Ileal Interposition for Ureteral Reconstruction Following Treatment for Abdominopelvic Malignancy: Complications and Outcomes From a Comprehensive Cancer Center.

OBJECTIVE: To characterize the outcomes of ileal interposition for the management of ureteral obstruction from tumor and ureteral stricture following treatment for abdominopelvic malignancy. MATERIALS AND METHODS: A retrospective database analysis was performed for all cases of ileal interposition performed by 5 surgeons from January 2013 to December 2020. Patients were ≥18 years of age and included if undergoing ileal interposition in either the primary setting of a surgical procedure for tumor extirpation or in the delayed setting. RESULTS: In total, 23 patients who underwent repair of 27 ureteral units were included. The mean age was 60.2 years. Median follow-up was 21.6 months. The most common primary diagnoses were urothelial (35%), colorectal (31%), and cervical (22%) cancer. The etiologies of ureteral obstruction were malignant in 48% and ureteral stricture in 52%. Types of repairs included unilateral interposition in 13 patients, bilateral interposition in 1 patient, interposition to an ileal conduit in 3 patients, and interposition with cystoplasty in 6 patients. There was a statistically significant difference between the mean preoperative (Creatinine 1.05 mg/dL, Estimated Glomerular Filtration Rate 77 ml/min/1.73 m2) renal function and postoperative (Creatinine 1.26 mg/dL, Estimated Glomerular Filtration Rate 67 mL/min/1.73 m2) renal function at the most recent follow-up (P = .024). Eight minor (grade 1-2) and 6 major (grade ≥3) complications developed for a minor and major complication rate of 35% and 26%, respectively. CONCLUSION: Ileal interposition is successfully utilized as a reconstructive technique at the time of enbloc resection involving the ureter and to address ureteral stricture in the delayed setting.

Adjuvant therapy in patients with sarcomatoid renal cell carcinoma: post hoc analysis from Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E2805.

OBJECTIVES: To study the effects of adjuvant therapy in patients with sarcomatoid renal cell carcinoma (sRCC) enrolled in the randomised phase III clinical trial E2805. PATIENTS AND METHODS: The original trial (E2805) was a randomised, double-blinded phase III clinical trial comparing outcomes in 1943 patients with RCC accrued between 2006 and 2010 and treated with up to 1 year of adjuvant placebo, sunitinib, or sorafenib. The present study analyses the cohort of patients with sRCC that participated in E2805. RESULTS: A total of 171 patients (8.8%) had sarcomatoid features. Of these, 52 patients received sunitinib, 58 received sorafenib, and 61 received placebo. Most patients were pT3-4 (71.1%, 63.7%, and 70.5%, respectively); 17.3%, 19.0%, and 27.9% had pathologically positive lymph nodes; and 59.6%, 62.1%, and 62.3% of the patients were University of California Los Angeles (UCLA) Integrated Staging System (UISS) very-high risk. In 49% of patients with subsequent development of metastatic disease, recurrence occurred in the lung, followed by 30% in the lymph nodes, and 13% in the liver. There was a high local recurrence rate in the renal bed (16%, 29%, and 18%, respectively). The 5-year disease-free survival (DFS) rates were 33.6%, 36.0%, and 27.8%, for sunitinib, sorafenib and placebo, respectively (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.45-1.20 for sunitinib vs placebo, and HR 0.82, 95% CI 0.53-1.28 for sorafenib vs placebo). CONCLUSIONS: Adjuvant therapy with sunitinib or sorafenib did not show an improvement in DFS or OS in patients with sRCC.

Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial.

BACKGROUND: Renal-cell carcinoma is highly vascular, and proliferates primarily through dysregulation of the vascular endothelial growth factor (VEGF) pathway. We tested sunitinib and sorafenib, two oral anti-angiogenic agents that are effective in advanced renal-cell carcinoma, in patients with resected local disease at high risk for recurrence. METHODS: In this double-blind, placebo-controlled, randomised, phase 3 trial, we enrolled patients at 226 study centres in the USA and Canada. Eligible patients had pathological stage high-grade T1b or greater with completely resected non-metastatic renal-cell carcinoma and adequate cardiac, renal, and hepatic function. Patients were stratified by recurrence risk, histology, Eastern Cooperative Oncology Group (ECOG) performance status, and surgical approach, and computerised double-blind randomisation was done centrally with permuted blocks. Patients were randomly assigned (1:1:1) to receive 54 weeks of sunitinib 50 mg per day orally throughout the first 4 weeks of each 6 week cycle, sorafenib 400 mg twice per day orally throughout each cycle, or placebo. Placebo could be sunitinib placebo given continuously for 4 weeks of every 6 week cycle or sorafenib placebo given twice per day throughout the study. The primary objective was to compare disease-free survival between each experimental group and placebo in the intention-to-treat population. All treated patients with at least one follow-up assessment were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00326898. FINDINGS: Between April 24, 2006, and Sept 1, 2010, 1943 patients from the National Clinical Trials Network were randomly assigned to sunitinib (n=647), sorafenib (n=649), or placebo (n=647). Following high rates of toxicity-related discontinuation after 1323 patients had enrolled (treatment discontinued by 193 [44%] of 438 patients on sunitinib, 199 [45%] of 441 patients on sorafenib), the starting dose of each drug was reduced and then individually titrated up to the original full doses. On Oct 16, 2014, because of low conditional power for the primary endpoint, the ECOG-ACRIN Data Safety Monitoring Committee recommended that blinded follow-up cease and the results be released. The primary analysis showed no significant differences in disease-free survival. Median disease-free survival was 5·8 years (IQR 1·6-8·2) for sunitinib (hazard ratio [HR] 1·02, 97·5% CI 0·85-1·23, p=0·8038), 6·1 years (IQR 1·7-not estimable [NE]) for sorafenib (HR 0·97, 97·5% CI 0·80-1·17, p=0·7184), and 6·6 years (IQR 1·5-NE) for placebo. The most common grade 3 or worse adverse events were hypertension (105 [17%] patients on sunitinib and 102 [16%] patients on sorafenib), hand-foot syndrome (94 [15%] patients on sunitinib and 208 [33%] patients on sorafenib), rash (15 [2%] patients on sunitinib and 95 [15%] patients on sorafenib), and fatigue 110 [18%] patients on sunitinib [corrected]. There were five deaths related to treatment or occurring within 30 days of the end of treatment; one patient receiving sorafenib died from infectious colitis while on treatment and four patients receiving sunitinib died, with one death due to each of neurological sequelae, sequelae of gastric perforation, pulmonary embolus, and disease progression. Revised dosing still resulted in high toxicity. INTERPRETATION: Adjuvant treatment with the VEGF receptor tyrosine kinase inhibitors sorafenib or sunitinib showed no survival benefit relative to placebo in a definitive phase 3 study. Furthermore, substantial treatment discontinuation occurred because of excessive toxicity, despite dose reductions. These results provide a strong rationale against the use of these drugs for high-risk kidney cancer in the adjuvant setting and suggest that the biology of cancer recurrence might be independent of angiogenesis. FUNDING: US National Cancer Institute and ECOG-ACRIN Cancer Research Group, Pfizer, and Bayer.

Surgical morbidity associated with administration of targeted molecular therapies before cytoreductive nephrectomy or resection of locally recurrent renal cell carcinoma.

PURPOSE: Targeted molecular therapies such as bevacizumab, sunitinib and sorafenib before surgical resection hold promise as rational treatment paradigms for patients with metastatic or locally recurrent renal cell carcinoma. To analyze the safety of this approach we evaluated surgical parameters and perioperative complications in patients treated with targeted molecular therapies before cytoreductive nephrectomy or resection of retroperitoneal renal cell carcinoma recurrence, and compared them to a matched patient cohort who underwent up-front surgical resection. MATERIALS AND METHODS: We evaluated surgical parameters and perioperative complications in 44 patients treated with targeted molecular therapies before cytoreductive nephrectomy or resection of local renal cell carcinoma recurrence, and in a matched cohort of 58 patients who underwent up-front surgery. RESULTS: Cohorts of patients treated with preoperative targeted molecular therapy and initial surgical resection were matched in terms of clinical characteristics, burden of metastatic disease and number of adverse prognostic factors. A total of 39 complications occurred in 17 (39%) patients treated with preoperative targeted molecular therapy and in 16 (28%) who underwent up-front resection (p = 0.287). There were no statistically significant differences in surgical parameters, incidence of perioperative mortality, re-exploration, readmission, thromboembolic, cardiovascular, pulmonary, gastrointestinal, infectious or incision related complications between patients treated with preoperative targeted molecular therapy and those who underwent up-front surgery. Duration, type and interval from targeted molecular therapy to surgical intervention were not associated with the risk of perioperative morbidity. CONCLUSIONS: Preoperative administration of targeted molecular therapies is safe, and does not increase surgical morbidity or perioperative complications in patients treated with cytoreductive nephrectomy or resection of recurrent retroperitoneal renal cell carcinoma.