The vast majority of men diagnosed with early-stage prostate cancer have surgery or other harsh treatments that can cause permanent side effects, but a study published Wednesday found that men in their 60s who had surgery did not live significantly longer than those whose cancers were merely monitored.
The clinical trial, performed at Massachusetts General Hospital and elsewhere, could be a turning point, shifting doctors toward more conservative treatment of men who are diagnosed with prostate cancer that has not spread beyond the gland, the authors said.
“What we found really suggests that treatment has a limited effect for most tumors,” said a study coauthor, Dr. Michael Barry, chief of general internal medicine at Massachusetts General Hospital. The prostate-specific antigen (PSA) blood test “is finding many cancers that wouldn’t have otherwise caused problems,” he added.
The trial, published in the New England Journal of Medicine involved 731 men with an average age of 67 who were diagnosed with early stage prostate cancer detected through PSA screening, digital rectal exams, and biopsies.
About half were randomly selected to have their prostate removed right away and the rest were monitored by doctors to see whether their cancer began to progress.
After 12 years, nearly 6 percent of men who had immediate surgery died of the cancer, compared with slightly more than 8 percent of those patients who were observed, which was not a great enough difference to reach statistical significance. A subset of patients with high PSA readings did live longer after surgery, however.
But men who had surgery had more side effects: About 17 percent of them wound up with urinary incontinence compared with 6 percent of those who skipped the treatment, and 81 percent in the surgery group had erectile dysfunction, compared with 44 percent of those whose cancers were monitored.
About 1 in 5 men in the “watchful waiting” group wound up opting for treatment during the study because of personal choice or because their cancers appeared to be progressing when they went for routine physicals; in the study, watchful waiting involved no set schedule of testing to monitor the cancers.
“There’s been a move toward offering observational approaches for men with low-grade, low-risk disease,” said Dr. Durado Brooks, director of the prostate and colorectal cancer program at the American Cancer Society. “This study provides additional information to help doctors and patients decide what to do.”
About two-thirds of the 240,000 American men diagnosed with prostate cancer each year have tumors that pose little risk of spreading, but nearly 90 percent of them get treated with surgery or radiation, which can also cause side effects such as impotence. In part that is because current tests are not able to accurately distinguish between aggressive cancers that will spread and kill if not treated and nonlethal tumors.
An editorial that accompanied the study pointed out that the researchers’ failure to enroll 1,200 men as originally planned may have made it impossible to detect a modest but significant reduction in deaths in the group that had immediate surgery. (When the study began, many men and their doctors did not want to risk skipping treatment in case it led to a higher death risk.)
Some cancer specialists said the study’s findings do not apply to younger men. A large percentage of those under age 65 with early disease will probably still opt for immediate treatment. “We can’t conclude from the study data that a healthy 50-year-old man with low-risk disease should skip treatment because the followup isn’t long enough to determine whether his disease will progress,” said Dr. Anthony D’Amico, chief of genitourinary radiation oncology at Brigham and Women’s Hospital.
Brooks added that studies would need to follow men for 20 years to ascertain whether immediate treatment protected younger men from eventually dying of the disease. “We simply don’t have long-term studies to make recommendations to younger men.”
Even for older men, D’Amico said, he considers a patient’s life expectancy rather than just his age. He usually recommends surveillance — which, unlike watchful waiting, includes frequent PSA screening and yearly biopsies — only in older patients who have health issues such as diabetes or heart disease.
Didier Sartor of Barrington, R.I., was one such patient. The 70-year-old with high blood pressure and elevated cholesterol levels opted not to treat his slow-growing cancer after he was initially diagnosed last December. “I had friends who were treated for prostate cancer and wasn’t looking forward to it, so was happy to avoid it,” he said. “While I’m still aware that I have cancer, I’m not too concerned about it.”
Other specialists believe this study adds to the growing body of evidence that younger men could also be candidates for active surveillance if their tumors, based on a biopsy, are graded as low-risk for spreading. “For someone in their 50s, it should be discussed,” said Dr. Philip Kantoff, head of the prostate cancer program at the Dana-Farber Cancer Institute. “There are differences in opinion on this, and none of us really know what the age cutoff should be.”
While the new research certainly suggests that PSA screening detects inconsequential cancers, it also found that PSA levels were a strong predictor of cancers that might later spread and kill. A subgroup of men in the study who had PSA levels of greater than 10 nanograms per milliliter had a 33 percent lower risk of dying from prostate cancer if they were immediately treated with surgery rather than observed, which was a statistically significant difference.
This finding could be applied by some doctors to curtail the high rate of biopsies. Many physicians order a biopsy in any patient who has a persistent PSA level of 2.5 nanograms per milliliter or above, a practice that was instituted in recent years after studies found that using 4 nanograms per milliliter as a cutoff missed a lot of cancers, said Brooks. “We’re doing many more biopsies now and finding an increased proportion of cancers that are the lower-risk kind.”
While Brooks said additional studies would be needed to justify changing biopsy practices, Barry said doctors should at least be thinking about raising the threshold for biopsies. “Maybe that’s a way to reduce some of the overdiagnosis and treatment,” he said.