High-risk Men Research Articles

Enhancing Early Detection of Prostate Cancer Using PSA-Guided Screening in High-Risk Men Under 50

Abstract Background Prostate Cancer remains a significant global public health concern. It is the most common cancer and the second leading cause of cancer death among men in the United States. Current guidelines, including those by the USPSTF, ACS and ASCO offer varying recommendations on PSA screening. Present clinical practice, primarily targeting men aged 50-69. Our study aimed to assess the feasibility and validity of using PSA for targeted screening in men under 50 who are at high risk, enhancing early detection of prostate cancer. Methods This retrospective analysis utilized data from our hospital’s prostate cancer screening program collected from 2022 to 2023, including104 individuals under 50. Participants were categorized based on PSA levels 4-10 ng/mL (n=71) and over10 ng/mL (n=33). We analyzed the number of cases diagnosed with prostate cancer and the correlation with PSA levels, Gleason Scores (GS), family history, and ethnicity/race. Results In the104 participants, 88 of them were diagnosed with prostate cancer, highlighting an 84.6% detection rate. Among PSA levels 4-10 ng/mL group, 36 out of 43 White or Caucasian and 13 out of 13 Black or African American men were identified as GS 6-10. In the group PSA over 10 ng/mL, 18 White or Caucasian and 6 Black or African American individuals with more aggressive disease (GS 6-10). Importantly, a substantial fraction of these cases had a first-degree relative with prostate cancer, emphasizing the influence of family history on PSA screening decision. Conclusion Our findings suggest that PSA-guided screening in men under 50 at high risk can enhance the early detection of prostate cancer. The significant presence of intermediate-risk prostate cancer (GS 6 or 7) in populations at higher risk due to ethnicity/race and family history. Our study highlights the potential benefits of revisiting current screening guidelines to lower the age threshold for high-risk populations.

B-321 Enhancing Early Detection of Prostate Cancer Using PSA-Guided Screening in High-Risk Men Under 50

Abstract Background Prostate Cancer remains a significant global public health concern. It is the most common cancer and the second leading cause of cancer death among men in the United States. Current guidelines, including those by the USPSTF, ACS and ASCO offer varying recommendations on PSA screening. Present clinical practice, primarily targeting men aged 50-69. Our study aimed to assess the feasibility and validity of using PSA for targeted screening in men under 50 who are at high risk, enhancing early detection of prostate cancer. Methods This retrospective analysis utilized data from our hospital's prostate cancer screening program collected from 2022 to 2023, including104 individuals under 50. Participants were categorized based on PSA levels 4-10 ng/mL (n=71) and over10 ng/mL (n=33). We analyzed the number of cases diagnosed with prostate cancer and the correlation with PSA levels, Gleason Scores (GS), family history, and ethnicity/race. Results In the104 participants, 88 of them were diagnosed with prostate cancer, highlighting an 84.6% detection rate. Among PSA levels 4-10 ng/mL group, 36 out of 43 White or Caucasian and 13 out of 13 Black or African American men were identified as GS 6-10. In the group PSA over 10 ng/mL, 18 White or Caucasian and 6 Black or African American individuals with more aggressive disease (GS 6-10). Importantly, a substantial fraction of these cases had a first-degree relative with prostate cancer, emphasizing the influence of family history on PSA screening decision. Conclusions Our findings suggest that PSA-guided screening in men under 50 at high risk can enhance the early detection of prostate cancer. The significant presence of intermediate-risk prostate cancer (GS 6 or 7) in populations at higher risk due to ethnicity/race and family history. Our study highlights the potential benefits of revisiting current screening guidelines to lower the age threshold for high-risk populations.

Alcohol Consumption Patterns and Mortality Among Older Adults With Health-Related or Socioeconomic Risk Factors

Alcohol consumption is a leading cause of morbidity and mortality that may be more important in older adults with socioeconomic or health-related risk factors. To examine the association of alcohol consumption patterns with 12-year mortality and its modification by health-related or socioeconomic risk factors. This prospective cohort study used data from the UK Biobank, a population-based cohort. Participants were current drinkers aged 60 years or older. Data were analyzed from September 2023 to May 2024. According to their mean alcohol intake in grams per day, participants' drinking patterns were classified as occasional: ≤2.86 g/d), low risk (men: >2.86-20.00 g/d; women: >2.86-10.00 g/d), moderate risk (men: >20.00-40.00 g/d; women: >10.00-20.00 g/d) and high risk (men: >40.00 g/d; women: >20.00 g/d). Health-related risk factors were assessed with the frailty index, and socioeconomic risk factors were assessed with the Townsend deprivation index. All-cause and cause-specific mortality were obtained from death certificates held by the national registries. Analyses excluded deaths in the first 2 years of follow-up and adjusted for potential confounders, including drinking patterns and preferences. A total of 135 103 participants (median [IQR] age, 64.0 [62.0-67.0] years; 67 693 [50.1%] women) were included. In the total analytical sample, compared with occasional drinking, high-risk drinking was associated with higher all-cause (hazard ratio [HR], 1.33; 95% CI, 1.24-1.42), cancer (HR, 1.39; 95% CI, 1.26-1.53), and cardiovascular (HR, 1.21; 95% CI, 1.04-1.41) mortality; moderate-risk drinking was associated with higher all-cause (HR, 1.10; 95% CI, 1.03-1.18) and cancer (HR, 1.15; 95% CI, 1.05-1.27) mortality, and low-risk drinking was associated with higher cancer mortality (HR, 1.11; 95% CI, 1.01-1.22). While no associations were found for low- or moderate-risk drinking patterns vs occasional drinking among individuals without socioeconomic or health-related risk factors, low-risk drinking was associated with higher cancer mortality (HR, 1.15; 95% CI, 1.01-1.30) and moderate-risk drinking with higher all-cause (HR, 1.10; 95% CI, 1.01-1.19) and cancer (HR, 1.19; 95% CI, 1.05-1.35) mortality among those with health-related risk factors; low-risk and moderate-risk drinking patterns were associated with higher mortality from all causes (low risk: HR, 1.14; 95% CI, 1.01-1.28; moderate risk: HR, 1.17; 95% CI, 1.03-1.32) and cancer (low risk: HR, 1.25; 95% CI, 1.04-1.50; moderate risk: HR, 1.36; 95% CI, 1.13-1.63) among those with socioeconomic risk factors. Wine preference (>80% of alcohol from wine) and drinking with meals showed small protective associations with mortality, especially from cancer, but only in drinkers with socioeconomic or health-related risk factors and was associated with attenuating the excess mortality associated with high-, moderate- and even low-risk drinking. In this cohort study of older drinkers from the UK, even low-risk drinking was associated with higher mortality among older adults with health-related or socioeconomic risk factors. The attenuation of mortality observed for wine preference and drinking only during meals requires further investigation, as it may mostly reflect the effect of healthier lifestyles, slower alcohol absorption, or nonalcoholic components of beverages.

Healthcare Appointments as Commitment Devices

Abstract We show that ordinary appointments can act as effective substitutes for hard commitment devices and increase demand for a critical healthcare service, particularly among those with self-control problems. We show this using an experiment that randomly offered HIV testing appointments and hard commitment devices to high-risk men in Malawi. Appointments more than double testing rates, with effects concentrated among those who demand commitment. In contrast, most men who take up hard commitments lose their investments. Appointments overcome commitment problems without the potential drawback of commitment failure, and have the potential to increase demand for healthcare in the developing world.

Sex-based utilization of guideline recommended statin therapy and cardiovascular disease outcomes: Data from a multisite healthcare network primary prevention cohort

BackgroundIn the US, women have similar cardiovascular death rates as men. However, less is known about sex differences in statin use for primary prevention and associated atherosclerotic cardiovascular disease (ASCVD) outcomes. MethodsStatin prescriptions using electronic health records were examined in patients without ASCVD (myocardial infarction (MI), revascularization or ischemic stroke) between 2013 and 2019. Guideline-directed statin intensity (GDSI) at index (at least moderate intensity, defined per pooled-cohort equation) and follow-up visits were compared between sexes across ASCVD risk groups, defined by the pooled-cohort equation. Cox regression hazard ratios were calculated for statin use and outcomes (myocardial infarction, stroke/transient ischemic attack (TIA), and all-cause mortality) stratified by sex. Interaction terms (statin and sex) were applied. ResultsAmong 282,298 patients, (mean age ∼ 50 years) 17.1 % women and 19.5 % men were prescribed any statin at index visit. Time to GDSI was similar between sexes, but the proportion of high-risk women on GDSI at follow-up were lower compared to high-risk men (2-years: 27.7 vs 32.0 %, and 5-years: 47.2 vs 55.2 %, p < 0.05). When compared to GDSI, no statin use was associated with higher risk of MI and ischemic stroke/TIA among both sexes. High-risk women on GDSI had a lower risk of mortality (HR=1.39 [1.22–1.59]) vs. men (HR=1.67 [1.50–1.86]) of similar risk (p value interaction=0.004). ConclusionIn a large contemporary healthcare system, there was underutilization of statins across both sexes in primary prevention. High-risk women were less likely to remain on GDSI compared to high-risk men. GDSI significantly improved the survival in both sexes regardless of ASCVD risk group. Future strategies to ensure continued use of GDSI, specifically among women, should be explored.

Abstract 819: Feasibility of patient-centered home care (PCHC) to reduce disparities in high-risk black men with advanced prostate cancer

Abstract The objective of our study is to evaluate the feasibility, acceptance, and impact of patient-centered home care (PCHC) on patient reported outcomes (PROs) and health-related quality of life (HQoL) of black men with advanced prostate cancer (CaP). Meeting patients where they are and offering treatment in or closer to their homes reduce psychological distress and increase treatment compliance, especially for disadvantaged patients in rural areas, those on low incomes, with poor access to transport, elderly and people with disabilities. In 2023, Mayo Clinic has developed the Cancer Care Beyond Walls (CCBW) program, a cancer care delivery model that integrates virtual with in facility treatment and provides a package of care to support administration of cancer-directed therapy (chemotherapy, immunotherapy, hormonal therapy) and/or supportive care in the patients’ homes. Our study will assess if patients and families are comfortable with cancer therapy at home, what factors influences their decision, and use this data to inform our understanding of the proportion of the black men with advanced CaP who would be willing to receive and would benefit from this level of care at home. Patients with advanced CaP from our practice requiring active anti-cancer therapy are administered a brief questionnaire regarding preference for location of therapy at the infusion center or in the home, with perceived difficulties and advantages of each approach. A focus group session with prostate cancer survivor advocates is also conducted to capture patients’ thoughts, feelings, attitudes, and questions towards cancer treatments being administered at home versus a hospital setting. In addition, we are conducting an observational study of 20 patients with advanced prostate cancer receiving supportive care/symptom management and/or anti-cancer therapy in the home as part of the Mayo Clinic CCBW Program to assess the safety of cancer directed therapy when administered at home by a home health provider with remote patient monitoring and command center support, and establish the impact of home cancer treatment administration on patient-reported function and global health/quality of life, patient-reported symptoms, clinical outcomes, and cost of care. Successful completion of the project will deliver data on patient understanding and acceptability of cancer care at home, strategies for overcoming barriers to care for underserved communities, and the foundation from which we discover, translate and apply new knowledge in administering personalized care to vulnerable populations. Citation Format: Roxana S. Dronca, Folakemi Odedina, Che Ngufor, Kimlin Ashing, Ernest Kaninjing, Solomon Rotimi. Feasibility of patient-centered home care (PCHC) to reduce disparities in high-risk black men with advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 819.

Extragenital Sexually Transmitted Infections Among High-Risk Men Who Have Sex With Men in Johannesburg, South Africa.

In South Africa, extragenital etiological sexually transmitted infection (STI) screening among men who have sex with men (MSM) is not routinely available. We aimed to determine the prevalence of STI pathogens at rectal and pharyngeal sites, syphilis seroprevalence, and associated risk factors among a selection of high-risk MSM without symptomatic urethritis attending a men's health clinic in Johannesburg, South Africa. A cross-sectional study was conducted in 2022. Enrolled clients self-reported demographic, sexual behavioral risks, and clinical information. Client or clinician-collected rectal and pharyngeal swabs were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis. C. trachomatis-positive rectal samples were reflex tested for lymphogranuloma venereum. Blood specimens were screened for syphilis. Univariate and multivariate regression models were used to determine factors independently associated with the presence of an extragenital STI or syphilis. Among the 97 participants (median age, 29 years), 24.7% had an extragenital STI and 9.4% had high nontreponemal antibody titers (rapid plasma reagin ≥1:16). Rectal STIs were detected in 26.4% participants: N. gonorrhoeae (14.3%), C. trachomatis (9.9%), and M. genitalium (5.5%). Pharyngeal STIs were less prevalent (4.1%). Overall, the prevalence of any STI was 41%. Sex under the influence of drugs (adjusted odds ratio, 4.94; 95% confidence interval, 1.56-15.69) and engaging in condomless receptive anal intercourse with a casual partner (adjusted odds ratio, 8.36; 95% confidence interval, 1.73-40.28) were independent risk factors for having an extragenital STI. The high burden of extragenital STIs and active syphilis in asymptomatic MSM underscores the importance of routine etiological screening in this key population, as the syndromic approach would not enable detection or treatment of these infections.

A Neuro-Influence Experiment to Evaluate the Persuasiveness of Pre-Exposure Prophylaxis Promotion Messages Among Men Who Have Sex With Men: Protocol for a Randomized Controlled Trial.

Pre-exposure prophylaxis (PrEP) is recommended by the US Centers for Disease Control and Prevention, but behavioral factors limit uptake, especially among men who have sex with men. A better understanding of how humans cognitively process information may inform health message development to promote PrEP uptake. This paper is informed by the neuroscience of persuasion and influence and describes the protocol of a neuro-influence experiment using functional near-infrared spectroscopy (fNIRS) to evaluate the persuasiveness of PrEP promotion messages among men who have sex with men in Baltimore, Maryland. We will conduct a randomized controlled trial using fNIRS to measure brain activation among 60 participants viewing PrEP promotion messages either developed through a crowdsourcing open contest implemented by the study team or developed with a traditional social marketing approach. We will evaluate the effectiveness of PrEP promotion messages by assessing brain activation in the regions associated with persuasion and changes in PrEP willingness, behavioral intention, initiation, and action between the 2 groups. This study is funded by the National Institutes of Health (National Institute of Mental Health: R34MH116725). Participant recruitment and data collection were completed in October 2023. The first results are expected to be submitted for publication in 2024. In addition to providing insight into the effectiveness of PrEP promotion messages, this study will examine the feasibility, acceptability, and utility of neuroimaging techniques to evaluate PrEP promotion messages for high-risk men who have sex with men. The findings can also demonstrate the utility of fNIRS as a tool for preproduct testing of health campaigns and enable the public health community to deliver more effective messages to improve health outcomes. DERR1-10.2196/52546.

Cognitive Behavioral Therapy Reduces Crime and Violence over Ten Years: Experimental Evidence

Several small, short-term, or nonexperimental studies show that cognitive behavioral–informed interventions reduce antisocial behaviors over one to two years, but persistence research is rare. We followed 999 high-risk men in Liberia ten years after randomization into eight weeks of low-cost, nonspecialist-led therapy; $200 cash; both; or neither. A decade later, antisocial behaviors (such as robbery and drug selling) fell 0.2 standard deviations from therapy alone—significantly greater than the one-year impacts. Meanwhile, men who received therapy plus cash were 0.25 standard deviations less antisocial—similar to one-year results. In both cases, impacts were concentrated in men exhibiting highest baseline risk. (JEL D91, K42, O15, O17)

Validation of a Genomic Classifier in the NRG Oncology/RTOG 0521 Phase III Trial of Docetaxel with Androgen Suppression and Radiotherapy for Localized High-Risk Prostate Cancer

Decipher is a prognostic genomic classifier (GC) validated in several prospective NRG Oncology Phase III trials. Herein, we validate the GC in pre-treatment biopsy samples for risk stratification in a cohort of high-risk men treated with definitive radiotherapy and androgen suppression with or without docetaxel chemotherapy. As per a pre-specified and approved NCI analysis plan (Navigator #1061), we obtained available formalin-fixed paraffin-embedded tissue from biopsy specimens from the NRG biobank from patients enrolled on the NRG/RTOG 0521 randomized phase III trial. After central review, the highest-grade tumors were profiled on clinical-grade whole-transcriptome arrays (Veracyte, San Diego, CA) and GC scores were obtained. Pre-specified categorical GC scores, adjusted for archival tissue analysis, were used to define higher (>0.46) and lower (≤0.46) risk groups. The primary objective was to validate the independent prognostic ability of GC for metastasis-free survival (MFS) with Cox multivariable analyses (MVA). Samples were obtained from 283 consented, evaluable patients with tissue (50% of trial) yielding 183 (65%) GC scores that passed quality metrics, 91 from control and 92 from the interventional arm. Median age was 66 years, median PSA was 19.3 ng/uL (IQR: 8.1-41.4), 81% had clinical stage ≥T2 and 80% had Gleason score ≥8 (47% ≥9). Median GC score was 0.55 (IQR: 0.38-0.78) and overall the arms were balanced for key covariates. With a median follow-up of 9.9 years (IQR: 9.3, 10.7), 67 MFS events including 34 distant metastases (DM) were observed. On MVA, only the GC (per 0.1 unit) was independently associated with MFS (HR 1.12, 95% CI 1.01-1.25) as well as DM (sHR 1.22, 95% CI 1.06-1.41), whereas the 4 pre-defined trial risk groups used for stratification (based on Gleason score, T-stage and PSA), randomization and patient age were not. For categorical GC, on MVA, higher-risk GC patients (65%) had worse DM (sHR 2.82, 95% CI 1.1-7.3) compared to those with lower GC. Cumulative incidence of DM at 10-years was 27% for higher GC vs 9% (95% CI 7-18%) for lower GC. No biomarker-by-treatment interaction with GC and the addition of docetaxel was detected. In pre-treatment biopsy samples from a randomized Phase 3 trial cohort, GC demonstrated its ability to further risk stratify clinically high-risk men demonstrating an independent association of GC score with DM and MFS. High-risk prostate cancer is a heterogeneous disease state and GC can improve risk stratification to help personalize shared decision-making. NRG-GU009/PREDICT-RT (NCT04513717) aims to determine the optimal therapy based on GC score for high-risk prostate cancer.

Utilization of Radical Prostatectomy vs. Radiation Therapy for Gleason Grade Group 5 Prostate Cancer before and after USPSTF Grade D Recommendation against Prostate-Specific Antigen Screening in 2012

The 2012 United States Preventive Services Task Force (USPSTF) Grade D recommendation against prostate-specific antigen (PSA) screening has resulted in a shift to higher-stage prostate cancer (PC) at diagnosis. While incidence of low-risk prostate cancer has declined, more men are diagnosed with high-risk disease, and multimodal treatment is often required. The impact of this epidemiologic shift on practice patterns, specifically radical prostatectomy (RP) versus definitive radiation therapy (RT), for men with localized PC at high risk of recurrence is unknown. Herein, we evaluate the utilization of RP versus RT in the United States for Gleason grade group 5 (GG5) prostate cancer before and after 2012. We identified 34,011 men with localized GG5 PC treated with (1) RP or (2) RT plus androgen deprivation therapy (ADT) between 2004 and 2017 in the National Cancer Database. We excluded those who were clinically node-positive, had metastatic disease, or received chemotherapy or palliative-intent treatment. Chi-square was used to compare the relative use of RP and RT before versus after January 1, 2012, corresponding to the year of USPSTF recommendation against PSA screening. Annual use of RP versus RT from 2004 to 2017 was compared in academic and non-academic centers using Cochran-Armitage test for trend. Joinpoint regression assessed if 2012 was significant for inflection of crude rates of RP. Finally, we modeled the effect of treatment year (i.e., 2012-2017 versus 2004-2011) on use of RP using multivariable logistic regression. Sensitivity analysis tested an interaction term for facility type (i.e., academic versus community). Tests were two-sided with a 0.05 level of significance. Of the eligible men, 10,745 (31.6%) had T3-T4 disease. Between 2004 and 2011, 36.5% (n = 5,483) underwent RP; between 2012 and 2017, 42.3% (n = 8,034) underwent RP (p = .02). Across all centers, use of RP increased from 31% to 41% (p for trend <.001). In academic centers, use of RP increased from 32% to 44% (p for trend <.001); in community centers, use of RP increased from 30% to 39% (p for trend <.001). 2012 was associated with significant inflection for increase in RP use in all centers. On multivariable analysis, there was an increased odds of receiving RP after 2012 (adjusted OR 1.34, 95% CI 1.28-1.40, p<.001). No differential effect by facility type was observed (p = .15). Utilization of RP for GG5 PC has significantly increased in the United States over the past decade, particularly after the USPSTF Grade D recommendation against PSA screening in 2012. It remains unknown whether oncologic or functional outcomes may be compromised in this group of high-risk men, many of whom require post-prostatectomy RT and/or ADT. While historically rare, prospective comparison of RP versus RT+ADT for GG5 PC may be helpful given the evolving epidemiology of localized PC.

Sex-Specific Associations of Obstructive Sleep Apnea Risk With Patient Characteristics and Functional Outcomes After Acute Myocardial Infarction: Evidence From the VIRGO Study.

Background Though associations between obstructive sleep apnea (OSA) and cardiovascular outcomes are well described, limited data exist regarding the impact of OSA on sex-specific outcomes after acute myocardial infarction (AMI). Methods and Results The VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study enrolled 3572 adults aged 18 to 55 years with AMI from the United States and Spain during 2008 to 2012. We included patients for whom the Berlin Questionnaire for OSA was scored at the time of AMI admission (3141; 2105 women, 1036 men). We examined the sex-specific association between baseline OSA risk with functional outcomes including health status and depressive symptoms at 1 and 12 months after AMI. Among both groups, 49% of patients were at high risk for OSA (1040 women; 509 men), but only 4.7% (148) of patients had a diagnosed history of OSA. Though patients with a high OSA risk reported worse physical and mental health status and depression than low-risk patients in both sexes, the difference in these functional outcomes was wider in women than men. Moreover, women with a high OSA risk had worse health status, depression, and quality of life than high-risk men, both at baseline and at 1 and 12 months after AMI. Conclusions Young women with a high OSA risk have poorer health status and more depressive symptoms than men at the time of AMI, which may place them at higher risk of poorer health outcomes over the year following the AMI. Further, the majority of patients at high risk of OSA are undiagnosed at the time of presentation of AMI.

European Association of Urology Biochemical Recurrence Risk Classification as a Decision Tool for Salvage Radiotherapy—A Multicenter Study

BackgroundThe European Association of Urology (EAU) has proposed a risk stratification for patients harboring biochemical recurrence (BCR) after radical prostatectomy (RP). ObjectiveTo assess whether this risk stratification helps in choosing patients for salvage radiotherapy (SRT). Design, setting, and participantsAnalyses of 2379 patients who developed BCR after RP (1989–2020), within ten European high-volume centers, were conducted. Early and late SRT were defined as SRT delivered at prostate-specific antigen values <0.5 and ≥0.5 ng/ml, respectively. Outcome measurements and statistical analysisMultivariable Cox models tested the effect of SRT versus no SRT on death and cancer-specific death. The Simon-Makuch method tested for survival differences within each risk group. Results and limitationsOverall, 805 and 1574 patients were classified as having EAU low- and high-risk BCR. The median follow-up was 54 mo after BCR for survivors. For low-risk BCR, 12-yr overall survival was 87% versus 78% (p = 0.2) and cancer-specific survival was 100% versus 96% (p = 0.2) for early versus no SRT. For high-risk BCR, 12-yr overall survival was 81% versus 66% (p < 0.001) and cancer-specific survival was 98% versus 82% (p < 0.001) for early versus no SRT. In multivariable analyses, early SRT decreased the risk for death (hazard ratio [HR]: 0.55, p < 0.01) and cancer-specific death (HR: 0.08, p < 0.001). Late SRT was a predictor of cancer-specific death (HR: 0.17, p < 0.01) but not death (p = 0.1). ConclusionsImproved survival was recorded within the high-risk BCR group for patients treated with early SRT compared with those under observation. Our results suggest recommending early SRT for high-risk BCR men. Conversely, surveillance might be suitable for low-risk BCR, since only nine patients with low-risk BCR died from prostate cancer during follow-up. Patient summaryThe impact of salvage radiotherapy (SRT) on cancer-specific outcomes stratified according to the European Association of Urology biochemical recurrence (BCR) risk classification was assessed. While men with high-risk BCR should be offered SRT, surveillance might be a suitable option for those with low-risk BCR.

Human Papillomavirus (HPV) Infection Awareness and Vaccine Acceptance among High-risk Men in Perak, Malaysia

Human Papillomavirus (HPV) causes anogenital warts and malignancies in both men and women. In Malaysia, HPV vaccine is currently available for young girls while men are expected to benefit from herd immunity. However, high-risk men e.g. those who practice homo and bisexual activities may not benefit from this herd immunity. Hence, it is important to assess their awareness of HPV and vaccine acceptance for appropriate counselling on vaccination. The objective of this study was to assess HPV and vaccine awareness, its acceptance, facilitators, and barriers among high-risk men. Men between the ages of 18 to 45 years from the Human Immunodeficiency Virus (HIV) and Sexually transmitted Disease (STD) clinics of a tertiary hospital and six Health Clinics in Perak were invited to participate. HPV awareness, vaccine acceptance, facilitators, and barriers to vaccination were assessed using a self-administered questionnaire. A total of 194 men participated in this study. Only a small percentage of them (35.6%) were aware about HPV and HPV vaccine (21.6%). However, most of them (87.1%) were willing to accept vaccination after receiving the necessary information. Common facilitators for vaccination were doctor’s recommendation (94.3%) government approval (84.5%) and free vaccination (82%) while the most common barriers were cost (68.0%) and side effects of the vaccine (49.5%). Our study showed low-level HPV and vaccine awareness among high-risk men. However, majority of them were willing to accept HPV vaccination. Recommendations from doctors and government approval were the two most important facilitators while cost and side effects were the common barriers to HPV vaccination.

Factors associated with willingness to take Pre-Exposure Prophylaxis (PrEP) among high-risk adolescent boys and young men in Masese fishing community, Uganda.

Pre-Exposure Prophylaxis (PrEP) is a known HIV prevention strategy for high-risk populations however, some high-risk communities have not yet fully embraced it. We sought to determine willingness to take PrEP and the associated factors among high-risk adolescent boys and young men (ABYM) in Masese fishing community, Jinja district, Eastern Uganda. We conducted a cross-sectional study, between October and November 2020, using a semi-structured questionnaire among ABYM aged 10-24 years in Masese fishing community, Eastern Uganda. We surveyed 479 participants, who had two or more sexual partners with inconsistent or no condom use. We carried out modified Poisson regression analysis to determine factors associated with willingness to take PrEP.Of 479 high-risk ABYM, 86.4% (n = 414) were willing to take PrEP. Confidence in PrEP safety (adj.PR = 1.56; 95%CI: 1.55, 2.24), availability of PrEP in areas easily accessible by ABYM (adj.PR = 1.40; 95%CI: 1.25, 1.57), and perceiving oneself as being at a very high risk of HIV infection (adj.PR = 1.11; 95%CI: 1.03, 1.20) were positively associated with willingness to take PrEP. On the other hand, being unmarried (adj.PR = 0.92; 95%CI: 0.87, 0.98) and earning more than USD 27 a month (adj.PR = 0.92; 95%CI: 0.87, 0.97) were negatively associated with willingness to take PrEP. There was high willingness to take PrEP among adolescent boys and young men in Masese fishing community. Confidence in PrEP safety, access to PrEP in their community and self-perception to be at high risk for HIV acquisition had a positive bearing on willingness to take PrEP while being unmarried and earning more than USD27 had a negative bearing on willingness to take PrEP. These findings suggest a need for target-specific interventions for unmarried men and those earning >USD27.

Pre-exposure prophylaxis uptake for high-risk men who have sex with men in China: a multi-city cross-sectional survey

BackgroundPre-exposure prophylaxis (PrEP) is a proven biomedical strategy to prevent HIV transmission among men who have sex with men (MSM). Despite oral PrEP is safe and effective in MSM, the use of PrEP has been discouraging, especially in high-risk MSM. And there are no relevant studies showing the use of PrEP in high-risk MSM. The purpose of this study was to get the rate of PrEP use and the factors influencing PrEP use among high-risk MSM.MethodsA cross-sectional study was conducted through an electronic questionnaire on the “i guardian Platform”, and “snowballing” method was used to recruit MSM in six cities in China, including Beijing, Shenzhen, Chengdu, Changsha, Jinan and Nanjing in China, from January to April 2021. Univariate and multivariate logistic regression analysis were used to analyze the factors associated with the use of PrEP among high-risk MSM who had heard about PrEP.ResultsAmong the 1865 high-risk MSM who had heard of PrEP, the rates of those who were willing to use PrEP, had knowledge awareness of PrEP, and had used PrEP were 96.7%, 24.7%, and 22.4%, respectively. Multivariate logistic regression analysis of PrEP use in high-risk MSM showed that more PrEP was used by those who were 26 years or older (OR = 1.86, 95%CI 1.17 ~ 2.99), had master degree or above (OR = 2.37, 95% CI 1.21 ~ 4.72), had unstable work (OR = 1.86, 95% CI 1.16 ~ 2.96), had tested five or more HIV times in the past year (OR = 3.09, 95% CI 1.65 ~ 6.04), had consulted PrEP (OR = 22.05, 95% CI 14.87 ~ 33.91) and had PrEP knowledge awareness (OR = 1.90, 95% CI 1.41 ~ 2.55) (P < 0.05).ConclusionsThe rate of PrEP use in high-risk MSM was relatively low. PrEP was used more by high-risk MSM with unstable jobs, higher education, frequent HIV testing, and PrEP counseling. Public education on PrEP for MSM should continue to be enhanced to help them use PrEP in a timely and accurate manner.

Relationship between androgen biosynthesis linked to 3βHSD1 and resistance to radiotherapy: A germline biomarker for combined androgen blockade with radiation in high-risk prostate cancer.

e17084 Background: Around 50% of men with advanced prostate cancer (PCa) have at least one germline copy of the adrenal-permissive (1245C) HSD3B1 allele. This allele leads to higher levels of the steroid biosynthesis enzyme, 3β-hydroxysteroid dehydrogenase (3βHSD1). Inheriting this allele is linked to worse outcomes in men with advanced PCa. To determine if (1245C) HSD3B1 could be causing early resistance to combined androgen deprivation and radiotherapy in localized PCa, we studied its role in modulating radioresistance. Methods: PCa cell lines were used to investigate the reciprocal effects of 3βHSD1 knockdown and overexpression in intrinsically high and low 3βHSD1 lines, respectively. PCa xenografts were used to confirm the results in vivo. The connection between androgen receptor (AR) expression and elevated DNA Damage Response (DDR) gene expression was validated using transcriptomic data from 680 radical prostatectomy specimens The ability of enzalutamide, a non-steroidal anti-androgen, to restore radiosensitivity in 1245C expressing lines was interrogated in vitro and in vivo. Results: 1245C HSD3B1 expressing PCa lines displayed increased clonogenic survival after ionizing radiation. Effects were dependent on the 3βHSD1 substrate, DHEA, confirming intratumoral androgen metabolism was required for radioresistance. Resistant lines showed enhanced DNA double-strand break (DSB) repair and heightened DDR gene expression. PCa xenografts with 1245C HSD3B1 were similarly more resistant to radiation using murine models that faithfully mimic human adrenal physiology. A correlation between AR expression and increased DDR gene expression was confirmed in 680 patient samples. Enzalutamide pretreatment resulted in a decrease in DSB repair ability and re-sensitized 1245C HSD3B1 PCa cells to radiation. Conclusions: 1245C HSD3B1 fuels prostate cancer treatment resistance by elevating regional androgen biosynthesis from adrenal steroid precursors, leading to DDR gene overexpression and enhanced DNA DSB repair kinetics. This work supports clinical validation of biomarker informed selective intensification strategies, e.g., combined androgen blockade, for high-risk men with the 1245C HSD3B1 allele receiving curative intent radiotherapy.

Basal-luminal subtyping of localized high-risk prostate cancer and benefit of adding docetaxel to definitive radiotherapy with androgen suppression in the NRG Oncology/RTOG 0521 phase III trial.

5094 Background: In prior studies, basal vs. luminal differentiation portends differential response to a) androgen suppression (AS) duration for high-risk prostate cancer (PCa) (NRG-GU-TS006) and b) docetaxel chemotherapy (CT) and AS for metastatic hormone-sensitive disease (CHAARTED). In NRG-GU-TS006, basal tumors appeared to benefit the most from longer duration of AS while those with luminal subtype did not whereas, in CHAARTED, luminal subtype had greater benefit from addition of CT. Herein, we examined basal-luminal subtyping to predict differential response to the addition of CT in the setting of high-risk PCa treated with AS and definitive radiotherapy (AS + RT) in NRG/RTOG 0521. Methods: Per pre-specified and approved NCI analysis plan (Navigator #1061), we obtained available NRG biobank biopsy specimens from patients enrolled on the NRG/RTOG 0521 phase III trial, which randomized patients to AS + RT +/- CT. The highest-grade tumors were profiled on clinical-grade whole-transcriptome arrays (Veracyte, San Diego, CA). Basal-luminal subtypes were generated using a 215-gene PCa subtyping classifier (PSC), a second generation PAM50 basal-luminal model. Treatment effects in Luminal Proliferating (LP) and non-LP subtypes were examined with Cox (for overall survival, OS, and metastasis-free survival, MFS) and Fine &amp; Gray (for distant metastasis, DM) multivariable (MVA) models adjusted for age and trial risk stratification, as well as with restricted mean survival times (RMST). Results: Of 183 samples available for analysis (91 from control and 92 from the CT arm), 52 (28%) were classified as LP subtype. Median follow-up for OS was 9.9 years. No significant differences in clinical or pathological variables were observed between LP and non-LP subtypes. In MVA, we did not detect any significant LP subtype-by-CT treatment interaction but observed evidence of non-proportional hazards (Grambsch-Therneau test, p&lt;0.05). In unselected patients, 5- and 10-year RMST difference between the arms was 0.9 (95% CI [-1.5, 3.4], p=0.46) and 5.7 (95% CI [-2.5, 13.9], p=0.17) months of OS. Stratifying by tumor subtype, at 5 years the RMST difference in months was 3.8 (95% CI [0.3, 7.2], p=0.03) for LP and -0.2 ([-3.4, 2.9], p=0.89) for non-LP. The RMST difference in months at 10-years was 13.7 (95% CI [-0.2, 27.5], p=0.053) for LP and 2.5 ([-7.6, 12.5], p=0.63) for non-LP. Conclusions: In pre-treatment biopsy samples from a Phase 3 trial cohort of localized high-risk men, luminal-basal subtyping of tumors demonstrated differential response to docetaxel CT. Similar to results from the CHAARTED trial of metastatic disease, LP tumors may derive greater benefit from addition of CT. Validation of these findings may enable effective earlier use of CT in men with PCa.

A nomogram for predicting osteoarthritis based on serum biomarkers of bone turnover in middle age: A cross-sectional study of PTH and β-CTx.

The objective of this study was to investigate the diagnostic model of osteoarthritis by bone turnover markers in Chinese middle-aged subjects. The study was designed as a cross-sectional investigation with 305 participants aged 45 to 64. Radiographs of tibiofemoral knee joints were used for diagnose osteoarthritis. Radiographic grading, evaluated using the Kellgren and Lawrence grading scale (K-L), was scored by 2 experienced observers who were blinded to the source of subjects. An optimal model was developed by logistic regression. And the prognostic performance of the selected model was assessed by the area under the receiver operating characteristic curve. The prevalence of osteoarthritis was 52.29% (n = 137/262) in middle age. β-CTx levels tended to increase according to the K-L grades, whereas PTH levels significantly decrease. levels of 25(OH)D, β-CTx, and PTH were each significantly associated with osteoarthritis risk (P < .05). Based on the estimated parameters of the optimal model, a nomogram was constructed for predicting osteoarthritis. These data suggest that the combination of PTH and β-CTx could significantly improve the prognosis of osteoarthritis in middle age, and that the nomogram can assist primary physicians in the identification of high-risk men.

Characterization of the oral microbiota among middle-aged men with and without human papillomavirus infection

ObjectivesTo characterize the oral microbiota among middle-aged men and identify differences between men with a prevalent oral high-risk (oncogenic) HPV infection and those without. Materials and MethodsThis was a case-control study nested within a prospective screening study for HPV-related cancers among middle-aged men. 16S rRNA sequencing was used to characterize the oral microbiota and the cobas HPV Test was used to detect presence of oral high-risk HPV types. We determined the overall composition of the oral microbiota and assessed differences in relative abundance of bacterial taxa as well as alpha and beta diversity among men with a prevalent oral high-risk HPV infection compared to men who were HPV-negative. ResultsAmong 13 high-risk HPV-positive and 30 HPV-negative men, we found significant differences in beta diversity but not alpha diversity. Fretibacterium, F0058, Kingella, Treponema, and Prevotella were more abundant among the high-risk HPV-positive men while Neisseria and Lactobacillus were more abundant among the HPV-negative men. ConclusionThis study adds to the evidence that the oral microbiota varies according to oral HPV infection status and may be associated with the natural history of oral HPV infection.