**8. Emerging treatments and trends**

Metastasectomy can be employed for metastatic disease in a number of sites including bone, lungs and brain. Good long-term outcomes have been observed, especially with careful

A combination of metastasectomy and post-operative SABR for brain metastasis has been employed with excellent results and has been shown to have less side effects than post-oper-

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

**patients (n)**

Sunitinib versus placebo 615 Sunitinib 6.8 years

Pazopanib versus placebo 1538 HR 0.86

Axitinib versus placebo 724 HR 0.870

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

**Disease-free survival (DFS)**

(HR 0.97 P = 0.718) Sunitinib 5.8 years (HR 1.02 P = 0.804) Placebo 6.6 years

Placebo 5.6 years (HR 0.76 P = 0.03)

P = 0.165

P = 0.3211

1943 Sorafenib 6.1 years

**Overall survival (OS)**

*No significant difference between groups*

Mature data not available.

Not available

Not available

At 5 years Sorafenib 80.5% Sunitinib 77.9% Placebo 80.3%

patient selection [46, 47].

164 Evolving Trends in Kidney Cancer

**7. Adjuvant treatment**

ASSURE Haas et al. [50]

S-TRAC

PROTECT Motzer et al. [52]

ATLAS

[53]

Ravaud et al. [51]

Gross-Goupil et al.

ative treatment with whole brain radiotherapy [48].

**Trial Drug Number of** 

placebo

Sorafenib/Sunitinib versus

An area of particular interest for oncologist is the search for reliable biomarkers, which will guide us into targeting our treatments to the patients who will benefit from them the most. Renal cell carcinoma is no exception and the hunt for a biomarker is of high interest to academics and drug companies alike. Biomarkers are being investigated in the areas of imaging serum, histology, and urine, both to determine treatment strategies and to differentiate between benign and malignant processes [55]. One biomarker of particular interest is carbonic anhydrase IX, which has demonstrated excellent specificity and ability to predict treatment response [56]. Researchers are also keen to identify reliable biomarkers for use with immune checkpoint inhibitors in the treatment of RCC, especially to help differentiate between the progression and pseudoprogression on treatment [57].

Research has been conducted on the use of vaccine therapy in RCC. Vaccines are designed to induce a specific immune response in the patient; however, this is yet to translate into an overall survival benefit [58, 59]. In the new era of targeted medicine and next-generation immunotherapy, the role of vaccines remains uncertain and only further research in this area, with associated success in randomised trials, will confirm vaccine therapy as a viable treatment strategy for the future.

Interesting evidence has been published on the use of SABR in patients who are not fit for partial nephrectomy. High doses of highly targeted radiotherapy are given to the tumour patients with the hope of ablation of the tumour. The treatment was well tolerated with low toxicity and good local control rates in 2 years [60]. Further ongoing evaluation of this technique is needed, but it is likely that use of SABR in this format will increase in the future.
