Surveillance for Renal Cell Cancer Recurrence: Which Patients Should Undergo Imaging, How Often, and When?

In 2015, 61,000 patients worldwide will be diagnosed with kidney cancer, and an estimated 14,000 patients will die as a result of this disease. The current approach for patients with limited or locally advanced kidney cancer is surgery, with definitive resection of the renal mass and removal of clinically apparent lymph nodes followed by close follow-up, which includes interval imaging, physical examination, and biochemical testing over a number of years. Approximately 40% of patients with disease limited to the kidney are at risk for relapse; the quandary is how to determine which of these patients who experience relapse will actually die as a result of their disease. Several organizations have guidelines for follow-up surveillance of higher-risk disease. The American Urological Association (AUA) stratifies risk of recurrence on the basis of tumor size and nodal status (low risk, pT1 N0 Nx v moderate to high risk, pT2-4N0 Nx or anystage N ). A patient with low-risk disease who has undergone partial nephrectomy should have a yearly chest x-ray with serial abdominal imaging for 3 years; the same patient after a radical nephrectomy should have serial chest x-rays but only one mandated baseline abdominal imaging. Moderateto high-risk patients should have baseline chest and abdominal imaging in the 3 to 6 months after surgery and continued imaging every 6 months for at least 3 years, then annually to year 5, with imaging beyond that as discretionary. The National Comprehensive Cancer Network similarly recommends chest x-ray or chest computed tomography (CT) with abdominal imaging at baseline and then continued imaging every 6 months for 3 years for patients who have undergone partial nephrectomy. Again, in patients who have undergone radical nephrectomy, this additional abdominal imaging is discretionary, and no imaging is mandated beyond 3 years. The NCCN recommendations for disease pT2 are essentially identical to those of the AUA. The European Association of Urology (EAU) bases risk on prognostic nomograms rather than TNM stage and recommends reduced surveillance for low-risk disease (ultrasound at 6 months and no chest imaging followed by imaging with CT or magnetic resonance imaging [MRI] every 6 months for the first year followed by yearly imaging through year 5). For higher-risk disease, CT or MRI imaging is recommended semiannually in year 1 followed by yearly imaging beyond 5 years. As highlighted in an earlier publication by Stewart et al, there is heterogeneity in the intensity and length of imaging; the AUA, NCCN and EAU approaches miss approximately 30% of all recurrences, including in some patients with pT1 disease after radical nephrectomy who undergo follow-up with the algorithm of reduced mandated imaging. The authors note that there are conflicting data to support different approaches to surveillance of patients after radical or partial nephrectomies; for example, those with higher-risk tumors are more likely to undergo radical than partial nephrectomy, but the incidence of local recurrence is higher after partial nephrectomy. The NCCN and AUA surveillance recommendations are used widely by insurance companies to decide which patients undergo which type of imaging, how often, and when. Thus, dangerous precedents can be set if there are inaccuracies in the assumptions. Risk of relapse is a surrogate for risk of death resulting from renal cell carcinoma (RCC). The most robust risk for relapse parameters include staging by TNM, performance status, and tumor grade. Other histologic features, such as cell type, presence of necrosis, and presence or absence of sarcomatoid features, have also been used. In 2007, the American Joint Committee on Cancer TNM staging was refined to differentiate local invasion of the adrenal gland versus metastasis to the adrenal gland to better aid in defining high-risk populations. There are at least three postsurgical risk nomograms that have been validated in the primary and locally advanced clear-cell RCC populations. These include University of California Los Angeles International Staging; Mayo Clinic Stage, Size, Grade, and Necrosis; and Memorial Sloan Kettering Cancer Center risk nomograms. These nomograms quite accurately identify that patients with nodal disease have a high rate of relapse, but again, they leave wide gaps in identifying which patients with earlier-stage disease will relapse or die as a result of their disease. For example, patients with University of California Los Angeles International Staging risk category 2 have a 5-year risk of relapse ranging from 10% to 40%. Other factors may confound determination of risk or pattern of relapse. Heterogeneity in surgical approach is an example. For the most part, clinically apparent lymph nodes are to be resected. In some institutions, a committed lymph node dissection is performed for disease T2 stage. A prospective randomized study of patients undergoing nephrectomy alone versus nephrectomy with lymph node dissection (European Organisation for Research and Treatment of Cancer trial 30881) showed no difference in survival JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 35 DECEMBER 1