Proposed mechanisms of action

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

There are multiple hypotheses behind the survival advantage associated with CN prior to immunotherapy. With specific relevance to immunotherapy, large bulky primary tumors may act as an immunologic sink, and thus, removal of the primary tumor and bulky retroperitoneal lymph nodes may allow for an increased effectiveness of immunotherapy [16, 18, 19]. The primary tumor may also produce numerous growth and angiogenic factors which may contribute to the development and viability of distant metastatic disease (VEGF, TGF-β1, PDGF, IL-8, IL-10, and FGF) [20–22]. A novel and interesting hypothesis reported by Gatenby et al. proposed that removal of the kidney and subsequent metabolic acidosis (rather than cytoreduction through removal of the primary tumor) was responsible for the increase in OS seen in the SWOG 8949 trial. The exact mechanism by which CN adds to OS is currently unknown.

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