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Histological Subtypes
Treatment for patients with metastatic non-clear-cell RCC, who constitute up to 25% of all RCC patients, is largely undefined and tested algorithms remain unsatisfactory. It is scientifically flawed to assume that the findings for clear cell RCC apply in the non-clear-cell setting. Of all subtypes, sarcomatoid features portend the worst prognosis and are statistically significantly associated with reduced survival after CN in several series. The largest series compared outcomes for CN in 92 patients with non-clear-cell RCC to 514 patients with clear cell histology. Patients with non-clear-cell mRCC were younger and had a higher incidence of nodal metastases, a higher incidence of sarcomatoid features and a worse prognosis than those with clear cell histology who underwent CN. Even in the absence of sarcomatoid features, non-clear-cell histology was associated with worse disease-specific survival (p = 0.017).
It should be borne in mind that response rates to targeted therapy are not as high as in patients with clear cell subtypes, but novel agents provide a clinically meaningful response in some individuals. The poorer prognosis of non-clear-cell RCC, and a reduced activity of systemic therapy, need to be balanced against a very limited benefit of CN in this group of patients. Unless complete surgical remission can be achieved by CN and metastasectomy, it may be a better approach in asymptomatic patients with a non-clear-cell RCC to commence systemic treatment with the primary tumor in place. This underscores the need for pretreatment biopsies in patients with mRCC and a primary tumor in place, in order to plan the best treatment strategy, which may involve CN in combination with systemic treatment.
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