Current Therapeutic Approaches to Renal Cell Carcinoma
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.
METASTATIC DISEASE
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
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 was 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 median 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 considered 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.
