Steven L. Chang

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

Comparative Effectiveness of Robot-Assisted and Open Radical Prostatectomy in the Postdissemination Era

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

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

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.

National Trends of Perioperative Outcomes and Costs for Open, Laparoscopic and Robotic Pediatric Pyeloplasty

PURPOSE Given the lack of randomized trials comparing robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP), we sought to re-examine the outcomes of these techniques using a cohort of patients treated in the postdissemination era. PATIENTS AND METHODS Overall, data from 5,915 patients with prostate cancer treated with RARP or ORP within the SEER-Medicare linked database diagnosed between October 2008 and December 2009 were abstracted. Postoperative complications, blood transfusions, prolonged length of stay (pLOS), readmission, additional cancer therapies, and costs of care within the first year after surgery were compared between the two surgical approaches. To decrease the effect of unmeasured confounders, instrumental variable analysis was performed. Multivariable logistic regression analyses were then performed. RESULTS Overall, 2,439 patients (41.2%) and 3,476 patients (58.8%) underwent ORP and RARP, respectively. In multivariable analyses, patients undergoing RARP had similar odds of overall complications, readmission, and additional cancer therapies compared with patients undergoing ORP. However, RARP was associated with a higher probability of experiencing 30- and 90-day genitourinary and miscellaneous medical complications (all P ≤ .02). Additionally, RARP led to a lower risk of experiencing blood transfusion and of having a pLOS (all P < .001). Finally, first-year reimbursements were greater for patients undergoing RARP compared with ORP (P < .001). CONCLUSION RARP and ORP have comparable rates of complications and additional cancer therapies, even in the postdissemination era. Although RARP was associated with lower risk of blood transfusions and a slightly shorter length of stay, these benefits do not translate to a decrease in expenditures.

Survival Analyses of Patients With Metastatic Renal Cancer Treated With Targeted Therapy With or Without Cytoreductive Nephrectomy: A National Cancer Data Base Study

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.

Pharmacological GLI2 inhibition prevents myofibroblast cell-cycle progression and reduces kidney fibrosis

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.

The impact of robotic surgery on the surgical management of prostate cancer in the USA

PURPOSE We performed a population based study comparing trends in perioperative outcomes and costs for open, laparoscopic and robotic pediatric pyeloplasty. Specific billing items contributing to cost were also investigated. MATERIALS AND METHODS Using the Perspective database (Premier, Inc., Charlotte, North Carolina), we identified 12,662 pediatric patients who underwent open, laparoscopic and robotic pyeloplasty (ICD-9 55.87) in the United States from 2003 to 2010. Univariate and multivariate statistics were used to evaluate perioperative outcomes, complications and costs for the competing surgical approaches. Propensity weighting was used to minimize selection bias. Sampling weights were used to yield a nationally representative sample. RESULTS A decrease in open pyeloplasty and an increase in minimally invasive pyeloplasty were observed. All procedures had low complication rates. Compared to open pyeloplasty, laparoscopic and robotic pyeloplasty had longer median operative times (240 minutes, p <0.0001 and 270 minutes, p <0.0001, respectively). There was no difference in median length of stay. Median total cost was lower among patients undergoing open vs robotic pyeloplasty (

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

7,221 vs