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Aggressive, individualized therapy may improve outcome in renal cell carcinoma
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Patients at high risk for recurrent renal cell carcinoma may require adjuvant therapy compared with surgery alone to improve outcome, according to data published in Cancer.
To provide a benchmark for emerging targeted cancer therapies, researchers from the University of California at Los Angeles analyzed a prospective database of clinical and pathological information for patients treated for renal cell carcinoma between 1989 and 2005.
The database included information for 1,632 patients with a median age of 60 years. The researchers classified patients into groups: low, intermediate and high risk for recurrent renal cell carcinoma. They measured disease-specific survival and response to systemic therapy in patients with advanced disease.
Ninety-one percent of patients received nephrectomy; overall five-year disease-specific survival was 55%, 10-year was 40% and 15-year was 29%.
Five and 10-year disease-specific survival were 97% and 92% for patients with localized disease who were at low risk, 81% and 61% for those at intermediate risk, and 62% and 41% for those at high risk.
Among patients with metastatic disease, five and 10-year disease-specific survival were 41% and 31% for those at low risk, 18% and 7% for those at intermediate risk, and 8% and 0% for those at high risk.
According to the researchers, complete response occurred in 7% of patients with metastatic disease who received immunotherapy (n=453; median survival=120+ months). Partial response occurred in 15% (median survival=42.8 months), stable disease in 33% (median survival=38.6 months) and progressive disease in 45% (median survival=11.6 months).
Cancer. 2008;113:2457-2463.
This is an update of a large, prospective UCLA database of renal cell carcinoma patients treated with surgery and high-dose interleukin-2 (IL-2) for those patients with metastatic disease. The researchers have published similar data many times previously, and present data here with longer follow-up. These data reinforce that ECOG performance status, TNM staging and tumor grade can stratify patients into different outcomes, whether they have metastatic or non-metastatic disease. These parameters provide prognostic information, but unfortunately do not inform about how to individualize therapy for patients. Such information is likely to come both from a deeper understanding of the modular biology of renal cell carcinoma and available treatments, and also from future prospective trials of specific therapies in specific patient subpopulations.
It is important to understand the major limitation of these data, acknowledged by the researchers, that these data are from a single, highly specialized institution. While these data can provide some general reference for outcome with newer therapies, it does not take the place of well-conducted, randomized prospective trials which have established the supremacy of targeted therapy over low-dose cytokines for a broad population of metastatic renal cell carcinoma patients. High-dose IL-2 remains the therapy with the highest cure rate and should be considered for highly select patients. The researchers also identify patients with localized renal cell carcinoma who have a high risk of recurrence after resection. There is a critical need for more effective adjuvant therapy as immunotherapy has not proven effective in that setting. Some of the new targeted therapies are being tested in that setting and will hopefully be effective, but results are many years away. Outcome for renal cell carcinoma patients has steadily improved with both surgical and medical advances, but the ultimate goal of cure for all patients remains elusive.
– Brian Rini, MD
Associate Director for Clinical Research,
Cleveland Clinic Taussig Cancer Institute