Clinicogenomic Characteristics and Treatment of Young-Onset Colorectal Cancer Patients Treated With Palliative Therapy in Real-World Practice.

Introduction: Young-onset colorectal cancer (YOCR) is increasing. This study aimed to determine the difference between advanced YOCR and non-YOCR patient outcomes.

Methods: We retrospectively included patients with recurrent/metastatic colorectal cancer treated with palliative systemic therapy between 2016 and 2018. Diagnosis at < 50 years was defined as YOCR. Targeted sequencing was used to assess the mutational status.

Results: Among the 969 patients included, 210 (21.7%) were YOCR. The median progression-free survival with first-line chemotherapy (PFS1) was 9.7 vs 9.4 months ( = .755), and the median overall survival (OS) was 25.9 vs 22.3 months ( = .581) in the YOCR and the non-YOCR group, respectively. However, the youngest patients diagnosed at < 30 years showed poorer survival outcomes (median PFS1, 3.9 months; median OS, 8.6 months) compared with other age groups. PFS1 did not differ between YOCR and non-YOCR by choice of treatment regimen. Among the 340 patients with targeted sequencing results, YOCR had fewer mutations (61% vs 80%), but had similar (53% vs 48%), (7% vs 3%), and class I mutations (4% vs 6%). The median tumor mutational burden (TMB) was 10.9 vs 12.5 mut/Mb in YOCR and non-YOCR patients, respectively ( = .064). TMB increased with age in tumors with high microsatellite instability (Pearson's = .69, = .028), but not in microsatellite-stable tumors ( = .02, = .658).

Conclusions: Survival outcomes with palliative systemic therapy were similar between recurrent/metastatic YOCR and non-YOCR with an age cut-off of 50 years. However, patients diagnosed at < 30 years of age showed poorer outcomes compared with other age groups.