Abstract
The UK-based ProtecT trial reports that, after a median of 10 years of follow up, there is no significant difference in prostate cancer–specific mortality between active monitoring, surgery, and radiotherapy. However, the likelihood of developing metastases is more than twice as great with active monitoring compared with treatment.
Active monitoring, surgery, and radiation are all valid options for men with PSA-detected prostate cancer, with mortality hovering around 1% for each choice, according to the first results from the UK-based ProtecT trial. The study, published in The New England Journal of Medicine, is the first to directly compare surgery and radiation in a randomized trial, finding them equally effective.
“Treatments work,” concludes the study's lead author Freddie Hamdy, MD, director of surgery and oncology at Oxford University Hospitals, adding that “active monitoring is a good option for men if they want it.”
The researchers enrolled 1,643 men, ages 50 to 69, diagnosed with early-stage, localized prostate cancer between 1999 and 2009. The men were randomly assigned to undergo surgery or radiation, or to engage in active monitoring, which involved regular PSA testing with the option to be treated later. Although prostate cancer–specific survival was at least 98.8% in all three groups after a median follow-up of 10 years, 33 men in the active monitoring group developed metastases, more than twice as many as in each treatment arm.
“The doubling of the metastatic rate is not clinically insignificant,” cautions Anthony D'Amico, MD, PhD, of Brigham and Women's Hospital in Boston, MA, who wrote an editorial on the study. The development of metastatic disease requires more intensive treatment than just a PSA-positive test would, such as androgen-suppression therapy to silence hormones that drive cancer growth.
Given that the study participants were relatively young and healthy at the outset—and had early, favorable-risk prostate cancer—D'Amico says he would not predict a high rate of disease-specific mortality in the first decade, but it could well rise in the next 10 years. The researchers continue to follow the participants.
Because the active monitoring protocol was developed nearly 20 years ago, Hamdy says that it does not precisely correspond to the way many clinicians follow patients today. Modern surveillance often includes multiparametric MRI as well as repeated biopsies. That level of surveillance might lead to more men opting for treatment before metastasis can occur, D'Amico says. That's especially true, he adds, because “modern surgical and radiotherapy techniques have less acute and late toxicities, especially when compared to lifelong hormonal therapy.”
In a companion study, also in The New England Journal of Medicine, the ProtecT researchers analyzed how monitoring, surgery, and radiation affected quality of life. Surgery was most likely to curb sexual function and cause urinary incontinence. Radiotherapy had the greatest impact on bowel function. However, men in all three groups reported similar quality of life overall.
Crucial questions about prostate cancer treatment remain unanswered. One, Hamdy says, is how to distinguish “lethal from nonlethal” disease, and thus choose the best treatment for each patient. “That really needs some very urgent research,” he says.
In addition, Hamdy and his colleagues are investigating the value of PSA screening, which has been controversial because it can point to indolent tumors that may not need treatment. Evidence that screening reduces prostate cancer–related deaths has been limited, but the researchers expect to know more next year, when the results of their CAP trial are released. –Amber Dance
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