Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART I-Initial Work-up and Medical Management.

PURPOSE: Benign prostatic hyperplasia (BPH) is a histologic diagnosis describing proliferation of smooth muscle and epithelial cells within the prostatic transition zone. The prevalence and severity of lower urinary tract symptoms (LUTS) in aging men are progressive and impact the health and welfare of society. This revised Guideline provides a useful reference on effective evidence-based management of male LUTS/BPH. See the accompanying algorithm for a summary of the procedures detailed in the Guideline (figures 1 and 2[Figure: see text][Figure: see text]). MATERIALS AND METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible English language studies published between January 2008 and April 2019, then updated through December 2020. Search terms included Medical Subject Headings (MeSH) and keywords for pharmacological therapies, drug classes, and terms related to LUTS or BPH. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). RESULTS: Nineteen guideline statements pertinent to evaluation, work-up, and medical management were developed. Appropriate levels of evidence and supporting text were created to direct both primary care and urologic providers towards streamlined and suitable practices. CONCLUSIONS: The work up and medical management of BPH requires attention to individual patient characteristics, while also respecting common principles. Clinicians should adhere to recommendations and familiarize themselves with standards of BPH management.

Active surveillance for intermediate-risk prostate cancer in African American and non-Hispanic White men.

BACKGROUND: The safety of active surveillance (AS) for African American men compared with non-Hispanic White (White) men with intermediate-risk prostate cancer is unclear. METHODS: The authors identified patients with modified National Comprehensive Cancer Network favorable ("low-intermediate") and unfavorable ("high-intermediate") intermediate-risk prostate cancer diagnosed between 2001 and 2015 and initially managed with AS in the Veterans Health Administration database. They analyzed definitive treatment, disease progression, metastases, prostate cancer-specific mortality (PCSM), and all-cause mortality by using cumulative incidences and multivariable competing-risks (disease progression, metastasis, and PCSM) or Cox (all-cause mortality) regression. RESULTS: The cohort included 1007 men (African Americans, 330 [32.8%]; Whites, 677 [67.2%]) followed for a median of 7.7 years; 773 (76.8%) had low-intermediate-risk disease, and 234 (23.2%) had high-intermediate-risk disease. The 10-year cumulative incidences of definitive treatment were not significantly different (African Americans, 83.5%; 95% confidence interval [CI], 78.5%-88.7%; Whites, 80.6%; 95% CI, 76.6%-84.4%; P = .17). Among those with low-intermediate-risk disease, there were no significant differences in the 10-year cumulative incidences of disease progression (African Americans, 46.8%; 95% CI, 40.0%-53.3%; Whites, 46.9%; 95% CI, 42.1%-51.5%; P = .91), metastasis (African Americans, 7.1%; 95% CI, 3.7%-11.8%; Whites, 10.8%; 95% CI, 7.6%-14.6%; P = .17), or PCSM (African Americans, 3.8%; 95% CI, 1.6%-7.5%; Whites, 3.8%; 95% CI, 2.0%-6.3%; P = .69). In a multivariable regression including the entire cohort, African American race was not associated with increased risks of definitive treatment, disease progression, metastasis, PCSM, or all-cause mortality (all P > .30). CONCLUSIONS: Outcomes in the Veterans Affairs Health System were similar for African American and White men treated for low-intermediate-risk prostate cancer with AS.

Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts.

OBJECTIVES: To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. DESIGN: Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa. SETTING: Multiple institutions that were members of international PRACTICAL consortium. PARTICIPANTS: All consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men. MAIN OUTCOME MEASURES: Prediction with hazard score of age of onset of aggressive cancer in validation set. RESULTS: In the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10-16). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score. CONCLUSIONS: Polygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.

Nutrition, physical activity, and lifestyle factors in prostate cancer prevention.

PURPOSE OF REVIEW: To review current evidence for prostate cancer prevention with nutrition, physical activity, and lifestyle interventions and identify future research directions. RECENT FINDINGS: Multiple preclinical and observational studies have observed that diet, exercise, and lifestyle interventions may play a role in mitigating disease progression, mortality, and overall disease burden for high-grade and fatal prostate cancer. Increased vegetable and fruit intakes, decreased red meat and saturated fat intakes, and increased exercise are potentially associated with decreased risk of incident disease and increased progression-free, prostate cancer-specific, and overall survival. Randomized controlled trials (RCTs) have demonstrated that selenium and vitamin C supplements are ineffective in preventing incident prostate cancer and that vitamin E supplements potentially increase incident prostate cancer risk. A large RCT of a high vegetable diet intervention among prostate cancer patients on active surveillance, the Men's Eating and Living study, will soon complete analysis. An RCT for an exercise intervention among men with metastatic castrate-resistant prostate cancer is currently accruing. SUMMARY: Although preclinical and observational studies have identified potential benefits for high vegetable, low fat, low meat diets, and increased exercise, Level I evidence is limited. To inform clinical care, future research should focus on RCTs evaluating clinical effectiveness.

Prostate Cancer Prevention: Concepts and Clinical Trials.

Prevention is an important treatment strategy for diminishing prostate cancer morbidity and mortality and is applicable to both early- and late-stage disease. There are three basic classifications of cancer prevention: primary (prevention of incident disease), secondary (identification and treatment of preclinical disease), and tertiary (prevention of progression or recurrence). Based on level I evidence, 5-alpha reductase inhibitors (5-ARIs) should be considered in selected men to prevent incident prostate cancer. Level I evidence also supports the consideration of dutasteride, a 5-ARI, for tertiary prevention in active surveillance and biochemical recurrence patients. Vitamins and supplements, including selenium or vitamin E, have not been proven in clinical trials to prevent prostate cancer and in the case of Vitamin E has been found to increase the risk of incident prostate cancer. Ongoing and future trials may further elucidate the role of diet and immunotherapy for prevention of prostate cancer.

Primary mucin-producing urothelial-type adenocarcinoma of the prostatic urethra diagnosed on TURP: a case report and review of literature.

BACKGROUND: Mucin-producing urothelial-type adenocarcinoma of the prostatic urethra is extremely rare. These lesions must be differentiated from other mucinous tumors including mucin-producing prostatic adenocarcinoma and metastases from either colonic or bladder primaries. CASE PRESENTATION: We report here a case of urothelial-type adenocarcinoma arising from the prostatic urethra. The patient is an 81 year-old man with a history of pT1 urothelial cell carcinoma of the bladder status post trans-urethral resection of bladder tumor (TURBT) who initially presented with irritative lower urinary tract symptoms and mucosuria refractory to Flomax and finasteride. A shared decision was made for the patient to undergo trans-urethral resection of prostate (TURP). At the time of surgery, a papillary tumor emanating from the prostatic urethra was found and no urothelial lesions were noted in the bladder. Pathology of the resected prostatic chips revealed an invasive adenocarcinoma with intestinal-type differentiation that stained positive for CK7, CK20, and villin, but negative for PSA, PSAP, uroplakin, and CDX-2. Colonoscopy was normal and CT scan did not show any evidence of colonic lesions nor visceral or lymph node metastases. Thus, the patient was diagnosed with a primary urothelial-type adenocarcinoma of the prostatic urethra. CONCLUSION: Herein we review the literature regarding this unusual entity, and discuss the differential diagnosis, immunohistochemistry, and the importance of correctly identifying this rare tumor.

Candidate SNP associations of optimism and resilience in older adults: exploratory study of 935 community-dwelling adults.

OBJECTIVE: Optimism and resilience promote health and well-being in older adults, and previous reports suggest that these traits are heritable. We examined the association of selected single-nucleotide polymorphisms (SNPs) with optimism and resilience in older adults. DESIGN: Candidate gene association study that was a follow-on at the University of California, San Diego, sites of two NIH-funded multi-site longitudinal investigations: Women's Health Initiative (WHI) and SELenium and vitamin E Cancer prevention Trial (SELECT). PARTICIPANTS: 426 women from WHI older than age 50 years, and 509 men older than age 55 years (age 50 years for African American men) from SELECT. MEASUREMENTS: 65 candidate gene SNPs that were judged by consensus, based on a literature review, as being related to predisposition to optimism and resilience, and 31 ancestry informative marker SNPs, genotyped from blood-based DNA samples and self-report scales for trait optimism, resilience, and depressive symptoms. RESULTS: Using a Bonferroni threshold for significant association (p = 0.00089), there were no significant associations for individual SNPs with optimism or resilience in single-locus analyses. Exploratory multi-locus polygenic analyses with p <0.05 showed an association of optimism with SNPs in MAOA, IL10, and FGG genes, and an association of resilience with a SNP in MAOA gene. CONCLUSIONS: Correcting for Type I errors, there were no significant associations of optimism and resilience with specific gene SNPs in single-locus analyses. Positive psychological traits are likely to be genetically complex, with many loci having small effects contributing to phenotypic variation. Our exploratory multi-locus polygenic analyses suggest that larger sample sizes and complementary approaches involving methods such as sequence-based association studies, copy number variation analyses, and pathway-based analyses could be useful for better understanding the genetic basis of these positive psychological traits.

Does the evidence for an inverse relationship between serum vitamin D status and breast cancer risk satisfy the Hill criteria?

A wide range of epidemiologic and laboratory studies combined provide compelling evidence of a protective role of vitamin D on risk of breast cancer. This review evaluates the scientific evidence for such a role in the context of the A.B. Hill criteria for causality, in order to assess the presence of a causal, inverse relationship, between vitamin D status and breast cancer risk. After evaluation of this evidence in the context of Hill's criteria, it was found that the criteria for a causal relationship were largely satisfied. Studies in human populations and the laboratory have consistently demonstrated that vitamin D plays an important role in the prevention of breast cancer. Vitamin D supplementation is an urgently needed, low cost, effective, and safe intervention strategy for breast cancer prevention that should be implemented without delay. In the meantime, randomized controlled trials of high doses of vitamin D(3) for prevention of breast cancer should be undertaken to provide the necessary evidence to guide national health policy.

Combination pharmacological therapies for the management of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a highly prevalent condition of older men caused by unregulated growth of the prostate gland. Clinical trials of medical therapy for BPH have consistently demonstrated that combined therapy with an α(1)-adrenergic receptor (AR) antagonist and a 5α-reductase inhibitor is superior to either agent alone. The addition of anticholinergic therapy to a treatment regimen could effectively improve symptoms in men with persistent storage lower urinary tract symptoms (LUTS) who have not seen a benefit with an α(1)-AR antagonist or 5α-reductase inhibitor. Among α(1)-AR antagonists, doxazosin, terazosin, tamsulosin, and alfuzosin, although with slight differences in adverse event profiles, are equivalent in effectiveness and efficacy. No data in the form of direct comparator trials exist to suggest a difference in clinical efficacy of finasteride and dutasteride, the two 5α-reductase inhibitors currently available. Current American Urological Association guidelines do not recommend phytotherapy or dietary supplements in any combination for the medical management of BPH. The current literature supports the safety and efficacy of the combination of an α(1)-AR antagonist and a 5α-reductase inhibitor in the treatment of symptomatic BPH and, in select patients, the use of an α(1)-AR antagonist and anticholinergic medication in the treatment of LUTS suggestive of BPH.

Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

CONTEXT: The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer. OBJECTIVE: To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS: A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011. INTERVENTIONS: Oral selenium (200 µg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years. MAIN OUTCOME MEASURES: Prostate cancer incidence. RESULTS: This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination. CONCLUSION: Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00006392.

Dietary intervention after definitive therapy for localized prostate cancer: results from a pilot study.

INTRODUCTION: Diet has been linked to prostate cancer risk. Dietary modification may inhibit prostate cancer progression. MATERIALS AND METHODS: As part of a randomized trial, we analyzed the effect of a diet based intervention on 25 prostate cancer patients who had previously undergone surgery or radiation. RESULTS AND CONCLUSIONS: In the intervention arm, vegetable intake increased (p < 0.05), fat intake decreased (p < 0.05), and mean plasma levels of ss-carotene and total carotenoids increased (p < 0.05). In the control arm, there were no significant changes in diet or blood carotenoids. These data support the feasibility of studying dietary interventions as salvage or adjuvant therapy after surgery or radiation for localized prostate cancer.

Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

CONTEXT: Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer. OBJECTIVE: To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS: A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer. INTERVENTIONS: Oral selenium (200 microg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years. MAIN OUTCOME MEASURES: Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer. RESULTS: As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group. CONCLUSION: Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00006392.

Local anesthetic reduces pain associated with transrectal ultrasound-guided prostate biopsy: a meta-analysis.

OBJECTIVES: To determine whether local anesthetic decreases the pain associated with transrectal ultrasound-guided prostate needle biopsy. METHODS: A systematic review and meta-analysis was performed of randomized clinical trials of periprostatic local anesthetic for prostate biopsy. The primary outcome was pain as determined by the visual analog scale. The standardized mean differences between groups were estimated using the DerSimonian and Laird random effects models. RESULTS: Fourteen trials with a total of 994 patients met the inclusion criteria for this study. Pooled data analysis demonstrated significantly decreased pain with the use of local anesthetic. The standardized mean difference in the pain score comparing local anesthetic to placebo or nothing was -1.05 (95% confidence interval -1.40 to -0.71, P <0.001). Begg's test (P = 0.34) and Egger's test (P = 0.50) showed no evidence of significant publication bias. Sensitivity analysis showed only slight changes in the effect estimate with sequential omission of each trial or with repetition of the analysis with subgroups of trials based on likely sources of heterogeneity. CONCLUSIONS: The results of our analysis have shown that compared with no anesthetic, periprostatic local anesthetic significantly decreases the pain associated with transrectal ultrasound-guided prostate needle biopsy.