Factors influencing treatment of veterans with advanced prostate cancer.

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.

Prediction-Augmented Shared Decision-Making and Lung Cancer Screening Uptake.

Importance: Addressing poor uptake of low-dose computed tomography lung cancer screening (LCS) is critical, especially for those having the most to gain-high-benefit persons with high lung cancer risk and life expectancy more than 10 years. Objective: To assess the association between LCS uptake and implementing a prediction-augmented shared decision-making (SDM) tool, which enables clinicians to identify persons predicted to be at high benefit and encourage LCS more strongly for these persons. Design, Setting, and Participants: Quality improvement interrupted time series study at 6 Veterans Affairs sites that used a standard set of clinical reminders to prompt primary care clinicians and screening coordinators to engage in SDM for LCS-eligible persons. Participants were persons without a history of LCS who met LCS eligibility criteria at the time (aged 55-80 years, smoked ≥30 pack-years, and current smoking or quit <15 years ago) and were not documented to be an inappropriate candidate for LCS by a clinician during October 2017 through September 2019. Data were analyzed from September to November 2023. Exposure: Decision support tool augmented by a prediction model that helps clinicians personalize SDM for LCS, tailoring the strength of screening encouragement according to predicted benefit. Main outcome and measure: LCS uptake. Results: In a cohort of 9904 individuals, the median (IQR) age was 64 (57-69) years; 9277 (94%) were male, 1537 (16%) were Black, 8159 (82%) were White, 5153 (52%) were predicted to be at intermediate (preference-sensitive) benefit and 4751 (48%) at high benefit, and 1084 (11%) received screening during the study period. Following implementation of the tool, higher rates of LCS uptake were observed overall along with an increase in benefit-based LCS uptake (higher screening uptake among persons anticipated to be at high benefit compared with those at intermediate benefit; primary analysis). Mean (SD) predicted probability of getting screened for a high-benefit person was 24.8% (15.5%) vs 15.8% (11.8%) for a person at intermediate benefit (mean absolute difference 9.0 percentage points; 95% CI, 1.6%-16.5%). Conclusions and Relevance: Implementing a robust approach to personalized LCS, which integrates SDM, and a decision support tool augmented by a prediction model, are associated with improved uptake of LCS and may be particularly important for those most likely to benefit. These findings are timely given the ongoing poor rates of LCS uptake.

Determinants of Bone-Modifying Agent Prescribing for Metastatic Castration-Resistant Prostate Cancer in a National Health Care Delivery System.

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.

Survival by first-line therapy and prognostic group among men with metastatic castration-resistant prostate cancer.

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.

Changes in Outpatient Health Care Use After COVID-19 Infection Among Veterans.

Importance: The association of COVID-19 infection with outpatient care utilization is unclear. Many studies reported population surveillance studies rather than comparing outpatient health care use between COVID-19-infected and uninfected cohorts. Objective: To compare outpatient health care use across 6 categories of care (primary care, specialty care, surgery care, mental health, emergency care, and diagnostic and/or other care) between veterans with or without COVID-19 infection. Design, Setting, and Participants: In a retrospective cohort study of Veterans Affairs primary care patients, veterans with COVID-19 infection were matched to a cohort of uninfected veterans. Data were obtained from the Veterans Affairs Corporate Data Warehouse and the Centers for Medicare & Medicaid Services Fee-for-Service Carrier/Physician Supplier file from January 2019 through December 2022. Data analysis was performed from September 2022 to April 2023. Exposure: COVID-19 infection. Main Outcomes and Measures: The primary outcome was the count of outpatient visits after COVID-19 infection. Negative binomial regression models compared outpatient use over a 1-year preinfection period, and peri-infection (0-30 days), intermediate (31-183 days), and long-term (184-365 days) postinfection periods. Results: The infected (202 803 veterans; mean [SD] age, 60.5 [16.2] years; 178 624 men [88.1%]) and uninfected (202 803 veterans; mean [SD] age, 60.4 [16.5] years; 178 624 men [88.1%]) cohorts were well matched across all covariates. Outpatient use in all categories (except surgical care) was significantly elevated during the peri-infection period for veterans with COVID-19 infection compared with the uninfected cohort, with an increase in all visits of 5.12 visits per 30 days (95% CI, 5.09-5.16 visits per 30 days), predominantly owing to primary care visits (increase of 1.86 visits per 30 days; 95% CI, 1.85-1.87 visits per 30 days). Differences in outpatient use attenuated over time but remained statistically significantly higher at 184 to 365 days after infection (increase of 0.25 visit per 30 days; 95% CI, 0.23-0.27 visit per 30 days). One-half of the increased outpatient visits were delivered via telehealth. The utilization increase was greatest for veterans aged 85 years and older (6.1 visits, 95% CI, 5.9-6.3 visits) vs those aged 20 to 44 years (4.8 visits, 95% CI, 4.7-4.8 visits) and unvaccinated veterans (4.5 visits, 95% CI, 4.3-4.6 visits) vs vaccinated veterans (3.2 visits; 95% CI, 3.4-4.8 visits). Conclusions and Relevance: This study found that outpatient use increased significantly in the month after infection, then attenuated but remained greater than the uninfected cohorts' use through 12 months, which suggests that there are sustained impacts of COVID-19 infection.

Differential adoption of castration-resistant prostate cancer treatment across facilities in a national healthcare system.

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.

Mental health care utilization among men with castration-resistant prostate cancer receiving abiraterone or enzalutamide.

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.

Adverse outcomes of SARS-CoV-2 infection with delta and omicron variants in vaccinated versus unvaccinated US veterans: retrospective cohort study.

OBJECTIVES: To determine the association between covid-19 vaccination types and doses with adverse outcomes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the periods of delta (B.1.617.2) and omicron (B.1.1.529) variant predominance. DESIGN: Retrospective cohort. SETTING: US Veterans Affairs healthcare system. PARTICIPANTS: Adults (≥18 years) who are affiliated to Veterans Affairs with a first documented SARS-CoV-2 infection during the periods of delta (1 July-30 November 2021) or omicron (1 January-30 June 2022) variant predominance. The combined cohorts had a mean age of 59.4 (standard deviation 16.3) and 87% were male. INTERVENTIONS: Covid-19 vaccination with mRNA vaccines (BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)) and adenovirus vector vaccine (Ad26.COV2.S (Janssen/Johnson & Johnson)). MAIN OUTCOME MEASURES: Stay in hospital, intensive care unit admission, use of ventilation, and mortality measured 30 days after a positive test result for SARS-CoV-2. RESULTS: In the delta period, 95 336 patients had infections with 47.6% having at least one vaccine dose, compared with 184 653 patients in the omicron period, with 72.6% vaccinated. After adjustment for patient demographic and clinical characteristics, in the delta period, two doses of the mRNA vaccines were associated with lower odds of hospital admission (adjusted odds ratio 0.41 (95% confidence interval 0.39 to 0.43)), intensive care unit admission (0.33 (0.31 to 0.36)), ventilation (0.27 (0.24 to 0.30)), and death (0.21 (0.19 to 0.23)), compared with no vaccination. In the omicron period, receipt of two mRNA doses were associated with lower odds of hospital admission (0.60 (0.57 to 0.63)), intensive care unit admission (0.57 (0.53 to 0.62)), ventilation (0.59 (0.51 to 0.67)), and death (0.43 (0.39 to 0.48)). Additionally, a third mRNA dose was associated with lower odds of all outcomes compared with two doses: hospital admission (0.65 (0.63 to 0.69)), intensive care unit admission (0.65 (0.59 to 0.70)), ventilation (0.70 (0.61 to 0.80)), and death (0.51 (0.46 to 0.57)). The Ad26.COV2.S vaccination was associated with better outcomes relative to no vaccination, but higher odds of hospital stay and intensive care unit admission than with two mRNA doses. BNT162b2 was generally associated with worse outcomes than mRNA-1273 (adjusted odds ratios between 0.97 and 1.42). CONCLUSIONS: In veterans with recent healthcare use and high occurrence of multimorbidity, vaccination was robustly associated with lower odds of 30 day morbidity and mortality compared with no vaccination among patients infected with covid-19. The vaccination type and number of doses had a significant association with outcomes.