Tissue-Based Assay Tests Similarly Across Racial Lines in Newly Diagnosed Prostate Cancer

Eric A. Klein, MD

To improve upon risk stratification for men with newly diagnosed prostate cancer, tissue-based molecular diagnostic assays like the Oncotype DX Genomic Prostate Score (GPS) assay have recently been introduced in the prostate cancer field. However, before their use becomes widely adopted in clinical practices, researchers believed that is was important to ensure that African American males who are at high risk for prostate cancer have equal detection results to Caucasian males.

Research has shown than African American and Caucasian men have different molecular profiles which include varying gene expression patterns. Little is known, however, about how these differences impact clinical outcomes or whether testing should be approached the same way for both patient groups. To determine this, a retrospective comparison of GPS results from 6 independent cohorts was analyzed.

Overall, 1345 patient records were evaluated, 201 of which belonged to African American men and 1144 of which belonged to Caucasian men. The results of the analysis showed similar predictive outcomes of aggressive prostate cancer in both racial groups. Based on this finding, the investigators of the analysis consider the Oncotype DX to be appropriate for use in both Caucasian and African American patients.

In an interview with Targeted Oncology following the American Urological Association (AUA) Virtual Annual Meeting, Eric A. Klein, MD, chairman, Glickman Urological & Kidney Institute, and staff member, Taussig Cancer Institute, Cleveland Clinic, discussed the importance of molecular testing in Caucasian and African American patients with newly diagnosed prostate cancer. He also discussed the pros and cons of active surveillance.

TARGETED ONCOLOGY: Can you discuss prognostic molecular assets for prostate cancer in general? Is this testing widely adopted and why is it so important to do these tests in different racial groups?

Klein: Like many tumors, we now have these tools where we can look at the genome of prostate cancers and, in general, there are 2 ways of doing that. One was is to look at men with metastatic disease where genotyping the metastatic tumor can dictate treatment. For example, the FDA just approved a new drug called rucaparib (Rubraca), which is a PARP inhibitor that is

appropriate to use in patients whose tumors have BRCA mutations or men who are born with a BRCA mutation. It’s been shown to improve survival, so that's why we use them.

In the space that we're talking about, a few years ago, there were 4 products that were available on the market. The products helped determine molecular aggressiveness of early-stage prostate cancer and helped clinical decision-making in terms of deciding who's a good candidate for active surveillance. We needed to know who might need to be treated because of worrisome cancer hiding in the prostate that was missed by the initial biopsy, and who might benefit from early radiation treatments after radical prostatectomy.

TARGETED ONCOLOGY: Can you can provide background retrospective analysis presented at AUA with the oncotype DX genomic prostate test?

Klein: Oncotype DX is 1 of the tests that measures the expression of 17 genes through a biopsy with just a little bit of the tumor to help determine the aggressiveness of the cancer, and we have shown that it can predict the likelihood of getting metastatic disease or dying of prostate cancer 20 years out.

This test has been on the market for several years now and has been adopted by some people in the active surveillance cohort. What this abstract looked at was whether the test performed

equally well in Caucasian and African American men. That's important because African American men are at high risk for developing prostate cancer, and we needed to know if this particular tool was useful in determining tumor aggressiveness.

TARGETED ONCOLOGY: Can you explain the result of the analysis?

Klein: We looked at about 1300 men and had a smaller group of African American men than Caucasian men in 2 big systems from the Center for Prostate Disease Research in Washington, D.C. and the Kaiser Permanente in Northern California.

We compared head-to-head how well the biopsy-based assay predicted for the presence of aggressive disease in these 2 patients groups, and we found that the test performs equally well in both groups. That should reassure us that self-identified race is not an important consideration when using this test. Physicians can have confidence in the test for all groups of men.

TARGETED ONCOLOGY: Based on these results, how can this test guide treatment in patients with prostate cancer?

Klein: The intended use is in patients who are considering active surveillance, which is a management strategy for early-stage, low-grade prostate cancer that is shown to be very safe

over the last several decades. Active surveillance involves finding the right patient with the right tumor biology. Instead of treating them and subjecting them to the toxicities of treatment, you follow them and re-evaluate them on a periodic basis, typically every 6 months with a digital rectal exam and a prostate-specific antigen (PSA) test. Once a year, you re-evaluate with an MRI of the prostate and take another prostate biopsy.

These tests when done on an initial biopsy, or even on a subsequent biopsy, can help tell whether the tumor has become more aggressive and one might be comfortable with in continuing on surveillance. The potential downside of surveillance is that you miss a tumor that becomes more aggressive and needs to be treated. That doesn't happen often, but it's important to pick up on that.

The other thing you can do is if a biopsy shows a high score, you can look little harder to see if there's some higher-grade cancer that would dictate treatment in the prostate.

TARGETED ONCOLOGY: What further research is needed to improve the way prostate cancer is approached in specific racial groups?

Klein: The biggest unmet need for active surveillance is trying to figure out how intensively patients who start on surveillance need to be followed.

In 1 particular study at Johns Hopkins, which was among the leaders of recommending active surveillance for certain patients, going back several decades, 1000 patients were followed for 15 years, and those patients either did well Very few died, but the cost of having a biopsy done every year is over-kill. Biopsies are not pleasant for patients. There is also a measurable risk of bacteremia and sepsis.

We need better ways of figuring out when someone has progressed to a level where they need to be treated, and I think the way to do that is going to be with artificial intelligence and machine learning where we can put into algorithms, all the demographic information about the patient, their tumor information, their genomic and gene expression information, as well as their MRI and PSA test. That's the main unmet need, and there are several groups that are working on that approach.