Liquid Biopsy and Precision Medicine Transform Colorectal Cancer Care for Younger Patients

Colorectal cancer diagnoses are rising significantly in people under 50, now accounting for nearly half of all new cases. A study published March 2 by the American Cancer Society found that nearly one-half of new colorectal cancer diagnoses are in people younger than 65, up from 27% in 1995. An estimated 55,230 individuals will die from colorectal cancer in 2026, nearly one-third of whom will be younger than 65 years.

Mayo Clinic in Arizona has launched a specialized cancer program specifically for people who are under 50 and diagnosed with colorectal or another type of gastrointestinal cancer. Mayo leaders say the goal now is to replicate the Arizona early-onset cancer program at its Minnesota and Florida campuses. While diagnoses and death rates from colorectal cancer have been declining in older people, the opposite is true for people under the age of 50, and colorectal cancer is now the leading cause of cancer-related death for people in that age group.

Precision medicine refers to customizing treatment based on the individual patient, including the molecular signature of their cancer. The program performs genomic sequencing on blood samples and cancer tissue even before patients walk in the door. The patients in Mayo's program get genetic testing, fertility counseling (treatments may affect fertility), optional fertility preservation, access to social workers and integrative specialists. The center uses a multidisciplinary team of specialists and a molecular profile of individual patients' tumors to treat and also detect the risk of cancer recurrence.

Recent advances have ushered in the era of precision medicine, where therapeutic decisions are increasingly guided by the molecular underpinnings of individual tumors. Central to this revolution is the advent of liquid biopsy, a minimally invasive method that captures circulating tumor DNA (ctDNA) fragments shed by malignant cells into the bloodstream. This technique offers unprecedented insight into the dynamic genomic landscape of colorectal cancer, enabling real-time monitoring of tumor evolution and the identification of actionable mutations that can be targeted with tailored therapies.

Liquid biopsy circumvents many constraints of traditional tissue biopsies, as it allows repeated sampling with minimal patient discomfort and risk. The analysis of ctDNA harnesses cutting-edge technologies that have evolved from the initial focus on single-gene mutations via polymerase chain reaction (PCR) assays toward comprehensive genomic profiling (CGP) facilitated by next-generation sequencing (NGS). This paradigm shift markedly enhances the resolution and breadth of genomic data, encompassing hundreds of genes and myriad variants that govern tumor behavior and therapeutic resistance.

For patients with advanced disease, liquid biopsy facilitates the identification of predictive biomarkers that inform the selection of targeted agents and immunotherapies. More importantly, it unveils emerging resistance mechanisms that can herald treatment failure, thereby enabling therapy adaptation before clinical progression is evident. Such dynamic monitoring is pivotal for the optimization of personalized treatment regimens, potentially improving survival outcomes and quality of life.

Beyond its role in managing metastatic colorectal cancer, liquid biopsy has demonstrated profound utility in the detection of minimal residual disease (MRD) following curative-intent surgery and locoregional therapies. Sensitive ctDNA assays can detect MRD with high specificity, stratifying patients according to their risk of recurrence. This stratification permits the optimization of adjuvant systemic therapies, sparing low-risk patients from unnecessary toxicity while targeting therapy intensification to those at highest risk.

The repeatability of liquid biopsy sampling offers a longitudinal view of tumor evolution that traditional biopsies cannot match. Changes in ctDNA profiles can flag shifts in dominant clones, emergence of resistant subpopulations, or response to therapy, creating opportunities for timely therapeutic intervention. Liquid biopsy thus transforms cancer monitoring from a passive observation to an active, responsive process aligned with the principles of dynamic precision medicine.

Scientists are working to figure out why it is that someone born during the 1990s has a fivefold higher risk of developing colorectal cancer than someone born during the 1960s. There's something different in young-onset colon and rectal cancer, making it important to understand the genetic basis and molecular signature of the tumor.

Experts urge individuals not to ignore symptoms like fatigue or blood in the stool, as delayed diagnosis is common in younger patients. Screening for colorectal cancer is recommended for everyone starting at age 45, or earlier for those with a family history. The center is attracting patients from across the Southwest and California, including patients with a genetic predisposition or family history. There's a research component to the Mayo program that includes the clinical trial testing of a colorectal cancer vaccine.