Neoadjuvant sunitinib for surgically complex advanced renal cell cancer of doubtful resectability: initial experience with downsizing to reconsider cytoreductive surgery.
ABSTRACT To evaluate neoadjuvant sunitinib in patients with synchronous metastatic renal cell cancer (mRCC) to downsize surgically complex tumours and reconsider cytoreductive surgery.
Retrospective analysis of ten consecutive mRCC patients treated with sunitinib in an expanded access program who presented with surgically complex primary tumours or bulky locoregional metastases. Surgery-limiting tumour sites (SLTSs) were defined as primary or retroperitoneal lesions with direct invasion of adjacent organs or encasement of vital structures on imaging. Patients received sunitinib 50 mg/day for 4 weeks on and 2 weeks off to be followed by cytoreductive surgery after downsizing and individual reassessment. Response was measured according to Response Evaluation Criteria in Solid Tumours (RECIST).
Six out of ten SLTSs revealed a reduction of tumour size with a median of 14% according to RECIST. None of the ten SLTSs had a partial response (PR), whilst at distant metastatic sites one complete remission and two PRs occurred. Downsizing of SLTSs appeared most prominent in the first 2-4 months, which resulted in reconsidering cytoreductive nephrectomy in three patients. These three tumours invaded the liver on imaging and were reduced by 11, 18 and 20%.
In this patient group with mRCC and surgically complex primary tumours or locoregional metastases, downsizing of SLTSs by neoadjuvant sunitinib was limited. Cytoreductive surgery was reconsidered in three patients. Given the overall reduction in tumour burden by sunitinib alone, further investigation to define the role of cytoreductive surgery is warranted.
- SourceAvailable from: Hendrik Paul Van Poppel[Show abstract] [Hide abstract]
ABSTRACT: Surgical intervention is the primary treatment for early-stage renal cell carcinoma (RCC), but alone it has limited benefit in patients with metastatic disease. The advent of targeted agents for RCC has improved the outcome in these patients, and there is increasing interest in exploring the efficacy and safety of these agents in combination with surgery in both early and advanced disease. This article reviews approved and emerging targeted therapies for RCC and outlines the rationale and implications for combining these therapies with surgery. A search of the literature, trial registries, and meeting proceedings was performed, and reports on surgery, receptor tyrosine kinase inhibitors, vascular endothelial growth factor antibodies, mammalian target of rapamycin inhibitors, and cytokine adjuvant therapy relating to RCC were critically reviewed. Nephrectomy has been shown to improve overall survival in patients with metastatic RCC (mRCC) treated with interferon alpha. Combining targeted therapy with surgery has the potential to improve efficacy and tolerability relative to cytokine therapy and prospective studies are underway. In the localized setting, there is some evidence of tumor downsizing with neoadjuvant targeted therapy. The tolerability and safety of targeted agents used perioperatively must be considered, particularly in the adjuvant setting where chronic therapy is required to prevent recurrence or metastasis. Novel agents with greater specificity and improved safety profiles are under development and have the potential to enhance efficacy and minimize the risk of complications. For patients with mRCC, randomized controlled trials are ongoing to define the role and sequence of nephrectomy in combination with targeted therapy. Until data are available, nephrectomy remains part of the mRCC treatment algorithm for patients with good performance status and a resectable tumor. Targeted therapy to downsize large primary tumors in nonmetastatic disease is investigational, but the rate of surgically relevant down-staging and tumor shrinkage seen with the current generation of agents is limited. In patients with high-risk nonmetastatic disease, adjuvant therapy must be administered only in the context of the ongoing clinical trials since there are no data showing efficacy in this setting.European Urology 12/2010; 58(6):819-28. · 10.48 Impact Factor
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ABSTRACT: We retrospectively analyzed our patients with advanced renal cell carcinoma who underwent presurgical targeted therapy with tyrosine kinase inhibitors to clarify the safety and clinical benefit. The histopathological effect of this treatment was also examined. Between July 2005 and February 2010, nine patients with advanced renal cell carcinoma who were treated with tyrosine kinase inhibitors before surgery were the subjects of this study. Consolidative surgery was considered when these tumors showed clinical response or stable disease while on targeted therapy without evidence of disease progression at other sites. The agents used were sorafenib in seven patients and sunitinib in two. The median duration of presurgical therapy was 12.2 weeks, and seven patients had less than 4 months of treatment. Tumor reduction at 10-30% was obtained in all patients but one. Perioperative complications were observed in five of nine patients. Major complications occurred in two patients, including intraoperative excessive bleeding and delayed localized intraperitoneal abscess. Minor complications were found in three. The characteristics of the histopathological effect of tyrosine kinase inhibitors consisted of marked atrophy of the capillary sinus, confirming the pharmacological mechanisms of these agents. Other findings included nuclear pyknosis and degeneration of tumor cells. Presurgical targeted therapy with tyrosine kinase inhibitors appears to be feasible in most patients with advanced renal cell carcinoma. However, the indications, the clinical benefit and the standard protocol still remain to be determined. Therapeutic effects in the histology were compatible to their pharmacological effects.Japanese Journal of Clinical Oncology 12/2010; 40(12):1173-9. · 1.90 Impact Factor
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ABSTRACT: To describe current radiological cross-sectional imaging in the detection and staging of advanced renal cell carcinoma (RCC), defined here as RCC reaching beyond the renal capsule, whether by immediate extension or by metastasis. Review and summary of current radiological and urological literature, including original articles and reviews, retrieved from the medical data base "PubMed". Multi-detector-row computed tomography (MDCT) shows a sensitivity of up to 100% and specificity of about 90% for retroperitoneal disease, venous tumour thrombus, and metastasis, but limited accuracy for lymphadenopathy in RCC. Magnetic resonance imaging (MRI) is applied as a problem-solving modality, with particular strength in imaging metastasis to brain and bone. However, dynamic, contrast-enhanced- (DCE-) and arterial-spin-labelling (ASL-) MRI may help to monitor early response to angiogenesis inhibitor drugs. Ultrasonography (US) shows limited capability of identifying retroperitoneal disease, venous tumour thrombus extension, and metastasis. Positron Emission Tomography with 18-fluoro-desoxy-glucose (FDG-PET) demonstrates modest accuracy for metastasis of RCC, with positive studies being suspicious, while negative studies cannot reliably exclude disease. MDCT represents the diagnostic mainstay for the detection and staging of RCC. In the wake of new systemic therapies for advanced RCC, including angiogenesis inhibitor drugs, monitoring treatment response may become a new task for cross-sectional imaging.World Journal of Urology 06/2010; 28(3):253-61. · 2.89 Impact Factor