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Estimating the risk of competing mortality is of importance in men with early prostate cancer to choose the most appropriate way of management and to avoid over- or under-treatment. In this study, we investigated the impact of the level of education in this context. The study sample consisted of 2630 patients with complete data on level of education (college, university degree, master craftsmen, comparable profession, or others), histopathological tumor stage (organ confined or extracapsular), lymph node status (negative or positive), and prostatectomy specimen Gleason score (<7, 7, or 8-10) who underwent radical prostatectomy between 1992 and 2007. Overall, prostate cancer-specific, competing, and second cancer-related mortalities were study endpoints. Cox proportional hazard models for competing risks were used to study combined effects of the variables on these endpoints. A higher level of education was independently associated with decreased overall mortality after radical prostatectomy (hazard ratio [HR]: 0.75, 95% confidence interval [95% CI]: 0.62-0.91, P = 0.0037). The mortality difference was attributable to decreased second cancer mortality (HR: 0.59, 95% CI: 0.40-0.85, P = 0.0052) and noncancer mortality (HR: 0.73, 95% CI: 0.55-0.98, P = 0.0345) but not to differences in prostate cancer-specific mortality (HR: 1.16, 95% CI: 0.79-1.69, P = 0.4536 in the full model). In conclusion, the level of education might serve as an independent prognostic parameter supplementary to age, comorbidity, and smoking status to estimate the risk of competing mortality and to choose optimal treatment for men with early prostate cancer who are candidates for radical prostatectomy.

Background: In patients with early prostate cancer, stratification by comorbidity could be of importance in clinical decision making as well as in characterizing patients enrolled into clinical trials. In this study, we investigated several comorbidity classifications as predictors of overall mortality after radical prostatectomy, searching for measures providing complementary prognostic information which could be combined into a single score., Methods: The study sample consisted of 2205 consecutive patients selected for radical prostatectomy with a mean age of 64 years and a mean follow-up of 9.2 years (median: 8.6). Seventy-four patients with incomplete tumor-related data were excluded. In addition to age and tumor-related parameters, six comorbidity classifications and the body mass index were assessed as possible predictors of overall mortality. Kaplan-Meier curves and Mantel-Haenszel hazard ratios were used for univariate analysis. The impact of different causes of death was analyzed by competing risk analysis. Cox proportional hazard models were calculated to analyze combined effects of variables., Results: Age, Gleason score, tumor stage, Charlson score, American Society of Anesthesiologists (ASA) physical status class and body mass index were identified a significant predictors of overall mortality in the multivariate analysis regardless whether two-sided and three-sided stratifications were used. Competing risk analysis revealed that the excess mortality in patients with a body mass index of 30 kg/m2 or higher was attributable to competing mortality including second cancers, but not to prostate cancer mortality., Conclusion: Stratifying patients by a combined consideration of the comorbidity measures Charlson score, ASA classification and body mass index may assist clinical decision making in elderly candidates for radical prostatectomy.

Objectives: Comorbidity assessment may assist in the treatment choice for elderly men with prostate cancer. There is, however, no consensus on the best comorbidity classification for this purpose. In this study, we used a heuristic approach to identify an optimal comorbidity classification in elderly men selected for radical prostatectomy., Methods and Materials: A total of 1,106 men aged 65 years or older who underwent radical prostatectomy for clinically localized prostate cancer were stratified by 11 3-sided comorbidity classifications. Overall survival was the study endpoint. The comorbidity classifications were evaluated considering 4 statistical (height of hazard ratios and P values, survival difference between high and low risk patients, dose-response relationship) and 4 clinical demands (survival rates in low and high risk group, balance of the proportion of the risk groups). The 3 best classifications in each category received 3, 2, or 1 point. After adding all points, the classification with the highest score was considered best., Results: With one exception, all comorbidity classifications were significant predictors of overall survival. Comparing the highest with the lowest risk group, the hazard ratios ranged between 1.67 and 3.93. Concerning the fulfillment of clinical and statistical demands, the American Society of Anesthesiologists (ASA) physical status classification and 1 derivative of it that included further more clearly defined diseases were the most promising candidates., Conclusions: Stratifying candidates for radical prostatectomy according to their mortality risk using the ASA classification as a backbone supplemented by a list of more clearly defined concomitant diseases could be useful in clinical practice and outcome studies., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Unlabelled: Study Type - Outcomes (cohort). Level of Evidence 2b. What's known on the subject? and What does the study add? Several comorbidity classifications have been investigated for their suitability to assist treatment decision-making in men with early prostate cancer. In unselected patients, some serious comorbidities have been shown to be associated with a 10-year competing mortality rate clearly superseding the 50% level. The present study shows that it is hardly possible to discern meaningful subsets of patients with a 10-year risk of competing mortality of >50% by using comorbidity classifications. This finding suggests that the selecting clinicians did well in estimating the medium-term survival probability in men referred for radical prostatectomy., Objective: • To identify subsets of patients who are most likely to die from competing causes ≤ 10 years after radical prostatectomy (RP)., Patients and Methods: • In all, 2205 consecutive patients who underwent RP for clinically localized prostate cancer between 1992 and 2005 were studied. The 10-year cumulative competing mortality rates were determined in several worst-case scenarios formed by using comorbidity classifications and combinations of them., Results: • In this sample of men selected for RP, even those with the most severe comorbidity level had a competing mortality risk of <50% ≤ 10 years after RP. • Depending on the comorbidity classification used, the 10-year cumulative competing mortality rates differed between 16 and 39% in the whole sample and between 18 and 48% in men aged ≥ 65 years., Conclusion: • Clinicians do well in estimating the further life span in candidates for RP. Comorbidity classifications may assist treatment choice in this population but are not able to discern meaningful subsets to be excluded from curative treatment because of a life expectancy falling below a limit of 10 years., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Background: Factors predicting survival in men with lymph node-positive prostate cancer are still poorly defined., Patients and Methods: 193 prostate cancer patients with histopathologically proven lymph node involvement with a median follow-up of 7.3 years were studied. 94% of patients received immediate hormonal therapy. Kaplan-Meier curves were calculated to evaluate overall survival rates and compared with the log-rank test. Cumulative disease-specific and competing mortality rates were calculated by competing risk analysis and compared with the Pepe-Mori test. Cox proportional hazard models were used to determine the independent significance of predictors of all-cause mortality., Results: Age (70 years or older vs. younger), Gleason score (8-10 vs. 7 or lower) and the number of involved nodes (3 or more vs. 1-2) were identified as independent predictors of all-cause mortality. When patients with 0-1 of these risk factors were compared with those with 2-3 risk factors, all-cause (rates after 10 years 21% vs. 71%, p < 0.0001), disease-specific (12 vs. 37%, p = 0.009) and competing mortality (9 vs. 33%, p = 0.02) differed significantly., Conclusions: Some of the excess mortality in patients with poor-risk lymph node-positive prostate cancer may be attributed to increased competing mortality, possibly caused by an interaction between comorbid diseases and hormonally treated persistent or progressive prostate cancer., (Copyright © 2012 S. Karger AG, Basel.)

Objectives: To compare comorbidity measures and to analyze survival rates in men undergoing radical prostatectomy at age 70 years or older., Materials and Methods: A total of 329 consecutive patients aged 70 or more years who underwent radical prostatectomy between 1992 and 2004 were studied. The patients were stratified by 5 comorbidity classifications, tumor stage, Gleason score, and PSA value. Mortality was subdivided into overall, comorbid, competing, prostate cancer-specific, and second cancer-specific mortality. Competing risk and Kaplan-Meier survival curves as well as Mantel-Haenszel hazard ratios were calculated. Comparisons were made with the log-rank test. Cox proportional hazard models were used to determine the independent significance of prognostic variables., Results: Considering the dose-response relationship, P values and the discrimination of 2 risk groups, the Charlson score was the best of the tested comorbidity classifications in men selected for radical prostatectomy at age 70 years or older. Beside the tumor-related factors Gleason score 8-10 (hazard ratio 2.61, P = 0.0234) and lymph node involvement (hazard ratio 2.89, P = 0.0145), a Charlson score of 1 or greater was identified as an independent predictor of overall mortality (hazard ratio 2.16, P = 0.0441). Without comorbidity or adverse tumor-related risk factors, elderly men had an excellent 10-year overall survival probability (77% to 100%, depending on the classification used), whereas 10-year overall survival was distinctly poor in the presence of lymph node metastases (30%) or Gleason score 8-10 disease (33%)., Conclusions: The Charlson comorbidity score may be used to stratify men selected for radical prostatectomy at age 70 years or older and to estimate long-term survival probability. In the absence of adverse tumor-related parameters or serious comorbidity, long-term survival probability is excellent in this subgroup., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objectives: To investigate the prognostic significance of the individual conditions contributing to the Charlson comorbidity score in patients selected for radical prostatectomy., Methods: A total of 1910 consecutive patients who underwent radical prostatectomy from 1992 to 2004 were studied. The Charlson score and its contributing single conditions were analyzed, and the patients were stratified into 3 age groups. Comorbid (noncancer), competing (nonprostate cancer), and overall mortality were used as the study endpoints. Mantel-Haenszel hazard ratios and Kaplan-Meier survival curves were calculated. Comparisons were made using the log-rank test., Results: Eleven comorbid conditions were significant predictors of any type of mortality in the different age groups. Eight conditions (congestive heart failure, peripheral vascular disease, cerebrovascular disease, diabetes, hemiplegia, moderate or severe renal disease, diabetes with end organ damage, moderate or severe liver disease, and metastatic solid tumor) were significant predictors of overall mortality. Two conditions (moderate or severe renal disease and metastatic solid tumor) were significant predictors of overall mortality in patients <63 years old. Five conditions (myocardial infarction, congestive heart failure, hemiplegia, moderate or severe renal disease, and diabetes with end organ damage) were significant predictors in patients aged 63-69 years, and 3 (peripheral vascular disease, cerebrovascular disease, and moderate or severe liver disease) were significant in patients aged >or=70 years., Conclusions: In patients selected for radical prostatectomy, the Charlson score can also predict the mortality risk in those >70 years of age. The selection for good risks alters, however, the prognostic weight of the individual comorbid diseases in this age group.

Purpose: We identified an age range in which comorbidity is most closely associated with premature mortality after radical prostatectomy., Materials and Methods: A total of 1,302 patients selected for radical prostatectomy were stratified according to the Charlson score, the American Society of Anesthesiologists physical status classification, the New York Heart Association classification of heart insufficiency and the classification of angina pectoris of the Canadian Cardiovascular Society. Furthermore, patients were subdivided into several age groups. Comorbid mortality and overall mortality were the study end points. The prognostic relevance of the comorbidity classifications was assessed by comparing Mantel-Haenszel HRs, p values and 10-year overall survival rates., Results: The discriminative capacity of all 4 investigated comorbidity classifications decreased when patients 70.0 years or older were included with decreasing HRs and increasing p values. Except for the American Society of Anesthesiologists classification HRs for comparing the high vs low risk groups tended to decrease and p values simultaneously tended to increase when patients younger than 63.0 years were included. In the age range of between 63.0 and 69.9 years 10-year overall survival rates differed by 14% to 28% between patients with a high vs low comorbid risk compared with 6% to 13% in the whole sample., Conclusions: The discriminative capacity of the investigated comorbidity classifications was greatest in the age group that was 63.0 to 69.9 years old. In patients younger than 63.0 or older than 70.0 years comorbidity classification seemed to contribute little to the prediction of comorbid mortality.

Objective: To investigate the consistency of several comorbidity classifications and concomitant diseases at radical prostatectomy (RP) during a 10-year period., Methods and Materials: In 1,297 patients who underwent RP between 1993 and 2002, age and several comorbidity classifications were derived from patient records and assigned to the year of surgery. Trends were evaluated using the Cochran-Armitage trend test., Results: Parallel to an increasing frequency of RPs and a shift toward more organ-confined tumors (P = 0.0094), the proportion of patients aged > or =70 years increased (P = 0.0077). The proportion of the American Society of Anesthesiologists (ASA) Physical Status class 3 increased (P < 0.0001), whereas that of ASA class 1 decreased (P < 0.0001). A Charlson score > or =1 has been assigned with an increasing frequency (P = 0.0008), whereas the trend with a Charlson score of > or =2 did not reach statistical significance (P = 0.07). In contrast to the latter 2 classifications, no significant trends were observed with classifications related to diabetes mellitus and heart disease., Conclusions: This study shows that the application of the ASA classification may change significantly over time, whereas cardiac and diabetes-related conditions, as well as the Charlson score were apparently less sensitive to changing classification standards in the RP setting.

Objectives: To investigate several comorbidity classifications as possible predictors of mortality, because the value of comorbidity as a prognostic factor is uncertain in patients older than 70 years of age and radical prostatectomy in patients older than 70 years is controversial., Methods: A total of 214 consecutive patients aged 70 years or older who underwent radical prostatectomy from December 1992 to December 2002 were stratified according to the Charlson score, American Society of Anesthesiologists physical status classification, New York Heart Association classification of cardiac insufficiency, classification of angina pectoris from the Canadian Cardiovascular Society, and age (70 to 72 versus 73 to 74 versus 75 years or older). The mean follow-up in the surviving patients was 5.1 years (range 1.3 to 12.5). A sample of 240 consecutive patients aged 67.0 to 69.9 years treated during the same period was used for comparison. The overall and comorbid mortality were the study endpoints. Mantel-Haenszel hazard ratios were calculated. Comparisons were made using the log-rank test., Results: Unlike for patients aged 67.0 to 69.9 years, for those 70 years old or older, only one of the investigated stratifications reached significance as a predictor of mortality. A New York Heart Association classification of 2+ versus 0 was significant for overall mortality (hazard ratio 5.8, P = 0.021) and comorbid mortality (hazard ratio 15.9, P = 0.046)., Conclusions: Comorbidity is of limited prognostic value in patients selected for radical prostatectomy and 70 years old or older.

The treatment of clinically locally advanced prostate carcinoma (stage cT3) remains controversial. One of the main reasons for this controversy results from the substantial staging error attached to the clinical diagnosis cT3 with overstaged T2 tumors and understaged node-positive cases. Treatment options in this situation include radical prostatectomy, external beam radiotherapy, immediate or delayed androgen deprivation treatment and the so-called 'watchful waiting'. Acceptable and often surprisingly good tumor-specific survival rates have been reported for radical prostatectomy in pT3 series--based on good clinical case selection--approaching those of pT2 series. In lymph node-positive pT3 cases, adjuvant hormone deprivation seems to prolong survival which it does not in lymph node-negative pT3 disease. A benefit of adjuvant external beam radiotherapy after radical prostatectomy for pT3 cases in prolonging overall survival has not been shown, despite the fact that it can prevent or delay biochemical and local recurrence. External beam radiotherapy as the only treatment for cT3 disease results in unfavorable tumor-specific survival rates, which can be significantly improved with adjuvant hormonal treatment with LHRH agonists. If, in case of advanced age and/or significant comorbidity, primary hormonal treatment is chosen, early hormonal deprivation therapy seems to offer marginal benefits in survival compared to delayed treatment., (Copyright (c) 2006 S. Karger AG, Basel.)

Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Several comorbidity classifications have been investigated for their suitability to assist treatment decision-making in men with early prostate cancer. In unselected patients, some serious comorbidities have been shown to be associated with a 10-year competing mortality rate clearly superseding the 50% level. The present study shows that it is hardly possible to discern meaningful subsets of patients with a 10-year risk of competing mortality of >50% by using comorbidity classifications. This finding suggests that the selecting clinicians did well in estimating the medium-term survival probability in men referred for radical prostatectomy. OBJECTIVE To identify subsets of patients who are most likely to die from competing causes ≤10 years after radical prostatectomy (RP)., PATIENTS AND METHODS In all, 2205 consecutive patients who underwent RP for clinically localized prostate cancer between 1992 and 2005 were studied. The 10-year cumulative competing mortality rates were determined in several worst-case scenarios formed by using comorbidity classifications and combinations of them., RESULTS In this sample of men selected for RP, even those with the most severe comorbidity level had a competing mortality risk of <50% ≤10 years after RP., Depending on the comorbidity classification used, the 10-year cumulative competing mortality rates differed between 16 and 39% in the whole sample and between 18 and 48% in men aged ≥65 years., CONCLUSION Clinicians do well in estimating the further life span in candidates for RP. Comorbidity classifications may assist treatment choice in this population but are not able to discern meaningful subsets to be excluded from curative treatment because of a life expectancy falling below a limit of 10 years. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prevalence and distribution of comorbidity and its association with perioperative complications in patients undergoing radical prostatectomy (RPE). Methods: In 431 unselected RPE patients, the American Society of Anesthesiologists Physical Status classification (ASA-PS), the New York Heart Association classification of cardiac insufficiency (NYHA), the classification of angina pectoris of the Canadian Cardiovascular Society (CCS), height, weight, the body mass index (BMI), and the number of concomitant diseases (NCD) were assessed and related to perioperative cardiovascular complications. Results: In RPE patients less than 70 years old, comorbidity rose nearly continuously with increasing age. However, after reaching an age of 70 years, the proportion of NYHA-0 patients increased (60–64 years, 86%; 65–69 years, 85%; ≥70 years, 87%). Furthermore, the severe comorbidities decreased in patients selected for RPE aged 70 or more years. There was a nonsignificant trend towards higher comorbidity in patients with perioperative cardiovascular complications. Conclusions: These data suggest that documentation of the distribution of ASA-PS, CCS, NYHA and of concomitant diseases might be helpful to characterize the general health status and the degree of selection of prostate cancer treatment populations especially in series with a high portion of patients aged 70 or more years. Concerning perioperative complications, the individual predictive value of comorbidity seems to be poor in the radical prostatectomy setting.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: The case of a 74-year-old man is reported who suffered from a locally advanced prostate cancer treated by neoadjuvant hormonal ablation, followed by prostatectomy. Histological examination of the prostatectomy specimen disclosed an adenocarcinoma with partial, Paneth-like, neuroendocrine differentiation. Extensive perineural tumor invasion was found with a total of 921 perineural tumor foci. Neuroendocrine differentiation of tumor cells was accentuated in perineural locations and was associated with an elevated expression of N-CAM and vimentin, and a reduced expression of E-Cadherin and Ki-67. We hypothesize that neuroendocrine differentiation may promote perineural invasion of prostate cancer cells by a “catherin-switch” and by mechanisms involving epithelial-mesenchymal transition. [Copyright &y& Elsevier]

Abstract: Objective:: To compare different comorbidity classifications as predictors of survival after radical prostatectomy (RPE). Methods:: 444 consecutive RPE patients (mean follow-up 6.9 years) were stratified according to age, Charlson score, American Society of Anesthesiologists Physical Status classification (ASA), New York Heart Association classification of cardiac insufficiency, classification of angina pectoris of the Canadian Cardiovascular Society and a combination of both cardiac risk scores. Comorbid and overall mortality were the study endpoints. Mantel-Haenszel hazard ratios, p values and 8-year survival probabilities were used for comparison. A modified Charlson score was created by a restriction to the five individual conditions significantly associated with comorbid mortality. Results:: When three strata (low, intermediate, high risk) were used, all stratifications displayed dose-response patterns and reached statistical significance as predictors of survival at least for the high-risk group. Only the ASA classification, however, discriminated three significantly different risk groups. Only the modified (restricted) Charlson score reached statistical significance as predictor of comorbid mortality in the age group of 70 or more years. Conclusion:: Although all investigated comorbidity classifications had some prognostic relevance in patients selected for RPE, their clinical applicability appears to be limited beyond the 70th year of life. The results of this study might, nevertheless, assist the treatment decision in patients with low-risk tumors eligible for modern watchful waiting strategies who mainly belong to the age group between 60–69 years where comorbidity seems to be of distinct prognostic value. [Copyright &y& Elsevier]