Elsevier

European Urology

Volume 60, Issue 5, November 2011, Pages 964-971
European Urology

Platinum Priority – Kidney Cancer
Editorial Thomas Bessede, Geraldine Pignot and Jean-Jacques Patard on pp. 972–974 of this issue
Safety of Presurgical Targeted Therapy in the Setting of Metastatic Renal Cell Carcinoma

https://doi.org/10.1016/j.eururo.2011.05.032Get rights and content

Abstract

Background

In patients with metastatic renal cell carcinoma (mRCC), the timing of systemic targeted therapy in relation to cytoreductive nephrectomy (CN) is under investigation.

Objective

To evaluate postoperative complications after the use of presurgical targeted therapy prior to CN.

Design, setting, and participants

A retrospective review of all patients who underwent a CN at The University of Texas M.D. Anderson Cancer Center from 2004 to 2010 was performed. Inclusion in this study required documented evidence of mRCC, with treatment incorporating CN.

Interventions

Patients receiving presurgical systemic targeted therapy prior to CN were compared to those undergoing immediate CN.

Measurements

Complications were assessed using the modified Clavien system for a period of 12 mo postoperatively.

Results and limitations

Presurgical therapy was administered to 70 patients prior to CN (presurgical), while 103 patients had an immediate CN (immediate). A total of 232 complications occurred in 57% of patients (99 of 173). Use of presurgical systemic targeted therapy was predictive of having a complication > 90 d postoperatively (p = 0.002) and having multiple complications (p = 0.013), and it was predictive of having a wound complication (p < 0.001). Despite these specific complications, presurgical systemic targeted therapy was not associated with an increased overall complication risk on univariable or multivariate analysis (p = 0.064 and p = 0.237) and was not predictive for severe (Clavien ≥3) complications (p = 0.625). This study is limited by its retrospective nature. As is inherent to any retrospective study reporting on complications, we are limited by reporting bias and the potential for misclassification of specific complications.

Conclusions

Despite an increased risk for specific wound-related complications, overall surgical complications and the risk of severe complications (Clavien ≥3) are not greater after presurgical targeted therapy in comparison to upfront cytoreductive surgery.

Introduction

Cytoreductive nephrectomy (CN) is currently a common practice in the multimodality treatment of patients with metastatic renal cell carcinoma (mRCC) as a result of two prospective randomized trials demonstrating a survival benefit in patients randomized to CN followed by interferon-α (IFN-α) compared to IFN-α alone [1], [2]. Over the past 6 yr, contemporary systemic “targeted” therapies have essentially replaced immunotherapies as the standard treatment for patients with mRCC. Although level I evidence supporting CN prior to contemporary systemic therapy is lacking, the use of CN has remained an integral part of treatment for mRCC.

Several aspects of CN are under evaluation, including the optimal timing of surgery in the course of systemic treatment, the safety of administrating presurgical systemic therapy, and determining how better to select patients who may derive the greatest benefit from CN [3], [4], [5], [6], [7]. In a phase 2 study performed at The University of Texas M.D. Anderson Cancer Center (MDACC), we evaluated the feasibility and safety of presurgical treatment with bevacizumab in patients with mRCC [4]. This was the first trial in patients with mRCC to evaluate the safety of presurgical treatment with antiangiogenesis therapy. Without a control for comparison, definitive statements could not be made regarding the relative risks of surgical morbidity associated with presurgical therapy.

As our experience with presurgical targeted therapy has grown at MDACC, we are obligated to remain critical of the outcomes associated with this treatment paradigm and to report on the safety with respect to surgical morbidity. In addition to published outcomes from other surgical series, our own experience has raised concerns regarding the potential effects of this sequence of therapy on postoperative outcomes. To validate our concerns, we assessed postoperative complications occurring with the use of presurgical systemic targeted therapy and compared these results to complications occurring after immediate CN in a contemporary series of patients.

Section snippets

Patient population

After approval from the institutional review board at MDACC, we performed a retrospective review on all surgical patients with mRCC from 2004 to 2010. Inclusion criteria encompassed all patients with pathologically confirmed RCC (any histology) and preoperative findings of M1 disease. A total of 173 patients were identified and available for analysis. Presurgical systemic targeted therapy was administered to 70 patients (presurgical), while the remaining 103 patients received immediate CN

Patient characteristics and outcomes

Baseline demographics were similar between the two groups (Table 2). The only statistically significant baseline difference was clinical N-stage (45.7% with clinically positive nodes in the presurgical group vs 29.1% in the immediate group; p = 0.035). Median follow-up for the entire cohort was 19.2 mo (range: 1.1–77.7), and median length of stay was 6 d (range: 1–107).

Presurgical and adjuvant systemic therapies

Presurgical systemic targeted therapies administered to patients prior to nephrectomy are listed in Figure 1. Duration of therapy

Discussion

Although the paradigm of presurgical therapy in this population appears to hold promise in initial clinical trials, currently, the proper integration of surgery and systemic therapy in the treatment of patients with mRCC is unknown. Until the results of ongoing clinical trials are known, upfront CN followed by systemic therapy will remain an integral part of the treatment of mRCC in properly selected patients [9], [10]. As in any advance in medicine, proven patient safety is of paramount

Conclusions

The use of presurgical therapy in patients with mRCC does not result in an increased overall complication rate or an increased risk of severe complications requiring an intervention (Clavien ≥3) when compared to immediate CN. However, there is an increased risk of wound complications and having multiple complications in patients treated with presurgical targeted therapy. Further insight into the role of nutritional status while on systemic therapy and prior to surgery may aid in identifying

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