Special Edition EAU–ICUD – Review – Kidney CancerICUD-EAU International Consultation on Kidney Cancer 2010: Treatment of Metastatic Disease
Introduction
Renal-cell carcinoma (RCC) accounts for 2% of all cancers. In Europe, 40 000 patients are diagnosed with RCC each year, leading to 20 000 deaths [1].
One-third of patients are initially diagnosed with locally invasive or stage IV disease. Recurrence occurs in about 25% of patients having surgical resection for localized disease even though it was considered as curative. The prognosis for patients with distant disease was generally poor, with a 5-yr survival rate not >10% [2]. Until the past 4 yr, systemic treatments in patients with metastatic RCC (mRCC) have proven largely ineffective. Regarding chemotherapy or hormonal therapy, no single agent has been reported to achieve a consistent response rate in >10% of patients. Only a very small percentage of patients are likely to develop long-term disease-free survival following interferon-α (IFN-α)– and/or interleukin-2 (IL-2)–based therapy [3], [4]. At Memorial Sloan-Kettering Cancer Center (MSKCC), the overall median survival in 670 patients who were treated with chemotherapy or immunotherapy in 24 consecutive clinical trials from 1975 to 1996 was 10 mo [5].
Two key pathways are essential to the pathophysiology of the clear-cell RCC subtype: the hypoxia response pathway associated with inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene and the mammalian target of rapamycin (mTOR) signalling pathway [6]. Several therapies targeting these two pathways, including sunitinib, sorafenib, temsirolimus, bevacizumab, and everolimus, are available for clinical use and have revolutionized the treatment of mRCC [7]. This article reviews current targeted treatment approaches in the first- and second-line mRCC settings, as well as modifications to existing treatment algorithms, based on recently available data.
Section snippets
Evidence acquisition
Medical literature was retrieved from PubMed up to April 2011. Additional relevant articles and abstract reviews were included from the bibliographies of the retrieved literature. All data were reviewed and final statements were approved by experts in the field.
Current treatment approaches utilizing novel targeted agents
At present, treatment for metastatic clear-cell RCC with molecularly targeted agents can be broadly divided into the following categories: previously untreated patients, those refractory or intolerant to immunotherapy, and those who have failed treatment with VEGF-targeted therapy [2]. An important consideration that influences treatment decisions is the MSKCC prognostic risk-stratification system, which is widely used to define patient profiles and provides an indication of overall survival
Conclusions
Sunitinib monotherapy and bevacizumab in combination with IFN-α may be considered first-line treatment options in patients with metastatic or unresectable clear-cell RCC and favourable or intermediate prognosis according to MSKCC criteria (grade A). In the first-line setting, temsirolimus is recommended in patients with poor prognostic features, according to modified MSKCC criteria (grade A). Cytokines, including high-dose IL-2, remain an option for first-line treatment of highly selected
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