Risk Of High-grade Prostate Cancer Research Articles

(213) Assessing Primary Care Physicians Awareness of 5-Alpha Reductase Inhibitors for Men with Benign Prostatic Hyperplasia

Abstract Introduction Primary care physicians (PCPs) commonly prescribe 5-alpha-reductase inhibitors (5-ARIs) for the management of benign prostatic hyperplasia (BPH). 5-ARIs can affect prostate-specific antigen (PSA) kinetics by decreasing PSA levels by approximately half, and therefore delay the early detection of prostate cancer (PCa). Objective To determine PCPs’ level of awareness and indications for urology referral in patients treated with 5-ARIs. Methods After IRB approval, an anonymous survey was emailed to affiliated PCPs at an academic urban institution. Questions focused on residency graduation year, patient volume, knowledge of 5-ARIs and their effects on PSA, role of 5-ARIs in PCa prevention, and indications for prostate biopsy referral. PCPs were stratified by residency graduation year before or after 2010, or medical specialty of Family Medicine or Internal Medicine. Survey responses were summarized with descriptive statistics and responses between groups (residency graduation year or medical specialty) were compared using Chi-squared test. Results A total of 182 PCPs were emailed, of which 30 responded (16.5% response rate). Thirteen PCPs (43.3%) graduated residency before 2010 and 17 (56.7%) after 2010. Sixteen PCPs (53.3%) were Family Medicine physicians and 14 (46.7%) were Internists. The majority of PCPs reported that every 6 months, they saw at least one patient with BPH (96.7%), ordered at least one PSA test (86.7%), and referred at least one patient for a prostate biopsy (56.7%). Forty percent of PCPs were not aware of the suppressive effects of 5-ARIs on PSA, 70.0% would not refer a patient for a prostate biopsy who is taking 5-ARIs and has an elevated corrected PSA, 70.0% were not sure or thought that 5-ARIs may decrease the risk of high-grade PCa, and 43.3% were not sure or thought that 5-ARIs are approved for the prevention of PCa. There were no significant differences in the knowledge of 5-ARIs and their effects on PSA, role of 5-ARIs in PCa prevention, or indications for prostate biopsy referral between PCPs who graduated residency before 2010 and after 2010, or between PCPs who were Family Medicine physicians and Internists (p>0.05 for all). Conclusions There is a general lack of awareness amongst PCPs on the knowledge of 5-ARIs and indications for biopsy referral in patients treated with 5-ARIs. An educational opportunity exists to optimize usage of 5-ARIs and avoid delaying PCa detection. Disclosure No.

Sexually and Non-sexually Transmitted Infections and The risk of Prostate Cancer

Abstract Introduction Prostate cancer (PCa) is by far the most common type of cancer among men in western countries. However, relatively little is known about its etiology despite the high morbidity and mortality rates, where only advanced age, ethnicity, and family history of prostate cancer are well-established non-modifiable risk factors. It has been suggested that chronic inflammation may be involved in the development of prostate carcinogenesis. Therefore, our objective was to investigate the role of sexually and non-sexually transmitted infections in the occurrence of prostate cancer with a specific interest in the aggressive types based on data from EPICAP. Methods EPICAP is a population-based case-control study conducted in the département of Hérault, France, between 2012 and 2014. A total of 819 incident cases and 879 controls were interviewed face-to-face using a standardized questionnaire gathering information on known or suspected risk factors of prostate cancer and personal history of specific sexually and non-sexually transmitted infections: Gonorrhea, Syphilis, Trichomonas, Herpes, Mononucleosis, Epstein Barr, Varicella-zoster, and Dengue. Odds Ratios (OR) and their 95% confidence interval were estimated using multivariate unconditional logistic regression. Results No association emerged for the history of sexually transmitted infections (OR 1.04, 95%CI: 0.84-1.25) and non-sexually transmitted infections (OR1.09, 95%CI: 0.89-1.34) and the risk of prostate cancer. Even for all the infections studied separately, there was no association with the risk of low-grade or high-grade prostate cancer. Conclusions Our results showed that sexually or non-sexually transmitted infections do not seem to be risk factors for prostate cancer in the EPICAP study. Therefore, further investigation is needed to help advance our understanding of the role of chronic inflammation in the etiology of prostate cancer, with a particular focus on its most aggressive types.

Association of Obesity with Prostate Cancer at Time of Biopsy: A MultiCentre 10-Year Retrospective Study

Background and Aim: The incidence of Prostate cancer (PCa) is on the rise in Cameroon, making it the most commonly diagnosed cancer amongst men. Factors, such as obesity, smoking, and the consumption of high fat diet have been reported to play a role in the aetiology and progression of cancers in general. However, the exact relationship between obesity and prostate cancer in Africans is still poorly described. The present study aimed to evaluate the association between obesity as measured by the body mass index (BMI) and high-grade prostate cancer in Cameroonians. Methods: This was a retrospective analyses of the clinical records of 300 consecutive men who underwent transrectal ultrasound-guided core needle prostate biopsy between January 2010 and January 2020. Patients were grouped as obese (BMI ≥30kg/m²) and non-obese (BMI <30kg/m²) and binary logistic regression modelling was used to compare the association between obesity and patient characteristics, such as age, digital rectal examination (DRE) findings, prostate specific antigen (PSA) level, prostate volume, PSA density, and Gleason score (GS). Results: The mean age at diagnosis of PCa was 65.46 ± 8.54 years (Range: 34-89 years), the mean BMI was 28.93 ± 4.57 kg/m² (Range: 18.35-42.37 kg/m²), and the median total PSA level was 44.2 ng/ml. In total, 142 men (47.3%) were obese and biopsies detected high-grade prostate cancer in 160 men (63.3%). Obese men were significantly younger and had a higher risk (OR= 2.74, p <0.001) of having high-grade PCa compared to nonobese men. Furthermore, 94 obese men (58.75%) had high-grade PCa. Obese men had higher age-adjusted PSA densities (P<0.001), while there was no statistical difference in DRE findings (OR= 1.06, p= 0.225). Conclusion: This study demonstrated that obesity is associated with a higher risk of high-grade prostate cancer. This risk is more pronounced among younger patients and DRE findings are not influenced by BMI.

Impact of modifiable lifestyle risk factors for prostate cancer prevention: a review of the literature.

Although prostate cancer (PCa) is one of the most common cancers among men, the impact of modifiable risk and protective factors is still being debated. This review aims to qualitatively summarize the most recent studies related to potential healthy lifestyle factors affecting the development of PCa. The literature focusing on modifiable risk factors for prostate cancer was reviewed. Medline and Embase via the Ovid database were searched, and all relevant and inherent articles were analyzed. Non-eligible publications, such as review articles, editorials, comments, guidelines, or case reports, were excluded. This review confirms that there is strong evidence that being overweight or obese increases the risk of advanced prostate cancer (assessed by body mass index (BMI), waist circumference, and waist-hip ratio), particularly considering central adiposity and ethnicity as contributing factors. The possible contribution of smoking still seems not entirely clear, while alcohol seems to affect PCa prevention in patients taking 5α-reductase inhibitors (5-ARIs). Dietary fibers may have anti-inflammatory properties and improve insulin sensitivity by reducing IGF bioactivity. In particular, dietary fiber intake like insoluble and legume fibers may be inversely associated with prostate cancer risk. Also, hyperglycemia and hyperinsulinemia, with untreated diabetic fasting blood glucose levels, could be modifiable prostate cancer risk factors. In two studies, aspirin was associated with a lower risk of lethal PCa and overall mortality. Concerning the role of vitamins, despite conflicting and divergent results, serum retinol concentration seems to be associated with an increased risk of prostate cancer and high-grade prostate cancer. Some studies resulted in disagreement about the role of selenium and vitamin E. We found inconsistent and controversial findings about the association between vitamin D and prostate cancer risk. Far from being conclusive evidence, our findings confirm some strong evidence already found in the previous literature and highlight the need to clarify the role of some risk factors whose role is not yet completely known. This effort would facilitate the cultural and social change that may allow the shift from the treatment of prostate cancer when diagnosed to the real efforts needed for systematic prevention.

Family structure and living arrangements as indicators of social isolation, and prostate cancer risk

Social isolation has been linked to a poorer prostate cancer prognosis. Little is known about how it could also influence its incidence. We investigated the association between family structure and living arrangements as potential indicators of social isolation, and prostate cancer risk, globally and according to disease aggressiveness.Data from the Prostate Cancer & Environment Study (PROtEuS), a case-control population-based study conducted between 2005 and 2012 in Montreal, Canada, were used. The study population comprised 1931 incident cases of prostate cancer, aged ≤75 years, and 1994 age-matched (±5 years) population controls. In-person interviews collected information on family composition and living arrangements recently and at age 40. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders.Single men had an increased risk of high-grade prostate cancer at diagnosis (OR 1.80; 95% CI 1.29–2.51), compared to men currently married or with a partner. Having at least one daughter was associated with a lower risk of aggressive cancer (OR 0.76; 95% CI 0.61–0.96) while no association was found with having son(s). An inverse dose-response relationship was observed between the number of people living with the subject 2 years before diagnosis/interview and prostate cancer risk (p-trend<0.001).These results suggest a protective role of a rich personal environment on the risk of developing prostate cancer. As several of the associations studied here are novel, replication is required.

Prostate-specific membrane antigen (PSMA), androgen modulation, folic acid, and high-grade prostate cancer: An intriguing nexus needing attention

Prostate cancer is the most common cancer, excluding skin cancer, diagnosed among men in the US. Autopsy studies confirm the high prevalence of indolent prostate cancers starting in the third decade of life. There are lifestyle and therapeutic factors that might be facilitating the transformation of indolent to high-grade cancers throughout life. Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed on prostate cancer cells and has diagnostic, prognostic and therapeutic implications. Emerging evidence has elucidated many of its biologic functions, including folate acquisition from the gut, transporting unmetabolized circulating folic acid into prostate cancer cells, involvement in physiologic and neoplastic angiogenesis and redirecting cell survival signaling pathways. Folates are utilized by the prostate for various aspects of reproductive biology. Synthetic oxidized folic acid has been used in grain and cereal fortification in the US since 1998; as a result, folate levels have more than doubled, and most individuals exhibit unmetabolized folic acid in the circulation. In fact, folic acid from fortified foods and supplements is the main driver of folate levels in the population. However, folic acid is a double-edged sword and can support nucleotide synthesis and prostate cancer cell proliferation. As such, the promotion of high-grade prostate cancer by folic acid, but not natural folates, has been evidenced in prospective trials. Ironically, androgen deprivation therapy (ADT), used in the treatment of prostate cancer, leads to increases in both PSMA expression and folate levels. Therefore, we hypothesize that avoiding folic acid intake from fortified foods and supplements will decrease the risk of high-grade prostate cancer and decrease prostate cancer progression, particularly among men undergoing treatment with ADT. Moreover, the nexus of PSMA, folic acid, androgen modulation and high-grade prostate cancer is discussed, along with practical and therapeutic implications. Finally, questions are raised which should spur interest in research that might translate into a reduction in high-grade prostate cancer.

5-alpha reductase inhibitors use in prostatic disease and beyond.

5-alpha reductase inhibitors (5-ARIs) are commonly used and widely available, with benefits observed from their effect on androgen signalling. Their effect relies on the inhibition of the 5-alpha reductase enzyme which aids in the conversion of testosterone to dihydrotestosterone. 5-ARIs have increasing clinical relevance outside of benign prostatic hyperplasia (BPH). Such development requires clinicians to have an updated review to guide clinical practices. This review details the pharmacology and mechanisms of action for 5-ARIs and how this relates to multiple clinical indications. Of note, is the debunked association between finasteride and increased risk of high-grade prostate cancer. Furthermore, adverse effects of 5-ARI use are detailed in this review, with specific mentions to post-finasteride syndrome. In addition to overviews pertaining to BPH and prostate cancer, much attention has also been focused on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The androgen axis may be associated with an increased virulence for SARS-CoV-2 in men, with some reporting a correlation between the severity of illness and androgenic alopecia. Since these observations, the role of antiandrogens, including 5-ARIs, has been explored further in SARS-CoV-2. Increasing understanding of pathological processes involving the androgen axis in which 5-ARIs work, has led to increasing clinical indications for 5-ARIs. Several novel off-label indications have been suggested including its potential role in the pathogenesis of SARS-CoV-2, but to date, these claims have not been substantiated. Previously held truths regarding the role of 5-ARIs and prostate carcinogenesis have been contested, inadvertently leading to the re-exploration of 5-ARIs utility in prostate cancer. With growing evidence into pathological processes involving the androgen axis, 5-ARIs are likely to become increasingly more used. This review serves as a timely update of 5 ARIs pharmacology, current indications and potential future directions.

Prostate-specific Antigen Density Cutoff of 0.15 ng/ml/cc to Propose Prostate Biopsies to Patients with Negative Magnetic Resonance Imaging: Efficient Threshold or Legacy of the Past?

BackgroundA prostate-specific antigen density (PSAd) cutoff of 0.15 ng/ml/cc is a commonly recommended threshold to identify patients with negative prostate magnetic resonance imaging (MRI) who should proceed to a prostate biopsy. We were unable to find any study that explicitly examined the properties of this threshold compared with others. ObjectiveTo investigate whether the 0.15 cutoff is justified for selecting patients at risk of harboring high-grade cancer (Gleason score ≥3 + 4) despite negative MRI. Design, setting, and participantsA cohort of 8974 prostate biopsies provided by the Prostate Biopsy Collaborative Group (PBCG) was included in the study. Outcome measurements and statistical analysisLocally weighted scatterplot smoothing was used to investigate whether there was a change in the risk of high-grade cancer around this value. We examined whether the use of this cutoff in patients with negative MRI corresponds to a reasonable threshold probability for a biopsy (defined as a 10% risk of high-grade disease). To do so, we applied the negative likelihood ratio of MRI, calculated from eight studies on prostate MRI, to the risk curve derived from the PBCG. Results and limitationsThere was no discontinuity in the risk of high-grade prostate cancer at a PSAd cutoff of 0.15. This cutoff corresponded to a probability of high-grade disease ranging from 2.6% to 10%, depending on MRI accuracy. Using 10% as threshold probability, the corresponding PSAd cutoff varied between 0.15 and 0.38, with the threshold increasing for greater MRI accuracy. Possible limitations include difference between studies on MRI and the use of ultrasound to measure prostate volume. ConclusionsThe 0.15 cutoff to recommend prostate biopsies in patients with negative MRI is justified only under an extreme scenario of poor MRI properties. We recommend a value of at least ≥0.20. Our results suggest the need for future studies to look at how to best identify patients who need prostate biopsies despite negative MRI, likely by using individualized risk prediction. Patient summaryIn this study, we investigated whether the commonly used prostate-specific antigen density cutoff of 0.15 is justified to identify patients with negative magnetic resonance imaging (MRI) who should proceed to a prostate biopsy. We found that this cutoff is appropriate only in case of very poor MRI quality, and a higher cutoff (≥0.20) should be used for the average MRI.

Association between obesity and frequency of high-grade prostate cancer on biopsy in men: A single-center retrospective study.

The present study aimed to investigate the relationship between BMI and the prostate cancer (PCa) risk at biopsy in Italian men. Retrospective analyses of the clinical data of 2,372 consecutive men undergoing ultrasound-guided multicore (≥10) prostate biopsy transrectally between May 2010 and December 2018 were performed. BMIs were categorized, according to Western countries' classification of obesity, as follows: <18.5 kg/m2 (underweight), 18.5-24.99 kg/m2 (normal weight), 25-30 kg/m2 (overweight) and >30 kg/m2 (obese). The distribution of patients undergoing biopsy was compared with a model population from the official survey data. Patient characteristics and the relationships between characteristics were investigated using correlation analysis, ANOVA, Kruskal-Wallis and Dunn's tests. The present study estimated the influence on cancer incidence not only of BMI but also of other patient characteristics using multi-variable logistic modelling and compared, using the models, the expected outcomes for patients who differed only in BMI. From a sample of 2,372 men, the present study enrolled 1,079 men due to a lack of clinical data [such as prostate specific antigen (PSA) and BMI data] in the other patients undergoing prostate biopsy. Their distribution was significantly different from the model distribution with the probability of undergoing biopsy increasing with increasing BMI. The median age was 69.4 years. The median BMI was 26.4 kg/m2, while the median PSA level was 7.60 ng/ml. In total, the biopsies detected PCa in 320 men (29.7%) and high-grade PCa (HGPCa) in 218 men (20.2%). Upon applying the aforementioned Western countries' criteria for BMI categories, there were 4 (0.4%) underweight, 318 (29.5%) of normal weight, 546 (50.6%) overweight, and 211 (19.6%) obese patients. ANOVA/Kruskal-Wallis tests revealed that overweight and obese men were younger than the normal-weight men, while there was no statistical difference in their PSA values. Furthermore, 29.3% of normal-weight men, 29.5% of overweight men and 29.9% of obese men were diagnosed with PCa, while 19.5% of normal-weight men, 20.1% of overweight men and 21.8% of obese men were affected by severe cancer. BMI was found to be positively correlated with PCa risk and negatively correlated with both age and PSA level. Age and PSA level were both positively correlated with PCa risk, while digital rectal examination (DRE) outcome was strongly indicative of PCa discovery if the test outcome was positive. Logistics models attributed a positive coefficient to BMI when evaluated against both PCa risk and HGPCa risk. In patients having a negative DRE outcome who differed only in BMI, logistic regression showed a 60% increased risk of PCa diagnosis in obese patients compared with in normal-weight patients. This risk difference increased when other characteristics were less indicative of PCa (younger age/lower PSA), while it decreased when patient characteristics were more indicative (older age/higher PSA, positive DRE). In conclusion, the present study demonstrated that, in men with higher BMIs, the risk of PCa is higher. The relative difference in risk between low and high BMI is most pronounced in younger patients having a lower PSA level and a negative DRE outcome.

Associations Between Vertebral Marrow Proton Density Fat Fraction and Risk of Prostate Cancer.

Bone marrow adipocytes may be responsible for cancer progression. Although marrow adipogenesis is suspected to be involved in prostate carcinogenesis, an association between marrow adiposity and prostate cancer risk has not been clearly established in vivo. This work included 115 newly diagnosed cases of histologically confirmed prostate cancer (range, 48–79 years) and 87 age-matched healthy controls. Marrow proton density fat fraction (PDFF) was measured by 3.0-T MR spectroscopy at the spine lumbar. Associations between marrow PDFF and risk of prostate cancer by stage of disease and grade sub-types were performed using multivariable polytomous logistic regression. There were no significant group differences in the vertebral marrow PDFF, despite prostate cancer patients having 6.6% higher marrow PDFF compared to the healthy controls (61.7 ± 9.8% vs. 57.9 ± 6.5%; t = 1.429, p = 0.161). After adjusting for various clinical and demographic characteristics, we found that elevated marrow PDFF was related to an increased risk of high-grade prostate cancer [odds ratios (OR) = 1.31; 95% confidence interval (CI), 1.08–1.57; p = 0.003]. Likewise, increased marrow PDFF had a significantly positive correlation with aggressive prostate cancer risk (OR = 1.54; 95% CI, 1.13–1.92; p <0.001). There were no associations between marrow PDFF and low-grade (p = 0.314) or non-aggressive (p = 0.435) prostate cancer risk. The data support the hypothesis that marrow adiposity was correlated with increased risk of aggressive prostate cancer, supporting a link between adipogenesis and prostate cancer risk.

Increased risk of high-grade prostate cancer among testicular cancer survivors.

IntroductionTesticular cancer survivors (TCS) have an increased risk of additional cancers, including prostate cancer. Our understanding of the natural history of prostate cancer in testicular cancer survivors is very limited due to its rare incidence.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) Registry from 1978 to 2011, we identified 282 TCS with subsequent prostate cancer and examined the tumor grade and clinical outcomes in contrast to men with primary prostate cancer in the general population.ResultsTCS with a subsequent prostate cancer diagnosis were more likely to be diagnosed at a younger age than men with primary prostate cancer (65.2% vs. 37.6% for age ≤65, 34.8% vs. 62.4% for age >65, p<0.001) and were more likely to have grade III/IV tumors (46.2% vs. 37.0%, p<0.002). Longer latency between testicular and prostate cancer diagnoses was associated with a higher risk of grade III/IV (p<0.001) cancer. Despite the increased risk for high-grade tumors, 10-year prostate cancer-specific survival and overall survival were not significantly different between TCS and men with primary prostate cancer. Based on the available information in SEER, we found that prior history of radiotherapy for testicular cancer had no impact on tumor grade or survival outcomes.ConclusionsProstate cancer in TCS was more likely to be diagnosed at a younger age and with higher grades. Risks of grade III/IV disease increased with longer latency between testicular and prostate cancer diagnoses. Radiotherapy for testicular cancer did not appear to have a significant impact on the outcome of subsequent prostate cancer.

Associations Between Polymorphisms in Genes Related to Oxidative Stress and DNA Repair, Interactions With Serum Antioxidants, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial.

Study of polymorphisms in genes related to the generation and removal of oxidative stress and repair of oxidative DNA damage will lead to new insights into the genetic basis of prostate cancer. In the Prostate Cancer Prevention Trial (PCPT), a double-blind, randomized controlled trial testing finasteride versus placebo for prostate cancer prevention, we intend to investigate the role of oxidative stress/DNA repair mechanisms in prostate cancer etiology and whether these polymorphisms modify prostate cancer risk by interacting with antioxidant status in both placebo and finasteride arms. We evaluated associations of selected candidate polymorphisms in genes in these pathways, and interactions with pre-diagnostic serum antioxidants, and the risk of prostate cancer among 1,598 cases and 1,706 frequency-matched controls enrolled in the PCPT. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable-adjusted logistic regression models. While there were no statistically significant associations observed in the placebo arm, several SNPs were associated with prostate cancer in the finasteride arm. Specifically, APEX1-rs1760944 was associated with increased risk of total prostate cancer (per minor allele: p-trend=0.04). OGG1-rs1052133 was positively (CG/GG vs. CC: OR=1.32, 95% CI: 1.01-1.73) and NOS3-rs1799983 was inversely (per minor allele: p-trend=0.04) associated with risk of low-grade prostate cancer. LIG3-rs1052536 and XRCC1-rs25489 were suggestively associated with reduced risk of high-grade prostate cancer (per minor allele: both p-trend=0.04). In the placebo arm, significant associations were observed among men with higher serum lycopene for APEX1-rs1760944 and NQO1-rs1800566, or higher serum β-cryptoxanthin for ERCC4-rs1800067. In the finasteride arm, stronger associations were observed among men with lower serum lycopene for NOS3-rs1799983, higher serum α-carotene, β-carotene, and β-cryptoxanthin for LIG3-rs1052536, or lower serum retinol for SOD2-rs1799725. These results suggest that germline variations in oxidative stress and DNA repair pathways may contribute to prostate carcinogenesis and that these associations may differ by intraprostatic sex steroid hormone status and be further modified by antioxidant status. Findings provide insights into the complex role of gene, gene-antioxidant and -finasteride interactions in prostate cancer etiology, and thus may lead to the development of preventative strategies.

Obesity, Physical Activity and Prostate Cancer: An Overview

Obesity and a lack of sufficient physical activity (PA) are recognized as risk factors for most civilization diseases, including cancer. This study synthesized the current evidence evaluating the relationship between excess body weight and prostate cancer (PCa) in the relation to the disease risk, progression, and mortality, and identifies biological plausibility of the association. We also estimated the importance of PA in intentional body weight loss. Several electronic major databases to identify eligible articles were searched until March 2022. A total 22 observational articles, the literature on the underlying biological mechanisms, and the crucial evidence of a role of PA in body weight maintenance and reduction were reviewed. The available knowledge suggests that association between body mass index and PCa is conflicting. However, the most research consistently shown that overweight/obesity was associated with higher risk of high-grade PCa and dying of PCa. Overweight/obesity can promote high-grade PCa through increased levels of secreted adipokines, increased formation of proinflammatory agents, and reduced concentration of adiponectin, among others. Being obese may by also linked with a higher risk of mortality. Exercise can decrease these health consequences related with obesity and may be effective in reduction of PCa-specific mortality, however, there are relative few studies on PA and PCa prevention among obese individuals.

Defining the Impact of Family History on Detection of High-grade Prostate Cancer in a Large Multi-institutional Cohort

BackgroundThe risk of high-grade prostate cancer, given a family history of cancer, has been described in the general population, but not among men selected for prostate biopsy in an international cohort. ObjectiveTo estimate the risk of high-grade prostate cancer on biopsy based on a family history of cancer. Design, setting, and participantsThis is a multicenter study of men undergoing prostate biopsy from 2006 to 2019, including 12 sites in North America and Europe. All sites recorded first-degree prostate cancer family histories; four included more detailed data on the number of affected relatives, second-degree relatives with prostate cancer, and breast cancer family history. Outcomes measurements and statistical analysisMultivariable logistic regressions evaluated odds of high-grade (Gleason grade group ≥2) prostate cancer. Separate models were fit for family history definitions, including first- and second-degree prostate cancer and breast cancer family histories. Results and limitationsA first-degree prostate cancer family history was available for 15 799 men, with a more detailed family history for 4617 (median age 65 yr, both cohorts). Adjusted odds of high-grade prostate cancer were 1.77 times greater (95% confidence interval [CI] 1.57−2.00, p < 0.001, risk ratio [RR] = 1.40) with first-degree prostate cancer, 1.38 (95% CI 1.07−1.77, p = 0.011, RR = 1.22) for second-degree prostate cancer, and 1.30 (95% CI 1.01−1.67, p = 0.040, RR = 1.18) for first-degree breast cancer family histories. Interaction terms revealed that the effect of a family history did not differ based on prostate-specific antigen but differed based on age. This study is limited by missing data on race and prior negative biopsy. ConclusionsMen with indications for biopsy and a family history of prostate or breast cancer can be counseled that they have a moderately increased risk of high-grade prostate cancer, independent of other risk factors. Patient summaryIn a large international series of men selected for prostate biopsy, finding a high-grade prostate cancer was more likely in men with a family history of prostate or breast cancer.

Predicting high-grade prostate cancer at initial biopsy: clinical performance of the ExoDx (EPI) Prostate Intelliscore test in three independent prospective studies

BackgroundThe ability to discriminate indolent from clinically significant prostate cancer (PC) at the initial biopsy remains a challenge. The ExoDx Prostate (IntelliScore) (EPI) test is a noninvasive liquid biopsy that quantifies three RNA targets in urine exosomes. The EPI test stratifies patients for risk of high-grade prostate cancer (HGPC; ≥ Grade Group 2 [GG] PC) in men ≥ 50 years with equivocal prostate-specific antigen (PSA) (2–10 ng/mL). Here, we present a pooled meta-analysis from three independent prospective-validation studies in men presenting for initial biopsy decision.MethodsPooled data from two prospective multi-site validation studies and the control arm of a clinical utility study were analyzed. Performance was evaluated using the area under the receiver-operating characteristic curve (AUC), negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity for discriminating ≥ GG2 from GG1 and benign pathology.ResultsThe combined cohort (n = 1212) of initial-biopsy subjects had a median age of 63 years and median PSA of 5.2 ng/mL. The EPI AUC (0.70) was superior to PSA (0.56), Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) (0.62), and The European Randomized Study of Screening for Prostate Cancer (ERSPC) (0.59), (all p-values <0.001) for discriminating GG2 from GG1 and benign histology. The validated cutoff of 15.6 would avoid 23% of all prostate biopsies and 30% of “unnecessary” (benign or Gleason 6/GG1) biopsies, with an NPV of 90%.ConclusionsEPI is a noninvasive, easy-to-use, urine exosome–RNA assay that has been validated across 3 independent prospective multicenter clinical trials with 1212 subjects. The test can discriminate high-grade (≥GG2) from low-grade (GG1) cancer and benign disease. EPI effectively guides the biopsy-decision process independent of PSA and other standard-of-care factors.

Effect of Statins on the Risk of Different Stages of Prostate Cancer: A Meta-Analysis

Introduction: The aim of this article was to investigate the relationship between statins and the risk of different stages or grades of prostate cancer. Methods: A comprehensive literature search was performed for articles published until December 18, 2020, on the PubMed, Embase, and the Cochrane Library databases. The pooled relative risk (RR) and 95% confidence interval (CI) were then analyzed using the STATA.16.0 software. Results: A total of 588,055 patients from 14 studies were included in the analysis. We found that the use of statins expressed a significant correlation with a lower risk of advanced prostate cancer (RR = 0.81, 95% CI: 0.73–0.91; RR = 0.86, 95% CI: 0.75–0.99, respectively). However, no evidence suggested that the use of statins was beneficial for the prevention of localized prostate cancer incidence. Similarly, the pooled results also revealed no association between the use of statins and the risk of high-grade and low-grade prostate cancer. Conclusion: It has been found that the use of statins is associated with a lower risk of advanced prostate cancer but was not related to the risk of localized, low-grade, or high-grade prostate cancer.

MP30-14 5-ARI USAGE ASSOCIATED WITH MORE ADVANCED PROSTATE CANCER AT DIAGNOSIS

You have accessJournal of UrologyProstate Cancer: Detection & Screening III (MP30)1 Sep 2021MP30-14 5-ARI USAGE ASSOCIATED WITH MORE ADVANCED PROSTATE CANCER AT DIAGNOSIS Emily Roebuck, Wei Sha, Caroline Lu, Caroline Miller, Earle F Burgess, Claud M Grigg, Jason Zhu, Kris E Gaston, Stephen B Riggs, Justin T Matulay, Peter E Clark, and James T Kearns Emily RoebuckEmily Roebuck More articles by this author , Wei ShaWei Sha More articles by this author , Caroline LuCaroline Lu More articles by this author , Caroline MillerCaroline Miller More articles by this author , Earle F BurgessEarle F Burgess More articles by this author , Claud M GriggClaud M Grigg More articles by this author , Jason ZhuJason Zhu More articles by this author , Kris E GastonKris E Gaston More articles by this author , Stephen B RiggsStephen B Riggs More articles by this author , Justin T MatulayJustin T Matulay More articles by this author , Peter E ClarkPeter E Clark More articles by this author , and James T KearnsJames T Kearns More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002027.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) risk is often modeled at referral based on Prostate Cancer Prevention Trial (PCPT) and Prostate Biopsy Collaborative Group (PBCG) risk calculators, which account for factors such as PSA, DRE, age, race, family history, and prior biopsy history. Prospective PCa chemoprevention trials noted an increased risk of high-grade prostate cancer among men using 5-ARIs, and subsequent retrospective data associates 5-ARI use with delayed diagnoses and worse cancer outcomes than non-users. The objective of this study was to assess clinical characteristics and treatment types between 5-ARI users versus non-users at prostate biopsy and PCa diagnosis. METHODS: Men undergoing prostate biopsy at our institution between January 2018–December 2021 were retrospectively reviewed for clinical and demographic data. Patients with previously diagnosed PCa were excluded. For categorical demographic or biopsy variables, Chi-square test was used to determine if there is a significant association between these variables and 5-ARI usage. For continuous demographic variables, quantile regression was used to compare the medians between 5-ARI users and non-users. False discovery rate (FDR) adjusted P value was used for multiple tests. RESULTS: Among 842 patients, 83 men were using 5-ARIs at time of biopsy (Table 1). Demographic characteristics including age, race, marital status, BMI, or family history were similar across the two cohorts. PSA was greater among 5-ARI users (p=.054). At PCa diagnosis, 5-ARI users tended to have higher clinical T stage (p<0.0001) and NCCN risk group stratification (p=.0119). Gleason Grade Group (p=0.372), prostate volume (p=.1838), DRE (p=.5849), and treatment type (p>.05 for all) were not statistically different between users and non-users. CONCLUSIONS: While not emphasized in common risk calculators, pre-diagnostic use of 5-ARI should be considered when deciding to biopsy. Our findings demonstrate 5-ARI usage associated with more advanced clinical T stage and higher NCCN risk though not Gleason Grade, suggesting that 5-ARI is a risk factor to consider at referral and highlighting the need to optimize diagnostic care for 5-ARI users. Source of Funding: No source of funding © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e505-e505 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Emily Roebuck More articles by this author Wei Sha More articles by this author Caroline Lu More articles by this author Caroline Miller More articles by this author Earle F Burgess More articles by this author Claud M Grigg More articles by this author Jason Zhu More articles by this author Kris E Gaston More articles by this author Stephen B Riggs More articles by this author Justin T Matulay More articles by this author Peter E Clark More articles by this author James T Kearns More articles by this author Expand All Advertisement Loading ...

PD65-03 PROSTATE SPECIFIC ANTIGEN THRESHOLD OF 1.0 PREDICTS LONG-TERM PROSTATE CANCER RISK FROM A PROSPECTIVE COHORT ANALYSIS

You have accessJournal of UrologyProstate Cancer: Detection & Screening VII (PD65)1 Sep 2021PD65-03 PROSTATE SPECIFIC ANTIGEN THRESHOLD OF 1.0 PREDICTS LONG-TERM PROSTATE CANCER RISK FROM A PROSPECTIVE COHORT ANALYSIS Christine Ibilibor, Jonathan Gelfond, Martin Goros, Teresa Johnson-Pais, Robin Leach, Ian M. Thompson, and Michael Liss Christine IbiliborChristine Ibilibor More articles by this author , Jonathan GelfondJonathan Gelfond More articles by this author , Martin GorosMartin Goros More articles by this author , Teresa Johnson-PaisTeresa Johnson-Pais More articles by this author , Robin LeachRobin Leach More articles by this author , Ian M. ThompsonIan M. Thompson More articles by this author , and Michael LissMichael Liss More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002109.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We investigated baseline prostate specific antigen (PSA) testing related to the future risk of prostate cancer development to inform optimal screening timepoints. METHODS: The San Antonio Biomarkers of Risk (SABOR) cohort is a contemporary, multi-ethnic, multi-racial population of men with no prostate cancer diagnosis at the time of enrollment in 2000. We calculated the risk of developing high-grade prostate cancer by applying the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPT RC) at enrollment and annually for up to 15-years of follow up. We used baseline risk factors and PSA to estimate long-term PCPT risk of high-grade prostate cancer using a linear mixed effects model. We stratified the risk groups by baseline PSA level above or below 1 ng/ml. RESULTS: We analyzed data from 4,170 men with a median follow up of 5.6 years (interquartile range of 0.9 to 11.6 years). The proportion of patients whose baseline PSA was > 1.0ng/ml with a PCPT risk of high-grade cancer greater than 5% at 5-, 10-, and 15-years of follow-up was 42.8%, 63.8%, and 77.9%, respectively, compared to 2.5%, 10.8%, and 28.1% for men whose baseline PSA was < 1.0ng/ml. Notably, when PCPT risk of high-grade disease and follow up time were modelled, age and African American race had a greater impact on risk of high-grade disease than PSA. CONCLUSIONS: Men with a baseline PSA level < 1 ng/ml maintain a low risk for the development of high-grade prostate cancer over a 5-year period, arguing for less frequent PSA testing in this population. Source of Funding: This research was supported in part by funding from the National Cancer Institute (U01 CA096492 and P30 CA054174) and the Cancer Prevention and Research Institute of Texas CPRIT (RP170345). Christine Ibilibor has received research support through the University of Texas Health Science Center at San Antonio Cancer CPRIT Research Training Award (RP170345) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1152-e1153 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christine Ibilibor More articles by this author Jonathan Gelfond More articles by this author Martin Goros More articles by this author Teresa Johnson-Pais More articles by this author Robin Leach More articles by this author Ian M. Thompson More articles by this author Michael Liss More articles by this author Expand All Advertisement Loading ...

Individual Patient Data Meta-analysis of Discrimination of the Four Kallikrein Panel Associated With the Inclusion of Prostate Volume

ObjectiveTo assess whether adding prostate volume to the kallikrein panel improves discrimination for ISUP Grade Group 2 or higher (GG2+) disease, as some men may have volume measurements available at the time of blood draw. While prostate volume predicts biopsy outcome, it requires an imaging procedure for measurement. The four kallikrein panel - commercially available as the 4Kscore - predicts risk of GG2+ disease and requires only a blood draw. Materials and MethodsA total of 9131 patients with available prostate volume and total PSA ≤25 ng/ml from 5 historical (sextant biopsy, pre-ISUP 2005 grading) and 4 contemporary cohorts (10+ cores, ISUP 2005 grading). Previously published kallikrein panel models were used to predict risk of GG2+. Volume was added to the model in each cohort and change in discrimination was meta-analyzed. ResultsIncreased prostate volume was associated with decreased risk of GG2+ disease after controlling for the kallikrein panel in 7/9 cohorts. However, kallikrein panel discrimination (0.817, 95% CI 0.802, 0.831) was not improved after including volume (AUC difference 0.002, 95% CI -0.003, 0.006). Heterogeneity (P <.0001) was driven by an AUC increase in 1 cohort of academic cancer centers (0.044, 95% CI 0.025, 0.064), with no evidence of heterogeneity after excluding this cohort (P = .15). ConclusionThe kallikrein panel provides a non-invasive approach to assess the risk of high-grade prostate cancer. Our results do not justify the inclusion of prostate volume in the four kallikrein panel. There is some evidence that the predictive value of prostate volume is provider dependent: further research is needed to address this question.

Rotterdam mobile phone app including MRI data for the prediction of prostate cancer: A multicenter external validation

ObjectivesThe Rotterdam Prostate Cancer Risk calculator (RPCRC) has been validated in the past years. Recently a new version including multiparametric magnetic resonance imaging (mpMRI) data has been released. The aim of our study was to analyze the performance of the mpMRI RPCRC app. MethodsA series of men undergoing prostate biopsies were enrolled in eleven Italian centers. Indications for prostate biopsy included: abnormal Prostate specific antigen levels (PSA>4 ng/ml), abnormal DRE and abnormal mpMRI. Patients’ characteristics were recorded. Prostate cancer (PCa) risk and high-grade PCa risk were assessed using the RPCRC app. The performance of the mpMRI RPCRC in the prediction of cancer and high-grade PCa was evaluated using receiver operator characteristics, calibration plots and decision curve analysis. ResultsOverall, 580 patients were enrolled: 404/580 (70%) presented PCa and out of them 224/404 (55%) presented high-grade PCa. In the prediction of cancer, the RC presented good discrimination (AUC = 0.74), poor calibration (p = 0.01) and a clinical net benefit in the range of probabilities between 50 and 90% for the prediction of PCa (Fig. 1). In the prediction of high-grade PCa, the RC presented good discrimination (AUC = 0.79), good calibration (p = 0.48) and a clinical net benefit in the range of probabilities between 20 and 80% (Fig. 1). ConclusionsThe Rotterdam prostate cancer risk App accurately predicts the risk of PCa and particularly high-grade cancer. The clinical net benefit is wide for high-grade cancer and therefore its implementation in clinical practice should be encouraged. Further studies should assess its definitive role in clinical practice.