Neurocognitive impairment associated with traditional and novel androgen receptor signaling inhibitors ± androgen deprivation therapy: a pharmacovigilance study.

BACKGROUND: Conflicting evidence exists regarding whether hormone therapy for prostate cancer is associated with neurotoxicity. Thus, we aim to characterize the association between different types of hormone therapy and neurocognitive impairment in a real-world pharmacovigilance database. METHODS: We queried VigiBase, the World Health Organization's international pharmacovigilance database, for reports of neurocognitive impairment among men who took hormone therapy from 1968 to 2021. We performed disproportionality analysis comparing rates of neurocognitive impairment with different types of hormone therapy versus other VigiBase drugs. Traditional hormonal therapy was defined as androgen deprivation therapy (ADT: gonadotropin-releasing-hormone agonists or antagonists) or first-generation androgen receptor (AR) antagonists. Novel AR signaling inhibitors (ARSIs) were defined as ARSIs with or without ADT. Differences were assessed using reporting odds ratio (ROR) with 95% confidence intervals (CI) and Empirical Bayes Estimator (EBE) values ≥1.0 signifying statistical significance. RESULTS: Odds of neurocognitive impairment were significantly elevated with traditional hormone therapy (ROR 1.47, 95% CI 1.34-1.62, EBE = 1.35) and novel ARSIs (ROR 2.40, 95% CI 2.28-2.54, EBE = 2.26). Odds of neurocognitive impairment were significantly elevated with enzalutamide (ROR 2.89, 95% CI 2.73-3.05, EBE = 2.70) and numerically increased with apalutamide (ROR 3.31, 95% CI 1.57-7.00, EBE = 0.98), but were decreased with abiraterone (ROR 0.68, 95% CI 0.55-0.84, EBE = 0.57). CONCLUSIONS: This study demonstrates elevated odds of neurocognitive impairment with hormone therapy in a real-world data set. Neurotoxicity risk was higher with novel ARSIs than traditional agents, and higher with enzalutamide than abiraterone. Due to limitations inherent to disproportionality analysis (measuring associations, not risk) and incomplete data prohibiting the ability to control for factors such as age or use of secondary drugs (e.g., concurrent use of novel ARSIs with ADT), results are exploratory in nature. The amalgamation of these and other conflicting data may contribute to clinical decision-making for men with prostate cancer eligible for treatment with these therapies, especially those with significant neurologic comorbidities.

Optimal assessment of quality of life for patients with prostate cancer.

The burden of cancer and oncologic treatment is reflected not only through morbidity and mortality, but also through impacts on patient quality of life (QoL). However, QoL has not been historically measured or addressed with the same rigorous methodology as traditional disease-related outcomes such as overall survival and progression, as these are driven by objective measurements and events. Prostate cancer (PCa) is one of the most prevalent non-cutaneous cancers in men around the world. Both the cancer and its treatment significantly impact patients' physical, emotional, sexual, social, and overall QoL. Ensuring assessment and integration of QoL in research and clinical care enables improvement in treatment outcomes that matter most to patients while also facilitating alignment of healthcare priorities with reimbursements. Great strides toward this end have been made over the last decade, but significant room for improvement remains. To ensure high quality, reliable data collection, QoL assessment tools must be psychometrically validated, standardized, widely implemented across trials, and regularly assessed to allow internal and external validity, longitudinal comparative effectiveness research, and quality control. Additional consideration should be taken for instruments used to measure the aspects of QoL specific to minority, caregiver, and elderly populations. Open clinical questions include how providers should weight changes in different QoL subscales and how clinically meaningful difference thresholds should be defined. Review of ongoing clinical trials encouragingly reveals an increased focus on measuring and improving QoL for men with PCa which will inform the way we utilize QoL assessments. However, additional efforts herein described are needed to fully optimize these processes. In summary, this review will explain the rationale for QoL assessments in PCa populations, discuss requirements for effective implementation, describe considerations for vulnerable and under-evaluated populations, and summarize ongoing clinical trials assessing patient QoL.

Understanding Hospital-Level Patterns of Nonoperative Management for Low-risk Thyroid and Kidney Cancer.

Importance: There is a growing trend toward conservative management for certain low-risk cancers. Hospital and health-system factors may play a role in determining how these patients are managed. Objective: To explore the contribution of hospitals on patients' odds of nonoperative management for low-risk cancer. Design, Setting, and Participants: In this cross-sectional study, individuals with low-risk papillary thyroid cancer and solitary kidney masses were identified, and those receiving nonoperative management vs surgery were compared. Patients with low-risk thyroid cancer and kidney cancer from 2015 to 2017 eligible for nonoperative management according to National Comprehensive Cancer Network guidelines within the National Cancer Database were included. Data were analyzed from October 2021 to March 2022. Main Outcomes and Measures: For each facility, the proportion of these patients who received operative and nonoperative management was calculated. A mixed-effects logistic regression model with a hospital-level random effects term was used to calculate factors associated with nonoperative management. Between-hospital variability was assessed using ranked caterpillar plots. Results: There were 19 570 individuals with low-risk thyroid cancer (15 344 women [78.4%]; mean [SD] age, 51.74 [95% CI, 51.39-52.08] years) and 41 403 with kidney cancer (25 253 men [61.0%]; mean [SD] age, 61.93 [95% CI, 61.70-62.17] years). In the group with low-risk thyroid cancer, 2.1% (419 patients) received nonoperative management, and in the group with kidney cancer, 9.5% (3928 patients) received nonoperative management. This varied between hospitals from 1.1% (95% CI, 1.0%-1.1%) in the bottom decile to 10.3% (95% CI, 8.0%-12.4%) in the top decile for low-risk thyroid cancer, and from 4.3% (95% CI, 4.1%-4.4%) in the bottom decile to 24.6% (95% CI, 22.7%-26.5%) in the top decile for small kidney masses. For both cancers, age was associated with increased odds of nonoperative treatment. The hospital-level odds of nonoperative management of thyroid and kidney cancer using unadjusted probabilities (observed proportions) were minimally correlated (Spearman ρ = .33; P < .001). Conclusions and Relevance: The findings of this study suggest that although health systems factors may be associated with the tendency to pursue nonoperative management, hospital-level factors may differ when comparing unrelated cancers.

Radiologists' Contribution to Variation in Detecting Clinically Significant Prostate Cancer in Men With Prostate MRI.

OBJECTIVE: Assess radiologists' contribution to variation in clinically significant prostate cancer (csPCa) detection in patients with elevated prostate-specific antigen (PSA) and multiparametric MRI (mpMRI). METHODS: This institutional review board-approved, retrospective cohort study was performed at a tertiary, academic, National Cancer Institute-designated Comprehensive Cancer Center with a multidisciplinary prostate cancer program. Men undergoing mpMRI examinations from January 1, 2015, to December 31, 2019, with elevated PSA (≥4 ng/mL) and biopsy within 6 months pre- or post-MRI or prostatectomy within 6 months post-mpMRI were included. Univariate and multivariable hierarchical logistic regression assessed impact of patient, provider, mpMRI examination, mpMRI report, and pathology factors on the diagnosis of Grade Group ≥ 2 csPCa. RESULTS: Study cohort included 960 MRIs in 928 men, mean age 64.0 years (SD ± 7.4), and 59.8% (555 of 928) had csPCa. Interpreting radiologist was not significant individually (P > .999) or combined with mpMRI ordering physician and physician performing biopsy or prostatectomy (P = .41). Prostate Imaging Reporting and Data System (PI-RADS) category 2 (odds ratio [OR] 0.18, P = .04), PI-RADS category 4 (OR 2.52, P < .001), and PI-RADS category 5 (OR 4.99, P < .001) assessment compared with no focal lesion; PSA density of 0.1 to 0.15 ng/mL/cc (OR 2.46, P < .001), 0.15 to 0.2 ng/mL/cc (OR 2.77, P < .001), or ≥0.2 ng/mL/cc (OR 4.52, P < .001); private insurance (reference = Medicare, OR 0.52, P = .001), and unambiguous extraprostatic extension on mpMRI (OR 2.94, P = .01) were independently associated with csPCa. PI-RADS 3 assessment (OR 1.18, P = .56), age (OR 0.99, P = .39), and African American race (OR 0.90, P = .75) were not. DISCUSSION: Although there is known in-practice variation in radiologists' interpretation of mpMRI, in our multidisciplinary prostate cancer program we found no significant radiologist-attributable variation in csPCa detection.

Does the 5-item Frailty Index predict surgical complications of endoscopic surgical management for benign prostatic obstruction? An analysis of the ACS-NSQIP.

PURPOSE: To assess whether the 5-item Frailty Index (5i-FI) predicts surgical complications of endoscopic surgery for benign prostatic obstruction (BPO) and examine the rates of these complications across BPO surgical modalities adjusting for patient frailty. METHODS: The ACS-NSQIP registry was queried for patients who underwent transurethral resection of the prostate (TURP), photoselective vaporization of the prostate (PVP), and laser enucleation of the prostate (LEP) between 2009 and 2019. Patients' frailties were estimated using the 5i-FI. We assessed the association between 5i-FI and the following endpoints: all complications, major complications (Clavien-Dindo ≥ 3), length of stay (LOS) ≥ 2 days, and 30-day postoperative readmission. Inverse probability of treatment weighting (IPTW) was used to account for selection bias in treatment allocation. IPTW-adjusted rates for 30-day complications were compared between surgical modalities. RESULTS: The cohort included 38,399 (62.6%) TURP, 19,121 (31.2%) PVP, and 3797 (6.2%) LEP. Men with 5i-FI score ≥ 2 were more likely to receive TURP (22.7%) and PVP (22.5%) than LEP (18.8%). 5i-FI ≥ 2 was associated with higher odds of all complications (OR 1.50), major complications (OR 1.63), LOS ≥ 2 (OR 1.31), and readmission (OR 1.65). After IPTW, LEP had the lowest rates for all complications (6.29%; 95%CI 5.48-7.20), major complications (2.30%; 95%CI 1.83-2.89), and readmission (3.80%; 95%CI 3.18-4.53). CONCLUSION: The 5i-FI score is an independent predictor of 30-day postoperative surgical complications after endoscopic BPO surgery. After IPTW, LEP and PVP were associated with lower rates of complications than TURP. However, frail patients were less likely to undergo PVP and LEP. Preoperative frailty assessment could improve risk stratification before BPO surgery.

Meditative and mind-body practice among patients with genitourinary malignancy.

INTRODUCTION AND OBJECTIVE: Research on the utility of meditative and mind-body (MB) practices has increased dramatically in the last two decades and both have been suggested as useful adjuncts in coping with stressors associated with cancer survivorship. There exists little data on use among genitourinary (GU) cancer survivors. This study seeks to describe meditative and MB utilization among GU cancer survivors. METHODS: Analysis of data from the 2012 and 2017 National Health Interview Survey was conducted. Patients aged 40 and older reporting a history of any cancer diagnosis (including 3 GU cancers) were included in the analysis. We explored questions about meditative and MB practices in the past 12 months. Complex Samples Logistic regression was performed to compare the relationship between cancer status and use of these practices. RESULTS: Self-reported meditative practices were more prevalent in 2017 (17%) than in 2012 (5%). Patients who self-reported a cancer diagnosis of any kind were significantly more likely to utilize meditative practices. Patients with kidney cancer were significantly more likely to meditate and trended towards higher MB utilization. In contrast, bladder cancer patients were less likely to meditate and use MB practices. Increases in meditation were greater than those seen for MB in all groups. CONCLUSIONS: Meditative and MB practices increased in prevalence between 2012 and 2017 with notable heterogeneity between cancer types. Given the potential benefit, more broad incorporation into survivorship programs may be warranted. Future work should explore the significance of this heterogeneity and the utility of these practices to patients with urologic malignancy.

Mobile Health App for Prostate Cancer Patients on Androgen Deprivation Therapy: Qualitative Usability Study.

BACKGROUND: Androgen deprivation therapy (ADT) increases the risk of metabolic adverse effects among patients with prostate cancer. The transformative impact of mobile health (mHealth) apps may benefit men managing activity and nutrition at home. OBJECTIVE: This study aimed to evaluate the usability and patient experience of a newly developed mHealth app among prostate cancer patients on ADT and physicians' beliefs about the potential benefits of using this app. METHODS: This study took place over 2 months, beginning in March 2019. A sample of 5 patients (age 45-75 years) initiating ADT participated in a semistructured focus group discussion with a facilitator. The study participants also included 5 specialist physicians who provided in-depth interviews. An institutional review board-approved script was used to guide both the focus group and physician interviews. Usability was tested through specific scenarios presented to the patients, including downloading the mHealth app, entering information on physical activity and meals, and navigating the app. The focus group and interviews were audio recorded and transcribed. Content analysis was used to analyze the transcripts iteratively and exhaustively. Thematic discrepancies between reviewers were resolved through consensus. RESULTS: The mean age of the patients was 62 years. This group included 4 White and 1 Latin American patients. The physician specialists included 2 urologists, 2 medical oncologists, and 1 radiation oncologist. Analyses revealed that the patients appreciated the holistic care enabled by the app. Difficulties were observed with registration of the app among 60% (3/5) of the patients; however, all the patients were able to input information about their physical activity and navigate the options within the app. Most patients (4/5, 80%) were able to input data on their recent meal. Among the health care physicians, the dominant themes reflected in the interviews included undermining of patients ability to use technology, patients' fear of technology, and concern for the ability of older patients to access technology. CONCLUSIONS: The patients reported an overall positive experience of using an mHealth app to record and track diet and exercise. Usability was observed to be an important factor for adoption and was determined by ease of registration and use, intuitive appearance of the app, and focus on holistic cancer care. The physicians believed that the app was easy to use but raised concerns about usability among older men who may not typically use smartphone apps.

Ambulatory-Based Bladder Outlet Procedures Offer Significant Cost Savings and Comparable 30-Day Outcomes Relative to Inpatient Procedures.

Introduction and Objectives: Budgetary constraints and novel minimally invasive surgical approaches have resulted in surgical care being increasingly provided at ambulatory centers rather than traditional inpatient settings. Despite increasing use of ambulatory-based procedure for bladder outlet obstruction (BOO) procedures, little is known about the effect of care setting on perioperative outcomes and costs. We sought to compare 30-day readmissions rates and costs of BOO procedure performed in the ambulatory vs inpatient setting. Methods: Using Florida and New York all-payer data from the 2014 Healthcare Cost and Utilization Project State Databases, we identified patients who underwent transurethral resection, thermotherapy, or laser/photovaporization for BOO. Patient demographics, regional data, 30-day readmissions rates, and costs (from converted charges) associated with the index procedure and revisits were analyzed. Predictors of 30-day revisits were also identified by fitting a multivariate logistic regression model with facility-level clustering. Results: Of the 15,094 patients identified, 1444 (9.6%) had a 30-day revisit at a median cost of $4263.43. The 30-day readmission rate for inpatient cases was significantly higher than that of surgeries performed in the ambulatory setting (12.0% vs 8.1%, p < 0.001). Payer status (private vs Medicare: odds ratio [OR] = 0.77, 95% confidence interval [CI] = 0.62-0.95; p = 0.02) and index care setting (ambulatory vs inpatient: OR = 0.48, 95% CI = 0.40-0.57; p < 0.001) predicted 30-day revisits. Conclusions: We identified that index care setting and payer status are independent predictors of 30-day revisit after BOO procedure, with the inpatient setting and Medicare insurance associated with higher odds of revisit. Ambulatory procedures are significantly less costly than procedures performed in the inpatient setting, even after accounting for ambulatory procedures leading to an admission. There is an obvious cost benefit of offering BOO procedure in the ambulatory setting to the appropriate patient. In the context of value-based health care initiatives, our findings have important implications for policymakers seeking to reduce variation in nonclinical sources of perioperative costs and outcomes.

Contemporary national trends in prostate cancer risk profile at diagnosis.

BACKGROUND: Over the past decade prostate cancer (PCa) diagnostic approaches have evolved away from aggressive prostate-specific antigen (PSA) screening. While a goal of these changes is to decrease over diagnosis and treatment, little is known about the downstream effects on PCa risk distribution at the time of diagnosis. To better understand these effects, we used a national cohort of men to investigate temporal trends in PCa risk profile at diagnosis. METHODS: Using the National Cancer Database, we identified men diagnosed with biopsy-confirmed clinically localized prostate adenocarcinoma (T1-4N0M0) from 2004 to 2014. We assessed temporal trends in proportional distribution of National Comprehensive Cancer Network risk groups as well as their sub-components (PSA, Gleason score, clinical T stage). We also evaluated trends in these sub-components among men with intermediate- and high-risk disease as well as those with metastatic disease. RESULTS: In our cohort of 755,567 men diagnosed between 2004 and 2014, there was a decrease in the proportion of men diagnosed with low-risk PCa (38.32 to 27.23%, p < 0.001) and a consequent increase in the proportion of localized intermediate-risk (40.49 to 46.72%, p < 0.001) and high-risk diagnoses (21.19 to 26.05%, p < 0.001). This was primarily driven by an increased proportion of Gleason 7 and Gleason 8-10 cancer, respectively. The number of men presenting with metastatic disease consistently increased from 3251 (2.88%) in 2004 to 6886 (7.19%) in 2014 (p < 0.001). CONCLUSIONS: The proportion of localized intermediate/high risk and metastatic PCa has substantially increased over the past decade, while the proportion of low-risk disease has decreased. This shift has been primarily driven by increased diagnosis of high-grade disease. National guidelines advising against PSA screening may have contributed to these findings.

Evaluation of Intense Androgen Deprivation Before Prostatectomy: A Randomized Phase II Trial of Enzalutamide and Leuprolide With or Without Abiraterone.

PURPOSE: Patients with locally advanced prostate cancer have an increased risk of cancer recurrence and mortality. In this phase II trial, we evaluate neoadjuvant enzalutamide and leuprolide (EL) with or without abiraterone and prednisone (ELAP) before radical prostatectomy (RP) in men with locally advanced prostate cancer. PATIENTS AND METHODS: Eligible patients had a biopsy Gleason score of 4 + 3 = 7 or greater, prostate-specific antigen (PSA) greater than 20 ng/mL, or T3 disease (by prostate magnetic resonance imaging). Lymph nodes were required to be smaller than 20 mm. Patients were randomly assigned 2:1 to ELAP or EL for 24 weeks followed by RP. All specimens underwent central pathology review. The primary end point was pathologic complete response or minimal residual disease (residual tumor ≤ 5 mm). Secondary end points were PSA, surgical staging, positive margins, and safety. Biomarkers associated with pathologic outcomes were explored. RESULTS: Seventy-five patients were enrolled at four centers. Most patients had high-risk disease by National Comprehensive Cancer Network criteria (n = 65; 87%). The pathologic complete response or minimal residual disease rate was 30% (n = 15 of 50) in ELAP-treated patients and 16% (n = four of 25) in EL-treated patients (two-sided P = .263). Rates of ypT3 disease, positive margins, and positive lymph nodes were similar between arms. Treatment was well-tolerated. Residual tumors in the two arms showed comparable levels of ERG, PTEN, androgen receptor PSA, and glucocorticoid receptor expression. Tumor ERG positivity and PTEN loss were associated with more extensive residual tumors at RP. CONCLUSION: Neoadjuvant hormone therapy followed by RP in locally advanced prostate cancer resulted in favorable pathologic responses in some patients, with a trend toward improved pathologic outcomes with ELAP. Longer follow-up is necessary to evaluate the impact of therapy on recurrence rates. The potential association of ERG and PTEN alterations with worse outcomes warrants additional investigation.

Lack of Benefit From the Addition of External Beam Radiation Therapy to Brachytherapy for Intermediate- and High-risk Prostate Cancer.

PURPOSE: A recent randomized controlled trial demonstrated that the addition of external beam radiation therapy (EBRT) to brachytherapy did not improve progression-free survival in select patients with intermediate-risk prostate cancer. We evaluated whether the addition of EBRT to brachytherapy improves prostate cancer-specific mortality (PCSM) for intermediate- and high-risk disease using a large national database. METHODS AND MATERIALS: We identified 5836 patients in the Surveillance, Epidemiology, and End Results-Medicare linked database with a diagnosis of National Comprehensive Cancer Network intermediate-risk (Gleason score 7, prostate-specific antigen 10-20 ng/mL, or stage cT2b-T2c) or high-risk (Gleason score 8-10 or prostate-specific antigen >20 ng/mL and stage ≤cT3a) prostate cancer who had undergone brachytherapy, with or without EBRT and androgen deprivation therapy (ADT). Patients were diagnosed from 2004 through 2009. Intermediate-risk patients with Gleason score ≤3+4 and 1 intermediate-risk factor were considered favorable and all others unfavorable. We used multivariable Fine-Gray competing risks regression to study PCSM while adjusting for sociodemographic and clinical factors and ADT use. RESULTS: Overall, 50.3% of intermediate- and high-risk patients who received brachytherapy and EBRT did not have significantly improved PCSM compared with that of the patients who received brachytherapy alone (adjusted hazard ratio [AHR] 1.46, 95% confidence interval [CI] 0.69-3.11; P=.322; 5-year PCSM 2.4% vs 1.0%). This lack of benefit was seen among favorable intermediate-risk (AHR 2.66, 95% CI 0.93-7.62, P=.069; 5-year PCSM 1.3% vs 0.6%), unfavorable intermediate-risk (AHR 0.68, 95% CI 0.16-2.96, P=.612; 5-year PCSM 1.0% vs 1.2%), and high-risk (AHR 1.82, 95% CI 0.67-4.98, P=.242; 5-year PCSM 5.3% vs 2.1%) subgroups. CONCLUSIONS: These results suggest that certain patients with intermediate- or high-risk prostate cancer treated with brachytherapy might not benefit from the addition of EBRT. A randomized controlled trial of brachytherapy plus ADT with or without EBRT for unfavorable intermediate- and favorable high-risk organ-confined prostate cancer should be undertaken.

Variation in Locoregional Prostate Cancer Care and Treatment Trends at Commission on Cancer Designated Facilities: A National Cancer Data Base Analysis 2004 to 2013.

BACKGROUND: Contemporary treatment trends for prostate cancer show increased rates of active surveillance. However, nationwide applicability of these reports is limited. Additionally, the effect of Commission on Cancer facility type on prostate cancer treatment patterns is unknown. PATIENTS AND METHODS: We used the National Cancer Data Base to identify men diagnosed with prostate cancer, between 2004 and 2013. Our cohort was stratified on the basis of the National Comprehensive Cancer Network prostate cancer risk classes. Cochran-Armitage tests were used to evaluate temporal trends. Random effects hierarchical logit models were used to assess treatment variation at Commission on Cancer facility and institution level. RESULTS: In 825,707 men, utilization of radiation therapy declined and utilization of radical prostatectomy increased for all prostate cancer risk groups between 2004 and 2013 (P < .0001). Observation for low-risk prostate cancer increased from 16.3% in 2004 to 2005 to 32.0% in 2012 to 2013 (P < .0001). Significant treatment variation was observed on the basis of Commission on Cancer facility type. Across all risk groups, the lowest rates of radical prostatectomy and highest rates of external beam radiation therapy were observed in community cancer programs. The highest rates of observation for low-risk disease were observed in academic centers. Treatment variation according to institution ranged from 14% (95% confidence interval, 0.12-0.15) for androgen deprivation therapy up to 59% (95% confidence interval, 0.45-0.73) for cryotherapy. CONCLUSION: The increased utilization of observation in low-risk prostate cancer is an encouraging finding, which appears to be mainly derived by a decrease in radiotherapy utilization in this risk group. Regardless of tumor characteristics, significant variations in treatment modality exist among different facility types and institutions.

Factors associated with the omission of androgen deprivation therapy in radiation-managed high-risk prostate cancer.

PURPOSE: Androgen deprivation therapy (ADT) has been shown to improve survival for men with unfavorable-risk prostate cancer (PCa). We investigated the utilization and factors associated with the omission of ADT in radiation-managed high-risk PCa. METHODS AND MATERIALS: We used the National Cancer Database to identify men with National Comprehensive Cancer Network high-risk PCa treated with external beam radiation therapy (EBRT) with or without brachytherapy boost from 2004 to 2012. Multivariable logistic regression adjusting for clinical and sociodemographic factors was used to identify independent predictors for ADT use. RESULTS: A total of 57,968 radiation-treated high-risk PCa men were included in our analysis. There were 49,363 patients (85.2%) treated with EBRT alone and 8605 patients (14.8%) treated with EBRT plus brachytherapy boost. Overall, 77% of men received ADT. In multivariable regression analysis, the use of brachytherapy boost was associated with a significantly lower utilization of ADT (70% vs. 78%; adjusted odds ratio [AOR]: 0.65; 95% CI: 0.62-0.69; p-Value <0.0001), as was treatment at an academic vs. nonacademic center (AOR: 0.90; 95% CI: 0.86-0.95; p-Value <0.0001) and treatment in 2010-2012 compared to 2004-2006 (AOR: 0.85; 95% CI: 0.81-0.90; p-Value <0.0001). Conversely, greater ADT use was seen with higher Gleason scores, PSA, and T-category (all p-Values <0.001). CONCLUSIONS: Approximately one in four men with radiation-managed high-risk PCa do not receive ADT, which may reflect concerns about its toxicity profile despite known improvements in overall survival. Practice patterns suggest that some providers believe dose escalation through brachytherapy boost may obviate the need for ADT in some high-risk patients, but this hypothesis requires further testing.

Assessment of energy density usage during 180W lithium triborate laser photoselective vaporization of the prostate for benign prostatic hyperplasia. Is there an optimum amount of kilo-Joules per gram of prostate?

OBJECTIVES: To assess the effect of energy density (kJ/mL) applied on adenoma during photoselective vaporization of the prostate (PVP) treatment for benign prostate hyperplasia (BPH) on functional outcomes, prostate-specific antigen (PSA) reduction and complications. PATIENTS AND METHODS: After exclusions, a total of 440 patients who underwent GreenLight (tm) laser XPS-180W lithium triborate PVP for the treatment of BPH were retrospectively reviewed. Data were collected from seven different international centres (Canada, USA, UK and France). Patients were stratified into four energy density groups (kJ/mL) according to intra-operative energy delivered and prostate volume as determined by preoperative transrectal ultrasonography (TRUS): group 1: <3 kJ/mL; group 2: 3-5 kJ/mL; group 3: 5-7 kJ/mL; and group 4: ≥7 kJ/mL. Energy density groups were chosen arbitrarily. PSA reduction and functional outcomes (International Prostate Symptom Score, quality of life, post-void residual urine volume, maximum urinary flow rate) were compared at 6, 12 and 24 months. Peri-operative complications and retreatment rates were also compared among the groups. RESULTS: The PSA reduction rates at 24 months after the procedure were 51, 61, 79 and 83% for the energy density groups <3, 3-5, 5-7 and ≥7 kJ/mL, respectively (P ≤ 0.01). This held true after accounting for baseline confounders. Energy density was not associated with higher complication rates, including haematuria, stricture formation, incontinence, refractory urinary retention, urinary tract infection and conversion to transurethral resection of the prostate. Functional outcomes at 2 years of follow-up were equivalent among the groups (P > 0.05 for all) and similar retreatment rates were observed (P = 0.36). CONCLUSION: Higher energy usage per cc of prostate was associated with a more significant reduction in PSA level (>50%) at 6, 12 and 24 months, suggesting increased vaporization of adenoma tissue; however, this did not translate into differences in functional outcomes at 2-year follow-up.

Occult High-risk Disease in Clinically Low-risk Prostate Cancer with ≥50% Positive Biopsy Cores: Should National Guidelines Stop Calling Them Low Risk?

OBJECTIVE: To identify contemporary, clinically low-risk patients with ≥50% cores positive and compare the risk of upgrading at prostatectomy with other low- or intermediate-risk patients. MATERIALS AND METHODS: We studied 14,902 patients with prostate cancer in the Surveillance, Epidemiology, and End Results database in 2010-2011 treated with prostatectomy. Patients were categorized by National Comprehensive Cancer Network clinical risk groups, separating low-risk patients by percent positive biopsy cores (PBC). We measured incidence of pathologic high-risk disease, defined as pT3a-T4 or Gleason 8-10, and multivariable logistic regression was used to determine if patients with clinical low-risk disease and ≥50% PBC were similar to other low- or intermediate-risk patients. This analysis was repeated with favorable and unfavorable intermediate risk. RESULTS: At prostatectomy, 9.2% of clinically low-risk patients with <50% PBC, 18.6% of clinically low-risk patients with ≥50% PBC, and 27.6% of clinically intermediate-risk patients had occult, high-risk disease (P <.001). On multivariable logistic regression, low-risk patients with ≥50% PBC were more likely than low-risk patients with <50% PBC to have pathologic high-risk disease (adjusted odds ratio [AOR] 2.28, 95% confidence interval 1.90-2.73, P <.001), had similar risk to favorable intermediate patients overall (AOR 1.09, 0.91-1.31, P = .33), and had higher risk than favorable intermediate patients aged over 60 years (AOR 1.28, 1.00-1.64, P = .04). Low-risk patients with ≥50% PBC had a mean tumor size similar to unfavorable intermediate-risk patients (21.3 vs 21.0 mm, P = .82). CONCLUSION: Nearly 1 in 5 clinically low-risk prostate cancer patients with ≥50% PBC harbor occult pT3a-T4 or Gleason 8-10, suggesting that national guidelines should not classify low-risk patients with ≥50% cores positive as "low risk," and patients should be made aware of this excess risk if considering active surveillance.

Photoselective Vaporization of the Prostate for Benign Prostatic Hyperplasia Using the 180 Watt System: Multicenter Study of the Impact of Prostate Size on Safety and Outcomes.

PURPOSE: We evaluated photoselective vaporization of the prostate using the GreenLight™ XPS™ 180 W system for benign prostatic hyperplasia treatment in a large multi-institutional cohort at 2 years. We particularly examined safety, outcomes and the re-treatment rate in larger prostates, defined as a prostate volume of 80 cc or greater, to assess the potential of photoselective vaporization of the prostate as a size independent procedure. MATERIALS AND METHODS: A total of 1,196 patients were treated at 6 international centers in Canada, the United States, France and England. All parameters were collected retrospectively, including complications, I-PSS, maximum urinary flow rate, post-void residual urine, prostate volume, prostate specific antigen and the endoscopic re-intervention rate. Subgroup stratified comparative analysis was performed according to preoperative prostate volume less than 80 vs 80 cc or greater on transrectal ultrasound. RESULTS: Median prostate size was 50 cc in 387 patients and 108 cc in 741 in the prostate volume groups less than 80 and 80 cc or greater, respectively. The rate of conversion to transurethral prostate resection was significantly higher in the 80 cc or greater group than in the less than 80 cc group (8.4% vs 0.6%, p <0.01). I-PSS, quality of life score, maximum urinary flow rate and post-void residual urine were significantly improved compared to baseline at 6, 12 and 24 months of followup without significant differences between the prostate size groups. The re-treatment rate at 2 years reported in 5 of 411 patients was associated with the delivery of decreased energy density (2.1 vs 4.4 kJ/cc) in the group without re-treatment. CONCLUSIONS: Photoselective vaporization of the prostate using the XPS 180 W system is safe and efficacious, providing durable improvement in functional outcomes at 2 years independent of prostate size when treated with sufficient energy.

Trends in disparate treatment of African American men with localized prostate cancer across National Comprehensive Cancer Network risk groups.

OBJECTIVE: To determine whether African Americans (AAs) with intermediate- to high-risk prostate cancer (PCa) receive similar treatment as white patients and whether any observed disparities are narrowing with time. METHODS: We used Surveillance, Epidemiology, and End Results to identify 128,189 men with localized intermediate- to high-risk PCa (prostate-specific antigen ≥10 ng/mL, Gleason score ≥7, or T stage ≥T2b) diagnosed from 2004 to 2010. We used multivariate logistic regression analyses to determine the impact of race on the receipt of definitive treatment. RESULTS: AA men were significantly less likely to receive curative-intent treatment than white men (adjusted odds ratio [AOR], 0.82; 95% confidence interval [CI], 0.79-0.86; P <.001). There was no evidence of this disparity narrowing over time (Pinteraction 2010 vs 2004 = .490). Disparities in the receipt of treatment between AA and white men were significantly larger in high-risk (AOR, 0.60; 95% CI, 0.56-0.64; P <.001) than in intermediate-risk disease (AOR, 0.92; 95% CI, 0.88-0.97; P = .04; Pinteraction <.001). After adjusting for treatment, demographics, and prognostic factors, AA men had a higher risk of prostate cancer-specific mortality (adjusted hazard ratio, 1.12; 95% CI, 1.01-1.25; P = .03). CONCLUSION: AA men with intermediate- to high-risk PCa are less likely to be treated with curative intent than white men. This disparity is worse in high-risk disease and is not improving over time. Factors underlying this treatment disparity should be urgently studied as it is a potentially correctable contributor to excess PCa mortality among AA patients.

Morbidity and mortality after benign prostatic hyperplasia surgery: data from the American College of Surgeons national surgical quality improvement program.

BACKGROUND AND PURPOSE: With the aging population, it is becoming increasingly important to identify patients at risk for postsurgical complications who might be more suited for conservative treatment. We sought to identify predictors of morbidity after surgical treatment of benign prostatic hyperplasia (BPH) using a large national contemporary population-based cohort. METHODS: Relying on the American College of Surgeons National Surgical-Quality Improvement Program (ACS-NSQIP; 2006-2011) database, we evaluated outcomes after transurethral resection of the prostate (TURP), laser vaporization of the prostate (LVP), and laser enucleation of the prostate (LEP). Outcomes included blood-transfusion rates, length of stay, complications, reintervention rates, and perioperative mortality. Multivariable logistic-regression analysis evaluated the predictors of perioperative morbidity and mortality. RESULTS: Overall, 4794 (65.2%), 2439 (33.1%), and 126 (1.7%) patients underwent TURP, LVP, and LEP, respectively. No significant difference in overall complications (P=0.3) or perioperative mortality (P=0.5) between the three surgical groups was found. LVP was found to be associated with decreased blood transfusions (odds ratio [OR]=0.21; P=0.001), length of stay (OR=0.12; P<0.001) and reintervention rates (OR=0.63; P=0.02). LEP was found to be associated with decreased prolonged length of stay (OR=0.35; P=0.01). Men with advanced age at surgery and non-Caucasians were at increased risk of morbidity and mortality. In contrast, normal preoperative albumin and higher preoperative hematocrit (>30%) levels were the only predictors of lower overall complications and perioperative mortality. CONCLUSIONS: All three surgical modalities for BPH management were found to be safe. Advanced age and non-Caucasian race were independent predictors of adverse outcomes after BPH surgery. In patients with these attributes, conservative treatment might be a reasonable alternative. Also, preoperative hematocrit and albumin levels represent reliable predictors of adverse outcomes, suggesting that these markers should be evaluated before BPH surgery.