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Stage IV Targeted molecular therapies using vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) (e.g., sunitinib, sorafenib, pazopanib and axitinib) or mammalian target of rapamycin inhibitors (e.g., temsirolimus and everolimus) have largely replaced immunotherapy agents (e.g., interferon-��) for systemic therapy. A randomized trial by Motzer et al[154] Hesperadin involving 750 patients with metastatic clear cell RCC showed that patients treated with sunitinib had longer progression free survival and overall survival compared with patients treated with interferon-��. Several studies have suggested that VEGF-TKIs may be less effective in treating papillary and chromophobe RCCs compared with clear cell RCCs[18,26,155-157]. At present, there is no established first-line therapy for metastatic non-clear cell RCC. As such, the NCCN suggests that the preferred option in these patients is enrollment in a clinical trial[126]. Potential agents include temsirolimus, sorafenib, sunitinib, pazopanib, axitinib, everolimus, bevacizumab or erlotinib[126]. Preliminary studies have suggested that temsirolimus has efficacy in treating papillary RCC[158-161]. Two randomized controlled studies found that cytoreductive nephrectomy followed by immunotherapy improved survival in patients with metastatic RCC compared to immunotherapy alone[162,163]. Similarly, a study of 314 patients with metastatic RCC found that cytoreductive nephrectomy followed by VEGF-TKI therapy improved survival compared with VEGF-TKI therapy alone (19.8 mo vs 9.4 mo, P Torin 1 The NCCN guidelines for stage 4 patients are as follows[2]: (1) Cases that involve a potentially resectable solitary metastatic site should undergo nephrectomy and surgical metastasectomy; (2) cases that involve a potentially resectable RCC with multiple metastatic sites should undergo cytoreductive nephrectomy in appropriate patients prior to systemic therapy; and (3) cases with medically or surgically unresectable disease should undergo systemic therapy. The NCCN suggests that stage IV patients should undergo baseline chest, abdominal and pelvic imaging by CT or MRI Apoptosis inhibitor pre-treatment or prior to observation, followed by repeat imaging every 6-16 wk as per physician discretion and per patient clinical status[22]. The imaging frequency may be modified depending on the rate of disease change and the sites of active disease[22]. CONCLUSION RCC is not a single uniform entity but a group of related neoplasms in which the histologic findings, cytogenetic abnormalities, biologic behavior and imaging appearances of the tumors are subtype dependent. The 3 main subtypes - clear cell, papillary and chromophobe - can often be differentiated non-invasively based on characteristic radiologic appearances.
