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VA Research Currents archive
September 10, 2015
Clarence Massey visits with radiation therapist Nader Girgis, who was part of his treatment team at the Brooklyn campus of the VA NY Harbor Healthcare System. (Photo by Mitch Mirkin)
It was in early 2010 that Clarence Massey first sensed something wasn't right. He didn't know it yet, but there was a tumor growing in his prostate gland. It was far enough along to start interfering with normal urination.
Massey lives in the historic Harlem neighborhood of New York City, just north of Central Park. He went to see his VA doctor in Manhattan and was sent to a urologist.
"They took bloodwork and urine samples," says Massey, now age 68. "I came back and they told me they think something may be wrong. So I had a biopsy. All this time, I was a bundle of nerves. I went back in and they told me it was positive."
He then went for a consult with cancer specialists at the Brooklyn VA. Both sites are part of the VA New York Harbor Healthcare System.
There are several treatment options for prostate cancer; Massey ended up doing nine weeks of external beam radiation. The treatment itself wasn't bad, he recalls: "Going through it was beautiful. I was singing."
The side effects, afterward, were a different story. "They hit me like a ton of bricks," says Massey. He couldn't control his urination. Sleeping was a challenge. He grew weaker.
The side effects waned after a couple of months. "I started coming around. I started feeling better and better."Fast-forward to 2015, and Massey now comes to the Brooklyn VA only once a year, to be checked by his cancer specialist—and to visit with the therapists and support staff who helped him through his crisis.
"I'm so grateful to the doctors here, and to the guys who work the radiation machine," shares Massey. "Every time I come here I stop back there to thank them again. It was a team effort. Everyone here was so kind."
Dr. David Schreiber, who treated Massey, also does research, and one of the questions his group has looked at is the role of race in prostate cancer. Their studies are part of a growing body of research attempting to answer questions that are critical for men like Massey: Do African American men, by dint of their DNA, have more aggressive tumors? And should their doctors, accordingly, take a more aggressive approach in tackling their disease?
What researchers know for sure is that African Americans are at higher risk for prostate cancer in the first place. They tend to be younger, on average, than white men when they are diagnosed—by about three years. Their tumors appear to be larger and faster-growing. Their blood levels of prostate-specific antigen—a common, if somewhat unreliable, marker for prostate cancer—tend to be higher. And they are more likely to die from the cancer—up to three times as likely.
What is unknown is whether all this is a function of race per se. Perhaps race is really a marker for lower income. Could it be that black men simply don't get the same access and quality when it comes to health care? That could explain why their tumors are more advanced when they first get in to see a doctor.
Most experts say the access factor probably accounts for part of the picture, but not all of it.
"The socioeconomic factors are definitely a component," says Schreiber. "There are patients who are getting diagnosed later, or not being treated. Some can't afford the co-pays."
Research suggests that VA and other "equal-access" health care systems do help level the playing field. They help erase the racial survival gap for men with prostate cancer.
A group at the VA Connecticut Healthcare System reported in 2013 that "mortality among black and white patients with prostate cancer is similar in equal-access healthcare systems." The conclusion was based on five previous studies done in the Department of Defense and VA health systems, and in England, where health care is basically free to all citizens. The team also collected original data on 1,270 Veterans followed for up to 16 years at nine VA sites.
More recently, a team with VA and UCLA studied more than 1,200 California Veterans with prostate cancer and found "no significant differences in tumor burden, treatment choice or survival outcomes between African Americans and Caucasians cared for in the equal-access VA health care setting."
On the other hand, several studies do point to biological differences between black and white men with prostate cancer. For instance, in 2011, a team with VA and Duke University found higher levels in black men of "aggressive disease biomarkers." The study used biopsied tissue from 131 men treated at the Durham VA Medical Center. Though the researchers admitted larger studies are needed, they say the findings provided "additional evidence that prostate cancer in black men may be biologically different than prostate cancer in white men."
One of the most comprehensive reviews to date of racial differences in prostate cancer, published in 2012, concluded that the "disparities seem to be complex in nature, involving biological, socio-economic and socio-cultural determinants."
In certain other diseases, the role of race—particularly its biological effects—seems clearer. For example, heart doctors know that African Americans and whites respond differently to warfarin, a commonly used blood thinner.
In a recent article about the drug, Dr. Elvin T. Price, a pharmacist with VA and the University of Arkansas for Medical Sciences, talked about "ancestry-informed genotype-guided strategies" as a way to boost warfarin's efficacy and limit its toxicity. In other words, at least for certain conditions, patients' racial or ethnic ancestry—along with their genetic profile—should be factored in to treatment plans.
For prostate cancer, though, the evidence on race, especially how it affects disease progression, remains murky. Schreiber, along with his colleague Dr. David Schwartz, chief of radiation oncology at the Brooklyn VA, and their team are among those working to solve the riddle.
A study they published in August 2015 in the journal Clinical Genitourinary Cancer looked at data on nearly 1,800 men from the national Surveillance, Epidemiology and End Results (SEER) database. They expected to find significant differences between blacks and whites in factors like the Gleason score, which basically tells how aggressive a prostate tumor is. The higher the score—the closer to 10—the more abnormal the cancer cells look under a microscope, and the more likely they are to spread. But the study found that the black and white patients were more alike than expected, from a pathology standpoint. There was little to suggest that prostate cancer takes a more aggressive course in black men.
"We couldn't detect much difference," says Schreiber. He notes that the finding contrasted with those from previous studies looking at the same question, but those studies were much smaller.
"We could now look at larger samples," says Schreiber, "but the findings from the smaller studies were based on samples of only around 60 or 100 men, so we think we have strong evidence. You would think that if there really is a significant difference, it would show up in 1,800 patients."
One limitation of Schreiber's study, though, is that the SEER data reflected only a snapshot in time. The men were all biopsied and underwent removal of the prostate relatively soon after diagnosis. Had they been left untreated, could it be the black men would have fared worse?
"It could be that that the disease was not yet aggressive at this early stage, when it was detected and treated. It could potentially convert later on and become more aggressive," notes Schreiber.
Another possibly he suggests is that African Americans could have more "micrometastatic" disease. "This means the cancer has made its way out of the prostate and into the bloodstream and deposited itself somewhere," explains Schreiber, "but it's so microscopic that it's undetectable. It could pop up years later."
Clarence Massey talks with Dr. David Schreiber, who cared for him during his bout with prostate cancer and continues to provide follow-ups. (Photo by Mitch Mirkin)
The real question for Schreiber's group is whether blacks are equally good candidates for a treatment strategy known as active surveillance. Actually, it's not so much a treatment at all. Formerly known as "watchful waiting," it involves closely monitoring and testing the patient over time, to see if the disease is progressing or not. In most cases, prostate cancer grows slowly and causes no problems. More men will die with the disease than from the disease. Many men can go without treatment and never suffer any symptoms. They are fortunate, since treatment could involve grim side effects such as impotence and incontinence. For those affected, quality of life can plummet.
Active surveillance has caught on as experts have come to see the risks of over-diagnosing and over-treating prostate cancer—namely, those slow-growing tumors that are unlikely to cause any harm during the patient's lifetime. According to a recent study led by Dr. Matthew Cooperberg, with VA and UCSF, between 1990 and 2009, fewer than 10 percent of men with low-risk prostate cancer were treated with active surveillance. For the period between 2010 and 2013, the figure jumped to 40 percent.
The challenge is figuring out which tumors don't fit this milder picture, and whether blacks are more likely to be in that category. For those with aggressive tumors, timely treatment can prevent an early death.
Says Schreiber: "The question is whether African Americans should have the same criteria for active surveillance as everyone else. Maybe their disease is by nature more aggressive, and they can't be safely surveilled—or maybe only a subset of these men can be safely surveilled, and the rest need treatment."
Even as they sift through all the conflicting findings, researchers like Schreiber seem to agree that biomarkers are the wave of the future—for prostate cancer as well as many other diseases. Doctors will prescribe treatment based on the specific proteins or other molecules found in a patient's blood—as determined by his or her genes. This is already happening, to an extent, with breast and lung cancer.
Schreiber cites a study just out in the Journal of Clinical Oncology in which researchers tested 20 previously established biomarkers of prostate cancer to see which, if any, showed up more frequently in African American men, versus those of European ancestry. The team, led by Dr. Kosj Yamoah at the H. Lee Moffitt Cancer Center in Tampa, came up with a final set of six markers that were in fact more common in the black patient sample. The researchers say their results "show that there are differences in the biology … of prostate cancer in African American men compared with European American men that affect" both diagnosis and treatment. "The ability to identify a subset of African American men who harbor aggressive disease will enable clinicians to more accurately risk stratify these patients for appropriate treatment recommendations."
The biomarker panel may still need to be tested in larger groups of men, but Schreiber says "something like this will be the future. How fast we'll get there, I don't know. But that's the goal for every type of cancer. We'll be able to individualize care and say, OK, you have these biomarkers, you get this treatment."
Yet even with this type of gene-based "precision" or personalized medicine, race may not drop out of the equation totally. As in the Yamoah study, certain biomarkers may serve to sort out low-risk from high-risk patients only within a particular racial or ethnic group, rather than for patients at large.
Flip it around, though, and you realize that race itself is merely a function of genetics. As Schreiber puts it: "Race is what we see, but underlying that is the genetics. That's what we don't see and don't yet fully understand. And that's what really dictates what's going on."
That point may be especially relevant for mixed-race patients. However these patients may identify racially, the bottom line for their doctors will be what proteins are expressed in their bodies, and in their tumors. If the patient's ancestry—as straightforward or as blended as it may be—can somehow help point to the right diagnosis and treatment, all the better.
Schreiber says that for now, his clinic "doesn't differentiate by race. We use the current standards, which are PSA, Gleason score, and physical exam to stratify patients. We don't necessarily say that because you're African American, you're automatically intermediate or high risk. That is not proven yet. It's developing research."
He adds: "From a treatment standpoint, if we offer a patient more aggressive treatment, such as hormones along with radiation, that would eliminate testosterone in the body for a certain period of time, and that entails certain side effects: loss of sex drive, inability to maintain an erection, hot flashes, swelling of the breasts, all of which men obviously don't want. There are also more serious side effects, such as heart disease. So to throw that at them just because they're African American—we don't have the data to support that."
For his part, Clarence Massey is glad to be over his ordeal, and thankful he and his team chose the right treatment. "I give credit to them, but mostly I give credit to God," he says. "I am blessed."
