Low-risk prostate cancer in older men is still being overtreated, according to two separate studies that examined the issue from different perspectives, both of which were published online July 14 in JAMA Internal Medicine.
One group of researchers found that primary androgen deprivation therapy fails to improve either overall or disease-specific survival in this patient population, yet it still is widely used as the initial treatment for localized disease. And another group found that urologists and radiation oncologists are the driving force behind the overly aggressive approach to low-risk prostate cancer in older men.
Both groups of investigators called for efforts to limit these harmful trends.
In the first study, Grace L. Lu-Yao, Ph.D., and her associates analyzed information on 66,717 cases of prostate cancer in the Surveillance, Epidemiology, and End Results (SEER) and Medicaid databases diagnosed in 1992-2009. All the patients were aged 66 years and older, and all had T1/T2 disease. There were 5,275 deaths from prostate cancer and 39,801 deaths from all causes during nearly 20 years of follow-up.
Primary androgen deprivation therapy failed to improve either overall or disease-specific survival at 5 years or 15 years. Further study using instrumental variable analysis to control for an imbalance in risk factors between users and nonusers of androgen deprivation therapy confirmed these results, as did several sensitivity analyses, "suggesting that our conclusions are robust" (JAMA Intern. Med. 2014 July 14 [doi: 10.1001/jamainternmed.2014.3028]).
"For patients with less aggressive cancers, deferred androgen deprivation therapy is safe and reduces the risks of treatment-associated adverse effects, such as osteoporosis, weight gain, decreased libido, decreased muscle tone, diabetes mellitus, and metabolic syndrome," wrote Dr. Lu-Yao of Rutgers Cancer Institute of New Jersey, New Brunswick, and her associates.
"Physicians and patients often believe that treatment is necessary and beneficial. Our data suggest that this may not be the case, at least for primary androgen deprivation therapy," they said.
In the other study, investigators examined physician and patient factors that influence treatment decisions in low-risk prostate cancer. They also analyzed SEER data, this time involving 12,068 men aged 66 years and older (median age, 72 years) who were diagnosed as having low-risk prostate adenocarcinoma in 2006-2009. These men were diagnosed by 2,145 urologists; 68% of them also consulted a radiation oncologist, said Dr. Karen E. Hoffman of the University of Texas M.D. Anderson Cancer Center, Houston, and her associates.
Fully 80% of the low-risk patients diagnosed by a urologist immediately received treatment; only 20% instead underwent observation, as is recommended. The use of observation varied markedly across urologists, with some performing observation for less than 5% of their patients and others performing observation for nearly 65%. Forty urologists (10.2%) had rates of observation that were significantly different from the mean.
In analyses that estimated the relative contributions of numerous factors to treatment decisions, "the diagnosing urologist was the most influential measured factor, responsible for 16.1% of the variance in management choice; just 7.9% of the variance was attributable to patient characteristics," Dr. Hoffman and her associates reported (JAMA Intern. Med. 2014 July 14 [doi: 10.1001/jamainternmed.2014.3021]).
Similarly, of the 7,554 men who consulted 870 radiation oncologists, a remarkable 91.5% underwent immediate treatment (usually radiotherapy), while only 8.5% underwent observation, as is recommended. The use of observation also varied markedly across radiation oncologists, with some advising observation for only 2% of their patients and others advising it for 47%. Again, the variance in treatment decisions attributable to radiation oncologists was at least double that attributable to patient factors.
"In our cohort, 70.0% of men aged 76-80 years and 55.1% of men older than 80 years still received up-front treatment," a striking proportion because the average life expectancy for men 77 years and older in the United States is less than 10 years. "Older men, especially those with multiple medical conditions, are not thought to gain a survival benefit from treatment of low-risk prostate cancer," Dr. Hoffman and her colleagues noted.
Their findings are important because most primary care physicians who refer their patients to specialists for prostate biopsy or consultation probably "assume that patients will receive similar management recommendations regardless of which [specialist] they see." These results demonstrate the opposite: Patients with low-risk prostate cancer could receive widely divergent treatment advice, solely depending on the specialists’ preferences.
Dr. Lu-Yao’s study was supported by the National Cancer Institute and the Cancer Institute of New Jersey. She reported ties to Merck and Schering-Plough, and one of her associates reported receiving research funding from Myriad. Dr. Hoffman’s study was supported by the Cancer Prevention and Research Institute of Texas, the National Cancer Institute, the American Cancer Society, the Duncan Family Institute, the University of Texas M.D. Anderson Cancer Center, and the National Institutes of Health. She reported no potential financial conflicts of interest, and one of her associates reported receiving research support from Varian Medical Systems.