BY KURT SAMSON
Older men diagnosed with depression who develop localized prostate cancer are more likely to have more aggressive cancers, receive less effective treatments, and survive for shorter times than those who are not depressed, a multi-institutional study has found.
“To the best of our knowledge, this is the first study demonstrating that a preexisting diagnosis of depressive disorder is independently associated with treatment choice and outcomes of localized prostate cancer,” said the lead author, Jim C. Hu, MD, MPH, the Henry E. Singleton Professor of Urology and Director of Robotic and Minimally Invasive Surgery at the David Geffen School of Medicine at UCLA.
The team also included Sandip M. Prasad, MD, MPhil, of Medical University of South Carolina, the first author; as well as Scott E. Eggener, Stuart R. Lipsitz, Michael R. Irwin, and Patricia A. Ganz.
The observational study, available online ahead of print in the Journal of Clinical Oncology (examined data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Medicare database. The researchers focused on 41,275 men diagnosed with localized prostate cancer between 2004 and 2007 and observed through 2009, including 1,894 who had a diagnosis-related group code of depressive disorder filed within two years prior to their cancer diagnosis.
Across all risk factors, men with depressive disorder had worse overall mortality, with a relative risk of 1.86, but there was no variation in clinicopathologic characteristics among the men. Those with depressive disorder were also less likely to seek out definitive therapy such as surgery or radiation and to instead elect androgen-deprivation therapy or expectant management/“watchful waiting.”
Hu explained that treatment disparity and negative outcomes may be the result of several factors, including bias against people with mental illness, depression's impact on cancer's biological processes, a patient's lack of investment in his general health and/or disinterest in more effective care, and physicians missing opportunities to more fully explain treatment options.
"The effect of depressive disorders on prostate cancer treatment and survival clearly warrants further study because both conditions are relatively common in men in the United States," he said. “Although demographic and socioeconomic differences are known to affect treatment and outcomes in prostate cancer, the effect of mental health disorders remains unclear.”
Studies in patients with other cancers, including breast and liver cancers, have also shown that depressed patients do not get the best treatment and tend to have worse overall survival, he added.
The new study also found that men with prostate cancer were more likely to be depressed if they were older, Caucasian or Hispanic, unmarried, lived in non-metropolitan areas, and had lower incomes as well as other medical problems. Overall, they were also more likely to have high-risk disease compared with men without depression, and saw a physician, on average, 43 times in the two years before cancer diagnosis, compared with an average of 27 visits by men without depression.
"This was surprising,” Hu said. “The results suggest a newly identified disparity in the management of men with incident prostate cancer, and additional efforts are needed to better understand and address this issue.”
The challenge is threefold, he continued. The first is to ensure that such patients are getting and taking their medication as indicated and showing up for radiation treatment: “I believe some providers may not be emphasizing the need, although it is probably more likely due to patients not adhering to instructions. Second, we need greater focus on this issue. The third challenge is to better understand why survival rates are lower in these patients. There may be biological factors.”
He said a smaller study is needed in order to more closely investigate the issues involved.
“We need to get away from a panoramic exploration--there appears to be a microcosm of patients who fall into this category. And we need focus groups on why they are less likely to undergo radiotherapy.”
He noted that this is similar to investigations when it was learned that suicides increased among some heart attack patients who balked at undergoing percutaneous coronary angioplasty, and the same has been found in women diagnosed with a certain type of aggressive breast cancer.
“One could infer that these patients are more vulnerable,” he said. “The best way to address this might be to provide greater access to care and better ways to identify depression, especially in aging men.”
Asked for his opinion for this article, Alexander S. Parker, PhD, the Cecilia and Dan Carmichael Family Associate Director for the Center for Individualized Medicine and Vice Chair of the Department of Health Sciences Research at Mayo Clinic in Jacksonville, Florida, said that while this is a large, very well-designed observational study addressing a long-standing issue in prostate cancer, it is important to recognize some of its limitations.
“We need to be careful not to over-interpret the results,” he said. “Chief among these limitations is that patients were followed for only five years and, equally important, the primary outcome was death from any cause rather than cancer-specific death.”
Parker, a professor of epidemiology and urology, said that while the authors reported that depression was associated with a mild increase in mortality after prostate cancer diagnosis and treatment, it is not clear that all the deaths were due to prostate cancer.
“A better endpoint would have been death due to prostate cancer. Unfortunately, accurate cause-of-death information is difficult to get when using large databases like SEER-Medicare. Other limitations center on the fact that the authors excluded several groups of men, including those younger than 67, those with a diagnosis of more than one cancer, and more than 25,000 men with Medicare claims that may not have been reliably filed. This means that we cannot generalize the finding from this study.”
The most compelling data, he said, is the evidence that depressed men were 25 to 30 percent less likely to choose definitive therapy for prostate cancer, regardless of whether they have low-, intermediate-, or high-risk disease. “The data from this study suggest that specific interventions can and should be developed and evaluated for their ability to help depressed men choose appropriate treatment for their cancer, especially those with intermediate- and high-risk cancers who could benefit from more definitive therapy.”
Given that there was very little evidence that depression delayed the diagnosis or dramatically affected survival, and no evidence of an effect on cancer-specific survival, this study by itself does not support the need for specific interventions to improve diagnosis and outcomes for depressed men,” Parker noted. “To be clear, these may indeed be needed; however, these data do not support them specifically.
“From the study it is only possible to conclude that there is evidence that depressed men are less likely to choose definitive therapy--potentially a big problem. It is not a stretch to imagine that if men are depressed they might be less likely to choose a more aggressive therapy that could save their lives but at the same time is associated with notable side effects such as incontinence and erectile dysfunction.”
Large-scale studies in younger men are difficult because there are fewer opportunities to use existing databases like Medicare, he continued. “It is very possible that the effect of depression on prostate cancer diagnosis and survival in younger men could be different, which is another important area for further study.”