H. Ballentine Carter, M.D., was awarded the 2016 Huggins Medal from the Society of Urologic Oncology. The award is named for Charles Huggins, who in 1966 was awarded the Nobel Prize for his discovery that hormonal therapy could control prostate cancer. This is the Society’s highest honor, given in recognition of Carter’s lifetime contributions in research and clinical practice.
If you’re thinking about active surveillance (AS), it’s important to understand that for many men, AS doesn’t last forever. That’s why all those follow-up biopsies are so important: prostate cancer can change over time, and a low grade – grade group 1 or Gleason score 6 – may creep higher. “It is important for men considering surveillance to have a clear understanding of the risk of grade reclassification and the chance of cure if that should occur,” says H. Ballentine Carter, M.D., the Bernard L. Schwartz Distinguished Professor of Urologic Oncology and the urologist who pioneered AS.
Active surveillance is a great option for many men with low-grade prostate cancer. The important caveat: Your situation may change over time.
That said, AS is more popular than ever, and deservedly so, Carter adds. “The new American Urological Association guidelines for prostate cancer state that for men with low-grade prostate cancers (grade group 1 or Gleason score 6) discovered early, active surveillance is the best care option. In fact, it is likely that soon, more men in this group will choose AS than surgery or radiation therapy.” But again, there’s that caveat: your situation may change over time.
Carter and colleagues have closely followed men enrolled in the Hopkins AS program for more than 15 years. “We have shown that grade progression occurs in approximately one in three men, that 95 percent of those with grade progression have grade group 2 (Gleason score 3+4), and that only 5 percent of men will be found to have grade group 3-5 or Gleason scores 4+3 or higher. That means the longterm risk of progression to grade group 3 or higher is only 1.5 percent, and progression to grade group 2 is less than 29 percent.”
Who’s at higher risk? There are some predictive factors, including high PSA density and the number of cancerous cores, Carter says. His team’s latest research has found one more clue: age at diagnosis.
“Older men are more likely to harbor aggressive prostate cancer, and more likely to die of prostate cancer than younger men,” says Carter. Even older men diagnosed with low-grade cancer: in a recent study, urology resident Sasha Druskin, M.D., and Brady epidemiologist Bruce Trock, Ph.D., evaluated more than 1,600 men aged 41 to 81 in the Hopkins AS program. After accounting for factors including race, PSA density and the amount of cancer at diagnosis, older age remained a key risk factor for grade reclassification. “We found that men age 70 or older at diagnosis had more than a twofold greater risk than men younger than 60 of being reclassified to grade group 2,” says Carter. Men between age 60 and 69 had a 1.4-fold greater risk.” Further, the likelihood of having a higher grade – grade group 3 or above – was threefold higher for men age 70 or older than for men younger than 60, and 1.8-fold higher for men between 60 and 69.
The findings also prompted a new question, Carter notes. If a man’s grade changes during surveillance, has he waited too long to be treated, “allowing the window of cure to close?”
Hopkins medical student Clarisa Diniz, working with Brady biostatistician Mufaddal Mamawala, addressed this question. They compared the rate of cancer recurrence after radical prostatectomy in men whose grade changed during AS to that of men who were diagnosed with a similar grade of disease and underwent prompt surgical treatment. “We hypothesized that men on surveillance would actually have lower rates of cancer recurrence, because our AS patients are very carefully selected for the presence of low-volume cancers,” Carter says. This proved true. “We found that men on surveillance had lower rates of PSA recurrence after surgery than men who underwent immediate surgery for grade groups 2 or greater. Thus, enrolling in surveillance – after being carefully selected – does not appear to raise the risk of losing the opportunity for cure, should treatment become necessary.”
Is active surveillance right for you? “For many men with low-risk prostate cancer, active surveillance (AS) is an ideal approach,” says Brady resident Jeffrey Tosoian, M.D. “However, it’s important to note that all low-risk cancers are not the same.”
Tosoian and a team of Brady investigators recently compared cancer characteristics of low-risk patients who enrolled in AS to those of men who underwent immediate radical prostatectomy. H. Ballentine Carter, M.D., the Bernard L. Schwartz Distinguished Professor of Urologic Oncology and the urologist who pioneered active surveillance at the Brady, led the study. Investigators also included Mufaddal Mamawala, Hiten Patel, Ridwan Alam, Jonathan Epstein, and Ashley Ross.
“Insignificant” cancer: Prostate cancer is considered pathologically “insignificant” if it is detected in fewer than three of 12 biopsy needle cores, and in less than half of all positive samples. “We found that the proportion of men meeting the ‘insignificant’ criteria was significantly higher – 73 percent vs. 18 percent – in men who chose AS than in men who were treated with surgery,” says Tosoian. “Furthermore, only 8 percent of AS patients had 4 or more positive biopsy samples, as compared to nearly half of the surgery group.”
“Low-risk men who have done well on AS at Hopkins have been “a distinct group of patients with a limited amount of cancer.”
The authors concluded that low-risk men who have done well on AS at Hopkins have been “a distinct group of patients with a limited amount of cancer. While many men with more extensive low risk cancers could do very well on AS, our experience has not yet tested this possibility.”