most guidelines. However, as multiparametric MRI gains traction beyond academic centers, men increasingly present having already undergone an initial MRGBx at an outside institution (OSI). The necessity of confirmatory MRGBx for these patients remains uncertain. We retrospectively examined a prospectively maintained registry of men who underwent MRGBx (Artemis, Eigen) at a single tertiary center (2014-2024). Eligible patients had an initial MRGBx and then returned for confirmatory MRGBx within 2 years. Patients were stratified by initial MRGBx location: in-house vs OSI. A total of 64 patients met inclusion criteria (26 in-house, 38 OSI). Overall, 48% were upgraded on confirmatory MRGBx, with 14% upgraded to GG3 or higher. The upgrading rate was 54% for the in-house group vs 45% for the OSI group (P = .6). Confirmatory biopsy led to a management change in 64% of patients. Our study provides evidence that confirmatory MRGBx remains important for patients on AS regardless of whether the initial MRGBx was performed in-house or at an OSI. Even after an initial MRI-fusion biopsy, 48% of all patients were upgraded on confirmatory testing, often prompting a management change. The inclusion of both targeted and systematic samples proved important, as some clinically significant upgrades were identified only through systematic sampling.