title: Surgical outcomes and complications associated with presurgical tyrosine kinase inhibition for advanced renal cell carcinoma (RCC).
abstract: BACKGROUND
  Tyrosine kinase inhibitors (TKI) have dramatically changed the management paradigm of advanced renal cell carcinoma (RCC) and are increasingly being used preoperatively to achieve cytoreduction.
  
  
  OBJECTIVE
  To review our case series of post-TKI surgical procedures to add to the current perioperative efficacy and complication profile.
  
  
  METHODS
  Between October 2006 and February 2010, 14 cytoreductive nephrectomies, radical nephrectomies, and metastectomies were performed after neoadjuvant sunitinib or sorafenib for advanced RCC. During the same time frame, a control group of 73 consecutive patients underwent radical nephrectomy, cytoreductive nephrectomy, or metastectomy in the absence of prior systemic therapy. We compared the incidence of perioperative complications and outcomes after surgical procedures between the two cohorts.
  
  
  RESULTS
  Median preoperative renal mass size was 11 cm (6.7-24.2 cm). Primary tumor shrinkage was seen in 57%; median shrinkage was 18% (8%-25%). The median treatment period was 17 weeks, and the median time from TKI discontinuation was 2 weeks. Compared with a control group and after adjusting for confounding covariates, presurgical TKI use was not associated with a significant increase in perioperative complications (50% vs. 40%, P = 0.25) or perioperative bleeding (36% vs. 34%, P = 0.97) but was associated with increased incidence and grade of intraoperative adhesions (86% vs. 58%, P = 0.001; grade 3 vs. 1, P = 0.002).
  
  
  CONCLUSIONS
  Compared with the published reports, we observed less hemorrhagic and wound healing issues but a significant increase in incidence and severity of intraoperative adhesions, which can present a formidable technical challenge. Potential reasons for our lower complication rate could be increased time from TKI discontinuation to surgery, longer time to postoperative TKI re-initiation, increased use of preoperative angioembolization, and the lack of preoperative bevacizumab administration. Presurgical TKI therapy can permit effective surgical cytoreduction with a safety and complication profile equivalent to that of non-TKI-nephrectomy; however safety data continue to evolve, and preoperative TKI use requires further prospective investigation.
authors.affiliation: Division of Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA. laurenhs@stanford.edu
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Harshman
authors.forename: R James
authors.initials: RJ
authors.lastname: Yu
authors.forename: Genevera I
authors.initials: GI
authors.lastname: Allen
authors.forename: Sandy
authors.initials: S
authors.lastname: Srinivas
authors.forename: Harcharan S
authors.initials: HS
authors.lastname: Gill
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Chung
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009392:Nephrectomy / Q000009:adverse effects / Q000379:methods; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D011183:Postoperative Complications; D011300:Preoperative Care; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use; D000077157:Sorafenib; D000077210:Sunitinib; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology / Q000601:surgery
chemical_list: D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib