Select black men are potential candidates for prostate hemi-ablation based on radical prostatectomy histopathology for intermediate-risk prostate cancer-a multicenter SEARCH cohort study.

IMPORTANCE AND OBJECTIVE: Partial gland ablation (PGA) is increasingly popular as a treatment for men with intermediate-risk prostate cancer (IR-PCa) to preserve functional outcomes while controlling their cancer. We aimed to determine the impact of race and clinical characteristics on the risk of upstaging (≥pT2c) and having adverse pathological outcomes including seminal vesicle invasion (SVI), extra prostatic extension (EPE) and lymph node invasion (LNI) at radical prostatectomy (RP) among men with IR disease eligible for PGA with hemi-ablation (HA). DESIGN: Retrospective analysis. SETTING: Multicenter. PARTICIPANTS AND MEASURES: We studied patients diagnosed with unilateral IR-PCa treated with RP between 1988 and 2020 at 9 different Veterans Affairs hospitals within the SEARCH cohort. We analyzed differences in clinicopathological characteristics and outcome variables (odds of ≥pT2c and SVI, EPE and LNI) by race using multivariable logistic regression after adjusting for covariates. RESULTS: Among 3127 patients, 33% were African American (AA) men with unilateral IR-PCa undergoing RP. Compared to non-AA men, AA individuals were younger (61 vs. 65 years, p < 0.001), presented with a higher prostate specific antigen (PSA) category (≥10 ng/ml; 34 vs. 26%, p < 0.001), and had a lower clinical stage (p < 0.001). Among the 2,798 (89.5%) with ≥pT2c stage, AA men exhibited higher ≥ pT2c rates (93 vs. 89%, p < 0.001), primarily due to increased pT2c staging (64 vs. 57%), where upstaging beyond pT2 was lower than non-AA men (29 vs. 32%). On multivariable analysis, AA men were found to have higher odds of ≥pT2c (odds ratio [OR]: 1.39 CI, 1.02-1.88, p = 0.04), lower odds of EPE (OR: 0.73 CI, 0.58-0.91, p < 0.01) and no statistically significant associations with LNI (OR: 0.79 CI, 0.42-1.46, p = 0.45) and SVI (OR: 1 CI, 0.74-1.35, p = 0.99) compared to non-AA men. On multivariable analysis, clinical features associated with higher odds of ≥pT2c were pre-operative PSA ≥ 15 (OR = 2.07, P = 0.01) and higher number of positive cores (HPC) on biopsy (OR = 1.36, P < 0.001). Similarly, PSA ≥ 15, Gleason grade ≥3 and HPC on biopsy were associated with higher odds of SVI, EPE and LNI, respectively. CONCLUSIONS: In men with IR-PCa undergoing RP, AA men demonstrated an overall higher likelihood of ≥pT2c with lower upstaging beyond pT2, lower likelihood of EPE and no significant difference in likelihood of SVI and LNI compared to non-AA men. These findings support select AA men to be potential candidates for PGA, such as HA. Clinical factors are predictive of higher pathological stage and adverse pathological outcomes at RP and could be considered when selecting candidates for PGA.

Prostate biopsy sepsis prevention: external validation of an alcohol needle washing protocol.

PURPOSE: Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) is associated with a 1-8% risk of post-biopsy sepsis (PBS). A recent study described an isopropyl alcohol needle washing protocol that significantly decreased PBS rates. The current study examined the efficacy of this technique in our clinic population. MATERIALS AND METHODS: Data were reviewed for 1250 consecutive patients undergoing TRUS-Bx at the Charlie Norwood VA Medical Center from January 2017 to January 2023. Needle washing was adopted in February 2021. Complications occurring within 30 days after TRUS-Bx were recorded. RESULTS: There were 912 patients in group 1 (without needle washing) and 338 in group 2 (with needle washing). Groups had equivalent demographic features, and men of African descent comprised 70% of patients. Standard 12 core biopsies were done in 83% and 82% in groups 1 and 2, respectively (p = 0.788). Total complication rates were 4% and 2% in groups 1 and 2, respectively (p = 0.077). There were 13 sepsis events in group 1 (1.4%) and none in group 2 (p = 0.027). Clavien-Dindo Grade I-III complications occurred in 25 (2.7%) and 7 (2.1%) patients in groups 1 and 2, respectively (p = 0.505). Standard antibiotic prophylaxis (PO fluoroquinolone and IM gentamicin) was given in 80% and 86% of patients in groups 1 and 2, respectively (p = 0.030). Subset analysis limited to patients who received standard prophylaxis showed a significant difference in sepsis rates (1.5% vs 0%; p = 0.036). CONCLUSIONS: Adoption of isopropyl alcohol needle washing was associated with a significant decrease in PBS events.

Addressing racial disparities in prostate cancer pathology prediction models: external validation and comparison of four models of pathological outcome prediction before radical prostatectomy in the multiethnic SEARCH cohort.

BACKGROUND: Certain widely used pathological outcome prediction models that were developed in tertiary centers tend to overpredict outcomes in the community setting; thus, the Michigan Urological-Surgery Improvement Collaborative (MUSIC) model was developed in general urology practice to address this issue. Additionally, the development of these models involved a relatively small proportion of Black men, potentially compromising the accuracy of predictions in this patient group. We tested the validity of the MUSIC and three widely used nomograms to compare their overall and race-stratified predictive performance. METHODS: We extracted data from 4139 (1138 Black) men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database of the Veterans Affairs health system. The predictive performance of the MUSIC model was compared to the Memorial-Sloan Kettering (MSK), Briganti-2012, and Partin-2017 models for predicting lymph-node invasion (LNI), extra-prostatic extension (EPE), and seminal vesicle invasion (SVI). RESULTS: The median PSA of Black men was higher than White men (7.8 vs. 6.8 ng/ml), although they were younger by a median of three years and presented at a lower-stage disease. MUSIC model showed comparable discriminatory capacity (AUC:77.0%) compared to MSK (79.2%), Partin-2017 (74.6%), and Briganti-2012 (76.3%), with better calibration for LNI. AUCs for EPE and SVI were 72.7% and 76.9%, respectively, all comparable to the MSK and Partin models. LNI AUCs for Black and White men were 69.6% and 79.6%, respectively, while EPE and SVI AUCs were comparable between races. EPE and LNI had worse calibration in Black men. Decision curve analysis showed MUSIC superiority over the MSK model in predicting LNI, especially among Black men. CONCLUSION: Although the discriminatory performance of all models was comparable for each outcome, the MUSIC model exhibited superior net benefit to the MSK model in predicting LNI outcomes among Black men in the SEARCH population.

Primary Palliative Care in Urology: Quality Improvement Summit 2021-2022.

INTRODUCTION: The AUA convened a 2021-2022 Quality Improvement Summit to bring together interdisciplinary providers to inform the current state and to discuss potential strategies for integrating primary palliative care into urology practice. We hypothesized that the Summit findings would inform a scalable primary palliative care model for urology. METHODS: The 3-part summit reached a total of 160 interdisciplinary health care professionals. Webinar 1, "Building a Primary Palliative Care Model for Urology," focused on a urologist's role in palliative care. Webinar 2, "Perspectives on Increasing the Use of Palliative Care in Advanced Urologic Disease," addressed barriers to possible implementation of a primary palliative care model. The in-person Summit, "Laying the Foundation for Primary Palliative Care in Urology," focused on operationalization of primary palliative care, clinical innovations needed, and relevant metrics. RESULTS: Participants agreed that palliative care is needed early in the disease course for patients with advanced disease, including those with benign and malignant conditions. The group agreed about the important domains that should be addressed as well as the interdisciplinary providers who are best suited to address each domain. There was consensus that a primary "quarterback" was needed, encapsulated in a conceptual model-UroPal-with a urologist at the hub of care. CONCLUSIONS: The Summit provides the field of urology with a framework and specific steps that can be taken to move urology-palliative care integration forward. Urologists are uniquely positioned to provide primary palliative care for their many patients with serious illness, both in the surgical and chronic care contexts.

Do Hispanic Puerto Rican men have worse outcomes after radical prostatectomy? Results from SEARCH.

BACKGROUND: We previously reported that outcomes after radical prostatectomy (RP) were similar among non-Hispanic Black, non-Hispanic White, and Hispanic White Veterans Affairs (VA) patients. However, prostate cancer (PC) mortality in Puerto Rican Hispanics (PRH) may be higher than in other Hispanic groups. Data focused on PRH patients is sparse; thus, we tested the association between PR ethnicity and outcomes after RP. METHODS: Analysis included men in SEARCH cohort who underwent RP (1988-2020, n = 8311). PRH patients (n = 642) were treated at the PR VA, and outcomes were compared to patients treated in the Continental US regardless of race. Logistic regression was used to test the associations between PRH and PC aggressiveness, adjusting for demographic and clinicopathological features. Multivariable Cox models were used to investigate PRH versus Continental differences in biochemical recurrence (BCR), metastases, castration-resistant PC (CRPC), and PC-specific mortality (PCSM). RESULTS: Compared to Continental patients, PRH patients had lower adjusted odds of pathological grade group ≥2 (p < 0.001), lymph node metastasis (p < 0.001), and positive margins (p < 0.001). In contrast, PRH patients had higher odds of extracapsular extension (p < 0.001). In Cox models, PRH patients had a higher risk for BCR (HR = 1.27, p < 0.001), metastases (HR = 1.49, p = 0.014), CRPC (HR = 1.80, p = 0.001), and PCSM (HR = 1.74, p = 0.011). Further adjustment for extracapsular extension and other pathological variables strengthened these findings. CONCLUSIONS: In an equal access setting, PRH RP patients generally had better pathological features, but despite this, they had significantly worse post-treatment outcomes than men from the Continental US, regardless of race. The reasons for the poorer prognosis among PRH men require further research.

Contemporary risk of biochemical recurrence after radical prostatectomy in the active surveillance era.

OBJECTIVES: To assess whether contemporary risks of biochemical recurrence (BCR) after radical prostatectomy (RP) in the AS era differ from historical estimates due to changes in tumor risk case mix and improvements in risk stratification. MATERIALS AND METHODS: We sampled 6,682 men who underwent RP for clinically localized disease between 2000 and 2017 from the VA SEARCH database. Kaplan Meier analysis was used to calculate incidence of BCR before and after 2010 overall and within tumor risk subgroups. Multivariable Cox proportional hazard regression analysis including an interaction term between era and tumor risk was used to compare risk of BCR before and after 2010 overall and across tumor risk subgroups. RESULTS: About 3,492 (52%) and 3,190 (48%) men underwent RP before and after 2010, respectively. In a limited multivariable model excluding tumor risk, overall BCR risk was higher post-2010 vs. pre-2010 (HR: 1.15, 95%CI: 1.05-1.25; 40% vs 36% at 8 years post-RP). However, this effect was eliminated after correcting for tumor risk (HR: 0.95, 95%CI: 0.87-1.04), suggesting that differences in tumor risk between eras mediated the change. Yet, within tumor-risk subgroups, BCR risk was significantly lower for favorable intermediate-risk (HR: 0.76, 95%CI:0.60-0.96) and unfavorable intermediate-risk PC (HR: 0.78, 95%CI: 0.67-0.90), but significantly higher for high-risk PC (HR: 1.22, 95%CI: 1.07-1.38) in the post-2010 era. 8-year risks of BCR in the post-2010 era were 21% (95%CI: 16%-25%), 25% (95%CI: 20%-30%), 41% (95%CI: 37%-46%), and 60% (95%CI: 56%-64%) for low-, FIR-, UIR-, and high-risk disease, respectively. Limitations include limited long-term follow-up in the post-2010 subgroup. CONCLUSIONS: Overall BCR risk has increased in the AS era, driven by a higher risk case mix and increased BCR risk among high-risk patients. Physicians should quote contemporary estimates of BCR when counseling patients.

Transgender patient undergoing Rezum therapy: a case report.

Rezum is a relatively new, minimally invasive approach that utilizes vaporized water to ablate prostatic tissue surrounding the proximal urethra in patients with benign prostatic hyperplasia. However, of the many notable studies involving Rezum's effectiveness in men, none have documented use of Rezum in the transgender community. With a growing population of transgender patients in the USA, prostate treatments will be offered for transgender women on a more regular basis. To the best of our knowledge, we introduce the first case of Rezum being utilized to treat benign prostatic hyperplasia in a patient self-identifying as a woman.

Ovarian malignancy in an individual with 46,XY ovotesticular disorder of sexual development - A case report.

Disorders of sexual development (DSD) are diseases resulting from aberrations in sex chromosomes, gonadal, and internal/external genitalia development resulting in various phenotypes. Ovotesticular DSD represents a rarer entity in this classification of disorders characterized by simultaneous presence of testicular and ovarian tissue. Gonadal tumors in those with DSDs is a known risk, although ovarian masses discovered in adults with ovotesticular DSD is a rare entity and there is little literature pertaining to this population. We present a case of an incidental adnexal mass discovered in an elderly patient ultimately elucidated as a malignant ovarian mass.

A rare case of emphysematous cystitis due to Candida glabrata.

Emphysematous cystitis (EC) is a rare condition characterized by gas within the bladder wall or lumen. EC is most commonly seen in elderly women with poorly controlled diabetes mellitus (DM). Escherichia coli and Klebsiella pneumoniae are most commonly implicated. We present a 68-year-old woman with poorly controlled DM who presented with altered mental state with growth of Candida glabrata in urine and blood cultures. CT abdomen and pelvis revealed air in the bladder lumen and the extraperitoneal space. Bladder rupture was suspected and bladder decompression was managed conservatively with a foley catheter.

Late-presenting with a tumor-like mass giant cell reaction related to retropubic midurethral sling.

Stress urinary incontinence (SUI) is a condition that most commonly affects aging women. Synthetic mid-urethral slings (MUS) have become the most common surgical treatment for SUI; however, complications such as mesh erosion and dyspareunia have been reported. This case report describes an 84-year-old female who presented with a tumor-like mass giant cell reaction surrounding the MUS and the management of this mass.

The Role of Alumni Networks and Career Advising in Early Career Stability of Urologists: Results of a Multi-institutional Study.

OBJECTIVE: To characterize training program and early career factors that impact decision-making and job retention following graduation in a diverse population of urologists. MATERIALS AND METHODS: We performed a computer-based survey distributed to residency graduates from 25 urology training programs. Five focus institutions were identified with a goal >30% response rate. The survey included questions about training program specifics and post-training employment characteristics. RESULTS: We obtained 180 responses from urology residency graduates of 25 programs. Overall, 72% (N = 129) remain in their initial post-training position at a median of 6years postgraduation (Interquartile Range (IQR) 3-10). On Cox-regression analysis stronger trainee-rated formal career advising was associated with lower risk of changing jobs (HR 0.77, 0.60-0.99, P = .048). Location/proximity to family was the most consistently cited as the top reason for selecting a job (41%). Sixty-three respondents (35%) joined practices employing graduates of the same residency program. Cox regression analysis showed that joining a practice with alumni of the same program was associated with lower risk of changing jobs from one's initial post-training position (HR 0.39, 95% CI 0.17-0.91, P = .03). CONCLUSION: In this multi-institutional study of urologists, we observed a high rate of job retention out to a median of 6years following completion of training, with formal career advising and joining alumni in practice being associated with job retention. Collectively, our data highlights that training programs should emphasize advising programs and alumni networking in guiding their graduates in the job search process.

Are associations between obesity and prostate cancer outcomes following radical prostatectomy the same in smokers and non-smokers? Results from the SEARCH Cohort.

PURPOSE: Obesity and smoking have been associated with poor prostate cancer (PC) outcomes. We investigated associations between obesity and biochemical recurrence (BCR), metastasis, castrate resistant-PC (CRPC), PC-specific mortality (PCSM), and all-cause mortality (ACM) and examined if smoking modified these associations. METHODS: We analyzed SEARCH Cohort data from men undergoing RP between 1990 and 2020. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between body mass index (BMI) as a continuous variable and weight status classifications (normal: 18.5 ≤ 25 kg/m2; overweight: 25-29.9 kg/m2; obese: ≥ 30 kg/m2) and PC outcomes. RESULTS: Among 6,241 men, 1,326 (21%) were normal weight, 2,756 (44%) overweight and 2159 (35%) obese; 1,841 (30%) were never-smokers, 2,768 (44%) former and 1,632 (26%) current-smokers. Among all men, obesity was associated with non-significant increased risk of PCSM, adj-HR = 1.71; 0.98-2.98, P = 0.057, while overweight and obesity were inversely associated with ACM, adj-HR = 0.75; 0.66-0.84, P < 0.001 and adj-HR = 0.86; 0.75-0.99, P = 0.033, respectively. Other associations were null. BCR and ACM were stratified for smoking status given evidence for interactions (P = 0.048 and P = 0.054, respectively). Among current-smokers, overweight was associated with an increase in BCR (adj-HR = 1.30; 1.07-1.60, P = 0.011) and a decrease in ACM (adj-HR = 0.70; 0.58-0.84, P < 0.001). Among never-smokers, BMI (continuous) was associated with an increase in ACM (adj-HR = 1.03; 1.00-1.06, P = 0.033). CONCLUSIONS: While our results are consistent with obesity as a risk factor for PCSM, we present evidence of effect modification by smoking for BCR and ACM highlighting the importance of stratifying by smoking status to better understand associations with body weight.

Exposure to Agent Orange and Risk of Bladder Cancer Among US Veterans.

Importance: To date, limited data exist regarding the association between Agent Orange and bladder cancer, and the Institute of Medicine concluded that the association between exposure to Agent Orange and bladder cancer outcomes is an area of needed research. Objective: To examine the association between bladder cancer risk and exposure to Agent Orange among male Vietnam veterans. Design, Setting, and Participants: This nationwide Veterans Affairs (VA) retrospective cohort study assesses the association between exposure to Agent Orange and bladder cancer risk among 2 517 926 male Vietnam veterans treated in the VA Health System nationwide from January 1, 2001, to December 31, 2019. Statistical analysis was performed from December 14, 2021, to May 3, 2023. Exposure: Agent Orange. Main Outcomes and Measures: Veterans exposed to Agent Orange were matched in a 1:3 ratio to unexposed veterans on age, race and ethnicity, military branch, and year of service entry. Risk of bladder cancer was measured by incidence. Aggressiveness of bladder cancer was measured by muscle-invasion status using natural language processing. Results: Among the 2 517 926 male veterans (median age at VA entry, 60.0 years [IQR, 56.0-64.0 years]) who met inclusion criteria, there were 629 907 veterans (25.0%) with Agent Orange exposure and 1 888 019 matched veterans (75.0%) without Agent Orange exposure. Agent Orange exposure was associated with a significantly increased risk of bladder cancer, although the association was very slight (hazard ratio [HR], 1.04; 95% CI, 1.02-1.06). When stratified by median age at VA entry, Agent Orange was not associated with bladder cancer risk among veterans older than the median age but was associated with increased bladder cancer risk among veterans younger than the median age (HR, 1.07; 95% CI, 1.04-1.10). Among veterans with a diagnosis of bladder cancer, Agent Orange was associated with lower odds of muscle-invasive bladder cancer (odds ratio [OR], 0.91; 95% CI, 0.85-0.98). Conclusions and Relevance: In this cohort study among male Vietnam veterans, there was a modestly increased risk of bladder cancer-but not aggressiveness of bladder cancer-among those exposed to Agent Orange. These findings suggest an association between Agent Orange exposure and bladder cancer, although the clinical relevance of this was unclear.

Diabetes and Prostate Cancer Outcomes in Men with Nonmetastatic Castration-Resistant Prostate Cancer: Results from the SEARCH Cohort.

BACKGROUND: The prognosis of diabetic men with advanced prostate cancer is poorly understood and understudied. Hence, we studied associations between diabetes and progression to metastases, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC). METHODS: Data from men diagnosed with nmCRPC between 2000 and 2017 at 8 Veterans Affairs Health Care Centers were analyzed using Cox regression to determine HRs and 95% confidence intervals (CI) for associations between diabetes and outcomes. Men with diabetes were classified according to: (i) ICD-9/10 codes only, (ii) two HbA1c values > 6.4% (missing ICD-9/10 codes), and (iii) all diabetic men [(i) and (ii) combined]. RESULTS: Of 976 men (median age: 76 years), 304 (31%) had diabetes at nmCRPC diagnosis, of whom 51% had ICD-9/10 codes. During a median follow-up of 6.5 years, 613 men were diagnosed with metastases, and 482 PCSM and 741 ACM events occurred. In multivariable-adjusted models, ICD-9/10 code-identified diabetes was inversely associated with PCSM (HR, 0.67; 95% CI, 0.48-0.92) while diabetes identified by high HbA1c values (no ICD-9/10 codes) was associated with an increase in ACM (HR, 1.41; 95% CI, 1.16-1.72). Duration of diabetes, prior to CRPC diagnosis was inversely associated with PCSM among men identified by ICD-9/10 codes and/or HbA1c values (HR, 0.93; 95% CI, 0.88-0.98). CONCLUSIONS: In men with late-stage prostate cancer, ICD-9/10 'code-identified' diabetes is associated with better overall survival than 'undiagnosed' diabetes identified by high HbA1c values only. IMPACT: Our data suggest that better diabetes detection and management may improve survival in late-stage prostate cancer.

A modeling study to estimate prostate cancer-specific mortality on active surveillance for men with favorable intermediate-risk prostate cancer: Results from the SEARCH cohort.

PURPOSE: Limited data exist to help surgeons decide between active surveillance (AS) versus treatment for men with favorable intermediate risk (FIR) prostate cancer. To estimate the theoretical excess risk of prostate cancer-specific mortality (PCSM) with AS versus radical prostatectomy (RP), we determined the risk of PCSM in FIR men undergoing RP and modeled the PCSM risk for AS using a range of increased PSCM scenarios ranging from 1.25x to 2x higher relative to RP. MATERIALS AND METHODS: We retrospectively reviewed data from men undergoing RP from 1988 to 2017 at 8 Veterans Affairs hospitals within the SEARCH cohort. Men with FIR PC were identified using the NCCN risk criteria. Risk of PCSM at 5, 10, and 15 years after RP was estimated. Using these estimates, PCSM was then modeled for AS using a range of increased risk of PCSM relative to RP ranging from 1.25x to 2x higher. RESULTS: For the 920 FIR men identified, 5-, 10-, and 15-year survival estimates for PCSM after RP were 99.9%, 99.0%, and 97.8%, respectively. If the risk of PCSM on AS were 1.25-2x greater than RP, there would be 0.54%-2.17% excess risk of PCSM at 15 years. CONCLUSIONS: The risk of death for FIR after RP is very low. Assuming even modestly increased PCSM with AS versus RP, the excess risk of death for AS in FIR is low even up to 15 years. These data support the consideration of AS as a relatively safe alternative to RP in FIR men, though prospective randomized trials are needed to validate these findings.

Time from biopsy to radical prostatectomy by race in an equal-access healthcare system: Results from the SEARCH cohort.

BACKGROUND: We previously showed that within an equal-access health system, race was not associated with the time between prostate cancer (PC) diagnosis and radical prostatectomy (RP). However, in the more recent time-period of the study (2003-2007), Black men had significantly longer times to RP. We sought to revisit the question in a larger study population with more contemporary patients. We hypothesized that time from diagnosis to treatment would not differ by race, even after accounting for active surveillance (AS) and the exclusion of men at very low to low risk of PC progression. METHODS: We analyzed data from 5885 men undergoing RP from 1988 to 2017 at eight Veterans Affairs Hospitals from SEARCH. Multiple linear regression was used to compare time from biopsy to RP and to examine the risk of delays (>90 and >180 days) between races. In sensitivity analyses we excluded men deemed to have initially chosen AS based on having >365 days from biopsy to RP and men at very low to low PC risk for progression according to National Comprehensive Cancer Network Clinical Practice Guidelines. RESULTS: At biopsy, Black men (n = 1959) were younger, had lower body mass index, and higher prostate specific antigen levels, (all p < 0.02), compared to White men (n = 3926). Time from biopsy to RP was longer in Black men (mean days: 98 vs. 92; adjusted ratio of mean number of days, 1.07 [95% confidence interval: 1.03-1.11], p < 0.001); however, there were no differences in delays >90 or >180 days after adjusting for confounders (all p ≥ 0.286). Results were similar following the exclusion of men potentially under on AS and at very low and low risk. CONCLUSIONS: In an equal-access healthcare system, we did not find evidence of clinically relevant differences in time from biopsy to RP in Black versus White men.

Allostatic load and cardiovascular outcomes in males with prostate cancer.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in men with prostate cancer (PC). Accumulated stress plays an important role in CVD development. The cumulative burden of chronic stress and life events can be measured using allostatic load (AL). METHODS: The initial cohort included males aged 18 years and older diagnosed with PC (2005-2019). AL was modeled as an ordinal variable (0-11). Fine-Gray competing risk regressions measured the impact of precancer diagnosis AL and postdiagnosis AL in 2-year major cardiac events (MACE). The effect of AL changes over time on MACE development was calculated via piecewise Cox regression (before, and 2 months, 6 months, and 1 year after PC diagnosis). RESULTS: We included 5261 PC patients of which 6.6% had a 2-year MACE. For every 1-point increase in AL before and within 60 days after PC diagnosis, the risk of MACE increased 25% (adjusted hazard ratio [aHR] =1.25, 95% confidence interval [CI] = 1.18 to 1.33) and 27% (aHR = 1.27, 95% CI = 1.20 to 1.35), respectively. Using AL as a time-varying exposure, the risk of MACE increased 19% (aHR = 1.19, 95% CI = 1.11 to 1.27), 22% (aHR = 1.22, 95% CI = 1.14 to 1.33), 28% (aHR = 1.28, 95% CI = 1.23 to 1.33), and 31% (aHR = 1.31, 95% CI = 1.27 to 1.35) for every 1-point increase in AL before, 2 months after, 6 months after, and 1 year after PC diagnosis, respectively. CONCLUSION: AL and its changes over time are associated with MACE in PC patients, suggesting a role of a biological measure of stress as a marker of CVD risk among men with PC.