Page 121 - Read Online

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

ROLE OF SYSTEMIC THERAPY AND METASTASECTOMY
Karam et al. were amongst the first to assess the combined role of metastasectomy and systemic therapy
[41]
in a retrospective analysis of 22 patients with mRCC, all of whom were treated with targeted therapy
followed by consolidative metastasectomy. Twenty-one patients were alive at the time of the study at a
median follow-up of approximately 2 years, while surgical-associated morbidity was low. Amongst these
patients, 11 patients developed a recurrence at a median 42 weeks from the time of metastasectomy, while
the other 11 patients had not recurred at a similar median interval. Of note, 9 patients received additional
[41]
systemic therapy after metastasectomy .

The use of neoadjuvant therapy followed by metastasectomy was further studied in 124 patients. In this
retrospective review, 75 patients received targeted therapy only, 26 underwent targeted therapy followed by
complete metastasectomy, and 23 underwent partial resection. In these patients, only complete resection
was associated with improved overall survival (HR = 0.50). Of note, this study is had significant selection
bias as there was an uneven distribution of poor-risk patients in the study groups. Nearly 23% of patients in
the targeted therapy group were considered poor-risk, as compared to 3.8% and 0% in the complete and
partial metastasectomy cohorts. [42]

ADJUVANT THERAPY AFTER METASTASECTOMY
Recently, the first RCT in a metastasectomy cohort randomized patients to sorafenib or observation after
undergoing complete resection. Sixty-eight patients were randomized, with approximately 80% in each
group harboring solitary metastases. They included patients who underwent cytoreductive nephrectomy
with ECOG ≤ 2, less than 3 metastases, and predominant clear cell histology. Recurrence-free survival was
37 months in the observation arm and 21 months in the sorafenib arm, with significantly more adverse
events in the treatment arm. Procopio et al. concluded that sorafenib after metastasectomy was not
[43]
recommended.

ECOG 2810 is a double-blind RCT, which sought to demonstrate that pazopanib improved disease-free
survival in patients who underwent complete metastasectomy as compared to placebo. The study included
129 patients randomized 1:1 for 52 weeks of therapy, seeking to observe a 42% improvement in disease-free
survival at 3 years. The study did not meet the primary endpoint (HR = 0.85, P = 0.47). On the contrary,
[44]
overall survival favored patients receiving placebo (HR for OS = 2.65, P = 0.05) .
Beyond the use of vascular endothelial growth factor inhibitors and immune checkpoint inhibitors, a
German group assessed the use of an adjuvant multi-peptide vaccine after metastasectomy. The vaccine was
distributed to 19 patients after complete metastasectomy, and this group was compared with a separate
contemporary cohort of 44 patients who underwent metastasectomy only. The vaccine was well-tolerated
and demonstrated an improvement in overall survival (HR of death = 0.19, P = 0.012) compared to patients
[45]
undergoing resection alone .
CURRENT ROLE OF METASTASECTOMY
The evidence supporting the role of metastasectomy, historically, is mostly retrospective and observational.
However, despite the limited prospective evidence, available studies suggest a benefit of complete resection
[38]
in the properly selected patient . A recent systematic review of 56 studies demonstrated that overall
survival ranges from 36-142 months for those undergoing metastasectomy vs. 8-27 months for those subject
to nonoperative management. Prognostic factors associated with overall survival included disease-free
survival from time of nephrectomy, number of metastases, patient performance status, and primary tumor
features, specifically grade, stage, presence of sarcomatoid features, and nodal status. The most important