**7. Adjuvant treatment**

Adjuvant therapy in oncology describes the use of additional treatment alongside the primary, definitive, usually surgical, treatment, in an attempt to achieve higher rates of progression-free and overall survival. In RCC, this has not been widely employed as many trials have shown adjuvant treatment in early stage renal cancer not to translate into an overall survival benefit [49, 50]. However, it is also recognised that many patients with early stage disease will also go on to relapse, and therefore, interest in this area has remained high and guidelines recommend that for intermediate- and high-risk patients, adjuvant treatment, as part of a clinical trial, should be considered [36, 49]. In ASSURE trial, sunitinib or sorafenib failed to demonstrate an improvement in disease-free survival (DFS) compared to placebo [51]. In S-TRAC trial, sunitinib did increase 5-year DFS, but not overall survival data, although the overall survival data have not yet improved [52]. In the PROTECT trial, pazopanib failed to


**Table 4.** Trials of tyrosine kinase inhibitors in the adjuvant renal cancer setting post-nephrectomy.

show a statistically significant improvement in DFS [53]. In the ATLAS trial, using axitinib in the adjuvant setting, the primary end point was not reached and the study was abandoned due to futility at the interim assessment point [54]. It is also worth noting that the majority of patients in these adjuvant trials had ccRCC histology. A summary of the reported trials is shown in **Table 4**.

Several trials are still ongoing using targeted therapies in high-risk patients post-nephrectomy including: SORCE trial (NCT00492258) assessing sorafenib and EVEREST trial (NCT01120249) investigating everolimus [50]. Further trials are underway to assess the use of immunotherapy in the adjuvant setting using a variety of checkpoint inhibitors. These include the IMmotion101 trial (NCT03024996) with atezolizumab, PROSPER trial (NCT03055013) comparing neoadjuvant and adjuvant nivolumab versus observation, KEYNOTE-564 trial (NCT03142334) evaluating pembrolizumab versus placebo and CheckMate 914 trial (NCT03138512) comparing nivolumab with ipilimumab versus placebo [50]. The results of these trials are likely to be reported in the coming years; however, the standard of care at present is not to prescribe adjuvant therapy, of any kind, post-nephrectomy in renal cell carcinoma.
