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Background: Prostate cancer racial disparities in mortality outcomes are the largest in all of oncology, and less aggressive treatment received by African American (AA) patients versus white patients is likely a contributing factor. However, the reasons underlying the differences in treatment are unclear.Methods: This study examined a prospective, population-based cohort of 1170 men with newly diagnosed nonmetastatic prostate cancer enrolled from 2011 to 2013 before treatment throughout North Carolina. By phone survey, each participant was asked to rate the aggressiveness of his cancer, and his response was compared to the actual diagnosis based on a medical record review. Participants were also asked to rate the importance of 10 factors for their treatment decision-making process.Results: Among AA and white patients with low-risk cancer (according to National Comprehensive Cancer Network guidelines), 78% to 80% perceived their cancers to be "not very aggressive." However, among high-risk patients, 54% of AA patients considered their cancers to be "not very aggressive," whereas 24% of white patients did (P < .001). Although both AA and white patients indicated that a cure was a very important decision-making factor, AAs were significantly more likely to consider cost, treatment time, and recovery time as very important. In a multivariable analysis, perceived cancer aggressiveness and cure as the most important factor were significantly associated with receiving any aggressive treatment and were associated with surgery (vs radiation). After adjustments for these factors and sociodemographic factors, race was not significantly associated with the treatment received.Conclusions: Racial differences in perceived cancer aggressiveness and factors important in treatment decision making provide novel insights into reasons for the known racial disparities in prostate cancer as well as potential targets for interventions to reduce these disparities. [ABSTRACT FROM AUTHOR]

Background: Partial prostate treatment has emerged as a potential method for treating patients with favorable-risk prostate cancer while minimizing toxicity. The authors previously demonstrated poor rates of biochemical disease control for patients with National Comprehensive Cancer Network (NCCN) intermediate-risk disease using partial gland treatment with brachytherapy. The objective of the current study was to estimate the rates of distant metastasis and prostate cancer-specific mortality (PCSM) for this cohort.Methods: Between 1997 and 2007, a total of 354 men with clinical T1c disease, a prostate-specific antigen (PSA) level < 15 ng/mL, and Gleason grade ≤3 + 4 prostate cancer underwent partial prostate treatment with brachytherapy to the peripheral zone under 0.5-Tesla magnetic resonance guidance. The cumulative incidences of metastasis and PCSM for the NCCN very low-risk, low-risk, and intermediate-risk groups were estimated. Fine and Gray competing risk regression was used to evaluate clinical factors associated with time to metastasis.Results: A total of 22 patients developed metastases at a median of 11.0 years (interquartile range, 6.9-13.9 years). The 12-year metastasis rates for patients with very low-risk, low-risk, and intermediate-risk disease were 0.8% (95% confidence interval [95% CI], 0.1%-4.4%), 8.7% (95% CI, 3.4%-17.2%), and 15.7% (95% CI, 5.7%-30.2%), respectively, and the 12-year PCSM estimates were 1.6% (95% CI, 0.1%-7.6%), 1.4% (95% CI, 0.1%-6.8%), and 8.2% (95% CI, 1.9%-20.7%), respectively. On multivariate analysis, NCCN risk category (low risk: hazard ratio, 6.34 [95% CI, 1.18-34.06; P = .03] and intermediate risk: hazard ratio, 6.98 [95% CI, 1.23-39.73; P = .03]) was found to be significantly associated with the time to metastasis.Conclusions: Partial prostate treatment with brachytherapy may be associated with higher rates of distant metastasis and PCSM for patients with intermediate-risk disease after long-term follow-up. Treatment of less than the full gland may not be appropriate for this cohort. [ABSTRACT FROM AUTHOR]

BACKGROUND: Accountable care organizations (ACOs) have been shown to reduce prostate cancer treatment among men unlikely to benefit because of competing risks (ie, potential overtreatment). This study assessed whether the level of engagement in ACOs by urologists affected rates of treatment, overtreatment, and spending. METHODS: A 20% sample of national Medicare data was used to identify men diagnosed with prostate cancer between 2012 and 2014. The extent of urologist engagement in an ACO, as measured by the proportion of patients in an ACO managed by an ACO‐participating urologist, served as the exposure. The use of treatment, potential overtreatment (ie, treatment in men with a ≥75% risk of 10‐year noncancer mortality), and average payments in the year after diagnosis for each ACO were modeled. RESULTS: Among 2822 men with newly diagnosed prostate cancer, the median rates of treatment and potential overtreatment by an ACO were 71.3% (range, 23.6%‐79.5%) and 53.6% (range, 12.4%‐76.9%), respectively. Average Medicare payments among ACOs in the year after diagnosis ranged from $16,523.52 to $34,766.33. Stronger urologist‐ACO engagement was not associated with treatment (odds ratio, 0.87; 95% confidence interval, 0.6‐1.2; P = .4) or spending (9.7% decrease in spending; P = .08). However, urologist engagement was associated with a lower likelihood of potential overtreatment (odds ratio, 0.29; 95% confidence interval, 0.1‐0.86; P = .03). CONCLUSIONS: ACOs vary widely in treatment, potential overtreatment, and spending for prostate cancer. ACOs with stronger urologist engagement are less likely to treat men with a high risk of noncancer mortality, and this suggests that organizations that better engage specialists may be able to improve the value of specialty care. Cancer 2018. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Prostate-specific antigen (PSA) measurement after definitive radiotherapy (RT) and androgen deprivation therapy for localized prostate cancer has been proposed as an early prognostic biomarker. In the current study, the authors investigated the association between 3-month post-RT PSA level and biochemical progression-free survival (bPFS), prostate cancer-specific survival (PCSS), and overall survival (OS).Methods: A total of 5783 patients with intermediate-risk or high-risk localized prostate cancer who were diagnosed between 2000 and 2015 and treated with RT and androgen deprivation therapy were identified from Veterans Affairs data. Patients were divided into groups based on 3-month post-RT PSA values: <0.10 ng/mL, 0.10 to 0.49 ng/mL, and ≥0.50 ng/mL. The effect of the 3-month PSA group on bPFS, PCSS, and OS was evaluated in multivariable Cox models adjusting for potential confounders.Results: There were 2651 patients with intermediate-risk and 3132 with high-risk disease; approximately 11% had a 3-month PSA level of ≥0.50 ng/mL. A higher 3-month PSA level was found to be strongly associated with each outcome; compared with patients in the group with a 3-month PSA value <0.10 ng/mL, the authors noted greater hazards for the patients with a 3-month PSA value ≥0.50 ng/mL (hazard ratio for bPFS: 5.23; PCSS: 3.97; and OS: 1.50 [P<.001 for all]) and the patients with a 3-month PSA value of 0.10 to 0.49 ng/mL (hazard ratio for bPFS: 2.41 [P<.001]; PCSS: 2.29 [P<.001]; and OS: 1.21 [P = .003]). When analyzed separately, the 3-month PSA level was found to be predictive of OS in the high-risk group (P<.001) but not the intermediate-risk group (P = .21).Conclusions: The 3-month post-RT PSA level appears to be a strong prognostic biomarker for bPFS, PCSS, and OS in patients with intermediate-risk and high-risk prostate cancer, particularly those with high-risk disease. The 3-month PSA measurement may augment clinical decision making and holds promise as a potential surrogate endpoint in clinical trials. Cancer 2018;124:2939-47. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Temporal trends in prostate cancer incidence and death rates have been attributed to changing patterns of screening and improved treatment (mortality only), among other factors. This study evaluated contemporary national-level trends and their relations with prostate-specific antigen (PSA) testing prevalence and explored trends in incidence according to disease characteristics with stage-specific, delay-adjusted rates.Methods: Joinpoint regression was used to examine changes in delay-adjusted prostate cancer incidence rates from population-based US cancer registries from 2000 to 2014 by age categories, race, and disease characteristics, including stage, PSA, Gleason score, and clinical extension. In addition, the analysis included trends for prostate cancer mortality between 1975 and 2015 by race and the estimation of PSA testing prevalence between 1987 and 2005. The annual percent change was calculated for periods defined by significant trend change points.Results: For all age groups, overall prostate cancer incidence rates declined approximately 6.5% per year from 2007. However, the incidence of distant-stage disease increased from 2010 to 2014. The incidence of disease according to higher PSA levels or Gleason scores at diagnosis did not increase. After years of significant decline (from 1993 to 2013), the overall prostate cancer mortality trend stabilized from 2013 to 2015.Conclusions: After a decline in PSA test usage, there has been an increased burden of late-stage disease, and the decline in prostate cancer mortality has leveled off. Cancer 2018;124:2801-2814. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Men diagnosed with localized prostate cancer seek information on how treatment options may impact their health-related quality of life (HRQOL). The authors used latent profile analysis (LPA) to group men according to their symptom burden and functional status and to identify patient characteristics associated with each HRQOL profile.Methods: Patients completed the Patient-Reported Outcomes Measurement Information System and the Expanded Prostate Index Composite measures 3 months after treatment initiation. Anxiety, depression, fatigue, sleep disturbance, pain, diarrhea, urinary obstruction, urinary incontinence, erectile function, and sex satisfaction were modeled jointly using LPA, and the analysis was adjusted for covariates to examine associations between patient characteristics and profiles.Results: One-third of the 373 men were not non-Hispanic white (26% were black). Four LPA profiles were identified. Men who experienced the "best HRQOL" were less likely to receive treatment, to be older, and to smoke. Men in the second best profile experienced symptoms similar to men in the best HRQOL group but reported poor sexual and urinary function, because they were more likely to receive therapy. The third profile included men with increased symptom burden and poor functioning who were likely to undergo prostatectomy and to have increased comorbidity. The "worst HRQOL" group experienced the worst symptoms and the poorest functioning, and these men were more likely to be younger, to have more comorbidities, and to smoke.Conclusions: LPA revealed that men who receive the same treatment can experience very different HRQOL impact. Understanding the factors most associated with poorer HRQOL allows clinicians to focus their care on individuals most in need of symptom management and support. Cancer 2018;124:2832-2840. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The 2012 United States Preventive Services Task Force recommendation against screening for prostate cancer has impacted rates of prostate-specific antigen (PSA) screening and appears to be associated with declining prostate cancer incidence. Our objective was to characterize health care utilization that may explain these observed trends.Methods: MarketScan claims, which capture >30 million privately insured patients in the United States, were queried for all men aged 40-64 years for the years 2008-2014. PSA testing, prostate biopsy, prostate cancer diagnosis, and definitive local treatment were determined using associated International Classification of Diseases, Ninth Revision and Current Procedural Terminology, Fourth Edition codes.Results: There were approximately 6 million qualifying men with a full year of data. PSA testing, prostate biopsy, and prostate cancer detection declined significantly between 2009 and 2014, most notably after 2011. The prostate biopsy rate per 100 patients with a PSA test decreased over the study period from 1.95 (95% confidence interval [CI], 1.92-1.97) to 1.52 (95% CI, 1.50-1.54). Prostate cancer incidence per prostate biopsy increased over the study period from 0.36 (95% CI, 0.35-0.36) to 0.39 (95% CI, 0.39-0.40). Of new prostate cancer diagnoses, the proportion managed with definitive local treatment decreased from 69% (95% CI, 69%-70%) to 54% (95% CI, 53%-55%). Both PSA testing and prostate cancer incidence decreased significantly after 2011 (P < .001).Conclusion: In a large cohort of privately insured men, PSA testing, prostate biopsy, prostate cancer incidence, and local definitive treatment for prostate cancer decreased between 2008 and 2014, most notably after 2011. This decrease may be driven by differential referral patterns from primary care providers to urologists. Cancer 2018;124:2733-2739. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Androgen-deprivation therapy (ADT) remains the cornerstone of management for patients with metastatic prostate cancer. Although the toxicities of ADT are well established, there is increasing controversy surrounding the association between cognitive dysfunction and the receipt of ADT, with some evidence suggesting an increased risk of dementia. The authors conducted a literature search to identify pertinent clinical studies in this field. This general review outlines the key findings and discusses the relative strengths and weaknesses when drawing conclusions about the risk of cognitive dysfunction or dementia with ADT use. Cancer 2018;124:1326-34. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated that prostate-specific antigen (PSA) screening significantly reduced prostate cancer mortality (rate ratio, 0.79; 95% confidence interval, 0.69-0.91). The US Prostate, Lung, Colorectal, and Ovarian (PLCO) trial indicated no such reduction but had a wide 95% CI (rate ratio for prostate cancer mortality, 1.09; 95% CI, 0.87-1.36). Standard meta-analyses are unable to account for key differences between the trials that can impact the estimated effects of screening and the trials' point estimates.Methods: The authors calibrated 2 microsimulation models to individual-level incidence and mortality data from 238,936 men participating in the ERSPC and PLCO trials. A cure parameter for the underlying efficacy of screening was estimated by the models separately for each trial. The authors changed step-by-step major known differences in trial settings, including enrollment and attendance patterns, screening intervals, PSA thresholds, biopsy receipt, control arm contamination, and primary treatment, to reflect a more ideal protocol situation and differences between the trials.Results: Using the cure parameter estimated for the ERSPC, the models projected 19% to 21% and 6% to 8%, respectively, prostate cancer mortality reductions in the ERSPC and PLCO settings. Using this cure parameter, the models projected a reduction of 37% to 43% under annual screening with 100% attendance and biopsy compliance and no contamination. The cure parameter estimated for the PLCO trial was 0.Conclusions: The observed cancer mortality reduction in screening trials appears to be highly sensitive to trial protocol and practice settings. Accounting for these differences, the efficacy of PSA screening in the PLCO setting is not necessarily inconsistent with ERSPC results. Cancer 2018;124:1197-206. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Strategies to improve bone health care in men receiving androgen deprivation therapy (ADT) are not consistently implemented. The authors conducted a phase 2 randomized controlled trial of 2 education-based models-of-care interventions to determine their feasibility and ability to improve bone health care.Methods: A single-center parallel-group randomized controlled trial of men with prostate cancer who were receiving ADT was performed. Participants were randomized 1:1:1 to 1) a patient bone health pamphlet and brief recommendations for their family physician (BHP+FP); 2) a BHP and support from a bone health care coordinator (BHP+BHCC); or 3) usual care. The primary efficacy outcome was receipt of a bone mineral density (BMD) test within 6 months. Secondary efficacy outcomes included guideline-appropriate calcium and vitamin D use and bisphosphonate prescriptions for men at high fracture risk. Feasibility endpoints included recruitment, retention, satisfaction, contamination, and outcome capture. The main analysis used logistic regression with a 1-sided P of .10. The trial is registered at ClinicalTrials.gov (identifier NCT02043236).Results: A total of 119 men were recruited. The BHP+BHCC strategy was associated with a greater percentage of men undergoing a BMD test compared with the usual-care group (78% vs 36%; P<.001). BMD ordering also was found to be increased with the BHP+FP strategy (58% vs 36%; P = .047). Both strategies were associated with higher percentages of patients using calcium and vitamin D, but only the BHP+FP arm was statistically significant (P = .039). No men were detected to be at high fracture risk. All but one feasibility endpoint was met.Conclusions: Educational strategies to improve bone health care appear feasible and are associated with improved BMD ordering in men receiving ADT. Cancer 2018;124:1132-40. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Metastatic biopsies are increasingly being performed in patients with advanced prostate cancer to search for actionable targets and/or to identify emerging resistance mechanisms. Due to a predominance of bone metastases and their sclerotic nature, obtaining sufficient tissue for clinical and genomic studies is challenging.Methods: Patients with prostate cancer bone metastases were enrolled between February 2013 and March 2017 on an institutional review board-approved protocol for prospective image-guided bone biopsy. Bone biopsies and blood clots were collected fresh. Compact bone was subjected to formalin with a decalcifying agent for diagnosis; bone marrow and blood clots were frozen in optimum cutting temperature formulation for next-generation sequencing. Frozen slides were cut from optimum cutting temperature cryomolds and evaluated for tumor histology and purity. Tissue was macrodissected for DNA and RNA extraction, and whole-exome sequencing and RNA sequencing were performed.Results: Seventy bone biopsies from 64 patients were performed. Diagnostic material confirming prostate cancer was successful in 60 of 70 cases (85.7%). The median DNA/RNA yield was 25.5 ng/μL and 16.2 ng/μL, respectively. Whole-exome sequencing was performed successfully in 49 of 60 cases (81.7%), with additional RNA sequencing performed in 20 of 60 cases (33.3%). Recurrent alterations were as expected, including those involving the AR, PTEN, TP53, BRCA2, and SPOP genes.Conclusions: This prostate cancer bone biopsy protocol ensures a valuable source for high-quality DNA and RNA for tumor sequencing and may be used to detect actionable alterations and resistance mechanisms in patients with bone metastases. Cancer 2018;124:1008-15. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Because of the recent grade C draft recommendation by the US Preventive Services Task Force (USPSTF) for prostate cancer screening between the ages of 55 and 69 years, there is a need to determine whether this could be cost-effective in a US population setting.Methods: This study used a microsimulation model of screening and active surveillance (AS), based on data from the European Randomized Study of Screening for Prostate Cancer and the Surveillance, Epidemiology, and End Results Program, for the natural history of prostate cancer and Johns Hopkins AS cohort data to inform the probabilities of referral to treatment during AS. A cohort of 10 million men, based on US life tables, was simulated. The lifetime costs and effects of screening between the ages of 55 and 69 years with different screening frequencies and AS protocols were projected, and their cost-effectiveness was determined.Results: Quadrennial screening between the ages of 55 and 69 years (55, 59, 63, and 67 years) with AS for men with low-risk cancers (ie, those with a Gleason score of 6 or lower) and yearly biopsies or triennial biopsies resulted in an incremental cost per quality-adjusted life-year (QALY) of $51,918 or $69,380, respectively. Most policies in which screening was followed by immediate treatment were dominated. In most sensitivity analyses, this study found a policy with which the cost per QALY remained below $100,000.Conclusions: Prostate-specific antigen-based prostate cancer screening in the United States between the ages of 55 and 69 years, as recommended by the USPSTF, may be cost-effective at a $100,000 threshold but only with a quadrennial screening frequency and with AS offered to all low-risk men. Cancer 2018;124:507-13. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Accountable care organizations (ACOs) can improve prostate cancer care by decreasing treatment variations (ie, avoidance of treatment in low-value settings). Herein, the authors performed a study to understand the effect of Medicare Shared Savings Program ACOs on prostate cancer care.Methods: Using a 20% Medicare sample, the authors identified men with newly diagnosed prostate cancer from 2010 through 2013. Rates of treatment, potential overtreatment (ie, treatment in men with a ≥75% chance of 10-year mortality from competing risks), and Medicare payments were measured using regression models. The impact of ACO participation was assessed using difference-in-differences analyses.Results: Before implementation of ACOs, the treatment rate was 71.8% (95% confidence interval [95% CI], 70.2%-73.3%) for ACO-aligned beneficiaries and 72.3% (95% CI, 71.7%-73.0% [P = .51]) for non-ACO-aligned beneficiaries. After implementation, this rate declined to 68.4% (95% CI, 66.1%-70.7% [P = .017]) for ACO-aligned beneficiaries and 69.3% (95% CI, 68.5%-70.1% [P<.001]) for non-ACO-aligned beneficiaries. There was no differential effect noted for ACO participation. The rate of potential overtreatment decreased from 48.2% (95% CI, 43.1%-53.3%) to 40.2% (95% CI, 32.4%-48.0% [P = .087]) for ACO-aligned beneficiaries and increased from 44.3% (95% CI, 42.1%-46.5%) to 47.0% (95% CI, 44.5%-49.5% [P = .11]) for non-ACO-aligned beneficiaries. These changes resulted in a significant relative decrease in overtreatment of 17% for ACO-aligned beneficiaries (difference-in-differences, 10.8%; P = .031). Payments were not found to be differentially affected by ACO alignment.Conclusions: The treatment of prostate cancer and annual payments decreased significantly between 2010 and 2013, but ACO participation did not appear to impact these trends. Among men least likely to benefit, Medicare Shared Savings Program ACO alignment was associated with a significant decline in prostate cancer treatment. Cancer 2018;124:563-70. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: This study assessed the use of active surveillance in men with low-risk prostate cancer and evaluated institutional factors associated with the receipt of active surveillance.Methods: A retrospective, hospital-based cohort of 115,208 men with low-risk prostate cancer diagnosed between 2010 and 2014 was used. Multivariate and mixed effects models were used to examine variation and factors associated with active surveillance.Results: During the study period, the use of active surveillance increased from 6.8% in 2010 to 19.9% in 2014 (estimated annual percentage change, +28.8%; 95% confidence interval [CI], + 19.6% to + 38.7%; P = .002). The adjusted probability of active-surveillance receipt by institution was highly variable. Compared with patients treated at comprehensive community cancer centers, patients treated at community cancer programs (odds ratio [OR], 2.00; 95% CI, 1.50-2.67; P < .001) and academic institutions (OR, 2.47; 95%, CI, 1.81-3.37; P < .001) had higher odds of receiving active surveillance. Compared with patients treated at very low-volume facilities, patients treated at very high-volume facilities had higher odds of receiving active surveillance (OR, 3.57; 95% CI, 1.94-6.55; P < .001). Patient and hospital characteristics accounted for 60.2% of the overall variation, whereas the treating institution accounted for 91.5% of the unexplained variability.Conclusions: Within this hospital-based cohort, the use of active surveillance for low-risk prostate cancer increased significantly over time. Significant variation was found in the use of active surveillance. Most of the variation was attributable to facility-related factors such as the facility type, facility volume, and institution. Policies to achieve consistent and higher rates of active surveillance, when appropriate, should be a priority of professional societies and patient advocacy groups. Cancer 2018;124:55-64. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Conservative management of aggressive prostate cancer in the elderly without definitive therapy has been associated with a 10-year prostate cancer-specific mortality of approximately 50%. The authors examined the prevalence of definitive therapy in elderly patients with intermediate-risk or high-risk disease.Methods: 411,343 patients who were diagnosed from 2004 through 2012 with intermediate-risk or high-risk prostate cancer were identified in the National Cancer Database. Multivariable logistic regression adjusting for sociodemographic characteristics and comorbidity was used to examine the association between age and receipt of definitive therapy, defined as radical prostatectomy or radiotherapy, and of primary androgen deprivation therapy (ADT) among patients who did not receive definitive therapy.Results: In total, 87.1% of high-risk patients and 91.9% of intermediate-risk patients received definitive therapy. When stratified by age, 93.7%, 92.1%, 90.8%, 87.6%, 80.9%, and 55.2% of high-risk patients and 96.1%, 94.7%, 93.4%, 89.7%, 82.7%, and 62.8% of intermediate-risk patients ages <60, 60 to 64, 65 to 69, 70 to 74, 75 to 79, and ≥80 years received definitive therapy, respectively. For both high-risk and intermediate-risk patients, increasing age was significantly associated with a decreased likelihood of receiving definitive therapy overall (both P < .001) and a greater likelihood of receiving primary ADT among those who did not receive definitive therapy (both P < .001).Conclusions: Older age was significantly associated with a decreased likelihood of receiving definitive therapy and an increased likelihood of receiving primary ADT in this national cohort of patients with intermediate-risk or high-risk prostate cancer. Notably, approximately 40% to 45% of patients aged ≥80 years did not receive definitive therapy. These findings are alarming given the dismal outcomes of conservatively managed unfavorable-risk prostate cancer. Cancer 2017;123:4832-40. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Racial disparities in prostate cancer treatment and outcomes are widespread and poorly understood. In the current study, the authors sought to determine whether access to care, measured across multiple dimensions, contributed to racial differences in prostate cancer.Methods: The Philadelphia Area Prostate Cancer Access Study (P2 Access) included 2374 men diagnosed with localized prostate cancer between 2012 and 2014. Men were surveyed to assess their experiences accessing care (response rate of 51.1%). The authors determined appointment availability at 151 urology practices using simulated patient telephone calls and calculated travel distances using geospatial techniques. Multivariable logistic regression models were used to determine the association between 5 different domains of access (availability, accessibility, accommodation, affordability, and acceptability) and receipt of treatment, perceived quality of care, and physician-patient communication.Results: There were 1907 non-Hispanic white and 394 black men in the study cohort. Overall, approximately 85% of the men received definitive treatment with no differences noted by race. Black men were less likely to report a high quality of care (69% vs 81%; P<.001) and good physician-patient communication (60% vs 71%; P<.001) compared with white men. In adjusted models, none of the 5 domains of access were found to be associated with definitive treatment overall or with radical prostatectomy. All access domains were associated with perceived quality of care and communication, although these domains did not mediate racial disparities.Conclusions: To the authors' knowledge, the current study presents the first comprehensive assessment of prostate cancer care access, treatment, and patient experience, demonstrating that although access was related to overall perceived quality of care and better physician-patient communication, it did not appear to explain observed racial differences. Cancer 2017;123:4449-57. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

The report in this issue by Pomerantz and colleagues demonstrates that men with metastatic prostate cancer harboring germline BRCA2 mutations are strongly associated with a prostate‐specific antigen response ≥50% during treatment with a platinum agent. However, more work will be required to classify other men who might benefit from platinum agents. See also pages 3532‐9. [ABSTRACT FROM AUTHOR]

BACKGROUND Breast cancer 2 ( BRCA2)-associated breast and ovarian cancers are sensitive to platinum-based chemotherapy. It is unknown whether BRCA2-associated prostate cancer responds favorably to such treatment. METHODS A retrospective analysis of a single-institution cohort of men with castration-resistant, metastatic prostate cancer was performed to determine the association between carrier status of pathogenic BRCA2 germline variants and prostate-specific antigen response to carboplatin-based chemotherapy. From 2001 through 2015, 8081 adult men with prostate cancer who had a consultation and/or underwent treatment at Dana-Farber Cancer Institute provided blood samples and consented to analyses of biologic material and clinical records. A subgroup of 141 men received at least 2 doses of carboplatin and docetaxel for castration-resistant disease (94% were also taxane refractory). These patients were categorized according to the absence or presence of pathogenic germline mutations in BRCA2 based on DNA sequencing from whole blood. The primary outcome was the response rate to carboplatin/docetaxel chemotherapy, defined according to a decline in prostate-specific antigen that exceeded 50% within 12 weeks of initiating this regimen. Associations between BRCA2 mutation status and response to carboplatin-based chemotherapy were tested using the Fisher exact test, with a 2-sided P value < .05 as the threshold for significance. RESULTS Pathogenic germline BRCA2 variants were observed in 8 of 141 men (5.7%; 95% confidence interval, 2.5%-10.9%). Six of 8 BRCA2 carriers (75%) experienced prostate-specific antigen declines >50% within 12 weeks, compared with 23 of 133 noncarriers (17%; absolute difference, 58%; 95% confidence interval, 27%-88%; P < .001). Prostate cancer cell lines functionally corroborated these clinical findings. CONCLUSIONS BRCA2-associated, castration-resistant prostate cancer is associated with a higher likelihood of response to carboplatin-based chemotherapy than non- BRCA2-associated prostate cancer. Cancer 2017;123:3532-9. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate the impact of travel distance to the treating facility on the risk of overall mortality (OM) among US patients with prostate cancer (PCa).Methods: In total, 775,999 patients who had PCa in all stages and received treatment with different strategies (radical prostatectomy, radiation therapy, observation, androgen-deprivation therapy, multimodal treatment, and chemotherapy) were drawn from the National Cancer Data Base from 2004 through 2012. Independent predictors of travel distance (intermediate [12.5-49.9 miles] and long [49.9-249.9 miles] vs short[<12.5 miles]) and its effect on OM were calculated using multivariable regression analyses. Additional analyses evaluated the distance effect on OM in selected subgroups.Results: In total, 54.5%, 33.4%, and 12.1% of patients traveled short, intermediate, and long distances, respectively. Residency in rural areas and the receipt of treatment at academic/high-volume centers independently predicted long travel distance. Non-Hispanic black men and Medicaid-insured men were less likely to travel long distances (all P < .001). Overall, traveling a long distance (hazard ratio, 0.87; 95% confidence interval, 0.83-0.92; P < .001) was associated with lower OM risk compared with traveling a short distance. This held true among non-Hispanic white men; privately insured and Medicare-insured men; those who underwent radical prostatectomy, received radiation therapy, and received multimodal strategies; and those who received treatment at academic/high-volume centers (P < .01), but not among non-Hispanic black men (P = .3). Long travel distance was associated with an increased OM in Medicaid-insured patients (P < .001).Conclusions: An OM benefit was observed among men who traveled long distances for PCa treatment, which is likely to be a reflection of centralization of care and more favorable patient-level characteristics in those travelers. Furthermore, the survival benefit mediated by long travel distances appears to be influenced by baseline socioeconomic, treatment, and facility-level factors. Cancer 2017;123:3241-52. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Several new prostate cancer treatments have emerged since 2000, including 2 radiotherapies with similar efficacy at the time of their introduction: intensity-modulated radiotherapy (IMRT) and stereotactic body radiation therapy (SBRT). The objectives of this study were to compare their early adoption patterns and identify factors associated with their use.Methods: By using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, patients who received radiation therapy during the 5 years after IMRT introduction (2001-2005) and the 5 years after SBRT introduction (2007-2011) were identified. The outcome of interest was the receipt of new radiation therapy (ie, IMRT or SBRT) compared with the existing standard radiation therapies at that time. The authors fit a series of multivariable, hierarchical logistic regression models accounting for patients nested within health service areas to examine the factors associated with the receipt of new radiation therapy.Results: During 2001 to 2005, 5680 men (21%) received IMRT compared with standard radiation (n = 21,555). Men who received IMRT were older, had higher grade tumors, and lived in more populated areas (P < .05). During 2007 through 2011, 595 men (2%) received SBRT compared with standard radiation (n = 28,255). Men who received ng SBRT were more likely to be white, had lower grade tumors, lived in more populated areas, and were more likely to live in the Northeast (P < .05). Adjusting for cohort demographic and clinical factors, the early adoption rate for IMRT was substantially higher than that for SBRT (44% vs 4%; P < .01).Conclusions: There is a stark contrast in the adoption rates of IMRT and SBRT at the time of their introduction. Further investigation of the nonclinical factors associated with this difference is warranted. Cancer 2017;123:2945-54. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiation therapy (SBRT) for localized prostate cancer involves high-dose-per-fraction radiation treatments. Its use is increasing, but concerns remain about treatment-related toxicity. The authors assessed the incidence and predictors of a global decline in health-related quality of life (HRQOL) after prostate SBRT.Methods: From 2008 to 2014, 713 consecutive men with localized prostate cancer received treatment with SBRT according to a prospective institutional protocol. Expanded Prostate Cancer Index Composite (EPIC-26) HRQOL data were collected at baseline and longitudinally for 5 years. EPIC-26 is comprised of 5 domains. The primary endpoint was defined as a decline exceeding the clinically detectable threshold in ≥4 EPIC-26 domains, termed multidomain decline.Results: The median age was 69 years, 46% of patients had unfavorable intermediate-risk or high-risk disease, and 20% received androgen-deprivation therapy. During 1 to 3 months and 6 to 60 months after SBRT, 8% to 15% and 10% to 11% of patients had multidomain declines, respectively. On multivariable analysis, lower baseline bowel HRQOL (odds ratio, 1.8; 95% confidence interval, 1.2-2.7; P < .01) and baseline depression (odds ratio, 5.7; 95% confidence interval, 1.3-24.3; P = .02) independently predicted for multidomain decline. Only 3% to 4% of patients had long-term multidomain declines exceeding twice the clinical threshold, and 30% of such declines appeared to be related to prostate cancer treatment or progression of disease.Conclusions: Prostate SBRT has minimal long-term impact on multidomain decline, and the majority of more significant multidomain declines appear to be unrelated to treatment. This emphasizes the importance of focusing not only on the side effects of prostate cancer treatment but also on other comorbid illnesses that contribute to overall HRQOL. Cancer 2017;123:1635-1642. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) outcomes are impacted by socioeconomic and biologic factors. Ethnicity plays a role in the former, but little is known about the responsiveness of metastatic PCa to androgen-deprivation therapy (ADT) among races.Methods: The Surveillance, Epidemiology, and End Results (SEER) registry was used to identify men who were diagnosed with distant, de novo, metastatic PCa from 2004 to 2012. Patterns of presentation, overall survival (OS), and PCa-specific mortality (PCSM) were determined for each race. E3805 clinical trial data also were retrospectively reviewed to assess outcomes of ADT and ADT plus docetaxel by race.Results: Of all PCa diagnoses in SEER, distant, de novo, metastatic disease was diagnosed in 4.2% of non-Hispanic whites, 5.8% of Hispanic whites, 5.7% of blacks, 5.5% of Asians/Pacific Islanders, and 8.8% of American Indians/Alaska Natives (P < .001; chi-square test). The median OS differed by race, with superior OS observed among Asian men (30 months) than among men of other races (range, 24-25 months; P < .001). Asians also had a superior median PCSM (54 months) compared with the other races (range, 35-40 months; P < .001). In E3805, chemohormonal therapy was associated with a median OS of 58.1 months (95% confidence interval, 48.8-72.9 months) and 57.6 months (95% confidence interval, 27.7-57.6 months) in non-Hispanic whites and blacks, respectively. Few Asians participated in the E3805 trial.Conclusions: Asian men have superior median OS and PCSM for distant, de novo, metastatic PCa than men of other race. Non-Hispanic whites and blacks who receive treatment with ADT or chemohormonal therapy have comparable outcomes. Cancer 2017;123:1536-1544. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to compare the overall survival of patients who undergo radical prostatectomy or radiotherapy versus noncancer controls to discern whether there is a survival advantage according to prostate cancer treatment and the impact of selection bias on these results.Methods: A matched cohort study was performed using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. In total, 34,473 patients ages 66 to 75 years were identified who were without significant comorbidity, were diagnosed with localized prostate cancer, and received treatment treated with surgery or radiotherapy between 2004 and 2011. These patients were matched to a noncancer control cohort. The rates of all-cause mortality that occurred within the study period were compared. Cox proportional hazards regression analysis was used to identify determinants associated with overall survival.Results: Of 34,473 patients who were included in the analysis, 21,740 (63%) received radiation therapy, and 12,733 (37%) underwent surgery. There was improved survival in patients who underwent surgery (hazard ratio, 0.35; 95% confidence interval, 0.32-0.38) and in those who received radiotherapy (hazard ratio, 0.72; 95% confidence interval, 0.68-0.75) compared with noncancer controls. Overall survival improved significantly in both treatment groups, with the greatest benefit observed among patients who underwent surgery (log rank P < .001).Conclusions: Population-based data indicated that patients with prostate cancer who received treatment with either surgery or radiotherapy had improved overall survival compared with a cohort of matched noncancer controls. Surgery produce longer survival compared with radiation therapy. These results suggest an inherent selection-bias because of unmeasured confounding variables. Cancer 2017;123:1617-1624. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Cancer patients are encouraged to obtain second opinions before starting treatment. Little is known about men with localized prostate cancer who seek second opinions, the reasons why, and the association with treatment and quality of care.Methods: We surveyed men who were diagnosed with localized prostate cancer in the greater Philadelphia area from 2012 to 2014. Men were asked if they obtained a second opinion from a urologist, and the reasons why. We used multivariable logistic regression models to evaluate the relationship between second opinions and definitive prostate cancer treatment and perceived quality of care.Results: A total of 2386 men responded to the survey (adjusted response rate, 51.1%). After applying exclusion criteria, the final analytic cohort included 2365 respondents. Of these, 40% obtained second opinions, most commonly because they wanted more information about their cancer (50.8%) and wanted to be seen by the best doctor (46.3%). Overall, obtaining second opinions was not associated with definitive treatment or perceived quality of cancer care. Men who sought second opinions because they were dissatisfied with their initial urologist were less likely to receive definitive treatment (odds ratio, 0.49; 95% confidence interval, 0.32-0.73), and men who wanted more information about treatment were less likely to report excellent quality of cancer care (odds ratio, 0.70; 95% confidence interval, 0.49-0.99) compared with men who did not receive a second opinion.Conclusions: Although a large proportion of men with localized prostate cancer obtained a second opinion, the reasons for doing so were not associated with treatment choice or perceived quality of cancer care. Future study is needed to determine when second opinions contribute to increasing the value of cancer care. Cancer 2017;123:1027-34. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Researchers have used prostate-specific antigen (PSA) values collected by central cancer registries to evaluate tumors for potential aggressive clinical disease. An independent study collecting PSA values suggested a high error rate (18%) related to implied decimal points. To evaluate the error rate in the Surveillance, Epidemiology, and End Results (SEER) program, a comprehensive review of PSA values recorded across all SEER registries was performed.Methods: Consolidated PSA values for eligible prostate cancer cases in SEER registries were reviewed and compared with text documentation from abstracted records. Four types of classification errors were identified: implied decimal point errors, abstraction or coding implementation errors, nonsignificant errors, and changes related to "unknown" values.Results: A total of 50,277 prostate cancer cases diagnosed in 2012 were reviewed. Approximately 94.15% of cases did not have meaningful changes (85.85% correct, 5.58% with a nonsignificant change of <1 ng/mL, and 2.80% with no clinical change). Approximately 5.70% of cases had meaningful changes (1.93% due to implied decimal point errors, 1.54% due to abstract or coding errors, and 2.23% due to errors related to unknown categories). Only 419 of the original 50,277 cases (0.83%) resulted in a change in disease stage due to a corrected PSA value.Conclusions: The implied decimal error rate was only 1.93% of all cases in the current validation study, with a meaningful error rate of 5.81%. The reasons for the lower error rate in SEER are likely due to ongoing and rigorous quality control and visual editing processes by the central registries. The SEER program currently is reviewing and correcting PSA values back to 2004 and will re-release these data in the public use research file. Cancer 2017;123:697-703. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Two large-scale prostate cancer screening trials using prostate-specific antigen (PSA) have given conflicting results in terms of the efficacy of such screening. One of those trials, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, previously reported outcomes with 13 years of follow-up. This study presents updated findings from the PLCO trial. METHODS The PLCO trial randomized subjects from 1993 to 2001 to an intervention or control arm. Intervention-arm men received annual PSA tests for 6 years and digital rectal examinations for 4 years. This study used a linkage with the National Death Index to extend mortality follow-up to a maximum of 19 years after randomization. RESULTS Men were randomized to the intervention arm (n = 38,340) or the control arm (n = 38,343). The median follow-up time was 14.8 years (25th/75th, 12.7/16.5 years) in the intervention arm and 14.7 years (25th/75th, 12.6/16.4 years) in the control arm. There were 255 deaths from prostate cancer in the intervention arm and 244 deaths from prostate cancer in the control arm; this meant a rate ratio (RR) of 1.04 (95% confidence interval [CI], 0.87-1.24). The RR for all-cause mortality was 0.977 (95% CI, 0.950-1.004). It was estimated that 86% of the men in the control arm and 99% of the men in the intervention arm received any PSA testing during the trial, and the estimated yearly screening-phase PSA testing rates were 46% and 84%, respectively. CONCLUSIONS Extended follow-up of the PLCO trial over a median of 15 years continues to indicate no reduction in prostate cancer mortality for the intervention arm versus the control arm. Because of the high rate of control-arm PSA testing, this finding can be viewed as showing no benefit of organized screening versus opportunistic screening. Cancer 2017;123:592-599. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) and visceral metastases have a worse prognosis than those with nonvisceral metastases. Treatment with the androgen receptor inhibitor enzalutamide in the phase 3 AFFIRM trial led to significant improvements in outcomes for patients with mCRPC. For the current report, the authors analyzed the efficacy of enzalutamide among patients from the AFFIRM trial who had visceral disease.Methods: Patients who had liver and/or lung metastases at baseline were selected for prespecified overall survival (OS) and exploratory post hoc analyses, including prostate-specific antigen (PSA) response and the time to PSA and radiographic progression.Results: In patients who had liver metastases (n = 92), enzalutamide was associated with a lower risk of radiographic progression (hazard ratio [HR], 0.645; 95% confidence interval [CI], 0.413-1.008), improved 12-month OS (37.7% vs 20.6%) and radiographic progression-free survival (rPFS) (11.6% vs 3.0%) rates, and higher PSA response rates (35.1% vs 4.8%) compared with placebo. Enzalutamide-treated patients who had lung metastases (n = 104) had improved median OS (HR, 0.848; 95% CI, 0.510-1.410), a substantially reduced risk of radiographic progression (HR, 0.386; 95% CI, 0.259-0.577), improved 12-month OS (65.1% vs 55.3%) and rPFS (30.9% vs 8.2%) rates, increased time to PSA progression (HR, 0.358; 95% CI, 0.204-0.627), and a better PSA response rate (52.1% vs 4.9%) compared with those who received placebo. No increase in treatment-related adverse events was observed for the visceral metastases cohort compared with the nonvisceral metastases cohort.Conclusions: Across multiple endpoints, patients who have visceral metastases have better outcomes with enzalutamide than with placebo. Cancer 2017;123:253-262. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Meeting quality of care standards in oncology is recognized as important by physicians, professional organizations, and payers. Data from a population-based cohort of patients with prostate cancer were used to examine whether receipt of care was consistent with published consensus metrics and whether receiving high-quality care was associated with less patient-reported treatment decisional regret.Methods: Patients with incident prostate cancer were enrolled in collaboration with the North Carolina Central Cancer Registry, with an oversampling of minority patients. Medical record abstraction was used to determine whether participants received high-quality care based on 5 standards: 1) discussion of all treatment options; 2) complete workup (prostate-specific antigen, Gleason grade, and clinical stage); 3) low-risk participants did not undergo a bone scan; 4) high-risk participants treated with radiotherapy (RT) received androgen deprivation therapy; and 5) participants treated with RT received conformal or intensity-modulated RT. Treatment decisional regret was assessed using a validated instrument.Results: A total of 804 participants were analyzed. Overall, 66% of African American and 73% of white participants received care that met all standards (P = .03); this racial difference was confirmed by multivariable analysis. Care that included "discussion of all treatment options" was found to be associated with less patient-reported regret on univariable analysis (P = .03) and multivariable analysis (odds ratio, 0.59; 95% confidence interval, 0.37-0.95).Conclusions: The majority of participants received high-quality care, but racial disparity existed. Participants who discussed all treatment options appeared to have less treatment decisional regret. To the authors' knowledge, this is the first study to demonstrate an association between a quality of care metric and patient-reported outcome. Cancer 2017;138-143. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Although androgen-deprivation therapy (ADT) remains the mainstay of castration-sensitive prostate cancer (CSPC) therapy, the disease's heterogeneity and the limited duration of the response have chaperoned the introduction of chemotherapy and the investigation of novel hormonal targeted agents in this setting. Combinations of ADT plus chemotherapy or novel hormonal therapies are being tested at various stages of CSPC with promising results. Furthermore, immunotherapy and experimental drugs are also being actively investigated in this setting. Intriguing multimodality strategies, chiefly deployed for early-stage disease with the aim of maximizing the efficacy and duration of the response, are being explored and may become valid therapeutic options in the future. Ultimately, striking a balance between the clinical gains of these combinations and possibly increased toxicity and reduced quality of life will be necessary. The development of precision medicine and accurate biomarkers is fundamental to progress. Cancer 2017;29-42. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: African American (AA) men are more likely than non-AA men to have a comorbid illness that could interact with androgen-deprivation therapy (ADT) and shorten survival. This study assessed the impact that race had on the risk of all-cause mortality (ACM) and other-cause mortality (OCM) among men definitively treated for favorable-risk prostate cancer (PC).Methods: Between 1997 and 2013, 7252 men with low-risk or favorable intermediate-risk PC were treated with brachytherapy with neoadjuvant ADT (n = 1501) or without neoadjuvant ADT (n = 5751) for a 4-month median duration. Cox and Fine-Gray multivariate regressions were used to analyze whether the risk of ACM and OCM increased among AA men versus non-AA men receiving ADT; adjustments were made for the age at brachytherapy, year of brachytherapy, cardiometabolic comorbidity status, risk group, and ADT treatment propensity score.Results: After a median follow-up of 8.04 years, 869 men (12.0%) died: 48 (5.52%) of PC and 821 (94.48%) of other causes. There was a significant association between AA race and an increased risk of both ACM (adjusted hazard ratio [AHR], 1.77; 95% confidence interval [CI], 1.06-2.94; P = .028) and OCM (AHR, 1.86; 95% CI, 1.08-3.19; P = .024) among AA men versus non-AA men who received ADT but not among those who did not receive ADT (AHR for ACM, 1.33; 95% CI, 0.93-1.91; P = .12; AHR for OCM, 1.39; 95% CI, 0.96-2.02; P = .08).Conclusions: ADT use may shorten survival in AA men with favorable-risk PC; therefore, its reservation for the treatment of higher risk PC, for which level 1 evidence supports its use, should be considered. Cancer 2016;122:3608-14. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most commonly diagnosed cancer, and the second leading cause of cancer-related death for men in the United States. Despite the approval of several new agents for advanced disease, each of these has prolonged survival by only a few months. Consequently, new therapies are sorely needed. For other cancer types, immunotherapy has demonstrated dramatic and durable treatment responses, causing many to hope that immunotherapies might provide an ideal treatment approach for patients with advanced prostate cancer. However, apart from sipuleucel-T, prostate cancer has been conspicuously absent from the list of malignancies for which immunotherapies have received recent approval from the US Food and Drug Administration. This has left some wondering whether immunotherapy will "work" for this disease. In this review, the authors describe current developments in immunotherapy, including approaches to engage tumor-targeting T cells, disrupt immune regulation, and alter the immunosuppressive tumor microenvironment. The authors then describe the recent application of these approaches to the treatment of prostate cancer. Given the Food and Drug Administration approval of 1 agent, and the finding that several others are in advanced stages of clinical testing, the authors believe that immunotherapies offer real hope to improve patient outcomes for men with prostate cancer, especially as investigators begin to explore rational combinations of immunotherapies and combine these therapies with other conventional therapies. Cancer 2016;122:3598-607. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Most major cancer organizations seek to reduce sociodemographic disparities in high-risk cancers partly by increasing access to theoretically high-quality, academic-oriented cancer care. The objective of this study was to determine whether academic centers have less sociodemographic treatment disparities than community centers using high-risk prostate cancer as a test case.Methods: The National Cancer Data Base was used to identify 138,019 patients who were diagnosed with nonmetastatic, high-risk prostate cancer from 2004 to 2012. Multivariable logistic analysis was used to identify independent determinants of definitive therapy. The Gray test and multivariable Cox regression were used to analyze the timing of therapy. All analyses were stratified by academic versus community cancer center.Results: Compared with white or privately insured patients, black, Hispanic, and uninsured patients with prostate cancer were less likely to receive definitive therapy at both community centers (adjusted odds ratio: 0.60 [95% confidence interval (CI), 0.56-0.64], 0.69 [95% CI, 0.61-0.78], and 0.25 [95% CI, 0.22-0.30], respectively) and academic cancer centers (adjusted odds ratio: 0.50 [95% CI, 0.46-0.54], 0.56 [95% CI, 0.50-0.64], and 0.31 [95% CI, 0.28-0.36], respectively). Among patients who received definitive therapy, black, Hispanic, and uninsured patients were more likely to experience treatment delays at both community centers (≥15, ≥ 10, and ≥19 days, respectively; all Gray P < .001) and academic centers (≥19, ≥ 11, and ≥18 days, respectively); treatment delays were observed among the aforementioned groups even after multivariable Cox regression analysis (P < .001 for all adjusted hazard ratios).Conclusions: Nationally, academic cancer centers demonstrate similarly high rates of sociodemographic disparities in cancer treatment patterns as community cancer centers. Making community centers conform to academic center standards may not necessarily reduce treatment disparities. Cancer 2016;122:3371-3377. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: There are several effective treatments for prostate cancer. To what extent a patient's functional status influences the treatment decision is unknown. This study examined the association between functional status and treatment among older men with prostate cancer.Methods: Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data were used to identify men who were 65 years old or older and were diagnosed with prostate cancer between 1998 and 2009. The primary outcome was treatment choice: conservative management, surgery, or radiation within 1 year of the diagnosis. The exposure was the functional status assessed as 4 measures within 3 domains: 1) physical function (activities of daily living [ADLs] and physical component summary score), 2) cognitive function (survey completer: self vs proxy), and 3) emotional well-being (mental component summary score). A multivariate, multinomial logistic regression was fitted with adjustments for several patient, tumor, and regional characteristics.Results: This study identified 508 conservative management patients, 195 surgery patients, and 603 radiation patients. Compared with men with no ADL dependency, those with any ADL dependency had lower odds of receiving surgery (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.38-0.99) or radiation (OR, 0.58; 95% CI, 0.43-0.78) versus conservative management. ADL dependency did not differ when surgery and radiation were compared. Patients with a proxy survey response were less likely to receive surgery or radiation versus conservative management.Conclusions: Functional status is associated with treatment choice for men with prostate cancer. Future research should examine whether this is due to physician recommendations, patient preferences, or a combination. Cancer 2016;122:3199-206. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Whether biochemical recurrence (BR) is a significant predictive factor of mortality after definitive radiation therapy for prostate cancer remains unknown. The aim of the current study was to investigate the relation between BR and overall mortality (OAM) in high-risk prostate cancer patients who were treated with carbon-ion radiotherapy (CIRT) and had long-term follow-up in 2 prospective trials.Methods: In the 2 phase 2 clinical trials, which involved 466 prostate cancer patients who received 63.0 to 66.0 Gy of CIRT (relative biological effect) in 20 fractions between 2000 and 2007, 324 patients who were deemed to be at high risk on the basis of the modified D'Amico classification criteria and received CIRT along with androgen-deprivation therapy (ADT) were examined. The OAM rate was adjusted for the ADT duration, and multivariate analyses using a Cox proportional hazards model were performed for OAM with BR as a time-dependent covariate.Results: The median follow-up period was 107.4 months, and the 5- and 10-year OAM rates after adjustments for the ADT duration were 7.0% (95% confidence interval [CI], 4.0%-9.4%) and 23.9% (95% CI, 16.4%-26.2%), respectively. A multivariate analysis revealed that the presence of BR (hazard ratio, 2.82; 95% Cl, 1.57-5.08; P = .001) was one of the predictive factors for OAM. On the other hand, the duration of ADT had no impact on OAM.Conclusions: BR after CIRT combined with ADT is an independent predictive factor for OAM in high-risk prostate cancer patients. The results of this study could be applied to other high-dose radiation therapies. Cancer 2016;122:3225-31. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. [ABSTRACT FROM AUTHOR]

Background: The role of hormone therapy (HT) with dose-escalated external-beam radiotherapy (DE-EBRT) in the treatment of intermediate-risk prostate cancer (IRPC) remains controversial. The authors report the long-term outcome of a phase 3 study of DE-EBRT with or without HT for patients with localized prostate cancer (LPC).Methods: From 1999 to 2006, 252 of an intended 338 patients with LPC were randomized to receive DE-EBRT with or without 5 months of neoadjuvant and concurrent bicalutamide 150 mg once daily. The study was closed early because of contemporary concerns surrounding bicalutamide. The primary outcome was biochemical failure (BF) incidence, and the secondary endpoints were overall survival (OS), local control (LC), and quality of life. The BF and OS rates were estimated using the cumulative incidence function and Kaplan-Meier methods and were compared using the Gray test and the log-rank test.Results: Eleven patients were excluded from analysis. Characteristics were well balanced in each treatment arm. Ninety-five percent of patients had IRPC. The prescribed dose increased from 75.6 grays (Gy) in 42 fractions to 78 Gy in 39 fractions over the period. At a median follow-up of 9.1 years, 98 BFs occurred, with no significant effect of HT versus no HT on the BF rate (40% vs 47%; P = .32), the OS rate (82% vs 86%; P = .37), the LC rate (52% vs 48 %; P = .32) or quality of life, in the patients who completed the questionnaires. Dose escalation to 75.6 Gy versus >75.6 Gy reduced the BF rate by 26% (P = .004).Conclusions: For patients who predominantly have IRPC, the addition of HT to DE-EBRT did not significantly affect BF, OS, or LC. Bicalutamide appeared to be well tolerated. The conclusions from the study are limited by incomplete recruitment. Cancer 2016;122:2595-603. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Men with favorable intermediate‐risk prostate cancer have excellent outcomes in comparison with men with unfavorable intermediate‐risk disease. In this issue of Cancer, Falchook et al report the largest study to date of men with favorable intermediate‐risk prostate cancer treated with dose‐escalated radiotherapy with or without androgen deprivation therapy. They demonstrate that overall survival is not associated with the use of androgen deprivation therapy and provide level 2 evidence to suggest the exclusion of androgen deprivation therapy in this population. See also pages 2341–9. [ABSTRACT FROM AUTHOR]

Background: Randomized trials have shown that androgen-deprivation therapy (ADT) improves survival for men with intermediate-risk prostate cancer treated with radiotherapy (RT). The benefit of ADT to patients with favorable intermediate-risk prostate cancer treated with modern dose-escalated RT is unknown. This study evaluated the effectiveness of ADT on survival of men with favorable intermediate-risk prostate cancer treated with dose-escalated RT.Methods: This study was a retrospective cohort analysis of men with favorable intermediate-risk prostate cancer from 2004 to 2007 in the National Cancer Data Base. Favorable intermediate-risk disease was defined as 1 adverse risk factor (prostate-specific antigen level of 10-20 ng/mL or Gleason score of 7) and clinical T1/T2 prostate cancer. All patients were treated with primary dose-escalated RT (≥75.6 Gy or RT with a brachytherapy boost). Overall survival was analyzed with propensity score adjustment and Cox multivariate modeling.Results: The study included 18,598 patients. The use of ADT decreased from 43.5% in 2004 to 39.5% in 2007. The propensity score-adjusted survival analysis demonstrated similar 8-year overall survival for men treated with dose-escalated RT and ADT and men treated with RT alone (77.7% vs 78.4%). ADT was not associated with improved survival in any age or comorbidity subgroup. In a sensitivity analysis using Cox multivariate modeling, the receipt of ADT was not associated with overall survival (hazard ratio, 0.99; 95% confidence interval, 0.91-1.07; P = .768).Conclusions: Adding ADT to modern dose-escalated RT was not associated with improved survival for patients with favorable intermediate-risk prostate cancer. The applicability of the survival benefit seen in older trials to modern patients is unclear. Because of the morbidity associated with ADT, dose-escalated RT alone for patients with favorable intermediate-risk prostate cancer may be a reasonable option. Cancer 2016;122:2341-2349. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiotherapy (SBRT) is a newer treatment option for patients with localized prostate cancer. The rates of diffusion of this technology across the United States are unknown. The goal of the current study was to describe the use of SBRT among patients with prostate cancer based on different risk groups (low, intermediate, or high risk) and by type of facility (community cancer program, comprehensive community cancer program, or academic program) in which patients were treated.Methods: Using the National Cancer Data Base, a national registry that contains approximately 70% of patients with cancer in the United States, the authors identified 274,466 men between the ages of 40 to 80 years who were diagnosed from 2004 to 2012 with localized prostate cancer and received radiation therapy (RT) as their initial treatment. The authors described the prevalence of SBRT use each year, and multivariable analysis was used to examine factors associated with the receipt of SBRT.Results: In 2004, SBRT use was low (<1% in all patient groups), and was observed to increase steadily each year. By 2012, 8.8% of low-risk patients treated at academic centers with RT received SBRT. Uptake of SBRT was highest in patients with low-risk or intermediate-risk disease. Multivariable analysis demonstrated that year of diagnosis, type of center, risk group, and race were all significantly associated with the use of SBRT.Conclusions: To the authors' knowledge, the current study is the first report of the adoption of SBRT for localized prostate cancer across the United States. Diffusion was noted to be slowest at community cancer programs, reflecting potential barriers of cost or expertise for this new technology. Adoption of SBRT was found to be highest among patients with low-risk or intermediate-risk disease, in accordance with the bulk of patients included in published SBRT studies. Cancer 2016;122:2234-41. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The objective of this article was to report the results from a randomized clinical trial comparing intensity-modulated radiotherapy (IMRT) with 3-dimensonal conformal radiotherapy (3DCRT) for the treatment of prostate cancer on a hypofractionated schedule.Methods: The authors randomly assigned 215 men who had localized prostate cancer to receive hypofractionated radiotherapy to a total dose of 70 grays (Gy) in 25 fractions (at 2.8 Gy per fraction) using either IMRT or 3DCRT. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity were prospectively evaluated according to modified Radiation Therapy Oncology Group criteria. Biochemical control was defined according to the Phoenix criteria (prostate-specific antigen nadir + 2 ng/mL).Results: In total, 215 patients were enrolled in the IMRT group (n = 109) or the 3DCRT group (n = 106). The 3DCRT arm had a 27% rate of grade ≥ 2 acute GU toxicity compared with a 9% rate in the IMRT arm (P = .001) and a 24% rate of grade ≥ 2 acute GI toxicity compared with a 7% rate in the IMRT arm (P = .001). The maximal rate of grade ≥2 late GU toxicity during the entire period of follow-up was 3.7% in the IMRT group versus 12.3% in the 3DCRT group (P = .02). The maximal rate of grade ≥2 late GI toxicity during the entire follow-up was 6.4% in the IMRT group versus 21.7% in the 3DCRT group (P = .001). The 5-year rate of freedom from biochemical failure was 95.4% in the IMRT arm and 94.3% in the 3DCRT arm (P = .678).Conclusions: IMRT reduced the delivery of significant radiation doses to the bladder and rectum using a similar target volume. This dosimetric advantage resulted in a lower rate of acute/late grade ≥ 2 GI and GU toxicity for IMRT compared with 3DCRT. Cancer 2016;122:2004-11. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: In the current study, the authors sought to both characterize the national trends in proton therapy use for prostate cancer and determine the factors associated with receipt of this limited resource, using what to the best of their knowledge is the largest nationwide cancer registry.Methods: The National Cancer Data Base was used to identify 187,730 patients diagnosed with nonmetastatic prostate cancer from 2004 through 2012 who received external beam radiotherapy as their initial form of definitive therapy. Multivariable logistic regression analysis adjusted for sociodemographic and clinical factors was used to identify independent determinants of proton therapy use.Results: The rate of proton therapy use increased significantly from 2.3% in 2004 to 5.2% in 2011 and 4.8% in 2012 (P value for trend <.0001). Proton therapy for prostate cancer was much more likely to be delivered at an academic compared with nonacademic center and to patients who were white, younger, healthier, from metropolitan areas, from zip codes with higher median household incomes, and who did not have an advanced stage of or high-grade disease (all P<.0001). Compared with white patients, those who were black and Hispanic were found to be significantly less likely to receive proton therapy even after robust multivariable adjustments (adjusted odds ratio, 0.20 [95% confidence interval, 0.18-0.22; P<.0001] and adjusted odds ratio, 0.57 [95% confidence interval, 0.48-0.66; P<.0001], respectively).Conclusions: The use of proton therapy to treat patients with prostate cancer more than doubled from 2004 to 2012, with striking racial disparities in its use noted despite robust multivariable adjustments. Long-term follow-up is needed to determine whether the increased use of proton therapy for prostate cancer is justified, and ongoing efforts should be made to ensure equal access to resource-limited oncologic therapies. Cancer 2016;122:1505-12. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: For certain men with low-risk prostate cancer, aggressive treatment results in marginal survival benefits while exposing them to urinary and sexual side effects. Nevertheless, expectant management has been underused. In the current study, the authors evaluated the association between various factors and expectant management use among veterans diagnosed with prostate cancer.Methods: The authors identified men diagnosed with prostate cancer in 2008. The outcome of interest was use of expectant management, based on documentation captured through an in-depth chart review. Multivariable regression models were fit to examine associations between use of expectant management and patient demographics, cancer severity, and facility characteristics. The authors assessed variation across 21 tertiary care regions and 52 facilities by generating predicted probabilities for receipt of expectant management.Results: Expectant management was more common among patients aged ≥75 years (40% vs 27% for those aged < 55 years; odds ratio, 2.57) and those with low-risk tumors (49% vs 20% for patients with high-risk tumors; odds ratio, 5.35). There was no association noted between patient comorbidity and receipt of expectant management (P = .90). There were also no associations found between facility factors and use of expectant management (all P>.05). Among ideal candidates for expectant management, receipt of expectant management varied considerably across individual facilities (0%-85%; P<.001).Conclusions: Patient age and tumor risk were found to be more strongly associated with use of expectant management than patient comorbidity. Although use of expectant management appears broadly appropriate, there was variation in expectant management noted between hospitals that was apparently not attributable to facility factors. Research determining the basis of this variation, with a focus on providers, will be critical to help optimize prostate cancer treatment for veterans. [ABSTRACT FROM AUTHOR]

Background: Given the costs of delivering care for men with prostate cancer remain poorly described, this article reports the results of time-driven activity-based costing (TDABC) for competing treatments of low-risk prostate cancer.Methods: Process maps were developed for each phase of care from the initial urologic visit through 12 years of follow-up for robotic-assisted laparoscopic prostatectomy (RALP), cryotherapy, high-dose rate (HDR) and low-dose rate (LDR) brachytherapy, intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and active surveillance (AS). The last modality incorporated both traditional transrectal ultrasound (TRUS) biopsy and multiparametric-MRI/TRUS fusion biopsy. The costs of materials, equipment, personnel, and space were calculated per unit of time and based on the relative proportion of capacity used. TDABC for each treatment was defined as the sum of its resources.Results: Substantial cost variation was observed at 5 years, with costs ranging from $7,298 for AS to $23,565 for IMRT, and they remained consistent through 12 years of follow-up. LDR brachytherapy ($8,978) was notably cheaper than HDR brachytherapy ($11,448), and SBRT ($11,665) was notably cheaper than IMRT, with the cost savings attributable to shorter procedure times and fewer visits required for treatment. Both equipment costs and an inpatient stay ($2,306) contributed to the high cost of RALP ($16,946). Cryotherapy ($11,215) was more costly than LDR brachytherapy, largely because of increased single-use equipment costs ($6,292 vs $1,921). AS reached cost equivalence with LDR brachytherapy after 7 years of follow-up.Conclusions: The use of TDABC is feasible for analyzing cancer services and provides insights into cost-reduction tactics in an era focused on emphasizing value. By detailing all steps from diagnosis and treatment through 12 years of follow-up for low-risk prostate cancer, this study has demonstrated significant cost variation between competing treatments. [ABSTRACT FROM AUTHOR]

Background: The utility of psychosocial interventions in reducing symptom burden and improving health-related quality of life (HRQOL) for men with localized prostate cancer has been demonstrated. However, studies have yet to demonstrate the efficacy of interventions in advanced prostate cancer (APC). This study examined the feasibility, acceptability, and preliminary efficacy of a technology-assisted, 10-week, group-based psychosocial intervention for diverse men with APC.Methods: The participants were 74 men (mean age, 68.84 years; non-Hispanic white, 57%; black, 40.5%) who were randomized to a cognitive-behavioral stress management (CBSM) treatment or health promotion (HP) attention-control condition. The participants were assessed at the baseline, weekly throughout the 10-week program, and 6 months after the baseline. Outcomes were assessed with the Patient-Reported Outcomes Measurement Information System along with established measures of HRQOL, CBSM intervention targets (eg, relaxation skills), and patient-reported acceptability.Results: Feasibility was demonstrated through good retention rates (>85%) and acceptable average attendance rates (>70%), and acceptability was demonstrated through very favorable weekly session evaluations (mean score, 4/5) and exit surveys (mean score, 3.6/4). Men randomized to the CBSM condition reported significant reductions (P < .05) in depressive symptoms and improvements in relaxation self-efficacy (P < .05) at the 6-month follow-up. CBSM participants reported trends for improvement in distress and functional well-being (P < .08) in comparison with those in the HP condition. Effect sizes ranged from medium (0.54) to large (1.87) and, in some instances, were clinically meaningful.Conclusions: Technology-based CBSM interventions among diverse men with APC may be feasible, acceptable, and efficacious. [ABSTRACT FROM AUTHOR]

The clinical benefits of androgen-deprivation therapy (ADT) for men with prostate cancer (PC) have been well documented and include living free from the symptoms of metastases for longer periods and improved quality of life. However, ADT comes with a host of its own serious side effects. There is considerable evidence of the adverse cardiovascular, metabolic, and musculoskeletal effects of ADT. Far less has been written about the psychological effects of ADT. This review highlights several adverse psychological effects of ADT. The authors provide evidence for the effect of ADT on men's sexual function, their partner, and their sexual relationship. Evidence of increased emotional lability and depressed mood in men who receive ADT is also presented, and the risk of depression in the patient's partner is discussed. The evidence for adverse cognitive effects with ADT is still emerging but suggests that ADT is associated with impairment in multiple cognitive domains. Finally, the available literature is reviewed on interventions to mitigate the psychological effects of ADT. Across the array of adverse effects, physical exercise appears to have the greatest potential to address the psychological effects of ADT both in men who are receiving ADT and in their partners. [ABSTRACT FROM AUTHOR]

The article focuses on challenges surrounding prostate cancer screening in the U.S. Topics discussed include effectivness of screening and treatment in reducing risk of death; analysis of European Randomized Study of Screening for Prostate Cancer for demonstrating reduction in prostate cancer specific mortality; and advantages of screening prostate-specific antigen to the same.

An introduction is presented for journal of American Cancer Society on evidence based approach to prostate-specific antigen(PSA) screening, diagnosis and treatment for prostate cancer. Topics include PSA screening among younger men with private health insurance in U.S by Kearns et al; metastatic prostate cancer diagnoses by research conducted by National Cancer Database; and use of prostate biopsy and treatment of men with prostate cancer. It also mentions of improvements in health care.

An editorial is presented on the effectiveness of prostate-specific antigen (PSA) in prostate cancer screening. It expresses views that PSA was not depicted for cancer and has used tumor marker for prostate cancer. An overview on the impact of PSA testing to digital rectal examination for prostate screening, is also emphasized.

The article reports on the changes to the screening guideline for the detection and treatment of prostate cancer issued by the U.S. Preventive Services Task Force (USPSTF). The task force has updated its screening recommendations based on its assessment of scientific evidence. The USPSTF has issued a new guideline, adjusting its recommendation from a D rating for prostate-specific antigen (PSA) screening of men for prostate cancer to a C rating for men aged 55 to 69 years.

BACKGROUND Previous publications have demonstrated conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy (RT) before the dose escalation era. The goal of the current study was to determine whether increasing BMI was associated with outcomes in men with localized CaP who were treated with dose-escalated RT. METHODS The authors identified patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity-modulated RT and image-guided RT from 2001 through 2010. BMI was analyzed as a continuous variable. Adjusting for confounders, multivariable competing risk and Cox proportional hazards regression models were used to assess the association between BMI and the risk of biochemical failure (BF), distant metastases (DM), cause-specific mortality (CSM), and overall mortality. RESULTS Of the 1442 patients identified, approximately 20% had a BMI <25 kg/m2, 48% had a BMI of 25 to 29.9 kg/m2, 23% had a BMI of 30 to 34.9 kg/m2, 6% had a BMI of 35 to 39.9 kg/m2, and 4% had a BMI of ≥40 kg/m2. The median follow-up was 47.6 months (range, 1-145 months), with a median age of 68 years (range, 36-89 years). The median dose was 78 grays (range, 76-80 grays) and 30% of patients received androgen deprivation therapy. Increasing BMI was found to be inversely associated with age ( P<.001) and pretreatment prostate-specific antigen level ( P = .018). On multivariable analysis, increasing BMI was associated with an increased risk of BF (hazard ratio [HR], 1.03; 95% confidence interval [95% CI], 1.00-1.07 [ P = .042]), DM (HR, 1.07; 95% CI, 1.02-1.11 [ P = .004]), CSM (HR, 1.15; 95% CI, 1.07-1.23 [ P<.001]), and overall mortality (HR, 1.05; 95% CI, 1.02-1.08 [ P = .004]). CONCLUSIONS For patients with CaP receiving dose-escalated intensity-modulated RT with daily image-guidance, increasing BMI appears to be associated with an increased risk of BF, DM, CSM, and overall mortality. Cancer 2015;121:3010-3017. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]