CLINICAL, PATHOLOGICAL AND MOLECULAR INSIGHTS IN METASTATIC COLORECTAL CANCER WITH BONE METASTASES: A RETROSPECTIVE STUDY

Metastatic colorectal cancer (mCRC) represents a complex disease entity characterized by diverse evolutionary trajectories stemming from its inherent heterogeneity, influenced by a myriad of clinical, pathological, and molecular factors. Among the spectrum of mCRC cases, those harboring bone metastases constitute a rare subset. Materials and methods: This retrospective study investigated 334 patients diagnosed with mCRC and treated at the Regional Institute of Oncology Iasi between 2012 and 2019, of whom 35 manifested bone metastases. Comprehensive characterization encompassing clinical, pathological, molecular features, and prognostic determinants was undertaken for this specific cohort. Results: The incidence of bone metastases was recorded at 10.5%, with a median age at diagnosis of 65 years, predominantly affecting males (60%), and demonstrating a predilection for primary tumors located in the left colon (57.1%). Peritoneal (26.5%) and hepatic (17.1%) metastases emerged as frequently associated secondary sites. Histologically, 73.5% of subjects presented with grade 2 differentiated tumors, with KRAS mutations identified in 37.1% of cases, while NRAS and BRAF mutations were detected in 2.8% only. The treatment most commonly used by clinicians was a chemotherapy doublet consisting of a fluoropyrimidine (5-fluorouracil or capecitabine) combined with oxaliplatin in 85.6% of cases, with the addition of an angiogenesis inhibitor (Bevacizumab) in 77.1% of cases. Prognostic indicators revealed a median progression-free survival of 10.7 months and an overall survival of 17.3 months. First line anti-EGFR biological treatment was associated with increased survival, meanwhile peritoneal metastases and NRAS mutation were unfavorable prognostic factors. Despite enriching the understanding of this rare cohort of mCRC patients, the study underscores the imperative for prospective investigations with augmented sample sizes to delineate better the characteristics of this specific subset. Conclusions: Patients exhibited worse PFS and OS compared to those described in the literature for other metastatic sites. Among the identified prognostic factors, anti-EGFR treatment was associated with a favorable outcome, while the presence of peritoneal metastases and NRAS mutation were indicative of a poorer prognosis.