Prostate CancerImpact 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
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.
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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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