In addition to today’s resource, please review:
Early-Onset Colorectal Cancer: From Genetic Discovery to Clinical Innovation [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Am Soc Clin Oncol Educ Book. 2025 Jun;45(3):e473618. doi: 10.1200/EDBK-25-473618. Epub 2025 Jul 10.
Abstract
The rising incidence of early-onset colorectal cancer (EOCRC) presents a growing challenge to traditional approaches in screening, treatment, and survivorship. EOCRC is increasingly recognized as a biologically distinct entity, driven by complex inter-related biological, genetic, behavioral, and socioenvironmental factors. This chapter reviews the molecular and clinical features that distinguish EOCRC, with attention to emerging precision oncology strategies, including germline testing, tumor genomic profiling, and biomarker-directed therapies. In metastatic disease, recent advances in targeting BRAF V600E, KRAS G12C, HER2 amplification, and microsatellite instability-high (MSI-H)/mismatch repair deficiency tumors have reshaped therapeutic paradigms. Tumor sidedness and metastatic site patterns are now recognized as predictive and prognostic factors. In localized disease, neoadjuvant immunotherapy for MSI-H tumors and nonoperative management are redefining standard care, with special relevance to younger patients seeking fertility preservation or organ-sparing approaches. The chapter also addresses key gaps in EOCRC care, including underutilization of fertility preservation counseling and limited guidance for cancer management during pregnancy. A multidisciplinary, lifecycle-based framework is essential to optimize outcomes and improve quality of life for this unique and growing patient population.Practical Applications
• All patients diagnosed with early-onset colorectal cancer (EOCRC) should undergo germline multigene panel testing, as recommended by current National Comprehensive Cancer Network guidelines, to inform treatment, surveillance, and cascade testing for at-risk relatives.• Fertility preservation counseling must be routinely integrated into the initial treatment planning process for reproductive-age patients with colorectal cancer as early interventions can significantly affect future reproductive outcomes and quality of life.• In patients with EOCRC with localized disease, neoadjuvant therapy decisions should carefully weigh long-term morbidity, fertility considerations, and organ preservation goals, with growing evidence supporting total neoadjuvant therapy and nonoperative management in appropriately selected patients.• Tumor genomic profiling should be universally performed in metastatic CRC to guide biomarker-driven therapies, including anti-EGFR rechallenge, BRAF- or human epidermal growth factor receptor 2–targeted regimens, KRAS G12C inhibitors, and immune checkpoint inhibitors for microsatellite instability-high/mismatch repair deficiency tumors.
Today, I review, link to, and excerpt from JAMA Internal Medicine’s The Rise in Early-Onset Cancer in the US Population—More Apparent Than Real [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. JAMA Intern Med. 2025 Nov 1;185(11):1370-1374. doi: 10.1001/jamainternmed.2025.4917.
All that follows is from the above resource.
Abstract
Importance: Rising rates of early-onset cancer have generated substantial media coverage and public concern. In response, early-onset cancer has become a federal research priority, and clinical guidelines have shifted to recommend earlier screening for some cancers. Yet, it remains unclear whether rising rates represent a true increase in cancer occurrence or that these may instead be explained by increased diagnostic scrutiny.
Observations: In aggregate, the 8 cancers with the fastest-rising incidence (>1% per year) in US adults younger than 50 years (thyroid, anus, kidney, small intestine, colorectum, endometrium, pancreas, and myeloma) have doubled in incidence since 1992, while the aggregate mortality for these cancers has remained flat. Colorectal and endometrial cancer showed a slight rise in mortality; for the others, stable or declining mortality alongside rising diagnoses suggests that greater detection (rather than more disease) accounts for the trend. In some cancers, such as thyroid and kidney cancer, overdiagnosis is well documented. For others, incidental detection or earlier diagnosis may explain the trends. While not among the fastest growing (0.6% per year), breast cancer remains the most common early-onset cancer, and despite rising diagnoses in women younger than 50 years, mortality has decreased by approximately half.
Conclusions and relevance: The rise in early-onset cancer incidence does not consistently signal a rise in the occurrence of clinically meaningful cancer. While some of the increase in early-onset cancer is likely clinically meaningful, it appears small and limited to a few cancer sites. Much of the increase appears to reflect increased diagnostic scrutiny and overdiagnosis. Interpreting rising incidence as an epidemic of disease may lead to unnecessary screening and treatment while also diverting attention from other more pressing health threats in young adults.
