Simple SummaryIn the last years, metastasis-directed treatments of oligometastatic renal cell carcinoma (RCC) have been widely investigated. Metachronous solitary or oligometastasis from RCC are considered the ideal candidates for target treatments, allowing the achievement of “non-evidence of disease” status. To date, there have been no randomized clinical trials demonstrating the absolute survival benefits of surgical metastasectomy (MST) for oligo progression of RCC compared to systemic treatments. The role of complete MST on oncological outcomes, at the time of local or distant disease recurrence, remains poorly addressed. This is the first study presenting the advantage of minimally invasive MST on long-term (ten years) overall survival probability in patients who experienced oligoprogression of RCC treated at a high-volume center, compared to cases who received ST only.AbstractObjectives: The role of surgical metastasectomy (MST) in solitary or oligometastasis from renal cell carcinoma (RCC) and its impact on survival outcomes remains poorly addressed. We evaluated the impact of MST on overall survival (OS) in patients with oligometastatic (m)RCC. Materials and methods: The institutional renal cancer prospective database was examined for cases treated with partial or radical nephrectomy who developed metastatic disease during follow-up. Patients with evidence of clinical metastasis at first diagnosis were excluded. Patients considered unfit for MST received systemic treatment (ST); all others received MST. The impact of MST vs. the ST only cohort was assessed with the Kaplan–Meier method. Age, gender, bilaterality, histology, AJCC stage of primary tumor, surgical margins, local vs. distant metastasis and MST were included in univariable and multivariable regression analyses to assess the predictors of OS. Results: Overall, at a median follow-up of 16 months after primary treatment, 168 patients with RCC developed asynchronous metastasis at the adrenal gland, lung, liver, spleen, peritoneal, renal fossa, bone, nodes, brain and thyroid gland. Nine patients unfit for any treatment were excluded. The site of metastasis was treated with surgical MST (77/159, 48.4%), with or without previous or subsequent ST, while 82/159 cases (51.2%) received ST only. The 2-year, 5-year and 10-year OS probabilities were 93.8%, 82.8% and 79.5%, respectively. After multivariable analysis, MST and the primary tumor AJCC stage were independent predictors of OS probabilities (p= 0.019 andp= 0.035, respectively). After Kaplan–Meier analysis, MST significantly improved OS probabilities versus patients receiving ST (p< 0.001). Limitations: The main drawbacks of our research were the small sample size from a single-tertiary referral institution, as well as the absent or different ST lines in the cohort of patients receiving MST. Conclusions: When an NED status is achievable, surgical MST of mRCC significantly impacts OS, delaying and not precluding further subsequent ST.