Metastasectomy outcomes in renal cell carcinoma: insights from hereditary leiomyomatosis and succinate dehydrogenase deficient cohorts.

Abstract

Background and objective: Metastatic hereditary leiomyomatosis renal cell cancer (HLRCC)-associated and succinate dehydrogenase-deficient (SDH-deficient) renal cell carcinoma (RCC) have aggressive oncological behavior. Thus, in this study we aimed to describe our experience with patients diagnosed with metastatic HLRCC-associated and SDH-deficient RCC who underwent surgical metastasectomy (SM).

Materials and methods: A retrospective study was conducted selecting patients with either germline variant confirmed HLRCC-associated or SDH-deficient RCC who underwent SM at our institution between 2002 and 2024. Clinical and oncological variables were analyzed. Kaplan-Meier analysis was used to estimate the median (95% confidence interval; CI) systemic therapy-free survival, time to subsequent SM, and overall survival (OS) following the initial SM.

Results: A total of 23 patients were identified; 17 (73.9%) had HLRCC-associated, and 6 (26.1%) had SDH-deficient RCC. The age at index renal surgery was 35 [24-47] years, and 38.6 years [27-52.4] at first SM. The median systemic therapy-free survival following initial SM was 2.58 years (95% CI: 0.31-4.86), and OS following initial SM was 8.17 years (95% CI: 2.94-13.39). At 1, 3, and 5 years after SM, 55%, 32%, and 32% of the patients, respectively, had not received systemic therapy. The OS at 3, 5, and 10 years after initial SM was 72%, 53%, and 40%, respectively.

Conclusions: SM in well-selected patients with metastatic HLRCC-associated and SDH-deficient RCC offers favorable oncologic outcomes and over 2 years of systemic therapy-free survival. This surgical approach should be carefully considered within a multidisciplinary setting, emphasizing thorough patient selection.