Clinical Investigation
Survival Following Radiation and Androgen Suppression Therapy for Prostate Cancer in Healthy Older Men: Implications for Screening Recommendations

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Purpose

The U.S. Preventive Services Task Force has recommended against screening men over 75 for prostate cancer. We examined whether older healthy men could benefit from aggressive prostate cancer treatment.

Methods and Materials

206 men with intermediate to high risk localized prostate cancer randomized to 70 Gy of radiation (RT) or RT plus 6 months of androgen suppression therapy (RT+AST) constituted the study cohort. Within subgroups stratified by Adult Comorbidity Evaluation-27 comorbidity score and age, Cox multivariable analysis was used to determine whether treatment with RT+AST as compared with RT was associated with a decreased risk of death.

Results

Among healthy men (i.e., with mild or no comorbidity), 78 were older than the median age of 72.4 years, and in this subgroup, RT+AST was associated with a significantly lower risk of death on multivariable analysis (adjusted hazard ratio = 0.36 (95% CI=0.13-0.98), p = 0.046, with significantly lower 8-year mortality estimates of 16.5% vs. 41.4% (p = 0.011). Conversely, among men with moderate or severe comorbidity, 24 were older than the median age of 73, and in this subgroup, treatment with RT+AST was associated with a higher risk of death (adjusted hazard ratio = 5.2 (1.3-20.2), p = 0.018).

Conclusion

In older men with mild or no comorbidity, treatment with RT+AST was associated with improved survival compared with treatment with RT alone, suggesting that healthy older men may derive the same benefits from prostate cancer treatment as younger men. We therefore suggest that prostate cancer screening recommendations should not be based on strict age cutoffs alone but should also take into account comorbidity.

Introduction

In August 2008, the U.S. Preventive Services Task force recommended that men over the age of 75 should not be screened for prostate cancer (1). The rationale was that the benefit of screening, if any, is likely to be small in this older age group with a typical life expectancy of less than 10 years, and given the risk of physical and psychological harm due to screening and overtreatment, it was concluded that “there is at least moderate certainty that the harms of screening for prostate cancer in men age 75 years or older outweigh the benefits.”

The task force recommendation for when to stop screening is based on age and does not take into account the patient's overall health status. However, it is known that at any given age, patients with multiple medical comorbidities will have a shorter life expectancy than those who are generally healthy and have no or few medical comorbidities 2, 3, 4. Therefore, it is possible that there are many men older than 75 who are healthy enough and have relatively long life expectancies who may benefit from screening as younger men would.

To provide some evidence for this hypothesis, we performed a postrandomization analysis of a randomized trial (DFCI 95-096) that had assigned 206 men with intermediate- to high-risk prostate cancer to treatment with either external beam radiation (RT) alone or RT plus androgen suppression therapy (AST) and found that RT+AST decreased all-cause mortality (ACM) (5). The goal of the current study was to determine whether older healthy men also derived a survival benefit from aggressive treatment, which would raise the possibility that healthy older men should also be given the same opportunity to be screened and diagnosed as younger men.

Section snippets

Patient population and treatment

At academic (Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center) and community-based (St Anne's Hospital, Metrowest Medical Center, and Suburban Oncology Center) medical centers in Massachusetts, between December 1, 1995, and April 15, 2001, 206 men (median age, 72.5 years; range, 49–82 years) with 1992 American Joint Commission on Cancer (AJCC) Clinical Stage T1b to T2bN0M0 adenocarcinoma of the prostate and at least one unfavorable prognostic

Baseline characteristics stratified by comorbidity

Of the 206 participants, there were 157 men with mild or no comorbidity (healthy men), and 49 men with moderate to severe comorbidity. The patient baseline characteristics, stratified by comorbidity, are shown in Table 1. The median age of the healthy men was 72.4 years, whereas the median age for those with moderate or severe comorbidity was 73 years. For those older than the respective medians, baseline characteristics including T-category, PSA, Gleason score, and age, were not significantly

Discussion

In this study, we performed a postrandomization analysis and found that among older healthy men, aggressive treatment of prostate cancer with RT+AST seemed to decrease ACM compared with treatment with RT alone. Conversely, we found that among older men with moderate or severe comorbidity, the addition of 6 months of AST to RT did not reduce ACM.

The clinical implications of these findings are threefold. First, they imply that a patient's level of comorbidity can affect whether he derives a

References (12)

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