Factors influencing treatment of veterans with advanced prostate cancer

Abstract

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.

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

“…Next, we confirmed men had CRPC using two criteria. For 6 months prior to their first CRPC therapy, men were required to have (1) receipt of continuous androgen deprivation therapy (ADT) as defined previously 4 and (2) a rising prostate‐specific antigen (PSA) level while on ADT. We defined a rising PSA on ADT as a PSA level prior to their initial CRPC drug that was greater than the most recent level, indicating castration resistance.…”

“…We included disease‐status variables, such as PSA levels and doubling time since these have a small effect on the choice of first‐line oral therapy selection. 4 We included a validated metastatic variable that became available after our cohort was constructed so that we could compare the presence of metastatic disease among patients started on the different first‐line therapies. 13 We also included a rurality measure and distance to the treating facility as a measure of access.…”

“…Over 30,000 men die of prostate cancer annually in the US, most from end‐stage castration‐resistant prostate cancer (CRPC) 1 . Prior to 2011, oral ketoconazole was the most common first‐line CRPC treatment, used twice as often as docetaxel, 2–4 though with no high‐level evidence supporting survival benefits. Since 2011, abiraterone and enzalutamide have become the most commonly used first‐line treatments for men with metastatic CRPC, largely replacing ketoconazole in first‐line settings as well as relegating docetaxel use toward less hormone‐responsive disease 4–8 .…”

Outcomes after definitive radiation therapy for localized prostate cancer in a national health care delivery system

“…We stratified patients by risk group at diagnosis using National Comprehensive Cancer Network (NCCN) definitions for low‐, intermediate‐, and high‐risk groups, as well as Grade Group based on clinical staging data. Data regarding ADT use as part of the initial treatment course were derived from the Veterans Administration Central Cancer Registry and using national pharmacy data similar to our prior work 20 . Because ADT is used in combination with radiotherapy in short‐ and long‐term regimens, we defined a cutoff to differentiate “short‐term” from “long‐term” ADT of 9 months.…”

“…Data regarding ADT use as part of the initial treatment course were derived from the Veterans Administration Central Cancer Registry and using national pharmacy data similar to our prior work. 20 Because ADT is used in combination with radiotherapy in short-and long-term regimens, we defined a cutoff to differentiate "short-term" from "long-term" ADT of 9 months. For example, any patients receiving <9 months of ADT as part of their initial treatment course were considered to have received short-term ADT, whereas any patients receiving ≥9 months ADT as part of their initial treatment were considered to have received long-term ADT.…”