With increasing age, men are significantly more likely to have high-risk prostate cancer. There is common use of PADT and WW/AS among these older men and less local therapy, particularly RP, compared with younger men. On univariate analysis, age predicted overall and prostate cancer–specific survival. However, when controlling for either treatment modality alone or treatment modality and risk, age was not an independent predictor of mortality from prostate cancer. These findings suggest that under-use of potentially curative local therapy among older men with high-risk disease may in part explain higher cancer-specific mortality rates observed with increasing age.
Overall survival is of course lower in patients of increasing age, reflecting the impact of other variables including comorbidities, increased susceptibility to major illness, and decreased immune response. However, our data support the hypothesis that prostate cancer evolution, and hence mortality, occurs not on the basis of patient age but instead on the basis of cellular mechanisms whose malignant potential can be categorized by established disease risk features. Therefore, older patients with clinically localized, high-risk disease, and a noncancer life expectancy of > 10 years should be considered for surgical treatment and/or radiation therapy. Recent studies have shown that with careful patient selection, gains in life expectancy in men older than age 70 years following radical or laparoscopic prostatectomy are comparable to those in younger men.8,16
Indeed, comorbidity has been found to be a more important predictor of surgical complications than age.24
Another recent report20
found that among men with higher-risk disease, mortality outcomes are improved following RP with either EBRT or PADT, findings that held with adjustment for age.
Our findings suggest a serious discrepancy among older patients between actual treatment practices and optimal treatment. Optimal treatment should be based primarily on disease risk and other clinical factors rather than chronologic age, yet actual treatment practices appear to reflect variation driven rather by physician practice style and patient age. In our analysis, the relatively few older men with high-risk disease who received local therapy had nearly a 50% reduction in risk-adjusted mortality compared with those in the same age cohort who received PADT or WW/AS. However, most older men were more likely to receive PADT, regardless of disease risk category, although the benefit of hormonal therapy in localized cancer is unclear4,25
and PADT is associated with potential musculoskeletal, cardiovascular, and other adverse effects.26,27
Multiple previous studies have similarly reported that older men were less likely to undergo the potentially curative treatments of RP or radiotherapy, regardless of disease risk and comorbidities.12,28–30
Men younger than 60 years of age are 25 times more likely to receive RP than men older than 70 years of age, likely due in part to physician tendencies to avoid surgery in older men.31,32
Indeed, individual physician preferences have been shown to play a significant role in determining whether patients receive PADT or any potentially life-prolonging treatment.31–34
Prior reports found that more than 15% of men older than age 75 years with high-risk disease were undertreated, and a majority never received curative therapy for their prostate cancer.10,35
Our results further suggest that prostate cancer survival differences across age strata are influenced by treatment decisions, which are themselves driven by age, not disease risk.
An earlier analysis12
of more than 2,000 men older than age 75 years in CaPSURE found that patient comorbidities and tumor-risk characteristics did not play a substantial role in treatment decision making. Similarly, in a study of PSA screening rates in US Veterans Affairs patients,36
among men older than age 85 years, those in the best health were screened less frequently than their counterparts in the worst health. The USPSTF recommendation against screening all men older than age 75 years also fails to consider comorbidity; such a broad statement could potentially harm older men in otherwise good health by missing treatable high-risk tumors.37
We found that within 5 years of follow-up of high-grade disease among men older than age 75 years, cancer-specific mortality reaches 20%; similar findings from other databases have been reported elsewhere.38
The estimation of life expectancy remains a difficult task, with both individual clinicians and life-table nomograms suffering from suboptimal accuracy.39,40
However, comorbidity and risk assessment remain critical to determining appropriate disease management to minimize both overtreatment of low-risk disease and undertreatment of high-risk disease. Overestimation of life expectancy can lead to overtreatment of lower-risk prostate cancer, especially in elderly men.14,34
Conversely, our data suggest that undertreatment, or unnecessary treatment with suboptimal therapy, is an equally important problem. The use of PADT increases dramatically with age despite a lack of evidence to support its efficacy as a monotherapy for localized disease.4,9
Developing more stringent criteria to help guide treatment in elderly men may enable a more uniform standard of care that could decrease morbidity and prevent unnecessary therapy.
The limitations of our study deserve mention. Comorbidity reporting is based on self-report and may not completely reflect the impact of comorbid illness on overall survival for each patient. However, the concordance of the proportional hazards and competing risks analyses is reassuring in this regard. Identifying cancer-specific mortality as determined by review of death certificates is limited by the thoroughness of information documented on the certificates, which in turn relies on the individual physician's knowledge of each patient's history. As a result, the database may underestimate mortality from prostate cancer because of the presence of other comorbidities and/or toxicities of treatment. It is important to consider why a given tumor was detected relatively late in life: a tumor detected in the context of a slowly rising PSA and prior negative biopsies may be quite different biologically from one detected in an older man who had never been screened previously. However, the focus of the CaPSURE registry is on management, not screening, so the database includes a variable depth of information on prediagnosis PSA values. Therefore, the impact of the intensity of prior screening on disease risk at diagnosis cannot be ascertained by using this database.
CaPSURE comprises data from community-based and academic urology practice sites across the country, but these sites were not chosen at random and the population cannot be assumed to represent a statistically valid sample of the US prostate cancer population. African Americans, for example, are moderately represented in the database, but other ethnic groups are underrepresented compared with the larger population. In addition, CaPSURE patients tend to have a higher socioeconomic status on average compared with the overall population.22
A total of 1,519 patients (11%) were excluded because of incomplete treatment and/or follow-up data. These gaps in the data are attributable to variability among the large number of physicians at multiple sites submitting data to the registry. There is no indication that the missing data are nonrandomly distributed across the age strata.
When diagnosed with prostate cancer, older men are more likely to have high-risk disease and are more likely to be treated with PADT rather than potentially curative local therapy. Older men also have lower overall survival. However, when controlling for treatment modality alone, or treatment modality and cancer risk category, age is not an independent predictor of prostate cancer–specific survival. These results may be due in part to differences in treatment by age group; older men are more likely to be treated by PADT or WW/AS. Those with high-risk tumors who receive local therapy have a 46% reduction in risk-adjusted mortality compared with men managed conservatively. These findings highlight the importance of making treatment decisions guided by disease risk and life expectancy rather than chronologic age. Most older men with low-risk disease are candidates for active surveillance, but selected patients with more aggressive tumors should not be denied the opportunity for potentially curative local therapy.