Researcher Explores Biologic Basis for Disparities in Prostate Cancer Outcomes

Kosj Yamoah, MD

A subset of biomarkers may predict the risk of clinicopathologic outcomes in an ethnicity-dependent manner, which may in turn explain ethnic disparities in prostate cancer outcomes between European and African-American men.

Results of a study presented at the 2015 ASCO Annual Meeting showed that 6 biomarkers—ERG, AMACR, SPINK1, NKX3-1, GOLM1, and androgen receptor—demonstrate a statistically significant differential expression in African-American patients versus European patients.¹

OncLive: What intrigues you about health disparities in prostate cancer?

In an interview with OncLive during the 2016 OncLive State of Science Summit on Genitourinary Cancers, Kosj Yamoah, MD, a radiation oncologist at Moffit Cancer Center and lead author of the above-mentioned studies, discussed some of these health disparities in prostate cancer and unanswered questions researchers still need to tackle.Yamoah: I have been passionate about the disparities in prostate cancer. The data across the board show that African-American men or men of African descent have a 1.6-fold increase in incidence of prostate cancer and about a 2.4-fold increase in mortality in prostate cancer. When looking at those 2 numbers, we recognize that there are 2 questions that come up. Why are they getting prostate cancer more than the average population, and why are they actually dying from prostate cancer much more? Also, the age that they get prostate cancer is a slightly younger age.

It is easy to look at all of this under more fair access or socioeconomic [status]. However, when examining the data a little more strongly, it really begins to point to a more biologic component of the disease that might not be clear. Therefore, I am beginning to study that.

What results have you seen so far?

The interesting part of this whole research is that, over the last few years, we have identified that prostate cancer is also a big problem among men living in Africa and in the Caribbean. It really points to more of a genomic basis for this, and that’s something that I’m studying currently.We have done a number of studies that have identified some biomarkers. The biomarkers—called specific gene mutations within the prostate cancer genome—are more prevalent in men of African descent compared with men of European ancestry. Therefore, we believe that, with further research, we will be able to use this information to personalize treatment.

What are some key concepts for community oncologists to be considering in this area?

With these specific gene targets, are they first gene targets that could be therapeutic, or are they just going to be used as stratification models? What I mean by stratification models is that, if a patient has this set of mutations, then he needs to be treated less or more aggressively because there’s an increased risk of disease recurrence. We can use that information to stratify patients for treatment, or we can actually look for those targets and see if we can actually use them to get new therapeutic agents to treat the disease better. There are a lot of avenues there, and that’s kind of the direction we are going.A lot of it has to do with the fact that medicine is really moving towards a more personalized [approach] where we don’t want to treat everyone with just one big regimen. What is the genomic makeup of the person and how can we really use that information to treat patients?

The message we want to carry across to the general oncologist is to begin paying attention to the patient who is coming in with the diagnosis—particularly for disparities in medicine. What are the unique characteristics of this patient that might require the oncologist to act differently, in terms of their treatment?

Classic example: the United States Preventative Task Force has issued a recommendation that we should not screen for PSA because there’s been [cases of] overtreatment. Yes, but then the problem with that recommendation is that the data predominantly come from men with prostate cancer from European ancestry. Now, what we are beginning to see is that, because of lack of screening, they are not picking up prostate cancer early enough in the African-American population. They are coming in with more advanced disease because we are not screening at age 40 or 50, even though they might have a pertinent family history of prostate cancer.

What are some questions you still want to answer in this area?

The community physicians and colleagues need to come together and get better educated on some of these differences in genomic risk, particularly with prostate cancer. That is an area of intense investigation and some controversy.The biggest question right now is, “What is the optimal regimen for a patient with prostate cancer from African ancestry, and is our current treatment regimen the best?” If not, how can we improve it?

References

1. Yamoah K, Johnson MH, Choeurng V, et al. Novel biomarker signature that may predict aggressive disease in African American men with prostate cancer. J Clin Oncol. 2015;33(25):2789-2796.
2. Yamoah K, Walker A, Spangler E, et al. African-American race is a predictor of seminal vesicle invasion after radical prostatectomy. Clin Genitourin Cancer. 2015;13(2):e65-72.

Other analyses have explored the disparities in prostate cancer. For example, it was found that African Americans, especially those with a Gleason score ≤6, may have an increased risk of seminal vesicle invasion after undergoing radical prostatectomy. This may be a representation of racial differences in the biology of prostate cancer’s disease progression, contributing to poorer outcomes.²