In a groundbreaking recommendation, the National Comprehensive Cancer Network (NCCN) has broadened the scope of prostate cancers that qualify for active surveillance in the United States to include men with "favorable" intermediate-risk disease.
"I think this is a very big deal," said James Mohler, MD, a urologist from Roswell Park Cancer Institute in Buffalo, New York, who is chair of the NCCN prostate cancer guideline panel.
The recommendations of the NCCN are often followed by clinicians, insurers, and institutions, and the NCCN is the first major organization in the United States to make this recommendation.
Active surveillance includes ongoing disease monitoring (with prostate-specific antigen [PSA] testing, biopsies, and imaging), but does not include definitive treatment, such as surgery or radiation, or related harms, such as erectile dysfunction and incontinence.
To date, the NCCN and other organizations, such as the American Urological Association, have recommended active surveillance only for very-low-risk and low-risk prostate cancers.
But the NCCN is now recommending active surveillance for intermediate-risk prostate cancer with a Gleason score of 7 (3+4), which is considered favorable. In other words, the grade 3 prostate cancer is predominant (accounting for at least 50% of the biopsied tissue) and the grade 4 is secondary (accounting for at least 5% but less than 50%).
Favorable intermediate risk also requires that less than 50% of a man's biopsy cores are positive, and that he has no more than one NCCN intermediate-risk factor. Those risk factors include a tumor stage of T2b to T2c and a PSA value of 10 to 20 ng/mL.
The new NCCN recommendation does not include active surveillance for "unfavorable" intermediate-risk cancer, such as that with a Gleason score of 7 (4+3).
The guidance is "especially good for older patients and those with more comorbidities," Dr Mohler explained. Strictly speaking, the intermediate-risk recommendation is for men with a life expectancy of less than 10 years, but the approach can also be considered for younger or more vital men, he noted.
Resistance From Clinicians and Patients
The new guidance might not be warmly welcomed by all clinicians. "There will be a fair amount of resistance to this," Dr Mohler told Medscape Medical News.
Another prostate cancer expert agreed, and upped the ante by predicting a negative reaction.
"I think there's going to be a lot of backlash from doctors and patients," said William Dale, MD, from the Departments of Urology and Geriatrics at Northwestern University in Chicago.
"It's already a challenge to explain to patients that low-risk prostate cancer may not need treatment," Dr Dale told Medscape Medical News. Raising the level of risk will only make those discussions more difficult, he said.
Dr Dale said that two issues are likely to make men "nervous" about intermediate-risk surveillance: the absence of the relatively comforting concept of "low risk"; and the fact that cancers with a Gleason score of 7 are more likely progress than low-risk cancers with a Gleason score of 6.
But Dr Mohler pointed out that "there appears to be little or no harm of active surveillance for a duration of 2 years" in men with very-low-, low-, or favorable intermediate-risk prostate cancer who then transition to curative active treatment.
"Anything we can do follow the 'do no harm' directive, we should do," he said.
The use of active surveillance in select men with intermediate-risk prostate cancer has been underway for years at major academic centers, such as the University of California, San Francisco.
However, the new NCCN recommendation is a "little more inclusive than what many urologists have used for selecting these [favorable intermediate-risk] patients," said Dr Mohler.
Specifically, it is "more liberal" in terms of the percentage of positive biopsies it allows and, thus, will allow an even higher percentage of intermediate-risk patients to be monitored with active surveillance, he explained.
The recommendation is based on a radiation oncology study in which 1024 patients with intermediate-risk prostate cancer underwent radiotherapy with or without androgen-deprivation therapy (Eur Urol. 2013;64:895-902).
In that study, Zachary Zumsteg, MD, from the Memorial Sloan Kettering Cancer Center in New York City, and colleagues analyzed recurrence-free survival and distant metastases outcomes, and concluded that intermediate-risk disease is "heterogenous," with "favorable and unfavorable subsets" — groupings that the NCCN is now using.
Last year, the idea that active surveillance should be used in favorable intermediate-risk disease was endorsed by Ann Radlow, MD, from the Harvard Radiation Oncology Program in Boston, and her colleagues, as reported by Medscape Medical News.
In their observational study, Dr Radlow's team compared 3972 men with low-risk prostate cancer with 1608 men with favorable intermediate-risk prostate cancer, all of whom were treated with brachytherapy at the Prostate Cancer Foundation in Chicago from 1997 to 2013 (JAMA Oncol. 2015;1:334-340). They found that rates of prostate-cancer-specific mortality and all-cause mortality were similar in the two groups, and concluded that this finding provides "evidence to support active surveillance as an initial approach for men with favorable intermediate-risk prostate cancer."
When men with prostate cancer are monitored, determining the criteria by which to define progression presents a challenge. Dr Mohler noted. The three major North American centers with the largest cohorts of active-surveillance patients have all used different criteria. The ongoing Canary Foundation's Prostate Active Surveillance Study, which began in 2008, should help clarify some of this murkiness, he said. "There's a lot not known" about the optimal undertaking of active surveillance, he added.
NCCN Has Led the Way
The NCCN Prostate Cancer Panel, under the direction of Dr Mohler, has been at the leading edge of active-surveillance recommendations for some time. In 2010, the NCCN was the first organization to recommend active surveillance as the sole initial therapy for many men, as reported by Medscape Medical News.
"I'd like to believe that the NCCN has made active surveillance more acceptable," Dr Mohler said.
The use of active surveillance has increased in recent years in the United States. Estimates range from a high of 50% of men with low-risk prostate cancer in Michigan, where an insurance-industry-funded awareness program is underway, to a low of 8% nationally, Dr Mohler reported.
Another estimate of the prevalence of the practice comes from CaPSURE, a prostate cancer registry that has been collecting data on men managed at 47 clinical, primarily community-based, sites. An analysis of the data collected from 2008 to 2013 showed that the primary treatment of 38.4% of men with low-risk tumors was watchful waiting or active surveillance, as reported by Medscape Medical News.
The United States has lagged behind certain European countries in the adoption of active surveillance. As of 2013, the use of active surveillance in Sweden was 78% for men with very-low-risk disease and 59% for men with low-risk disease, said Stacy Loeb, MD, from New York University in New York City, who presented results from Sweden last year at the annual meeting of the American Urological Association
Dr Mohler and Dr Dale have disclosed no relevant financial relationships.
Medscape Medical News © 2016 WebMD, LLC
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Cite this: 'Very Big Deal': NCCN Okays Watching More Prostate Cancer - Medscape - Jan 13, 2016.