Elsevier

European Urology

Volume 63, Issue 4, April 2013, Pages 693-701
European Urology

Prostate Cancer
Impact of Age and Comorbidities on Long-term Survival of Patients with High-risk Prostate Cancer Treated with Radical Prostatectomy: A Multi-institutional Competing-risks Analysis

https://doi.org/10.1016/j.eururo.2012.08.054Get rights and content

Abstract

Background

Survival after surgical treatment using competing-risk analysis has been previously examined in patients with prostate cancer (PCa). However, the combined effect of age and comorbidities has not been assessed in patients with high-risk PCa who might have heterogeneous rates of competing mortality despite the presence of aggressive disease.

Objective

To examine the risk of 10-yr cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathologic characteristics of patients treated with radical prostatectomy (RP) for high-risk PCa.

Design, setting, and participants

Within a multi-institutional cohort, 3828 men treated with RP for high-risk PCa (defined as the presence of at least one of these risk factors: prostate-specific antigen >20 ng/ml, biopsy Gleason score 8–10, clinical stage ≥T3) were identified.

Intervention

All patients underwent RP and pelvic lymph node dissection.

Outcome measurements and statistical analysis

Competing-risk Poisson regression analyses were performed to simultaneously assess the 10-yr CSM and OCM rates after RP. The same analyses were also conducted after stratification of patients according to age at surgery, comorbidity status assessed by the Charlson Comorbidity Index (CCI), and number of risk factors (one vs two or more).

Results and limitations

Overall, 229 patients (5.9%) died from PCa; 549 (14.3%) died from other causes. The 10-yr CSM and OCM rates ranged from 5.1% to 12.8% and from 4.3% to 37.4%, respectively. Age and CCI were the major determinants of OCM; their impact on CSM was minimal. OCM was the leading cause of death in all patient groups except in young men (≤59 yr) with no comorbidities, regardless of the number of risk factors (10-yr CSM and OCM 6.9–12.8% and 5.5–6.3%, respectively). The main limitation was the lack of patients managed conservatively.

Conclusions

Even in the context of high-risk PCa, long-term CSM after RP is modest and represents the leading cause of death only in young, healthy patients. Conversely, older and sicker patients with multiple risk factors are at the highest risk of dying from OCM while sharing very low CSM rates.

Introduction

Radical prostatectomy (RP) is considered the first-line treatment of patients with localized prostate cancer (PCa) and a life expectancy of at least 10 yr [1]. Nonetheless, the survival benefit associated with RP is variable. For example, a large proportion of patients with low-risk PCa may harbor an indolent type of cancer that, in some cases, may even not necessitate active treatment [2], [3], [4]. However, more aggressive disease, defined by high prostate-specific antigen (PSA) and high clinical stage and/or PCa grade at diagnosis, is associated with worse survival after surgery [5], [6].

Even in the presence of aggressive disease, only a minority of patients treated with RP die from PCa [5], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. This may be due to two main reasons: (1) durable cancer control obtained by surgery either alone or in combination with adjuvant therapies and (2) the influence of other-cause mortality (OCM) on patient survival. For these reasons, the effect of cancer-specific mortality (CSM) on the outcome of older and/or morbid men with high-risk disease might be limited due to their reduced life expectancy. These men may also be less capable of tolerating cancer-related therapies, which, in turn, would reduce the benefit associated with surgical resection of PCa.

Not all patients with aggressive disease at diagnosis have the same long-term cancer outcomes. For example, surgically treated patients with multiple adverse PCa features have significantly lower survival rates as compared with those with less aggressive disease even within the “high-risk” category [7], [11], [12], [14]. Therefore, the effect of CSM and OCM on patient survival might significantly change according to both cancer and patient characteristics. To address this issue, we examined CSM and OCM rates in large multi-institutional series of surgically managed high-risk PCa patients, using a competing-risks approach. Our study aims at assessing the risk–benefit ratio of RP on the basis of patient age, comorbidity profile, and PCa features. This would ultimately optimize the selection of patients with high-risk PCa as candidates for RP.

Section snippets

Study population

Between 1987 and 2010, 5638 patients treated with RP and pelvic lymph node dissection for high-risk PCa (defined as the presence of at least one of the following risk factors: PSA >20 ng/ml, clinical stage T3 or higher, or biopsy Gleason sum 8–10) [1] at seven worldwide tertiary care centers were considered. Of these, 976 (17%) were excluded due to the lack of data on their comorbidity profile, 398 (7%) due to unavailable follow-up, and the remaining 436 (7.7%) due to missing data on either

Results

Average age at surgery was 65 yr (median: 66; interquartile range [IQR]: 60–70 yr). Overall, 2592 patients (67.7%) and 1236 patients (32.3%) had a CCI of 0 and ≥1, respectively. Most patients (67.2%) had only one risk factor and received no adjuvant treatment (78.7%). Following stratification of patients according to age groups, 25.4%, 24.1%, 30.2%, and 20.3% of patients were age ≤59, 60–64, 65–69, and ≥70 yr, respectively (Table 1). Patients in the oldest age category were more likely to have

Discussion

We assessed the long-term impact of CSM and OCM on survival of roughly 4000 men with high-risk PCa treated with RP alone or in combination with adjuvant therapies at seven different tertiary referral centers. After stratification of patients according to age, comorbidity profile, and number of risk factors, we found that OCM represented the leading cause of death in all patient subgroups, with the exception of young, healthy individuals.

Our results are several-fold. First, we reiterate previous

Conclusions

Our study provides a valuable aid for the assessment of long-term CSM and OCM according to patient age and comorbidity profile in men treated with RP for high-risk PCa. In these patients, long-term CSM was modest and represented the leading cause of death only in young, healthy patients, regardless of the number of risk factors. Interestingly, in older but healthy patients, the risk of dying from PCa was similar to that of younger men. Conversely, older and less healthy patients with multiple

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