Current Therapeutic Approaches to Renal Cell Carcinoma

• What is the approach to follow-up after treatment of localized RCC?

After a patient undergoes treatment for a localized RCC, the goal is to optimize oncologic outcomes, monitor for treatment sequelae, such as renal failure, and focus on survivorship. At this time, there is no consensus in the literature or across published national and international guidelines with regards to the appropriate schedule for surveillance to achieve these goals. In principle, the greatest risk for recurrence occurs within the first 3 years, so many guidelines focus on this timeframe. Likewise, the route of spread tends to be hematogenous, so patients present with pulmonary, bone, and brain metastases, in addition to local recurrence within the renal bed. Symptomatic recurrences often are seen with bone and brain metastases, and thus bone scans and brain imaging are not listed as part of routine surveillance protocols in asymptomatic patients. Although there is inconclusive evidence that surveillance protocols improve outcomes in RCC, many professional associations have outlined recommendations based on expert opinion [34]. The American Urological Association released guidelines in 2013 and the National Comprehensive Cancer Network (NCCN) released their most recent set of guidelines in 2016 [21,35]. These guidelines use TNM staging to risk-stratify patients and recommend follow up.

Case Continued

CT scan with contrast of the chest, abdomen, and pelvis as well as bone scan are done. CT of the abdomen and pelvis demonstrates a 7.8-cm left renal mass arising from the lower pole of the left kidney. Paraesophageal lymphadenopathy and mesenteric nodules are also noted. CT of the chest demonstrates bilateral pulmonary emboli. Bone scan is significant for increased activity related to the pathological fracture involving the right humerus. The patient undergoes surgery to stabilize the pathologic fracture of his humerus. He is diagnosed with metastatic RCC (clear cell histology) and undergoes palliative debulking nephrectomy.

• How is prognosis defined for metastatic RCC?

Prognostic Models

Limited-stage RCC that is found early can be cured surgically, with estimated 5-year survival rates for stage T1 and T2 disease approaching 90%; however, long-term survival for metastatic disease is poor, with rates ranging from 0% to 20% [13]. Approximately 30% of patients have metastatic disease at diagnosis, and about one-third of patients who have undergone treatment for localized disease experience relapse [36,37]. Common sites of metastases include lung, lymph nodes, bone, liver, adrenal gland, and brain.

Prognostic scoring systems have been developed to define risk groups and assist with determining appropriate therapy in the metastatic setting. The most widely used validated prognostic factor model is that from the Memorial Sloan-Kettering Cancer Center (MSKCC), which was developed using a multivariate analysis derived from data of patients enrolled in clinical trials and treated with interferon alfa [38]. The factors included in the MSKCC model are Karnofsky performance status less than 80, time from diagnosis to treatment with interferon alfa less than 12 months, hemoglobin level less than lower limit of laboratory’s reference range, LDH level greater than 1.5 times the upper limit of laboratory’s reference range, and corrected serum calcium level greater than 10 mg/dL. Risk groups are categorized as favorable (0 risk factors), intermediate (1 to 2 risk factors), and poor (3 or more risk factors) [39]. Median survival for favorable-, intermediate-, and poor-risk patients was 20, 10, and 4 months, respectively [40].