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Case-Based Review
Current Therapeutic Approaches to Renal Cell Carcinoma
Journal of Clinical Outcomes Management. 2016 August;23(8)
References
Another prognostic model, the International Metastatic RCC Database Consortium, or Heng, model was developed to evaluate prognosis in patients treated with VEGF-targeted therapy [41]. This model was developed from a retrospective study of patients treated with sunitinib, sorafenib, and bevacizumab plus interferon alfa or prior immunotherapy. Prognostic factors in this model include 4 of the 5 MSKCC risk factors (hemoglobin level, corrected serum calcium level, Karnofsky performance status, and time to initial diagnosis). Additionally, this model includes both absolute neutrophil and platelet counts greater than the upper limit of normal. Risk groups are identified as favorable (0 risk factors), intermediate (1 to 2 risk factors), and poor (3 or more risk factors). Median survival for favorable-, intermediate-, and poor-risk patients were not reached, 27 months, and 8.8 months, respectively. The University of California, Los Angeles scoring algorithm to predict survival after nephrectomy and immunotherapy (SANI) in patients with metastatic RCC is another prognostic model that can be used. This simplified scoring system incorporates lymph node status, constitutional symptoms, metastases location, histology, and thyroid stimulating hormone (TSH) level [42].
The role of debulking or cytoreductive nephrectomy in treatment of metastatic RCC is well established. Large randomized studies have demonstrated a statistically significant medial survival benefit for patients undergoing nephrectomy plus interferon alfa therapy compared with patients treated with interferon alfa alone (13.6 months versus 7.8 months, respectively) [43]. The role of cytoreductive nephrectomy in combination with antiangiogenic agents is less clear. While a retrospective study investigating outcomes of patients with metastatic RCC receiving anti-VEGF agents showed a prolonged survival with nephrectomy, results of large randomized trials are not yet available [44,45]. Patients with lung-only metastases, good prognostic features, and a good performance status are historically the most likely to benefit from cytoreductive surgery.
Case Continued
Based on the MSKCC prognostic factor model, the patient is deemed to be in the intermediate-risk group (Karnofsky performance status of 80, calcium 9.5 mg/dL, LDH 204 U/L, hemoglobin 13.6 g/dL). He is started on treatment for his bilateral pulmonary emboli and recovers well from orthopedic surgery as well as palliative debulking nephrectomy.
• What is the appropriate first-line therapy in managing this patient’s metastatic disease?
Several approaches to systemic therapy for advanced RCC have been taken based on the histologic type of the tumor. Clear-cell is by far the predominant histologic type in RCC. Several options are available as first-line treatment for patients with metastatic clear-cell RCC ( Table 2 ) [46–54]. These include biologic agents such as high-dose interleukin-2 (IL-2) immune therapy, as well as targeted therapies including TKIs and anti-VEGF antibodies. The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is recommended as first-line therapy in patients with poor prognosis only. Second-line therapies for clear-cell RCC following antiangiogenic therapy include TKIs, mTOR inhibitors, nivolumab (PD-1 inhibitor), and the combination of the TKI lenvatinib and mTOR inhibitor everolimus [55]. In addition, after initial cytokine therapy, TKIs, temsirolimus, and the anti-VEGF antibody
bevacizumab are other treatment options available to patients. Best supportive care should always be provided along with initial and subsequent therapies. Clinical trials are also an appropriate choice as first-line or subsequent therapies. All of these therapies require periodic monitoring to prevent and quickly treat adverse effects. Table 3
