Risk Of Prostate Cancer Death Research Articles

Risk of prostate cancer death in men diagnosed with prostate cancer at cystoprostat-ectomy. A nationwide population-based study.

One out of three men who undergo cystoprostatectomy for bladder cancer is diagnosed with incidental prostate cancer (PCa) at histopathological examination. Many of these men are PSA tested as part of their follow-up, but it is unclear if this is needed. The aim of this study was to assess the risk of PCa death in these men and the need of PSA-testing during follow-up. Between 2002 and 2020, 1,554 men were diagnosed with PCa after cystoprostatectomy performed for non-metastatic bladder cancer and registered in the National Prostate Cancer Register (NPCR) of Sweden. We assessed their risk of death from PCa, bladder cancer and other causes up to 15 years after diagnosis by use of data in The Cause of Death Register. The use of androgen deprivation therapy (ADT) as a proxy for PCa progression was assessed by fillings in The Prescribed Drug Register. Fifteen years after diagnosis, cumulative incidence of death from PCa was 2.6% (95% CI 2.3%-2.9%), from bladder cancer 32% (95% CI: 30%-34%) and from other causes 40% (95% CI: 36%-44%). Only 35% of men with PCa recorded as primary cause of death in The Cause of Death Register had started ADT before date of death, indicating sticky-diagnosis bias with inflated risk of PCa death. For a large majority of men diagnosed with incidental PCa at cystoprostatectomy performed for bladder cancer, the risk of PCa death is very small so there is no rationale for PSA testing during follow-up.

Prostate Cancer Incidence and Mortality in Men Exposed to α1-Adrenoceptor Antagonists.

α1-antagonists are commonly used to treat benign prostatic hyperplasia. Preclinical studies suggest they induce cell death and inhibit tumor growth. This study evaluates the risk of prostate cancer death in men using α1-antagonists. A population-based cohort study in Stockholm, Sweden (January 1, 2007 to December 31, 2019) including 451,779 men with a prostate-specific antigen (PSA) test. Study entry was one year after the first PSA test. Men were considered exposed at their second filled prescription. Primary outcome: prostate cancer mortality. Secondary outcomes: all-cause mortality and prostate cancer incidence. Cox proportional hazard regression models were used to calculate adjusted hazard ratios (HRs) and 95% CIs for all outcomes. Inverse probability weighting with marginal structural models accounted for time-dependent confounders. Of 351,297 men in the cohort, 39,856 (11.3%) were exposed to α1-antagonists. Median follow-up for prostate cancer mortality was 8.9 years and median exposure time to α1-antagonists was 4.4 years. There was no evidence of an association between α1-antagonist use and prostate cancer mortality, all-cause mortality, or high-grade prostate cancer. α1-antagonist-use was associated with an increased risk of prostate cancer (HR: 1.11, 95% CI: 1.06-1.17) and low-grade prostate cancer (HR: 1.22, 95% CI: 1.11-1.33). Men treated with α1-antagonists had more frequent PSA testing. Our findings show no significant association between α1-adrenoceptor antagonist exposure and prostate cancer mortality or high-grade prostate cancer. Although the preclinical evidence indicates a potential chemopreventive effect, this study's findings do not support it.

Temporal trend in risk of prostate cancer death in men with favourable-risk prostate cancer.

Changes in work-up and histopathological assessment have caused stage and grade migration in men with prostate cancer (PCa). The aim of this study was to assess temporal trends in risk of PCa death for men with favourable-risk PCa managed with primary radical prostatectomy or observation. Men aged 75 or younger with Charlson Comorbidity index 0-1 diagnosed with favourable-risk PCa (T1-T2, prostate specific antigen [PSA] <20 ng/mL and Gleason score 6 or 7[3+4]) in the period 2000-2016 who were treated with primary radical prostatectomy or managed with observation in PCBaSe 4.0. Treatment groups were compared following propensity score matching, and risk of PCa death was estimated by use of Cox regression analyses. A total of 9,666 men were selected for each treatment strategy. The 7-year cumulative incidence of PCa death decreased in all risk and treatment groups. For example, the incidence in men diagnosed with low-risk PCa and managed with observation was 1.2% in 2000-2005, which decreased to 0.4% in 2011-2016. Corresponding incidences for men with intermediate-risk PCa managed with observation were 2.0% and 0.7%. The relative risk of PCa death was lower in men with low-risk PCa managed with radical prostatectomy compared to observation: in 2000-2005 hazard ratio (HR) 0.20 (95% confidence interval [CI] 0.10-0.38) and in 2011-2016 HR 0.35 (95% CI 0.05-2.26). Corresponding risks for men with intermediate-risk PCa were HR 0.28 (95% CI 0.16-0.47) and HR 0.21 (95% CI 0.04-1.18). The absolute risk reduction of radical prostatectomy compared to observation for men with low-risk PCa was 1% in 2000-2005 and 0.4% in 2011-2016, and for men with intermediate-risk PCa 1.1% in 2000-2005 and 0.7% in 2011-2016. Men diagnosed in 2011-2016 with low-risk and favourable intermediate-risk PCa have a similar relative benefit but smaller absolute benefit of curative treatment compared to men diagnosed in 2000-2005.

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.

Time trends in the use of curative treatment in men 70 years and older with nonmetastatic prostate cancer.

Undertreatment of otherwise healthy men in their seventies with prostate cancer has been reported previously. Using information in a Swedish prostate cancer research database, patterns of management and cancer-specific mortality were compared across age groups in over 70,000 men diagnosed with intermediate- or high-risk nonmetastatic prostate cancer between 2008 and 2020. Crude probabilities of death were estimated non-parametrically. Staging procedures, primary treatment, and cancer death were compared using regression models, adjusting for patient and tumor characteristics. During the study period, the proportion of men treated with curative intent increased in ages 70-74 (intermediate-risk from 45% to 72% and high-risk from 49% to 84%), 75-79 (intermediate-risk from 11% to 52% and high-risk from 12% to 70%), and 80-84 years (intermediate-risk from < 1% to 14% and high-risk from < 1% to 30%). Older age was associated with lower likelihoods of staging investigations and curative treatment, also after adjustment for tumor characteristics and comorbidity. Men treated with curative intent and those initially managed conservatively had lower crude risks of prostate cancer death than men receiving androgen deprivation treatment (ADT). In adjusted analyses, ADT was associated with higher prostate cancer mortality than curative treatment across ages and risk groups. Among men managed conservatively, prostate cancer mortality was higher in ages 70 and above. Use of curative treatment increased substantially in older men with prostate cancer between 2008 and 2020. Our findings suggest reduced age-bias and under-treatment, likely reflecting improved individualized decision-making and adherence to guidelines recommending more active management of older men.

Exploring the relation of active surveillance schedules and prostate cancer mortality.

Active surveillance (AS), where treatment is deferred until cancer progression is detected by a biopsy, is acknowledged as a way to reduce overtreatment in prostate cancer. However, a consensus on the frequency of taking biopsies while in AS is lacking. In former studies to optimize biopsy schedules, the delay in progression detection was taken as an evaluation indicator and believed to be associated with the long-term outcome, prostate cancer mortality. Nevertheless, this relation was never investigated in empirical data. Here, we use simulated data from a microsimulation model to fill this knowledge gap. In this study, the established MIcrosimulation SCreening Analysis model was extended with functionality to simulate the AS procedures. The biopsy sensitivity in the model was calibrated on the Canary Prostate Cancer Active Surveillance Study (PASS) data, and four (tri-yearly, bi-yearly, PASS, and yearly) AS programs were simulated. The relation between detection delay and prostate cancer mortality was investigated by Cox models. The biopsy sensitivity of progression detection was found to be 50%. The Cox models show a positive relation between a longer detection delay and a higher risk of prostate cancer death. A 2-year delay resulted in a prostate cancer death risk of 2.46%-2.69% 5 years after progression detection and a 10-year risk of 5.75%-5.91%. A 4-year delay led to an approximately 8% greater 5-year risk and an approximately 25% greater 10-year risk. The detection delay is confirmed as a surrogate for prostate cancer mortality. A cut-off for a "safe" detection delay could not be identified.

Isolating the Drivers of Racial Inequities in Prostate Cancer Treatment.

Black individuals in the United States are less likely than White individuals to receive curative therapies despite a 2-fold higher risk of prostate cancer death. While research has described treatment inequities, few studies have investigated underlying causes. We analyzed a cohort of 40,137 Medicare beneficiaries (66 and older) linked to the Surveillance Epidemiology and End Results (SEER) cancer registry who had clinically significant, non-metastatic (cT1-4N0M0, grade group 2-5) prostate cancer (diagnosed 2010-2015). Using the Kitagawa-Oaxaca-Blinder decomposition, we assessed the contributions of patient health and health care delivery on the racial difference in localized prostate cancer treatments (radical prostatectomy or radiation). Patient health consisted of comorbid diagnoses, tumor characteristics, SEER site, diagnosis year, and age. Health care delivery was captured as a prediction model with these health variables as predictors of treatment, reflecting current treatment patterns. A total of 72.1% and 78.6% of Black and White patients received definitive treatment, respectively, a difference of 6.5 percentage points. An estimated 15% [95% confidence interval (CI): 6-24] of this treatment difference was explained by measured differences in patient health, leaving the remaining estimated 85% (95% CI: 74-94) attributable to a potentially broad range of health care delivery factors. Limitations included insufficient data to explore how specific health care delivery factors, including structural racism and social determinants, impact differential treatment. Our results show the inadequacy of patient health differences as an explanation of the treatment inequity. Investing in studies and interventions that support equitable health care delivery for Black individuals with prostate cancer will contribute to improved outcomes.

Prognosis of Gleason Score 9–10 Prostatic Adenocarcinoma in Needle Biopsies: A Nationwide Population-based Study

BackgroundSince 2014, prostate cancer is reported using five-tier grouping of Gleason scores. Studies have suggested prognostic heterogeneity within the groups. ObjectiveWe assessed the risk of prostate cancer death for men diagnosed with Gleason scores 4 + 5, 5 + 4, and 5 + 5 on needle biopsy in a population-based cohort. Design, setting, and participantsWe used the data from Prostate Cancer data Base Sweden (PCBaSe) 4.0 for a survival analysis. Among 199 620 men reported to have prostate cancer in 2000–2020, 172 112 were diagnosed on needle biopsy. The primary treatment was classified as androgen deprivation therapy (66%), deferred treatment (5%), radical prostatectomy (7%), or radical radiotherapy (21%). Outcome measurements and statistical analysisThe risks of death from prostate cancer in men with Gleason score 9–10 at 5 and 10 yr were used as endpoints. Multivariable Cox regression models controlling for socioeconomic factors and primary treatment were used for time-to-event analyses of death from prostate cancer and death from any causes. Results and limitationsA total of 20 419 (12%) men had a Gleason score of 9–10, including Gleason scores of 4 + 5, 5 + 4, and 5 + 5 in 14 333 (70%), 4223 (21%), and 1863 (9%) men, respectively. The risks of prostate cancer death for men with Gleason scores 4 + 5, 5 + 4, and 5 + 5 at 10 yr of follow-up were 0.45 (confidence interval [CI] 0.44–0.46), 0.56 (0.55–0.58), and 0.66 (0.63–0.68), respectively. The risks of death of any cause for men with Gleason scores 4 + 5, 5 + 4, and 5 + 5 at 10 yr were 0.73 (CI 0.72–0.74), 0.81 (0.80–0.83), and 0.87 (0.85–0.89), respectively. ConclusionsWe demonstrate in the largest and most complete cohort analyzed to date that collapsing the Gleason scores by grouping results in loss of prognostic information in men with Gleason score 9–10 cancer. Patient summarySurvival of prostate cancer patients with the highest tumor grades varies depending on grade composition.

Risk of prostate cancer death after radical radiotherapy with neoadjuvant and adjuvant therapy with bicalutamide or gonadotropin-releasing hormone agonists

Background Oncological outcome after radical radiotherapy (RRT) combined with neoadjuvant and adjuvant androgen suppression therapy (AST) may differ according to type of AST. The aim of this nationwide register-based study was to investigate risk of prostate cancer (Pca) death after different neoadjuvant and adjuvant ASTs; (i) bicalutamide, (ii) gonadotropin-releasing hormone agonists (GnRH) or (iii) combined bicalutamide and GnRH (CAB), together with RRT. Materials and Methods Data for 6882 men diagnosed with high-risk Pca between 2007 and 2020 and treated with primary RRT was retrieved from Prostate Cancer data Base Sweden (PCBaSe) 5.0. Time to Pca death according to type of neoadjuvant and adjuvant AST was assessed by use of Kaplan–Meier plots and Cox proportional hazard models adjusted for putative confounders. Results Data were stratified by RRT type since the effect of AST in risk of Pca death differed according to type of RRT. Compared with the reference RRT combined with neoadjuvant CAB/adjuvant GnRH, risk of Pca death for men treated with CAB/bicalutamide and conventionally fractionated external beam radiotherapy (CF-EBRT) was hazard ratio (HR) 0.73 (95% CI: 0.50–1.04), hypofractionated EBRT (HF-EBRT), HR 1.35 (95% CI: 0.65–2.81) and EBRT with high dose rate brachytherapy (EBRT-HDRBT), HR 0.85 (95% CI: 0.37–1.95). Risk of Pca death for men treated with bicalutamide/bicalutamide and: (i) CF-EBRT was HR 2.35 (95% CI: 1.42–3.90), (ii) HF-EBRT, HR 0.70 (95% CI: 0.26–1.85), (iii) HF-EBRT, HR 4.07 (95% CI: 1.88–8.77) vs the reference. Conclusion In this observational study, risk of Pca death between men receiving different combinations of AST varied according to RRT type. No difference was found in risk of Pca death for men treated with bicalutamide or GnRH as adjuvant therapy to RRT following neoadjuvant CAB. Risk of Pca death was increased for men with monotherapy neo-/adjuvant bicalutamide in combination with CF-EBRT or EBRT-HDRBT.

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

BackgroundProstate-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. ObjectiveTo 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. Design, setting, and participantsThe 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. InterventionBaseline PSA. Outcome measurements and statistical analysisWe 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. Results 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. ConclusionsWe 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.

Abstract 6486: Single nucleotide polymorphisms that predict serum cholesterol as a prostate cancer prognostic factor - a Mendelian randomization study

Abstract Introduction: Intracellular cholesterol metabolism plays an important role in prostate cancer progression and emergence of treatment resistance. However, it remains unclear whether serum cholesterol and lipoproteins are associated with prostate cancer outcomes. Studies on serum cholesterol and cancer are often confounded by lifestyle factors such as diet and obesity. A possible solution is to use instrumental variables, such as SNPs predicting serum cholesterol. According to the Mendelian randomization theory, germline SNP distribution is unaffected by confounding variables such as diet and lifestyle factors. Objective: To estimate whether SNPs that predict serum cholesterol and lipoproteins also predict mortality among a cohort of men with prostate cancer. Methods: Our study cohort consisted of 3,241 men diagnosed with prostate cancer between 1996-2015, using data collected by the Finnish Randomized Study of Screening for Prostate Cancer. Blood samples were genotyped by PRACTICAL consortium. A UCSC genome browser was utilized for selecting 85 SNPs in lipid metabolism-associated genes. Dates and causes of deaths between 1996-2015 were obtained from the Statistics Finland's statistics on causes of death. Information on serum cholesterol and lipoprotein measurements were obtained from a regional laboratory database.Scores predicting serum cholesterol, LDL, HDL and triglyceride level by SNP genotype were created using linear regression and lasso regression. Risk of prostate cancer death and overall mortality by level of the SNP risk score were evaluated with multivariable-adjusted Cox regression. Follow-up started at prostate cancer diagnosis and continued until death, emigration or common closing date of Dec 31, 2015.Results: SNP score predicting total cholesterol stratified prostate cancer patients both for disease-specific (HR 1.27, 95% CI 0.49-3.28 for highest tertile vs. lowest) and overall survival (HR 1.43, 95% CI 0.94-2.20, p for trend = 0.077), albeit statistical significance was not reached. Similar survival differences were observed for SNP score predicting triglyceride level, but not for scores predicting LDL or HDL.Conclusions: SNPs predicting serum cholesterol and triglycerides are likely prognostic factors for survival of prostate cancer patients. This suggest serum cholesterol and lipoproteins areimportant in prostate cancer progression. Total cholesterol SNP scoreProstate-cancer specific survival Overall survival Citation Format: Sebastian Boele, Aino Siltari, Paavo Raittinen, Johanna Schleutker, Kimmo Taari, Kirsi Talala, Teuvo Tammela, Anssi Auvinen, Teemu J. Murtola. Single nucleotide polymorphisms that predict serum cholesterol as a prostate cancer prognostic factor - a Mendelian randomization study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6486.

Standardized prostate cancer incidence and mortality rates following initial non-malignant biopsy result.

To compare the incidence of subsequent prostate cancer diagnosis and death following an initial non-malignant systematic transrectal ultrasonography (TRUS) biopsy with that in an age- and calendar-year matched population over a 20-year period. This population-based analysis compared a cohort of all men with initial non-malignant TRUS biopsy in Denmark between 1995 and 2016 (N = 37 231) with the Danish population matched by age and calendar year, obtained from the NORDCAN 9.1 database. Age- and calendar year-corrected standardized prostate cancer incidence (SIR) and prostate cancer-specific mortality ratios (SMRs) were calculated and heterogeneity among age groups was assessed with the Cochran's Q test. The median time to censoring was 11 years, and 4434 men were followed for more than 15 years. The corrected SIR was 5.2 (95% confidence interval [CI] 5.1-5.4) and the corrected SMR was 0.74 (95% CI 0.67-0.81). Estimates differed among age groups (P < 0.001 for both), with a higher SIR and SMR among younger men. Men with non-malignant TRUS biopsy have a much higher incidence of prostate cancer but a risk of prostate cancer death below the population average. This underlines that the oncological risk of cancers missed in the initial TRUS biopsy is low. Accordingly, attempts to increase the sensitivity of initial biopsy are unjustified. Moreover, current follow-up after non-malignant biopsy is likely to be overaggressive, particularly in men over the age of 60 years.

A 22-y prospective study of fish intake in relation to prostate cancer incidence and mortality

Background:Fish and seafood n−3 fatty acids may prevent or delay the progression of prostate cancer, but epidemiologic studies do not uniformly support this hypothesis. Objective:We examined the relation of fish and seafood n−3 fatty acid intakes with prostate cancer incidence and mortality. Design:We conducted a prospective cohort study among 20 167 men participating in the Physician's Health Study who were free of cancer in 1983. Results:During 382 144 person-years of follow-up, 2161 men were diagnosed with prostate cancer and 230 died of prostate cancer. Fish intake was unrelated to prostate cancer incidence. Survival analysis among the men diagnosed with prostate cancer revealed that those consuming fish ≥5 times/wk had a 48% lower risk of prostate cancer death than did men consuming fish less than once weekly [relative risk (RR) = 0.52; 95% CI: 0.30, 0.91; P for trend = 0.05]. A similar association was found between seafood n−3 fatty acid intake and prostate cancer mortality (RRQ5 versus Q1 = 0.64; 95% CI: 0.42, 0.99; P for trend = 0.02). These associations became stronger when the analyses were restricted to clinically detected cases. Conclusion:These results suggest that fish intake is unrelated to prostate cancer incidence but may improve prostate cancer survival.

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.

Adjuvant therapy with antiandrogens vs. gonadotropin releasing hormone agonists combined with radiotherapy and risk of prostate cancer death in men with high-risk prostate cancer

Adjuvant therapy with antiandrogens vs. gonadotropin releasing hormone agonists combined with radiotherapy and risk of prostate cancer death in men with high-risk prostate cancer

Time without PSA recurrence after radical prostatectomy as a predictor of future biochemical recurrence, metastatic disease and prostate cancer death: a prospective Scandinavian cohort study

ObjectiveAlthough surveillance after radical prostatectomy routinely includes repeated prostate specific antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be...

Young Age on Starting Prostate-specific Antigen Testing Is Associated with a Greater Reduction in Prostate Cancer Mortality: 24-Year Follow-up of the Göteborg Randomized Population-based Prostate Cancer Screening Trial

BackgroundThe risk of death from prostate cancer (PC) depends on age, but the age at which to start prostate-specific antigen (PSA) screening remains uncertain. ObjectiveTo study the relationship between risk reduction for PC mortality and age at first PSA screening. Design, setting, and participantsThe randomized Göteborg-1 trial invited men for biennial PSA screening between the ages of 50 and 70 yr (screening, n = 10 000) or no invitation but exposure to opportunistic PSA testing (control, n = 10 000). InterventionRegular versus opportunistic PSA screening or no PSA. Outcome measurements and statistical analysisWe modeled the nonlinear association between starting age and the absolute risk reduction in PC mortality in three settings: (1) intention-to-screen (randomized arms); (2) historical control (screening group and 1990–1994 registry data); and (3) attendees only (screening attendees and matched controls). We tested whether the effect of screening on PC mortality depends on the age at starting screening by comparing survival models with and without an interaction between trial arm and age (intention-to-screen and attendees only). Results and limitationsYounger age on starting PSA testing was associated with a greater reduction in PC mortality. Starting screening at age 55 yr approximately halved the risk of PC death compared to first PSA at age 60 yr. The test of association between starting age and the effect of screening on PC mortality was slightly greater than the conventional level of statistical significance (p = 0.052) for the entire cohort, and statistically significant among attendees (p = 0.002). This study is limited by the low number of disease-specific deaths for men starting screening before age 55 yr and the difficulty in discriminating between the effect of starting age and screening duration. ConclusionsGiven that prior screening trials included men aged up to 70 yr on starting screening, our results suggest that the effect size reported in prior trials underestimates that of currently recommended programs starting at age 50–55 yr. Patient summaryIn this study from the Göteborg-1 trial, we looked at the effect of prostate-specific antigen (PSA) screening in reducing men’s risk of dying from prostate cancer given the age at which they begin testing. Starting at a younger age reduced the risk of prostate cancer death by a greater amount. We recommend that PSA screening should start no later than at age 55 yr.

Polygenic risk of any, metastatic, and fatal prostate cancer in the Million Veteran Program.

Genetic scores may provide an objective measure of prostate cancer risk and thus inform screening decisions. We evaluated whether a polygenic hazard score based on 290 genetic variants (PHS290) is associated with prostate cancer risk in a diverse population, including Black men, who have higher average risk of prostate cancer death but are often treated as a homogeneously high-risk group. This was a retrospective analysis of the Million Veteran Program, a national, population-based cohort study of US military veterans conducted 2011-2021. Cox proportional hazards analyses tested for association of genetic and other risk factors (including self-reported race and ethnicity and family history) with age at death from prostate cancer, age at diagnosis of metastatic (nodal or distant) prostate cancer, and age at diagnosis of any prostate cancer. A total of 590 750 male participants were included. Median age at last follow-up was 69 years. PHS290 was associated with fatal prostate cancer in the full cohort and for each racial and ethnic group (P < .001). Comparing men in the highest 20% of PHS290 with those in the lowest 20% (based on percentiles from an independent training cohort), the hazard ratio for fatal prostate cancer was 4.42 (95% confidence interval = 3.91 to 5.02). When accounting for guideline-recommended risk factors (family history, race, and ethnicity), PHS290 remained a strong independent predictor of any, metastatic, and fatal prostate cancer. PHS290 stratified US veterans of diverse ancestry for lifetime risk of prostate cancer, including metastatic and fatal cancer. Predicting genetic risk of lethal prostate cancer with PHS290 might inform individualized decisions about prostate cancer screening.

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.

The prostate tissue-based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy.

Current biomarkers are inadequate prognostic predictors in localized prostate cancer making treatment decision‐making challenging. Previously, we observed that the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer‐associated stromal cells – the telomere biomarker – is strongly associated with progression to metastasis and prostate cancer death after prostatectomy independent of currently used pathologic indicators. Here, we optimized our method allowing for semi‐automated telomere length determination in single cells in fixed tissue, and tested the telomere biomarker in five cohort studies of men surgically treated for clinically localized disease (N = 2,255). We estimated the relative risk (RR) of progression to metastasis (N = 311) and prostate cancer death (N = 85) using models appropriate to each study's design adjusting for age, prostatectomy stage, and tumor grade, which then we meta‐analyzed using inverse variance weights. Compared with men who had less variable telomere length among prostate cancer cells and longer telomere length in prostate cancer‐associated stromal cells, men with the combination of more variable and shorter telomere length had 3.76 times the risk of prostate cancer death (95% confidence interval [CI] 1.37–10.3, p = 0.01) and had 2.23 times the risk of progression to metastasis (95% CI 0.99–5.02, p = 0.05). The telomere biomarker was associated with prostate cancer death in men with intermediate risk disease (grade groups 2/3: RR = 9.18, 95% CI 1.14–74.0, p = 0.037) and with PTEN protein intact tumors (RR = 6.74, 95% CI 1.46–37.6, p = 0.015). In summary, the telomere biomarker is robust and associated with poor outcome independent of current pathologic indicators in surgically treated men.