Postoperative complications and short-term oncological outcomes of patients aged ≥80 years undergoing robot-assisted radical cystectomy.

PURPOSE: To assess complication rates and early oncological outcomes of patients aged ≥80 years who underwent robot-assisted radical cystectomy (RARC). METHODS: A total of 368 consecutive patients underwent radical cystectomy from April 2001 to September 2013 in a tertiary referral center. Sixty-one patients aged ≥80 years underwent RARC and constitute the cohort of interest. Complications arising within 30 and 90 days of surgery were graded using the modified Clavien classification and were additionally categorized by organ system using a standardized complication reporting system. Recurrence-free survival, disease-specific survival and overall survival were calculated using Kaplan-Meier curves. RESULTS: Median age was 83 years (range 80-94). Twenty-nine (48 %) of all tumor specimens were stage ≥pT3. The median number of nodes removed was 19 (range 6-67). The soft tissue positive margin rate was 10 %. A total of 27 (44 %) patients had complications within 90 days, of which 9 had major complications. Two patients (3 %) died from surgical complications within 90 days. At a median follow-up of 13 months, 12 (20 %) patients had developed recurrent cancer and subsequently died from disease. An additional 13 (21 %) patients died from non-cancer-related causes. The median overall survival time was 36.0 months. At 2 years, recurrence-free, cancer-specific and overall survival rates were 73, 74 and 61 %, respectively. CONCLUSIONS: In patients aged ≥80 years, RARC is feasible with acceptable perioperative morbidity and favorable short-term oncological outcomes. Therefore, RARC should be considered a valid option for carefully selected patients aged ≥80 years with bladder cancer.

Is continent cutaneous urinary diversion a suitable alternative to orthotopic bladder substitute and ileal conduit after cystectomy?

OBJECTIVE: To evaluate functional outcomes of continent cutaneous urinary diversion (CCUD) after radical cystectomy (RC) and to compare diversion-related complications and long-term renal function in a contemporary cohort of patients undergoing urinary diversion with CCUD, orthotopic bladder substitute (OBS) and ileal conduit (IC). PATIENTS AND METHODS: In all, 322 patients underwent RC and CCUD, OBS or IC from January 2002 to June 2013. CCUD was performed using either a modified Indiana pouch or an appendiceal stoma. For patients with CCUD, continence status and time intervals between clean intermittent catheterisations at last follow-up were recorded. For all three diversion types, diversion-related complications and renal function outcome, as determined by the estimated glomerular filtration rate (eGFR) at baseline and at different time intervals after surgery, were evaluated. Multivariate regression analysis was used to evaluate the association of diversion type, baseline variables and diversion-related complications with renal function over time. RESULTS: Of all 322 patients, 73 (23%) received a CCUD, 79 (25%) received an OBS, and 170 (53%) received an IC. After a median follow-up of 36 months, the continence rate for patients with a CCUD was 89%. In all, 64 (88%) patients with a CCUD were able to catheterise every 4-8 h and five (7%) were able to catheterise every 8-10 h. After a median follow-up of 35 months, rates of diversion-related complications were similar among patients who underwent a CCUD, an OBS or an IC. Patients who received an IC had poorer renal function preoperatively than those who received a CCUD or an OBS. However, at 1 year after surgery and thereafter, the three groups had comparable renal function. On multivariate analysis, the type of urinary diversion was not associated with decline in renal function. However, patient age at surgery, diabetes mellitus, baseline eGFR, postoperative non-obstructive hydronephrosis and uretero-enteric stricture were associated with decline in renal function. CONCLUSIONS: A CCUD is associated with excellent functional outcomes. The rates of diversion-related complications and renal function outcomes are comparable with those from an OBS and an IC. A CCUD should be considered a valid alternative for patients who undergo cystectomy and require urinary diversion.

Combining smoking information and molecular markers improves prognostication in patients with urothelial carcinoma of the bladder.

OBJECTIVES: Tissue-based markers improve the accuracy of prediction models in urothelial carcinoma of the bladder (UCB). Current smoking status and cumulative exposure also affect outcomes. To evaluate whether the combination of molecular markers and smoking features further improved the prognostication of patients who underwent radical cystectomy (RC) for UCB. MATERIALS AND METHODS: A total of 588 patients underwent RC and bilateral lymphadenectomy for UCB from 1995 to 2005. Immunohistochemistry for p53, p21, pRB, p27, Ki-67, and survivin was performed on tissue microarrays from the RC specimen. Smoking features were routinely assessed at diagnosis. Multivariable Cox regression models assessed time to disease recurrence and cancer-specific mortality. RESULTS: Of the 588 patients, 128 were never (22%), 283 former (48%), and 177 current smokers (30%). In total, 227 patients experienced disease recurrence, whereas 190 died of UCB. Smoking status was independently associated with both outcomes (hazard ratio [HR] = 1.48 and 2.62, for former and current vs. never smokers, respectively, P<0.001). All markers were significantly associated with both outcomes (P<0.05) except for survivin. The combination of the 4 cell cycle markers p53, p21, pRB, and p27 increased the discrimination of clinicopathologic model for former and current vs. never smokers with c-indices 0.779 and 0.780, respectively (base model c-indices of 0.741 and 0.740 for former and current vs. never smokers, respectively). The further addition of smoking features and biomarker status improved the discrimination of the model (c-indices of 0.783 and 0.786 for former and current vs. never smokers, respectively). CONCLUSIONS: We confirmed that smoking information and tissue markers status improve prognostication of UCB outcomes after RC; the combination of both reaching the highest level of discrimination.

Effect of diabetes mellitus and metformin use on oncologic outcomes of patients treated with radical cystectomy for urothelial carcinoma.

OBJECTIVES: Evidence suggests a positive effect of metformin on cancer incidence and outcome. To date, the effect of metformin use on prognosis in urothelial carcinoma of the bladder (UCB) remains uninvestigated. We tested the hypothesis that metformin use affects oncologic outcomes of patients treated with radical cystectomy for UCB. METHODS AND MATERIALS: We retrospectively evaluated 1,502 patients treated at 4 institutions with radical cystectomy and pelvic lymphadenectomy without neoadjuvant therapy. Cox regression models addressed the association of diabetes mellitus (DM) and metformin use with disease recurrence, cancer-specific mortality, and any-cause mortality. RESULTS: A total of 200 patients (13.3%) had DM, 80 patients (5.3%) used metformin. Within a median follow-up of 34 months, 509 patients (33.9%) experienced disease recurrence, 402 patients (26.8%) died of UCB, and 551 patients (36.7%) died from any cause. In univariable Cox regression analyses, DM without metformin use was associated with increased risk of disease recurrence (hazard ratio [HR]: 1.40, 95% confidence interval [CI] 1.05-1.87, P = 0.02), cancer-specific mortality (HR: 1.60, 95% CI 1.17-2.17, P = 0.003), and any-cause mortality (HR: 1.55, 95% CI 1.18-2.03, P = 0.002), whereas metformin use was associated with decreased risk of disease recurrence (HR: 0.61, 95% CI 0.37-0.98, P = 0.04), cancer-specific mortality (HR: 0.56, 95% CI 0.33-0.97, P = 0.04), and any-cause mortality (HR: 0.54, 95% CI 0.33-0.88, P = 0.01). In multivariable Cox regression analyses, DM treated without metformin use remained associated with worse cancer-specific mortality (HR: 1.53, 95% CI 1.12-2.09, P = 0.007) and any-cause mortality (HR: 1.52, 95% CI 1.16-2.00, P = 0.003) but not disease recurrence. CONCLUSIONS: Diabetic patients who do not use metformin appear to be at higher risk of cancer-specific and any-cause mortality than patients without DM. It remains unclear, whether the severity of DM in this group of patients or the use of metformin itself affects outcomes of UCB. The mechanisms behind the effect of DM on patients with UCB and the potential protective effect of metformin need further elucidation.

Long-term cancer-specific outcomes of TaG1 urothelial carcinoma of the bladder.

BACKGROUND: Few studies have investigated the natural history of TaG1 urothelial carcinoma of the bladder (UCB). OBJECTIVE: To assess the long-term outcomes of patients with TaG1 UCB and the impact of immediate postoperative instillation of chemotherapy (IPIC). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 1447 patients with TaG1 UCB treated between 1996 and 2007 at eight centers. Median follow-up was 67.2 mo (interquartile range: 67.9). Patients were stratified into three European Association of Urology (EAU) guidelines risk categories; high-risk patients (n=11) were excluded. INTERVENTION: Transurethral resection of the bladder with or without IPIC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox regression models addressed factors associated with disease recurrence, disease progression, death of disease, and any-cause death. RESULTS AND LIMITATIONS: Of the 1436 patients, 601 (41.9%) and 835 (58.1%) were assigned to low- and intermediate-risk categories, respectively. The actuarial estimate of 5-yr recurrence-free survival was 56% (standard error: ± 1). Advancing age (p=0.04), tumor >3 cm (p=0.001), multiple tumors (p<0.001), and recurrent tumors (p<0.001) were independently associated with increased risk of disease recurrence, whereas IPIC was associated with decreased risk (p=0.001). The actuarial estimate of 5-yr progression-free survival was 95% ± 1. Advancing age (p<0.001) and multiple tumors (p=0.01) were independent risk factors for disease progression. Five-year cancer-specific survival was 98% ± 1. Advancing age (p=0.001) and previous recurrence (p=0.04) were associated with increased risk, whereas female gender (p=0.02) was associated with decreased risk of cancer-specific mortality. Compared with low-risk patients, intermediate-risk patients were at significantly higher risk of disease recurrence, disease progression, and cancer-specific mortality (all p<0.01). Limitations include the retrospective design of the study and the lack of a central pathology review. CONCLUSIONS: TaG1 UCB patients experience heterogeneous risks of disease recurrence. We validated the EAU guidelines risk stratification in TaG1 UCB patients. IPIC was associated with a reduced risk of disease recurrence in patients with low- and intermediate-risk TaG1 UCB.

Association of diabetes mellitus and metformin use with oncological outcomes of patients with non-muscle-invasive bladder cancer.

OBJECTIVE: To assess the association between diabetes mellitus (DM) and metformin use with prognosis and outcomes of non-muscle-invasive bladder cancer (NMIBC) PATIENTS AND METHODS: We retrospectively evaluated 1117 patients with NMIBC treated at four institutions between 1996 and 2007. Cox regression models were used to analyse the association of DM and metformin use with disease recurrence, disease progression, cancer-specific mortality and any-cause mortality. RESULTS: Of the 1117 patients, 125 (11.1%) had DM and 43 (3.8%) used metformin. Within a median (interquartile range) follow-up of 64 (22-106) months, 469 (42.0%) patients experienced disease recurrence, 103 (9.2%) experienced disease progression, 50 (4.5%) died from bladder cancer and 249 (22.3%) died from other causes. In multivariable Cox regression analyses, patients with DM who did not take metformin had a greater risk of disease recurrence (hazard ratio [HR]: 1.45, 95% confidence interval [CI] 1.09-1.94, P = 0.01) and progression (HR: 2.38, 95% CI 1.40-4.06, P = 0.001) but not any-cause mortality than patients without DM. DM with metformin use was independently associated with a lower risk of disease recurrence (HR: 0.50, 95% CI 0.27-0.94, P = 0.03). CONCLUSION: Patients with DM and NMIBC who do not take metformin seem to be at an increased risk of disease recurrence and progression; metformin use seems to exert a protective effect with regard to disease recurrence. The mechanisms behind the impact of DM on patients with NMIBC and the potential protective effect of metformin need further elucidation.

Effect of statin use on outcomes of non-muscle-invasive bladder cancer.

OBJECTIVES: To assess the impact of statin use on outcomes of patients with non-muscle-invasive bladder cancer (NMIBC). To measure the effect of statin use on the efficacy of intravesical bacillus Calmette-Guérin (BCG) therapy. PATIENTS AND METHODS: A retrospective analysis was performed on 1117 patients treated with transurethral resection of the bladder (TURB) for NMIBC at three institutions between 1996 and 2007. Statin use at the time of diagnosis was recorded for each patient. Univariable Cox regression models addressed the association of statin use with disease recurrence, disease progression, cancer-specific mortality and overall mortality in all patients, patients with primary NMIBC, patients not treated with BCG, and patients treated with BCG. RESULTS: Overall, 341 patients (30.5%) used statins and 776 (69.5%) did not. Within a median (interquartile range) follow-up of 62.7 (25.0-110.7) months, 469 patients (42.0%) experienced disease recurrence, 103 (9.2%) progression, 50 (4.5%) cancer-specific mortality, and 299 (26.8%) any-cause mortality. In univariable Cox regression analyses, statin use was not associated with any of these four endpoints (P > 0.05 for all). In subgroup analyses, statin use was also not associated with prognosis in patients with primary NMIBC or patients not receiving BCG (P > 0.05 for all four endpoints). Statin use was not associated with response to BCG (P > 0.05 for all four endpoints). CONCLUSION: Statin users did not experience different outcomes compared with non-users and statin use did not affect the efficacy of BCG immunotherapy; these data do not support modification or discontinuation of statin therapy for patients with NMIBC.

Obesity is associated with worse outcomes in patients with T1 high grade urothelial carcinoma of the bladder.

PURPOSE: To our knowledge the impact of body mass index on oncologic outcomes in nonmuscle invasive bladder cancer has not been evaluated. We hypothesized that higher body mass index is associated with worse outcomes in patients with clinical primary T1 high grade urothelial carcinoma of the bladder. MATERIALS AND METHODS: We retrospectively analyzed data from 892 patients with primary nonmuscle invasive bladder cancer from 7 centers. Patients were treated with transurethral resection of the bladder with or without intravesical therapy. Body mass index was analyzed as a continuous and a categorical variable (nonobese-body mass index less than 30 kg/m(2) vs obese-body mass index 30 kg/m(2) or greater). Disease progression was defined as the development of T2 or higher tumor stage. RESULTS: Median followup was 42.8 months (IQR 56). Of the patients 44.3% were obese and median body mass index was 29.2 kg/m(2) (IQR 8). On univariable analyses higher body mass index and age were associated with an increased risk of disease recurrence, progression, cancer specific mortality and any cause mortality (all p ≤ 0.001). On multivariable analyses that adjusted for the effects of gender, concomitant carcinoma in situ, tumor size, number of tumors and intravesical therapy, higher body mass index and age remained independent predictors of disease recurrence, progression, cancer specific mortality and any cause mortality (all p <0.05). This study was limited by its design (ie lack of data on repeat transurethral resection of the bladder and intravesical therapy protocol). CONCLUSIONS: Patients diagnosed with clinical T1 high grade urothelial carcinoma of the bladder who are obese have worse cancer specific outcomes compared to their nonobese counterparts. Further work is needed to improve our understanding of clinical T1 high grade outcomes in the growing population of obese patients.

Impact of statin use on oncologic outcomes in patients with urothelial carcinoma of the bladder treated with radical cystectomy.

PURPOSE: Statins are cholesterol lowering agents used to prevent cardiovascular disease. Evidence suggests a dichotomous effect of statins with cancer inhibiting and promoting properties. To our knowledge the effect of statins on the prognosis of muscle invasive urothelial carcinoma of the bladder remains uninvestigated to date. We tested the hypothesis that statin use impacts oncological outcomes in patients treated with radical cystectomy for urothelial carcinoma of the bladder. MATERIALS AND METHODS: We retrospectively evaluated the records of 1,502 patients treated with radical cystectomy and pelvic lymphadenectomy without neoadjuvant therapy at a total of 4 institutions. Cox regression models were used to determine the association of statins with disease recurrence and cancer specific mortality. RESULTS: A total of 642 patients (42.7%) were on statins. At a median followup of 34 months 509 patients (33.9%) experienced disease recurrence and 402 (26.8%) had died of urothelial carcinoma of the bladder. Statin users were older (p = 0.003), had a higher body mass index (median 32 vs 28 kg/m(2), p <0.001) and were more likely to have positive soft tissue surgical margins (9% vs 4%, p <0.001). On univariable Cox regression analysis statins, female gender, advanced age, higher body mass index, smoking status, tumor stage, tumor grade, soft tissue surgical margin status, lymphovascular invasion, lymph node metastasis and adjuvant chemotherapy were associated with disease recurrence (p ≤ 0.05) and cancer specific mortality (p ≤ 0.02). On multivariable Cox regression analysis statin use was not associated with either outcome. CONCLUSIONS: Statin users were at higher risk for disease recurrence and cancer specific mortality on univariable but not multivariable analysis. These data do not support modification of statin use in patients with high risk urothelial carcinoma of the bladder who will be treated with radical cystectomy.