Open Access

ARTICLE

Does timing of targeted therapy for metastatic renal cell carcinoma impact treatment toxicity and surgical complications? Acomparison of primary and adjuvant approaches

Nishant Patel¹, Jason Woo¹, Michael A. Liss¹, Kerrin L. Palazzi¹, J. Michael Randall², Reza Mehrazin³, Ramzi Jabaji¹, Hossein S. Mirheydar¹, Kyle Gillis¹, Hak J. Lee¹, Anthony L. Patterson³, Christopher J. Kane¹, Frederick Millard², Ithaar H. Derweesh¹

1 Department of Urology, University of California San Diego Health System, La Jolla, California, USA
2 Department of Medicine, University of California San Diego Health System, La Jolla, California, USA
3 Department of Urology, University of Tennessee Health Science Center, Memphis, Tennessee, USA
Address correspondence to Dr. Ithaar H Derweesh, Moores UCSD Cancer Center, 3855 Health Sciences Drive, Mail Code: 0987, La Jolla, CA 92093-0987 USA

Canadian Journal of Urology 2016, 23(2), 8227-8233.

Abstract

Introduction: 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).
Materials and 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).
Conclusion: 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.

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