Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Older, sicker men with non-aggressive prostate cancer had a significantly greater risk of dying of causes other than prostate cancer, a risk that increased with age at diagnosis and comorbidities, data from a large cohort study affirmed.
During 14 years of follow-up, other-cause mortality ranged from 24% for men with no comorbid conditions at diagnosis to 57% for men with three or more comorbidities. For men who were 65 at diagnosis, the mortality hazard versus no baseline comorbidities increased with the number of comorbid conditions from 1.2 to 2.6.
The impact of comorbidity burden on other-cause mortality increased with age ranges from younger than 60 to older than 75 at diagnosis but was greater in older ages, as reported online inAnnals of Internal Medicine.
Yet use of aggressive therapy predominated, regardless of comorbidity burden, including for 60% of men with three or more comorbidities, David F. Penson, MD, of Vanderbilt University in Nashville, Tenn., and co-authors concluded.
"Our data provide a framework to which all patients can apply their attitudes and assess their likelihood of treatment-related benefit on the basis of their age, comorbidity, and disease characteristics," the authors wrote.
"Our data show that men ages 60 years or older with three or more comorbid conditions approach 50% mortality at 10 years after diagnosis," they continued. "Therefore, given the low likelihood of short-term prostate cancer mortality and the high likelihood of other-cause mortality, older men with more than three major comorbid conditions who are choosing primary treatment should strongly weigh the risk of death from other causes before realizing any potential survival benefit from aggressive therapy."
Although estimated life expectancy should figure prominently in treatment decisions, available data suggest physician skill in this area is lacking, often leading to inappropriate treatment. One recent retrospective study showed that men with Charlson morbidity scores of 3 or greater receive aggressive treatment in the form of surgery or radiation in a majority of cases, despite a 70% risk of dying of other causes within 8 years of prostate cancer diagnosis (Cancer 2011;117:2058-2066).
Several factors may contribute to inappropriate treatment, the authors continued. Available data on other-cause mortality associated with comorbidity have come from single-institution case series or have involved only one type of treatment or treatment option. Instruments for determining the risk of other-cause mortality are "prohibitively cumbersome" for use in clinical practice.
In an effort to inform on clinical decision making specific to prostate cancer, Penson and colleagues queried the Prostate Cancer Outcomes Study (PCOS) database, a population-based cohort study of men with newly diagnosed prostate cancer. The cohort was derived from a subset of patients in the NCI Surveillance, Epidemiology, and End Results (SEER) program.
The PCOS cohort included men with nonmetastatic prostate cancer diagnosed from Oct. 1, 1994 through Oct. 31, 1995. All participants completed a baseline survey within 6 months of diagnosis, and each patient's medical record was reviewed 1 and 5 years after diagnosis.
Penson and colleagues stratified the PCOS cohort by clinical and pathologic characteristics, using D'Amico criteria: diagnostic PSA, Gleason score, and clinical stage at diagnosis.
The analysis comprised 3,183 men: 1,221 with no comorbidities, 1,020 with one, 523 with two, and 419 with three or more. In general, aggressive treatment was employed less often in men with a greater comorbidity burden. Even so, the investigators found that 256 of 419 (61%) of men with three or more comorbid conditions received aggressive therapy.
During the 14 years of follow-up, estimated other-cause (non-prostate cancer) mortality was 24% among men with no comorbidities at baseline, 33% for men with one comorbidity, 46% for men with two comorbidities, and 57% for men with three or more comorbid conditions.
After adjustment for age, race, SEER geographic area, tumor risk, and type of treatment, the hazard ratios for other-cause mortality versus men with no comorbidities were 1.2, 1.7, and 2.4 for men with one, two, or three or more comorbidities.
Advancing age added to the other-cause mortality hazard conferred by comorbidity burden. For example, men with three or more comorbidities had an estimated 10-year other-cause mortality of 26% if they were younger than 60 at diagnosis. The mortality increased to 40% for men 61 to 74 and to 71% for men 75 or older.
The investigators found that 29% of men with no comorbidities received nonaggressive treatment (androgen deprivation or watchful waiting), as did 33% of men with one comorbidity, 18% of men with two comorbidities, and 20% of men with three or more comorbid conditions.
The author of an accompanying editorial emphasized the complexities of integrating comorbidity and life expectancy into clinical decision making.
"Patients should be aware that the cumulative incidence of prostate cancer mortality and other-cause mortality in men aged 70 years or older is similar for those with three or more comorbid conditions and those at high risk for tumor aggressiveness," Lazzaro Repetto, MD, of Sanremo Hospital in Italy and colleagues wrote.
"Furthermore, the study showed that in the overall population, patients with zero or one comorbid condition who were receiving nonaggressive treatment had a statistically significantly higher risk for prostate cancer death than did those treated aggressively."
The data generated by Penson and colleagues make a good case for using age, tumor grade, and comorbidity burden to identify men who are unlikely to benefit from aggressive therapy, they added.
Attitudes toward nonaggressive treatment of prostate cancer have changed in the almost 20 years since men in the Penson study had newly diagnosed prostate cancer, said Edward Messing, MD, of the University of Rochester in New York. So have the patients, such that older men with comorbidities are living longer.
"How urologists are practicing now is a little bit different than how they practiced a few years ago," Messing, who was not involved in the study, told MedPage Today. "A few years ago, most urologists and radiation therapists would treat patients regardless of the severity of the disease and ... regardless of comorbidities."
"That clearly was not a wise approach, and I think both urology and radiation therapy have been appropriately chastised for that. That is not going on now to the same degree."
The study did not address the effect of aggressive treatment on complications, quality of life, or survival, Messing added. Moreover, treatment of prostate cancer has evolved considerably since 1994 and 1995, when the patients in study were treated.
"The message is that you don't have to treat these people and if you are treating them, don't do it," he said. "But it's not clear that they actually presented compelling information that would do that."