Do targeted agents offer clinical benefit as presurgical therapy?

In the era of targeted therapy, management of patients with primary metastatic renal cell carcinoma and the tumour in place is again under investigation in randomized controlled trials. Proper patient selection for cytoreductive nephrectomy (CN) remains challenging. Presurgical targeted therapy may have potential advantages in this setting.

Data on CN and presurgical targeted therapy were reviewed in the literature.

Despite validated prognostic scores, outcome after CN is additionally influenced by factors impacting on surgical morbidity and mortality. Patient age, comorbidity, tumour size and extent, metastatic load, surgical approach and skills are not well represented by current prognostic models.The strongest predictor of poor survival following CN is progression within 90 days of surgery. A period of presurgical targeted therapy may identify those patients with rapid disease progression prior to a planned nephrectomy or metastasectomy from which they may not benefit. In nonrandomized prospective studies of presurgical therapy, up to 26 % of patients progressed at metastatic sites prior to planned surgery. Those with intermediate risk and absence of progression had a more than 70% probability to survive 2 years or longer after CN.

In the absence of biomarkers, presurgical therapy may contribute to individualizing treatment decisions. The advantages and disadvantages of this concept are investigated in a randomized EORTC trial of upfront CN versus CN after presurgical sunitinib in the absence of progression.