Search

Introduction: The use of expensive oral targeted agents for advanced prostate cancer can be influenced by those who stand to gain from their use. The 340B drug pricing program allows eligible hospitals to purchase medications at steep discounts, generating millions of dollars in savings. The extent to which hospitals engage in higher-risk prescribing due to program incentives is unclear., Methods: Medicare claims were used to perform a retrospective study of men with advanced prostate cancer. The primary outcome was targeted therapy use in men with high noncancer mortality risk. Secondary outcomes included androgen biosynthesis inhibitor use in men with cardiovascular history, androgen receptor inhibitor use in men with neurocognitive history, and therapy within 14 days of death. Proportional hazards models were used to assess time-to-event outcomes, while logistic regression was used for binary outcomes., Results: In men with high noncancer mortality risk, targeted therapy use did not differ at 340B participating compared to nonparticipating hospitals (hazard ratio [HR] 1.1, 95% CI 0.67-1.5). There was no difference in androgen biosynthesis inhibitor use in men with a prior cardiac event (HR 0.96, 95% CI 0.70-1.3) or androgen receptor inhibitor use in men with a prior neurocognitive event (HR 1.5, 95% CI 0.65-3.4) in those treated at 340B participating compared to nonparticipating hospitals. Therapy use in the last 14 days of life did not vary by 340B participation (odds ratio 1.3, 95% CI 0.86-1.9)., Conclusions: In men with advanced prostate cancer, high-risk prescribing and futility measures did not vary by participation in the 340B drug pricing program.

Background: The use of androgen biosynthesis and second-generation androgen receptor inhibitors for advanced prostate cancer is increasing. Because these therapies alter the androgen pathway, they have been associated with cardiometabolic and neurocognitive toxicities. Although their safety profiles have been assessed in clinical trials, real-world data are limited., Methods: A 20% sample of national Medicare claims was used to perform a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer treated with androgen biosynthesis (ie, abiraterone) and second-generation androgen receptor inhibitors between 2012 and 2019. Outcomes were assessed after the first fill of either class of drug for the 12-month period after starting therapy. The primary outcome was a hospital admission or emergency department visit for a cardiometabolic event. Secondary outcomes included neurocognitive events and fractures. Multivariable regression was used to assess the association between the class of drug and occurrence of an adverse event., Results: There were 3488 (60%) men started on an androgen biosynthesis inhibitor and 2361 (40%) started on an androgen receptor inhibitor for the first time. Cardiometabolic adverse events were more common in men managed with androgen biosynthesis inhibitor (9.2% vs 7.5%, P = .027). No difference between androgen biosynthesis and androgen receptor inhibitors was observed for neurocognitive events (3.3% vs 3.4%, respectively; P = .71) or fractures (4.2% vs 3.6%, respectively; P = .26)., Conclusions: Men with advanced prostate cancer initiating an androgen biosynthesis inhibitor for the first time more commonly had cardiometabolic events than those started on androgen receptor inhibitors. Neurocognitive events and fractures did not differ by drug class., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: There is increasing awareness that patients with prostate cancer frequently harbor germline variants that may carry important implications for them and their family members. Given the variable clinical guidelines, there remains a need to better understand which patients with prostate cancer are likely to harbor pathogenic or likely pathogenic (P/LP) germline variants. We sought to understand factors associated with P/LP germline variants in patients with metastatic or localized prostate cancer qualifying for National Comprehensive Cancer Network genetic testing criteria., Materials and Methods: Patients diagnosed with prostate cancer were offered genetic testing in accordance with National Comprehensive Cancer Network guidelines. Patient-level factors, including demographic, clinical, and pathologic data, were tracked in a prospectively collected registry. The association of the presence of a P/LP variant in germline testing results with patient-level factors was assessed using univariate and multivariate logistic regression. Variables were tested for overall significance with chi-squared tests., Results: Five hundred five patients underwent germline testing and had clinical data available. Rates of P/LP germline variants were 7.6% (20/264) in patients with metastatic disease and 11.2% (27/241) in patients with localized disease. The most prevalent P/LP variants were CHEK2 (34%), BRCA2 (22%), ATM (10%), and HOXB13 (10%)., Conclusions: In this cohort of patients undergoing guideline-informed germline testing, P/LP germline variants were found in similar proportions across all age ranges and clinical characteristics. Only age at genetic testing for patients with metastatic disease was demonstrated to be predictive of the presence of a P/LP germline variant, highlighting the challenges associated with refining current clinical testing guidelines.

Cancer treatment has become increasingly expensive, partially due to the use of specialty drugs. The costs of these drugs are often passed down to patients, who may face the consequences of paying for more than they can afford, leading to financial toxicity. The 340B drug pricing program is a health care policy that may provide an opportunity to mitigate the financial consequences of cancer care. The 340B program requires manufacturers to sell outpatient drugs at a discount to hospitals caring for a significant number of socioeconomically disadvantaged individuals. The program intended for hospitals to use savings from discounted purchases to expand their safety net to vulnerable patients. Some studies have shown that participating hospitals do this by offering more charity and discounted care, whereas others have demonstrated that hospitals fail to sufficiently expand their safety net. A potential flaw of the program is the lack of guidance from governing bodies on how hospitals should use savings from discounted purchases. There has been growing discussion among stakeholders to reform the 340B program given the mixed findings of its effectiveness. With the rising costs of specialty drugs and associated prevalence of financial toxicity in patients with cancer, there is an opportunity to address these issues through reform that improves the program. Directing hospitals to offer specific safety net opportunities, such as passing along discounted drug prices to vulnerable populations, could help the growing number of patients who are financially burdened by medications at the core of the 340B program., (© 2024 American Cancer Society.)

Purpose: CDK12 inactivation in metastatic castration-resistant prostate cancer (mCRPC) may predict immunotherapy responses. This phase 2 trial evaluated the efficacy of immune checkpoint inhibitor (ICI) therapy in patients with CDK12-altered mCRPC., Patients and Methods: Eligible patients had mCRPC with deleterious CDK12 alterations and any prior therapies except ICI. Cohort A received ipilimumab (1 mg/kg) with nivolumab (3 mg/kg) every 3 weeks for up to four cycles, followed by nivolumab 480 mg every 4 weeks. Cohort C received nivolumab alone 480 mg every 4 weeks. Patients with CDK12-altered nonprostate tumors were enrolled in cohort B and not reported. The primary endpoint was a 50% reduction in PSA (PSA50). Key secondary endpoints included PSA progression-free survival, overall survival, objective response rate, and safety., Results: PSA was evaluable in 23 patients in cohort A and 14 in cohort C. Median lines of prior therapy were two in cohorts A and C, including any prior novel hormonal agent (74% and 79%) and chemotherapy (57% and 36%). The PSA50 rate was 9% [95% confidence interval (CI), 1%-28%] in cohort A with two responders; neither had microsatellite instability or a tumor mutational burden >10 mutations/megabase. No PSA50 responses occurred in cohort C. Median PSA progression-free survival was 7.0 months (95% CI, 3.6-11.4) in cohort A and 4.5 months (95% CI, 3.4-13.8) in cohort C. Median overall survival was 9.0 months (95% CI, 6.2-12.3) in cohort A and 13.8 months (95% CI, 3.6-not reached) in cohort C., Conclusions: There was minimal activity with ICI therapy in patients with CDK12-altered mCRPC., (©2024 American Association for Cancer Research.)

Background: Patients with lymph node positive (pN+) disease found at the time of radical prostatectomy with pelvic lymphadenectomy for clinically localized prostate cancer (CaP) are at high risk of disease persistence and progression. Contemporary management trends of pN+ CaP are not well described., Materials and Methods: Patients in the Michigan Urologic Surgery Improvement Collaborative (MUSIC) with clinically localized prostate cancer who underwent radical prostatectomy between 2012 and 2023 with cN0/pN+ disease were identified. The primary outcome was to evaluate patient and practice-level factors associated with time to secondary post-RP treatment. Secondary outcomes included practice-level variation in management of pN+ CaP and rates of secondary treatment modality. To assess factors associated with secondary treatment, a Cox proportional hazards model of a 60-day landmark analysis was performed., Results: We identified 666 patients with pN+ disease. Overall, 66% underwent secondary treatment within 12 months post-RP. About 19% of patients with detectable post-RP PSA did not receive treatment. Of patients receiving secondary treatment after 60-days post-RP, 34% received androgen deprivation therapy (ADT) alone, 27% received radiation (RT) alone, 36% received combination, and 4% received other systemic therapies. In the multivariable model, pathologic grade group (GG)3 (HR 1.5; 95%CI: 1.05-2.14), GG4-5 (HR 1.65; 95%CI: 1.16-2.34), positive margins (HR 1.46; 95%CI: 1.13-1.88), and detectable postoperative PSA ≥0.1 ng/ml (HR 3.46; 95%CI: 2.61-4.59) were significantly associated with secondary post-RP treatment. There was wide variation in adjusted practice-level 12-month secondary treatment utilization (28%-79%)., Conclusions: The majority pN+ patients receive treatment within 12 months post-RP which was associated with high-risk pathological features and post-RP PSA. Variation in management of pN+ disease highlights the uncertainty regarding the optimal management. Understanding which patients will benefit from secondary treatment, and which type, will be critical to minimize variation in care., Competing Interests: Declaration of competing interest Robert E. Dess – Jansen (Advisory Board). Todd Morgan – Tempus (Advisory Board), Myriad Genetics (Research Funding), Stratify Genomics (Advisory Board)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Expensive oral specialty drugs for advanced prostate cancer can be associated with treatment disparities. The 340B program allows hospitals to purchase medications at discounts, generating savings that can improve care of the socioeconomically disadvantaged. This study assessed the effect of hospital 340B participation on advanced prostate cancer., Methods: The authors performed a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer from 2012 to 2019. The primary outcome was use of an oral specialty drug. Secondary outcomes included monthly out-of-pocket costs and treatment adherence. We evaluated the effects of 1) hospital 340B participation, 2) a regional measure vulnerability, the social vulnerability index (SVI), and 3) the interaction between hospital 340B participation and SVI on outcomes., Results: There were 2237 and 1100 men who received care at 340B and non-340B hospitals. There was no difference in specialty drug use between 340B and non-340B hospitals, whereas specialty drug use decreased with increased SVI (odds ratio, 0.95, p = .038). However, the interaction between hospital 340B participation and SVI on specialty drug use was not significant. Neither 340B participation, SVI, or their interaction were associated with out-of-pocket costs. Although hospital 340B participation and SVI were not associated with treatment adherence, their interaction was significant (p = .020). This demonstrated that 340B was associated with better adherence among socially vulnerable men., Conclusions: The 340B program was not associated with specialty drug use in men with advanced prostate cancer. However, among those who were started on therapy, 340B was associated with increased treatment adherence in more socially vulnerable men., (© 2024 American Cancer Society.)

Introduction: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with prognoses varying from months to years at time of castration-resistant diagnosis. Optimal first-line therapy for those with different prognoses is unknown., Methods: We conducted a retrospective cohort study of men in a national healthcare delivery system receiving first-line therapy for mCRPC (abiraterone, enzalutamide, docetaxel, or ketoconazole) from 2010 to 2017, with follow-up through 2019. Using commonly drawn prognostic labs at start of mCRPC therapy (hemoglobin, albumin, and alkaline phosphatase), we categorized men into favorable, intermediate, or poor prognostic groups depending on whether they had none, one to two, or all three laboratory values worse than designated laboratory cutoffs. We used Kaplan-Meier methods to examine prostate specific antigen (PSA) progression-free and overall survival (OS) according to prognostic group and first-line therapy, and multivariable cox regression to determine variables associated with survival outcomes., Results: Among 4135 patients, median PSA progression-free survival (PFS) was 6.9 months (95% confidence interval [CI] 6.6-7.3), and median OS 18.8 months (95% CI 18.0-19.6), ranging from 5.7 months (95% CI 4.8-7.0) in the poor prognosis group to 31.3 months (95% CI 29.7-32.9) in the favorable group. OS was similar regardless of initial treatment received for favorable and intermediate groups, but worse for those in the poor prognostic group who received ketoconazole (adjusted hazard ratio 2.07, 95% CI 1.2-3.6). PSA PFS was worse for those who received ketoconazole compared to abiraterone across all prognostic groups (favorable HR 1.76, 95% CI 1.34-2.31; intermediate HR 1.78, 95% CI 1.41-2.25; poor HR 8.01, 95% CI 2.93-21.9)., Conclusion: Commonly drawn labs at mCRPC treatment start may aid in predicting survival and response to therapies, potentially informing discussions with care teams. First-line treatment selection impacts disease progression for all men with mCRPC regardless of prognostic group, but impacted OS only for men with poor prognosis at treatment start., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Urologists practicing in single-specialty groups with ownership in radiation vaults are more likely to treat men with prostate cancer. The effect of divestment of vault ownership on treatment patterns is unclear., Methods: A 20% sample of national Medicare claims was used to perform a retrospective cohort study of men with prostate cancer diagnosed between 2010 and 2019. Urology practices were categorized by radiation vault ownership as nonowners, continuous owners, and divested owners. The primary outcome was use of local treatment, and the secondary outcome was use of intensity-modulated radiation therapy (IMRT). A difference-in-differences framework was used to measure the effect of divestment on outcomes compared to continuous owners. Subgroup analyses assessed outcomes by noncancer mortality risk (high [>50%] vs. low [≤50%])., Results: Among 72 urology practices that owned radiation vaults, six divested during the study. Divestment led to a decrease in treatment compared with those managed at continuously owning practices (difference-in-differences estimate, -13%; p = .03). The use of IMRT decreased, but this was not statistically significant (difference-in-differences estimate, -10%; p = .13). In men with a high noncancer mortality risk, treatment (difference-in-differences estimate, -28%; p < .001) and use of IMRT (difference-in-differences estimate, -27%; p < .001) decreased after divestment., Conclusions: Urology group divestment from radiation vault ownership led to a decrease in prostate cancer treatment. This decrease was most pronounced in men who had a high noncancer mortality risk. This has important implications for health care reform by suggesting that payment programs that encourage constraints on utilization, when appropriate, may be effective in reducing overtreatment., (© 2023 American Cancer Society.)

Background: Deciding whether to treat or conservatively manage patients with prostate cancer is challenging. Recent changes in guidelines, advances in treatment technologies, and policy can influence decision making surrounding management, particularly for those for whom the decision to treat is discretionary. Contemporary trends in management of newly diagnosed prostate cancer are unclear., Methods: Using national Medicare data, men with newly diagnosed prostate cancer were identified between 2014 and 2019. Patients were classified by 5- and 10-year noncancer mortality risk. Multinomial logistic regression models were fit to assess adjusted trends in management over time. The primary outcome was management of prostate cancer: local treatment (inclusive of surgery, radiation, brachytherapy, or cryotherapy), hormone therapy, or observation., Results: Local treatment was the most common form of management and stable across years (68%). Use of observation increased (21%-23%, P < .001) and use of hormone therapy decreased (11%-8%, P < 0.001). After stratifying by 10-year non-cancer mortality risk, observation increased among men with low (22.3%-26.1%, P < .001) and moderate (19.9%-23.5%, P < .001) mortality risk. Conversely, use of treatment increased among those with high (62.8%-68.0%, P = .004) and very high (45.5%-54.1%, P < .001) risk of noncancer mortality. These trends were similar across groups when stratified by 5-year noncancer mortality risk., Conclusion: Nationally, use of local treatment remains common and was stable throughout the study period. However, while local treatment declined among men with a lower risk of noncancer mortality, it increased among men with a higher risk of non-cancer mortality., Competing Interests: Disclosures The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To examine survival and disease control outcomes, including metastasis-related survival outcomes, in a large contemporary cohort of patients undergoing radical prostatectomy for localized prostate cancer., Methods: We conducted a retrospective study of men with localized prostate cancer treated with radical prostatectomy from 2005 to 2015 with follow-up through 2019 in the Veterans Health Administration. We defined biochemical recurrence (BCR) as a prostate-specific antigen ≥0.2 ng/mL. We used a validated natural language processing encoded dataset to identify incident metastatic prostate cancer. We estimated overall survival from time of surgery, time of BCR, and time of first metastasis using the Kaplan-Meier method. We then estimated time from surgery to BCR, BCR to metastatic disease, and prostate-cancer-specific survival from various time points using cumulative incidence considering competing risk of death., Results: Of 21,992 men undergoing radical prostatectomy, we identified 5951 (27%) who developed BCR. Of men with BCR, 677 (11%) developed metastases. We estimated the 10-year cumulative incidence of BCR and metastases after BCR were 28% and 20%, respectively. Median overall survival after BCR was 14years, with 10-year survival of 70%. From the time of metastasis, median overall survival approached 7years, with 10-year overall survival of 34%. Prostate cancer-specific survival for the entire cohort at 10years was 94%., Conclusion: In this large contemporary national cohort, survival for men with biochemically recurrent prostate cancer is longer than historical cohorts. When counseling patients and designing clinical studies, these updated estimates may serve as more reliable reflections of current outcomes., Competing Interests: Declaration of Competing Interest Stensland: Reports grant funding from F32 CA 264874. Caram: No conflict. Herr: No conflict. Burns: Reports grant funding from NIH NCI R01 CA242559. Sparks: Reports grant funding from NIH NCI R01 CA242559. Elliott: No conflict. Shin: No conflict. Morgan: No conflict. Zaslavsky: No conflict. Hollenbeck: Reports institutional grant funding from NCI, ARHQ, ACS and National Institute of Aging, reports Associate Editor role at Urology. Tsodikov: Reports R01 grant funding from NCI. Skolarus: Reports grant funding from NIH NCI R01 CA242559., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To examine the effect of urologist participation in value-based payment models on the initial management of men with newly diagnosed prostate cancer., Methods: Medicare beneficiaries with prostate cancer diagnosed between 2017 and 2019, with 1 year of follow-up, were assigned to their primary urologist, each of whom was then aligned to a value-based payment model (the merit-based incentive payment system [MIPS], accountable care organization [ACO] without financial risk, and ACO with risk). Multivariable mixed-effects logistic regression was used to measure the association between payment model participation and treatment of prostate cancer. Additional models estimated the effects of payment model participation on use of treatment in men with very high risk (i.e., >75%) of non-cancer mortality within 10 years of diagnosis (i.e., a group of men for whom treatment is generally not recommended) and price-standardized prostate cancer spending in the 12 months after diagnosis., Results: Treatment did not vary by payment model, both overall (MIPS-67% [95% CI 66%-68%], ACOs without risk-66% [95% CI 66%-68%], ACOs with risk-66% [95% CI 64%-68%]). Similarly, treatment did not vary among men with very high risk of non-cancer mortality by payment model (MIPS-52% [95% CI 50%-55%], ACOs without risk-52% [95% CI 50%-55%], ACOs with risk-51% [95% CI 45%-56%]). Adjusted spending was similar across payment models (MIPS-$16,501 [95% CI $16,222-$16,780], ACOs without risk-$16,140 [95% CI $15,852-$16,429], ACOs with risk-$16,117 [95% CI $15,585-$16,649])., Conclusions: How urologists participate in value-based payment models is not associated with treatment, potential overtreatment, and prostate cancer spending in men with newly diagnosed disease., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Despite guidelines recommending bone-modifying agents (BMAs) to decrease skeletal-related events (SREs) in men with metastatic castration-resistant prostate cancer (mCRPC), BMAs are underutilized. In this retrospective cohort study, we report the factors associated with BMA use in a national health care delivery system., Methods: We used the Veterans Affairs Corporate Data Warehouse to identify men with mCRPC between 2010 and 2017. BMA prescribing frequency was evaluated, and the association between patient- and disease-specific factors with BMA use was assessed using multivariable logistic regression., Results: Among 3,980 men identified with mCRPC (mean age 73.5 years, 29% Black), 47% received a BMA; median time to BMA from start of mCRPC treatment was 102 days. Factors associated with BMA use included previous BMA use (adjusted odds ratio [aOR], 7.81 [95% CI, 6.48 to 9.47]), diagnosis code for bone metastases (aOR, 1.26 [95% CI, 1.08 to 1.46]), and concomitant corticosteroid use (aOR, 1.53 [95% CI, 1.29 to 1.82]). Decreased BMA use was associated with advancing age (aOR, 0.85 per 10 years [95% CI, 0.78 to 0.92]), Charlson comorbidity index ≥2 (aOR, 0.76 [95% CI, 0.63 to 0.93]), Black race (aOR, 0.83 [95% CI, 0.70 to 0.98]), and decreased estimated glomerular filtration rate (eGFR; aOR, 0.19 [95% CI, 0.11 to 0.32] for eGFR 0-29 mL/minutes; aOR, 0.76 [95% CI, 0.64 to 0.91] for 30-59 mL/minutes)., Conclusion: Patients who are older, Black, or have more comorbidities are less likely to receive guideline concordant care to prevent SREs. These observations highlight the unique challenges of caring for patients with mCRPC and the need for future studies to increase BMA use in these populations.

Introduction: We performed a study to evaluate the association between urologist performance in the Merit-Based Incentive Payment System (MIPS), and quality and spending for prostate cancer care., Methods: Medicare beneficiaries with prostate cancer diagnosed between 2017 and 2019 were assigned to their primary urologist. Associated MIPS scores were identified and categorized based on thresholds for payment adjustment as low (worst), moderate, and high (best). Multivariable mixed effects models were used to measure the association between MIPS performance and adherence to quality measures and price standardized spending for prostate cancer., Results: Adherence to quality measures did not vary across MIPS performance groups for pretreatment counselling by both a urologist and radiation oncologist (low-76%, [95% CI 73%-80%], moderate-77% [95% CI 74%-79%], and high-75% [95% CI 74%-76%]) and avoiding treatment in men with a high risk of noncancer mortality within 10 years of diagnosis (low-40% [95% CI 35%-45%], moderate-39% [95% CI 36%-43%], high-38% [95% CI 36%-39%]). Men on active surveillance managed by high performers more likely received a confirmatory test (44% [95% CI 43%-46%]) compared to those managed by moderate (38% [95% CI 33%-42%]) performers, but not low performers (36% [95% CI 29%-44%]). There was no difference in adjusted spending across MIPS performance groups., Conclusions: Better performance in MIPS is associated with a higher rate of confirmatory testing in men initiating active surveillance for prostate cancer. However, performance was not associated with other dimensions of quality nor spending.

Introduction: Some worry that physician practices acquired by private equity may increase the use of services to maximize revenue. We assessed the effects of private equity acquisition on spending, use of treatment, and diagnostic testing in men with prostate cancer., Methods: We used a 20% sample of national Medicare claims to perform a retrospective cohort study of men with prostate cancer diagnosed from 2014 through 2019. The primary outcome was prostate cancer spending in the first 12 months after diagnosis. Secondary outcomes included the use of treatment and a composite measure of diagnostic testing (e.g., imaging, genomics) in the first 12 months after diagnosis. Multilevel modeling was used to adjust for differences in patient and market characteristics. The effect of practice acquisition on each outcome was assessed using a difference-in-differences design., Results: There were 409 and 4021 men with prostate cancer managed by urologists in acquired and nonacquired practices, respectively. After acquisition, prostate cancer spending was comparable between acquired and nonacquired practices (difference-in-differences estimate $1182, p = 0.36). Acquisition did not affect the use of treatment (difference-in-differences estimate 3.7%, p = 0.30) or the use of diagnostic testing in men who were treated (difference-in-differences -5.5%, p = 0.12) and those managed conservatively (difference-in-differences -2.0%, p = 0.82)., Conclusions: In the year following acquisition of urology practices, private equity did not increase prostate cancer spending, the use of treatment or diagnostic testing in men with prostate cancer. Future work should evaluate the effects of private equity acquisition on practice patterns and quality over a longer time horizon., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Private equity is increasingly engaged in the acquisition of urology practices. The implications of strategies to enhance practice value deployed by these firms for patients are unclear., Methods: We conducted a retrospective study of urologist performance in the MIPS (Merit-based Incentive Payment System) program for 2017 to 2020 using national Medicare data from the Quality Payment Program file. The primary outcome was the overall MIPS score. Secondary outcomes included MIPS component scores (ie, quality, interoperability, improvement activities, cost) and the percentage of urologists receiving a bonus payment. Generalized estimating equations were used to estimate the relationship between private equity acquisition and outcomes using a difference-in-differences framework., Results: Between 2017 and 2020, 181 urologists were in a urology practice acquired by private equity with MIPS data available the year before and after acquisition. Compared to urologists in practices not acquired by private equity, those in acquired practices had worse overall MIPS performance after acquisition (difference-in-differences estimate, -14 points, P = .04). The decrease in the overall score was driven by worse performance in the quality score (difference-in-differences estimate, -28 points, P < .001). Finally, acquisition resulted in a decrease in the percentage of urologists receiving bonus payments (difference-in-differences estimate, -43%, P < .001)., Conclusions: Private equity acquisition of urology practices was associated with significantly lower MIPS performance. As private equity acquisition of urology practices becomes more prevalent, key stakeholders should ensure that the quality of patient care is maintained and that the involvement of for-profit entities in health care is being made transparent to patients.

Purpose: Accurate information regarding real-world outcomes after contemporary radiation therapy for localized prostate cancer is important for shared decision-making. Clinically relevant end points at 10 years among men treated within a national health care delivery system were examined., Methods: National administrative, cancer registry, and electronic health record data were used for patients undergoing definitive radiation therapy with or without concurrent androgen deprivation therapy within the Veterans Health Administration from 2005 to 2015. National Death Index data were used through 2019 for overall and prostate cancer-specific survival and identified date of incident metastatic prostate cancer using a validated natural language processing algorithm. Metastasis-free, prostate cancer-specific, and overall survival using Kaplan-Meier methods were estimated., Results: Among 41,735 men treated with definitive radiation therapy, the median age at diagnosis was 65 years and median follow-up was 8.7 years. Most had intermediate (42%) and high-risk (33%) disease, with 40% receiving androgen deprivation therapy as part of initial therapy. Unadjusted 10-year metastasis-free survival was 96%, 92%, and 80% for low-, intermediate-, and high-risk disease. Similarly, unadjusted 10-year prostate cancer-specific survival was 98%, 97%, and 90% for low-, intermediate-, and high-risk disease. The unadjusted overall survival was lower across increasing disease risk categories at 77%, 71%, and 62% for low-, intermediate-, and high-risk disease (p < .001)., Conclusions: These data provide population-based 10-year benchmarks for clinically relevant end points, including metastasis-free survival, among patients with localized prostate cancer undergoing radiation therapy using contemporary techniques. The survival rates for high-risk disease in particular suggest that outcomes have recently improved., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Competing Interests: Declaration of Competing Interest The author has no competing interests to disclose, financial or otherwise.

Competing Interests: Declaration of Competing Interest The authors have no competing interests or conflicts of interest to disclose.

Background: Despite clinical guidelines advocating for use of conservative management in specific clinical scenarios for men with prostate cancer, there continues to be tremendous variation in its uptake. This variation may be amplified among men with competing health risks, for whom treatment decisions are not straightforward. The degree to which characteristics of the health care delivery system explain this variation remains unclear., Methods: Using national Medicare data, men with newly diagnosed prostate cancer between 2014 and 2019 were identified. Hierarchical logistic regression models were used to assess the association between use of treatment and health care delivery system determinants operating at the practice level, which included measures of financial incentives (i.e., radiation vault ownership), practice organization (i.e., single specialty vs. multispecialty groups), and the health care market (i.e., competition). Variance was partitioned to estimate the relative influence of patient and practice characteristics on the variation in use of treatment within strata of noncancer mortality risk groups., Results: Among 62,507 men with newly diagnosed prostate cancer, the largest variation in the use of treatment between practices was observed for men with high and very high-risk of noncancer mortality (range of practice-level rates of treatment for high: 57%-71% and very high: 41%-61%). Addition of health care delivery system determinants measured at the practice level explained 13% and 15% of the variation in use of treatment among men with low and intermediate risk of noncancer mortality in 10 years, respectively. Conversely, these characteristics explained a larger share of the variation in use of treatment among men with high and very high-risk of noncancer mortality (26% and 40%, respectively)., Conclusions: Variation among urology practices in use of treatment was highest for men with high and very high-risk noncancer mortality. Practice characteristics explained a large share of this variation., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Abiraterone and enzalutamide are castration-resistant prostate cancer (CRPC) therapies with potentially distinct associations with mental health symptoms given their differing antiandrogen targets., Methods: We used national Veterans Health Administration data to identify patients with CRPC who received first-line abiraterone or enzalutamide from 2010 to 2017. Using Poisson regression, we compared outpatient mental health encounters per 100 patient-months on drug between the abiraterone and enzalutamide cohorts adjusting for patient factors (e.g., age). We compared mental health encounters in the year before versus after starting therapy using the McNemar test., Results: We identified 2902 CRPC patients who received abiraterone (n = 1992) or enzalutamide (n = 910). We found no difference in outpatient mental health encounters between the two groups (adjusted incident rate ratio [aIRR] 1.04, 95% confidence interval [CI] 0.95-1.15). However, men with preexisting mental health diagnoses received 81.3% of the outpatient mental health encounters and had higher rates of these encounters with enzalutamide (aIRR 1.21, 95% CI 1.09-1.34). Among patients with ≥1 year of enrollment before and after starting abiraterone (n = 1139) or enzalutamide (n = 446), there was no difference in mental health care utilization before versus after starting treatment (17.0% of patients vs. 17.6%, p = 0.60, abiraterone; 16.4% vs. 18.4%, p = 0.26, enzalutamide)., Conclusion: We found no overall differences in mental health care utilization between CRPC patients who received first-line abiraterone versus enzalutamide. However, men with preexisting mental health diagnoses received the majority of mental health care and had more mental health visits with enzalutamide., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Management of men with advanced prostate cancer has evolved to include urologists, made possible by oral targeted agents (eg, abiraterone or enzalutamide) that can be dispensed directly to patients in the office. We sought to investigate whether this increasingly common model improves access to these agents, especially for Black men who are historically undertreated., Methods: We used 20% national Medicare data to perform a retrospective cohort study of men with advanced prostate cancer from 2011 through 2019, managed by urology practices with and without in-office dispensing. Using a difference-in-difference framework, generalized estimating equations were used to measure the effect of in-office dispensing on prescriptions for abiraterone and/or enzalutamide, adjusting for differences between patients, including race., Results: New prescription fills for oral targeted agents increased after the adoption of in-office dispensing (+4.4%, 95% confidence interval [CI] = 3.4% to 5.4%) relative to that for men managed by practices without dispensing (+2.4%, 95% CI = 1.4% to 3.4%). The increase in the postintervention period (difference-in-difference estimate) was 2% higher (95% CI = 0.6% to 3.4%) for men managed by practices adopting dispensing relative to men managed by practices without dispensing. The effect was strongest for practices adopting dispensing in 2015 (difference-in-difference estimate: +4.2%, 95% CI = 2.3% to 6.2%). The effect of dispensing adoption did not differ by race., Conclusion: Adoption of in-office dispensing by urology practices increased prescription fills for oral targeted agents in men with advanced prostate cancer. This model of delivery may improve access to this important class of medications., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: To examine the effect of urology practice market competition on use of treatment in men with newly diagnosed prostate cancer., Methods: We performed a retrospective national cohort study of 48,067 Medicare beneficiaries with newly diagnosed prostate cancer between 2014 and 2018. The primary exposure was urology practice-level market competition. Markets were established by the flow of patients to a practice using a variable radius approach. Practice level competition was measured annually using the Herfindahl-Hirschman Index. The primary outcome was use of treatment for prostate cancer (ie, surgery, radiation, or cryotherapy) stratified by 10-year risk of noncancer mortality., Results: Between 2014 and 2018, there was a decrease in the total percent of urologists practicing in small single-specialty groups (49%-41%) with an increase in multispecialty practices (38%-47%). After adjusting for demographic and clinical characteristics, a lower percentage of men underwent treatment in practices with low competition relative to those managed in practices with high competition (70% vs 67.0%, P < .001). Among men with the highest risk of noncancer mortality, those managed in practices in the least competitive markets were less likely to receive treatment relative to men managed by practices in the most competitive markets (48% vs 60%, P-value<.001)., Conclusion: Reduction in competition between urology practices is not associated with greater use of treatment in men with newly diagnosed prostate cancer, particularly in those with a high risk of noncancer mortality., Competing Interests: DECLARATION OF COMPETING INTEREST None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: We examine changes in the volume of patients with advanced prostate cancer and prescriptions for abiraterone and enzalutamide among urology practices with and without in-office dispensing., Methods: Using data from the National Council for Prescription Drug Programs, we identified in-office dispensing by single-specialty urology practices from 2011 to 2018. As the greatest growth in implementing dispensing occurred among large groups in 2015, outcomes were measured at the practice level in 2014 (before) and 2016 (after) for dispensing and non-dispensing practices. Outcomes included the volume of men with advanced prostate cancer managed by a practice and prescriptions for abiraterone and/or enzalutamide. Using national Medicare data, generalized linear mixed models were fit to compare the practice-level ratio of each outcome (2016 relative to 2014) adjusting for regional contextual factors., Results: In-office dispensing increased from 1% to 30% of single-specialty urology practices from 2011 to 2018, with 28 practices implementing dispensing in 2015. In 2016 compared to 2014, adjusted changes in the volume of patients with advanced prostate cancer managed by a practice were similar between non-dispensing (0.88, 95% CI 0.81-0.94) and dispensing (0.93, 95% CI 0.76-1.09) practices ( P = .60). Prescriptions for abiraterone and/or enzalutamide increased in both non-dispensing (2.00, 95% CI 1.58-2.41) and dispensing (8.99, 95% CI 4.51-13.47) practices ( P < .01)., Conclusions: In-office dispensing is increasingly common in urology practices. This emerging model is not associated with changes in patient volume but is associated with increased prescriptions for abiraterone and enzalutamide.

Background: Over the past decade, abiraterone and enzalutamide have largely replaced ketoconazole as oral treatments for castration-resistant prostate cancer (CRPC). We investigated the differential adoption of abiraterone and enzalutamide across facilities in a national healthcare system to understand the impact a facility has on the receipt of these novel therapies., Methods: Using data from the VA Corporate Data Warehouse, we identified a cohort of men with CRPC who received the most common first-line therapies: abiraterone, enzalutamide, docetaxel, or ketoconazole between 2010 and 2017. We described variability in the adoption of abiraterone and enzalutamide across facilities by time period (2010-2013 or 2014-2017). We categorized facilities depending on the timing of adoption of abiraterone and enzalutamide relative to other facilities and described facility characteristics associated with early and late adoption., Results: We identified 4998 men treated with ketoconazole, docetaxel, abiraterone, or enzalutamide as first-line CRPC therapy between 2010 and 2017 at 125 national facilities. When limiting the cohort to oral therapies, most patients treated earlier in the study period (2010-2013) received ketoconazole. A dramatic shift was seen by the second half of the study period (2014-2017) with most men treated with first-line abiraterone (61%). Despite this shift and a new standard of care, some facilities persisted in the widespread use of ketoconazole in the later period, so-called late adopting facilities. After multivariable adjustment, patients who received treatment at a late adopting facility were more likely receiving care at a lower complexity, rural facility, with less urology and hematology/oncology workforce (all p < 0.01)., Conclusion: Many facilities persisted in their use of ketoconazole as first-line CRPC therapy, even when other facilities had adopted the new standard of care abiraterone and enzalutamide. Further work is needed to identify the effect of this late adoption on outcomes important to patients., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To assess the effects of adding advanced practice providers to surgical practices on surgical complications, readmissions, mortality, episode spending, length of stay, and access to care., Summary Background Data: There has been substantial growth in the number of nurse practitioners and physician assistants (ie, advanced practice providers) in the United States. The extent to which advanced practice providers have been integrated into surgical practice, and their impact on surgical outcomes and access is unclear., Methods: Using a 20% sample of national Medicare claims, we performed a retrospective cohort study of fee-for-service beneficiaries undergoing one of 4 major procedures (coronary artery bypass graft, colectomy, major joint replacement, and cystectomy) between 2010 and 2016. We limited our study population for each procedure to patients treated by single-specialty surgical groups to ensure that the advanced practice providers have direct interactions with its surgeons and patients. All outcomes were measured at the practice level for the year before and the year after the addition of the first advanced practice provider. Outcomes included: complications, readmission, mortality, episode payments, length of stay. Models were adjusted for age, race, sex, comorbidity, socioeconomic class and procedure type. Secondary outcome: practice-level office visits by surgical group type., Results: The number of advanced practice providers increased by 13%, from 6713 to 7596 between 2010 and 2016. The largest relative increases occurred in general (46.9%) and urologic (27.6%) surgical practices. The year after an advanced practice provider was added to a surgical practice, the odds of complications were 17% and 16% lower at 30- and 90-days postprocedure, respectively. Additionally, 90-day readmissions were 18% less likely and length of stay was 0.33 days shorter (a 7.1% reduction). Average 30-day and90-day episode spending was $1294.73 and $1427.76 lower, respectively ( P < 0.001). General surgical, orthopedic, and urology practices realized increases of 49.0 (95% CI 13.5-84.5), 112.0 (95% CI 83.0-140.5), and 205.0 (95% CI 117.5-292.0) in-office visits per surgeon, respectively., Conclusions: The addition of advanced practice providers to single-specialty surgical groups is associated with improvements in surgical outcomes and access. Future work should clarify the mechanisms by which advanced practice providers within surgical practices contribute to health outcomes to identify best practices for deployment., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Immune checkpoint inhibitor therapy and nab-paclitaxel have each shown efficacy in platinum-refractory advanced urothelial cancer. We conducted a single-arm phase 2 trial of the combination of nab-paclitaxel and pembrolizumab in platinum-refractory or cisplatin-ineligible advanced urothelial cancer (NCT03240016)., Materials and Methods: Eligible patients had RECIST 1.1 measurable and cisplatin-ineligible or platinum-refractory advanced urothelial cancer. Patients received nab-paclitaxel at starting dose of 125 mg/m 2 intravenously on days 1 and 8 and pembrolizumab 200 mg intravenously on day 1 in 21-day cycles until progression, intolerable toxicity, or death. Nab-paclitaxel was permitted to be discontinued after 6 cycles. The nab-paclitaxel starting dose was reduced to 100 mg/m 2 after planned interim analysis. Primary end point was overall response rate by RECIST 1.1. Secondary end points included safety/toxicity, duration of response, progression-free survival), and overall survival., Results: Between February 2018 and April 2021, 36 response-evaluable patients were enrolled. There was an equal split of platinum-refractory and cisplatin-ineligible patients. Confirmed overall response rate was 50.0% (18/36) including 3 complete and 15 partial responses; 31/36 patients experienced some tumor shrinkage. At a median follow-up of 19.7 months, median duration of response was 4.4 months (95% CI: 4.0-8.6), median progression-free survival 6.8 months (95% CI: 4.4-not reached), and median overall survival 18.2 months (95% CI: 10.6-not reached). Grade ≥3 adverse events occurred in 21/36 patients including fatigue (n=6) and anemia (n=4). Ten patients had immune-mediated adverse events., Conclusions: The combination of nab-paclitaxel and pembrolizumab exhibited promising activity in advanced urothelial cancer and warrants further study in this population. After reduction in nab-paclitaxel starting dose, no unanticipated or unexpected toxicities emerged.

Purpose: Indications for germline testing in prostate cancer patients have expanded substantially over the past decade. With a near-universal shortage of genetic counselors and increasing demand, increased access to genetic counseling is crucial. We sought to prospectively implement and assess a clinician-led approach to genetic counseling and testing., Materials and Methods: Patients with metastatic or localized prostate cancer meeting National Comprehensive Cancer Network® criteria for consideration of genetic testing were offered pre-test genetic counseling by their urologist or medical oncologist as part of their routine clinical care and concurrently approached for enrollment in the Germline Genetics in Prostate Cancer Study. Consented patients filled out a post-counseling survey using validated instruments to assess the quality of counseling. For patients who elected to undergo genetic testing, an additional validated questionnaire was completed following disclosure of results. The primary outcome was the proportion of patients undergoing testing, with a target >60% of patients. The secondary outcome was overall satisfaction with counseling, with a target >85% of patients., Results: A total of 275 patients enrolled, and 203 patients elected to undergo genetic testing. Post-counseling surveys were obtained from 265 patients, and post-genetic testing surveys were obtained from 132 patients. Patient satisfaction was high, with 98% of patients reporting being satisfied with the overall quality of pre-test counseling, and 74% of patients elected to undergo genetic testing., Conclusions: These results support the effectiveness of clinician-led genetic counseling in prostate cancer. With clinician training, this approach can be utilized to expand access to appropriate germline genetic testing.

Objective: To determine the implications of the merit-based incentive payment system (MIPS) for urology practices. MIPS is a Medicare payment model that determines whether a physician is financially penalized or receives bonus payment based on performance in four categories: quality, practice improvement, promotion of interoperability, and spending., Methods: We performed a cross-sectional analysis of urologist performance in MIPS for 2017 and 2019 using Medicare data. Urologist practice organization was categorized as single-specialty (small, medium, large) or multispecialty groups. MIPS scores were estimated by practice organization. Logistic regression models were used to examine the association between urology practice characteristics, including proportion of dual eligible beneficiaries, and bonus payment adjustment as defined by Medicare methodology. Rates of consolidation (movement from smaller to larger practices) between 2017 and 2019 were compared between those who were and those who were not penalized in 2017., Results: Urologists in small practices performed worse in MIPS and had a significantly lower adjusted odds ratio of receiving bonus payments in both 2017 and 2019 compared to larger group practices (odds ratio [OR] 0.04, 95% confidence interval [95%CI] 0.03-0.05 in 2017 and OR 0.37, 95%CI 0.30-0.47 in 2019). Increasing percent of dual eligible beneficiaries within a patient panel was associated with decreased odds of receiving bonus payment in both performance years. Urologists penalized in 2017 had higher rates of consolidation by 2019 compared to those who were not (14% vs 5%, P <.05)., Conclusion: Small urology practices and those caring for a higher proportion of dual eligible beneficiaries tended to perform worse in MIPS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Abiraterone and enzalutamide are the most common oral agents for the treatment of men with advanced prostate cancer. To understand their safety profiles in real-world settings, we examined the association between the use of abiraterone or enzalutamide and the risk of metabolic or cardiovascular adverse events while on treatment., Methods: Men with advanced prostate cancer and their use of abiraterone or enzalutamide were identified in a 20% sample of the 2010-2017 national Medicare claims. The primary composite outcome was the occurrence of a major metabolic or cardiovascular adverse event, defined as an emergency room visit or hospitalization associated with a primary diagnosis of diabetes, hypertension, or cardiovascular disease. The secondary composite outcome was the occurrence of a minor metabolic or cardiovascular adverse event, defined as an outpatient visit associated with a primary diagnosis of the aforementioned conditions. Risks were assessed separately for abiraterone and enzalutamide using Cox regression. All statistical tests were 2-sided., Results: Compared with men not receiving abiraterone, men receiving abiraterone were at increased risk of both a major composite adverse event (hazard ratio [HR] = 1.77, 95% confidence interval [CI] = 1.53 to 2.05; P < .001) and a minor composite adverse event (HR = 1.24, 95% CI = 1.05 to 1.47; P = .01). Compared with men not receiving enzalutamide, men receiving enzalutamide were at an increased risk of a major composite adverse event (HR = 1.22, 95% CI = 1.01 to 1.48; P = .04) but not a minor composite adverse event (HR = 1.04, 95% CI = 0.83 to 1.30; P = .75)., Conclusion: Careful monitoring and management of men on abiraterone or enzalutamide through team-based approaches are critical., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The Timing Of Androgen Deprivation (TOAD) trial found an overall survival benefit for immediate vs delayed androgen deprivation therapy (ADT) for prostate-specific antigen (PSA)-relapsed or noncurable prostate cancer. However, broad eligibility criteria allowed entry of a heterogeneous participant group, including those with prior ADT exposure, raising concerns about subsequent androgen sensitivity. For these reasons, we completed previously specified subgroup analyses to assess if prior ADT was associated with ADT timing efficacy after PSA relapse., Methods: We examined TOAD trial patient-level data for participants with PSA relapse after local therapy. We performed Kaplan-Meier analyses for overall survival stratified by prior ADT and randomized treatment arm (immediate or delayed ADT). We compared group characteristics using Mann-Whitney U and Fisher exact tests. All hypothesis tests were 2-sided., Results: We identified 261 patients with PSA relapse, 125 of whom received prior ADT. Patients with prior ADT had higher PSA at presentation (12.1 vs 9.0 ng/mL; P < .001), more cT3 disease (38.4% vs 25.0%; P = .007), and more likely received radiotherapy as local treatment (80.0% vs 47.8%; P < .001) but were otherwise similar to patients without prior ADT exposure. Within this prior ADT group, those who received immediate ADT (n = 56) had improved overall survival compared with those who received delayed ADT (n = 69; P = .02). This benefit was not observed in the group with no prior ADT (P = .98)., Conclusions: The survival benefit demonstrated in the TOAD trial may be driven by patients who received ADT prior to trial entry. We provide possible explanations for this finding with implications for treatment of PSA-relapsed prostate cancer and future study planning., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Androgen deprivation therapy (ADT) use is associated with an increased risk of developing depression and anxiety. Little is known about how the mental health of these men is treated., Materials and Methods: We identified men with prostate cancer who received ADT between 2001 and 2015 using Optum's de-identified Clinformatics Data Mart Database. We determined the incidence of depression or anxiety diagnoses, mental health treatments, and the specialty of providers initiating psychotropic medications, after the start of ADT. Outcomes were compared with those of men with prostate cancer not receiving ADT and men without prostate cancer., Results: Of 37 388 men with prostate cancer treated with ADT, 3964 (10.6%) received a new diagnosis of depression or anxiety. Of those 3964 men, 1892 (47.7%) did not receive a documented treatment, 10 (0.3%) received psychotherapy, 1321 (33.3%) a selective serotonin reuptake inhibitor, and 744 (18.8%) a benzodiazepine. The median time from initiation of ADT to a depression or anxiety diagnosis was 9.3 months. Primary care physicians were the most common prescribers of psychotropic medications (72.2%). The proportion of men not receiving mental health treatments of interest (47.7%) was similar compared to men without prostate cancer (49.1%), but statistically significantly lower compared to men with prostate cancer not receiving ADT (52.7%)., Conclusions: In men with prostate cancer receiving ADT with a new diagnosis of depression or anxiety, nearly half are not receiving mental health care while one in five is introduced to a benzodiazepine. Further investigation toward improving the mental health care for men on ADT is needed., (Published by Oxford University Press 2022.)

Urologists are increasingly prescribing oral targeted therapies to patients with advanced prostate cancer. Concurrent with this trend, urology practices are allowing patients to fill their prescription onsite or through a pharmacy established by the practice. We examined prescription patterns for abiraterone or enzalutamide between eventually dispensing single-specialty urology practices, nondispensing single-specialty urology practices, and multispecialty practices using a 20% random sample of the 2013-2017 national Medicare claims. We determined physician dispensing through manual search of publicly available information. From 2015 through 2017, higher percentages of patients managed by eventually dispensing single-specialty urology practices had a filled prescription of abiraterone or enzalutamide compared with patients managed in nondispensing single-specialty urology practices (eg, in 2017, 8.9%, 95% confidence interval = 7.3% to 10.9%, vs 5.9%, 95% confidence interval = 5.0% to 7.0%, respectively; 2-sided P < .001). Insofar as physician dispensing is associated with higher use of abiraterone or enzalutamide, it may represent a means to improve treatment access., (© The Author(s) 2022. Published by Oxford University Press.)

Objective: To understand the influence of drug manufacturers on the prescribing patterns of medical oncologists and urologists, we examined the relationship between promotional payments from the manufacturers of abiraterone and enzalutamide and prescriptions for either drug by medical oncologists and urologists., Methods: Promotional payments for abiraterone or enzalutamide made to medical oncologists and urologists between January 2014 and December 2017 reported through the Open Payments Program were categorized as $0, $1$999, and $1000 or more. Prescriptions filled between January 2013 and December 2017 were identified in the Medicare Part D File. Associations between promotional payments and prescribing were assessed using generalized linear models., Results: From 2013 through 2017, the number of medical oncologists and urologists prescribing abiraterone or enzalutamide increased by 38% - 298%, respectively. The odds of prescribing among medical oncologists receiving $1--$999 and those receiving $1,000 or more were 1.69 (95%CI:1.59--1.79) and 2.61 (95% CI: 2.14--3.18) times that of medical oncologists receiving no payments. Among urologists receiving $1--$999 and those receiving $1,000 or more, the odds of prescribing were 4.04 (95%CI: 3.59--4.54) and 13.57 (95%CI: 9.69--19.0) times that of urologists receiving no payments., Conclusion: Increasing promotional payments were associated with prescribing among medical oncologists and urologists, with a stronger relationship evident for urologists. Prescribing patterns for abiraterone and enzalutamide, particularly among urologists, may be influenced by payments from drug manufacturers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Abiraterone and enzalutamide are commonly used oral cancer therapies for patients with prostate cancer, both with potentially high out-of-pocket costs for patients. We investigated the prevalence of financial assistance mechanisms used to alleviate out-of-pocket costs and the association of these mechanisms with timing of treatment initiation of abiraterone or enzalutamide., Methods: Using data from the medical center's specialty pharmacy, we identified first prescriptions for abiraterone or enzalutamide between January 1, 2017, and March 31, 2019. Prescriptions dispensed at an external pharmacy or that were discontinued for reasons unrelated to cost were excluded. Patient demographics, insurance coverage, out-of-pocket cost, and number of days between prescribed date and pill-to-mouth date were collected., Results: Among 220 prescriptions in our final cohort, 185 were filled through our internal specialty pharmacy, 23 through a manufacturer-sponsored patient assistance program (PAP), and 12 were never filled because of cost. One third of the prescriptions in our final cohort (n = 66) were filled with financial assistance: PAP (10%), copay cards (9%), and grants (11%). The median amount of assistance received for the first fill was $2,860 US dollars (USD) (interquartile range $1,856-$10,717 USD). Prescriptions with an out-of-pocket cost < $100 USD were filled in the shortest time (median 5 days), whereas those filled through a PAP had the longest time to initiation (median 30.5 days)., Conclusion: Among patients prescribed oral therapies for prostate cancer at a single institution, one third of patients received financial assistance. Although receiving assistance is likely to improve financial toxicity, waiting for assistance may lead to longer time to initiation of medication., Competing Interests: Andrea R. RomanConsulting or Advisory Role: AbbVie/Genentech, Karyopharm TherapeuticsNo other potential conflicts of interest were reported.

Context: Opioid prescribing to cancer patients is declining, but it is unknown whether reductions have been tailored to those at highest risk of opioid-related harms., Objectives: Examine whether declines in opioid dispensing to patients receiving active cancer treatment are sharper in patients with substance use disorder (SUD) or mental health diagnoses., Methods: We used 2008-2018 national, commercial healthcare claims data to examine adjusted and unadjusted trends in opioid dispensing (receipt of ≥1 fill; average daily dosage; receipt of high-dose opioids; receipt of concurrent opioids and benzodiazepines) to patients ages ≥18 receiving treatment for one of four cancer types (breast; colorectal; head and neck; sarcoma; N = 324,789 patients). To compare declines across subgroups with varying risk of opioid-related harms, we stratified by SUD and mental health diagnosis. To address potential confounding, we estimated subgroup-specific trends using generalized estimating equations, adjusting for covariates., Results: Across groups, rate of ≥1 opioid fill per quarter fell 32.5% (95% CI: 31.8%-33.2%) from 2008 to 2018; daily dose among those receiving opioids fell 37.6% (95% CI: 36.7%-38.6%). In most cases, these declines were not sharper in subgroups at greater risk of opioid-related harms. For example, patients with opioid use disorder experienced the smallest declines in dispensing frequency, and there was no evidence that declines were sharper in patients with mental health diagnoses., Conclusion: Sharp declines in opioid prescribing during the drug overdose crisis have affected a wide range of patients undergoing cancer treatment and may not have been sufficiently tailored to patient characteristics. Research on implications for opioid-related harms and pain management is needed., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. All rights reserved.)

Background . While advanced practice providers (APPs) are increasingly integrated into care delivery models, little is known about their impact in surgical settings. Given that many patients undergo surgery in multispecialty group practice settings, we examined the impact of APP integration into such practices on outcomes after major surgery. Methods . We used a 20% sample of national Medicare claims to identify 190 101 patients who underwent 1 of 4 major surgeries (coronary artery bypass graft [CABG], colectomy, major joint replacement, and cystectomy) at multispecialty group practices from 2010 through 2016. The level of APP integration was measured as the ratio of APPs to physicians within each practice. Rates of mortality, major complications, and readmission within 30 days of discharge after the index surgery were compared between patients treated in practices with low, medium, and high levels of APP integration using multivariable regression analysis. Results . Relative to patients treated in practices with low APP integration, those treated in practices with medium or high APP integration had significantly lower rates of mortality (2.4% [low integration] vs 1.9% [medium integration] vs 2.0% [high integration]; P < .01), major complications (34.1% [low] vs 31.2% [medium] vs 30.2% [high]; P < .01), and readmission (11.7% [low] vs 10.6% [medium] vs 10.1% [high]; P < .01). This relationship was consistent for virtually all outcomes when considering each surgery type individually. Conclusions . Integration of APPs into multispecialty group practices was associated with improved postoperative outcomes after major surgery. Future research should identify the mechanisms by which APPs improve outcomes to inform optimal utilization.

The substantial biological heterogeneity of metastatic prostate cancer has hindered the development of personalized therapeutic approaches. Therefore, it is difficult to predict the course of metastatic hormone-sensitive prostate cancer (mHSPC), with some men remaining on first-line androgen deprivation therapy (ADT) for several years while others progress more rapidly. Improving our ability to risk-stratify patients would allow for the optimization of systemic therapies and support the development of stratified prospective clinical trials focused on patients likely to have the greatest potential benefit. Here, we applied a liquid biopsy approach to identify clinically relevant, blood-based prognostic biomarkers in patients with mHSPC. Gene expression indicating the presence of CTCs was greater in CHAARTED high-volume (HV) patients (52% CTC high ) than in low-volume (LV) patients (23% CTC high ; * p = 0.03). HV disease ( p = 0.005, q = 0.033) and CTC presence at baseline prior to treatment initiation ( p = 0.008, q = 0.033) were found to be independently associated with the risk of nonresponse at 7 months. The pooled gene expression from CTCs of pre-ADT samples found AR, DSG2, KLK3, MDK, and PCA3 as genes predictive of nonresponse. These observations support the utility of liquid biomarker approaches to identify patients with poor initial response. This approach could facilitate more precise treatment intensification in the highest risk patients.

Purpose: To assess how active surveillance for prostate cancer is apportioned across specialties and how testing patterns and transition to treatment vary by specialty., Methods: We used a 20% national sample of Medicare claims to identify men diagnosed with prostate cancer from 2010 through 2016 initiating surveillance (N = 13,048). Patients were assigned to the physician responsible for the bulk of surveillance care based on billing patterns. Freedom from treatment was assessed by specialty of the responsible physician (urology, radiation oncology, medical oncology, and primary care). Multinomial logistic regression models were used to examine associations between specialty and treatment patterns., Results: Urologists were responsible for surveillance in 93.7% of patients in 2010 and 96.2% of patients in 2016 ( P for trend = .01). Testing patterns varied by specialty. For example, patients of medical oncologists had more frequent prostate-specific antigen testing compared with patients of urologists (1.85 v 2.39 tests per year, respectively; P < .01). Three years after diagnosis, a significantly smaller proportion of patients managed by radiation oncologists (64.3%) remained on surveillance compared with patients managed by other physicians (75.8%-79.5%; P < .01). Although radiation was the most common treatment among all men who transitioned to treatment, a disproportionate percentage of patients followed by radiation oncologists (28.9%) ultimately underwent radiation compared with patients followed by other physicians (15.1%-15.4%; P < .01)., Conclusion: Nontrivial percentages of patients on active surveillance are managed by physicians outside of urology. Given the interspecialty variations observed, efforts to strengthen the evidence underlying surveillance pathways and to engage other specialties in guideline development are needed., Competing Interests: Ted A. SkolarusPatents, Royalties, Other Intellectual Property: UpToDate royalties for prostate cancer survivorship chapter Brent K. HollenbeckPatents, Royalties, Other Intellectual Property: Receive royalties for IP related to the development of the Bladder Cancer Index, which measures quality of life in patients with bladder cancerOther Relationship: ElsevierNo other potential conflicts of interest were reported.

Introduction: Consensus is lacking about whether or how to treat men with prostate cancer, making it susceptible to nonclinical factors. The extent to which financial incentives afforded through differences in commercial prices for prostatectomy are associated with use of treatment, and prostatectomy in particular, is unknown., Methods: MarketScan® data were used to identify 38,863 privately insured men aged 64 years or younger diagnosed with prostate cancer between 2010 and 2016. Commercial prices for prostatectomy, defined by professional payments to urologists, were aggregated to the market level. Multivariable logistic regression was used to measure the association of commercial prices for prostatectomy and the use of treatment., Results: The adjusted use of treatment decreased from 87.1% for men diagnosed in 2010 to 71.1% for those diagnosed in 2016 (p <0.01 for trend). Among the treated, prostatectomy was the most common modality every year (eg 71.1% for those diagnosed in 2016). For every $1,000 increase in commercial prices, the adjusted odds of undergoing treatment decreased by 7% (OR 0.93, 95% CI 0.89-0.97, p <0.01). Among the treated, commercial prices were not significantly associated with use of prostatectomy (OR 0.99 for every $1,000 increase, 95% CI 0.89-1.10, p=0.85)., Conclusions: Higher commercial prices for prostatectomy were associated with decreased use of treatment. The use of prostatectomy was not associated with its commercial prices.

Objective: To characterize national trends in urologist workforce, practice organization, and management of incident prostate cancer., Methods: Using Medicare claims data from 2010 to 2016, we identified all urologists billing Medicare and the practice with which they were affiliated. We characterized groups as solo, small single specialty, large single specialty, multispecialty, specialist, or hospital-owned practices. Using a 20% sample of national Medicare claims, we identified all patients with incident prostate cancer and identified their primary treatment., Results: The number of urologists increased from 9,305 in 2010 to 9,570 in 2016 (P = .03), while the number of practices decreased from 3,588 to 2,861 (P < .001). The proportion of urologists in multispecialty groups increased from 17.1% in 2010 to 28.2% in 2016, while those within solo practices declined from 26.2% to only 15.8% over the same time period. A higher proportion of patients at hospital-owned practices were treated with observation (P < .001) and surgery (P < .001), while a higher proportion of patients at large single specialty practices were treated with radiation therapy (P < .001)., Conclusion: We characterized shifts in urologist membership from smaller, independent groups to larger, multispecialty or hospital-owned practices. This trend coincides with higher utilization of observation and surgical treatment for prostate cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Treatments for metastatic castration-resistant prostate cancer (CRPC) differ in toxicity, administration, and evidence. In this study, clinical and nonclinical factors associated with the first-line treatment for CRPC in a national delivery system were evaluated., Methods: National electronic laboratory and clinical data from the Veterans Health Administration were used to identify patients with CRPC (ie, rising prostate-specific antigen [PSA] on androgen deprivation) who received abiraterone, enzalutamide, docetaxel, or ketoconazole from 2010 through 2017. It was determined whether clinical (eg, PSA) and nonclinical factors (eg, race, facility) were associated with the first-line treatment selection using multilevel, multinomial logistic regression. The average marginal effects (AMEs) were calculated of patient, disease, and facility characteristics on ketoconazole versus more appropriate CRPC therapy., Results: There were 4998 patients identified with CRPC who received first-line ketoconazole, docetaxel, abiraterone, or enzalutamide. After adjustment, increasing age was associated with receipt of abiraterone (adjusted odds ratio [aOR], 1.07; 95% credible interval [CrI], 1.06-1.09) or enzalutamide (aOR, 1.10; 95% CrI, 1.08-1.11) versus docetaxel. Greater preexisting comorbidity was associated with enzalutamide versus abiraterone (aOR, 1.53; 95% CrI, 1.23-1.91). Patients with higher PSA values at the start of treatment were more likely to receive docetaxel than oral agents and less likely to receive ketoconazole than other oral agents. African American men were more likely to receive ketoconazole than abiraterone, enzalutamide, or docetaxel (AME, 2.8%; 95% CI, 0.7%-4.9%). This effect was attenuated when adjusting for facility characteristics (AME, 1.9%; 95% CI, -0.4% to 4.1%)., Conclusions: Clinical factors had an expected effect on the first-line treatment selection. Race may be associated with the receipt of a guideline-discordant first-line treatment., (© 2021 American Cancer Society.)

Medical insurance claims are becoming increasingly common data sources to answer a variety of questions in biomedical research. Although comprehensive in terms of longitudinal characterization of disease development and progression for a potentially large number of patients, population-based inference using these datasets require thoughtful modifications to sample selection and analytic strategies relative to other types of studies. Along with complex selection bias and missing data issues, claims-based studies are purely observational, which limits effective understanding and characterization of the treatment differences between groups being compared. All these issues contribute to a crisis in reproducibility and replication of comparative findings using medical claims. This paper offers practical guidance to the analytical process, demonstrates methods for estimating causal treatment effects with propensity score methods for several types of outcomes common to such studies, such as binary, count, time to event and longitudinally-varying measures, and also aims to increase transparency and reproducibility of reporting of results from these investigations. We provide an online version of the paper with readily implementable code for the entire analysis pipeline to serve as a guided tutorial for practitioners. The online version can be accessed at https://rydaro.github.io/. The analytic pipeline is illustrated using a sub-cohort of patients with advanced prostate cancer from the large Clinformatics TM Data Mart Database (OptumInsight, Eden Prairie, Minnesota), consisting of 73 million distinct private payer insurees from 2001-2016., Competing Interests: Conflicts of Interest: The authors have no competing interests and nothing to disclose.

Importance: Use of next-generation sequencing (NGS) to identify clinically actionable genomic targets has been incorporated into routine clinical practice in the management of advanced solid tumors; however, the clinical utility of this testing remains uncertain., Objective: To determine which patients derived the greatest degree of clinical benefit from NGS profiling., Design, Setting, and Participants: Patients in this cohort study underwent fresh tumor biopsy and blood sample collection for genomic profiling of paired tumor and normal DNA (whole-exome or targeted-exome capture with analysis of 1700 genes) and tumor transcriptome (RNA) sequencing. Somatic and germline genomic alterations were annotated and classified according to degree of clinical actionability. Results were returned to treating oncologists. Data were collected from May 1, 2011, to February 28, 2018, and analyzed from May 1, 2011, to April 30, 2020., Main Outcomes and Measures: Patients' subsequent therapy and treatment response were extracted from the medical record to determine clinical benefit rate from NGS-directed therapy at 6 months and exceptional responses lasting 12 months or longer., Results: During the study period, NGS was attempted on tumors from 1138 patients and was successful in 1015 (89.2%) (MET1000 cohort) (538 men [53.0%]; mean [SD] age, 57.7 [13.3] years). Potentially clinically actionable genomic alterations were discovered in 817 patients (80.5%). Of these, 132 patients (16.2%) received sequencing-directed therapy, and 49 had clinical benefit (37.1%). Exceptional responses were observed in 26 patients (19.7% of treated patients). Pathogenic germline variants (PGVs) were identified in 160 patients (15.8% of cohort), including 49 PGVs (4.8% of cohort) with therapeutic relevance. For 55 patients with carcinoma of unknown primary origin, NGS identified the primary site in 28 (50.9%), and sequencing-directed therapy in 13 patients resulted in clinical benefit in 7 instances (53.8%), including 5 exceptional responses., Conclusions and Relevance: The high rate of therapeutically relevant PGVs identified across diverse cancer types supports a recommendation for directed germline testing in all patients with advanced cancer. The high frequency of therapeutically relevant somatic and germline findings in patients with carcinoma of unknown primary origin and other rare cancers supports the use of comprehensive NGS profiling as a component of standard of care for these disease entities.

We consider comparative effectiveness research (CER) from observational data with two or more treatments. In observational studies, the estimation of causal effects is prone to bias due to confounders related to both treatment and outcome. Methods based on propensity scores are routinely used to correct for such confounding biases. A large fraction of propensity score methods in the current literature consider the case of either two treatments or continuous outcome. There has been extensive literature with multiple treatment and binary outcome, but interest often lies in the intersection, for which the literature is still evolving. The contribution of this article is to focus on this intersection and compare across methods, some of which are fairly recent. We describe propensity-based methods when more than two treatments are being compared, and the outcome is binary. We assess the relative performance of these methods through a set of simulation studies. The methods are applied to assess the effect of four common therapies for castration-resistant advanced-stage prostate cancer. The data consist of medical and pharmacy claims from a large national private health insurance network, with the adverse outcome being admission to the emergency room within a short time window of treatment initiation., (© 2021 John Wiley & Sons, Ltd.)