Inflammatory bowel disease induces inflammatory and pre-neoplastic changes in the prostate.

BACKGROUND: Inflammatory bowel disease (IBD) has been implicated as a risk factor for prostate cancer, however, the mechanism of how IBD leads to prostate tumorigenesis is not known. Here, we investigated whether chronic intestinal inflammation leads to pro-inflammatory changes associated with tumorigenesis in the prostate. METHODS: Using clinical samples of men with IBD who underwent prostatectomy, we analyzed whether prostate tumors had differences in lymphocyte infiltrate compared to non-IBD controls. In a mouse model of chemically-induced intestinal inflammation, we investigated whether chronic intestinal inflammation could be transferred to the wild-type mouse prostate. In addition, mouse prostates were evaluated for activation of pro-oncogenic signaling and genomic instability. RESULTS: A higher proportion of men with IBD had T and B lymphocyte infiltration within prostate tumors. Mice with chronic colitis showed significant increases in prostatic CD45 + leukocyte infiltration and elevation of three pro-inflammatory cytokines-TIMP-1, CCL5, and CXCL1 and activation of AKT and NF-kB signaling pathways. Lastly, mice with chronic colitis had greater prostatic oxidative stress/DNA damage, and prostate epithelial cells had undergone cell cycle arrest. CONCLUSIONS: These data suggest chronic intestinal inflammation is associated with an inflammatory-rich, pro-tumorigenic prostatic phenotype which may explain how gut inflammation fosters prostate cancer development in men with IBD.

It's all in the name: Does nomenclature for indolent prostate cancer impact management and anxiety?

BACKGROUND: Despite consensus guidelines, many men with low-grade prostate cancer are not managed with active surveillance. Patient perception of the nomenclature used to describe low-grade prostate cancers may partly explain this discrepancy. METHODS: A randomized online survey was administered to men without a history of prostate cancer, presenting a hypothetical clinical scenario in which they are given a new diagnosis of low-grade prostate cancer. The authors determined whether diagnosis nomenclature was associated with management preference and diagnosis-related anxiety using ratings given on a scale from 1 to 100, adjusting for participant characteristics through multivariable linear regression. RESULTS: The survey was completed by 718 men. Compared with Gleason 6 out of 10 prostate cancer, the term grade group 1 out of 5 prostate cancer was associated with lower preference for immediate treatment versus active surveillance (ß = -9.3; 95% CI, -14.4, -4.2; P < .001), lower diagnosis-related anxiety (ß = -8.3; 95% CI, -12.8, -3.8; P < .001), and lower perceived disease severity (ß = -12.3; 95% CI, -16.5, -8.1; P < .001) at the time of initial diagnosis. Differences decreased as participants received more disease-specific education. Indolent lesion of epithelial origin, a suggested alternative term for indolent tumors, was not associated with differences in anxiety or preference for active surveillance. CONCLUSIONS: Within a hypothetical clinical scenario, nomenclature for low-grade prostate cancer affects initial perception of the disease and may alter subsequent decision making, including preference for active surveillance. Disease-specific education reduces the differential impact of nomenclature use, reaffirming the importance of comprehensive counseling and clear communication between the clinician and patient.

Cause of death during prostate cancer survivorship: A contemporary, US population-based analysis.

BACKGROUND: More than 3.6 million men in the United States harbor a diagnosis of prostate cancer (PCa). The authors sought to provide in-depth analyses of the causes of death for contemporary survivors. METHODS: The authors performed a population-based cohort study in the United States (2000-2016) to assess causes of death for men diagnosed with PCa stratified by demographics and tumor stage. Using general population data, they calculated standardized mortality ratios (SMRs) as observed-to-expected death ratios. RESULTS: In total, 752,092 men with PCa, including 200,302 who died (27%), were assessed. A total of 29,048 men with local/regional disease (17%) died of PCa, whereas more than 4-fold men died of other causes (n = 143,719 [83%]). SMRs for death from noncancer causes (0.77; 95% confidence interval [CI], 0.77-0.78) suggested that these men were less likely than the general population to die of most other causes. The most common noncancer cause of death was cardiac-related (23%; SMR, 0.76; 95% CI, 0.75-0.77). Among men with distant PCa, 90% of deaths occurred within 5 years of diagnosis. Although deaths due to PCa composed the majority of deaths (74%), SMRs suggested that men with distant PCa were at heightened risk for death from most other noncancer causes (1.50; 95% CI, 1.46-1.54) and, in particular, for cardiac-related death (SMR, 1.48; 95% CI, 1.41-1.54) and suicide (SMR, 2.32; 95% CI, 1.78-2.96). Further analyses demonstrated that causes of death varied by patient demographics. CONCLUSIONS: Causes of death during PCa survivorship vary by patient and tumor characteristics. These data provide valuable information regarding health care prioritization during PCa survivorship. LAY SUMMARY: Men with early-stage prostate cancer are 4-fold more likely to die of other causes, whereas those with advanced prostate cancer are at increased risk for several causes not related to prostate cancer in comparison with the general population. These findings can help guide physicians taking care of men with a diagnosis of prostate cancer.

Survival following upfront chemotherapy for treatment-naïve metastatic prostate cancer: a real-world retrospective cohort study.

BACKGROUND: Upfront chemotherapy prolongs overall survival for men with metastatic, hormone-sensitive prostate cancer (mHSPC) based on data from clinical trials. We sought to assess the association between upfront chemotherapy and overall survival in men with mHSPC in a real-world cohort. METHODS: We performed a retrospective cohort study of men with de novo, treatment-naïve metastatic prostate cancer from a large, national cancer database in the United States (2014-2015). Men in the upfront chemotherapy group received chemotherapy within 4 months of diagnosis (n = 1033, 28%) versus no chemotherapy or chemotherapy later than 12 months after diagnosis (controls; n = 2704, 72%). Overall survival was assessed using Kaplan-Meier estimates and compared using multivariable Cox regression analysis. RESULTS: After a median follow-up of 23 months, median overall survival was 35.7 months in the upfront chemotherapy group and 32.5 months for controls (log-rank p < 0.001). After adjusting for patient and clinical variables, upfront chemotherapy was associated with longer overall survival (hazard ratio 0.78, 95% confidence interval 0.68-0.89, p < 0.001). In exploratory analyses, the association between upfront chemotherapy and overall survival did not differ by age groups, race, or number of comorbidities (all interaction p > 0.2). CONCLUSIONS: In this real-world cohort, upfront chemotherapy for mHSPC was associated with longer overall survival. These data support the continued use of chemotherapy for men with mHSPC regardless of race or age if they are fit for chemotherapy and underscore the importance of evaluating cancer therapeutics outside of clinical trials to demonstrate treatment efficacy in populations that may be underrepresented in clinical trials.

Insurance coverage, stage at diagnosis, and time to treatment following dependent coverage and Medicaid expansion for men with testicular cancer.

INTRODUCTION: We sought to assess the impact of Affordable Care Act Dependent Care Expansion (ACA-DCE), which allowed dependent coverage for adults aged 19-25, and Medicaid expansion on outcomes for men with testicular cancer. METHODS: Using a US-based cancer registry, we performed adjusted difference-in-difference (DID) analyses comparing outcomes between men aged 19-25 (n = 8,026) and 26-64 (n = 33,303) pre- (2007-2009) and post-ACA-DCE (2011-2016) and between men in states that expanded Medicaid (n = 2,296) to men in those that did not (n = 2,265)pre- (2011-2013) and post-Medicaid expansion (2015-2016). RESULTS: In ACA-DCE analysis, rates of uninsurance decreased (DID -5.64, 95% confidence interval [CI] -7.23 to -4.04%, p<0.001) among patients aged 19-25 relative to older patients aged 26-64. There was no significant DID in advanced stage at diagnosis (stage≥II; p = 0.6) or orchiectomy more than 14 days after diagnosis (p = 0.6). For patients who received chemotherapy or radiotherapy as their first course of treatment, treatment greater than 60 days after diagnosis decreased (DID -4.84%, 95% CI -8.22 to -1.45%, p = 0.005) among patients aged 19-25 relative to patients aged 26-64. In Medicaid expansion states, rates of uninsurance decreased (DID -4.20%, 95% CI -7.67 to -0.73%, p = 0.018) while patients receiving chemotherapy or radiotherapy greater than 60 days after diagnosis decreased (DID -8.76, 95% CI -17.13 to -0.38%, p = 0.040) compared to rates in non-expansion states. No significant DIDs were seen for stage (p = 0.8) or time to orchiectomy (p = 0.1). CONCLUSIONS: Men with testicular cancer had lower uninsurance rates and decreased time to delivery of chemotherapy or radiotherapy following ACA-DCE and Medicaid expansions. Time to orchiectomy and stage at diagnosis did not change following either insurance expansion.

Association between inflammatory bowel disease and prostate cancer: A large-scale, prospective, population-based study.

Inflammatory bowel disease (IBD) is an established risk factor for colorectal cancer. Recent reports suggesting IBD is also a risk factor for prostate cancer (PC) require further investigation. We studied 218 084 men in the population-based UK Biobank cohort, aged 40 to 69 at study entry between 2006 and 2010, with follow-up through mid-2015. We assessed the association between IBD and subsequent PC using multivariable Cox regression analyses, adjusting for age at assessment, ethnic group, UK region, smoking status, alcohol drinking frequency, body mass index, Townsend Deprivation Index, family history of PC and previous prostate-specific antigen testing. Mean age at study entry was 56 years, 94% of the men were white, and 1.1% (n = 2311) had a diagnosis of IBD. After a median follow-up of 78 months, men with IBD had an increased risk of PC (adjusted hazard ratio [aHR] = 1.31, 95% confidence interval [CI] = 1.03-1.67, P = .029). The association with PC was only among men with the ulcerative colitis (UC; aHR = 1.47, 95% CI = 1.11-1.95, P = .0070), and not Crohn's disease (aHR 1.06, 95% CI = 0.63-1.80, P = .82). Results are limited by lack of data on frequency of health care interactions. In a large-scale, prospective cohort study, we detected an association between IBD, and UC specifically, with incident PC diagnosis.

Changes in prostate-specific antigen at the time of prostate cancer diagnosis after Medicaid expansion in young men.

BACKGROUND: The objective of this study was to determine the effect of Medicaid expansion under the Patient Protection and Affordable Care Act (January 1, 2014) on the epidemiology of high-risk prostate-specific antigen (PSA) levels (≥20 ng/mL) at the time of prostate cancer (PCa) diagnosis. The authors hypothesized that better access to care would result in a reduction of high-risk features at diagnosis. METHODS: A retrospective cohort study was performed of 122,324 men aged <65 years who were diagnosed with PCa within the National Cancer Database. Difference-in-difference (DID) analyses adjusting for sociodemographic variables using linear regression compared PSA levels at diagnosis before expansion (2012-2013) and after expansion (2015-2016) between men residing in states that did or did not expand Medicaid. RESULTS: From 2012 to 2016, the proportion of men with PSA levels ≥20 ng/mL increased (from 18.9% to 19.8%) in nonexpansion states and decreased (from 19.9% to 18.2%) in expansion states. Compared with men in nonexpansion states, men in expansion states experienced a decline in PSA ≥20 ng/mL (DID, -2.33%; 95% CI, -3.21% to -1.44%; P < .001). Accordingly, the proportion of men presenting with high-risk disease decreased in expansion states relative to nonexpansion states (DID, -1.25%; 95% CI, -2.26% to 0.25%; P = .015). A similar statistically significant decrease in PSA levels ≥20 ng/mL was noted among black men (DID, -3.11%; 95% CI, -5.25% to 0.96%; P = .005). CONCLUSIONS: In Medicaid expansion states, there was an associated decrease in the proportion of young men presenting with PSA ≥20 ng/mL at the time of PCa diagnosis. These results suggest that Medicaid expansion improved access to PCa screening. Longer term data should assess oncologic outcomes.

Medicaid Expansion Did not Improve Time to Treatment for Young Patients With Metastatic Renal Cell Carcinoma.

INTRODUCTION: The absence of health insurance coverage has been associated with worse outcomes for patients with metastatic renal cell carcinoma (mRCC). Medicaid expansion in the United States was an important provision of the Affordable Care Act, which increased the number of low-income individuals eligible for Medicaid starting in January 2014 in several states. The effect of Medicaid expansion on access to healthcare for patients with mRCC is unknown. MATERIALS AND METHODS: We performed a retrospective cohort study of 6844 patients aged < 65 years with mRCC at diagnosis within the National Cancer Database. We compared the time to treatment and the rates of no insurance before (2012-2013) and after (2015-2016) expansion between patients living in states that had and had not expanded Medicaid using difference-in-difference (DID) analyses. DIDs were calculated using linear regression analysis with adjustment for sociodemographic covariates. RESULTS: The rate of no insurance did not change in the expansion states compared with the nonexpansion states (DID, -0.55%; 95% confidence interval, -3.32% to 2.21%; P = .7). The percentage of patients receiving treatment within 60 days of diagnosis had increased in the expansion states from 43% to 49% and in the nonexpansion states from 42% to 46% after expansion. No change was found in treatment within 60 days of diagnosis among all patients (DID, 2.81%; 95% confidence interval, -2.61% to 8.22%; P = .3). CONCLUSIONS: Medicaid expansion was not associated with improved healthcare access for patients with mRCC as reflected by timely treatment. Future work should assess the association between Medicaid expansion and oncologic outcomes.

Success of Prostate and Testicular Cancer Awareness Campaigns Compared to Breast Cancer Awareness Month According to Internet Search Volumes: A Google Trends Analysis.

OBJECTIVE: To compare the efficacy of men's and women's cancer awareness campaigns using internet relative search volume (RSV) as a surrogate for public interest. METHODS: We utilized Google Trends to determine the RSV for "breast cancer," "prostate cancer," and "testicular cancer" from 2010 to 2017. Baseline annual RSV for each cancer was calculated as the median annual RSV, exclusive of the awareness month period. RSV was then determined for each cancer-specific awareness month and compared to baseline. The primary outcome was 2-fold rise in RSV above baseline. RESULTS: Breast Cancer Awareness Month led to a significant increase in cancer-specific RSV in October each year during the study period (mean increase 180.1%). In contrast, none of the men's cancer awareness campaigns led to a significant increase in cancer-specific RSV in any year during the study period. RSV for prostate cancer increased by 2.4% and 4.1% in September and November, respectively. RSV for testicular cancer increased by 9.3% and 6.2% in April and November, respectively. CONCLUSION: Men's cancer awareness campaigns did not increase cancer-specific RSV, whereas Breast Cancer Awareness Month consistently increased RSV. While additional metrics are needed to evaluate the efficacy of public health campaigns, the current data suggest the need for new approaches to generate public interest in male-specific malignancies.

Tumor Location May Predict Adverse Pathology and Survival Following Definitive Treatment for Bladder Cancer: A National Cohort Study.

BACKGROUND: While urothelial carcinoma of the bladder is often considered a multifocal disease, the location of the dominant tumor may be prognostic. OBJECTIVE: To determine the association between intravesical tumor location and both adverse pathological outcomes as well as overall survival. DESIGN, SETTINGS, AND PARTICIPANTS: Patients in the National Cancer Database (2010-2015) with nonmetastatic urothelial carcinoma of the bladder who underwent primary treatment with radical cystectomy (RC; n=3464) or chemoradiotherapy (CRT; n=699). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regressions assessed the prognostic ability of tumor location to predict adverse pathology at RC (nodal metastases [pN+] or advanced stage [pT3-4]). Cox regressions were used to determine the effect of tumor location on overall survival in patients treated with RC or CRT. RESULTS AND LIMITATIONS: Following RC, 822 (24%) patients were pN+ and 1551 (55%) were pT3-4. Trigonal tumors were most likely to have adverse pathology (31% pN+ and 59% pT3-4), while anterior wall tumors were the least (19% pN+ and 50% pT3-4). Relative to the anterior wall, trigone (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.12-2.43, p=0.012) and bladder neck (OR 1.79, 95% CI 1.11-2.90, p=0.018) tumors were associated with increased odds of pN+ and dome (OR 1.56, 95% CI 1.08-2.24, p=0.017) with pT3-4. In those patients treated with primary CRT, trigone involvement was associated with worse survival (HR 1.58, 95% CI 1.17-2.13, p=0.003). Limitations included unmeasured variables and a relatively few number of patients with certain tumor locations. CONCLUSIONS: Trigone and bladder neck tumors are associated with increased odds of nodal involvement, and dome with a higher tumor stage at RC. Patients with trigone involvement may have worse overall survival following CRT. PATIENT SUMMARY: Location of the tumor within the bladder may be associated with worse cancer staging at the time of the surgery and worse survival following chemoradiotherapy.

Risk factors for hypogonadism in young men with erectile dysfunction.

BACKGROUND: The objective of this study is to evaluate the hormone profile of young men with the chief complaint of erectile dysfunction (ED) and determine the comorbidities in this population. METHODS: A retrospective chart review of men aged 18 to 40 years who presented with ED and had a hormone evaluation but without prior medication for hormone manipulation from 2002 to 2016 was performed at a tertiary care institution. Data were obtained on demographics, comorbidities, medications, and hormonal evaluations. RESULTS: A total of 2292 men with ED were identified and 2130 of them received testosterone level evaluation. The most common comorbidities that men were actively being treated for were depression (22.3%), anxiety (16.1%), hypertension (15.6%), diabetes (7.2%), cancer (6.2%), and cardiovascular disease (3.3%). The average total testosterone level was 368 ± 160 ng/dL; 10.7% of men had hypogonadism. Multivariate analysis demonstrated age, body mass index (BMI), depression, and cancer predicted a hypogonadal status. Patients with BMI > 28.2 kg/m, age > 34 years, cancer diagnosis, or depression were 3.350-fold, 1.447-fold, 2.317-fold, or 1.420-fold more likely to be diagnosed hypogonadal than nonoverweight, age ≤ 34 years, noncancer, or nondepressive patients. CONCLUSION: The majority of men under the age of 40 with ED exhibit a normal hormonal milieu. Young ED men with BMI > 28.2 kg/m, age >34 years, cancer diagnosis, or depression are at risk for hypogonadism.

Inconsistent Adoption of World Health Organization V (2010) Semen Analysis Reference Ranges in the United States Eight Years After Publication.

OBJECTIVE: To determine the percentage of laboratories in the United States that have adopted the World Health Organization 2010 (WHO 5) semen analysis (SA) reference values 6years after their publication. METHODS: Laboratories were identified via 3 approaches: using the Clinical Laboratory Improvement Amendments (CLIA) website, the CDC's 2015 Assisted Reproductive Technology Fertility Clinical Success Rate Report, and automated web searches. Laboratories were contacted by phone or email to obtain de-identified SA reports and reference ranges. RESULTS: We contacted 617 laboratories in 46 states, of which 208 (26.7%) laboratories in 45 states were included in our analysis. 132 (63.5%) laboratories used WHO 5 criteria, 57 (27.4%) used WHO 4 criteria, and 19 (9.1%) used other criteria. WHO 5 criteria adoption rates varied by geographic region, ranging from 87.5% (35/40) in the Midwest to 50.0% (33/66) in the West. There was a greater adoption rate of WHO 5 reference values in academic affiliated (23/26, 88.5%) compared to non-academic affiliated laboratories (110/182, 60.4%) (P = .028). CONCLUSION: While the majority of laboratories have adopted WHO 5 criteria following its release 6years ago, a large percentage (36.5%) use what is now considered outdated criteria. This variability could result in the characterization of a male's semen values as being "within reference range" at one center and "outside of reference range" at another. This inconsistency in classification may result in confusion for the both patient and physician and potentially shift the burden of infertility evaluation and treatment to the female partner.