Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes

Impact of microsatellite status in early-onset colonic cancer.

The molecular profile of early-onset colonic cancer is undefined. This study evaluated clinicopathological features and oncological outcomes of young patients with colonic cancer according to microsatellite status. Anonymized data from an international collaboration were analysed. Criteria for inclusion were patients younger than 50 years diagnosed with stage I-III colonic cancer that was surgically resected. Clinicopathological features, microsatellite status, and disease-specific outcomes were evaluated. A total of 650 patients fulfilled the criteria for inclusion. Microsatellite instability (MSI) was identified in 170 (26.2 per cent), whereas 480 had microsatellite-stable (MSS) tumours (relative risk of MSI 2.5 compared with older patients). MSI was associated with a family history of colorectal cancer and lesions in the proximal colon. The proportions with pathological node-positive disease (45.9 versus 45.6 per cent; P = 1.000) and tumour budding (20.3 versus 20.5 per cent; P = 1.000) were similar in the two groups. Patients with MSI tumours were more likely to have BRAF (22.5 versus 6.9 per cent; P < 0.001) and KRAS (40.0 versus 24.2 per cent; P = 0.006) mutations, and a hereditary cancer syndrome (30.0 versus 5.0 per cent; P < 0.001; relative risk 6). Five-year disease-free survival rates in the MSI group were 95.0, 92.0, and 80.0 per cent for patients with stage I, II, and III tumours, compared with 88.0, 88.0, and 65.0 per cent in the MSS group (P = 0.753, P = 0.487, and P = 0.105 respectively). Patients with early-onset colonic cancer have a high risk of MSI and defined genetic conditions. Those with MSI tumours have more adverse pathology (budding, KRAS/BRAF mutations, and nodal metastases) than older patients with MSI cancers

Colorectal Cancer in the Young: Research in Early Age Colorectal Cancer Trends (REACCT) Collaborative.

Background: The incidence of colorectal cancer (CRC) is increasing in the young (under 50). Defining the clinicopathological features and cancer-specific outcomes of patients with early-onset CRC is important to optimize screening and treatment strategies. This study evaluated disease-specific features and oncological outcomes of patients with early-onset CRC. Methods: Anonymized data from an international collaboration were analyzed. The inclusion criteria for this study were patients aged <50 years with stage I-III disease surgically resected with curative intent. Overall and disease-free survival were calculated using the Kaplan-Meier method. Results: A total of 3378 patients were included, with a median age of 43 (18-49) and a slight male preponderance (54.3%). One-third had a family history of colorectal cancer. Almost all (>95%) of patients were symptomatic at diagnosis. The majority (70.1%) of tumors were distal to the descending colon. Approximately 40% were node positive. Microsatellite instability was demonstrated in one in five patients, representing 10% of rectal and 27% of colon cancers. A defined inherited syndrome was diagnosed in one-third of those with microsatellite instability. Rectal cancer displayed a worse prognosis stage for stage. Five-year disease-free survival for stage I, II, and III colon cancer was 96%, 91%, and 68%, respectively. The equivalent rates for rectal cancer were 91%, 81%, and 62%. Conclusions and relevance: The majority of EOCRC would be captured with flexible sigmoidoscopy. Extending screening to young adults and public health education initiatives are potential interventions to improve survivorship