title: The possible role of postoperative azotemia in enhanced survival of patients with metastatic renal cancer after cytoreductive nephrectomy.
abstract: Cytoreductive nephrectomy prior to systemic therapy significantly increases survival in patients with metastatic renal cancer. This result is generally ascribed to the benefits of resection of the primary tumor including reduction of tumor burden, removal of a source for growth factors and metastases, and enhanced immune response. On the basis of mathematical models of tumor invasion, we propose that the observed effects of cytoreductive nephrectomy may be caused by resection of the kidney rather than the cancer. The models predict that the graded metabolic acidosis associated with mild renal failure after unilateral nephrectomy may alter the dynamics of the tumor-host interface sufficiently to reduce and even reverse the rate of invasion. A review of patient data from the surgical arm of the Southwest Oncology Group (SWOG) 8949(2) trial demonstrates significantly improved survival in patients who experienced postoperative increase in blood urea nitrogen (BUN) and creatinine compared with those who did not (17-month survival versus 4-month survival; P = 0.0007). This is generally consistent with the predictions of the mathematical models. If confirmed, these results suggest novel and broadly applicable tumor therapies.
authors.affiliation: Departments of Radiology and Applied Mathematics, University of Arizona, Tucson, AZ 85721, USA. rgatenby@radiology.arizona.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Gatenby
authors.forename: Edward T
authors.initials: ET
authors.lastname: Gawlinski
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Tangen
authors.forename: Robert C
authors.initials: RC
authors.lastname: Flanigan
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
mesh_terms: D000138:Acidosis / Q000097:blood / Q000209:etiology / Q000378:metabolism; D001806:Blood Urea Nitrogen; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D003404:Creatinine / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008954:Models, Biological; D009392:Nephrectomy; D012189:Retrospective Studies; D015996:Survival Rate; D014511:Uremia / Q000097:blood / Q000209:etiology / Q000378:metabolism*
chemical_list: D003404:Creatinine