AT THE AUA ANNUAL MEETING

NEW ORLEANS (FRONTLINE MEDICAL NEWS)Long-term active surveillance seems to be a safe and effective way to avoid overtreatment in men with low- and very low-risk prostate cancer, while still offering a very good chance of catching progressive disease.

According to new data presented at the annual meeting of the American Urological Association, less than 3% of men developed metastatic disease or died from prostate cancer over 15 years of follow-up. The men’s risk of progression dramatically declined over time, decreasing by 30% after each annual, unchanged biopsy.

The findings should reassure both physicians and patients, all of whom want to balance the potential side effects of prostate cancer treatment with the risk of progressive disease, said Dr. Stacy Loeb of New York University, New York.

“Physicians in the U.S. have been slow to adopt the practice of active surveillance, which is much more common in other parts of the world,” said Dr. Loeb, who moderated the press briefing where the data were unveiled. She has worked with Swedish researchers, who determined that 84% of men with very low-risk cancers and 66% of those with low-risk cancers are being managed this way. “The question we have to ask is why we have been so slow to adopt this. Hopefully, studies like these, showing so many men free of disease even at 15 years, will encourage greater acceptance in this country.”

The briefing highlighted several studies on active surveillance; two of these were performed on the Johns Hopkins Active Surveillance Program cohort, which has enrolled about 1,300 men since 1995. Most (71%) have very low-risk cancer; the remainder have low-risk cancer.

The Hopkins protocol calls for a clinical exam and prostate specific antigen (PSA) test twice a year, annual prostate biopsy, and imaging every either year, said Dr. Jeffrey Tosoian, a urology resident at the university.

Triggers for treatment include a change in biopsy or patient decision. Changes in PSA and clinical exam alone don’t trigger treatment, but may prompt a stepped-up monitoring schedule or additional diagnostic studies.

The Hopkins cohort is a fairly typical prostate cancer group. The patients’ mean age at diagnosis is about 66 years, and their mean PSA level is 5.2 ng/mL. Mean follow-up time is now 5 years, but Dr. Tosoian also presented 10- and 15-year data.

At 5 years, 36% of the group had converted to some form of treatment. By 10 and 15 years, conversion had occurred in 50% and 56%, respectively. Not surprisingly, the rate of death from any cause increased as patients aged, from 4% by year 5, to 7% and 31% by years 10 and 15.

But the rate of prostate cancer-specific death was very low throughout the study period: 0.15% at year 5 and 1% at years 10 and 15. Over the entire 15 years, less than 1% of the men died from prostate cancer or developed metastatic disease.

These findings were somewhat more positive than those recently reported by a team at Sunnybrook University, Toronto ( J. Clin. Oncol. 2015;33:272-7 ). That surveillance protocol is less stringent than the one at Hopkins, Dr. Tosoian said, with biopsies every 3-5 years, based on clinical findings and PSA levels.

In that cohort of 819 patients with a median follow-up of 6 years, 3% developed metastatic disease by 15 years and 1.5% died from it, but the men were nine times more likely to die from some other cause than their cancer.

“Certainly, our more intensive monitoring at Hopkins was associated with more treatment, but also with lower death and metastatic rates,” Dr. Tosoian said. “So there are still trade-offs in balancing overtreatment, but the real risk of cancer mortality is quite small.”

However, the question of how long must watchful waiting continue remains. Understandably, most men don’t want to commit to years and years of annual prostate biopsies, said Dr. Ridwan Alam, also of Johns Hopkins.

Dr. Alam presented 15-year data on 808 men who were completely compliant with the program ( J. Urology 2015;193:1950-5 ). Restricting the cohort in this way gives a much more accurate prediction; he said up to 18% of men without disease progression will drop out of active surveillance because they find the process onerous, especially the biopsies.

For the first 2 years of follow-up, the rate of disease reclassification was nearly 0% in both low- and very low-risk groups. “But after that, there was a pretty big gap developing between the two, with the low-risk group doing worse,” Dr. Alam said. By 10 years, 60% of the very low-risk group still had no disease progression; that number remained stable throughout the remainder of the study period. Among low-risk men, however, 60% did have a disease stage reclassification by 7 years; by 10 years, nearly 80% had progressed.

Despite that, the overall risk of reclassification declined sharply over time, decreasing by 30% after every stable biopsy. “If a patient reached 7-9 years without a reclassification, his risk of disease by 15 years was virtually 0,” Dr. Alam said. “This may help reassure men and their doctors about the risks of surveillance, and also reduce the dropout rate by giving them a sense of security – a sense that we really can trust the data and make good decisions based on it.”

Neither Dr. Tosoian nor Dr. Alam had any financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

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