Metabolic syndrome is associated with aggressive prostate cancer regardless of race.

PURPOSE: Recent meta-analyses suggest the Metabolic Syndrome (MS) increases high-grade prostate cancer (PC), although studies are inconsistent and few black men were included. We investigated MS and PC diagnosis in black and white men undergoing prostate biopsy in an equal access healthcare system. We hypothesized MS would be linked with aggressive PC, regardless of race. METHODS: Among men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, medical record data abstraction of diagnosis or treatment for hypertension (≥ 130/85 mmHg), dyslipidemia (HDL < 40 mg/dL), hypertriglyceridemia (≥ 150 mg/dL), diabetes, hyperglycemia (fasting glucose ≥ 100 ml/dL), and central obesity (waist circumference ≥ 40 inches) were done. Biopsy grade group (GG) was categorized as low (GG1) or high (GG2-5). Multinomial logistic regression was used to examine MS (3-5 components) vs. no MS (0-2 components) and diagnosis of high grade and low grade vs. no PC, adjusting for potential confounders. Interactions between race and MS were also tested. RESULTS: Of 1,051 men (57% black), 532 (51%) had MS. Men with MS were older, more likely to be non-black, and had a larger prostate volume (all p ≤ 0.011). On multivariable analysis, MS was associated with high-grade PC (OR = 1.73, 95% CI 1.21-2.48, p = 0.003), but not overall PC (OR = 1.17, 95% CI 0.88-1.57, p = 0.29) or low grade (OR = 0.87, 95% CI 0.62-1.21, p = 0.39). Results were similar in black and non-black men (all p-interactions > 0.25). CONCLUSION: Our data suggest that metabolic dysregulation advances an aggressive PC diagnosis in both black and non-black men. If confirmed, prevention of MS could reduce the risk of developing aggressive PC, including black men at higher risk of PC mortality.

Racial differences in circulating mitochondria-derived peptides may contribute to prostate cancer health disparities.

INTRODUCTION: The mitochondrial genome has small open reading frames (sORF) which produce measurable mitochondrial-derived peptides (MDPs), including humanin, SHLP2, and MOTS-c. Previously, among men undergoing prostate biopsy, we found higher serum SHLP2 was linked with lower prostate cancer (PC) risk in European American men (EAM), while null associations were found in African American men (AAM). Here, in different patients undergoing prostate biopsy, we tested the link between SHLP2, humanin and MOTS-c and PC risk by race. METHODS: Plasma SHLP2, humanin, and MOTS-c were measured in 198 men (50/49 EAM/AAM cases; 50/49 EAM/AAM controls) undergoing biopsy. Logistic and multinomial regression models tested associations between each MDP and PC diagnosis, low-grade (grade group, GG1) and high-grade (GG2-5). Models were adjusted for age, body mass index, digital rectal examination, and prostate specific antigen (PSA). We tested interactions between MDPs and race. RESULTS: Among controls, humanin was similar by race (p = 0.60), but both SHLP2 (p = 0.007) and MOTS-c (p = 0.026) were lower in AAM controls versus EAM controls. Among EAM, higher MDP values were associated with lower PC risk (all p ≤ 0.001), with null associations in AAM (all p-interactions ≤ 0.01). Similarly, higher MDP expression was associated with decreased risk of low- and high-grade PC in EAM (all p ≤ 0.005) with null associations in AAM. CONCLUSIONS: Higher MDP levels were associated with lower PC risk in EAM but not AAM. Generally, AAM controls had lower MDP levels. These data support MDPs and mitochondrial dysfunction in PC, suggesting greater dysfunction in AAM may contribute to excess PC risk. Future larger studies are needed to confirm these results.

Are higher pre-diagnosis follicle stimulating hormone levels associated with long-term prostate cancer risk?

BACKGROUND: Follicle stimulating hormone (FSH) is a pituitary hormone that helps regulate testosterone homeostasis. Although it is generally accepted that FSH levels increase with LHRH-agonist therapy for prostate cancer (PC), the specific impact of FSH levels on risk of PC diagnosis is largely unknown. The objective of this study was to perform a population-level analysis to assess the association between FSH levels and PC diagnosis. METHODS: All men (n = 386,018) who had a pre-PC diagnosis FSH level and complete data were identified within the Veterans Affairs Health System between 1999 and 2018. The association between FSH level and time from FSH test to PC diagnosis was tested using stratified Cox proportional hazards models. Multivariable models were adjusted for age, year, race, body mass index, and Charlson comorbidity index. Due to nonproportional hazards over time, time to PC was modeled separately: ≤4 years after an FSH test and >4 years following an FSH test. RESULTS: Median age at first FSH level was 64 years (interquartile range [IQR]: 54-72), median year of FSH was 2010 (IQR: 2005-2014), and 70% of the cohort was white. Median follow-up was 76 months (IQR: 38-126) during which 17,519 men (4.5%) were diagnosed with PC. On multivariable analysis, in the first 4 years after FSH test, there was no association between FSH and time to PC diagnosis. Starting from 4 years after FSH test, on multivariable analysis, a higher FSH level was associated with lower risk of PC with continuous modeling, but found no association with log continuous and categorical modeling. CONCLUSIONS: In this population-level study among male veterans receiving an FSH test for an unknown clinical indication, associations between FSH levels and PC risk were inconsistent and likely driven by selection bias and confounding variables. Future studies should consider different study designs.

Association between Delay to Radical Prostatectomy and Clinically Meaningful Outcomes among Patients with Intermediate and High-Risk Localized Prostate Cancer.

PURPOSE: There are limited data regarding the effect of treatment delays on important long-term outcomes among men with intermediate/high-risk prostate cancer (PC). MATERIALS AND METHODS: We identified 3,962 men with intermediate/high-risk disease from the SEARCH cohort treated with radical prostatectomy (RP) from 1988 to 2018. Cox proportional hazard models assessed the association between time from biopsy to RP (up to 1 year) and time to castration-resistant PC (CRPC), metastasis and all-cause mortality. Interaction terms were used to test for effect modification by risk group. RESULTS: Of the 3,962 men, 167 developed CRPC, 248 developed metastases and 884 died after a median followup of 85 months. Longer delays between biopsy and RP were associated with a decreased risk of CRPC (adjusted HR=0.88, 95% CI: 0.80-0.98, p=0.02), independent of D'Amico risk group (interaction p >0.05). In men with intermediate and high-risk disease, we found no statistically significant association between length of time to RP and risk of developing metastases (p=0.5 and 0.9, respectively) or all-cause mortality (p=0.1 and 0.1, respectively). CONCLUSIONS: Among men with intermediate and high-risk PC, we found no statistically significant increased risk of adverse long-term outcomes, including CRPC, metastasis and death, for men who had treatment delays up to 1 year following PC diagnosis.

Safety of concomitant therapy with radium-223 and abiraterone or enzalutamide in a real-world population.

BACKGROUND: Real-world utilization and outcomes of combination therapy for men with metastatic castrate-resistant prostate cancer (mCRPC) are largely unknown. We evaluated the overall survival (OS) and skeletal-related events (SREs) among men who received radium-223 with or without concomitant abiraterone or enzalutamide in the Veterans Affairs (VA) Health System. METHODS: We reviewed charts of all mCRPC patients who received radium-223 in the VA from January 2013 to September 2017. We used Cox models to test the association between concomitant therapy versus radium-223 alone on OS and SRE. Sensitivity analyses were performed for concomitant use of denosumab/bisphosphonates. RESULTS: Three hundred and eighteen patients treated with radium-223 were identified; 116/318 (37%) received concomitant abiraterone/enzalutamide. Two hundred and seventy-seven (87%) patients died during follow-up. Patients who received concomitant therapy were younger at radium-223 initiation (median age 68 vs. 70, p = .027) and had a longer follow-up (median 29.5 vs. 17.9 months, p = .030). There was no OS benefit for those on concomitant therapy (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.67-1.12, p = .28). There was a trend for an increased SRE risk for patients on concomitant therapy (HR: 1.87, 95% CI: 0.96-3.61, p = .066), but this was not significant. When analyses were limited to men using bone heath agents, similar results were seen for OS (HR: 0.86, 95% CI 0.64-1.15, p = .30) and SRE (HR: 2.36, 95% CI: 0.94-5.94, p = .068). CONCLUSIONS: Despite the common use of concomitant therapy in this real-world study, there was no difference in OS among mCRPC patients. A nonsignificant increased SRE risk was observed. Further work needs to evaluate the optimal sequence, timing, and safety of combination therapies.

The impact of the social construct of race on outcomes among bacille Calmette-Guérin-treated patients with high-risk non-muscle-invasive bladder cancer in an equal-access setting.

BACKGROUND: The objective of this study was to describe bladder cancer outcomes as a function of race among patients with high-risk non-muscle-invasive bladder cancer (NMIBC) in an equal-access setting. METHODS: A total of 412 patients with high-risk NMIBC who received bacille Calmette-Guérin (BCG) from January 1, 2010, to December 31, 2015, were assessed. The authors used the Kaplan-Meier method to estimate event-free survival and Cox regression to determine the association between race and recurrence, progression, disease-specific, and overall survival outcomes. RESULTS: A total of 372 patients who had complete data were included in the analysis; 48 (13%) and 324 (87%) were Black and White, respectively. There was no difference in age, sex, smoking status, or Charlson Comorbidity Index by race. White patients had a higher socioeconomic status with a greater percentage of patients living above the poverty level in comparison with Black patients (median, 85% vs 77%; P < .001). A total of 360 patients (97%) received adequate induction BCG, and 145 patients (39%) received adequate maintenance BCG therapy. There was no significant difference in rates of adequate induction or maintenance BCG therapy according to race. There was no significant difference in recurrence (hazard ratio [HR], 1.53; 95% confidence interval [CI], 0.64-3.63), progression (HR, 0.77; 95% CI, 0.33-1.82), bladder cancer-specific survival (HR, 1.01; 95% CI, 0.30-3.46), or overall survival (HR, 0.97; 95% CI, 0.56-1.66) according to Black race versus White race. CONCLUSIONS: In this small study from an equal-access setting, there was no difference in the receipt of BCG or any differences in bladder cancer outcomes according to race.

Family history of prostate cancer and prostate tumor aggressiveness in black and non-black men;results from an equal access biopsy study.

PURPOSE: To test for racial differences in associations between family history (FH) of prostate cancer (PC) and prostate cancer aggressiveness in a racially diverse equal access population undergoing prostate biopsy. SUBJECTS/PATIENTS AND METHODS: We prospectively enrolled men undergoing prostate biopsy at the Durham Veterans Administration from 2007 to 2018 and assigned case or control status based on biopsy results. Race and FH of PC were self-reported on questionnaires. Logistic regression was used to test the association between FH and PC diagnosis overall and by tumor aggressiveness [high- (Grade Group 3-5) or low-grade (Grade Group 1-2) vs. no cancer], overall, and stratified by race. Models were adjusted for age and year of consent, race, PSA level, digital rectal exam findings, prostate volume, and previous (negative) biopsy receipt. RESULTS: Of 1,225 men, 323 had a FH of PC and 652 men were diagnosed with PC on biopsy. On multivariable analysis, FH was associated with increased odds of high-grade PC in black (OR 1.85, p = 0.041) and all men (OR 1.56, p = 0.057) and was unrelated to overall or low-grade PC diagnosis, overall, or stratified by race (all p ≥ 0.325). In sensitivity analyses among men without a previous biopsy, results were slightly more pronounced. CONCLUSION: In this setting of equal access to care, positive FH of PC was associated with increased tumor aggressiveness in black men, but not non-black men undergoing prostate biopsy. Further research is required to tease apart the contribution of genetics from increased PC awareness potentially influencing screening and biopsy rates in men with FH.

Monocyte counts and prostate cancer outcomes in white and black men: results from the SEARCH database.

PURPOSE: Circulating inflammatory markers may predict prostate cancer (PC) outcomes. For example, a recent study showed that higher peripheral blood monocyte counts were associated with aggressive PC in Asian men undergoing radical prostatectomy (RP). Herein, we investigated whether peripheral monocyte count can predict long-term PC outcomes after RP in black and white men. METHODS: We retrospectively reviewed data on 2345 men undergoing RP from 2000 to 2017 at eight Veterans Affairs hospitals. Data on monocyte count within 6 and 12 months prior to surgery were collected. The study outcomes were biochemical recurrence (BCR), castration-resistant PC (CRPC), metastasis, all-cause mortality (ACM), and PC-specific morality (PCSM). Cox-proportional hazard models were used to assess the associations between pre-operative monocyte count and the above-mentioned outcomes accounting for confounders. RESULTS: Of 2345 RP patients, 972 (41%) were black and 1373 (59%) were white men. In multivariable analyses, we found no associations between monocyte count and BCR among all men (HR: 1.36, 95%CI 0.90-2.07) or when analyses were stratified by race (HR: 1.30, 95%CI 0.69-2.46, in black men; HR:1.33, 95%CI 0.76-02.33, in white men). Likewise, no overall or race-specific associations were found between monocyte count and CRPC, metastases, ACM, and PCSM, all p ≥ 0.15. Results were similar for monocyte count measured at 12 months prior to RP. CONCLUSION: In black and white PC patients undergoing RP, peripheral monocyte count was not associated with long-term PC outcomes. Contrary to what was found in Asian populations, monocyte count was not associated with PC outcomes in this study.

Low Carbohydrate Diets and Estimated Cardiovascular and Metabolic Syndrome Risk in Prostate Cancer.

PURPOSE: A low carbohydrate diet (LCD) was shown to suggestively slow prostate cancer (PC) growth. In noncancer patients, LCDs improve metabolic syndrome (MetS) without weight loss. However, concerns about negative impact on cardiovascular disease (CVD) risk remain. The objective of this secondary analysis is to determine the impact of an LCD on risk of MetS and estimated CVD risk in patients with PC. MATERIALS AND METHODS: Pooled data were analyzed from 2 randomized trials testing LCD vs control on 1) preventing insulin resistance after starting hormone therapy (CAPS1) and 2) slowing PC growth in recurrent PC after failed primary treatment (CAPS2). Both trials included a usual care control vs LCD intervention in which patients were instructed to limit carbohydrate intake to ≤20 gm/day, and in CAPS1 only, to walk for ≥30 minutes/day for ≥5 days/week. MetS components (hypertension, high triglycerides, low high-density lipoprotein cholesterol, central obesity and diabetes), 10-year CVD risk estimated using the Framingham Score with either body mass index (BMI) or lipids, and remnant cholesterol were compared between arms using mixed models adjusting for trial. RESULTS: LCD resulted in a significantly reduced risk of MetS (p=0.004) and remnant cholesterol (p <0.001). Moreover, LCD resulted in significantly lower estimated CVD risk using BMI (p=0.002) over the study with no difference in estimated CVD risk using lipids (p=0.14). CONCLUSIONS: LCD resulted in a significantly reduced risk of MetS and remnant cholesterol, and a significantly lower estimated CVD risk using BMI. By comparison, there was no difference in estimated CVD risk using lipids. Study limitations include small sample size, short followup, and inability to distinguish effects of carbohydrate restriction and weight loss. Long-term studies are needed to confirm this finding.

Dutasteride Improves Nocturia but Does Not Lead to Better Sleep: Results from the REDUCE Clinical Trial.

PURPOSE: In men, complaints of nocturia causing poor sleep are often attributed to benign prostatic hyperplasia and treated with benign prostatic hyperplasia medications. We assessed whether treating lower urinary tract symptoms with dutasteride altered either nocturia or sleep quality using data from REDUCE. MATERIALS AND METHODS: REDUCE was a 4-year randomized, multicenter trial comparing dutasteride 0.5 mg/day vs placebo for prostate cancer chemoprevention. Study participants were men considered at increased risk for prostate cancer. Eligibility included age 50-75 years, prostate specific antigen 2.5-10 ng/ml, and 1 negative prostate biopsy. At baseline, 2 years and 4 years, men completed the International Prostate Symptom Score and Medical Outcomes Study Sleep Scale, a 6-item scale assessing sleep. To test differences in nocturia and Medical Outcomes Study Sleep Scale over time, we used linear mixed models adjusted for baseline confounders. Subanalyses were conducted in men symptomatic from lower urinary tract symptoms, nocturia, poor sleep, or combinations thereof. RESULTS: Of 6,914 men with complete baseline data, 80% and 59% were assessed at 2 and 4-year followup, respectively. Baseline characteristics were balanced between treatment arms. Dutasteride improved nocturia at 2 (-0.15, 95% CI -0.21, -0.09) and 4 years (-0.24, 95% CI -0.31, -0.18) but did not improve sleep. When limited to men symptomatic from lower urinary tract symptoms, nocturia, poor sleep or combinations thereof, results mirrored findings from the full cohort. CONCLUSIONS: In men with poor sleep who complain of nocturia, treatment of lower urinary tract symptoms with dutasteride modestly improves nocturia but has no effect on sleep. These results suggest men with poor sleep who complain of nocturia may not benefit from oral benign prostatic hyperplasia treatment.

Partial Validation of the Sleep Health Construct in the Medical Outcomes Study Sleep Questionnaire.

Sleep health is postulated as a multi-dimensional construct comprised of sleepiness/alertness, timing, duration, efficiency, and satisfaction. New questionnaires for its measurement have been proposed. We performed secondary data analyses and analyzed responses on a widely used, well-established sleep questionnaire to determine whether the construct might be detectable with an existing questionnaire. Healthy men (n = 7604) aged 55-75 completed the six-item Medical Outcomes Study Sleep Questionnaire (MOSSQ) at baseline in a large, randomized clinical trial [the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial). Two components clearly emerged from a Principal Components Analysis, suggesting that both sleep disturbance and sleep satisfaction are differentiated by the MOSSQ. Selected elements of sleep health are accessible with relatively few questionnaire items. Widespread previous usage of the MOSSQ in both descriptive and interventional research suggests that many previously collected databases could address at least two components of this construct.

Abdominal and pelvic adipose tissue distribution and risk of prostate cancer recurrence after radiation therapy.

BACKGROUND: Fat distribution varies between individuals of similar body mass index (BMI). We hypothesized that visceral obesity is more strongly associated with poor prostate cancer outcomes than overall obesity defined by BMI. MATERIALS AND METHODS: We quantified abdominal visceral and subcutaneous fat area (VFA and SFA), and pelvic periprostatic adipose tissue area (PPAT), using computed tomography scans from radiation-treated prostate cancer patients at the Durham North Carolina Veterans Administration Hospital. Multivariable-adjusted Cox regression examined associations between each adiposity measure and risk of recurrence, overall and stratified by race and receipt of androgen deprivation therapy (ADT). RESULTS: Of 401 patients (59% black) treated from 2005 to 2011, 84 (21%) experienced recurrence during 9.3 years median follow-up. Overall, obesity defined by BMI was not associated with recurrence risk overall or stratified by race or ADT, nor was any measure of fat distribution related to the risk of recurrence overall or by race. However, higher VFA was associated with increased risk of recurrence in men who received radiation only (hazard ratio [HR], 1.79; 95% confidence interval [CI], 0.87-3.66), but inversely associated with recurrence risk in men treated with radiation and ADT (HR, 0.49; 95% CI, 0.24-1.03; P-interaction = .002), though neither association reached statistical significance. Similar patterns of ADT-stratified associations were observed for PPAT and SFA. CONCLUSIONS: Associations between abdominal and pelvic adiposity measures and recurrence risk differed significantly by ADT receipt, with positive directions of association observed only in men not receiving ADT. If confirmed, our findings suggest that obesity may have varying effects on prostate cancer progression risk dependent on the hormonal state of the individual.

Sleep quality and prostate cancer aggressiveness: Results from the REDUCE trial.

BACKGROUND: Disrupted sleep has been associated with increased risk of certain cancers. Little data exist in prostate cancer. We tested the association between sleep quality and prostate cancer diagnosis overall and by tumor grade in the Reduction by Dutasteride of Prostate Cancer Events chemoprevention trial. We hypothesized that worse sleep quality would be associated with increased tumor aggressiveness. METHODS: At baseline, 5614 men completed a validated six-item questionnaire on sleep quality. We generated a composite score categorized into tertiles to measure overall sleep quality and assessed each sleep quality question individually. Logistic regression was used to test associations between baseline sleep quality and overall, low-grade and high-grade prostate cancer diagnosis at 2-year study-mandated biopsy. Models were stratified by nocturia. RESULTS: Overall sleep quality was unrelated to overall or low-grade prostate cancer. Worse overall sleep quality was associated with elevated odds of high-grade prostate cancer (odds ratio [OR]T3vsT1 1.15; 95% confidence interval [CI]: 0.83-1.60 and ORT2vsT1 1.39; 95% CI: 1.01-1.92). Men reporting trouble falling asleep at night sometimes vs never had elevated odds of high-grade prostate cancer (OR: 1.51; 95% CI: 1.08-2.09) while trouble staying awake during the day was associated with decreased odds of low-grade prostate cancer (OR: 0.65; 95% CI: 0.49-0.86). Results were similar within strata of nocturia severity. CONCLUSIONS: Overall, associations between sleep quality and prostate cancer were inconsistent. However, there was some evidence for a positive association between insomnia and high-grade prostate cancer, and an inverse relationship between daytime sleepiness and low-grade prostate cancer; findings that should be validated by future studies.

Race does not predict skeletal-related events and all-cause mortality in men with castration-resistant prostate cancer.

BACKGROUND: The impact of race on prostate cancer skeletal-related events (SREs) remains understudied. In the current study, the authors tested the impact of race on time to SREs and overall survival in men with newly diagnosed, bone metastatic castration-resistant prostate cancer (mCRPC). METHODS: The authors performed a retrospective study of patients from 8 Veterans Affairs hospitals who were newly diagnosed with bone mCRPC in the year 2000 or later. SREs comprised pathologic fracture, spinal cord compression, radiotherapy to the bone, or surgery to the bone. Time from diagnosis of bone mCRPC to SREs and overall mortality was estimated using the Kaplan-Meier method. Cox models tested the association between race and SREs and overall mortality. RESULTS: Of 837 patients with bone mCRPC, 232 patients (28%) were black and 605 (72%) were nonblack. At the time of diagnosis of bone mCRPC, black men were found to be more likely to have more bone metastases compared with nonblack men (29% vs 19% with ≥10 bone metastases; P = .021) and to have higher prostate-specific antigen (41.7 ng/mL vs 29.2 ng/mL; P = .005) and a longer time from the diagnosis of CRPC to metastasis (17.9 months vs 14.3 months; P < .01). On multivariable analysis, there were no differences noted with regard to SRE risk (hazard ratio [HR], 0.80; 95% CI, 0.59-1.07) or overall mortality (HR, 0.87; 95% CI, 0.73-1.04) between black and nonblack people, although the HRs were <1, which suggested the possibility of better outcomes. CONCLUSIONS: No significant association between black race and risk of SREs and overall mortality was observed in the current study. These data have suggested that efforts to understand the basis for the excess risk of aggressive prostate cancer in black men should focus on cancer development and progression in individuals with early-stage disease.

Obesity, race, and long-term prostate cancer outcomes.

BACKGROUND: The authors previously found that obesity was linked with prostate cancer (PC)-specific mortality (PCSM) among men who underwent radical prostatectomy (RP). Herein, in a larger RP cohort, the authors investigated whether the association between obesity and long-term PC outcomes, including PCSM, differed by race. METHODS: Data from 5929 patients who underwent RP and were in the Shared Equal Access Regional Cancer Hospital (SEARCH) database were analyzed. Prior to RP, body mass index (BMI) was measured and recorded in the medical records. BMI was categorized as normal weight (<25 kg/m2 ), overweight (25-29.9 kg/m2 ), and obese (≥30 kg/m2 ). The authors assessed the association between BMI and biochemical disease recurrence (BCR), castration-resistant prostate cancer (CRPC), metastasis, and PCSM, accounting for confounders. RESULTS: Of the 5929 patients, 1983 (33%) were black, 1321 (22%) were of normal weight, 2605 (44%) were overweight, and 2003 (34%) were obese. Compared with white men, black men were younger; had higher prostate-specific antigen levels; and were more likely to have a BMI ≥30 kg/m2 , seminal vesicle invasion, and positive surgical margins (all P ≤ .032). During a median follow-up of 7.4 years, a total of 1891 patients (32%) developed BCR, 181 patients (3%) developed CRPC, 259 patients (4%) had metastasis, and 135 patients (2%) had died of PC. On multivariable analysis, obesity was found to be associated with an increased risk of PCSM (hazard ratio, 1.78; 95% confidence interval, 1.04-3.04 [P = .035]). No interaction was found between BMI and race in predicting PCSM (P ≥ .88), BCR (P ≥ .81), CRPC (P ≥ .88), or metastasis (P ≥ .60). Neither overweight nor obesity was associated with risk of BCR, CRPC, or metastasis (all P ≥ .18). CONCLUSIONS: Obese men undergoing RP at several Veterans Affairs hospitals were found to be at an increased risk of PCSM, regardless of race.

Competing Risks of Mortality among Men with Biochemical Recurrence after Radical Prostatectomy.

PURPOSE: Men with biochemical recurrence after radical prostatectomy need information on competing risks of mortality to inform prognosis and guide treatment. We quantified the risk of prostate cancer metastasis and mortality, and other cause mortality across key clinical predictors. MATERIALS AND METHODS: We analyzed 1,225 men with biochemical recurrence after radical prostatectomy from 2001 to 2017 in the VA SEARCH database. Multivariable competing risks regression was used to identify predictors and quantify cumulative incidence of metastasis, prostate cancer specific mortality and other cause mortality. Recursive partitioning analysis was used to identify optimum variable cut points for prediction of prostate cancer specific mortality and other cause mortality. RESULTS: During a median followup of 5.6 years after biochemical recurrence (IQR 2.7-9.1), 243 (20%) men died of other causes and 68 (6%) died of prostate cancer. Multivariable competing risks regression showed that high D'Amico tumor risk and prostate specific antigen doubling time at biochemical recurrence less than 9 months were associated with metastasis and prostate cancer specific mortality (p ≤0.001). Ten-year prostate cancer specific mortality was 14% and 9% for those with high risk tumors and prostate specific antigen doubling time less than 9 months, respectively. Advanced age and worse comorbidity were associated with other cause mortality (p ≤0.001). Ten-year other cause mortality was higher among men 70 years old or older with any Charlson comorbidity (1-3+) (40% to 49%) compared to those with none (20%). Recursive partitioning analysis identified optimal variable cut points for prediction of prostate cancer specific mortality and other cause mortality, with 10-year prostate cancer specific mortality ranging from 3% to 59% and 10-year other cause mortality ranging from 17% to 50% across risk subgroups. CONCLUSIONS: Among men with biochemical recurrence after radical prostatectomy, there is significant heterogeneity in prognosis that can be explained by available clinical variables. Men in their 70s with any major comorbidity are 2 to 10 times more likely to die of other causes than of prostate cancer.

Serum Lipids prior to Starting Androgen Deprivation Therapy and Risk of Castration Resistant Prostate Cancer and Metastasis: Results from the SEARCH Database.

PURPOSE: We tested the association of serum lipid levels prior to androgen deprivation therapy with the risk of castration resistant prostate cancer and metastasis. MATERIALS AND METHODS: We identified 302 men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database who received androgen deprivation therapy after radical prostatectomy for nonmetastatic disease, had never received statins before androgen deprivation therapy and had available serum lipid data within 2 years prior to androgen deprivation therapy. Cox proportional hazards models were used to test associations between total cholesterol (less than 200 vs 200 mg/dl or greater), low density lipoprotein (less than 130 vs 130 mg/dl or greater), high density lipoprotein (40 or greater vs less than 40 mg/dl) and triglycerides (less than 150 vs 150 mg/dl or greater) and the risk of castration resistant prostate cancer and metastasis after androgen deprivation therapy while adjusting for potential confounders. Subanalyses were restricted to men who remained statin nonusers after androgen deprivation therapy. RESULTS: Median followup after androgen deprivation therapy was 67 months. Castration resistant prostate cancer and metastasis developed in 42 and 44 men, respectively. Men with elevated cholesterol received androgen deprivation therapy in an earlier year and had longer followup and a higher rate of statin use after androgen deprivation therapy. On multivariable analysis total cholesterol and low density lipoprotein were unrelated to castration resistant prostate cancer. Low high density lipoprotein (less than 40 vs 40 mg/dl or greater) was suggestively linked to an increased risk of castration resistant prostate cancer (HR 1.86, 95% CI 0.99-3.48). The association was stronger in men who remained statin nonusers after androgen deprivation therapy (HR 3.64, 95% CI 1.45-9.17). Results for metastasis were similar to those for castration resistant prostate cancer. CONCLUSIONS: Among men with nonmetastatic prostate cancer who started androgen deprivation therapy serum cholesterol was unrelated to castration resistant prostate cancer or metastasis. Low high density lipoprotein was suggestively associated with risks of increased castration resistant prostate cancer and metastasis, particularly in statin never users. Further studies are needed to explore a potential role for lipids in prostate cancer progression after androgen deprivation therapy.

Racial Discrepancies in Overall Survival among Men Treated with 223Radium.

PURPOSE: Several recent studies on metastatic castration resistant prostate cancer demonstrated improved overall survival in black vs white men. 223Radium is Food and Drug Administration approved for metastatic castration resistant prostate cancer based on a survival benefit in the ALSYMPCA (A Phase III Study of Radium-223 Dichloride in Patients with Symptomatic Hormone Refractory Prostate Cancer with Skeletal Metastases) trial, in which 94% of participants were white. We identified a real world population of patients with metastatic castration resistant prostate cancer who received 223radium to compare differences in baseline characteristics and outcomes in black vs nonblack men. MATERIALS AND METHODS: We reviewed the charts of all men who received 223radium in the entire Veterans Affairs system. We compared treatment patterns and baseline characteristics between black and nonblack men. We used Cox models to analyze predictors of time from 223radium start to overall survival and time to skeletal related events. RESULTS: We identified 318 patients treated with 223radium, including 87 (27%) who were black. Median followup after 223radium initiation was 25.3 months (IQR 13.8-37.1). Black men were younger than nonblack men when starting 223radium (median age 67 vs 70 years, p <0.001) and they had higher prostate specific antigen (median 159.9 vs 90.2 ng/ml, p=0.014) and alkaline phosphatase (median 163 vs 135 IU/l, p=0.017). A greater proportion of black men received docetaxel prior to 223radium (77% vs 55%, p <0.001). On multivariable analysis black race was associated with a decreased risk of mortality from the time of 223radium initiation (HR 0.75, 95% CI 0.57-0.99, p=0.045). CONCLUSIONS: Black men had longer overall survival than nonblack men, although they appeared to receive radium later in the disease course. Further studies are required to verify our findings and explore biological differences between black and nonblack men with metastatic castration resistant prostate cancer.

Statin use and longitudinal changes in prostate volume; results from the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial.

OBJECTIVE: To test the association between statin use and prostate volume (PV) change over time using data from the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, a 4-year randomised controlled trial testing dutasteride for prostate cancer chemoprevention. SUBJECTS/PATIENTS AND METHODS: We identified men with a baseline negative prostate biopsy from REDUCE who did not undergo prostate surgery or develop prostate cancer over the trial period. Men reported statin use at baseline. PV was determined from transrectal ultrasonography performed to guide prostate biopsy at baseline, and 2- and 4-years after randomisation. Multivariable generalised estimating equations tested differences in PV change over time by statin use, overall and stratified by treatment arm. We tested for interactions between statins and time in association with PV using the Wald test. RESULTS: Of 4106 men, 17% used statins at baseline. Baseline PV did not differ by statin use. Relative to non-users, statin users had decreasing PVs over the trial period (P = 0.027). Similar patterns were seen in the dutasteride and placebo arms, although neither reached statistical significance. The mean estimated PV was modestly but significantly lower in statin users relative to non-users in the dutasteride arm at 2-years (4.5%, P = 0.032) and 4-years (4.0%, P = 0.033), with similar (3-3.3%) but non-significant effects in the placebo arm. CONCLUSION: If confirmed, our present findings support a role for statins in modestly attenuating PV growth, with a magnitude of effect in line with previously reported prostate-specific antigen-lowering effects of statins (~4%). Future studies are needed to assess whether this putative role for statins in PV growth could impact lower urinary tract symptom development or progression.

Obese men undergoing radical prostatectomy: Is robotic or retropubic better to limit positive surgical margins? Results from SEARCH.

OBJECTIVES: To evaluate the association between obesity and positive surgical margins in patients undergoing retropubic radical prostatectomy versus robotic-assisted laparoscopic prostatectomy. METHODS: We retrospectively reviewed the data of 3141 men undergoing retropubic radical prostatectomy and 1625 undergoing robotic-assisted laparoscopic prostatectomy between 1988 and 2017 at eight Veterans Health Administration hospitals. The positive surgical margin location (peripheral, apical, bladder neck, overall) was determined from pathology reports. We adjusted for age, race, prostate-specific antigen, surgery year, prostate weight, pathological grade group, extracapsular extension, seminal vesicle invasion, hospital surgical volume and surgical method (in analyses not stratified by surgical method). Interactions between body mass index and surgical approach were tested. RESULTS: Among all patients, higher body mass index was associated with increased odds of overall, peripheral and apical positive surgical margins (OR 1.02-1.03, P ≤ 0.02). Although not statistically significant, there was a trend between higher body mass index and increased odds of bladder neck positive surgical margins (OR 1.03, P = 0.09). Interactions between body mass index and surgical method were significant for peripheral positive surgical margins only (P = 0.024). Specifically, there was an association between body mass index and peripheral positive surgical margins among men undergoing retropubic radical prostatectomy (OR 1.04, P < 0.001), but not robotic-assisted laparoscopic prostatectomy (OR 1.00, P = 0.98). Limitations include lacking individual surgeon data and lacking central pathology review. CONCLUSIONS: In this multicenter cohort, higher body mass index was associated with increased odds of positive surgical margins at all locations except the bladder neck. Furthermore, there was a significant association between obesity and peripheral positive surgical margins in men undergoing retropubic radical prostatectomy, but not robotic-assisted laparoscopic prostatectomy. Long-term clinical significance requires further study.