Malek Meskawi

A Review of Integrated Staging Systems for Renal Cell Carcinoma

CONTEXT Several outstanding integrated staging systems (ISSs) have been devised for patients with renal cell carcinoma (RCC). OBJECTIVE To review the available literature on existing ISSs. EVIDENCE ACQUISITION A nonsystematic search was conducted using Medline and PubMed databases. Original articles, review articles, and editorials addressing the development and validation of ISSs in RCC published up to February 2012 were identified. The search was limited to the English language. Keywords included kidney cancer, renal cell carcinoma, nomogram, risk group, prognosis, predictive accuracy, external validation, and discrimination. Links to related articles and cross-reading of citations in related articles were surveyed. All articles with a pertinent level of evidence were included and represent the basis for the current review article. EVIDENCE SYNTHESIS In nephrectomy patients, a variety of models have been developed for prediction of recurrence and survival, both in the preoperative and postoperative settings. Several of those models relied on variables that are not routinely available in clinical practice. Not all tools were externally validated. In patients treated with systemic therapy, novel tools that were developed and validated in the targeted therapy era replaced tools devised during the cytokine era. CONCLUSIONS The development of ISSs for prediction of risk or prognosis in the context of RCC has evolved and improved. In the targeted therapy era, the urologic community should focus on direct comparisons of existing tools with the intent of identifying the optimal ISS for each specific end point.

Assessment of Cancer Control Outcomes in Patients With High-risk Renal Cell Carcinoma Treated With Partial Nephrectomy

OBJECTIVE To test whether cancer control outcomes justify the consideration of partial nephrectomy in patients with large tumors (Stage pT2 or greater) or high-grade tumors (Fuhrman grade III-IV) or lesions extending beyond the kidney (Stage pT3a). METHODS We abstracted the data for 8847, 11 547, and 5232 patients with tumors >7 cm, Fuhrman grade III-IV, and Stage T3a from the Surveillance, Epidemiology, and End Results database, respectively. All were treated with either partial nephrectomy or radical nephrectomy from 1988 to 2008. The 2- and 5-year cancer-specific mortality rates were compared between the partial nephrectomy and radical nephrectomy groups after propensity score matching. Separate multivariate analyses were conducted within each subcohort and specifically quantified the effect of partial nephrectomy on cancer-specific mortality. RESULTS For each of the 3 examined groups, the patients treated with partial nephrectomy failed to demonstrate statistically significant cancer-specific mortality differences relative to radical nephrectomy patients. The hazard ratio for the tumors >7 cm, Fuhrman grade III-IV, and Stage pT3a was 0.67 (95% confidence interval 0.39-1.17, P = .2), 0.81 (95% confidence interval 0.58-1.12, P = .21), and 0.99 (95% confidence interval 0.61-1.61, P = 1.0). CONCLUSION Even in patients with adverse pathologic features, partial nephrectomy does not compromise cancer-specific mortality. This implies that when functional outcomes are considered in patients with high-risk features, the decision to perform partial nephrectomy should not depend on the stage or grade, but rather on the technical ability to remove the tumor with a negative margin and provide sufficient functional renal remnant.

Prediction of Complications Following Partial Nephrectomy: Implications for Ablative Techniques Candidates

BACKGROUND Current guidelines recommend local tumour ablation (LTA) over partial nephrectomy (PN) in nonsurgical candidates; however, objective definitions of these candidates are lacking. OBJECTIVE To identify specific patients who would benefit from LTA more than PN. DESIGN, SETTING, AND PARTICIPANTS A population-based assessment was performed of 2476 patients in the Surveillance Epidemiology and End Results-Medicare database who had cT1a kidney cancer treated with either LTA or PN, between 2000 and 2009. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The outcome of the study was the relevant perioperative complications rate. A multivariable logistic regression model was fitted to predict the risk of complications after PN. Model-derived coefficients were used to calculate the risk of complication in case of PN among patients treated with LTA. Locally weighted scatterplot smoothing method was used to plot the observed complication rate against the predicted risk of complication in case of PN. RESULTS AND LIMITATIONS At multivariable logistic regression, age (odds ratio [OR]: 1.04; p<0.001), Charlson comorbidity index (OR: 1.14; p<0.001), acute kidney injury (OR: 1.91; p=0.04), or chronic kidney disease (OR: 2.16; p=0.002), tumour size (OR: 1.02; p=0.01), and minimally invasive approach (OR: 0.77; p<0.03) emerged as significant predictors of complications. When LTA was chosen over PN, the reduction in the risk of complications was greatest in high-risk patients, intermediate in intermediate-risk patients, and least in low-risk patients. CONCLUSIONS When postoperative complications are evaluated, the benefit of choosing LTA is not the same in all patients diagnosed with T1a kidney cancer. Specifically, patients at high risk of complications in case of PN may benefit the most from LTA and represent ideal LTA candidates. PATIENT SUMMARY Elderly patients at high risk of complications in case of surgical treatment with partial nephrectomy for kidney cancer should be instructed that local tumour ablation might decrease their perioperative morbidity.

Updated assessment of neoblader utilization and morbidity according to urinary diversion after radical cystectomy: A contemporary US-population-based cohort

BACKGROUND In this paper, we examine contemporary utilization rates and determinants of neobladder (NB) after radical cystectomy (RC) relative to ileal conduit (IC), as well as provide an updated assessment of postoperative morbidity and mortality between NB and IC. METHODS Relying on the Nationwide Inpatient Sample (NIS), we abstracted patients who underwent RC between 2000 and 2010. Subsequently, NB and IC recipients were identified. Use of NB was assessed after accounting for case-mix. Propensity-based matched analyses were used to account for treatment selection biases. Generalized linear regression analyses focused on intra- and postoperative complications, prolonged length of stay, blood transfusions and in-hospital mortality. RESULTS The utilization rate of NB was 6.9% in 2000 and 9.1% in 2010 (p < 0.001). Younger, healthier, privately-insured and wealthier male individuals were more likely to receive a NB. High-volume hospitals were more likely to offer NB. In the post-propensity matched cohort, urinary diversion type failed to be significantly associated with the examined endpoints, except for intra- and postoperative complications (IC vs. NB odds ratio [OR]: 1.15, p = 0.04). INTERPRETATION Despite comparable morbidity and mortality odds between NB and IC, as of the most contemporary year of the study (2010), IC remains the preferred urinary diversion type. Several sociodemographic factors were associated with NB.

Partial and radical nephrectomy provide comparable long-term cancer control for T1b renal cell carcinoma

To examine utilization rates of partial nephrectomy relative to radical nephrectomy for T1b renal cell carcinoma in contemporary years, to identify sociodemographic and disease characteristics associated with partial nephrectomy use, and to compare effectiveness of partial versus radical nephrectomy with respect to cancer control.

A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma

BACKGROUND To provide an updated review of adverse events associated with sunitinib, pazopanib, bevacizumab, temsirolimus, axitinib, everolimus and sorafenib and their management. MATERIALS AND METHODS We performed a PubMed and Cochrane-based review of side effects associated with the seven agents including product monographs to provide an outline of treatment measures aiming to reduce their toxicities. Subject and outcome of interest, design type, sample size, pertinence and quality, and detail of reporting were the indicators of manuscript quality. RESULTS All targeted therapies cause adverse events. Most adverse events may be prevented or tested before they escalate to severe levels. CONCLUSION Prevention, early recognition, and prompt management of side effects are of key importance and avoid unnecessary dose reductions, which may undermine treatment efficacy.

Benefit in regionalisation of care for patients treated with radical cystectomy: a nationwide inpatient sample analysis

To quantify in absolute terms the potential benefit of regionalisation of care from low‐ to high‐volume hospitals.

Radical Cystectomy in the Elderly: National Trends and Disparities in Perioperative Outcomes and Quality of Care

Introduction: To examine national trends of radical cystectomy (RC) for urothelial carcinoma of urinary bladder in octogenarian patients and to assess the rates of adverse outcomes. Materials and Methods: Within the Nationwide Inpatient Sample (NIS), we focused on RCs performed between 1998 and 2007. Age was stratified as <80 versus ≥80 years. Propensity-based matched analyses were used to account for treatment selection biases. Generalized linear regression analyses were fitted to predict adverse perioperative events according to age. Results: Of 12,274 RC patients, 1,605 were ≥80 years (13.1%). The RC rates in octogenarians increased significantly from 9.9% in 1998 to 13.7% in 2007. Most elderly patients were treated at low-/intermediate-volume hospitals (81.7%) and nonacademic centers (60.6%). After propensity score matching, the inpatient mortality rate was higher in octogenarians (4.6 vs. 2.6%, p < 0.001). In multivariable analyses, octogenarians were at increased risk of blood transfusions (OR: 1.30) and postoperative complications (OR: 1.22). Conclusions: Most octogenarians undergoing RC are treated at low-/intermediate-volume hospitals and at nonacademic centers. The inpatient hospital mortality is about twice as high in these patients, and adverse perioperative outcomes are more frequent. Such patients may benefit from RC at high-volume and/or academic centers to maximally reduce adverse perioperative outcomes.

An evidence-based guide to the selection of sequential therapies in metastatic renal cell carcinoma.

Targeted therapies have introduced a paradigm shift in the management of metastatic renal cell carcinoma. Currently, four molecules (sunitinib, pazopanib, bevacizumab plus interferon, temsirolimus) are considered in first-line therapy, and three other molecules for second, or subsequent lines of therapy (everolimus, axitinib, sorafenib). In addition, other molecules and sequencing schemes are being tested in ongoing phase II/III studies. We conducted a systematic review using PubMed and several other databases up to December 2011 of prospective and retrospective studies on treatment management of metastatic renal cell carcinoma using targeted therapies, with a special focus on use of sequential treatment. Based on phase III data, the optimal sequencing scheme for patients with clear cell or even non-clear cell histological subtype appears to consist of sunitinib, followed by axitinib, followed by everolimus. Subsequent treatment options rely on lower evidence studies and could consist of fourth-line sorafenib or sunitinib rechallenge. Such therapies would qualify as last recourse options. In another context, temsirolimus may be used in patients who fulfill the Memorial Sloan-Kettering Cancer Center poor risk criteria or who have poor performance status. We conclude that in the current setting, sequential therapy represents the cornerstone of effective management of metastatic renal cell carcinoma.

Impact of academic affiliation on radical cystectomy outcomes in North America: A population-based study

BACKGROUND : The objective of this study was to examine the rates of blood transfusions, prolonged length of stay, intraoperative and postoperative complications, as well as in-hospital mortality, stratified according to institutional academic status in patients undergoing radical cystectomy (RC). METHODS : Within the Health Care Utilization Project Nationwide Inpatient Sample (NIS), we focused on patients in whom RC was performed between 1998 and 2007. Multivariable logistic regression analyses were fitted to predict the likelihood of blood transfusions, prolonged length of stay, intraoperative and postoperative complications, and in-hospital mortality. Covariates included age, race, gender, Charlson Comorbidity Index (CCI), hospital region, insurance status, annual hospital caseload (AHC), year of surgery and urinary diversion. RESULTS : Overall, 12 262 patients underwent RC. Of those, 7892 (64.4%) were from academic institutions. Patients treated at academic institutions were younger and healthier at baseline (all p < 0.001). RCs performed at academic institutions were associated with fewer postoperative complications (28.8% vs. 32.9%, p < 0.001), shorter length of stay (54.0% vs. 56.2%, p = 0.02) and lower in-hospital mortality rates (2.1 vs. 3.0%, p = 0.002). In multivariable analyses, patients who underwent RC at an academic hospital were 12% less likely to succumb to postoperative complications (odds ratio=0.88, p = 0.003). INTERPRETATION : Even after adjusting for AHC, RCs performed at academic institutions are associated with better postoperative outcomes than RCs performed at non-academic institutions. From a public health prospective, performing RCs at academic institutions may help reduce costs associated with the management of complications and prolonged length of stay.