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Page 2 of 12 Feuer et al. J Cancer Metastasis Treat 2021;7:68 https://dx.doi.org/10.20517/2394-4722.2021.164

INTRODUCTION
Nearly 30% of patients with renal cell carcinoma (RCC) have metastatic disease at the time of diagnosis .
[1]
[2]
Amongst men treated for localized RCC, approximately 25% progress in developing metastatic disease .
Metastases commonly present in the lung (60%-75%), lymph nodes (60%-65%), bone (39%-40%), liver (19%-
[3]
40%) and brain (5%-7%) . Presently, treatment options for metastatic RCC (mRCC) include observation,
clinical trial enrollment, systemic therapy, and metastasectomy (with or without SBRT and/or ablative
[3]
techniques). There are no recommendations regarding which of these modalities is preferred .
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 specifically 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]
[5]
Nevertheless, metastasectomy remains a recommended management option for mRCC in select patients .
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.

THE EARLY ROLE OF METASTASECTOMY
The role of metastasectomy has evolved over the past several decades as the landscape of treatments for
mRCC has transitioned from the cytokine era to targeted therapies and immuno-oncology, as well as
combinations of these therapies. The first large, retrospective series to examine the role of metastasectomy
in the cytokine era was conducted in 278 patients and demonstrated that solitary metastasis, longer disease-
free interval (DFI), and younger age were associated with extended survival. In this study, 5-year survival
was approximately 55% . A subsequent study retrospectively evaluated 152 resections in 101 patients.
[6]
Disease-free survival was noted to be low, ~7%, at 60 months, but resection was determined to be feasible
with low morbidity. Overall survival was not assessed .
[7]

Another retrospective analysis, conducted by Alt et al. during the cytokine era, assessed 887 patients who
[8]
underwent nephrectomy for RCC and subsequently developed metastases. After controlling for patient
performance status, timing, location, and the number of metastases, they found that complete
metastasectomy was associated with prolongation of cancer-specific survival (4.8 years vs. 1.3 years). In
patients with lung-only metastases, 5-year cancer-specific survival was 73.6% with complete resection vs.
19% amongst patients who were managed non-operatively . These early studies demonstrated that in the
[8]
absence of effective systemic therapy, complete metastasectomy was an effective treatment strategy for
patients with mRCC.

IMAGING IN METASTATIC RENAL CELL CARCINOMA STAGING
The primary imaging techniques for the initial staging of a primary renal mass include computerized
tomography (CT) and magnetic resonance imaging (MRI). Generally, CT is utilized as the primary
modality, conserving MRI for situations in which iodinated contrast is contraindicated or when further soft
tissue delineation is necessary for accurate staging . The National Comprehensive Cancer Network
[9]
recommends that chest imaging be obtained with a chest radiograph (CXR). Meanwhile, these guidelines
suggest that CT of the chest, CT of the brain, and/or a bone scan are obtained if clinically indicated .
[3]
However, the American College of Radiology Appropriateness Criteria recommends obtaining CT of the
[10]
chest for stage ≥ T2 tumors, as small pulmonary metastases may be missed on CXR .