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Figure.
Cumulative Incidence of Prostate Cancer–Specific Mortality by Race
Cumulative Incidence of Prostate Cancer–Specific Mortality by Race

A Gleason score of 6 indicates low-grade disease and a Gleason score of 7 to 10 indicates intermediate- to high-grade disease. Race was defined via the Surveillance, Epidemiology, and End Results (SEER) race recode variable as black vs nonblack (including white, other, and unknown races) for the purposes of this study. Race was collected and documented by SEER registries via information from medical records, face sheets (patients’ 1-page clinical information summary), clinician notes, photographs, and any other medical record sources available to registries. This Figure represents 192 224 patients with diagnoses between 2010 and 2015.

Table.  
Adjusted Hazard Ratios for Prostate Cancer–Specific Mortality for Patients Diagnosed as Having Localized Prostate Cancer From 2010 Through 2015 in the SEER Prostate AS/WW Database and From 2004 Through 2015 in the General SEER Cohort
Adjusted Hazard Ratios for Prostate Cancer–Specific Mortality for Patients Diagnosed as Having Localized Prostate Cancer From 2010 Through 2015 in the SEER Prostate AS/WW Database and From 2004 Through 2015 in the General SEER Cohort
1.
Rubin  MA, Girelli  G, Demichelis  F.  Genomic correlates to the newly proposed grading prognostic groups for prostate cancer.  Eur Urol. 2016;69(4):557-560. doi:10.1016/j.eururo.2015.10.040PubMedGoogle ScholarCrossref
2.
Carroll  PH, Mohler  JL.  NCCN guidelines updates: prostate cancer and prostate cancer early detection.  J Natl Compr Canc Netw. 2018;16(5S):620-623. doi:10.6004/jnccn.2018.0036PubMedGoogle ScholarCrossref
3.
Sundi  D, Ross  AE, Humphreys  EB,  et al.  African American men with very low-risk prostate cancer exhibit adverse oncologic outcomes after radical prostatectomy: should active surveillance still be an option for them?  J Clin Oncol. 2013;31(24):2991-2997. doi:10.1200/JCO.2012.47.0302PubMedGoogle ScholarCrossref
4.
National Cancer Institute Surveillance, Epidemiology, and End Results Program. Prostate With Watchful Waiting database. 2018. https://seer.cancer.gov/seerstat/databases/prostate-ww/index.html. Accessed May 28, 2018.
5.
Mahal  BA, Aizer  AA, Ziehr  DR,  et al.  Racial disparities in prostate cancer–specific mortality in men with low-risk prostate cancer.  Clin Genitourin Cancer. 2014;12(5):e189-e195. doi:10.1016/j.clgc.2014.04.003PubMedGoogle ScholarCrossref
6.
Cooperberg  MR, Erho  N, Chan  JM,  et al.  The diverse genomic landscape of clinically low-risk prostate cancer.  Eur Urol. 2018;74(4):444-452. doi:10.1016/j.eururo.2018.05.014PubMedGoogle ScholarCrossref
Research Letter
December 18, 2018

Prostate Cancer–Specific Mortality Across Gleason Scores in Black vs Nonblack Men

Author Affiliations
  • 1Harvard Radiation Oncology Program, Boston, Massachusetts
  • 2Department of Medicine, University of California, San Francisco
  • 3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
  • 4Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco
JAMA. 2018;320(23):2479-2481. doi:10.1001/jama.2018.11716

The Gleason score is the best independent predictor of prostate cancer outcomes.1 The principle distinction between Gleason 6 disease vs Gleason 7 to 10 disease is that Gleason 6 disease does not necessarily need definitive treatment.2 Nevertheless, the implications of Gleason score are less clear in black men because of disparate prostate cancer outcomes, particularly for Gleason 6 disease, in which risk assessment and management of disease in black men is controversial.2,3 We investigated prostate cancer–specific mortality by Gleason score and race.

Methods

The Surveillance, Epidemiology, and End Results (SEER) Prostate Active Surveillance/Watchful Waiting (AS/WW) database identified men diagnosed as having localized prostate cancer from 2010 through 2015.4 This national database is the first to capture both a quality-assured AS/WW variable (available from 2010-2015) and a validated composite socioeconomic status (SES) variable (the Yost Index).4 Prostate cancer–specific mortality was obtained as of December 31, 2015, by SEER using active and passive surveillance of national and statewide databases. The Dana-Farber/Harvard Cancer Center institutional review board granted a waiver of informed consent for this study.

Multivariable Fine-Gray competing risks regressions defined adjusted hazard ratios (aHRs) and associated 95% CIs for prostate cancer–specific mortality by race (black vs nonblack) and clinical Gleason score (6 vs 7-10) with a race × clinical Gleason score interaction term and adjustments for the variables listed in the Table. An analysis was also performed in patients from the general SEER database who underwent longer follow-up and who had diagnoses from 2004 through 2015 (without AS/WW data).

Statistical testing was 2-sided with P<.005 considered significant given the large data set. Analyses were performed with Stata/SE 15.1 (StataCorp).

Results

Of 192 224 men (31 841 black; 160 383 nonblack [white, other, and unknown]) included, black patients compared with nonblack patients were younger (median age, 62 vs 65 years) and had more clinical T1- to T2a-stage disease (81.3% vs 75.3%) and more Gleason 7 to 10 disease (60.1% vs 55.8%) (P < .001 for all comparisons). Prostate cancer deaths with Gleason 6 disease occurred in 51 of 12 707 (0.40%) black patients vs 155 of 70 938 (0.22%) nonblack patients, and for Gleason 7 to 10 disease, prostate cancer deaths occurred in 275 of 19 134 (1.44%) black patients vs 1206 of 89 445 (1.35%) nonblack patients (Table).

Median follow-up was 36 months. Gleason 6 disease was associated with a lower risk of prostate cancer death (206 of 83 645 [0.25%]) compared with Gleason 7 to 10 disease (1481 of 108 579 [0.77%]) (aHR, 0.25; 95% CI, 0.22-0.30; P < .001). The risk of prostate cancer death was not statistically significantly different between black patients (326 of 31 841 [1.02%]) and nonblack patients (1361 of 160 383 [0.85%]) (aHR, 1.10; 95% CI, 0.96-1.25; P = .17) in the cohort. However, black patients with Gleason 6 disease had a higher risk of prostate cancer death compared with nonblack patients (aHR, 1.95; 95% CI, 1.42-2.67; P < .001), while no significant difference was observed with Gleason 7 to 10 disease (aHR, 1.01; 95% CI, 0.87-1.16; P = .94) (P<.001 for interaction) (Figure and Table). All covariates were significantly associated with prostate cancer death, including favorable associations with AS/WW and increasing SES (Table).

Similar findings were observed in 403 022 patients with a longer median follow-up of 65 months (62 736 black; 340 286 nonblack); racial disparities between black patients vs nonblack patients were greatest in Gleason 6 disease (12-year prostate cancer mortality rate, 2.2% vs 1.4%) compared with Gleason 7 to 10 disease (12-year prostate cancer mortality rate, 5.5% in black patients vs 5.3% in nonblack patients) (P<.001 for interaction) (Table).

Discussion

Racial disparities were greatest in low-grade Gleason 6 disease, in which black men were twice as likely to die of prostate cancer compared with nonblack men. Although absolute rates of prostate cancer death were small after short follow-up, disparities were greater at 12 years in a cohort with longer follow-up. In contrast to previous analyses,5 the SEER AS/WW database allowed adjustments for SES and AS/WW, thereby better controlling for socioeconomic and treatment selection differences and supporting the hypothesis that low-grade prostate cancer may be distinct in black men.6 Other potential contributors include racial differences in patient characteristics, prognostic value of biopsy, and patterns of care. Ultimately, these findings demonstrate the need to further study and characterize low-grade disease in black men. This study was limited by short follow-up and possible unadjusted confounding variables. Future studies with longer follow-up will be needed to further characterize low-grade disease in black men and to determine the clinical significance of the small absolute differences and whether they continue to increase over time.

Section Editor: Jody W. Zylke, MD, Deputy Editor.
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Article Information

Accepted for Publication: September 20, 2018.

Corresponding Author: Franklin W. Huang, MD, PhD, Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, 513 Parnassus Ave, Box 1346, HSE 1424, San Francisco, CA 94143 (franklin.huang@ucsf.edu).

Author Contributions: Drs Mahal and Huang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Mahal, Huang.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Mahal, Taplin, Huang.

Critical revision of the manuscript for important intellectual content: Mahal, Berman, Huang.

Statistical analysis: Mahal, Huang.

Obtained funding: Mahal, Huang.

Administrative, technical, or material support: Mahal, Huang.

Supervision: Mahal, Taplin, Huang.

Other—clinical perspective: Berman.

Conflict of Interest Disclosures: None reported.

Funding/Support: Dr Mahal is funded by the Prostate Cancer Foundation–American Society for Radiation Oncology Award to End Prostate Cancer. Dr Taplin is funded by Prostate Cancer Foundation challenge grant 6296701. Dr Huang is funded by the Prostate Cancer Foundation Young Investigator Award and the Department of Defense Prostate Cancer Research Program.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Rubin  MA, Girelli  G, Demichelis  F.  Genomic correlates to the newly proposed grading prognostic groups for prostate cancer.  Eur Urol. 2016;69(4):557-560. doi:10.1016/j.eururo.2015.10.040PubMedGoogle ScholarCrossref
2.
Carroll  PH, Mohler  JL.  NCCN guidelines updates: prostate cancer and prostate cancer early detection.  J Natl Compr Canc Netw. 2018;16(5S):620-623. doi:10.6004/jnccn.2018.0036PubMedGoogle ScholarCrossref
3.
Sundi  D, Ross  AE, Humphreys  EB,  et al.  African American men with very low-risk prostate cancer exhibit adverse oncologic outcomes after radical prostatectomy: should active surveillance still be an option for them?  J Clin Oncol. 2013;31(24):2991-2997. doi:10.1200/JCO.2012.47.0302PubMedGoogle ScholarCrossref
4.
National Cancer Institute Surveillance, Epidemiology, and End Results Program. Prostate With Watchful Waiting database. 2018. https://seer.cancer.gov/seerstat/databases/prostate-ww/index.html. Accessed May 28, 2018.
5.
Mahal  BA, Aizer  AA, Ziehr  DR,  et al.  Racial disparities in prostate cancer–specific mortality in men with low-risk prostate cancer.  Clin Genitourin Cancer. 2014;12(5):e189-e195. doi:10.1016/j.clgc.2014.04.003PubMedGoogle ScholarCrossref
6.
Cooperberg  MR, Erho  N, Chan  JM,  et al.  The diverse genomic landscape of clinically low-risk prostate cancer.  Eur Urol. 2018;74(4):444-452. doi:10.1016/j.eururo.2018.05.014PubMedGoogle ScholarCrossref
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