Anne Schuckman

Enhanced Recovery Protocol after Radical Cystectomy for Bladder Cancer

PURPOSE Enhanced recovery after surgery protocols aim to improve patient care and decrease complications and hospital stay. We evaluated our enhanced recovery after surgery protocol, focusing on length of stay, early complication and readmission rates after radical cystectomy for bladder cancer. MATERIALS AND METHODS From May 2012 to July 2013 a perioperative protocol was applied in 126 consecutive patients who underwent open radical cystectomy and urinary diversion. Nonconsenting patients (2), those with previous diversion (2) and prolonged postoperative intubation (3), and those who underwent additional surgery (9) were excluded from study. The protocol focuses on avoiding bowel preparation and nasogastric tube, early feeding, nonnarcotic pain management and the use of cholinergic and μ-opioid antagonists. Outcomes were compared to those in matched controls from our bladder cancer database. RESULTS A total of 110 patients with a median age of 69 years were included in analysis, of whom 68% underwent continent urinary diversion. Of the patients 82% had a bowel movement by postoperative day 2. Median length of stay was 4 days. The 30-day minor and major complication rates were 64% and 14%, respectively. The most common minor complication was anemia requiring transfusion in 19% of patients, urinary tract infection in 13% and dehydration in 10%. The latter 2 complications were the most common etiologies for readmission. The 30-day readmission rate was 21% (23 patients). Patients 75 years old or older had a longer length of stay (5 vs 4 days, p = 0.03) and a higher minor complication rate (72% vs 51%, p = 0.04) than younger patients. CONCLUSIONS Our enhanced recovery after surgery protocol expedites bowel function recovery and shortens hospital stay after RC and urinary diversion without an increase in the hospital readmission rates.

Factors influencing post‐recurrence survival in bladder cancer following radical cystectomy

Study Type – Prognosis (individual cohort)

Neoadjuvant chemotherapy with gemcitabine/cisplatin vs. methotrexate/vinblastine/doxorubicin/cisplatin for muscle-invasive urothelial carcinoma of the bladder: A retrospective analysis from the University of Southern California☆

OBJECTIVES We evaluated pathologic and survival outcomes of GC (gemcitabine/cisplatin) and methotrexate/vinblastine/doxorubicin/cisplatin (M-VAC) neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS A retrospective analysis of prospectively collected data on 116 patients who received NAC (GC: n = 58; M-VAC: n = 58) before radical cystectomy and superextended pelvic lymph node dissection for clinical stage T2-4N0M0 bladder cancer was performed. The outcomes were complete response rate (CRR; pT0N0), partial response rate (PRR; pT0N0, pTaN0, pT1N0, or pTisN0), overall mortality (OM), and recurrence. The Kaplan-Meier method and multivariable Cox regression analysis were used to analyze OM. The cumulative incidence method and Fine and Grays competing risk regression analysis were used to analyze recurrence. RESULTS The median follow-up duration was 2.1 years for the GC group and 7.4 years for the M-VAC group (P < 0.001). There were no statistically significant differences between the GC and M-VAC groups with regard to CRR (27.3% vs. 17.1%, P = 0.419) or PRR (45.5% vs. 37.1%, P = 0.498). The predicted 5-year freedom from OM rate (P = 0.634) and cumulative incidence of recurrence rate (P = 0.891) did not differ between the GC and M-VAC groups. Multivariable analysis showed that there was no independent association between type of NAC and OM (P = 0.721) or recurrence (P = 0.065). CONCLUSIONS Pathologic and survival outcomes did not differ in patients who received GC and M-VAC NAC. These data support the use of the GC regimen in the neoadjuvant setting.

Venous thromboembolism following radical cystectomy: significant predictors, comparison of different anticoagulants and timing of events.

PURPOSE We determined the rate, timing and predictors of venous thromboembolism after open radical cystectomy for urothelial bladder cancer. We also compared the use of warfarin (1971 to 2008) and unfractionated heparin (2008 to 2012) as prophylaxis. MATERIALS AND METHODS We retrospectively reviewed the records of 2,316 patients who underwent open radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer with intent to cure at our institution between 1971 and 2012. The rate and timing of symptomatic venous thromboembolism that developed within 3 months of surgery was calculated in the cohort. Multivariate stepwise logistic regression was used to find significant predictors of symptomatic venous thromboembolism and compare the warfarin based and heparin based prophylaxis protocols. RESULTS A total of 109 symptomatic venous thromboembolism cases developed for a rate of 4.7%, including 2.1% for deep vein thrombosis and 2.6% for pulmonary embolism. Of these cases 57.8% developed after discharge home at a median of 20 days postoperatively (range 2 to 91). Four significant predictors of venous thromboembolism were identified, including body mass index (p = 0.0015), surgical margins (p = 0.025), diversion type (p = 0.023) and hospitalization duration (p <0.0001). Use of prophylactic heparin vs warfarin was not a significant predictor (p = 0.31). CONCLUSIONS Venous thromboembolism remains a significant complication of open radical cystectomy. Using an in-house, heparin based anticoagulation protocol consistent with current AUA (American Urological Association) guidelines has not decreased the rate of venous thromboembolism compared to historical warfarin use. On closer evaluation most venous thromboembolism cases in our population occurred after discharge home. Future studies are needed to establish the benefits of extended duration venous thromboembolism prophylaxis regimens that cover the critical post-hospitalization period.

Impact of micropapillary urothelial carcinoma variant histology on survival after radical cystectomy

OBJECTIVES The role of micropapillary urothelial carcinoma (MUC) variant histology as an independent prognostic factor for survival after radical cystectomy has not been studied. Our aim was to examine the impact of MUC on survival. MATERIALS AND METHODS A retrospective analysis of prospectively collected data from the University of Southern California (USC) Bladder Cancer Database was performed. Between 1985 and 2008, 1,380 patients underwent radical cystectomy and superextended pelvic lymph node dissection for bladder cancer. All surgical specimens underwent central pathologic review by dedicated genitourinary pathologists. Histologic type was categorized as urothelial carcinoma (UC; n = 1,347) or MUC (n = 33). The outcomes were overall survival (OS) and recurrence-free survival (RFS). The Kaplan-Meier method and Cox proportional regression models were used to analyze survival data. RESULTS The median follow-up duration was 10 years (range, 0-25 years). Baseline characteristics were similar between histologic types except MUC was associated with advanced clinical (cTanyN1-3: 2% vs. 9%, P = 0.03) and pathologic (pTanyN1-3: 22% vs. 46%, P = 0.01) TNM stage, multifocality (38% vs. 58%, P = 0.02), and high nuclear grade (83% vs. 97%, P = 0.03). The predicted 5-year OS (61% and 67%, Log rank P = 0.96) and RFS (69% and 58%, Log rank P = 0.33) rates did not differ between patients with UC and MUC. Multivariable analysis showed that histologic type was not independently associated with OS (HR 0.91, 95% CI 0.55-1.49, P = 0.70) or RFS (HR 0.97, 95% CI 0.55-1.73, P = 0.92). CONCLUSIONS Outcomes of radical cystectomy for patients with MUC are similar to those with UC when controlling for other clinical and pathologic factors.

Cardiopulmonary bypass and renal cell carcinoma with level IV tumour thrombus: can deep hypothermic circulatory arrest limit perioperative mortality?

Study Type – Therapy (case series)

Ureteroenteric Strictures After Open Radical Cystectomy and Urinary Diversion: The University of Southern California Experience

OBJECTIVE To evaluate the risk factors, management, and outcomes of benign ureteroenteric strictures (UES) in patients undergoing open radical cystectomy (RC) and urinary diversion for urothelial bladder carcinoma. MATERIALS AND METHODS Using our institutional review board-approved institutional bladder cancer database, we identified 1964 patients who underwent RC for urothelial bladder carcinoma between 1971 and 2008. Patients underwent a uniform refluxing ureteroenteric anastomosis technique to ileum. In patients with UES, we reviewed clinicopathologic, management, and outcome variables. A multivariate logistic regression model was used to identify independent UES predictors. RESULTS Forty-nine patients and 51 renal units were retrospectively identified with benign UES (2.6%). Median follow-up was 12.4 years (0.2-27.3 years) and median time from RC to UES diagnosis was 10 months (2 months-10 years). Although one-third were asymptomatic, common presentations included flank pain (22%) and urinary tract infection (9%). Thirty-one patients underwent primary endoscopic treatments, including dilatation and stenting, of whom, 13 patients (42%) underwent secondary endoscopic treatment and 9 patients (29%) underwent open revision. Three patients underwent primary open management. Median glomerular filtration rate did not change after management (49-48 mL/min); however, imaging showed improvement in 50% of cases. A multivariate logistic regression model revealed no association with age, body mass index, Charlson comorbidity index, perioperative radiation or chemotherapy, or preoperative serum albumin in predicting UES. CONCLUSION Benign UES are uncommon after RC and urinary diversion using a consistent meticulous surgical approach. More commonly on the left, UES generally present a few months after RC. Although no specific predisposing factor was determined, surgical technique plays an important role.

Hexaminolevulinate blue-light cystoscopy in non-muscle-invasive bladder cancer: review of the clinical evidence and consensus statement on appropriate use in the USA

Hexaminolevulinate (HAL) is a tumour photosensitizer that is used in combination with blue-light cystoscopy (BLC) as an adjunct to white-light cystoscopy (WLC) in the diagnosis and management of non-muscle-invasive bladder cancer (NMIBC). Since being licensed in Europe in 2005, HAL has been used in >200,000 procedures, with consistent evidence that it improves detection compared with WLC alone. Current data support an additional role in the reduction of recurrence of NMIBC. Since the approval of HAL by the FDA in 2010, experience of HAL–BLC in the USA continues to expand. To define areas of need and to identify the benefits of HAL–BLC in clinical practice, a focus group of expert urologists specializing in the management of patients with bladder cancer convened to review the clinical evidence, share their experiences and reach a consensus regarding the optimal use of HAL–BLC in the USA. The focus group concluded that HAL–BLC should be considered for initial assessment of NMIBC, surveillance for recurrent tumours, diagnosis in patients with positive urine cytology but negative WLC findings, and for tumour staging.

Outcomes After Urothelial Recurrence in Bladder Cancer Patients Undergoing Radical Cystectomy

OBJECTIVE To identify factors prognostic for survival after urothelial recurrence after radical cystectomy for bladder cancer. METHODS Of the 2029 patients with bladder cancer who underwent radical cystectomy at our institution, 80 (3.9%) patients experienced recurrence in the urothelium (upper urinary tract or urethra) and had sufficient follow-up for further analysis. Clinicopathologic characteristics were analyzed by univariate and multivariable analyses to identify factors prognostic for postrecurrence disease-specific (PRDSS) and overall (PROS) survival. RESULTS At median follow-up of 12 years, 25 (31.3%) and 55 (68.7%) patients experienced recurrence in the upper tract and urethra, respectively. Median time to recurrence, PRDSS, and PROS were 25.9, 58.4, and 48.7 months, respectively. Older age (P = .018), patients with tumors that were upstaged at cystectomy compared with their clinical stage (P = .049), and positive surgical margins (P = .022) were associated with a lower PROS. The presence of symptoms at follow-up was associated with a poor PRDSS (P = .028), which was confirmed by multivariable analysis. Patients experiencing urothelial recurrence within 2 years of cystectomy had a lower PRDSS (P = .002) and PROS (P = .003), which was confirmed by multivariable analysis. Site of urothelial recurrence did not influence time to recurrence (P = .87), PRDSS (P = .72), or PROS (P = .57). CONCLUSION Urothelial cancer relapse in the upper urinary tract or urethra has a comparable clinical course, and may be cured with extirpative surgery, with median PROS of 48.7 months after recurrence. Patients experiencing early urothelial recurrence face worse prognosis and should be considered candidates for adjuvant therapy.

Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Study

Purpose: We compared blue light flexible cystoscopy with white light flexible cystoscopy for the detection of bladder cancer during surveillance. Materials and Methods: Patients at high risk for recurrence received hexaminolevulinate intravesically before white light flexible cystoscopy and randomization to blue light flexible cystoscopy. All suspicious lesions were documented. Patients with suspicious lesions were referred to the operating room for repeat white and blue light cystoscopy. All suspected lesions were biopsied or resected and specimens were examined by an independent pathology consensus panel. The primary study end point was the proportion of patients with histologically confirmed malignancy detected only with blue light flexible cystoscopy. Additional end points were the false‐positive rate, carcinoma in situ detection and additional tumors detected only with blue light cystoscopy. Results: Following surveillance 103 of the 304 patients were referred, including 63 with confirmed malignancy, of whom 26 had carcinoma in situ. In 13 of the 63 patients (20.6%, 95% CI 11.5–32.7) recurrence was seen only with blue light flexible cystoscopy (p <0.0001). Five of these cases were confirmed as carcinoma in situ. Operating room examination confirmed carcinoma in situ in 26 of 63 patients (41%), which was detected only with blue light cystoscopy in 9 of the 26 (34.6%, 95% CI 17.2–55.7, p <0.0001). Blue light cystoscopy identified additional malignant lesions in 29 of the 63 patients (46%). The false‐positive rate was 9.1% for white and blue light cystoscopy. None of the 12 adverse events during surveillance were serious. Conclusions: Office based blue light flexible cystoscopy significantly improves the detection of patients with recurrent bladder cancer and it is safe when used for surveillance. Blue light cystoscopy in the operating room significantly improves the detection of carcinoma in situ and detects lesions that are missed with white light cystoscopy.