Surgical metastasectomy has historically been linked to better survival results, resulting in a twofold decrease in the risk of death and a 50% 5year OS rate [3]. Numerous factors have been recognized as significant predictors of enhanced outcomes after surgical metastasectomy in mRCC patients. The completeness of metastasectomy is regarded as the paramount factor influencing survival, yielding substantially extended OS and PFS compared to incomplete metastasectomy or the absence of MDT [4]. In an institutional analysis involving 586 patients, 158 of whom underwent metastasectomy, Lyon et al. [5] demonstrated that complete surgical metastasectomy improved 2year cancer specific survival (CSS) compared with nonmetastasectomy patients (84% vs. 54%, p<0.001). Most recently, Laru et al. [6] reported the effect of metastasectomy on OS and CSS using the Finnish Cancer Registry. Of 483 patients with synchronous mRCC undergoing cytoreductive nephrectomy, 153 underwent metastasectomy (57 complete, 96 incomplete), while 330 did not. The groups that underwent complete, incomplete, and no metastasectomy had median OS and median CSS of 59.3 and 60.8 months, 21.9 and 25.1 months, and 14.5 and 14.8 months, respectively (p<0.001 for differences). The subgroup analysis indicated no enhancement in survival estimates for the incomplete metastasectomy group relative to the no metastasectomy group (hazard ratio [HR], 1.04-1.10; p>0.40), underscoring the significance of complete metastasectomy [6]. In comparison to firstline systemic therapy, firstline complete metastasectomy significantly increased CSS when compared to both immuneoncology (IO)based combination therapy (IO-IO/tyrosine kinase inhibitor [TKI]-IO: 6.1 years vs. 3.5 years; HR, 0.28; p=0.007) and TKI monotherapy (6.1 years vs. 2.6 years; HR, 0.45; p<0.001) [7].

MDT is more likely to benefit patients whose risk profiles, as determined by the International Metastatic RCC Database Consortium (IMDC) criteria, are more favorable. Meagher et al. [8] reported significant OS benefits in only favorable (92.7 m vs. 25.8 m, p=0.003) and intermediate-risk (26.3 m vs. 20.1 m, p=0.038) groups using the REMARCC (Registry of Metastatic RCC) database. Compared to patients undergoing metastasectomy with favorable risk profiles, those in the IMDC intermediate and poor risk groups had a 6 and 7.5- fold higher chance of poor survival outcomes [9].

Additional selection criteria encompass tumor histology and metastatic pattern. The advantage of surgical metastasectomy was not evidenced in patients exhibiting sarcomatoid characteristics [10]. Yu et al. [11] have demonstrated that metastasis to multiple organ sites, a disease-free interval of 12 months or less between the primary nephrectomy and the diagnosis of metachronous metastatic disease, and primary tumor T stage 3 or above are associated with poor OS. A worse prognosis is linked to metastases to the liver, bone, or brain than to the lung after metastasectomy [1]. Collectively, careful patient selection is essential to ensuring disease control and patient safety in the absence of established guidelines.

Despite the fact that RCC was once thought to be radioresistant, SBRT has demonstrated promise as a minimally toxic and effective tumor control option for OMRCC. The extracranial metastatic lesions in the SABR-ORCA (stereotactic ablative radiation therapy for oligometastatic renal cell carcinoma) meta-analysis treated with SBRT had 1-year local control rates of 89.1% and 1-year OS rates of 86.8%, with only a 0.7% rate of grade 3-4 side effects [12]. In a prospective phase II trial by Tang et al. [13], 1-year PFS and 1-year systemic therapy-free survival rates were 64% and 82%, respectively, when SBRT was used instead of systemic treatment. Sequential SBRT improves the patient's quality of life by enabling prolonged systemic therapy breaks for specific OM-RCC patients.

Sequential SBRT may be advantageous for OMRCC patients with the following conditions: (1) metachronous metastasis with time intervals between the primary tumor and metastasis exceeding 1 year; (2) indolent biology; and (3) IMDC favorable and intermediate-risk. Nevertheless, there are no prospective randomized studies to back it up.

The recurrence rate after complete metastasectomy for mRCC is high. According to Lyon et al. [5], 72% of patients receiving complete metastasectomy experienced metastasis recurrence. The median duration of metastasis-free survival after complete metastasectomy was 1.4 years. The median subsequent metastasis-free survival is more prolonged in the metachronous group relative to the synchronous metastasis group (1.9 years vs. 0.6 years). These findings highlight the importance of an adjuvant treatment strategy following a complete metastasectomy [5]. Among various studies on the role of adjuvant therapy after complete metastasectomy, the Keynote 564 trial is the only phase 3, randomized double-blind study demonstrating the benefit of adjuvant systemic treatment in patients who received nephrectomy with metastasectomy [14]. Patients with high-risk RCC were randomly assigned to receive pembrolizumab versus placebo for a year. High recurrence risk was defined as stage 2 tumors with nuclear grade 4 or sarcomatoid differentiation, stage 3 or higher tumors, regional lymph node metastasis, or M1-NED. The study demonstrated that adjuvant pembrolizumab significantly improved disease-free survival compared to placebo (77.3% vs. 68.1% at 24 months; HR, 0.68; p=0.002). A subgroup analysis revealed that patients with M1-NED experienced the most pronounced benefit (HR, 0.29). In a recent interim analysis presented at American Society of Clinical Oncology, with a median follow-up of approximately 57 months, pembrolizumab demonstrated a statistically significant and clinically meaningful OS benefit (HR, 0.62; p=0.0024), with positive effects seen across various subgroups, including patients with M0 disease, M1 NED, PD-L1 combined positive score ≥1 or <1, and the presence or absence of sarcomatoid features [15].