Abstract
Metastasectomy was initially described in the 1970s as a therapeutic strategy for patients with metastatic renal cell carcinoma. Since that time, systemic therapy options have grown exponentially, most recently with the introduction of immunotherapy. We aimed to review the contemporary literature regarding the role of metastasectomy in the era of targeted therapy and immunotherapy. Historically, metastasectomy has benefited patients with small volume, single-organ metastases, with favorable outcomes amongst younger, healthier patients with metastases to specific sites. The interplay between the employment of metastasectomy and systemic therapy has been limited to small, retrospective series with significant patient selection bias. More recently, investigators have conducted randomized controlled trials exploring the use of targeted therapies in the adjuvant setting after metastasectomy. Initial randomized data suggested no benefit in using sorafenib in this setting, and a subsequent study demonstrated possible harm in using pazopanib after metastasectomy. However, the role of other novel systemic therapies, including immunotherapy, nor the timing of use, have been meaningfully explored. Metastasectomy appears to be a valuable therapeutic option in the properly selected patient, requiring a multi-disciplinary management strategy and, pending future trials, a multimodal treatment approach.
Highlights
30% of patients with renal cell carcinoma (RCC) have metastatic disease at the time of diagnosis[1]
We aim to review the literature pertaining to the historical role of metastasectomy, including a discussion of outcomes-based upon metastatic site, and determine the role of metastasectomy in the era of immunotherapy
It is well-established that renal cell carcinoma exhibits significant intratumoral heterogeneity[58,59]. These genomic differences have been associated with differences in therapeutic response to PD-L1 inhibitors[60]. These findings suggest that the use of neoadjuvant, therapy to decrease metastatic burden prior to metastasectomy may increase the likelihood of complete resection, thereby conferring a survival benefit in these patients
Summary
30% of patients with renal cell carcinoma (RCC) have metastatic disease at the time of diagnosis[1]. Treatment options for metastatic RCC (mRCC) include observation, clinical trial enrollment, systemic therapy, and metastasectomy (with or without SBRT and/or ablative techniques). With the rapid evolution of systemic therapy options in the era of targeted therapies and immuno-oncology, level I evidence for the role of surgery in metastatic disease, and metastasectomy, remains sparse. This is due to study limitations associated with patient performance status, disease distribution, and the surgical accessibility of metastatic sites, all of which are associated with significant selection bias[4]. Metastasectomy remains a recommended management option for mRCC in select patients[5]
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