Discovery
January 22, 2016

The Brady's Active Surveillance program has reached a milestone: 20 years of carefully following men with low-risk prostate cancer. "What we have learned since 1995 can help many men with low-grade, low-risk prostate cancer, and their doctors, determine their best course of treatment," says urologist H. Ballentine Carter, M.D., the Bernard L. Schwartz Distinguished Professor of Urologic Oncology, a pioneer in the active surveillance of prostate cancer. "There is increasing evidence that monitoring favorable-risk prostate cancer does not lead to worse outcomes when compared to immediate treatment. This is good news for the majority of men diagnosed today."

When the Active Surveillance program first started, "many urologists believed this approach was ill-advised for any man with a diagnosis of prostate cancer," Carter notes, "for fear of losing the opportunity to be cured. Virtually every man diagnosed — more than 90 percent — was treated with either some form of radiation or surgery. All this has changed, in large part to a better understanding of what happens to men with favorable risk prostate cancer who remain untreated." Brady resident Jeff Tosoian, M.D., M.P.H., and Mufaddal Mamawala, the biostatistician in charge of keeping track of men in the Brady's Active Surveillance program, recently reported on what happened to men who, over the last 15 years, entered this program rather than undergoing immediate treatment. They delivered their findings at the American Urological Association's 2015 meeting in New Orleans; their results were published online September 1 and fast-tracked for publication in the Journal of Clinical Oncology. About 1,300 men have entered the program so far. Their average age is 66, Carter says, and two-thirds of these men entered with "very low-risk prostate cancer." They had Gleason score 6 cancer in no more than two biopsy cores; cancer was present in 50 percent or less of each core; their PSA density (PSA divided by prostate volume) was 0.15 or less; and they had no cancer that could be felt on a rectal examination. The remaining one-third of these men had "low-risk" prostate cancer. This means that they had no cancer that could be felt on a rectal exam, a PSA below 10 ng/ml, and Gleason 6 cancer on their biopsy.

"A number of interesting findings from this update should help inform men regarding the safety of active surveillance," says Carter. "First, we can now tell men that if they qualify for the active surveillance program and are monitored carefully, their risk of dying from another cause instead of prostate cancer over the next 15 years after diagnosis is 4 percent (24 to 1). Fewer than 1 percent — only 0.4 percent, (a risk of 250 to 1) — of men in our active surveillance program either died of prostate cancer or developed advanced disease. Second, over 15 years, fewer than 5 percent of these men developed a more serious grade of cancer (Gleason 4+3 or above)." The key here is who is eligible for the program: the criteria are very specific, making sure that only men with the least risk of having aggressive cancer even get enrolled. Also, these men are monitored faithfully, with regular follow-up visits and biopsies.

The key here is who is eligible for the program — only men with the least risk of having aggressive cancer. Also, these men are monitored faithfully, with regular follow-up visits and biopsies. 

ACTIVE SURVEILLANCE: A TAILOR-MADE APPROACH?

"In our program, we have generally recommended relatively intense monitoring, with prostate biopsies done annually for most men," says Carter. However, it may be that some men could be monitored safely with a longer interval between biopsies. In a recent study using data collected over the last 15 years in the Active Surveillance program, Hopkins medical student Ridwan Alam and biostatistician Mufaddal Mamawala examined the likelihood that a man in active surveillance will eventually be diagnosed on biopsy with a higher-grade cancer that would likely need treatment. Their results were published in the Journal of Urology.

They found that the risk of "grade reclassification" — finding a higher grade of cancer on biopsy — is highest during the first two years on surveillance. "About half of all grade reclassification occurs then, in men with both very low-risk and low-risk disease." This is thought to be because the first biopsy or two might simply have missed higher-grade cancer that was there all the time. Grade reclassification also occurred, outside those first two years, in men with "low-risk," instead of "very low-risk" disease. Another striking finding: With each prostate biopsy that showed the cancer was holding steady, still indolent, and with no change in grade, the risk of finding more aggressive disease fell by 30 percent.

Carter and colleagues have used these findings to construct a risk calculator for men on active surveillance. It will be available soon, and will be easy to use, Carter says. "Men and their physicians will put in the year of diagnosis, age, PSA density, whether or not the cancer was found on one or both sides of the prostate, and total number of biopsies without reclassification. The calculator will then estimate the risk of finding a higher grade of cancer at the next biopsy." Using this risk-assessment tool, Carter has found that 30 percent of men in the Brady's active surveillance program have "less than a one-in-10 chance that a repeat biopsy in the next year would show higher-grade cancer." And 25 percent have a one-in-four risk of grade reclassification at the next biopsy. "Thus, for men at lowest risk, a prostate biopsy may be deferred for several years."