Real-world utilization, patient characteristics, and treatment patterns among men with localized prostate cancer tested with the 17-gene genomic prostate score® (GPSTM) assay.

OBJECTIVES: Descriptive study focusing on real-world utilization and characteristics of men with prostate cancer tested with the 17-gene Genomic Prostate Score® (GPS™) assay by linking administrative claims and electronic health record (EHR) data with GPS results. METHODS: This retrospective, observational cohort study (January 1, 2013 to December 31, 2020) included men aged 40-80 years with localized prostate cancer claims, continuous enrollment in Optum's Integrated Claims data set, ≥1 day of EHR clinical activity, and a GPS result. Men were classified as undergoing definitive therapy (DT) (prostatectomy, radiation, or focal therapy) or active surveillance (AS). AS and DT distribution were analyzed across GPS results, National Comprehensive Cancer Network® (NCCN®) risk, and race. Costs were assessed 6 months after the first GPS result (index); clinical outcomes and AS persistence were assessed during the variable follow-up. All variables were analyzed descriptively. RESULTS: Of 834 men, 650 (77.9%) underwent AS and 184 (22.1%) DT. Most men had Quan-Charlson comorbidity scores of 1-2 and a tumor stage of T1c (index). The most common Gleason patterns were 3 + 3 (79.6%) (AS cohort) and 3 + 4 (55.9%) (DT cohort). The mean (standard deviation) GPS results at index were 23.2 (11.3) (AS) and 30.9 (12.9) (DT). AS decreased with increasing GPS result and NCCN risk. Differences between races were minimal. Total costs were substantially higher in the DT cohort. CONCLUSIONS: Most men with GPS-tested localized prostate cancer underwent AS, indicating the GPS result can inform clinical management. Decreasing AS with increasing GPS result and NCCN risk suggests the GPS complements NCCN risk stratification.

A west African ancestry-associated SNP on 8q24 predicts a positive biopsy in African American men with suspected prostate cancer following PSA screening.

BACKGROUND: African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of the PCa susceptibility variants exhibit distinct allele frequencies and risk estimates across different races and contribute substantially to the large disparities of PCa incidence among races. We previously reported that a single-nucleotide polymorphism (SNP) in 8q24, rs7824364, was strongly associated with west African ancestry and increased risks of PCa in both AA and Puerto Rican men. In this study, we determined whether this SNP can predict biopsy positivity and detection of clinically significant disease (Gleason score [GS] ≥ 7) in a cohort of AA men with suspected PCa. METHODS: SNP rs7824364 was genotyped in 199 AA men with elevated total prostate-specific antigen (PSA) (>2.5 ng/mL) or abnormal digital rectal exam (DRE) and the associations of different genotypes with biopsy positivity and clinically significant disease were analyzed. RESULTS: The variant allele carriers were significantly over-represented in the biopsy-positive group compared to the biopsy-negative group (44% vs. 25.7%, p = 0.011). In the multivariate logistic regression analyses, variant allele carriers were at a more than a twofold increased risk of a positive biopsy (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.06-4.32). Moreover, the variant allele was a predictor (OR = 2.26, 95% CI = 1.06-4.84) of a positive biopsy in the subgroup of patients with PSA < 10 ng/mL and normal DRE. The variant allele carriers were also more prevalent in cases with GS ≥ 7 compared to cases with GS < 7 and benign biopsy. CONCLUSIONS: This study demonstrated that the west African ancestry-specific SNP rs7824364 on 8q24 independently predicted a positive prostate biopsy in AA men who were candidates for prostate biopsy subsequent to PCa screening.

A Multi-Institutional Study of Magnetic Resonance/Ultrasound Fusion-Guided Nanoparticle-Directed Focal Therapy for Prostate Ablation.

PURPOSE: Focal therapy aims to provide a durable oncologic treatment option for men with prostate cancer (PCa), while preserving their quality of life. Most focal therapy modalities rely on the direct tissue effect, resulting in a possible nontargeted approach to ablation. Here, we report the results of the first human feasibility trial utilizing nanoparticle-directed focal photothermal ablation for PCa. MATERIALS AND METHODS: A prospective, open-label, single-arm, multicenter study of men with localized PCa in Gleason Grade Group 1 to 3 was conducted. Men received a single infusion of gold nanoparticles (AuroShells), followed by magnetic resonance (MR)/ultrasound (US) fusion-guided laser excitation of the target tissue to induce photothermal ablation. MRI was used to assess the effectiveness of prostate tissue ablation at 48 to 96 hours, 3 months, and 12 months post treatment. At 3 months, a targeted fusion biopsy of the lesion(s) was conducted. At 12 months, a targeted fusion biopsy and standard templated biopsy were performed. Treatment success was determined based on a negative MR/US fusion biopsy outcome within the treated area. RESULTS: Forty-six men were enrolled in the study, and 44 men with 45 lesions completed nanoparticle infusion and laser treatment. The mean PSA level at baseline was 9.5 ng/mL, which decreased to 5.9 ng/mL at 3 months and to 4.7 ng/mL at 12 months (P < .0001). The oncologic success rates at 3 and 12 months resulted in 29 (66%) and 32 (73%) of 44 patients, respectively, being successfully treated, confirmed with negative MR/US fusion biopsies within the ablation zone. Among Gleason Grade Group, maximum lesion diameter on MRI, prostate volume, and Prostate Imaging Reporting and Data System scoring, the maximum lesion diameter was significantly associated with the odds of treatment failure at 12 months (P = .046). CONCLUSIONS: Nanoparticle-directed focal laser ablation of neoplastic prostate tissue resulted in 73% of patients with successful treatment at 12 months post treatment, confirmed by negative MR/US fusion biopsy of the treated lesion and a systematic biopsy. CLINICAL TRIAL REGISTRATION NO.: 02680535.

Current Landscape of Surgical Assessment Models in Urology Residency Training.

PURPOSE: Assessing trainees' surgical proficiency is an important aspect of urological surgical training. The current standard is the Urology Milestone Project, initially implemented in 2013. This evaluation is limited in that it contains only 3 questions on surgical competency per surgical modality with assessments occurring semi-annually without real-time operative feedback. However, since the Urology Milestones Project's inception a plethora of competency-based surgical assessment tools have been described. We aim to perform a comprehensive review of the literature of these available tools and analyze their strengths and weaknesses as a way of providing a repository of available assessment strategies for further development of a more comprehensive and standardized assessment tool. MATERIALS AND METHODS: A review of the primary literature was performed using key words such as "surgical assessment tools urology," "surgical assessment tools prostate," "bladder surgical assessment tools," "renal surgical assessment tools urology," and "surgical assessment tools urology task specific." Technical and nontechnical skill assessments were included. One reviewer identified and analyzed studies that published assessment tools for use in surgical and urological training. RESULTS: A total of 1,497 articles published between 1997-2022 were identified. Of these, 34 met the inclusion criteria. Eighteen (52.9%) were specialty nonspecific and 16 (47.1%) were specific for urological training. Of the 18 tools developed for general surgical principles, 12 (66.7%) had some form of validity, 9 (50.0%) were significantly reliable, and 2 (11.1%) were externally validated. Of the 16 tools developed specifically for use in urology training, 13 (81.3%) had some form of validity, 7 (43.8%) were significantly reliable, and none were externally validated. Of these 16 tools, 12 (75.0%) were procedure-specific and 4 (25.0%) were developed for general use in endourological procedures. CONCLUSIONS: Surgical training is evolving toward a competency-based model, as evidenced by the increase in assessment tools created within the past 10 years. These instruments not only provide objective feedback to trainees, but also monitor progression. However, they are heterogeneous in construct and utilization. There remains a need for the adoption of a standardized, valid, and reliable tool, ie, both procedure-specific and generalizable across multiple procedures for use in urology training.

Metformin and testosterone replacement therapy inversely associated with hormone-associated cancers (prostate, colorectal and male breast cancers) among older White and Black men.

BACKGROUND: The independent and joint association of metformin and testosterone replacement therapy (TTh) with the incidence of prostate, colorectal, and male breast cancers remain poorly understood, including the investigation of the risk of these cancers combined (HRCs, hormone-associated cancers) among men of different racial and ethnic background. METHODS: In 143,035 men (≥ 65 yrs old) of SEER-Medicare 2007-2015, we identified White (N = 110,430), Black (N = 13,520) and Other Race (N = 19,085) men diagnosed with incident HRC. Pre-diagnostic prescription of metformin and TTh was ascertained for this analysis. Weighted multivariable-adjusted conditional logistic and Cox proportional hazards models were conducted. RESULTS: We found independent and joint associations of metformin and TTh with incident prostate (odds ratio [OR]joint = 0.44, 95% confidence interval [CI]: 0.36-0.54) and colorectal cancers (ORjoint = 0.47, 95% CI: 0.34-0.64), but not with male breast cancer. There were also inversed joint associations of metformin and TTh with HRCs (ORjoint = 0.45, 95% CI: 0.38-0.54). Similar reduced associations with HRCs were identified among White, Black, and Other Race men. CONCLUSION: Pre-diagnostic use of metformin and TTh were, independently and jointly, inversely associated with incident prostate and colorectal cancers. The risk of HRCs was also reduced among White, Black and Other Race men. Greatest reduced associations of prostate and colorectal cancers and HRCs were mainly observed in combination of metformin and TTh. Larger studies are needed to confirm the independent and joint association of metformin plus TTh with these cancers in understudied and underserved populations.

Gold nanoshell-localized photothermal ablation of prostate tumors in a clinical pilot device study.

Biocompatible gold nanoparticles designed to absorb light at wavelengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance-ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function.

The role of testosterone replacement therapy and statin use, and their combination, in prostate cancer.

PURPOSE: Previous studies have reported conflicting results in the associations of testosterone replacement therapy (TTh) and statins use with prostate cancer (PCa). However, the combination of these treatments with PCa stage and grade at diagnosis and prostate cancer-specific mortality (PCSM) and by race/ethnicity remains unclear. METHODS: We identified non-Hispanic White (NHW, N = 58,576), non-Hispanic Black (NHB, n = 9,703) and Hispanic (n = 4,898) men diagnosed with PCa in SEER-Medicare data 2007-2011. Pre-diagnostic prescription of TTh and statins was ascertained for this analysis. Multivariable-adjusted logistic and Cox proportional hazards models were used to evaluate the association of TTh and statins use with PCa stage and grade and PCSM. RESULTS: 22.5% used statins alone, 1.2% used TTh alone, and 0.8% used both. TTh and statins were independently, inversely associated with PCa advanced stage and high grade. TTh plus statins was associated with 44% lower odds of advanced stage PCa (OR 0.56, 95% CI 0.35-0.91). As expected, similar inverse associations were present in NHWs as the overall cohort is mostly comprised NHW men. In Hispanic men, statin use with or without TTh was inversely associated with aggressive PCa. CONCLUSIONS: Pre-diagnostic use of TTh or statins, independent or in combination, was inversely associated with aggressive PCa, including in NHW and Hispanics men, but was not with PCSM. The findings for use of statins with aggressive PCa are consistent with cohort studies. Future prospective studies are needed to explore the independent inverse association of TTh and the combined inverse association of TTh plus statins on fatal PCa.

Caffeine intake is not associated with serum testosterone levels in adult men: cross-sectional findings from the NHANES 1999-2004 and 2011-2012.

OBJECTIVE: The association of caffeine intake with testosterone remains unclear. We evaluated the association of caffeine intake with serum testosterone among American men and determined whether this association varied by race/ethnicity and measurements of adiposity. METHODS: Data were analyzed for 2581 men (≥20 years old) who participated in the cycles of the NHANES 1999-2004 and 2011-2012, a cross-sectional study. Testosterone (ng/mL) was measured by immunoassay among men who participated in the morning examination session. We analyzed 24-h dietary recall data to estimate caffeine intake (mg/day). Multivariable weighted linear regression models were conducted. RESULTS: We identified no linear relationship between caffeine intake and testosterone levels in the total population, but there was a non-linear association (pnonlinearity < .01). Similarly, stratified analysis showed nonlinear associations among Mexican-American and Non-Hispanic White men (pnonlinearity ≤ .03 both) and only among men with waist circumference <102 cm and body mass index <25 kg/m2 (pnonlinearity < .01, both). CONCLUSION: No linear association was identified between levels of caffeine intake and testosterone in US men, but we observed a non-linear association, including among racial/ethnic groups and measurements of adiposity in this cross-sectional study. These associations are warranted to be investigated in larger prospective studies.

Coffee Intake and Incidence of Erectile Dysfunction.

Coffee intake is suggested to have a positive impact on chronic diseases, yet its role in urological diseases such as erectile dysfunction (ED) remains unclear. We investigated the association of coffee intake with incidence of ED by conducting the Health Professionals Follow-Up Study, a prospective analysis of 21,403 men aged 40-75 years old. Total, regular, and decaffeinated coffee intakes were self-reported on food frequency questionnaires. ED was assessed by mean values of questionnaires in 2000, 2004 and 2008. Multivariable adjusted Cox proportional hazards models were used to compute hazard ratios for patients with incident ED (n = 7,298). No significant differences were identified for patients with incident ED after comparing highest (≥4 cups/day) with lowest (0 cups/day) categories of total (hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.90, 1.11) and regular coffee intakes (HR = 1.00, 95% CI: 0.89, 1.13). When comparing the highest category with lowest category of decaffeinated coffee intake, we found a 37% increased risk of ED (HR = 1.37, 95% CI: 1.08, 1.73), with a significant trend (P trend = 0.02). Stratified analyses also showed an association among current smokers (P trend = 0.005). Overall, long-term coffee intake was not associated with risk of ED in a prospective cohort study.

Informed decision making before prostate-specific antigen screening: Initial results using the American Cancer Society (ACS) Decision Aid (DA) among medically underserved men.

BACKGROUND: The American Cancer Society (ACS) recommends men have the opportunity to make an informed decision about screening for prostate cancer (PCa). The ACS developed a unique decision aid (ACS-DA) for this purpose. However, to date, studies evaluating the efficacy of the ACS-DA are lacking. The authors evaluated the ACS-DA among a cohort of medically underserved men (MUM). METHODS: A multiethnic cohort of MUM (n = 285) was prospectively included between June 2010 and December 2014. The ACS-DA was presented in a group format. Levels of knowledge on PCa were evaluated before and after the presentation. Participants' decisional conflict and thoughts about the presentation also were evaluated. Logistic regression analyses were performed to determine factors associated with having an adequate level of knowledge. RESULTS: Before receiving the ACS-DA, 33.1% of participants had adequate knowledge on PCa, and this increased to 77% after the DA (P < .0001). On multivariate analysis, higher education level (odds ratio, 11.19; P = .001) and history of another cancer (odds ratio, 7.45; P = .03) were associated with having adequate knowledge after receiving the DA. Levels of decisional conflict were low and were correlated with levels of knowledge after receiving the DA. The majority of men also rated the presentation as favorable and would recommend the ACS-DA to others. CONCLUSIONS: Use of the ACS-DA was feasible among MUM and led to increased PCa knowledge. This also correlated with low levels of decisional conflict. The ACS-DA presented to groups of men may serve as a feasible tool for informed decision making in a MUM population. Cancer 2017;123:583-591. © 2016 American Cancer Society.

Local treatments for metastases of renal cell carcinoma: a systematic review.

Local treatment of metastases such as metastasectomy or radiotherapy remains controversial in the treatment of metastatic renal cell carcinoma. To investigate the benefits and harms of various local treatments, we did a systematic review of all types of comparative studies on local treatment of metastases from renal cell carcinoma in any organ. Interventions included metastasectomy, radiotherapy modalities, and no local treatment. The results suggest that patients treated with complete metastasectomy have better survival and symptom control (including pain relief in bone metastases) than those treated with either incomplete or no metastasectomy. Nevertheless, the available evidence was marred by high risks of bias and confounding across all studies. Although the findings presented here should be interpreted with caution, they and the identified gaps in knowledge should provide guidance for clinicians and researchers, and directions for further research.

Association of sleep duration and quality with serum testosterone concentrations among men and women: NHANES 2011-2016.

BACKGROUND: The association between testosterone concentrations and sleep duration is poorly understood. OBJECTIVE: To evaluate the association between sleep duration and quality with serum testosterone concentrations and its variation by sex and age. METHODS: Data were analyzed for 8748 men and women (≥20 years old) who participated in the cycles of the National Health and Nutrition Examination Survey 2011-2016, a cross-sectional study. Total testosterone (ng/dL) was measured and categorized (low, moderate, and high) based on established cut-offs for men and its tertile distribution among women. Sleep duration was classified as ≤6, 7-8, and ≥9 h. Sleep quality was classified as poor or good based on the frequency of trouble falling or staying asleep or sleeping too much. Weighted multivariable adjusted and multinomial logistic regression models were conducted to assess these associations. RESULTS: The association between sleep duration and testosterone concentrations, varied according to sex and age. Sleep deprivation (≤6 h) was associated with high testosterone (odds ratio = 3.62; 95% confidence interval: 1.37, 9.53) among young men (20-40 years old); meanwhile, middle-aged men (41-64 years old) who reported more sleep duration had low testosterone (odds ratio = 2.03; 95% confidence interval: 1.10, 3.73). A J-shaped association between sleep duration and low testosterone (odds ratio≤6 h  = 1.57; 95% confidence interval: 1.10, 2.27; odds ratio≥9  h  = 2.06; 95% confidence interval: 1.18, 3.59) was observed in women aged 41-64 years. We did not find any association with sleep quality. CONCLUSION: The association of sleep duration with serum testosterone concentrations varies with sex and age group. Prospective studies are warranted to confirm these sex and age group differences.

Incidence of prostate, colorectal and male breast cancers in relation with statins and testosterone replacement therapy: SEER-Medicare 2007-2015.

INTRODUCTION: Statins and testosterone replacement therapy (TTh) have been inconsistently associated with a reduced risk of hormone-related cancers (HRCs, prostate [PCa], colorectal [CRC], and male breast cancers [BrCa]). Yet, the joint association of statins and TTh with the incidence of these cancers, and whether these associations vary by race, remains poorly understood. The objective of this retrospective cohort study is to examine the independent and joint effects of pre-diagnostic use of statins and TTh on the risk of HRCs, including PCa, CRC, and male BrCa. MATERIALS: and Methods: In 105,690 men (≥65 yrs) identified using the SEER-Medicare 2007-2015 data, we identified 82,578 White and 10,256 Black men. Pre-diagnostic prescription of statins and TTh was ascertained for this analysis and categorized into four groups (Neither users, statins alone, TTh alone and Dual users). Multivariable Time-varying Cox proportional hazards and Accelerated Failure Time (AFT) models were performed. RESULTS: We found inverse joint associations of statins and TTh with incident HRCs before (aHR: 0.39; 95 % CI: 0.35-0.44) and after 3 years of follow-up (aHR: 0.74; 95 % CI: 0.67-0.82). This included a lower risk for advanced stage HRC (only <3 years follow-up). Similar joint associations were identified with incident PCa, aggressive PCa, incident CRC, and its specific right- and left-sided CRC (only <3 years follow-up). In general, the inverse associations persisted among White (mainly <3 years follow-up) and Black men (high-grade HRC and <3 years follow-up). Findings from the AFT analysis were similar. DISCUSSION: Pre-diagnostic use of statins and TTh were, independently and jointly, associated with reduced risks of HRC and specific cancer sites at three years of follow-up overall, and among White and Black men. Greatest associations of HRCs risk reduction were observed among dual users (statins plus TTh). Further studies are needed to validate these findings, including larger samples of Black men, and male BrCa sites.

Evaluating the impact of pre-diagnostic use of statins and testosterone replacement therapy on mortality outcomes in older men with hormone-related cancers: Surveillance, Epidemiology, and End Results-Medicare 2007-2015.

BACKGROUND: The link between the pre-diagnostic use of statins and testosterone replacement therapy and their impact on hormone-related cancers, prostate cancer, colorectal cancer, and male breast cancer survival remains a topic of controversy. Further, there is a knowledge gap concerning the joint effects of statins and testosterone replacement therapy on hormone-related cancer survival outcomes. OBJECTIVE: To examine the independent and joint effects of pre-diagnostic use of statins and testosterone replacement therapy on the risk of all-cause and cause-specific mortality among older men diagnosed with hormone-related cancers, including prostate cancer, colorectal cancer, and male breast cancer. METHODS: In 41,707 men (≥65 years) of Surveillance, Epidemiology, and End Results-Medicare 2007-2015, we identified 31,097 prostate cancer, 10,315 colorectal cancer, and 295 male breast cancer cases. Pre-diagnostic prescription of statins and testosterone replacement therapy was ascertained and categorized into four groups (Neither users, statins alone, testosterone replacement therapy alone, and Dual users). Multivariable-adjusted Cox proportional hazards and competing-risks (Fine-Gray subdistribution hazard) models were conducted. RESULTS: No significant associations were found in Cox-proportional hazard models for hormone-related cancers. However, in the Fine-Gray competing risk models among high-grade hormone-related cancers, statins alone had an 11% reduced risk of hormone-related cancer-specific death (hazard ratio: 0.89; 95% confidence interval: 0.81-0.99; p 0.0451). In the prostate cancer cohort with both statistical models, the use of testosterone replacement therapy alone had a 24% lower risk of all-cause death (hazard ratio: 0.76; 95% confidence interval: 0.59-0.97; p 0.0325) and a 57% lower risk of prostate cancer-specific death (hazard ratio: 0.43; 95% confidence interval: 0.24-0.75; p 0.0029). Similar inverse associations were found among aggressive prostate cancer cases with testosterone replacement therapy alone and statins alone. No significant associations were found in the colorectal cancer and male breast cancer sub-groups. CONCLUSION: Pre-diagnostic use of statins and testosterone replacement therapy showed a survival benefit with reduced mortality in high-grade hormone-related cancer patients (only statins) and aggressive prostate cancer patients in both statistical models. Findings of testosterone replacement therapy use in aggressive prostate cancer settings could facilitate clinical trials. Further studies with extended follow-up periods are needed to substantiate these findings.

Use of weight loss medications in relation with prostate, colorectal and male breast cancers among older men: SEER-Medicare 2007-2015.

BACKGROUND: The association of weight loss medications with prostate (PCa), colorectal (CRC) or male breast cancers, including assessment of these cancers combined (HRCs, hormone-associated cancers) remain poorly understood. Testosterone replacement therapy (TTh) is reported to be inversely associated with obesity, PCa and CRC, but it is unclear whether TTh modifies the association of weight loss medications with HRCs. METHODS: In 49,038 men (≥ 65 years) of SEER-Medicare, we identified 15,471 men diagnosed with PCa, 4836 with CRC, and 141 with male breast cancers. Pre-diagnostic prescription of weight loss medications and TTh was ascertained for this analysis. Weighted multivariable-adjusted conditional logistic and Cox proportional hazards (mortality) models were conducted. RESULTS: We found an inverse association between use of weight loss medications and incident PCa (OR 0.59, 95% CI 0.57-0.62), CRC (OR 0.86, 95% CI 0.80-0.92), and HRCs (OR 0.65, 95% CI 0.62-0.68). Similar associations were observed for advanced stage at diagnosis of PCa and CRC. Effects of weight loss medications on PCa and HRC remained significant irrespective of the use of TTh but were only suggestive with CRC with positive TTh use. No associations were observed with male breast cancer and HRCs mortality. CONCLUSION: Pre-diagnostic use of weight loss medications reduced the incidence of PCa, CRC, and HRCs. These associations persisted in the same direction irrespective of the history of TTh use. Future studies are needed to confirm these findings and to identify underlying biological mechanisms of weight loss medications and TTh on the risk of cancer.

Joint association of statins and testosterone replacement therapy with cardiovascular disease among older men with prostate cancer: SEER-Medicare 2007-2015.

BACKGROUND: Use of statins and testosterone replacement therapy (TTh) have been independently linked with prostate cancer (PCa) and cardiovascular diseases (CVD). However, there is a research gap about the joint association of statins and TTh with CVD among PCa survivors and a matched cancer-free cohort. METHODS: In SEER-Medicare 2007-2015 (N = 35,990 men), we identified 17,995 PCa survivors, and 17,995 age- and index-matched cancer-free men. Pre-diagnostic prescription of statins and TTh was ascertained for this analysis and examined in two matched cohorts. Weighted multivariable-adjusted conditional logistic regression models were used to evaluate the independent and joint associations of statins and TTh with CVD. RESULTS: We found that independently statins (OR = 0.48, 95% CI: 0.44-0.53) and TTh (OR = 0.74, 95% CI: 0.0.61-0.90) were each inversely associated with CVD in the overall sample. TTh plus statins was inversely associated with CVD (OR = 0.50, 95% CI: 0.36-0.70, Pinteraction = 0.03). Similar associations were observed among the matched cancer-free cohort. Among PCa survivors, only statins (OR = 0.62, 95% CI: 0.56-0.68) and combination of TTh plus statins (OR = 0.63, 95% CI: 0.44-0.90) were inversely associated with CVD, but not the independent use of TTh. CONCLUSION: Pre-diagnostic use of statins and TTh, independent or in combination, were inversely associated with CVD in the overall and cancer-free populations, but among PCa survivors it was mainly use of statins, not TTh. Greater reduced effects on CVD were observed with statins or in combination with statins, but not with TTh. Future studies need to confirm these associations among older men with aggressive PCa.

Low testosterone and high cholesterol levels in relation to all-cause, cardiovascular disease, and cancer mortality in White, Black, and Hispanic men: NHANES 1988-2015.

PURPOSE: The role of testosterone (T) deficiency (T ≤ 300 ng/dL) and hypercholesterolemia (total cholesterol ≥ 240 mg/dL) in the risk of all-cause cardiovascular diseases (CVD) and cancer mortality among a nationally representative sample of non-Hispanic White (NHW), non-Hispanic Black (NHB) and Hispanic men remains poorly understood. METHODS: Data included a full sample (NHANES 1988-1991, 1999-2004, 2011-2014) and subset sample (excluding 2011-2012, no estradiol and SHBG levels available) of 5379 and 3740 men, respectively. Participants were aged ≥ 20 y with serum T and cholesterol data (median follow-up 7.6 years). Weighted multivariable-adjusted Cox proportional hazards models were used in this study. RESULTS: In the overall population of full and subset samples, hypercholesterolemia was inversely associated with all-cause (HR = 0.76, 95% CI, 0.63-0.91) and cancer mortality (HR = 0.56, 95% CI, 0.34-0.90). Similar findings were observed among NHW men, but higher T levels increased the risk of CVD mortality in the subset sample (T3 vs T1, Ptrend = 0.02). Among NHB men in the full and subset samples, T deficiency increased the risk of CVD mortality, but T3 vs. T1 decreased it (Ptrend = 0.03), and hypercholesterolemia decreased cancer mortality. Among Hispanic men in the full and subset samples, T deficiency increased, and hypercholesterolemia decreased the risk of CVD mortality. CONCLUSION: Hypercholesterolemia was inversely associated with cancer mortality. However, higher levels of T were positively associated with CVD mortality among NHW and were inversely associated with CVD mortality among NHB and Hispanic men. Larger prospective studies are warranted to clarify the underlying relationship between T and cholesterol with mortality among racial and ethnic groups.

Rating the quality of evidence and the strength of recommendations using GRADE.

OBJECTIVES: Urologists can benefit from a standardized system for guideline development and presentation. This article introduces the GRADE system and explains how it may be useful for Urologic physicians, in their practice and in their healthcare systems. METHODS: The GRADE system is reviewed. Specific aspects of how GRADE rates the quality of the evidence and the strength of recommendations are explored. RESULTS: GRADE can provide explicit and structured guidance, which separates the quality of evidence from the strength of recommendations. This information can be used by consumers of guidelines, including patients, physicians, and policy makers. CONCLUSIONS: Urologists can benefit from a more transparent and rigorous framework when formulating recommendations. GRADE is an emergent proposal with broader implications for healthcare policy as well.