Jeffrey J. Leow

Adjuvant Chemotherapy for Invasive Bladder Cancer: A 2013 Updated Systematic Review and Meta-Analysis of Randomized Trials

CONTEXT The role of adjuvant chemotherapy remains poorly defined for the management of muscle-invasive bladder cancer (MIBC). The last meta-analysis evaluating adjuvant chemotherapy, conducted in 2005, had limited power to fully support its use. OBJECTIVE To update the current evidence of the benefit of postoperative adjuvant cisplatin-based chemotherapy compared with control (ie, surgery alone) in patients with MIBC. EVIDENCE ACQUISITION A comprehensive literature review was performed to identify all randomized controlled trials (RCTs) comparing adjuvant cisplatin-based chemotherapy with control for patients with MIBC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to May 2013. An updated systematic review and meta-analysis was performed. EVIDENCE SYNTHESIS A total of 945 patients included in nine RCTs (five previously analyzed, one updated, and three new) were examined. For overall survival, the pooled hazard ratio (HR) across all nine trials was 0.77 (95% confidence interval [CI], 0.59-0.99; p=0.049). For disease-free survival, the pooled HR across seven trials reporting this outcome was 0.66 (95% CI, 0.45-0.91; p=0.014). This disease-free survival benefit was more apparent among those with positive nodal involvement (p=0.010). CONCLUSIONS This updated and improved meta-analysis of randomized trials provides further evidence of an overall survival and disease-free survival benefit in patients with MIBC receiving adjuvant cisplatin-based chemotherapy after radical cystectomy.

Propensity-matched comparison of morbidity and costs of open and robot-assisted radical cystectomies: a contemporary population-based analysis in the United States.

BACKGROUND Radical cystectomy (RC) is a morbid procedure associated with high costs. Limited population-based data exist on the complication profile and costs of robot-assisted RC (RARC) compared with open RC (ORC). OBJECTIVE To evaluate morbidity and cost differences between ORC and RARC. DESIGN, SETTING, AND PARTICIPANTS We conducted a population-based, retrospective cohort study of patients who underwent RC at 279 hospitals across the United States between 2004 and 2010. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable logistic and median regression was performed to evaluate 90-d mortality, postoperative complications (Clavien classification), readmission rates, length of stay (LOS), and direct costs. To reduce selection bias, we used propensity weighting with survey weighting to obtain nationally representative estimates. RESULTS AND LIMITATIONS The final weighted cohort included 34 672 ORC and 2101 RARC patients. RARC use increased from 0.6% in 2004 to 12.8% in 2010. Major complication rates (Clavien grade ≥ 3; 17.0% vs 19.8%, p = 0.2) were similar between ORC and RARC (odds ratio [OR]: 1.32; p = 0.42). RARC had 46% decreased odds of minor complications (Clavien grade 1-2; OR: 0.54; p = 0.03). RARC had

Influence of the National Trauma Data Bank on the Study of Trauma Outcomes: Is it Time to Set Research Best Practices to Further Enhance Its Impact?

4326 higher adjusted 90-d median direct costs (p = 0.004). Although RARC had a significantly shorter LOS (11.8 d vs 10.2 d; p = 0.008), no significant differences in room and board costs existed (p = 0.20). Supply costs for RARC were significantly higher (

A Systematic Review and Meta-analysis of Adjuvant and Neoadjuvant Chemotherapy for Upper Tract Urothelial Carcinoma

6041 vs

Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up

3638; p < 0.0001). Morbidity and cost differences were not present among the highest-volume surgeons (≥ 7 cases per year) and hospitals (≥ 19 cases per year). Limitations include use of an administrative database and lack of oncologic characteristics. CONCLUSIONS The use of RARC has increased between 2004 and 2010. Compared with ORC, RARC was associated with decreased odds of minor but not major complications and with increased expenditures attributed primarily to higher supply costs. Centralization of ORC and RARC to high-volume providers may minimize these morbidity and cost differences. PATIENT SUMMARY Using a US population-based cohort, we found that robotic surgery for bladder cancer decreased minor complications, had no impact on major complications and was more costly than open surgery.

Association of PD-L1 expression on tumor-infiltrating mononuclear cells and overall survival in patients with urothelial carcinoma

BACKGROUND Risk-adjusted analyses are critical in evaluating trauma outcomes. The National Trauma Data Bank (NTDB) is a statistically robust registry that allows such analyses; however, analytical techniques are not yet standardized. In this study, we examined peer-reviewed manuscripts published using NTDB data, with particular attention to characteristics strongly associated with trauma outcomes. Our objective was to determine if there are substantial variations in the methodology and quality of risk-adjusted analyses and therefore, whether development of best practices for risk-adjusted analyses is warranted. STUDY DESIGN A database of all studies using NTDB data published through December 2010 was created by searching PubMed and Embase. Studies with multivariate risk-adjusted analyses were examined for their central question, main outcomes measures, analytical techniques, covariates in adjusted analyses, and handling of missing data. RESULTS Of 286 NTDB publications, 122 performed a multivariable adjusted analysis. These studies focused on clinical outcomes (51 studies), public health policy or injury prevention (30), quality (16), disparities (15), trauma center designation (6), or scoring systems (4). Mortality was the main outcome in 98 of these studies. There were considerable differences in the covariates used for case adjustment. The 3 covariates most frequently controlled for were age (95%), Injury Severity Score (85%), and sex (78%). Up to 43% of studies did not control for the 5 basic covariates necessary to conduct a risk-adjusted analysis of trauma mortality. Less than 10% of studies used clustering to adjust for facility differences or imputation to handle missing data. CONCLUSIONS There is significant variability in how risk-adjusted analyses using data from the NTDB are performed. Best practices are needed to further improve the quality of research from the NTDB.

Improving Selection Criteria for Early Cystectomy in High-Grade T1 Bladder Cancer: A Meta-Analysis of 15,215 Patients

CONTEXT The role of adjuvant chemotherapy (AC) or neoadjuvant chemotherapy (NC) remains poorly defined for the management of upper tract urothelial carcinoma (UTUC), although some studies suggest a benefit. OBJECTIVE To update the current evidence on the role of NC and AC for UTUC patients. EVIDENCE ACQUISITION We searched for all studies investigating NC or AC for UTUC in Medline, Embase, the Cochrane Central Register of Controlled Trials, and abstracts from the American Society of Clinical Oncology meetings prior to February 2014. A systematic review and meta-analysis were performed. EVIDENCE SYNTHESIS No randomized trials investigated the role of AC for UTUC. There was one prospective study (n=36) investigating adjuvant carboplatin-paclitaxel and nine retrospective studies, with a total of 482 patients receiving cisplatin-based or non-cisplatin-based AC after nephroureterectomy (NU) and 1300 patients receiving NU alone. Across three cisplatin-based studies, the pooled hazard ratio (HR) for overall survival (OS) was 0.43 (95% confidence interval [CI], 0.21-0.89; p=0.023) compared with those who received surgery alone. For disease-free survival (DFS), the pooled HR across two studies was 0.49 (95% CI, 0.24-0.99; p=0.048). Benefit was not seen for non-cisplatin-based regimens. For NC, two phase 2 trials demonstrated favorable pathologic downstaging rates, with 3-yr OS and disease-specific survival (DSS) ≤ 93%. Across two retrospective studies investigating NC, there was a DSS benefit, with a pooled HR of 0.41 (95% CI, 0.22-0.76; p=0.005). CONCLUSIONS There appears to be an OS and DFS benefit for cisplatin-based AC in UTUC. This evidence is limited by the retrospective nature of studies and their relatively small sample size. NC appears to be promising, but more trials are needed to confirm its utility. PATIENT SUMMARY After a comprehensive search of studies examining the role of chemotherapy for upper tract urothelial cancer, the pooled evidence shows that cisplatin-based adjuvant chemotherapy was beneficial for prolonging survival.

Impact of surgeon volume on the morbidity and costs of radical cystectomy in the USA: a contemporary population‐based analysis

n Europe, an estimated 151 297 new cases of bladder cancer were diagnosed in 2012, with an age-standardised incidence rate (per 100 000 persons) of 17.7 for males and 3.5 for females. Overall, the annual crude incidence rate is 20.4/100 000. In 2012, there were 52 395 deaths from bladder cancer with an annual crude mortality rate of 7.1/100 000 [1]. Approximately 70% of patients with bladder cancer are >65 years of age. The most common presenting symptom is painless haematuria, seen in >80% of patients. Others may also present with irritative symptoms such as dysuria, frequency or urgency. Symptoms of metastases such as bone or flank pain are rare. Most diagnosed cases of muscle-invasive bladder cancer (MIBC; 80%–90%) present as primary invasive bladder cancer. However, up to 15% of patients have a history of non-muscle-invasive bladder cancer (NMIBC), mainly high-risk cases.

The impact of resident involvement in minimally-invasive urologic oncology procedures

BACKGROUND Programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) pathway negatively regulates T-cell-mediated responses. The prognostic impact of PD-L1 expression needs to be defined in urothelial carcinoma (UC). PATIENTS AND METHODS Formalin-fixed paraffin-embedded tumor samples from 160 patients with UC were retrieved. PD-L1 expression was evaluated by immunohistochemistry using a mouse monoclonal anti-PD-L1 antibody (405.9A11). PD-L1 positivity on tumor cell membrane was defined as ≥5% of tumor cell membrane staining. The extent of tumor-infiltrating mononuclear cells (TIMCs) as well as PD-L1 expression on TIMCs was scored from 0 to 4. A score of 2, 3, or 4 was considered PD-L1-positive. Clinico-pathological variables were documented. The Cox regression model was used to assess the association of PD-L1 expression with overall survival (OS) in patients who developed metastases. RESULTS TIMCs were present in 143 of the 160 patient samples. Out of 160 samples, 32 (20%) had positive PD-L1 expression in tumor cell membrane. Out of 143 samples with TIMCs, 58 (40%) had positive PD-L1 expression in TIMCs. Smoking history, prior BCG use and chromosome 9 loss did not correlate with PD-L1 expression in either tumor cell membrane or TIMCs. PD-L1 positivity was not different between non-invasive or invasive UC. In patients who developed metastases (M1) and were treated with systemic therapy (n = 100), PD-L1 positivity on tumor cell membrane was seen in 14% of patients and did not correlate with OS (P = 0.45). Out of 89 M1 patients who had evaluable PD-L1 on TIMCs, PD-L1 expression was seen in 33% of patients and was significantly associated with longer OS on multivariate analysis (P = 0.0007). CONCLUSION PD-L1 is widely expressed in tumor cell membrane and TIMCs in UC. PD-L1 in tumor cells was not predictive of OS. However, positive PD-L1 expression in TIMCs was significantly associated with longer survival in those patients who developed metastases.

Review: indications for ultrasound use in low- and middle-income countries

PURPOSE High-grade T1 (HGT1) bladder cancer is the highest risk subtype of non-muscle-invasive bladder cancer, with highly variable prognosis, poorly understood risk factors, and considerable debate about the role of early cystectomy. We aimed to address these questions through a meta-analysis of outcomes and prognostic factors. METHODS PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and American Society of Clinical Oncology abstracts were searched for cohort studies in HGT1. We pooled data on recurrence, progression, and cancer-specific survival from 73 studies. RESULTS Five-year rates of recurrence, progression, and cancer-specific survival were 42% (95% CI, 39% to 45%), 21% (95% CI, 18% to 23%), and 87% (95% CI, 85% to 89%), respectively (56 studies, n = 15,215). In the prognostic factor meta-analysis (33 studies, n = 8,880), the highest impact risk factor was depth of invasion (T1b/c) into lamina propria (progression: hazard ratio [HR], 3.34; P < .001; cancer-specific survival: HR, 2.02; P = .001). Several other previously proposed factors also predicted progression and cancer-specific survival (lymphovascular invasion, associated carcinoma in situ, nonuse of bacillus Calmette-Guérin, tumor size > 3 cm, and older age; HRs for progression between 1.32 and 2.88, P ≤ .002; HRs for cancer-specific survival between 1.28 and 2.08, P ≤ .02). CONCLUSION In this large analysis of outcomes and prognostic factors in HGT1 bladder cancer, deep lamina propria invasion had the largest negative impact, and other previously proposed prognostic factors were also confirmed. These factors should be used for prognostication and patient stratification in future clinical trials, and depth of invasion should be considered for inclusion in TNM staging criteria. This meta-analysis can also help define selection criteria for early cystectomy in HGT1 bladder cancer, particularly for patients with deep lamina propria invasion combined with other risk factors.