January 14, 2010 — For the first time, the National Comprehensive Cancer Network's (NCCN) practice guidelines for prostate cancer recommend the use of active surveillance as the sole initial treatment — not just an option — for many men with prostate cancer.
Specifically, active surveillance should be offered as the one and only initial treatment to 2 groups of patients: men with "low risk" and a life expectancy of less than 10 years, and men with "very low risk" and a life expectancy of less than 20 years.
"This could be as many as 40% of all men diagnosed with prostate cancer in the United States," James Mohler, MD, chair of the NCCN Guidelines Panel for Prostate Cancer, told Medscape Oncology.
Dr. Mohler, who is also chair of the Department of Urology at Roswell Park Cancer Institute in Buffalo, New York, said the increased emphasis on active surveillance, also known as watchful waiting, comes as evidence emerges about both the problem of overtreatment and the value of active surveillance.
"Growing evidence suggests that overtreatment of prostate cancer commits too many men to side effects that outweigh a very small risk of prostate cancer death," he summarized in a press statement.
However, another expert in active surveillance, Peter Carroll, MD, MPH, who applauded the NCCN's promotion of the strategy, thinks that its approach needs modification. He also said that there is a lot at stake for urologists, "who may have the whole issue of prostate cancer taken out of their hands."
The NCCN stipulations about life expectancy are impractical, suggested Dr. Carroll, who is chair of urology at the University of California, San Francisco.
"Clinicians do not consult life-expectancy tables or do calculations. They look the patient in the eye and make an estimation — and they tend to overestimate," he told Medscape Oncology.
Life expectancy should not be an issue anyway, Dr. Carroll suggested.
"All low-risk men should discuss active surveillance with their doctors, including young men who are likely to live another 40 years," he said.
Currently, only 8% to 12% of all prostate cancer is treated with active surveillance, said Dr. Carroll.
Dr. Carroll suggested that urologists and their patients need to be educated about active surveillance before issues related to the treatment of prostate cancer go the way of prostate-specific antigen (PSA) testing. "The controversy over PSA testing is now being played out in many mainstream venues, like the New York Times and the Wall Street Journal, and not necessarily urology publications," Dr. Carroll said.
"One of the top 10 news stories of 2009 on CNN is about how men may not need to get a PSA test," he said. "I find that very disturbing," he added.
Dr. Mohler and the NCCN seem to share some of Dr. Carroll's sense of urgency. "The committee felt strongly it was time to say something," Dr. Mohler added.
Other experts stressed that patient and clinician acceptance of active surveillance will grow in time, especially as data mature.
dam Kibel, MD, who is an investigator in the Surveillance Therapy Against Radical Treatment (START) trial, the first-ever North American phase 3 trial comparing active surveillance and treatment, said there are unknowns. "We don't know if active surveillance is more effective than treatment [with radiotherapy or prostatectomy] as an initial intervention in these patients."
"It is wholly possible that either radical prostatectomy or radiotherapy is more effective," added Dr. Kibel, who is chair of urology at the Washington University School of Medicine in St. Louis, Missouri.
Dr. Kibel said that the use of active surveillance hinges on a bet.
"The bet is that we can detect disease progression before it causes the patient harm," he explained.
Both Dr. Carroll and Dr. Kibel said the risk of patient harm is very small in the context of well-executed active surveillance. "Patients need to understand that there is some risk," said Dr. Carroll.
The NCCN endorsement of active surveillance should give the approach a shot in the arm, suggested Grace Lu-Yao, PhD, MPH, cancer epidemiologist at the Cancer Institute of New Jersey in New Brunswick, and author of a recent study of men on watchful waiting.
"It's likely to help some patients and clinicians consider the option more seriously," she told Medscape Oncology. She pointed out that watchful waiting has been option has in various treatment guidelines, including those of the National Cancer Institute since "at least the early 1990s."
The NCCN on Choosing Men for Active Surveillance
The NCCN defines active surveillance, in part, as "actively monitoring the course of disease with the expectation to intervene if the cancer progresses."
Patients with a low risk are defined as having a stage T1 to T2a tumor, having a Gleason score of 2 to 6, and having a PSA level below 10 ng/mL.
Patients with a very low risk, which is a new designation for the NCCN, are listed as:
- having a stage T1a tumor
- having a Gleason score of 6 or below
- having a PSA level below 10 ng/mL
- having fewer than 3 positive biopsy cores (with <50% cancer in each)
- having a PSA density below 0.15 ng/mL per gram.
For men with a low risk for recurrence and less than 10 years of life expectancy, the recommended monitoring for disease progression is the same as for very-low-risk men with less than 20 years of life expectancy.
In each case, the NCCN calls for PSA testing as often as every 6 months and a digital rectal exam as often as every 12 months. Following a required initial needle biopsy, subsequent biopsy is optional and can be repeated within 18 months, especially if there were 10 or more cores initially. The biopsy can be repeated within 6 months if there were fewer than 10 cores initially.
According to the NCCN, for low-risk men with more than 10 years of life expectancy, a repeat biopsy is required — it is not optional — as often as every 12 months.
This group of men should also be offered radiotherapy and radical prostatectomy as treatment options, says the NCCN.
Dr. Carroll said that the quality of the initial biopsy is key to choosing men for active surveillance. "It must be a well-performed extended-pattern biopsy," he said.
Dr. Mohler said that, in figuring out who is a candidate for active surveillance, estimating life expectancy is an important step.
"Life expectancy is typically less than 20 years for men by age 57," he said, referring to the Social Security Administration's current listing of average life expectancy for American males.
The NCCN also advises that if an individual is in their life's best quartile of health, 50% should be added to the estimation; if in the worst quartile, 50% should be subtracted; and if in the middle 2 quartiles, the estimation should not be altered.
Offering Active Surveillance to Men
The NCCN, in outlining its principles of active surveillance, said that active surveillance should be considered by the patient and "all of his physicians (urologist, radiation oncologist, medical oncologist, and primary care physician)."
In discussing active surveillance with patients who are good candidates, clinicians might want to emphasize the positive, suggested Dr. Mohler, referring to his own methods and not NCCN guidance.
Dr. Mohler said that previous research indicates that there is a period of observation during which low- and very-low-risk men can safely forgo treatment with radiotherapy or prostatectomy.
"No one is harmed in their curability by an 18-month period of observation," he said, citing research by active-surveillance pioneer Laurence Klotz, MD, from Sunnybrook and Women's College Health Sciences Centre in Toronto, Ontario, and others"Active surveillance affords a man the opportunity to watch his cancer for a short time," he said.
Dr. Mohler explained that this time period allows for an assessment of PSA doubling time, which is one of the indicators of possible disease progression.
"Eighteen months is enough time for 3 more PSA values and a follow-up biopsy," Dr. Mohler noted.
Dr. Kibel, speaking of his experience with the START trial, which randomizes patients to either treatment (radical prostatectomy or radiotherapy) or active surveillance, suggested that education is a key to patient acceptance of active surveillance.
Once educated, some patients in START clearly prefer active surveillance, he said. "Many patients end up being concerned about possibly being randomized to treatment."
Data on Active Surveillance
Dr. Mohler said that the NCCN's confidence about recommending active surveillance stems in part from data from 3 centers — Sunnybrook; the University of California, San Francisco; and Johns Hopkins in Baltimore, Maryland.
"Experience at these centers makes it increasingly clear what happens to men who choose active surveillance," Dr. Mohler said.
In a recently published study by Dr. Klotz and colleagues at Sunnybrook (J Clin Oncol. 2010;28:126-131), the 10-year prostate cancer actuarial survival was 97.2% among low-risk men being treated with active surveillance. One third of the patients were reclassified as higher risk and offered treatment.
Dr. Carroll said that about 600 men are currently being treated with active surveillance at his center at the University of California, San Francisco.
With a median follow-up of "about 3.5 to 4 years," 24% of the patients have gone on to receive treatment, he said.
About one third of those men eventually chose treatment because of anxiety about surveillance" he explained. About two thirds were treated because of clinical changes or disease progression, he added.There is also an important caveat about the patients in San Francisco: not all of them are "good candidates based on NCCN criteria," said Dr. Carroll.
Of the 600 patients, about one third have a higher Gleason score or some other clinical measure that places them outside the NCCN definition of very low or low risk.
Dr. Carroll explained that he and his colleagues are attempting to develop a "continuum of risk" rather than "rigid risk groups," to provide patients with a numerical value of risk instead placing them in a "box."
"Prostate cancer represents a spectrum of disease," he said, explaining that the risk categorizations of low, intermediate, and high are in need of a "more refined assessment."
Dr. Mohler said that he has 260 men under active surveillance in his personal practice. With a median follow-up of about 5 years, there have been 11 deaths, but none were from prostate cancer, he said. Also, 40% of the men are African Americans, which suggests that the approach works among these men as well, he said.
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