Racial and Ethnic Disparities in Use of Novel Hormonal Therapy Agents in Patients With Prostate Cancer.

Importance: Novel hormonal therapy (NHT) agents have been shown to prolong overall survival in numerous randomized clinical trials for patients with advanced prostate cancer (PCa). There is a paucity of data regarding the pattern of use of these agents in patients from different racial and ethnic groups. Objective: To assess racial and ethnic disparities in the use of NHT in patients with advanced PCa. Design, Setting, and Participants: This cohort study comprised all men diagnosed with de novo advanced PCa (distant metastatic [M1], regional [N1M0], and high-risk localized [N0M0] per Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy [STAMPEDE] trial criteria) with Medicare Part A, B, and D coverage between January 1, 2011, and December 31, 2017, in a Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database including prescription drug records. Data analysis took place from January through May 2023. Exposures: Race and ethnicity (Black [non-Hispanic], Hispanic, White, or other [Alaska Native, American Indian, Asian, Pacific Islander, or not otherwise specified and unknown]) abstracted from the SEER data fields. Main Outcomes and Measures: The primary outcome was receipt of an NHT agent (abiraterone, enzalutamide, apalutamide, or darolutamide) using a time-to-event approach. Results: The study included 3748 men (median age, 75 years [IQR, 70-81 years]). A total of 312 (8%) were Black; 263 (7%), Hispanic; 2923 (78%), White; and 250 (7%) other race and ethnicity. The majority of patients had M1 disease (2135 [57%]) followed by high-risk N0M0 (1095 [29%]) and N1M0 (518 [14%]) disease. Overall, 1358 patients (36%) received at least 1 administration of NHT. White patients had the highest 2-year NHT utilization rate (27%; 95% CI, 25%-28%) followed by Hispanic patients (25%; 95% CI, 20%-31%) and patients with other race or ethnicity (23%; 95% CI, 18%-29%), with Black patients having the lowest rate (20%; 95% CI, 16%-25%). Black patients had significantly lower use of NHT compared with White patients, which persisted at 5 years (37% [95% CI, 31%-43%] vs 44% [95% CI, 42%-46%]; P = .02) and beyond. However, there was no significant difference between White patients and Hispanic patients or patients with other race or ethnicity in NHT utilization (eg, 5 years: Hispanic patients, 38% [95% CI, 32%-46%]; patients with other race and ethnicity: 41% [95% CI, 35%-49%]). Trends of lower utilization among Black patients persisted in the patients with M1 disease (eg, vs White patients at 5 years: 51% [95% CI, 44%-59%] vs 55% [95% CI, 53%-58%]). After adjusting for patient, disease, and sociodemographic factors in multivariable analysis, Black patients continued to have a significantly lower likelihood of NHT initiation (adjusted subdistribution hazard ratio, 0.76; 95% CI, 0.61-0.94, P = .01). Conclusions and Relevance: In this cohort study of Medicare beneficiaries with advanced PCa, receipt of NHT agents was not uniform by race, with decreased use observed in Black patients compared with the other racial and ethnic groups, likely due to multifactorial obstacles. Future studies are needed to identify strategies to address the disparities in the use of these survival-prolonging therapies in Black patients.

For us by us: Instituting mentorship models that credit minoritized medical faculty expertise and lived experience.

The woefully low proportion of scientists and clinicians underrepresented in medicine (UIM), including members of African-American/Black, Hispanic/Latinx, American Indian/Alaska Native or Native Hawaiian/Pacific Islander communities, is well characterized and documented. Diversity in medicine is not only just, but it improves quality and outcomes. Yet, diversity in academic medicine remains stagnant, despite national recognition and urgent calls to improve diversity, equity, and inclusion across health sciences. One strategy that has shown to improve diversity in many sectors is high quality mentoring. While many institutions have adopted mentoring programs, there remains a lack of mentorship that is equitable, individualized, and sets a clear timeline for academic milestones that will position UIM mentees at the optimal trajectory for promotion and retention. A barrier to assembling these programs is the small number of UIM among the senior faculty ranks who are able to serve in this role, given the disproportionate burden to serve on a multitude of academic committees, task forces, and workgroups to fulfill institutional mandates to diversify representation. These time-consuming services, documented in the literature as the "minority tax," are generally uncompensated and unaccounted for in terms of consideration for promotion, leadership positions, and other measures of career advancement. The Justice, Equity, Diversity, and Inclusion Academic Mentors (JAM) Council represents a novel, culturally responsive, and anti-racist approach to achieve a more equitable and inclusive institutional environment. This approach strategically leverages the intergenerational wisdom and experience of senior UIM faculty via time-protected effort with the overall goals of improving rates of promotion, retention, and career satisfaction of early career UIM colleagues. This community case study describes the rationale, resources needed, processes, and proposed workflow required to launch the JAM Council, as well as the major roles and responsibilities for JAM mentors and mentees, which may be considered by academic medical centers focused on improving diversity among the faculty ranks.

Racial and Ethnic Disparities in Prostate Cancer Outcomes in the Veterans Affairs Health Care System.

Importance: Prostate cancer (PCa) disproportionately affects African American men, but research evaluating the extent of racial and ethnic disparities across the PCa continuum in equal-access settings remains limited at the national level. The US Department of Veterans Affairs (VA) Veterans Hospital Administration health care system offers a setting of relatively equal access to care in which to assess racial and ethnic disparities in self-identified African American (or Black) veterans and White veterans. Objective: To determine the extent of racial and ethnic disparities in the incidence of PCa, clinical stage, and outcomes between African American patients and White patients who received a diagnosis or were treated at a VA hospital. Design, Setting, and Participants: This retrospective cohort study included 7 889 984 veterans undergoing routine care in VA hospitals nationwide from 2005 through 2019 (incidence cohort). The age-adjusted incidence of localized and de novo metastatic PCa was estimated. Treatment response was evaluated, and PCa-specific outcomes were compared between African American veterans and White veterans. Residual disparity in PCa outcome, defined as the leftover racial and ethnic disparity in the outcomes despite equal response to treatment, was estimated. Exposures: Self-identified African American (or Black) and White race and ethnicity. Main Outcomes and Measures: Time to distant metastasis following PCa diagnosis was the primary outcome. Descriptive analyses were used to compare baseline demographics and clinic characteristics. Multivariable logistic regression was used to evaluate race and ethnicity association with pretreatment clinical variables. Multivariable Cox regression was used to estimate the risk of metastasis. Results: Data from 7 889 984 veterans from the incidence cohort were used to estimate incidence, whereas data from 92 269 veterans with localized PCa were used to assess treatment response. Among 92 269 veterans, African American men (n = 28 802 [31%]) were younger (median [IQR], 63 [58-68] vs 65 [62-71] years) and had higher prostate-specific antigen levels (>20 ng/mL) at the time of diagnosis compared with White men (n = 63 467; [69%]). Consistent with US population-level data, African American veterans displayed a nearly 2-fold greater incidence of localized and de novo metastatic PCa compared with White men across VA centers nationwide. Among veterans screened for PCa, African American men had a 29% increased risk of PCa detection on a diagnostic prostate biopsy compared with White (hazard ratio, 1.29; 95% CI, 1.27-1.31; P < .001). African American men who received definitive primary treatment of PCa experienced a lower risk of metastasis (hazard ratio, 0.89; 95% CI, 0.83-0.95; P < .001). However, African American men who received nondefinitive treatment classified as "other" were more likely to develop metastasis (adjusted hazard ratio, 1.29; 95% CI, 1.17-1.42; P < .001). Using the actual rate of metastasis from veterans who received definitive primary treatment, a persistent residual metastatic burden for African American men was observed across all National Comprehensive Cancer Network risk groups (low risk, 4 vs 2 per 100 000; intermediate risk, 13 vs 6 per 100 000; high risk, 19 vs 9 per 100 000). Conclusions and Relevance: This cohort analysis found significant disparities in the incidence of localized and metastatic PCa between African American veterans and White veterans. This increased incidence is a major factor associated with the residual disparity in PCa metastasis observed in African American veterans compared with White veterans despite their nearly equal response to treatment.

A Circulating Tumor Cell-RNA Assay for Assessment of Androgen Receptor Signaling Inhibitor Sensitivity in Metastatic Castration-Resistant Prostate Cancer.

Rationale: Our objective was to develop a circulating tumor cell (CTC)-RNA assay for characterizing clinically relevant RNA signatures for the assessment of androgen receptor signaling inhibitor (ARSI) sensitivity in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: We developed the NanoVelcro CTC-RNA assay by combining the Thermoresponsive (TR)-NanoVelcro CTC purification system with the NanoString nCounter platform for cellular purification and RNA analysis. Based on the well-validated, tissue-based Prostate Cancer Classification System (PCS), we focus on the most aggressive and ARSI-resistant PCS subtype, i.e., PCS1, for CTC analysis. We applied a rigorous bioinformatic process to develop the CTC-PCS1 panel that consists of prostate cancer (PCa) CTC-specific RNA signature with minimal expression in background white blood cells (WBCs). We validated the NanoVelcro CTC-RNA assay and the CTC-PCS1 panel with well-characterized PCa cell lines to demonstrate the sensitivity and dynamic range of the assay, as well as the specificity of the PCS1 Z score (the likelihood estimate of the PCS1 subtype) for identifying PCS1 subtype and ARSI resistance. We then selected 31 blood samples from 23 PCa patients receiving ARSIs to test in our assay. The PCS1 Z scores of each sample were computed and compared with ARSI treatment sensitivity. Results: The validation studies using PCa cell line samples showed that the NanoVelcro CTC-RNA assay can detect the RNA transcripts in the CTC-PCS1 panel with high sensitivity and linearity in the dynamic range of 5-100 cells. We also showed that the genes in CTC-PCS1 panel are highly expressed in PCa cell lines and lowly expressed in background WBCs. Using the artificial CTC samples simulating the blood sample conditions, we further demonstrated that the CTC-PCS1 panel is highly specific in identifying PCS1-like samples, and the high PCS1 Z score is associated with ARSI resistance samples. In patient bloods, ARSI-resistant samples (ARSI-R, n=14) had significantly higher PCS1 Z scores as compared with ARSI-sensitive samples (ARSI-S, n=17) (Rank-sum test, P=0.003). In the analysis of 8 patients who were initially sensitive to ARSI (ARSI-S) and later developed resistance (ARSI-R), we found that the PCS1 Z score increased from the time of ARSI-S to the time of ARSI-R (Pairwise T-test, P=0.016). Conclusions: Using our new methodology, we developed a first-in-class CTC-RNA assay and demonstrated the feasibility of transforming clinically-relevant tissue-based RNA profiling such as PCS into CTC tests. This approach allows for detecting RNA expression relevant to clinical drug resistance in a non-invasive fashion, which can facilitate patient-specific treatment selection and early detection of drug resistance, a goal in precision oncology.