Mitchell C. Benson, MD, PhD
Active surveillance is increasingly employed in men diagnosed with low-risk prostate cancer despite a lack of high-level clinical trial evidence supporting this approach, and physicians should engage in careful patient selection before recommending the strategy, according to Mitchell C. Benson, MD.
That note of caution was among the key points that Benson stressed during a presentation on localized prostate cancer that he delivered at the 8th Annual Interdisciplinary Prostate Cancer Congress in New York City.
“In terms of local therapies, radiation therapy and radical surgery remain effective treatments but it’s the active surveillance that we have to be most careful of if we want to do no harm to our patients,” said Benson, who is the Herbert and Florence Irving Professor at Columbia University Medical Center, New York-Presbyterian Hospital.
“The question is, can we delay treatment without compromising curability and that’s the dilemma,” Benson said in an interview. “We need to make sure that we are not compromising curability and we don’t know that with 100% certainty.”Treatment Patterns and Evidence
Benson said that the proportion of newly diagnosed patients who do not undergo radiation or surgery has increased dramatically in recent years. Researchers who examined two large US databases found that noncurative initial management for patients with low-risk disease increased from 13%-21% in 2004, depending on the database, to 20%-32% in 2010.1
Yet although the use of the strategy has increased, the supporting evidence is derived primarily from expert opinion or bench research and not from randomized clinical trials, said Benson.
“Although there is a tremendous amount of information and stress and urgency to not treat, the reality is that we don’t have a lot of level 1 evidence that no treatment is the appropriate thing,” he said. “We’re being pushed toward active surveillance and we really don’t know with any degree of certainty that we’re not doing harm.”
Indolent prostate cancer has been defined since 1994 as a Gleason score ≤6, PSA density <0.150 ng/mL/g, <3 cores involved, and <50% of any single core involved,2
Several studies have supported active surveillance for this patient population, Benson noted. He said Dall’Era et al3
found a low rate of prostate cancer–specific mortality ranging from 0.2% to 1% in a study of patient outcomes from seven institutions. However, Benson said the median follow-up was short, ranging from 1.8 years to 6.8 years.
Benson pointed instead to a study of long-term outcomes of 945 patients with low- or intermediate-risk prostate cancer who were managed with an active surveillance protocol at Sunnybrook Health Sciences Centre in Toronto between 1995 and 2013.4
Intermediate risk was defined as a PSA >10ng/ml, Gleason score 7, or clinical stage T2b/2c.
Patients with an intermediate risk experienced lower rates of overall survival compared with low-risk patients at 10 years (68.4% vs 83.6%, respectively) and at 15 years (50.3% vs 68.8%, respectively).
Notably, Benson said, intermediate-risk patients had a lower rate of prostate cancer–specific survival (CSS). The CSS rates for intermediate-risk patients were 95.5% at 10 years and 88.5% at 15 years, compared with 98.2% at 10 years and 96.3% at 15 years for low-risk patients. That translated into a CSS risk that was 3.75 times higher for patients in the intermediate group, Benson said.
“We can do a good job even with intermediate-risk disease as it relates to prostate cancer specific survival but the numbers are getting small, the confidence intervals are stretching, so we have to be careful,” said Benson.
Benson sharply criticized the conclusions of another study, the PIVOT trial, which found that radical prostatectomy did not significantly reduce all-cause mortality compared with observation among men with localized prostate cancer through 12 years’ follow-up.5
He said the conduct of the trial and the patient selection were seriously flawed. “This study should never have been accepted for publication,” he said.Selection Strategies