Risk Of Prostate Cancer Mortality Research Articles

Prostate Risk and Monitoring During Testosterone Replacement Therapy.

Men with hypogonadism have reduced risk of prostate cancer mortality; whether testosterone treatment increases the risk of prostate safety events in men with hypogonadism remains controversial. Several studies including four larger randomized trials-the Testosterone Trials, TEstosterone and Atherosclerosis Progression in Aging Men (TEAAM) Trial, Testosterone for Diabetes Mellitus Trial, and Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) Trial-treated men with testosterone or placebo for one year or longer and reported prospectively-ascertained prostate safety data. The TRAVERSE Trial, because of its large size, longer duration, and adjudication of prostate events, has provided comprehensive data on the risk of adverse prostate events during TRT. Among men with hypogonadism, carefully screened to exclude those at high risk of prostate cancer, the incidences of high-grade or any prostate cancer, acute urinary retention, surgical procedure for benign prostatic hyperplasia, prostate biopsy, or new pharmacologic therapy for lower urinary tract symptoms were low and did not differ between the testosterone and placebo groups. Testosterone did not worsen lower urinary tract symptoms. TRT was associated with a greater increase in PSA than placebo in the first year of treatment. Conclusions: Testosterone treatment of men with hypogonadism, screened to exclude those at high risk of prostate cancer, is associated with low risk of adverse prostate events. Baseline evaluation of prostate cancer risk and a standardized monitoring plan can minimize the risk of unnecessary prostate biopsy while enabling the detection of high-grade prostate cancers in men receiving TRT.

The association between neighborhood obesogenic factors and prostate cancer risk and mortality: the Southern Community Cohort Study.

Prostate cancer is one of the leading causes of cancer-related mortality among men in the United States. We examined the role of neighborhood obesogenic attributes on prostate cancer risk and mortality in the Southern Community Cohort Study (SCCS). From the total of 34,166 SCCS male participants, 28,356 were included in the analysis. We assessed the relationship between neighborhood obesogenic factors [neighborhood socioeconomic status (nSES) and neighborhood obesogenic environment indices including the restaurant environment index, the retail food environment index, parks, recreational facilities, and businesses] and prostate cancer risk and mortality by controlling for individual-level factors using a multivariable Cox proportional hazards model. We further stratified prostate cancer risk analysis by race and body mass index (BMI). Median follow-up time was 133 months [interquartile range (IQR): 103, 152], and the mean age was 51.62 (SD: ± 8.42) years. There were 1,524 (5.37%) prostate cancer diagnoses and 98 (6.43%) prostate cancer deaths during follow-up. Compared to participants residing in the wealthiest quintile, those residing in the poorest quintile had a higher risk of prostate cancer (aHR = 1.32, 95% CI 1.12-1.57, p = 0.001), particularly among non-obese men with a BMI < 30 (aHR = 1.46, 95% CI 1.07-1.98, p = 0.016). The restaurant environment index was associated with a higher prostate cancer risk in overweight (BMI ≥ 25) White men (aHR = 3.37, 95% CI 1.04-10.94, p = 0.043, quintile 1 vs. None). Obese Black individuals without any neighborhood recreational facilities had a 42% higher risk (aHR = 1.42, 95% CI 1.04-1.94, p = 0.026) compared to those with any access. Compared to residents in the wealthiest quintile and most walkable area, those residing within the poorest quintile (aHR = 3.43, 95% CI 1.54-7.64, p = 0.003) or the least walkable area (aHR = 3.45, 95% CI 1.22-9.78, p = 0.020) had a higher risk of prostate cancer death. Living in a lower-nSES area was associated with a higher prostate cancer risk, particularly among Black men. Restaurant and retail food environment indices were also associated with a higher prostate cancer risk, with stronger associations within overweight White individuals. Finally, residing in a low-SES neighborhood or the least walkable areas were associated with a higher risk of prostate cancer mortality.

Multivitamin use after diagnosis and prostate cancer survival among men with nonmetastatic prostate cancer.

Multivitamin use is common among cancer patients. Whether post-diagnostic multivitamin supplementation is beneficial for prostate cancer survival is largely unknown, and some evidence even suggests potential harm. We prospectively assessed post-diagnostic multivitamin use in relation to prostate cancer survival among 4756 men with nonmetastatic prostate cancer at diagnosis in the Health Professionals Follow-up Study (1986-2016). Cox regression models were used to evaluate the association between post-diagnostic multivitamin use and frequency and risk of lethal prostate cancer (distant metastases or prostate cancer-specific death) and all-cause mortality. We observed 438 lethal prostate cancer and 2609 deaths during a median follow-up of 11 years. Compared to non-users, post-diagnostic multivitamin use was not associated with risk of lethal prostate cancer (HR [95% CI], 0.98 [0.74-1.30]) or all-cause mortality (1.00 [0.88-1.12]), after adjustment for potential confounders. Similarly, null associations were observed across various categories of use frequency. Compared to non-users, men who used multivitamins regularly (6-9 tablets/week) after cancer diagnosis had similar risk of lethal prostate cancer (0.96 [0.72-1.28]) and all-cause mortality (0.99 [0.88-1.12]). We found no evidence that post-diagnostic multivitamin use among men with nonmetastatic prostate cancer was associated with better or worse survival in a well-nourished population.

Testosterone replacement therapy is not associated with increased prostate cancer incidence, prostate cancer-specific, or cardiovascular disease-specific mortality in Finnish men

Background Concerns have been expressed over the safety of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH). Previous studies have shown controversial results regarding the association of TRT with the risk of cardiovascular events or prostate cancer (PCa) incidence, aggressiveness, and mortality. This study explores the overall risk of PCa and risk by tumor grade and stage, as well as mortality from PCa and cardiovascular disease (CVD), among men treated with TRT compared to men without LOH and TRT use. Materials and methods The study included 78,615 men of age 55–67 years at baseline from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Follow-up started at randomization and ended at death, emigration, or a common closing date January 1st, 2017. Cox proportional hazards regression model with time-dependent variables and adjustment for age, trial arm, use of other medications, and Charlson comorbidity index was used. Comprehensive information on TRT purchases during 1995–2015 was obtained from the Finnish National Prescription Database. PCa cases were identified from the Finnish Cancer Registry and causes of death obtained from Statistics Finland. Results Over the course of 18 years of follow-up, 2919 men were on TRT, and 285 PCa cases were diagnosed among them. TRT users did not exhibit a higher incidence or mortality rate of PCa compared to non-users. On the contrary, men using TRT had lower PCa mortality than non-users (HR = 0.52; 95% CI 0.3–0.91). Additionally, TRT users had slightly lower CVD and all-cause mortality compared to non-users (HR = 0.87; 95% CI 0.75–1.01 and HR = 0.93; 95% CI 0.87–1.0, respectively). No time- or dose-dependency of TRT use was evident in any of the analyses. Conclusion Men using TRT were not associated to increased risk for PCa and did not experience increased PCa- or CVD-specific mortality compared to non-users. Further studies considering blood testosterone levels are warranted.

Biochemical Recurrence and Risk of Mortality Following Radiotherapy or Radical Prostatectomy

Stratifying patients with biochemical recurrence (BCR) after primary treatment for prostate cancer based on the risk of prostate cancer-specific mortality (PCSM) is essential for determining the need for further testing and treatments. To evaluate the association of BCR after radical prostatectomy or radiotherapy and its current risk stratification with PCSM. This population-based cohort study included a total of 16 311 male patients with 10 364 (64%) undergoing radical prostatectomy and 5947 (36%) undergoing radiotherapy with curative intent (cT1-3, cM0) and PSA follow-up in Stockholm, Sweden, between 2003 and 2019. Follow-up for all patients was until death, emigration, or end of the study (ie, December 31, 2018). Data were analyzed between September 2022 and March 2023. Primary outcomes of the study were the cumulative incidence of BCR and PCSM. Patients with BCR were stratified in low- and high-risk according to European Association of Urology (EAU) criteria. Radical prostatectomy or radiotherapy. A total of 16 311 patients were included. Median (IQR) age was 64 (59-68) years in the radical prostatectomy cohort (10 364 patients) and 69 (64-73) years in the radiotherapy cohort (5947 patients). Median (IQR) follow-up for survivors was 88 (55-138) months and 89 (53-134) months, respectively. Following radical prostatectomy, the 15-year cumulative incidences of BCR were 16% (95% CI, 15%-18%) for the 4024 patients in the low D'Amico risk group, 30% (95% CI, 27%-32%) for the 5239 patients in the intermediate D'Amico risk group, and 46% (95% CI, 42%-51%) for 1101 patients in the high D'Amico risk group. Following radiotherapy, the 15-year cumulative incidences of BCR were 18% (95% CI, 15%-21%) for the 1230 patients in the low-risk group, 24% (95% CI, 21%-26%) for the 2355 patients in the intermediate-risk group, and 36% (95% CI, 33%-39%) for the 2362 patients in the high-risk group. The 10-year cumulative incidences of PCSM after radical prostatectomy were 4% (95% CI, 2%-6%) for the 1101 patients who developed low-risk EAU-BCR and 9% (95% CI, 5%-13%) for 649 patients who developed high-risk EAU-BCR. After radiotherapy, the 10-year PCSM cumulative incidences were 24% (95% CI, 19%-29%) for the 591 patients in the low-risk EAU-BCR category and 46% (95% CI, 40%-51%) for the 600 patients in the high-risk EAU-BCR category. These findings suggest the validity of EAU-BCR stratification system. However, while the risk of dying from prostate cancer in low-risk EAU-BCR after radical prostatectomy was very low, patients who developed low-risk EAU-BCR after radiotherapy had a nonnegligible risk of prostate cancer mortality. Improving risk stratification of patients with BCR is pivotal to guide salvage treatment decisions, reduce overtreatment, and limit the number of staging tests in the event of PSA elevations after primary treatment.

Fish consumption and risk of prostate cancer or its mortality: an updated systematic review and dose-response meta-analysis of prospective cohort studies.

Since the release of the last meta-analysis on the association between fish intake and prostate cancer risk, several cohort studies have been published. Moreover, none of the previous meta-analyzes examined the dose-response association between fish intake and prostate cancer. Therefore, the current dose-response meta-analysis was conducted to summarize available findings on the associations of fish intake with the risk of prostate cancer in men. Online databases of PubMed, Scopus, and Web of Science were systematically searched up to September 2022. We included prospective cohort studies that examined the associations of fish intake with the risk of prostate cancer (total, localized, and advanced prostate cancer), its mortality, and cancer progression. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated for the highest versus lowest categories of fish intake using random-effects models. Also, linear and non-linear dose-response analyzes were conducted. In total, 25 prospective cohort studies, recruiting 1,216,474 men, were included in the systematic review, and 22 studies were included in the meta-analysis. During the follow-up periods, ranging from 6 to 33 years, a total of 44,722 cases of prostate cancer were recorded. The comparison between the highest and lowest intakes of total fish revealed the summary RRs of 0.97 (95% CI: 0.86-1.10) for total, 1.01 (95% CI: 0.91-1.13) for advanced, and 0.90 (95% CI: 0.72-1.12) for localized prostate cancer, indicating no significant association. Moreover, the summary RR was 0.55 (95% CI: 0.33-0.92) for prostate cancer mortality and 0.84 (95% CI: 0.65-1.10) for prostate cancer progression, indicating an inverse association between fish intake and prostate cancer mortality. Also, in the dose-response analyzes, each 20 gram/day increase in total fish intake was associated with a 12% lower risk of prostate cancer mortality. Our findings support the protective association between total fish intake and the risk of prostate cancer mortality.

Obesity and prostate cancer screening, incidence, and mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Though obesity, measured by body mass index (BMI), is an established risk factor for several cancer sites, there is conflicting evidence on whether obesity increases prostate cancer risk or mortality and, if it does, whether it increases risk directly or indirectly by affecting prostate cancer screening efficacy. We examined associations between BMI and prostate cancer screening outcomes, incidence, and mortality in men randomly assigned to the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (n = 36 756) between 1993 and 2001. Participants received annual screening with the prostate-specific antigen test and digital rectal exam. Associations between baseline BMI and screening outcomes were assessed via multinomial logistic regression, and associations with prostate cancer incidence and mortality were assessed via Cox proportional hazards regression. Individuals with higher BMI were less likely to screen positive via the prostate-specific antigen test and/or digital rectal exam and more likely to have an inadequate screen (all Ptrend < .01). Higher BMI was inversely associated with prostate cancer incidence (per 5 kg/m2 BMI increase: hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.91 to 0.97), including incidence of early stage (HR = 0.94, 95% CI = 0.90 to 0.97) and advanced-stage (HR = 0.91, 95% CI = 0.82 to 1.02) disease, but positively associated with prostate cancer mortality (HR = 1.21, 95% CI = 1.06 to 1.37). The association with mortality was not modified by screening outcome (Pinteraction = .13). Within this screened population, individuals with higher BMI had lower risk of prostate cancer diagnosis but higher risk of prostate cancer mortality. As higher BMI was not positively associated with advanced-stage prostate cancer risk, the increased mortality is unlikely to be due to delayed prostate cancer detection.

Post-diagnostic health behaviour scores and risk of prostate cancer progression and mortality

BackgroundIndividual behaviours are associated with prostate cancer (PC) progression. Behavioural scores, comprised of multiple risk factors, allow assessment of the combined impact of multiple behaviours.MethodsWe examined the association between six a priori scores and risk of PC progression and mortality among 2156 men with PC in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) cohort: two scores developed based on the PC survivorship literature (‘2021 Score [+ Diet]’); a score developed based on pre-diagnostic PC literature (‘2015 Score’); and three scores based on US recommendations for cancer prevention (‘WCRF/AICR Score’) and survival (‘ACS Score [+ Alcohol]’). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for progression and PC mortality via parametric survival models (interval censoring) and Cox models, respectively.ResultsOver a median (IQR) of 6.4 (1.3, 13.7) years, we observed 192 progression and 73 PC mortality events. Higher (i.e., healthier) 2021 Score + Diet and WCRF/AICR Scores were inversely associated with risk of PC progression (2021 + Diet: HRcontinuous = 0.76, 95% CI: 0.63–0.90. WCRF/AICR: HRcontinuous = 0.83, 95% CI: 0.67–1.02) and mortality (2021 + Diet: HRcontinuous = 0.65, 95% CI: 0.45–0.93. WCRF/AICR: HRcontinuous = 0.71; 95% CI: 0.57–0.89). The ACS Score + Alcohol was only associated with progression (HRcontinuous = 0.89, 95% CI: 0.81–0.98) while the 2021 Score was only associated with PC mortality (HRcontinuous = 0.62, 95% CI: 0.45–0.85). The 2015 was not associated with PC progression or mortality.ConclusionFindings strengthen the evidence that behavioural modifications following a prostate cancer diagnosis may improve clinical outcomes.

Re: WHO Classification of Tumours, 5th Edition, Volume 8: Urinary and Male Genital Tumours

Prostate-specific antigen (PSA) levels in midlife are strongly associated with the long-term risk of lethal prostate cancer in cohorts not subject to screening. This is the first study evaluating the association between PSA levels drawn as part of routine medical care in the Norwegian population and prostate cancer incidence and mortality.To determine the association between midlife PSA levels <4.0 ng/ml, drawn as part of routine medical care, and long-term risk of prostate cancer death.The Norwegian Prostate Cancer Consortium collected >8 million PSA results from >1 million Norwegian males ≥40 yr of age. We studied 176 099 men (predefined age strata: 40–54 and 55–69 yr) without a prior prostate cancer diagnosis who had a nonelevated baseline PSA level (<4.0 ng/ml) between January 1, 1995 and December 31, 2005.Baseline PSA.We assessed the 16-yr risk of prostate cancer mortality. We calculated the discrimination (C-index) between predefined PSA strata (<0.5, 0.5–0.9, 1.0–1.9, 2.0–2.9, and 3.0–3.9 ng/ml) and subsequent prostate cancer death. Survival curves were plotted using the Kaplan-Meier method.The median follow-up time of men who did not get prostate cancer was 17.9 yr. Overall, 84% of men had a baseline PSA level of <2.0 ng/ml and 1346 men died from prostate cancer, with 712 deaths (53%) occurring in the 16% of men with the highest baseline PSA of 2.0–3.9 ng/ml. Baseline PSA levels were associated with prostate cancer mortality (C-index 0.72 for both age groups, 40–54 and 55–69 yr). The fact that the reason for any given PSA measurement remains unknown represents a limitation.We replicated prior studies that baseline PSA at age 40–69 yr can be used to stratify a man's risk of dying from prostate cancer within the next 15–20 yr.A prostate-specific antigen level obtained as part of routine medical care is strongly associated with a man’s risk of dying from prostate cancer in the next two decades.

Baseline Serum Prostate-specific Antigen Value Predicts the Risk of Subsequent Prostate Cancer Death—Results from the Norwegian Prostate Cancer Consortium

Background and objectiveProstate-specific antigen (PSA) levels in midlife are strongly associated with the long-term risk of lethal prostate cancer in cohorts not subject to screening. This is the first study evaluating the association between PSA levels drawn as part of routine medical care in the Norwegian population and prostate cancer incidence and mortality. The objective of the study was to determine the association between midlife PSA levels <4.0 ng/ml, drawn aspart of routine medical care, and long-term risk of prostate cancer death. MethodsThe Norwegian Prostate Cancer Consortium collected >8 million PSA results from >1 million Norwegian males (more than or equal to) 40 yr of age. We studied 176 099 men (predefined age strata: 40–54 and 55–69 yr) without a prior prostate cancer diagnosis who had a nonelevated baseline PSA level (<4.0 ng/ml) between January 1,1995 and December 31, 2005. We assessed the 16-yr risk of prostate cancer mortality. We calculated the discrimination (C-index) between predefined PSA strata (<0.5, 0.5–0.9, 1.0–1.9, 2.0–2.9, and 3.0–3.9 ng/ml) and subsequent prostate cancer death. Survival curves were plotted using the Kaplan-Meier method. Key findings and limitationsThe median follow-up time of men who did not get prostate cancer was 17.9 yr. Overall, 84% of men had a baseline PSA level of <2.0 ng/ml and 1346 men died from prostate cancer, with 712 deaths (53%) occurring in the 16% of men with the highest baseline PSA of 2.0–3.9 ng/ml. Baseline PSA levels were associated with prostate cancer mortality (C-index 0.72 for both age groups, 40–54 and 55–69 yr). The fact that the reason for any given PSA measurement remains unknown represents a limitation. Conclusions and clinical implicationsWe replicated prior studies that baseline PSA at age 40–69 yr can be used to stratify a man’s risk of dying from prostate cancer within the next 15–20 yr. Patient summaryA prostate-specific antigen level obtained as part of routine medical care is strongly associated with a man’s risk of dying from prostate cancer in the next two decades.

Racial inequities in the quality of surgical care among Medicare beneficiaries with localized prostate cancer.

US Black men are twice as likely to die from prostate cancer as men of other races. Lower quality care may contribute to this higher death rate. Sociodemographic and clinical data were obtained for men in Surveillance, Epidemiology, and End Results-Medicare diagnosed with clinically localized prostate cancer (cT1-4N0/xM0/x) and managed primarily by radical prostatectomy (2005-2015). Surgical volume was determined for facility and surgeon. Relationships between race, surgeon and/or facility volume, and characteristics of treating facility with survival (all-cause and cancer-specific) were assessed using multivariable Cox regression and competing risk analysis. Black men represented 6.7% (n=2123) of 31,478 cohort. They were younger at diagnosis, had longer time from diagnosis to surgery, lower socioeconomic status, higher prostate-specific antigen (PSA), and higher comorbid status compared with men of other races (p<.001). They were less likely to receive care from a surgeon or facility in the top volume percentile (p<.001); less likely to receive surgical care at a National Cancer Institute-designated cancer center and more likely seen at a minority-serving hospital; and less likely to travel ≥50 miles for surgical care. On multivariable analysis stratified by surgical volume, Black men receiving care from a surgeon or facility with lower volumes demonstrated increased risk of prostate cancer mortality (hazard ratio, 1.61; 95% confidence interval, 1.01-2.69) adjusting for age, clinical stage, PSA, and comorbidity index. Black Medicare beneficiaries with prostate cancer more commonly receive care from surgeons and facilities with lower volumes, likely affecting surgical quality and outcomes. Access to high-quality prostate cancer care may reduce racial inequities in disease outcomes, even among insured men. Black men are twice as likely to die of prostate cancer than other US men. Lower quality care may contribute to higher rates of prostate cancer death. We used surgical volume to evaluate the relationship between race and quality of care. Black Medicare beneficiaries with prostate cancer more commonly received care from surgeons and facilities with lower volumes, correlatingwith a higher risk of prostate cancer death and indicating scarce resources for care. Access to high-quality prostate cancer care eases disparities in disease outcomes. Patient-centered interventions that increase access to high-quality care for Black men with prostate cancer are needed.

Association between Alcohol Intake and Prostate Cancer Mortality and Survival.

We conducted a systematic review and meta-analysis to investigate the role of alcohol consumption with the prognosis of prostate cancer (PCa). Published reports were gathered on 15 October 2022, from PUBMED/MEDLINE and EMBASE. We found 19 independent eligible studies on the association between consumption of alcoholic beverages and the risk of fatal PCa (n = 5), PCa mortality (n = 5) in healthy subjects, and PCa patients' survival (n = 7) or surrogates thereof (n = 2). We used random effects meta-analysis to obtain a summary risk estimate (SRE) and 95% confidence intervals (95%CI) for incidence of fatal PCa and PCa mortality. The meta-analysis revealed no association between alcohol consumption and fatal prostate cancer incidence risk in healthy subjects with an indication for publication bias, but omitting the study that mainly increased the between-study heterogeneity, the SRE becomes significant (SRE 1.33, 95%CI 1.12-1.58), and the heterogeneity disappeared (I2 = 0%) with no indication of publication bias. No association of alcohol consumption was found with mortality risk in PCa patients (SRE 0.97, 95%CI 0.92-1.03) and PCa mortality risk in healthy subjects (SRE 1.03, 95%CI 0.82-1.30). In conclusion, this study suggests that there is some evidence of an association between high alcohol consumption and an increased risk of incidence of fatal prostate cancer in healthy subjects. Given the inconsistencies this result warrants further confirmation.

Understanding the Role of Urology Practice Organization and Racial Composition in Prostate Cancer Treatment Disparities.

Black men have a higher risk of prostate cancer diagnosis and mortality but are less likely to receive definitive treatment. The impact of structural aspects on treatment is unknown but may lead to actionable insights to mitigate disparities. We sought to examine the associations between urology practice organization and racial composition and treatment patterns for Medicare beneficiaries with incident prostate cancer. Using a 20% sample of national Medicare data, we identified beneficiaries diagnosed with prostate cancer between January 2010 and December 2015 and followed them through 2016. We linked urologists to their practices with tax identification numbers. We then linked patients to practices on the basis of their primary urologist. We grouped practices into quartiles on the basis of their proportion of Black patients. We used multilevel mixed-effects models to identify treatment associations. We identified 54,443 patients with incident prostate cancer associated with 4,194 practices. Most patients were White (87%), and 9% were Black. We found wide variation in racial practice composition and practice segregation. Patients in practices with the highest proportion of Black patients had the lowest socioeconomic status (43.1%), highest comorbidity (9.9% with comorbidity score ≥ 3), and earlier age at prostate cancer diagnosis (33.5% age 66-69 years; P < .01). Black patients had lower odds of definitive therapy (adjusted odds ratio, 0.87; 95% CI, 0.81 to 0.93) and underwent less treatment than White patients in every practice context. Black patients in practices with higher proportions of Black patients had higher treatment rates than Black patients in practices with lower proportions. Black patients had lower predicted probability of treatment (66%) than White patients (69%; P < .05). Despite Medicare coverage, we found less definitive treatment among Black beneficiaries consistent with ongoing prostate cancer treatment disparities. Our findings are reflective of the adverse effects of practice segregation and structural racism, highlighting the need for multilevel interventions.

Post-diagnostic Zinc Supplement Use and Prostate Cancer Survival Among Men With Nonmetastatic Prostate Cancer.

Biological and experimental evidence support restoration of normal zinc levels in malignant prostate cells as a promising prostate cancer treatment, yet the influence of zinc supplementation after diagnosis on prostate cancer survival in a human population is unknown. We prospectively assessed post-diagnostic zinc supplementation in relation to prostate cancer survival among 5,788 men with nonmetastatic prostate cancer in the Health Professionals Follow-up Study (1986-2019). We used Cox regression models to estimate the multivariable hazard ratios and 95% confidence intervals of lethal prostate cancer (distant metastases or prostate cancer-specific death) and all-cause mortality according to post-diagnostic zinc supplement use and dosage. During a median follow-up of 11 years, we documented 527 lethal prostate cancer events and 3,198 all-cause deaths. Fifteen percent of men reported zinc supplement use post-diagnosis. Compared to nonusers, post-diagnostic zinc supplement use was associated suggestively with a lower risk of lethal prostate cancer (HR [95% CI], 0.82 [0.60-1.13]) and significantly with all-cause mortality (0.84 [0.74-0.96]). The inverse association was mostly observed among men who used post-diagnostic zinc supplements of 1-24 mg/d (lethal prostate cancer: 0.55 [0.32-0.96]; all-cause mortality: 0.77 [0.64-0.93]), while higher dosage did not show a lower risk. Post-diagnostic low-dose zinc supplement use among nonmetastatic prostate cancer patients was associated with lower risk of lethal prostate cancer and all-cause mortality. A potential benefit of low-dose post-diagnostic zinc supplement for prostate cancer survival merits further study.

Risk of prostate cancer and death after benign transurethral resection of the prostate-A 20-year population-based analysis.

The oncological risks after benign histology on a transurethral resection of the prostate (TURP) remain largely unknown. Here, the risk of prostate cancer incidence and mortality following a benign histological assessment of TURP is investigated in a population-based setting. Between 1995 and 2016, 64,059 men in Denmark underwent TURP without prior biopsy of the prostate; 42,558 of these men had benign histology. The risks of prostate cancer, prostate cancer with a Gleason score ≥ 3 + 4, and prostate cancer-specific death were assessed with competing risks. Specific risks for pre-TURP prostate-specific antigen (PSA) levels at 10 and 15 years were visualized by locally estimated scatterplot smoothing. The median age at TURP was 72 years (interquartile range [IQR], 65-78 years), and the median follow-up was 15 years (IQR, 10-19 years). The 10-year risks of any prostate cancer and prostate cancer with a Gleason score ≥ 3 + 4 and the 15-year risk of prostate cancer death showed clear visual relations with increasing PSA. The 15-year cumulative incidence of prostate cancer-specific death after benign TURP was 1.4% (95% confidence interval [CI], 1.3%-1.6%) for all men and 0.8% (95% CI, 0.6%-1.1%) for men with PSA levels <10 ng/ml. The primary limitation was exclusion due to missing PSA data. Men with low PSA levels and a benign TURP can be reassured about their cancer risk and do not need to be monitored differently than any other men. Patients with high PSA levels can be considered for further follow-up with prostate magnetic resonance imaging. These findings add to the literature suggesting that normal histology from the prostate entails a low risk of death from the disease. There is little knowledge about the oncological risks after the surgical treatment of benign prostatic hyperplasia. This study shows a very low risk of adverse oncological outcomes in men with prostate-specific antigen (PSA) levels below 10 ng/ml at the time of transurethral resection of the prostate. Patients with higher PSA levels may need more extensive follow-up.

Fostering shared decision-making about prostate cancer screening among African American men patients and their primary care providers: a randomized behavioral clinical trial

BackgroundProstate cancer is the third most prevalent cancer in the American population. Furthermore, the prognosis is worse in African American as there is increased morbidity and mortality associated with it.PurposeThe purpose of this study is to evaluate the effectiveness of a new online method to educate the patient population regarding prostate cancer risk, diagnosis, treatments, and their decisions about whether to be screened for the early detection of prostate cancer.MethodsTwo hundred Black male patients are recruited from different clinical sites and randomized to either the control arm (usual care) or the intervention arm (educational program). We will compare the effectiveness of the intervention to see if patients are discussing the need of getting a prostate-specific antigen (PSA) test, and the possible benefits and harms that may result of having or not having the test, with their primary care providers.DiscussionShared decision-making (SDM) is the current standard in most cancer-screening guidelines and also a standard of person-centered care. However, there is a lack of evidence-based approaches to improve decision quality in clinical settings and an increased ambiguity of applying SDM for PSA-based screening among Black men in primary care. Our proposal to evaluate a decisional-aid intervention and measure the actual application of SDM during clinical encounters has a high potential to advance the translation path of implementing shared decision-making in clinical settings and provide evidence of the applicability of the guideline in general.Innovation and overall impactGiven the 2018 USPSTF updated guidelines recommending shared decision-making about PSA-based screening, the increased risk of prostate cancer mortality in Black men, the challenges of evidence-based decision-making due to the underrepresentation of Blacks in major randomized clinical trials, and implicit racial bias among primary care providers, the time is ripe for interventions to improve shared decision-making about prostate cancer screening in Black men. In this study, we address communication and knowledge gaps between Black men and their primary care providers. The intervention, if proven effective, can be readily scaled across primary care practices across the U.S. and may be adapted to other types of cancer where guidelines have included shared decision-making as well. Early detection of prostate cancer may decrease mortality and morbidity in the long term.

Postdiagnostic Inflammatory, Hyperinsulinemic, and Insulin-Resistant Diets and Lifestyles and the Risk of Prostate Cancer Progression and Mortality.

Inflammatory and insulin pathways have been linked to prostate cancer; postdiagnostic behaviors activating these pathways may lead to poor outcomes. The empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH), and empirical dietary index for insulin resistance (EDIR), and associated lifestyle indices (ELIH, ELIR) predict biomarkers of inflammation (EDIP: IL6, TNFaR2, CRP) and insulin secretion (EDIH/ELIH: c-peptide; EDIR/ELIR: TAG:HDL) from whole foods and behaviors. Associations of these indices with time to prostate cancer progression (primary, n = 2,056) and prostate cancer-specific mortality (PCSM; secondary, n = 2,447) were estimated among men diagnosed with nonmetastatic prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor cohort diet and lifestyle sub-study. Because the true (versus clinically documented) date of progression is unobserved, we used parametric (Weibull) survival models to accommodate interval-censoringand estimated adjusted HR and 95% confidence intervals (CI) for prostate cancer progression per 1-SD increase in index. Cox proportional hazards models were used to estimate PCSM associations. During a median [interquartile range (IQR)] 6.4 years (IQR, 1.3-12.7), 192 progression and 73 PCSM events were observed. Inflammatory (EDIP: HR, 1.27; CI, 1.17-1.37), hyperinsulinemic (EDIH: HR, 1.24; CI, 1.05-1.46. ELIH: HR, 1.34; CI, 1.17-1.54), and insulin-resistant (EDIR: HR, 1.22; CI, 1.00-1.48. ELIR: HR, 1.36; CI, 1.12-1.64) indices were positively associated with risk of prostate cancer progression. There was no evidence of associations between the indices and PCSM. Both inflammatory and insulinemic dietary and lifestyle patterns are associated with risk of prostate cancer progression. For men with prostate cancer, consuming dietary patterns that limit chronic systemic inflammation and insulin hypersecretion may improve survivorship, especially when coupled with active lifestyle and healthy body weight. See related commentary by Kucuk, p. 1673.

Risk of New-Onset Prostate Cancer for Metformin Versus Sulfonylurea Use in Type 2 Diabetes Mellitus: A Propensity Score-Matched Study.

The aim of this study was to compare the risks of new-onset prostate cancer between metformin and sulfonylurea users with type 2 diabetes mellitus (T2DM). This population-based retrospective cohort study included male patients with T2DM presenting to public hospitals/clinics in Hong Kong between January 1, 2000, and December 31, 2009. We only included patients prescribed either, but not both, metformin or sulfonylurea. All patients were followed up until December 31, 2019. The primary outcome was new-onset prostate cancer and the secondary outcome was all-cause mortality. One-to-one propensity score matching was performed between metformin and sulfonylurea users based on demographics, comorbidities, antidiabetic and cardiovascular medications, fasting blood glucose level, and hemoglobin A1c level. Subgroup analyses based on age and use of androgen deprivation therapy were performed. The final study cohort consisted of 25,695 metformin users (mean [SD] age, 65.2 [11.8] years) and 25,695 matched sulfonylurea users (mean [SD] age, 65.3 [11.8] years) with a median follow-up duration of 119.6 months (interquartile range, 91.7-139.6 months) after 1:1 propensity score matching of 66,411 patients. Metformin users had lower risks of new-onset prostate cancer (hazard ratio, 0.80; 95% CI, 0.69-0.93; P=.0031) and all-cause mortality (hazard ratio, 0.89; 95% CI, 0.86-0.92; P<.0001) than sulfonylurea users. Metformin use was more protective against prostate cancer but less protective against all-cause mortality in patients aged <65 years (P for trend <.0001 for both) compared with patients aged ≥65 years. Metformin users had lower risk of all-cause mortality than sulfonylurea users, regardless of the use of androgen deprivation therapy (P for trend <.0001) among patients who developed prostate cancer. Metformin use was associated with significantly lower risks of new-onset prostate cancer and all-cause mortality than sulfonylurea use in male patients with T2DM.

AUTHOR REPLY

The majority of men diagnosed with prostate cancer in the PSA-screening era are eligible for active surveillance and is often the initial therapy in men with low-risk prostate cancer. Active surveillance may reduce unnecessary treatments for patients without increasing risk of prostate cancer mortality.123 However, Black men represented only 7%-13% in these prospective cohort studies. Compared to White men, it has been previously shown that Black men have an increased prostate cancer incidence, higher baseline prostate-specific antigen value, more aggressive prostate cancer features, greater frequency of biochemical recurrence after treatment, and higher overall cancer-specific mortality.

PD07-11 VITAMIN D HAS A STRONGER IMPACT ON PROSTATE TUMOR GENE EXPRESSION IN BLACK MEN

You have accessJournal of UrologyCME1 May 2022PD07-11 VITAMIN D HAS A STRONGER IMPACT ON PROSTATE TUMOR GENE EXPRESSION IN BLACK MEN Neil Mistry, Cordero McCall, Moray Campbell, and Adam Murphy Neil MistryNeil Mistry More articles by this author , Cordero McCallCordero McCall More articles by this author , Moray CampbellMoray Campbell More articles by this author , and Adam MurphyAdam Murphy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002526.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Black men have a higher risk of prostate cancer (PCa) mortality and also have a higher prevalence of vitamin D deficiency. The VITAL clinical trial showed that patients randomized to 2000 IU of vitamin D3 had a significant reduction in advanced cancers compared to placebo (1.7% vs. 2.1%; HR, 0.83; P = .04). Black men also trended towards lower PCa mortality in that trial. Thus, we sought to investigate prostate cancer responsiveness to vitamin D by evaluating differentially expressed genes (DEG) in Black vs. non-Black men’s prostate tumors in high and low vitamin D states. METHODS: We enrolled 169 men in a cross-sectional study evaluating serum vitamin D status and adverse pathology at radical prostatectomy. We selected 78 men. RNA sequencing was done using punch biopsies of >70% epithelium in the dominant tumor nodule and contralateral benign tissue to assess DEG between Black and non-Black tumors. ChIP-seq for vitamin D receptor (VDR) binding sites was used on RC43T (Black PCa cell line) and LNCaP to identify vitamin D responsive genes. Samples were stratified by vitamin D status (above vs. below race-specific median) and race (Black vs non-Black). RESULTS: There were 57 Black and 21 non-Black men. There were 39 lower risk tumors (Gleason score ≤ 3+4) and 39 higher risk tumors (GS ≥ 3+4 with tertiary 5). In a high vitamin D state, we found 2,101 DEGs in Black tumors vs normal tissue (Figure 1a) compared to only 15 DEGs in non-Black tumors vs normal tissue (Figure 1b). A direct comparison of Black vs non-Black tumors in a high vitamin D state demonstrated 434 DEGs (Figure 1c). When comparing tumors with above vs below-median vitamin D in all patients, we found 2,992 DEGs. Of these, 1,746 DEGs contained VDR binding sites and were found in RC43T while only 10 DEGs with VDR binding sites were found in LNCaP (Figure 1d). CONCLUSIONS: Vitamin D directly impacts gene expression in prostate cancer. Tumors in Black men express more genes that have VDR binding sites than tumors in non-Black men. Due to this unique relationship, Vitamin D may have a role in chemoprevention for clinically localized prostate cancer in Black men. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e103 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neil Mistry More articles by this author Cordero McCall More articles by this author Moray Campbell More articles by this author Adam Murphy More articles by this author Expand All Advertisement PDF DownloadLoading ...