Racial Discrepancies in Overall Survival among Men Treated with
            <sup>223</sup>
            Radium

Zhao, Hanson; Howard, Lauren E.; Hoedt, Amanda M. De; Terris, Martha K.; Amling, Christopher L.; Kane, Christopher J.; Cooperberg, Matthew R.; Aronson, William J.; Klaassen, Zachary; Polascik, Thomas J.; Vidal, Adriana C.; Freedland, Stephen J.

doi:10.1097/ju.0000000000000524

Cited by 29 publications

(33 citation statements)

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“…These collectively demonstrate that DNA repair pathway genes, mutations in SPOP , and DNA repair signatures are increased in African American men, which may suggest enhanced responses to radiation therapy, although further studies are warranted to test this hypothesis 21‐23 . Differential responses to systemic therapy between Black and White patients with castration‐resistant prostate cancer have been observed with sipuleucel‐T, 24 radium‐223, 25 and androgen receptor‐targeting agents 26 . Furthermore, data from The Cancer Genome Atlas of men of predominant African ancestry versus European ancestry demonstrated substantial heterogeneity in the prostate tumor genome and transcriptome, suggesting biologic contributors to racial disparities 27 …”

Section: Discussionmentioning

confidence: 87%

Outcomes of Black men with prostate cancer treated with radiation therapy in the Veterans Health Administration

McKay

Sarkar

Kumar

et al. 2020

Cancer

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BackgroundPopulation‐based studies demonstrate that Black men in the United States have an increased risk of death from prostate cancer. Determinants of racial disparities are multifactorial, including socioeconomic and biologic factors.MethodsThe authors conducted a pooled analysis of patients derived from 152 centers within the Veterans Health Administration. The cohort included men who had nonmetastatic prostate diagnosed between 2001 and 2015 and received definitive radiation therapy. The primary endpoint was prostate cancer‐specific mortality (PCSM). Secondary endpoints included all‐cause mortality (ACM) and the time from a prostate‐specific antigen level ≥4 ng/mL to biopsy and radiation therapy. A Cox regression model was performed to adjust for differences between clinical parameters.ResultsAmong the 31,131 patients included in the cohort, 9584 (30.8%) were Black. The 10‐year cumulative incidence of death from prostate cancer was lower in Black men compared with White men (4.0% vs 4.8%; P = .004). In a competing risk model, Black race was associated with a decreased risk of PCSM (subdistribution hazard ratio, 0.79; 95% CI, 0.69‐0.92; P = .002). Similarly, the 10‐year cumulative incidence of death from any cause was lower in Black men (27.6% vs 31.8%; P < .001). In multivariable analysis, Black men had a 10% decreased risk of ACM (hazard ratio, 0.90; 95% CI, 0.85‐0.95; P < .001).ConclusionsThe current results indicate relatively lower PCSM and ACM among Black men who were included in a large Veterans Health Administration cohort and received radiation therapy as primary treatment for nonmetastatic prostate cancer. There is an ongoing need to continue to understand and mitigate the factors associated with disparities in health care outcomes.

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Section: Discussionmentioning

confidence: 87%

Outcomes of Black men with prostate cancer treated with radiation therapy in the Veterans Health Administration

McKay

Sarkar

Kumar

et al. 2020

Cancer

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“…Halabi et al [19] also examined pooled data from nine phase III trials with docetaxel/prednisone in patients with mCRPC in multivariable analysis adjusted for established risk factors; they observed both differences in multiple baseline patient characteristics and a survival benefit (HR: 0.81; 95% CI, 0.72-0.91) favoring African Americans (n = 500) versus Caucasians (n = 7528) [19]. This was recently confirmed in a trial of radium-223 [20]. McNamara et al also reported better OS in response to abiraterone acetate or enzalutamide in chemotherapy naïve African American mCRPC patients [21].…”

Section: Discussionmentioning

confidence: 93%

“…A pooled retrospective analysis of eight multicenter trials in "hormone-refractory" prostate cancer showed that black men had significantly lower risk for death than white men [18]. This was recently confirmed by a pooled clinical trial analysis of docetaxel-treated mCRPC men and in a trial of radium-223 [19,20]. A poster presented at the Genitourinary Symposium in 2019 reported similar observations with enzalutamide and abiraterone acetate [21].…”

Section: Introductionmentioning

confidence: 83%

Survival of African-American and Caucasian men after sipuleucel-T immunotherapy: outcomes from the PROCEED registry

Sartor

Armstrong

Ahaghotu³

et al. 2020

Prostate Cancer Prostatic Dis

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Purpose African Americans experience greater prostate cancer risk and mortality than do Caucasians. An analysis of pooled phase III data suggested differences in overall survival (OS) between African American and Caucasian men receiving sipuleucel-T. We explored this in PROCEED (NCT01306890), an FDA-requested registry in over 1900 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T. Patients and methods OS for patients who received ≥1 sipuleucel-T infusion was compared between African American and Caucasian men using an all patient set and a baseline prostate-specific antigen (PSA)-matched set (two Caucasians to every one African American with baseline PSAs within 10% of each other). Univariable and multivariable analyses were conducted. Survival data were examined using Kaplan-Meier and Cox proportional hazard methodologies. Results Median follow-up was 46.6 months. Overall survival differed between African American and Caucasian men with hazard ratios (HR) of 0.81 (95% confidence interval [CI]: 0.68-0.97, P = 0.03) in the all patient set and 0.70 (95% CI: 0.57-0.86, P < 0.001) in the PSA-matched set. Median OS was longer in African Americans than in Caucasian men for both analysis sets, e.g., 35.3 and 25.8 months, respectively, in the PSA-matched set. Similar results were observed in the all patient set. Differences were larger when treatment began at lower baseline PSA; curves were more similar among patients with higher baseline PSA. In patients with baseline PSA below the median, the HR was 0.52 (95% CI: 0.37-0.72, P < 0.001), with median OS of 54.3 versus 33.4 months. Known prognostic factors and African American race (multivariable analyses; HR: 0.60, 95% CI: 0.48-0.74, P < 0.001) were independently associated with OS. Use of post-sipuleucel-T anticancer interventions was balanced between races. Conclusion In this exploratory analysis of a registry including nearly 12% African American men with mCRPC, OS was significantly different between African Americans and Caucasians, indicating further research is warranted.

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“…This study was approved by the institutional review board at the Durham VA Medical Center. Our study cohort has been previously described 10 . We identified all men ( n = 318) in the entire nationwide VA Healthcare System who received radium‐223 between January 2013 and September 2017.…”

Section: Methodsmentioning

confidence: 99%

Safety of concomitant therapy with radium‐223 and abiraterone or enzalutamide in a real‐world population

et al. 2021

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Background Real‐world utilization and outcomes of combination therapy for men with metastatic castrate‐resistant prostate cancer (mCRPC) are largely unknown. We evaluated the overall survival (OS) and skeletal‐related events (SREs) among men who received radium‐223 with or without concomitant abiraterone or enzalutamide in the Veterans Affairs (VA) Health System. Methods We reviewed charts of all mCRPC patients who received radium‐223 in the VA from January 2013 to September 2017. We used Cox models to test the association between concomitant therapy versus radium‐223 alone on OS and SRE. Sensitivity analyses were performed for concomitant use of denosumab/bisphosphonates. Results Three hundred and eighteen patients treated with radium‐223 were identified; 116/318 (37%) received concomitant abiraterone/enzalutamide. Two hundred and seventy‐seven (87%) patients died during follow‐up. Patients who received concomitant therapy were younger at radium‐223 initiation (median age 68 vs. 70, p = .027) and had a longer follow‐up (median 29.5 vs. 17.9 months, p = .030). There was no OS benefit for those on concomitant therapy (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.67–1.12, p = .28). There was a trend for an increased SRE risk for patients on concomitant therapy (HR: 1.87, 95% CI: 0.96–3.61, p = .066), but this was not significant. When analyses were limited to men using bone heath agents, similar results were seen for OS (HR: 0.86, 95% CI 0.64–1.15, p = .30) and SRE (HR: 2.36, 95% CI: 0.94–5.94, p = .068). Conclusions Despite the common use of concomitant therapy in this real‐world study, there was no difference in OS among mCRPC patients. A nonsignificant increased SRE risk was observed. Further work needs to evaluate the optimal sequence, timing, and safety of combination therapies.

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Racial Discrepancies in Overall Survival among Men Treated with ²²³ Radium

Cited by 29 publications

References 0 publications

Outcomes of Black men with prostate cancer treated with radiation therapy in the Veterans Health Administration

Outcomes of Black men with prostate cancer treated with radiation therapy in the Veterans Health Administration

Survival of African-American and Caucasian men after sipuleucel-T immunotherapy: outcomes from the PROCEED registry

Safety of concomitant therapy with radium‐223 and abiraterone or enzalutamide in a real‐world population

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Racial Discrepancies in Overall Survival among Men Treated with 223 Radium

Cited by 29 publications

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Outcomes of Black men with prostate cancer treated with radiation therapy in the Veterans Health Administration

Outcomes of Black men with prostate cancer treated with radiation therapy in the Veterans Health Administration

Survival of African-American and Caucasian men after sipuleucel-T immunotherapy: outcomes from the PROCEED registry

Safety of concomitant therapy with radium‐223 and abiraterone or enzalutamide in a real‐world population

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Racial Discrepancies in Overall Survival among Men Treated with ²²³ Radium