title: Does timing of targeted therapy for metastatic renal cell carcinoma impact treatment toxicity and surgical complications? A comparison of primary and adjuvant approaches.
abstract: BACKGROUND
  To compare surgical complications and tyrosine kinase inhibitor (TKI)-toxicities in patients who underwent primary cytoreductive nephrectomy (CN) followed by adjuvant TKI therapy versus those who underwent neoadjuvant TKI therapy prior to planned CN for metastatic renal cell carcinoma (mRCC).
  
  
  METHODS
  Two-center retrospective analysis. Sixty-one mRCC patients underwent TKI therapy with sunitinib between July 2007 to January 2014. Patients were divided into three groups: primary CN followed by adjuvant TKI (n = 27, Group 1), neoadjuvant TKI prior to CN (n = 21, Group 2), and primary TKI alone (no surgery, n = 13, Group 3). Primary outcome was frequency and severity of surgical complications (Clavien). Secondary outcome was frequency and severity of TKI-related toxicities (NIH Common Toxicity Criteria). Multivariable analysis was carried out for factors associated with complications.
  
  
  RESULTS
  There were no significant differences in demographics, ECOG status, and median number TKI cycles (p = 0.337). Mean tumor size (cm) was larger in Group 3 (12.8) than Group 2 (8.9) and Group 1 (9.3), p = 0.014. TKI-related toxicities occurred in 100%, 90.5%, and 88.9% in Group 3, Group 2, and Group 1 (p = 0.469). There was no difference in incidence of high grade (p = 0.967) and low grade (p = 0.380) TKI-toxicities. Overall surgical complication rate was similar between Group 2 (47.6%) and Group 1 (33.3%), p = 0.380. Group 2 had more high grade surgical complications (28.6%) than Group 1 (0%), p = 0.004. Multivariable analysis demonstrated increasing age was independently associated with development of surgical complications (HR 1.059, p = 0.040).
  
  
  CONCLUSIONS
  Patients receiving neoadjuvant TKI therapy prior to CN experienced more high grade surgical complications than patients who underwent primary CN. Potential for increased high grade surgical complications requires further investigation and may impact pretreatment counseling.
authors.affiliation: Department of Urology, University of California San Diego Health System, La Jolla, California, USA.
authors.forename: Nishant
authors.initials: N
authors.lastname: Patel
authors.forename: Jason
authors.initials: J
authors.lastname: Woo
authors.forename: Michael A
authors.initials: MA
authors.lastname: Liss
authors.forename: Kerrin L
authors.initials: KL
authors.lastname: Palazzi
authors.forename: J Michael
authors.initials: JM
authors.lastname: Randall
authors.forename: Reza
authors.initials: R
authors.lastname: Mehrazin
authors.forename: Ramzi
authors.initials: R
authors.lastname: Jabaj
authors.forename: Hossein S
authors.initials: HS
authors.lastname: Mirheydar
authors.forename: Kyle
authors.initials: K
authors.lastname: Gillis
authors.forename: Hak J
authors.initials: HJ
authors.lastname: Lee
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Patterson
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kane
authors.forename: Frederick
authors.initials: F
authors.lastname: Millard
authors.forename: Ithaar H
authors.initials: IH
authors.lastname: Derweesh
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000556:secondary / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy / Q000379:methods*; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents