Platinum Priority – Kidney CancerEditorial Thomas Bessede, Geraldine Pignot and Jean-Jacques Patard on pp. 972–974 of this issueSafety of Presurgical Targeted Therapy in the Setting of Metastatic Renal Cell Carcinoma
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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Surgical outcomes of cytoreductive nephrectomy in patients receiving systemic immunotherapy for advanced renal cell carcinoma
2024, Urologic Oncology: Seminars and Original InvestigationsDeferred cytoreductive nephrectomy in the management of metastatic renal cell carcinoma: A systematic review and meta-analysis
2023, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :Among studies reporting on perioperative mortality and/or complications, 6 did not report the timeframe for complications [16–18,26–27,33], 4 reported 30-day rates [19,25,32,35], and one evaluated complications within 12-months [34]. Given the longer period of follow-up, Chapin et al. [34] reported higher overall and high-grade complication rates relative to the other studies included. Three studies compared overall complication rates between upfront and deferred CN [32,34–35].
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