The Impact of Targeted Molecular Therapies on the Level of Renal Cell Carcinoma Vena Caval Tumor Thrombus

Abstract

Background

Targeted molecular therapies (TMTs) previously have demonstrated oncologic activity in renal cell carcinoma (RCC) by reducing the size of primary tumors and metastases.

Objective

To assess the cytoreductive effect of TMTs on inferior vena cava tumor thrombi.

Design, setting, and participants

A multi-institutional database of patients treated with TMTs for RCC was reviewed. The subset with in situ level II or higher caval thrombi (above renal vein) was assessed for radiographic response in thrombus size and level. Pre- and posttreatment characteristics of this population were assessed for predictors of response in height, diameter, and level of the tumor thrombi.

Measurements

The main outcome measured was a change in the clinical level of tumor thrombus following TMT. We also measured radiographic responses in thrombus size and location before and after TMT.

Results and limitations

Twenty-five patients met the inclusion criteria. Before TMT, thrombus level was II in 18 patients (72%), III in 5 patients (20%), and IV in 2 patients (8%). The first-line therapy was sunitinib in 12 cases; alternative TMTs were administered in 13. The median duration of therapy was two cycles (range: one to six cycles). Following TMT, 7 patients (28%) had a measurable increase in thrombus height, 7 (28%) had no change, and 11 (44%) had a decrease. One patient (4%) had an increase in thrombus-level classification, 21 (84%) had stable thrombi, and in 3 (12%) the thrombus level decreased. There was only one case (4%) where the surgical approach was potentially affected by tumor thrombus regression (level IV to III). No statistically significant predictors of tumor thrombus response to TMTs were found.

Limitations include the descriptive and retrospective study design. Because TMTs were initiated according to physician and/or patient preferences, and not all patients were treated in anticipation of surgery, no conclusions could be drawn regarding selection and duration of therapy. Thus it may not be appropriate to extrapolate our experience to all patients with locally advanced RCC. Although this is the largest reported experience with in situ caval tumor thrombi treated with TMT, this series lacks sufficient statistical power to assess the usefulness of TMTs adequately in tumor thrombus cytoreduction.

Conclusions

TMT had a minimal clinical effect on RCC tumor thrombi. Only patients treated with sunitinib had clinical thrombus regression; however, the clinical magnitude and relevance of this effect is not clear and should be investigated prospectively.

Introduction

Venous tumor thrombi are reported to be present in approximately 10% of patients with renal cell carcinoma (RCC) [1], [2]. Up to 60% of these patients also have concurrent subclinical metastases [3]. The current treatment paradigm in this population is radical nephrectomy and tumor thrombectomy. Aggressive resection is necessary because at this time it is the only known curative therapy for locally advanced RCC [2]. However, the risk of perioperative morbidity and mortality from radical nephrectomy and thrombectomy increases in conjunction with the level of the thrombus [1]. Neoadjuvant systemic therapy may potentially decrease the tumor thrombus burden and thus improve the safety and feasibility of resection. Additionally, neoadjuvant therapy is appealing because it may allow early treatment of occult micrometastatic disease, potentially improving the curative potential of surgical resection.

In the current literature only a few case reports have described the effect of neoadjuvant targeted molecular therapy (TMT) on tumor thrombus level [4], [5], [6], [7], [8], [9], [10]. These limited studies indicate promising results in terms of reducing the size and level of the thrombus; however, the appropriate use of neoadjuvant therapy in this setting remains to be determined. The aim of our investigation was to study the clinical effect of systemic TMT on the in situ RCC tumor thrombus size and level.