Decreased Overall and Bladder Cancer-Specific Mortality with Adjuvant Chemotherapy After Radical Cystectomy: Multivariable Competing Risk Analysis.

UNLABELLED: Adding chemotherapy to radical cystectomy (RC) may improve outcome. Neoadjuvant treatment is advocated by guidelines based on meta-analysis data but is severely underused in clinical practice. Adjuvant treatment of patients at risk could be an alternative. We analyzed a sample of 798 patients who underwent RC between 1993 and 2011 for high-risk superficial or muscle-invasive urothelial or undifferentiated bladder cancer, of which 23% received adjuvant cisplatin-based chemotherapy and %5 received neoadjuvant chemotherapy. The use of adjuvant chemotherapy was an independent predictor of decreased overall mortality (hazard ratio [HR]: 0.50; 95% confidence interval [CI], 0.38-0.66; p<0.0001) and bladder cancer-specific mortality (HR: 0.71; 95% CI, 0.52-0.97; p=0.0321), but it was not associated with competing mortality. Similar figures were obtained when analyzing the number of cisplatin-containing cycles administered or when restricting the analysis to patients with lymph node-positive or extravesical but lymph node-negative disease, suggesting a mortality-reducing treatment effect after adjusting for several patient- and tumor-related confounders. Future trials should directly compare the concepts of neoadjuvant and adjuvant application of chemotherapy in candidates for RC. PATIENT SUMMARY: Adjuvant chemotherapy may decrease overall and bladder cancer-specific mortality after radical cystectomy (RC). Future trials should directly compare the concepts of neoadjuvant and adjuvant application of chemotherapy in candidates for RC.

Survival analysis in men undergoing radical prostatectomy at an age of 70 years or older.

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.

Detailed analysis of Charlson comorbidity score as predictor of mortality after radical prostatectomy.

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.

Interaction between age and comorbidity as predictors of mortality after radical prostatectomy.

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.

Magnetic resonance imaging of bone metastases in patients with nonseminomatous germ cell tumors.

OBJECTIVE: To investigate the role of magnetic resonance imaging (MRI) of bone metastases in nonseminomatous germ cell tumors. METHODS AND MATERIALS: There were 5 consecutive patients with bone metastases from nonseminomatous germ cell tumors treated between 2003 and 2006 who underwent imaging studies, including MRI. The characteristic imaging findings are discussed in the light of the clinical course. RESULTS: Of the 5 patients, 3 had symptoms related to bone involvement at diagnosis. All patients received conventional x-ray of their bony lesions, but only 1 of them was considered abnormal. Skeletal MRI was obtained in all patients. A bone scan was available in 3 cases with spinal involvement. It was normal in 1 case and detected only a minority of the lesions visible on MRI in the other 2 cases. Follow-up MRIs were available in all patients. A partial resolution of bone involvement during chemotherapy was observed in only 1 of them. In 2 cases, there was a slight progression of a diffuse alteration of the bone marrow during treatment. In 1 patient, severe spinal bone marrow changes were visible on MRI 2 years after cessation of treatment without evidence of disease recurrence. CONCLUSIONS: MRI may disclose bone metastases in nonseminomatous germ cell tumors, which otherwise may be missed. MRI findings of bone lesions during treatment do not directly reflect the course of the disease and have to be interpreted with caution using clinical information.

Changing comorbidity classification patterns at radical prostatectomy during a 10-year period.

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.

Perioperative complications of radical cystectomy in a contemporary series.

OBJECTIVES: Radical cystectomy is the preferred standard treatment for patients with muscle-invasive bladder cancer. With improvements in intra- and perioperative care lower complication rates have been reported. We retrospectively evaluated our series of patients who underwent radical cystectomy for advanced bladder cancer for perioperative complications as well as operative time, postoperative hospital stay and transfusion rates. PATIENTS AND METHODS: Between April 1993 and August 2005, 516 radical cystectomies were performed for muscle infiltrating transitional cell carcinoma and other types of neoplastic diseases of the bladder at our institution. The average age was 66.3 yr (31-89). RESULTS: The perioperative mortality rate was 0.8%. A total of 141 patients (27.3%) developed at least one perioperative complication. The most frequent medical complications were subileus in 20 (3.9%) patients, deep venous thrombosis in 24 (4.7%), and enterocolitis in 10 (1.9%). Surgical complications included pelvic lymphoceles in 42 (8.1%) patients, wound dehiscence in 46 (8.9%), pelvic hematoma in 4 (0.8%), peritonitis in 4 (0.8%) and small bowel obstruction in 4 (0.8%). The total early reoperation rate was 6.2%. Operative time, postoperative hospital stay and average number of blood units transfused decreased over the period 1993-2005. CONCLUSIONS: Radical cystectomy today is a procedure with an acceptable rate of perioperative morbidity and mortality. Improvements in surgical technique and anaesthesia as well as increased quality of perioperative care in recent years have resulted in reduced morbidity and shorter hospital stay.

Comorbidity is poor predictor of survival in patients undergoing radical prostatectomy after 70 years of age.

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.

Comparison of tumor- and comorbidity-related predictors of mortality after radical prostatectomy.

OBJECTIVES: To identify and compare tumor- and non-tumor-related predictors of survival after radical prostatectomy and to incorporate the latter into the tumor node metastasis classification of prostate cancer. MATERIAL AND METHODS: A total of 402 patients who underwent radical prostatectomy (mean follow-up period 6.9 years) were stratified according to postoperative tumor stage, Gleason score, prostate-specific antigen level, age and five comorbidity classifications. Cox proportional hazard models were used to identify independent prognostic factors predicting overall survival. RESULTS: Comorbidity (American Society of Anesthesiologists Physical Status classification), Gleason score and age, but not tumor stage, were independent predictors of overall survival. Based on tumor stage and the identified independent prognostic factors, an easily applicable prognostic score was developed to predict overall mortality. CONCLUSION: A prognostic classification of radical prostatectomy patients based on Gleason score, comorbidity and age and supplementary to a coarsened variant of the tumor node metastasis classification may be of clinical value.

Feasibility and limitations of comorbidity measurement in patients undergoing radical prostatectomy.

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.

Qualitative and quantitative assessment of urinary cytokeratin 8 and 18 fragments compared with voided urine cytology in diagnosis of bladder carcinoma.

OBJECTIVES: To evaluate the value of urine tests based on the detection of cytokeratins 8 and 18 for the diagnosis of bladder cancer compared with urine cytology. METHODS: Samples from 112 patients before transurethral resection (group 1), 40 patients before secondary surgical treatment (group 2), 29 healthy control subjects (group 3, controls), and 10 women with acute urinary tract infection (group 4, controls) were examined with the UBC Rapid and UBC II enzyme-linked immunosorbent assay (ELISA) tests and voided urine cytology. RESULTS: Of the 112 patients in group 1, 90 had transitional cell carcinoma. For the UBC Rapid, UBC ELISA, and cytology, the sensitivity and specificity was 64.4%, 46.6%, and 70.5% and 63.6%, 86.3%, and 79.5%, respectively. The cytology had the greatest accuracy (72.3%) compared with both cytokeratin tests (54.4% and 64.2%). For all three tests, sensitivity increased with tumor grade and stage. In group 2, 16 of 40 patients had residual carcinoma. The sensitivity was similar for all three tests, and the specificity of cytology was lower compared with its specificity in group 1 (47.9% versus 70.5% in group 1). In the controls with or without urinary tract infection, the specificity of cytology was greater than that of both other tests. The combination of the UBC ELISA test with cytology increased the sensitivity to 83% (specificity 68%). CONCLUSIONS: Both cytokeratin tests detected patients with transitional cell carcinoma, but were inferior to voided urine cytology in test quality.

Which conditions contributing to the Charlson score predict survival after radical prostatectomy?

PURPOSE: The Charlson score is likely to be the most frequently used comorbidity measure in prostate cancer. However, to our knowledge the individual prognostic significance of contributing conditions has not been previously studied in a radical prostatectomy sample. MATERIALS AND METHODS: A total of 444 consecutive patients were entered into this study. The 19 conditions contributing to the Charlson score were obtained from the preoperative cardiopulmonary risk assessment and the hospital discharge document. Mantel-Haenszel hazard ratios were estimated for comorbid (noncancer) and overall survival. Thereafter, the Charlson score was refined by excluding conditions with low predictive value. RESULTS: Mean followup was 5.9 years. Only 3 single conditions (congestive heart failure, peripheral vascular disease and severe renal disease) were significantly associated with excess overall mortality. Concerning comorbid mortality, in addition to these 3 diseases, chronic pulmonary disease was associated with increased risk. Refinement of the Charlson score improved the circumscription of patients at risk for premature death after radical prostatectomy. CONCLUSIONS: This study suggests that restricting the Charlson score to some clinically meaningful diseases may increase its usefulness in candidates for radical prostatectomy. The conventional Charlson score did not add clinically meaningful information supplementary to congestive heart failure, which is the most important single contributing condition.

Comparison of the American Society of Anesthesiologists Physical Status classification with the Charlson score as predictors of survival after radical prostatectomy.

OBJECTIVES: To compare the American Society of Anesthesiologists Physical Status (ASA) classification with the Charlson score in the radical prostatectomy setting. The ASA classification is a widely accepted way to evaluate perioperative risk. At present, the Charlson score is probably the most frequently used comorbidity measure to predict long-term survival after radical prostatectomy. METHODS: A total of 444 consecutive patients were enrolled in this study. The ASA classification was obtained from the anesthesia chart, and the Charlson score was assigned based on conditions noted during the preoperative cardiopulmonary risk assessment or mentioned on the discharge document. Kaplan-Meier time-event curves and Mantel-Haenszel hazard ratios were estimated for comorbid (noncancer) and overall survival. RESULTS: After a mean follow-up of 5.9 years, both classifications were able to predict comorbid and overall survival in dose-response patterns. The ASA classification was superior in terms of a clearer discrimination of the survival curves (lower P values, higher hazard ratios). Both classifications identified a high-risk group (ASA 3 and Charlson score 2 or more), but only the ASA classification sufficiently defined a low-risk group (ASA 1). CONCLUSIONS: In experienced hands, the ASA classification is a promising tool to improve the classification of prognostic comorbidity in the radical prostatectomy setting and may be used as an alternative to the Charlson score.

Preoperative cardiopulmonary risk assessment as predictor of early noncancer and overall mortality after radical prostatectomy.

OBJECTIVES: To evaluate the capability of the preoperative cardiopulmonary risk assessment to predict early noncancer and overall mortality after radical prostatectomy for clinically localized prostate cancer. METHODS: In 444 consecutive radical prostatectomy patients, the American Society of Anesthesiologists Physical Status classification and the presence of cardiac insufficiency (New York Heart Association classification), angina pectoris (Canadian Cardiovascular Society classification), diabetes, hypertension, history of thromboembolism, and chronic obstructive or restrictive pulmonary disease were assessed. Kaplan-Meier time-event curves and Mantel-Haenszel hazard ratios were estimated for noncancer (other deaths were censored) and overall mortality. Cox proportional hazard models were used to analyze possible combined effects of risk factors. RESULTS: During an average follow-up of 4.7 years, 36 patients died: 15 of noncancer causes, 14 of prostate cancer, 6 of other cancers, and 1 in a car accident. The comorbidity scores for American Society of Anesthesiologists Physical Status classification, New York Heart Association classification, and Canadian Cardiovascular Society classification and combinations between the latter two scores were significantly associated with early noncancer mortality in a dose-response pattern. Furthermore, patients with chronic obstructive pulmonary disease were at increased risk. The association with overall mortality was less strong. CONCLUSIONS: The preoperative cardiopulmonary risk assessment may be used as a predictor of early noncancer and overall mortality after radical prostatectomy and should be evaluated further as a source of prognostic information in surgical oncology.