Metastatic renal cell carcinoma: risk of rapid progression to pathological fractures and factors influencing post-treatment survival – a Swedish Nationwide cohort study

Background: Renal Cell Carcinoma (RCC) represents about 2% of all cancers in Sweden. While RCC is known for its potential to metastasize to the skeleton, few studies have examined the risk factors for pathological fractures and their impact on survival. The Fuhrman grade and AJCC staging systems are commonly used to assess disease aggressiveness, but their relationship to fracture risk and post-fracture outcomes remains unclear. Methods: This study cross-linked data from the Swedish Fracture Register (SFR) and the Swedish Renal Cancer Register (SNR) to identify RCC patients with pathological fractures. Fracture characteristics, cancer staging (Fuhrman, TNM, AJCC), and histological subtypes were analysed. Survival was estimated using the Kaplan-Meier method. Results: One hundred four RCC patients (72 men, 32 women) with pathological fractures were included, with clear cell carcinoma being most common (n = 93). Fuhrman grade 3 (n = 34) and fractures in the femur (n = 44) and humerus (n = 37) predominated. Median time from cancer diagnosis to fracture was 11 months. Higher Fuhrman grade, TNM, and AJCC stages were significantly associated with shorter time to fracture (p < 0.001). The median overall survival was 31 months and was related to Fuhrman grade (p = 0.013) and AJCC stage (p < 0.001). The median survival post-fracture was 8 months, with no significant association with cancer grade or stage. Conclusion: Advanced Fuhrman grade and AJCC stage predict faster progression to pathological fractures in RCC. Given the poor prognosis after pathological fractures, early risk stratification and individualized treatment approaches are essential to improve outcomes.