The role of metastasectomy in patients with early onset metastatic colorectal cancer.

3541 Background: According to the literature, metastasectomies in colorectal cancer patients can lead to a significant increase in outcomes. However, the behavior of early-onset CRC (EO-CRC), which refers to cancer occurring in adults between 18 and 49 years, when subjected to metastasectomy, remains unclear. Clinical and prognostic data on this setting are limited and conflicting. Our study aimed to evaluate clinical, prognostic, and molecular differences in early-onset colorectal cancer (EO-CRC) patients undergoing metastasectomy to identify potentially relevant differences compared to a control group of late-onset CRC (LO-CRC). Methods: We retrospectively collected data from 1123 metastatic colorectal cancer patients from 5 different Italian Institutions. 673 (59.9%) EO-CRC and 450 (40.1%) LO-CRC as a control group. All patients had one or more metastatic sites, molecular profiling available (including RAS, BRAF, and MSI status), and underwent at least one line of treatment for metastatic disease. The main objective of the study was to evaluate clinical outcomes for the EO-CRC patients undergoing metastasectomy in comparison to patients included in the control group according to molecular profile. Results: In the EO-CRC group, the median age was 44.1 (20.0-50.9), while in the control group, it was 64.4 (51.0-86.2). Among EO-CRCs patients, 388 out of 673 (57.6%) underwent metastasectomy, whereas, in LO-CRCs patients, only 181 out of 450 (40.2%) had the procedure. In the general population, patients who underwent metastasectomy demonstrated a higher median overall survival (mOS) compared to those who did not undergo the procedure. However, within the metastasectomy group, EO-CRCs patients exhibited a lower mOS compared to LO-CRCs patients (46.0 versus 60.0 months, p < 0.0001). Similar results were obtained when evaluating subgroups of RAS-BRAF wild type patients (53.0 months versus 81.0 months, p < 0.0001) and RAS-BRAF mutated patients (42.0 months versus 45.0 months, p < 0.0001). Conclusions: Although EO-CRC patients seem more likely to undergo surgical resection for metastatic disease, our findings suggest a worse overall prognosis for patients with early-onset colorectal cancer compared to late-onset patients. Interestingly, this seems to occur regardless of the molecular status. These observations could have a considerable impact on clinical practice and research. Further investigations will be necessary to better understand the specific clinical and molecular characteristics of this growing group of patients to better define the most appropriate therapeutic strategy.