Adjuvant therapy for renal cell carcinoma Dr.Mina Tajvidi oncologist

Surgery Surgery is curative in the majority of patients without metastatic RCC and is therefore the preferred treatment for patients with stages I, II, and III disease Treatment can involve either a radical nephrectomy or a variety of renal-sparing approaches (partial nephrectomy or ablative techniques) in carefully selected patients, depending upon the extent of disease. In carefully selected patients who present with a resectable primary tumor and a concurrent single metastasis, surgical resection of the metastasis, in conjunction with radical nephrectomy, may be curative

Immunotherapy immunotherapy with either interleukin-2 or interferon alfa represented the primary modalities for the treatment of patients with metastatic RCC

Interleukin-2 Immunotherapy with high-dose bolus interleukin-2 (IL-2) can activate an immune response against RCC that results in tumor regressions in a minority of patients. Although treatment is associated with severe toxicity, responses often persist for many years, even in the absence of additional therapy, and the majority of complete responders remain free of relapse long-term. High-dose IL-2 remains an important option for carefully selected patients who are able to tolerate the toxicity associated with this approach and who have access to this treatment, because of its ability to induce durable long- term remissions in approximately 10 percent of patients.

Interferon alfa Using a variety of preparations, doses, and schedules, the overall response rate may be as high as 15 percent; the median time to response is about four months, and most responses are partial and rarely persist beyond one year The use of IFNa has largely been replaced by molecularly targeted agents that have demonstrated improved efficacy compared to IFNa without additional toxicity.

Molecularly targeted therapy An understanding of the pathogenesis of RCC at the molecular level has identified the vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) as targets for therapeutic intervention

Anti-angiogenic (VEGF pathway) Two different approaches have clinical activity in blocking the VEGF pathway : the use of small molecule tyrosine kinase (TK) inhibitors (sunitinib, sorafenib, pazopanib) to block the intracellular domain of the VEGF receptor and a monoclonal antibody (eg, bevacizumab) to bind circulating VEGF and prevent its activating the VEGF receptor

mTOR inhibitors The mammalian target of rapamycin (mTOR) pathway is downstream of the phosphoinositide 3-kinase and Akt pathway that is regulated by the PTEN tumor suppressor gene Inhibition of the mTOR pathway has the potential to inhibit tumor progression at multiple levels. Temsirolimus, an inhibitor of mTOR, significantly increased survival of poor-prognosis patients in a phase III trial when used as the initial treatment for patients with advanced disease Everolimus, another inhibitor of mTOR, significantly increased progression-free survival compared to placebo in a phase III trial in patients who have progressed after treatment with a VEGF-targeted agent

Chemotherapy Clear cell RCC:Chemotherapy does not have an established role in the management of patients with advanced or metastatic RCC, in contrast to other malignancies Additional clinical trials will be required to determine whether this approach may have a role in patients who are no longer responsive to molecularly targeted therapies.

Chemotherapy Nonclear cell RCC: patients with nonclear cell RCC do not appear to respond to immunotherapy The activity of molecularly targeted agents (sunitinib, sorafenib, temsirolimus) in patients with non-clear cell RCC has yet to be formally evaluated, although preliminary results and subset analyses from various clinical trials suggest that these agents have some activity. Subsets of non-clear cell tumors also occasionally respond to chemotherapy. Major responses have been reported with various combinations of platinum agents, taxanes, gemcitabine, or ifosfamide in patients with collecting duct tumors and sarcomatoid RCCs. Renal medullary carcinoma may also be responsive to platinum-based combination chemotherapy regimens, anthracyclines, or to bortezomib

Hormonal agents Progestational agents have been extensively evaluated in patients with advanced RCC, but do not appear to have antitumor activity Medroxyprogesterone is the most widely studied. Despite occasional reports of responses, a review of medroxyprogesterone treatment concluded that RCCs are neither hormone- dependent nor hormone-responsive

Radiation therapy Despite the characterization of RCC as a radioresistant tumor, conventional and stereotactic radiation therapy (RT) are frequently useful to treat a single or limited number of metastases. In these settings, the utility of RT is similar to that in other metastases from other tumor types. RT has also been used as an adjuvant following nephrectomy in patients at high risk for local recurrence