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Evidence suggests prostate cancer biologically different in black men
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One in three black men likely will develop asymptomatic prostate cancer by the age of 85 years, according a study published in Cancer.
The findings of that study — conducted by Ruth Etzioni, PhD, biostatistician with the division of public health sciences at Fred Hutchinson Cancer Research Center, and colleagues — renewed the debate about whether prostate cancer is less detectable and, therefore, more aggressive in black men than in men of other ethnicities.
“Based on our findings, we feel that there is a case to be made for screening black men at earlier ages and possibly more often than other men,” Etzioni told HemOnc Today. “To determine how we should screen black men differently, we need to know how the disease differs in black men.”
It has been well documented that prostate cancer incidence is 60% higher among black men, and that mortality rates are more than twice as high among black individuals than white men.
Some contend the disparities are societal, whereas others cite distinct biological differences.
Potential biological differences
Edward M. Schaeffer, MD, PhD, department chair of urology at Northwestern University Feinberg School of Medicine, believes many of the genomes for prostate cancer can be traced to West Africa. Schaeffer is conducting a multi-institutional trial to analyze the advanced biomarkers for prostate cancer in black men to describe biological differences.
Tumor location also may differ in black men, leading to early-stage disease that goes undetected on biopsy, Schaeffer said.
“We looked at prostate cancers that were in their infancies and found that black men are about twice as likely to have tumors in the anterior areas of the prostate — farther away from the rectum — than a traditional tumor would be in a Caucasian patient,” Schaeffer told HemOnc Today. “Are black patients less likely to follow up on an abnormal test? Yes, they are. But when you look at the actual tumors and you match them up, there are differences biologically and they are more aggressive.”
If there are more cancer cells in the anterior region of the prostate, black men could go undiagnosed more often than white men, according to John D. Carpten, PhD, professor and chair of translational genomics at Keck School of Medicine of USC.
“Hypothetically, if tumors were derived in the anterior region more frequently in one population and you perform a biopsy, you may miss some of those cancers,” Carpten told HemOnc Today. “A lot more research needs to be done on much larger cohorts to really nail that association.”
According to a 2014 study by Cropp and colleagues, an indicator within the chromosome 8q24 region showed a distinct association with prostate cancer in men of West African descent.
“There is evidence that region of the genome is more related to West African ancestry,” Carpten said. “No one has been able to show functionally the true biological meaning behind that. Right now, it’s all based on population genetics and not on actual biology and function.”
Questions remain
Still, other studies have not confirmed these genetic differences.
A study by Jennifer Cullen, PhD, MPH, research assistant professor in the department of surgery of Uniformed Services University, and colleagues — published in 2015 in European Urology — showed black men and white men experienced similar tumor aggressiveness and outcomes, as measured by a 17-genome Genomic Prostate Score (Genomic Health). Cullen and colleagues also conducted a study, published in European Urology Focus, that shows what Cullen calls “a strikingly higher prevalence” of ERG oncoprotein expression for white vs. black men, and improved PFS for white men with ERG–positive tumors.
“Therefore, when approaching studies designed to identify molecular markers of disease aggressiveness, we make few assumptions about racial comparability until we have data on hand to confirm,” Cullen told HemOnc Today. “In our military cohort, with its overrepresentation of African American men, we are uniquely positioned to address the role of race in such study questions.”
A study presented by Bardot and colleagues at this month’s American Urological Association Annual Meeting, also showed similar genomic predictors among all races with the Prolaris test (Myriad Genetics).
“We still know African American men have the highest rate of prostate cancer and there could be other molecular events that are different, but Prolaris performed the same irrespective to race, risk strata and treatment,” Michael K. Brawer, MD, vice president of medical affairs at Myriad Genetics, told HemOnc Today. “But, the primary analysis was to look at men who had gone through curative therapy and did or did not develop metastasis with a minimum of 5 years of follow-up. There could be other mutations that are different in blacks than in whites.”
Historically, the proportion of black individuals in clinical trials has been an impediment to research. A review of 227 treatment trials and 27 prevention trials by Kwiatkowski and colleagues showed 82.9% of participants were white and 6.2% were black.
Those disparities have made it difficult to accurately assess why prostate cancer incidence and mortality are greater among black men.
Etzioni’s research team reported black men have a 30% to 43% risk for developing preclinical prostate cancer — or 28% to 56% higher than the risk in the general population.
The risk for a clinical diagnosis ranged from 33% to 70% higher among black men than in the general population, and the risk for progression to metastatic disease by the time of diagnosis was 44% to 75% higher for black men.
“One of the challenges is that a lot of African American men tend to be seen in more community-based health environments rather than in large academic medical centers,” Carpten said. “It will require more of a targeted and unique approach to be able to reach those men and get them tested.”
Because the thresholds set for PSA biomarkers generally are derived from predominately European American cohorts, it is difficult to know if black men should be assigned slightly different genomic biomarkers, Carpten added.
“If someone were to go back and look at PSA data from 2,000 African American men and 2,000 Caucasian men, I’m not quite sure what the differences would be,” he said. “Is the sensitivity and specificity for PSA worse for black men vs. white men? I don’t know if we have the answer to that question.”
Judd W. Moul, MD, former chair of urology at Duke Cancer Center, first proposed calibrating PSA screenings for black men in 1994. With the sophisticated 4Kscores (Opko, BioReference Laboratories and GenPath) and prostate health indexes, applying different Gleason score thresholds for high-risk black men may be appropriate, Schaeffer said.
“A score that may appear to be normal in a white man may be abnormal in a black man,” Schaeffer said. “A 50-year-old African American man with a PSA of 3 may not be OK. We do not know how to incorporate ancestry into our equation. I would like to see us do a blood test and a swab of the cheek.” – by Chuck Gormley
References:
Brawer M, et al. Abstract MP28-19. Presented at: American Urological Association Annual Meeting; May 12-16, 2017; Boston.
Cropp CD, et al. Prostate. 2014;doi:10.1002/pros.22871.
Cullen J, et al. Eur Urol. 2015;doi:10.1016/j.eururo.2014.11.030.
Cullen J, et al. Eur Urol Focus. 2017;doi:10.1016/j.euf.2017.02.016.
Kwiatowski K, et al. Cancer. 2013;doi:10.1002/cncr.28168.
Tsodikov A, et al. Cancer. 2017;doi:10.1002/cncr.30687.
For more information:
Michael K. Brawer, MD, can be reached at Myriad Genetics Inc. 320 Wakara Way, Salt Lake City, UT 84108; email: mbrawer@myriad.com.
John D. Carpten, PhD, can be reached at University of Southern California, 1450 Biggy St., NRT G502, Los Angeles, CA 90089-9601; email: carpten@usc.edu.
Jennifer Cullen, PhD, MPH, can be reached at Norman M. Rich Department of Surgery, Uniformed Services University, 1530 E. Jefferson St., Rockville, MD 20852; email: jcullen@cpdr.org.
Ruth Etzioni, PhD, can be reached at Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 100 Fairview Ave. North, M2-B230, Seattle, WA 98109-1024; email: retzioni@fredhutch.org.
Edward M. Schaeffer, MD, PhD, can be reached at Northwestern Memorial HealthCare, 541 N. Fairbanks Court, Suite 18-1850, Chicago, IL 60611; email: edward.schaeffer@nm.org.
Disclosure: Brawer reports employment as senior vice president, medical affairs, of Myriad Genetics Laboratories. Carpten, Cullen, Etzioni and Schaeffer report no relevant financial disclosures.