Roman Mayr

Comorbidity and Performance Indices as Predictors of Cancer-Independent Mortality But Not of Cancer-Specific Mortality After Radical Cystectomy for Urothelial Carcinoma of the Bladder

BACKGROUND Comorbidity and performance indices allow assessment of preoperative health status. However, the optimal tool for use in patients with urothelial carcinoma of the bladder (UCB) who are undergoing radical cystectomy (RC) has not yet been established. OBJECTIVE To evaluate correlation of Adult Comorbidity Evaluation-27 (ACE27), Charlson Comorbidity Index, Age-Adjusted Charlson Comorbidity Index, Eastern Cooperative Oncology Group performance status, and American Society of Anesthesiologists (ASA) score with survival. DESIGN, SETTING, AND PARTICIPANTS A retrospective multicenter study was carried out on 555 unselected consecutive patients who underwent RC for UCB from 2000 to 2010. INTERVENTION RC with pelvic lymph node dissection in patients with UCB without neoadjuvant chemotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Cox regression models were calculated with established variables to assess predictive capacity for cancer-specific mortality (CSM) and cancer-independent mortality (CIM). RESULTS AND LIMITATIONS All indices were independent predictors for CIM but not for CSM. The ASA score was the only index that significantly increased the predictive accuracy of the predefined CIM model (+2.3%; p=0.045). To create a clinically valuable tool, we devised a weighted prognostic model including age and the best prognosticators within the performance and comorbidity scores (ASA/ACE27 0-1/2-3). A 3-yr CIM rate of 8%, 26%, and 47% was calculated for the low-, intermediate-, and high-risk groups, respectively. Patients >75 yr of age with ASA 3/4 and ACE27 >1 exhibited a CIM risk seven times greater than patients ≤75 yr with ASA 1/2 and ACE27 0/1. This study is limited by the short follow-up and its retrospective nature. CONCLUSIONS Comorbidity and performance assessment is mandatory in the preoperative prediction of CIM for patients undergoing RC for UCB. The present results indicate that the ASA score is the tool of choice. External and prospective validation is warranted.

Prediction of 90-day Mortality After Radical Cystectomy for Bladder Cancer in a Prospective European Multicenter Cohort

BACKGROUND Despite recent improvements, radical cystectomy (RC) is still associated with adverse rates for 90-d mortality. OBJECTIVE To validate the performance of the Isbarn nomogram incorporating age and postoperative tumor characteristics for predicting 90-d RC mortality in a multicenter series and to generate a new nomogram based strictly on preoperative parameters. DESIGN, SETTING, AND PARTICIPANTS Data of 679 bladder cancer (BCa) patients treated with RC at 18 institutions in 2011 were prospectively collected, from which 597 patients were eligible for final analysis. INTERVENTION RC for BCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS An established prediction tool, the Isbarn nomogram, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver operating characteristics-derived area under the curve. Calibration plots examined the relationship between predicted and observed probabilities. Univariable and multivariable logistic regression models were fitted to assess the impact of preoperative characteristics on 90-d mortality. RESULTS AND LIMITATIONS The 30-, 60-, and 90-d mortality rates in the development cohort (n=597) were 2.7%, 6.7%, and 9.0%, respectively. The Isbarn nomogram predicted individual 90-d mortality with an accuracy of 68.6%. Our preoperative multivariable model identified age (odds ratio [OR]:1.052), American Society of Anesthesiologists score (OR: 2.274), hospital volume (OR: 0.982), clinically lymphatic metastases (OR: 4.111), and clinically distant metastases (OR: 7.788) (all p<0.05) as independent predictors of 90-d mortality (predictive accuracy: 78.8%). Our conclusions are limited by the lack of an external validation of the preoperative model. CONCLUSIONS The Isbarn nomogram was validated with moderate discrimination. Our newly developed model consisting of preoperative characteristics might outperform existing models. Our model might be particularly suitable for preoperative patient counseling. PATIENT SUMMARY The current report validated an established nomogram predicting 90-d mortality in patients with bladder cancer after radical cystectomy (RC). We developed a new prediction tool consisting of strictly preoperative parameters, thus allowing clinicians an optimal consultation for RC candidates.

Predictive capacity of four comorbidity indices estimating perioperative mortality after radical cystectomy for urothelial carcinoma of the bladder

Study Type – Prognosis (case series)

The Role of C-Choline-PET/CT-Guided Secondary Lymphadenectomy in Patients with PSA Failure after Radical Prostatectomy: Lessons Learned from Eight Cases.

Introduction. 11C-choline-PET/CT is a promising technique for detection/restaging of patients with biochemical failure (BF) after curative therapy for prostate cancer (PCA). The aim of this paper was to evaluate the PSA response in patients with BF after radical prostatectomy (RP) who underwent secondary lymphadenectomy (LAD) due to 11C-choline-PET/CT findings. Material and Methods. Eight patients with BF and positive lymph nodes in 11C-choline-PET/CT after RP were retrospectively included in the study. Extended LAD until the common iliac arteries was performed in all patients. Results. Six of 8 patients had histologically proven lymph node metastases. Four patients showed an initial PSA reduction after LAD, and in 4 patients the PSA increased. Two of the latter had no histological lymph node metastases. Conclusions. Because 50% of our patients showed an initial PSA response, our data suggest that positive 11C-choline-PET/CT after RP and BF could help to select patients that could benefit from secondary LAD.

The Charlson Comorbidity Index Predicts Survival after Disease Recurrence in Patients following Radical Cystectomy for Urothelial Carcinoma of the Bladder

Objective: To identify prognostic clinical and histopathological parameters, including comorbidity indices at the time of radical cystectomy (RC), for overall survival (OS) after recurrence following RC for urothelial carcinoma of the bladder (UCB). Materials and Methods: A retrospective multicenter study was carried out in 555 unselected consecutive patients who underwent RC with pelvic lymph node dissection for UCB from 2000 to 2010. A total of 227 patients with recurrence comprised our study group. Cox proportional hazards regression models were calculated with established variables to assess their independent influence on OS after recurrence. Results: The median time from RC to recurrence and the median OS after recurrence was 10.9 and 5.4 months, respectively. Neither the time to recurrence nor the type of recurrence (systematic vs. local) was predictive of the OS. In contrast, age (hazard ratio (HR) 1.53, p = 0.011), lymph node metastasis (HR 1.56, p = 0.007), and positive surgical margins (HR 1.53, p = 0.046) significantly affected the OS after disease recurrence. In addition, the dichotomized Charlson comorbidity index (CCI; dichotomized into >2 vs. 0-2) was the only comorbidity score with an independent prediction of OS (HR 1.41, p = 0.033). We observed a significant gain in the base models predictive accuracy, i.e. from 68.4 to 70.3% (p < 0.001), after inclusion of the dichotomized CCI. Conclusions: We present the first outcome study of comorbidity indices used as predictors of OS after disease recurrence in patients undergoing RC for UCB. The CCI at the time of RC had no significant influence on the time to recurrence but represented an independent predictor of OS after disease recurrence.

The Use of Neoadjuvant Chemotherapy in Patients With Urothelial Carcinoma of the Bladder: Current Practice Among Clinicians

Micro‐Abstract Neoadjuvant chemotherapy before radical cystectomy is recommended in patients with bladder cancer in clinical stages T2‐T4a, cN0M0. We analyzed the frequency and current practice of neoadjuvant chemotherapy in 679 patients using uni‐ and multivariable regression analyses and using a questionnaire. We found a great discrepancy between guideline recommendations and practice patterns, despite medical indication and interdisciplinary tumor board discussion. Introduction: Guidelines recommend neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in patients with urothelial carcinoma of the bladder in clinical stages T2‐T4a, cN0M0. We examined the frequency and current practice of NAC and sought to identify predictors for the use of NAC in a prospective contemporary cohort. Materials and Methods: We analyzed prospective data from 679 patients in the PROMETRICS (PROspective MulticEnTer RadIcal Cystectomy Series 2011) database. All patients underwent RC in 2011. Uni‐ and multivariable regression analyses identified predictors of NAC application. Furthermore, a questionnaire was used to evaluate the practice patterns of NAC at the PROMETRICS centers. Results: A total of 235 patients (35%) were included in the analysis. Only 15 patients (2.2%) received NAC before RC. Younger age (< 70 years; P = .035), lower case volume of the center (< 30 RC/year; P < .001), and advanced tumor stage (≥ cT3; P = .038) were identified as predictors for NAC. Of the 200 urologists who replied to the questionnaire, 69% (n = 125) declared tumor stage cT3‐4 a/o N1M0 to be the best indication for NAC application, although 45% of the urologists stated that they would not perform NAC despite recommendations. The decision for NAC was made by the individual urologist in 69% of cases, and only 29% reported that all cases were discussed in an interdisciplinary tumor board. Conclusion: NAC was rarely applied in the present cohort. We observed a discrepancy between guideline recommendations and practice patterns, despite medical indication and pre‐therapeutic interdisciplinary discussion. The potential benefit of NAC within a multimodal approach seems to be neglected by many urologists.

Comparative Analysis of Gender-Related Differences in Symptoms and Referral Patterns prior to Initial Diagnosis of Urothelial Carcinoma of the Bladder: A Prospective Cohort Study

Objective: To analyze gender-specific differences regarding clinical symptoms, referral patterns and tumor biology prior to initial diagnosis of urothelial carcinoma of the bladder (UCB). Methods: A consecutive series of patients with an initial diagnosis of UCB was included. All patients completed a questionnaire on demographics, clinical symptoms and referral patterns. Results: In total, 68 patients (50 men, 18 women) with newly diagnosed UCB at admission for transurethral resection of bladder tumors were recruited. Dysuria was more often observed in women (55.6 vs. 38.0%, p = 0.001). Direct consultation of the urologist was conducted by 84.0% of males and 66.7% of females (p = 0.120). One third of the women saw their general practitioner and/or gynecologist once or twice (p = 0.120) before referral to the urologist. Furthermore, women were significantly more often treated for urinary tract infections than men (61.1 vs. 20.0%, p = 0.005). Cystoscopy at first presentation to the urologist was more often performed in men than women (88.0 vs. 66.7%, p = 0.068), with a more favorable tumor detection rate at first cystoscopy in men (96.0 vs. 50.0%, p < 0.001). Conclusions: Delayed referral patterns might lead to deferred diagnosis of UCB and consequently to adverse outcome. Thus, primary care physicians might consider referring patients with bladder complaints to specialized care earlier.

Recurrence and progression in patients with non-muscle invasive bladder cancer: prognostic models including multicolor fluorescence in situ hybridization molecular grading.

To test the prognostic value of multicolor fluorescence in situ hybridization analyses of tumor cells in urine for prediction of the recurrence and progression of tumor in patients with intermediate risk non‐muscle invasive bladder cancer.

Radical cystectomy and the implications of comorbidity.

Radical cystectomy (RC) with pelvic lymph node dissection constitutes the gold standard treatment for muscle-invasive urothelial carcinoma of the bladder and high-risk nonmuscle-invasive disease refractory to instillation therapy. Although RC is performed with curative intent, the overall 5-year survival has been reported to be as low as 62% in the current literature. Various clinicopathological parameters determine post-RC outcome, but besides these, the role of comorbidity has gained increasing attention. In the current clinical practice, comorbidity information is quantified using various evaluated comorbidity indices. In this paper, we discuss the most recent data on comorbidity and performance indices assessed in patients undergoing RC and highlight their clinical implications.

Sarcopenia as a comorbidity‐independent predictor of survival following radical cystectomy for bladder cancer

A multicentre study was conducted to investigate the impact of sarcopenia as an independent predictor of oncological outcome after radical cystectomy for bladder cancer.