Dataset Information

Plasma cells are enriched in localized prostate cancer in Black men and are associated with improved outcomes.

ABSTRACT: Black men die more often of prostate cancer yet, interestingly, may derive greater survival benefits from immune-based treatment with sipuleucel-T. Since no signatures of immune-responsiveness exist for prostate cancer, we explored race-based immune-profiles to identify vulnerabilities. Here we show in multiple independent cohorts comprised of over 1,300 patient samples annotated with either self-identified race or genetic ancestry, prostate tumors from Black men or men of African ancestry have increases in plasma cell infiltrate and augmented markers of NK cell activity and IgG expression. These findings are associated with improved recurrence-free survival following surgery and nominate plasma cells as drivers of prostate cancer immune-responsiveness.

SUBMITTER: Weiner AB

PROVIDER: S-EPMC7876147 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Plasma cells are enriched in localized prostate cancer in Black men and are associated with improved outcomes.

Weiner Adam B AB Vidotto Thiago T Liu Yang Y Mendes Adrianna A AA Salles Daniela C DC Faisal Farzana A FA Murali Sanjana S McFarlane Matthew M Imada Eddie L EL Zhao Xin X Li Ziwen Z Davicioni Elai E Marchionni Luigi L Chinnaiyan Arul M AM Freedland Stephen J SJ Spratt Daniel E DE Wu Jennifer D JD Lotan Tamara L TL Schaeffer Edward M EM

Nature communications 20210210 1

Black men die more often of prostate cancer yet, interestingly, may derive greater survival benefits from immune-based treatment with sipuleucel-T. Since no signatures of immune-responsiveness exist for prostate cancer, we explored race-based immune-profiles to identify vulnerabilities. Here we show in multiple independent cohorts comprised of over 1,300 patient samples annotated with either self-identified race or genetic ancestry, prostate tumors from Black men or men of African ancestry have ...[more]

PMID: 33568675

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Project description:ImportanceBlack men have a 2-fold increased risk of dying from prostate cancer compared with White men. However, race-specific differences in response to initial treatment remain unknown.ObjectiveTo compare overall and treatment-specific outcomes of Black and White men with localized prostate cancer receiving definitive radiotherapy (RT).Data sourcesA systematic search was performed of relevant published randomized clinical trials conducted by the NRG Oncology/Radiation Therapy Oncology Group between January 1, 1990, and December 31, 2010. This meta-analysis was performed from July 1, 2019, to July 1, 2021.Study selectionRandomized clinical trials of definitive RT for patients with localized prostate cancer comprising a substantial number of Black men (self-identified race) enrolled that reported on treatment-specific and overall outcomes.Data extraction and synthesisIndividual patient data were obtained from 7 NRG Oncology/Radiation Therapy Oncology Group randomized clinical trials evaluating definitive RT with or without short- or long-term androgen deprivation therapy. Unadjusted Fine-Gray competing risk models, with death as a competing risk, were developed to evaluate the cumulative incidences of end points. Cox proportional hazards models were used to evaluate differences in all-cause mortality and the composite outcome of distant metastasis (DM) or death. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.Main outcomes and measuresSubdistribution hazard ratios (sHRs) of biochemical recurrence (BCR), DM, and prostate cancer-specific mortality (PCSM).ResultsA total of 8814 patients (1630 [18.5%] Black and 7184 [81.5%] White) were included; mean (SD) age was 69.1 (6.8) years. Median follow-up was 10.6 (IQR, 8.0-17.8) years for surviving patients. At enrollment, Black men were more likely to have high-risk disease features. However, even without adjustment, Black men were less likely to experience BCR (sHR, 0.88; 95% CI, 0.58-0.91), DM (sHR, 0.72; 95% CI, 0.58-0.91), or PCSM (sHR, 0.72; 95% CI, 0.54-0.97). No significant differences in all-cause mortality were identified (HR, 0.99; 95% CI, 0.92-1.07). Upon adjustment, Black race remained significantly associated with improved BCR (adjusted sHR, 0.79; 95% CI, 0.72-0.88; P < .001), DM (adjusted sHR, 0.69; 95% CI, 0.55-0.87; P = .002), and PCSM (adjusted sHR, 0.68; 95% CI, 0.50-0.93; P = .01).Conclusions and relevanceThe findings of this meta-analysis suggest that Black men enrolled in randomized clinical trials present with more aggressive disease but have better BCR, DM, and PCSM with definitive RT compared with White men, suggesting that other determinants of outcome, such as access to care, are important factors of achieving racial equity.

Project description:BACKGROUND:To understand the threat posed by localized prostate cancer and the potential impact of surgery or radiation, patients and healthcare providers require information on long-term outcomes following conservative management. OBJECTIVE:To describe 15-yr survival outcomes and cancer therapy utilization among men 65 years and older managed conservatively for newly diagnosed localized prostate cancer. DESIGN, SETTINGS, AND PARTICIPANTS:This is a population-based cohort study with participants living in predefined geographic areas covered by the Surveillance, Epidemiology, and End Results program. The study includes 31 137 Medicare patients aged ?65 yr diagnosed with localized prostate cancer in 1992-2009 who initially received conservative management (no surgery, radiotherapy, cryotherapy, or androgen deprivation therapy [ADT]). All patients were followed until death or December 31, 2009 (for prostate cancer-specific mortality [PCSM]) and December 31, 2011 (for overall mortality). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Competing-risk analyses were used to examine PCSM, overall mortality, and utilization of cancer therapies. RESULTS AND LIMITATIONS:The 15-yr risk of PCSM for men aged 65-74 yr diagnosed with screening-detected prostate cancer was 5.7% (95% confidence interval [CI] 3.7-8.0%) for T1c Gleason 5-7 and 22% (95% CI 16-35%) for Gleason 8-10 disease. After 15 yr of follow-up, 24% (95% CI 21-27%) of men aged 65-74 yr with screening-detected Gleason 5-7 cancer received ADT. The corresponding result for men with Gleason 8-10 cancer was 38% (95% CI 32-44%). The major study limitations are the lack of data for men aged <65 yr and detailed clinical information associated with secondary cancer therapy. CONCLUSIONS:The 15-yr outcomes following conservative management of newly diagnosed Gleason 5-7 prostate cancer among men aged ?65 yr are excellent. Men with Gleason 8-10 disease managed conservatively face a significant risk of PCSM. PATIENT SUMMARY:We examined the long-term survival outcomes for a large group of patients diagnosed with localized prostate cancer who did not have surgery, radiotherapy, cryotherapy, or androgen deprivation therapy in the first 6 mo after cancer diagnosis. We found that the 15-yr disease-specific survival is excellent for men diagnosed with Gleason 5-7 disease. The data support conservative management as a reasonable choice for elderly patients with low-grade localized prostate cancer.

Dataset Information

Plasma cells are enriched in localized prostate cancer in Black men and are associated with improved outcomes.

Publications

Plasma cells are enriched in localized prostate cancer in Black men and are associated with improved outcomes.

Similar Datasets

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