Which comorbidity classification is best suited to identify patients at risk for 90-day and long-term non-bladder cancer mortality after radical cystectomy?

PURPOSE: There is no consensus on the best comorbidity measure in candidates for radical cystectomy. The aim of this study was to identify tool best suited to identify patients at risk for 90-day or premature long-term non-bladder cancer mortality. METHODS: We studied 1268 patients who underwent radical cystectomy to identify patients at risk for 90-day and later-than-90-day mortality, respectively. Six classifications were investigated as possible predictors of both types of mortality. Multivariable models including age as continuous variable and each classification separately were calculated. A heuristic ranking was based on the evaluation of the hazard ratios, p values, Akaike's information criteria, and concerning the logit models also the areas under the curve. RESULTS: The median follow-up was 5.7 years. Within 90 days after surgery, the mortality rate was 4.2%. The greatest independent contribution concerning the prediction of 90-day mortality was seen with the American Society of Anesthesiologists (ASA) physical status classification (classes 3-4 versus 1-2: hazard ratio 7.98, 95% confidence interval 3.54-18.01, p < 0.0001). In the longer term, countable diseases (Canadian Cardiovascular Society classification of angina pectoris, conditions contributing the Charlson score) were of greater importance. The results of heuristic ranking were confirmed by multivariate analyses including age and all classifications together. CONCLUSIONS: Besides to chronological age, clinicians should pay particular attention to the ASA classification to identify patients at risk for 90-day mortality after radical cystectomy, whereas long-term mortality is more determined by countable comorbid diseases.

Validation of a Questionnaire-Suitable Comorbidity Index in Patients Undergoing Radical Cystectomy.

OBJECTIVE: To investigate the capability of a modified self-administrable comorbidity index recommended in the standard sets for neoplastic diseases published by the International Consortium for Health Outcomes Measurement (ICHOM) to predict 90-day and long-term mortality after radical cystectomy. METHODS: A single-center series of 1,337 consecutive patients who underwent radical cystectomy for muscle-invasive or high-risk non-muscle-invasive urothelial or undifferentiated bladder cancer were stratified by the modified self-administrable comorbidity index and Charlson score, respectively. Multivariate logit models (for 90-day mortality) and proportional-hazards models (for overall and non-bladder cancer mortality) were used for statistical workup. RESULTS: Considering 90-day mortality, both comorbidity indexes contributed independent information when analyzed together with age (p < 0.0001). The Charlson score performed slightly better (area under the curve [AUC] 0.74 vs. 0.72 for the ICHOM-recommended comorbidity index). Considering 5-year overall mortality in 727 patients with complete observation, the performance of both measures was similar (AUC 0.63 vs. 0.62, including age AUC 0.66 for both indexes). With 6-sided stratifications, the modified self-administrable comorbidity index separated the risk groups slightly better (p values for directly neighboring curves: 0.0068-0.1043 vs. 0.0001-0.8100). CONCLUSION: The ICHOM-recommended modified self-administrable comorbidity index is capable of predicting 90-day mortality and long-term non-bladder cancer mortality after radical cystectomy similarly to the commonly used Charlson score.

Incidence and survival outcomes in patients with upper urinary tract urothelial carcinoma diagnosed with variant histology and treated with nephroureterectomy.

OBJECTIVE: To evaluate the incidence and survival outcomes of histological variants of upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analysed data from 1610 patients treated with RNU for clinically non-metastatic UTUC between 1990 and 2016 in several centres participating in the UTUC Collaboration. Histological variants were classified as micropapillary, squamous, sarcomatoid and other, including other rare variants (<10 cases for each). Multivariable competing risk analyses were conducted to assess the effect of variant histology on overall recurrence and cancer-specific mortality (CSM). RESULTS: Overall, 1460 patients (91%) had pure urothelial carcinoma (PUC), whereas 150 (9%) were diagnosed with a variant histology, including 89 (5.0%), 41 (2.0%), 10 (1.0%) and 10 (1.0%) cases of micropapillary, squamous, sarcomatoid and other tumours, respectively. Variant histology was associated with the presence of adverse pathological features compared with PUC, including non-organ-confined disease (59% vs 38%; P < 0.001), lymph node invasion (28% vs 24%; P = 0.02), high-grade disease (88% vs 71%; P < 0.001), tumour necrosis (28% vs 16%; P = 0.001) and positive surgical margins (15% vs 8%; P = 0.01). In competing risk analysis, micropapillary variant was the only factor associated with worse recurrence (sub-hazard ratio [SHR] 2.27, 95% confidence interval [CI] 1.25-4.79; P = 0.02) whereas sarcomatoid variant was associated with worse CSM (SHR 16.8, 95% CI 6.86-41.17; P < 0.001). CONCLUSION: We found that one out of 10 patients with UTUC treated with RNU had variant histology. Only micropapillary and sarcomatoid variants were associated with poorer oncological outcomes after adjusting for available confounding factors.

Predicting 90-day and long-term mortality in octogenarians undergoing radical cystectomy.

BACKGROUND: Radical cystectomy bears a considerable perioperative mortality risk particularly in elderly patients. In this study, we searched for predictors of perioperative and long-term competing (non-bladder cancer) mortality in elderly patients selected for radical cystectomy. METHODS: We stratified 1184 consecutive patients who underwent radical cystectomy for high risk superficial or muscle-invasive urothelial or undifferentiated carcinoma of bladder into two groups (age < 80 years versus 80 years or older). Multivariable and cox proportional hazards models were used for data analysis. RESULTS: Whereas Charlson score and the American Society of Anesthesiologists (ASA) physical status classification (but not age) were independent predictors of 90-day mortality in younger patients, only age predicted 90-day mortality in patients aged 80 years or older (odds ratio per year 1.24, p = 0.0422). Unlike in their younger counterparts, neither age nor Charlson score or ASA classification were predictors of long-term competing mortality in patients aged 80 years or older (hazard ratios 1.07-1.10, p values 0.21-0.77). CONCLUSIONS: This data suggest that extrapolations of perioperative mortality or long-term mortality risks of younger patients to octogenarians selected for radical cystectomy should be used with caution. Concerning 90-day mortality, chronological age provided prognostic information whereas comorbidity did not.

An orthotopic xenograft model for high-risk non-muscle invasive bladder cancer in mice: influence of mouse strain, tumor cell count, dwell time and bladder pretreatment.

BACKGROUND: Novel theranostic options for high-risk non-muscle invasive bladder cancer are urgently needed. This requires a thorough evaluation of experimental approaches in animal models best possibly reflecting human disease before entering clinical studies. Although several bladder cancer xenograft models were used in the literature, the establishment of an orthotopic bladder cancer model in mice remains challenging. METHODS: Luciferase-transduced UM-UC-3LUCK1 bladder cancer cells were instilled transurethrally via 24G permanent venous catheters into athymic NMRI and BALB/c nude mice as well as into SCID-beige mice. Besides the mouse strain, the pretreatment of the bladder wall (trypsin or poly-L-lysine), tumor cell count (0.5 × 106-5.0 × 106) and tumor cell dwell time in the murine bladder (30 min - 2 h) were varied. Tumors were morphologically and functionally visualized using bioluminescence imaging (BLI), magnetic resonance imaging (MRI), and positron emission tomography (PET). RESULTS: Immunodeficiency of the mouse strains was the most important factor influencing cancer cell engraftment, whereas modifying cell count and instillation time allowed fine-tuning of the BLI signal start and duration - both representing the possible treatment period for the evaluation of new therapeutics. Best orthotopic tumor growth was achieved by transurethral instillation of 1.0 × 106 UM-UC-3LUCK1 bladder cancer cells into SCID-beige mice for 2 h after bladder pretreatment with poly-L-lysine. A pilot PET experiment using 68Ga-cetuximab as transurethrally administered radiotracer revealed functional expression of epidermal growth factor receptor as representative molecular characteristic of engrafted cancer cells in the bladder. CONCLUSIONS: With the optimized protocol in SCID-beige mice an applicable and reliable model of high-risk non-muscle invasive bladder cancer for the development of novel theranostic approaches was established.

Impact of photodynamic diagnosis-assisted transurethral resection of bladder tumors on the prognostic outcome after radical cystectomy: results from PROMETRICS 2011.

PURPOSE: Results of a retrospective single-institution study recently suggested improved prognostic outcomes in patients undergoing photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) prior to radical cystectomy (RC). We sought to validate the prognostic influence of PDD-assisted TURBT on survival after RC by relying on a multi-institutional dataset. METHODS: To provide a homogeneous study population, patients with organ metastasis at the time of RC and/or after neoadjuvant chemotherapy were excluded from analysis, which resulted in overall 549 bladder cancer (BC) patients from 18 centers of the Prospective Multicenter Radical Cystectomy Series 2011 (PROMETRICS 2011). To evaluate the influence of PDD conducted during primary or final TURBT on cancer-specific mortality (CSM) and overall mortality (OM) after RC, bootstrap-corrected multivariate Cox proportional-hazards regression models were applied (median follow-up: 25 months; IQR: 19-30). Sensitivity analyses were performed for both patients with pure urothelial carcinoma and patients undergoing one single TURBT only. RESULTS: In 88 (16.0 %) and 100 (18.2 %) patients, PDD was used in primary and final TURBTs, respectively. In 335 (61.0 %) patients, a single TURBT was performed prior to RC; in 194 patients (35.3 %), TURBT had been performed in a different center. CSM and OM rates at 3 years were 32 and 40 %, respectively. Use of PDD during primary or final TURBT was no independent predictor of CSM or OM. These results were internally valid and were confirmed in sensitivity analyses. CONCLUSIONS: PDD utilization during TURBT prior to RC does not independently impact the prognosis of BC patients after RC.

Trends of lymphadenectomy in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy.

INTRODUCTION: To evaluate temporal trends in the delivery and extent of lymphadenectomy (LND) in radical nephroureterectomy (RNU) performed in upper tract urothelial carcinoma (UTUC) patients. METHODS: We evaluated a multi institutional collaborative database composed by 1512 consecutive patients diagnosed with UTUC treated with RNU between 1990 and 2016. Year of surgery were grouped in five periods: 1990-1996, 1997-2002, 2003-2007, 2008-2012 and 2013-2016. Data about LND were available for all patients and numbers of nodes removed and positive were reported by dedicate uropathologists. The Mann-Whitney and Chi square tests were used to compare the statistical significance of differences in medians and proportions, respectively. RESULTS: Five hundred forty-five patients (36.0%) received a concomitant LND while 967 (64.0%) did not; 41.9% of open RNU patients received a concomitant LND compared to 24.4% of laparoscopic RNU patients. The rate of concomitant LND increased with time in the overall, laparoscopic and open RNU patients (all p < 0.03). Patients treated with open RNU also had an increasing likelihood to receive an adequate concomitant LND (p < 0.001) while those undergoing a laparoscopic approach did not (p = 0.1). Patients treated with concomitant LND had a median longer operative time of 20 min (p = 0.01). There were no differences in perioperative outcomes and complications between patients who received a concomitant LND and those who did not (p > 0.1). CONCLUSION: Although an increased trend was observed, most patients treated with RNU did not receive LND. Surgeons using a laparoscopic RNU were less likely to perform a concomitant LND, and when done, they remove less nodes.

Prediction of cancer-specific survival after radical cystectomy in pT4a urothelial carcinoma of the bladder: development of a tool for clinical decision-making.

OBJECTIVE: To externally validate the pT4a-specific risk model for cancer-specific survival (CSS) proposed by May et al. (Urol Oncol 2013; 31: 1141-1147) and to develop a new pT4a-specific nomogram predicting CSS in an international multicentre cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) PATIENTS AND METHODS: Data from 856 patients with pT4a UCB treated with RC at 21 centres in Europe and North-America were assessed. The risk model proposed by May et al., which includes female gender, presence of positive lymphovascular invasion (LVI) and lack of adjuvant chemotherapy administration as adverse predictors for CSS, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver-operating characteristic-derived area under the curve. A nomogram for predicting CSS in pT4a UCB after RC was developed after internal validation based on multivariable Cox proportional hazards regression analysis evaluating the impact of clinicopathological variables on CSS. Decision-curve analyses were applied to determine the net benefit derived from the two models. RESULTS: The estimated 5-year-CSS after RC was 34% in our cohort. The risk model devised by May et al. predicted individual 5-year-CSS with an accuracy of 60.1%. In multivariable Cox proportional hazards regression analysis, female gender (hazard ratio [HR] 1.45), LVI (HR 1.37), lymph node metastases (HR 2.54), positive soft tissue surgical margins (HR 1.39), neoadjuvant (HR 2.24) and lack of adjuvant chemotherapy (HR 1.67, all P < 0.05) were independent predictors of an adverse CSS rate and formed the features of our nomogram with a predictive accuracy of 67.1%. Decision-curve analyses showed higher net benefits for the use of the newly developed nomogram in our cohort over all thresholds. CONCLUSIONS: The risk model devised by May et al. was validated with moderate discrimination and was outperformed by our newly developed pT4a-specific nomogram in the present study population. Our nomogram might be particularly suitable for postoperative patient counselling in the heterogeneous cohort of patients with pT4a UCB.

Age, American Society of Anesthesiologists physical status classification and Charlson score are independent predictors of 90-day mortality after radical cystectomy.

PURPOSE: Radical cystectomy (RC) is a major surgical procedure accompanied with meaningful complications and countable perioperative mortality. To identify the risk factors predicting the perioperative morbidity and mortality is essential. The study aimed to identify relevant, patient-specific factors associated with 90-day mortality following RC, which may serve as a foundation for improving healthcare delivery to patients with bladder cancer. METHODS: We investigated a sample of 1015 consecutive patients in order to identify predictors of 90-day mortality after RC. Beside tumor-related parameters, ASA classification, NYHA, Canadian Cardiovascular Society classification of angina pectoris, Charlson score, age, gender and the single conditions contributing to the Charlson score were included in the multivariable analyses. The patient data were collected retrospectively, except the ASA score that was obtained prospectively. RESULTS: We identified a model containing the parameters age (OR 1.05, p = 0.023), ASA classification of 3-4 (OR 6.19, p < 0.001) and Charlson score (OR 1.22, p = 0.003) to predict 90-day mortality. Among the single conditions to the Charlson score, moderate or severe renal disease (OR 3.94, p < 0.001) and liver disease (OR 3.24, p = 0.037) were most closely related to 90-day mortality. CONCLUSIONS: Age, ASA classification and Charlson score as well as moderate or severe renal disease and liver disease appear to be independent predictors of 90-day mortality after RC. Given the highly significant association of ASA score with 90-day mortality and the relative ease and width disposability of this measure, this classification should be, after external validation, incorporated into daily clinical practice in treatment of patients planned to RC.

Impact of Adjuvant Intravesical Bacillus Calmette-Guérin Treatment on Patients with High-Grade T1 Bladder Cancer.

PURPOSE: To evaluate the impact of adjuvant intravesical bacillus Calmette-Guérin (BCG) treatment in patients with high-grade transitional cell carcinoma of bladder. PATIENTS AND METHODS: A total of 207 consecutive patients who underwent transurethral resection for high-grade T1 transitional cell carcinoma of bladder at our institution between January 1, 2005 and December 31, 2012. Of those patients, 77 underwent early cystectomy without BCG instillation and were excluded from the analysis. The overall survival and cancer-specific mortality were compared in 2 different therapy options groups (group of patients who received adjuvant BCG instillation vs. the group of patients who did not receive BCG therapy). Overall mortality was estimated by the Kaplan-Meier method, univariate comparisons were made with the log rank test. The cumulative incidence of deaths from bladder cancer (BC) was determined by univariate and multivariate competing risk analysis. Cox proportional hazard models for competing risks were used to study the combined effects of the variables on BC-specific mortality. RESULTS: The 5-year overall survival in patients with BCG instillation vs. patients who did not receive BCG therapy was 74 vs. 28% (p = 0.0016). In the univariate analysis, the adjuvant intravesical BCG treatment was associated with decreased cancer-specific mortality (p = 0.0062). In the multivariable analysis, the age and the BCG instillation were independent factors of overall survival (hazard ratio 0.26, 95% CI 0.15-0.46, p < 0.0001) and cancer-specific mortality (hazard ratio 0.29, 95% CI 0.12-0.71, p = 0.0067). CONCLUSION: Dispensing from adjuvant intravesical BCG treatment is associated with increased overall- and disease-specific mortality in patients with T1 high-grade transitional cell carcinoma of bladder. This observation confirms that adjuvant BCG instillation is a crucial part of treatment in this patient population.

Decision curve analysis and external validation of the postoperative Karakiewicz nomogram for renal cell carcinoma based on a large single-center study cohort.

PURPOSE: To predict outcome of patients with renal cell carcinoma (RCC) who undergo surgical therapy, risk models and nomograms are valuable tools. External validation on independent datasets is crucial for evaluating accuracy and generalizability of these models. The objective of the present study was to externally validate the postoperative nomogram developed by Karakiewicz et al. for prediction of cancer-specific survival. METHODS: A total of 1,480 consecutive patients with a median follow-up of 82 months (IQR 46-128) were included into this analysis with 268 RCC-specific deaths. Nomogram-estimated survival probabilities were compared with survival probabilities of the actual cohort, and concordance indices were calculated. Calibration plots and decision curve analyses were used for evaluating calibration and clinical net benefit of the nomogram. RESULTS: Concordance between predictions of the nomogram and survival rates of the cohort was 0.911 after 12, 0.909 after 24 months and 0.896 after 60 months. Comparison of predicted probabilities and actual survival estimates with calibration plots showed an overestimation of tumor-specific survival based on nomogram predictions of high-risk patients, although calibration plots showed a reasonable calibration for probability ranges of interest. Decision curve analysis showed a positive net benefit of nomogram predictions for our patient cohort. CONCLUSION: The postoperative Karakiewicz nomogram provides a good concordance in this external cohort and is reasonably calibrated. It may overestimate tumor-specific survival in high-risk patients, which should be kept in mind when counseling patients. A positive net benefit of nomogram predictions was proven.

Risk stratification for locoregional recurrence after radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: To externally validate the Christodouleas risk model incorporating pathological tumor stage, lymph node (LN) count and soft tissue surgical margin (STSM) and stratifying patients who develop locoregional recurrence (LR) after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). In addition, we aimed to generate a new model including established clinicopathological features that were absent in the Christodouleas risk model. METHODS: Prospectively assessed multicenter data from 565 patients undergoing RC for UCB in 2011 qualified for final analysis. For the purpose of external validation, risk group stratification according to Christodouleas was performed. Competing-risk models were calculated to compare the cumulative incidences of LR after RC. RESULTS: After a median follow-up of 25 months (interquartile range 19-29), the LR-rate was 11.5 %. The Christodouleas model showed a predictive accuracy of 83.2 % in our cohort. In multivariable competing-risk analysis, tumor stage ≥pT3 (HR 4.32, p < 0.001), positive STSM (HR 2.93, p = 0.005), lymphovascular invasion (HR 3.41, p < 0.001), the number of removed LNs <10 (HR 2.62, p < 0.001) and the administration of adjuvant chemotherapy (HR 0.40, p = 0.008) independently predicted the LR-rate. The resulting risk groups revealed significant differences in LR-rates after 24 months with 4.8 % for low-risk patients, 14.7 % for intermediate-risk patients and 38.9 % for high-risk patients (p < 0.001 for all), with a predictive accuracy of 85.6 %, respectively. CONCLUSIONS: The Christodouleas risk model has been successfully externally validated in the present prospective series. However, this analysis finds that overall model performance may be improved by incorporating lymphovascular invasion. After external validation of the newly proposed risk model, it may be used to identify patients who benefit from an adjuvant therapy and suit for inclusion in clinical trials.

Prognostic impact of infiltration of the vagina and/or uterus in women undergoing anterior pelvic exenteration for urothelial carcinoma of the bladder: results of a contemporary multicentre series.

PURPOSE: To evaluate for the first time the prognostic significance of female invasive patterns in stage pT4a urothelial carcinoma of the bladder in a large series of women undergoing anterior pelvic exenteration. PATIENTS AND METHODS: Our series comprised of 92 female patients in total of whom 87 with known invasion patterns were eligible for final analysis. Median follow-up for evaluation of cancer-specific mortality (CSM) was 38 months (interquartile ranges, 21-82 months). The impact on CSM was evaluated using multivariable Cox proportional-hazards regression analysis; predictive accuracy (PA) was assessed by receiver operating characteristic analysis. RESULTS: Vaginal invasion was noted in 33 patients (37.9 %; group VAG), uterine invasion in 20 patients (23 %; group UT), and infiltration of both vagina and uterus in 34 patients (39.1 %; group VAG + UT). Groups VAG and UT significantly differed from group VAG + UT with regard to the presence of positive soft tissue margins (STM) only. Five-year-cancer-specific survival probabilities in the groups VAG, UT, and VAG + UT were 21, 20, and 21 %, respectively (p = 0.955). On multivariable analysis, only STM status (HR = 2.02, p = 0.023) independently influenced CSM. C-indices of multivariable models for CSM with and without integration of invasive patterns were 0.570 and 0.567, respectively (PA gain 0.3 %, p = 0.526). CONCLUSIONS: Infiltration of the vagina, the uterus or both is associated with poor 5-year survival rates. With regard to CSM, no difference was detectable between patients with different invasion patterns, thus justifying further collectively including these invasive patterns as stage pT4a.

Concomitant seminal vesicle invasion in pT4a urothelial carcinoma of the bladder with contiguous prostatic infiltration is an adverse prognosticator for cancer-specific survival after radical cystectomy.

PURPOSE: To evaluate the prognostic value of concomitant seminal vesicle invasion (cSVI) in patients with urothelial carcinoma of the bladder (UCB) and contiguous prostatic stromal infiltration in a large cystectomy series. METHODS: A total of 385 patients with UCB and contiguous prostatic infiltration comprised our study. Patients were divided in two groups according to cSVI. Median follow-up was 36 months (interquartile range 11-74); the primary end point was cancer-specific mortality. The prognostic impact of cSVI was evaluated using multivariable Cox regression analysis. The predictive accuracy was assessed by a receiver operating characteristic analysis. RESULTS: A total of 229 patients (59.5 %) without cSVI comprised group A, and 156 patients (40.5 %) with cSVI comprised group B. Positive lymph nodes (63 vs. 44 %, p < 0.001) and positive surgical margins (34 % vs. 14 %, p < 0.001) were more common in patients with cSVI. The 5- and 10-year cancer-specific survival rates were 41 % and 32 % (group A) and 21 and 17 % (group B) (p < 0.001). In multivariable analysis, pathological nodal stage (hazard ratio [HR] 2.19, p < 0.001), soft tissue surgical margin (HR 1.57, p = 0.010), clinical tumor stage (HR 1.46, p = 0.010), adjuvant chemotherapy (HR 0.40, p < 0.001), and cSVI (HR 1.69, p < 0.001) independently impacted cancer-specific mortality. The c-indices of the multivariable models with and without inclusion of cSVI were 0.658 (95 % confidence interval 0.60-0.71) and 0.635 (95 % confidence interval 0.58-0.69), respectively, resulting in a predictive accuracy gain of 2.3 % (p = 0.002). CONCLUSIONS: In patients with UCB and prostatic stromal invasion, cSVI adversely affected cancer-specific survival compared to patients without cSVI. The inclusion of cSVI significantly improved the predictive accuracy of our multivariable model regarding survival.

Primary tumor size in renal cell cancer in relation to the occurrence of synchronous metastatic disease.

OBJECTIVES: To investigate the controversially discussed relationship between tumor size and the occurrence of primary synchronous metastatic disease in renal cell cancer (RCC). PATIENTS AND METHODS: A consecutive RCC cohort of 2,058 patients (150 primary metastatic) who underwent surgery between 1995 and 2010 was investigated. Rates of synchronous metastases were calculated for stratified groups of tumor size. Uni- and multivariate logistic regression models were calculated for the correlation of tumor size with primary metastatic disease. RESULTS: The rate of metastatic disease increased with increasing tumor size. Tumor size was significantly correlated with synchronous metastatic disease (p < 0.001, c-index 0.772), but for RCCs ≤4 cm in size no significant correlation was found. Regarding tumors ≤5 cm in size, the correlation became significant (p = 0.028, c-index 0.621). A multivariate logistic regression model for the prediction of synchronous metastatic disease including tumor size, age and comorbidity yielded a significant c-index of 0.82 and was used to construct a nomogram. CONCLUSION: Our data confirm the correlation between tumor size and the rate of synchronous metastatic disease. Small renal tumors <4 cm in size have a low risk of synchronous metastatic disease. The risk becomes significantly associated with tumor size for tumors ≤5 cm.

Systematic assessment of complications and outcome of radical cystectomy undertaken with curative intent in patients with comorbidity and over 75 years of age.

OBJECTIVE: To evaluate the complications, survival and oncological outcome of patients ≥75 years of age after radical cystectomy for muscle-invasive bladder cancer. PATIENTS AND METHODS: Between April 1993 and August 2010, 765 patients with muscle-invasive bladder cancer underwent radical cystectomy at one high-volume center. Of these, 70 patients were ≥75 years of age. All 70 patients had at least one severe systemic comorbidity with an American Society of Anesthesiologists score of 3. Primary endpoints of this retrospective study were overall and recurrence-free survival with a mean follow-up of 22 months (1-159). Perioperative parameters such as need for blood transfusions, hospital stay, mortality, short- and long-term complications were also assessed. Complications were graded according to the Clavien-Dindo classification. RESULTS: Perioperative complications occurred in 23/70 patients (33%) with a 30-day mortality rate of 1.4%. 16/70 patients (23%) developed late complications requiring hospitalization. Within 30 days of surgery, according to the Clavien-Dindo grading, 27% had no complications, 3% grade 1, 49% grade 2, 14% grade 3, 6% grade 4 and 1.4% grade 5 complications. Within 31-90 days after surgery, 76% had grade 1 complications, 3% grade 2, 6% grade 3, 9% grade 4 and 6% grade 4 complications. The calculated 5- and 8-year overall survival rates were 30 and 25%, respectively, with a recurrence-free survival rate of 52% at 5 and 42% at 8 years. CONCLUSIONS: Radical cystectomy is an appropriate and effective treatment for comorbid elderly patients. The oncological long-term outcome is the same as in younger patients while overall survival is comparatively lower. Mortality and complication-related morbidity are comparable to those in younger patients with modern perioperative management.

Perioperative complications after radical prostatectomy: open versus robot-assisted laparoscopic approach.

BACKGROUND: The best technique of radical prostatectomy - open versus robot-assisted approach - is controversially discussed. In this study, we compared the complication rates of open and robot-assisted radical prostatectomy during the introduction and subsequent routine use of a da Vinci® robotic device while open surgery remained the standard approach. PATIENTS AND METHODS: Between January 1st, 2006, and June 4th, 2012, 2,754 men underwent radical prostatectomy at our department. Among them, 317 received robot-assisted and 2,438 open surgery. According to the requirements for prostate cancer centers certified by the Deutsche Krebsgesellschaft (German Cancer Society), a prospective database recording perioperative complications was built up. The complication rates of open and robot-assisted radical prostatectomy were compared with the χ(2) or Fisher exact test. The distributions of quantitative variables were compared with U tests. RESULTS: Whereas the demographic factors favored patients selected for robot-assisted radical prostatectomy, there were no differences between open and robot-assisted surgery concerning length of stay, autologous blood transfusion rates and the incidence of perioperative complications. CONCLUSIONS: Open and robot-assisted radical prostatectomy had comparable complication rates. With better patient- and tumor-related parameters as well as decreasing transfusion rates in the robot-assisted subgroup, this observation might reflect the learning curves of the involved robotic surgeons.

Urinary tract-related quality of life after radical prostatectomy: open retropubic versus robot-assisted laparoscopic approach.

BACKGROUND: The best technique of radical prostatectomy--open retropubic versus robot-assisted surgery--is a subject of controversy. PATIENTS AND METHODS: Between January 1st, 2007 and December 31st, 2011, 2,177 men underwent radical prostatectomy at our department. 252 (12%) cases were laparoscopic robot-assisted, the remainder open retropubic procedures. In Germany, certified prostate cancer centers are required to collect urinary tract-related outcome data after radical prostatectomy using the International Consultation of Incontinence Questionnaire Male Lower Urinary Tract Symptoms. The questionnaire data were used to compare both surgical approaches concerning the urinary tract-related outcome 1, 2 and 3 years postoperatively. RESULTS: Neither the voiding score nor the incontinence score or the bother scale sum differed between the two cohorts at any of the measurement times. CONCLUSIONS: Concerning continence recovery, in this series, there were no detectable differences between robot-assisted and open radical prostatectomy.

Radical cystectomy in patients over 70 years of age: impact of comorbidity on perioperative morbidity and mortality.

PURPOSE: To analyze the impact of comorbidity on the perioperative complication rate after radical cystectomy in patients over 70 year of age. METHODS: Between April 1993 and August 2010, 830 radical cystectomies were performed at our institution. Of the 830 patients, 365 patients (44.0%) were ≥70-year-old (median age 74 year). This group of elderly patients was compared with a younger group of 465 patients (56.0% of the whole cohort) aged under 70 year (median 63 year). RESULTS: The group of elderly patients had a significantly higher prevalence of concomitant diseases e.g., hypertension (57.3% vs. 38.5%), coronary heart disease (27.1% vs. 14.8%) and diabetes (25.5% vs. 14.6%). Perioperative complications were significantly more frequent in the elderly group: 31.0% versus 21.5% overall complication rate, P = 0.002. Mortality rate was almost similar in both groups: 0.6% (elderly) versus 0.5% (younger). Within the elderly group, the overall complication rate was significantly higher in patients with an ASA score ≥3 (37.0%) than in patients with an ASA score ≤2 (25.0%) (P < 0.02). Multivariate logistic regression analysis was used to identify that chronic obstructive lung disease, ASA score and age were independent predictive factors for perioperative complications. CONCLUSIONS: Elderly patients have a higher prevalence of concomitant systemic diseases. Some concomitant diseases can affect surgical outcome after radical cystectomy, particularly the frequency and character of perioperative complications. It is therefore of paramount importance to conduct a comorbidity assessment and preoperative conditioning of each patient, with a special focus on the patient's individual risk factors and age.

Decreasing Non-bladder-cancer Mortality After Radical Cystectomy.

Life expectancy is increasing in many parts of the world. Using proportional hazard models for competing risks, we investigated whether this increase has changed outcomes after radical cystectomy in a sample of 1419 consecutive patients treated between 1993 and 2018. During the observation period, the mean age and the proportion of patients with American Society of Anesthesiologists physical status class 3 or 4 increased, whereas the proportion of patients with heart disease decreased. Competing mortality (causes other than bladder cancer) decreased in all subgroups (hazard ratios [HRs] per year ranged from 0.931 to 0.963) and after controlling for increasing age (HRs ranged from 1.018 to 1.081). In an optimal model resulting from an analysis including age (HR per year 1.048, 95% confidence interval [CI] 1.027-1.070; p < 0.0001), comorbidity, tumor-related variables, body mass index, (neoadjuvant and adjuvant) chemotherapy and smoking status, the HR per increment for year of surgery was 0.928 (95% CI 0.886-0.973; p = 0.0019). The effect of year of surgery was greater than the decrease in competing mortality that may be expected with increasing life expectancy (4 yr for females, 6 yr for males). PATIENT SUMMARY: In a review of data for 1993-2018, we found that death from other causes after removal of the bladder (radical cystectomy) for bladder cancer decreased over time. This decreasing trend might increase the age limit at which bladder cancer patients can benefit from radical cystectomy in the future.