Outcomes of different therapeutic modalities for patients with metachronous oligometastatic renal-cell carcinoma (RCC): Analyses of a single-institution database.
Authors: Cigliola Antonio , Re Chiara , Maiorano Brigida Anna , Tateo Valentina , Nuccio Antonio , Mercinelli Chiara , Deantoni Chiara Lucrezia , Pastorino Giovanni Luigi , Brembilla Giorgio , Colecchia Maurizio , De Cobelli Francesco , Di Muzio Nadia , Larcher Alessandro , Rosiello Giuseppe , Briganti Alberto , Montorsi Francesco , Capitanio Umberto , Necchi Andrea 
Published: February 2025

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Background:
There is limited data in the literature concerning the management of patients (pts) with metachronous oligometastatic RCC. This study aimed to compare survival outcomes with various therapeutic modalities from a referral center cohort database.
Methods:
Pts with recurrent RCC from previous radical surgery for localized tumor, presenting with ≤5 metastatic lesions, were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and PFS from subsequent therapy (PFS2). Descriptive statistics and Cox-proportional hazard-regression models for PFS and OS were used. Survival rates were estimated with Kaplan-Meier method. P-values <0.05 were considered statistically significant.
Results:
In total, 142 pts were identified, treated from 02/2006 to 08/2023. 30 pts received active surveillance (AS), 48 metastasectomy (M), 30 stereotactic body radiotherapy (SBRT) and 34 first-line systemic therapy (1L). Median follow-up was 61.4 months (mo). There were no significant differences between groups according to age (p=0.29), ECOG performance status (p=0.99), Charlson Comorbidity Index (CCI) (p=0.81), International Metastatic RCC Database Consortium (IMDC) score (p=0.06) and time to metastatic relapse (p=0.27). The number of organs involved (NO) and the number of lesions (NL) were significantly different between groups with lower lesion counts for RT in both cases (p=0.02 and p<0.001, respectively), while sites of metastases (SM) did not differ (p=0.09). Subsequent therapies consisted of AS (2%), M (10.2%), SBRT (10%) and systemic therapy (77.5%). Median PFS was 14 mo for AS (95% CI: 9-26), 15 mo for M (95% CI: 10-49), 21 mo for RT (95% CI: 12-48), and 12 mo for 1L (95% CI: 10-16), with significant differences observed across treatment arms (p=0.026). No significant differences were found in OS (p=0.05) or in PFS2 (p=0.57). ECOG performance status was associated with OS (HR: 2.13, 95% CI: 1.34-3.11, p=0.002) but not with PFS (HR: 1.02, 95% CI: 0.75-1.40, p=0.85). No significant associations were found between CCI and either PFS or OS (HR: 0.94, p=0.16 and HR:1.12, p=0.19 respectively). Additionally, no associations were found between time of recurrence and neither PFS (HR: 0.99, 95% CI:0.99-1.00, p=0.07) nor OS (HR:0.99, 95% CI: 0.98-1.00, p=0.08). NO, SM and NL were not associated with either PFS or OS.
Conclusions:
The study highlights the importance of multidisciplinary discussions in pts with metachronous oligometastatic RCC, as there are potentially significant differences in PFS across treatment strategies. Limitations include retrospective nature, potential selection and confounding biases.