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Feuer et al. J Cancer Metastasis Treat 2021;7:68 https://dx.doi.org/10.20517/2394-4722.2021.164 Page 3 of 12

Nuclear medicine may play a role in mRCC diagnosis and staging. Positron emission tomography
[11]
(PET)/CT represents a modality that may provide better sensitivity for the diagnosis of metastases .
Fluorine 18-sodium fluoride ligand has been demonstrated to be sensitive for the detection of bone
[10]
metastases . More recently, PET/CT using Zr-89-girentuximab, a monoclonal antibody-based ligand, was
demonstrated to be more sensitive than CT alone, than F-fluorodeoxyglucose (18F)-PET/CT for detecting
[12]
bone and soft tissue lesions in patients with good and intermediate-risk mRCC .
THE ROLE OF METASTASECTOMY IN SPECIFIC ORGAN SITES
The role of metastasectomy has been reviewed extensively in the literature, often in series assessing the role
of metastasectomy by specific organ site. Metastasectomy outcomes by organ site are summarized in
Table 1.

Lung
The role of metastasectomy in the management of pulmonary metastases in the setting of mRCC has been
well-characterized. Pfannschmidt et al. retrospectively assessed pulmonary metastasectomy in 191
[13]
patients, including patients with no primary tumor site recurrence and no extrapulmonary metastases.
Complete resection was achieved in 145 cases. This study demonstrated an overall 5-year survival of 36.9%,
41.5% in patients who underwent complete resection vs. 22.1% amongst those with partial resections. The
authors dichotomized prognostic indicators based on values that demonstrated the most significant
discrimination between good and poor outcomes. They noted a significant survival difference amongst
patients with < 7 metastases as compared to ≥ 7 individual sites (46.8% vs. 14.5%). Finally, they noted that
DFI greater than 23 months was associated with an improvement in 5-year survival (47% vs. 24.7%) .
[13]
A German study analyzed the impact of the histologic characteristics of the primary tumor on survival in
107 consecutive patients undergoing pulmonary metastasectomy. Complete resections were performed in
97.2% of patients, and 33.6% received systemic therapy prior to pulmonary metastasectomy. The mean
survival was 63.4 months with 5- and 10-year survival rates of 47% and 9%, respectively. The authors found
that node status, primary tumor histologic grade, and primary tumor stage were all associated with worse
survival outcomes despite metastasectomy. The effect of systemic therapy was not evaluated. [14]

Kudelin et al. reviewed 116 patients who underwent pulmonary metastasectomy with intrathoracic lymph
[15]
node dissection. In this cohort, 34.5% of patients had systemic therapy prior to metastasectomy. Five- and
ten-year survival was noted to be 49% and 21%, respectively. Age > 70, female gender and the number of
metastases were noted to be poor prognostic factors. Only age > 70 remained significant in multivariate
analysis .
[15]
[16]
More recently, Saricam et al. evaluated the role of pulmonary metastasectomy in 48 patients,
demonstrating a median survival of 56.2 months, with a 5-year survival of 62.5%. The study noted that DFI
> 32 months, fewer, and smaller volume metastases (< 4 cc ) were factors associated with better prognosis .
3
[16]
Bone
Bone metastases are present in approximately 40% of patients with mRCC . To assess prognostic
[3]
[17]
indicators, Kume et al. reviewed 94 patients with bone metastases at multiple tertiary referral centers. The
authors noted that sarcomatoid differentiation, vertebral bone involvement, concurrent non-bone
metastases, alkaline phosphatase increases > 1.5 times the upper limit of normal, and C-reactive protein
increases > 0.3 mg/dL were associated with poor prognosis .
[17]