Introduction

Kidney cancer. Principles and practice. Second edition. Primo N. Lara, Jr. Eric Jonasch (Editors). Springer International Publishing (2015)


Approximately 30% of patients undergoing nephrectomy for localized renal cell carcinoma (RCC) will end up developing metastases [1, 2].

Additional therapies to reduce the rate of relapse are needed. As of 2015, surgery alone remains the standard of care for localized RCC, with no adjuvant therapy having a proven survival benefit. The recent development of new and effective systemic therapies for the treatment of metastatic disease holds promise of improving the rates of surgical cure.

Adjuvant therapy is the use of systemic therapy after a local radical treatment in attempt to increase the chance of cure. The rationale for the use of adjuvant systemic therapy is to treat micrometastases early in the disease course in order to have the greatest potential effect in reducing or eliminating future cancer burden. While the ideal goal of treatment should be eradication of micrometastatic disease in order to establish cure and improve overall survival, improvement in disease-free survival is an increasingly accepted end point of adjuvant trials [3]. Several factors are critical in the successful use of adjuvant therapy. First, accurate estimation of the risk of recurrence for an individual patient is necessary in order to decide whether adjuvant therapy is warranted. Second, the chosen agent must have enough activity against the cancer cells in order to affect recurrence. Finally, an ideal adjuvant therapy should have low toxicity and ease of administration in order to promote patient compliance.

A number of randomized adjuvant trials in RCC have been conducted over the past 30 years. First-generation adjuvant studies were conducted prior to the era of targeted therapies and included trials of chemotherapy, hormonotherapy, and immunotherapy. While these were the best available systemic agents at the time, such therapies were minimally effective in the metastatic setting, and the results of adjuvant studies were overwhelmingly negative. With the advent of effective molecular pathway-directed therapies for RCC, we have now entered the era of secondgeneration adjuvant studies. Vascular endothelial growth factor receptor (VEGF-R)and mammalian target of rapamycin (mTOR)-targeted drugs have revolutionized the management of metastatic disease and are currently being actively studied in the postoperative, preventative setting.

Results are not yet available from many of these new generation trials, and speculation abounds as to whether these new interventions will alter the disease course when administered in the adjuvant setting.

In this chapter, risk assessment strategies for patients in the post-nephrectomy setting will be discussed, as well as a review of the results of first-generation adjuvant studies, and an overview of the ongoing second-generation trials.


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