Colorectal Cancer Awareness Month: Progress, Challenges, and Novel Research

March is recognized globally as Colorectal Cancer Awareness Month, a time to highlight the importance of prevention, early detection, and ongoing clinical research aimed at improving outcomes for patients with this significant oncologic challenge. Even as awareness and screening have saved lives, continued innovation is crucial to address rising rates in younger adults and disparities in care.

The Burden of Colorectal Cancer

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. According to the American Cancer Society’s 2026 report, an estimated 158,850 new cases of colorectal cancer will be diagnosed in the United States in 2026, and 55,230 people will die from the disease. American Cancer Society

Significant disparities exist in CRC incidence and mortality. The Alaska Native population experiences the highest rates globally (81 cases per 100,000 people and 32 deaths per 100,000), more than double the rates observed among White Americans. The American Indian population also faces a disproportionately high burden. Colorectal Cancer Alliance

Shifting Trends: Rising Rates in Younger Adults

Recent data reveals a concerning trend: while incidence and mortality continue to decline among adults aged 65 and older, rates are increasing among individuals younger than 65, particularly in cancers arising in the distal colon and rectum. Incidence is rising by 3% per year among adults aged 20–49 and by 0.4% per year among those aged 50–64, while decreasing by 2.5% per year among people aged 65 and older. Early-onset colorectal cancer is increasing across all racial and ethnic groups, and younger patients are often diagnosed at advanced stages, underscoring the need for improved screening strategies. Colorectal Cancer Alliance

Alliance for Clinical Trials in Oncology: Pioneering Research

The Alliance for Clinical Trials in Oncology is actively conducting a wide portfolio of clinical trials designed to address these challenges, uniting more than 25,000 cancer specialists across 115 main institutions and 1,400 affiliated sites in the United States and Canada. These studies explore innovative approaches across GI cancers, including genetics, systemic therapy optimization, ablative strategies for metastatic disease, supportive care, survivorship interventions, financial toxicity, and early cancer detection. AACR

New Trials Launched in 2026

Alliance A212101: Family Communication After Genetic Testing

This trial (NCT07143487) investigates how genetic risk information should be communicated within families after a new diagnosis of colorectal cancer. Up to 30% of colorectal cancer cases may have a genetic basis, with about 15% of these patients carrying a pathogenic germline variant. The study compares proband-mediated communication (patients sharing results with relatives) and provider-mediated communication (healthcare professionals contacting relatives directly). The primary endpoint is the proportion of first-degree relatives undergoing germline testing within 6 months. AACR

PAGODA Trial (Alliance A232402 CD): Proactive Chemotherapy Dose Adjustment

The PAGODA trial (NCT07283939) evaluates a structured strategy for guiding chemotherapy dose adjustments during FOLFOX treatment for gastrointestinal cancers. The goal is to reduce treatment interruptions by proactively adjusting chemotherapy dosing. Patients are randomized to either standard-of-care FOLFOX or a FOLFOX regimen guided by the PAGODA algorithm. The primary endpoint is the proportion of chemotherapy cycles with unplanned treatment delays during cycles 2–7. AACR

Ongoing Trials

ERASur Trial: Ablative Therapy for Metastatic Disease

The ERASur study (NCT05673148) is evaluating whether adding total ablative therapy (TAT) to standard-of-care systemic therapy can improve outcomes in patients with limited metastatic colorectal cancer. AACR

Alliance A022102: Modified FOLFIRINOX vs. Modified FOLFOX

This phase III study (NCT05677490) is evaluating whether modified FOLFIRINOX can improve outcomes compared with modified FOLFOX as first-line treatment for advanced gastroesophageal adenocarcinoma. AACR

Alliance A222004: Cancer-Associated Anorexia

This phase III trial (NCT04939090) evaluates treatment strategies for cancer-associated anorexia, comparing olanzapine to megestrol acetate. AACR

DEFEND Trial (Alliance A222302): Telehealth Exercise Program

The DEFEND study (NCT07059884) evaluates whether a structured exercise program delivered through telehealth can preserve function and prevent disability in patients receiving curative-intent chemotherapy. AACR

PROOF Trial (Alliance A232403): Financial Hardship Screening

The PROOF trial (NCT06963723) evaluates whether regular digital screening for financial hardship can improve outcomes among adults with advanced or metastatic cancer. AACR

Prevention and Early Detection

Project REACH: Smoking Cessation in Rural Survivors

Project REACH (NCT05008848) evaluates a text-based smoking cessation strategy among rural cancer survivors, including those with a prior diagnosis of colorectal cancer. AACR

Alliance A212102: Blood Samples for Multicancer Early Detection

This observational study (NCT05334069) aims to create a blinded reference set of blood samples to support the development of blood-based multicancer early detection tests. AACR

AYA ACCESS Study: Genetic Services for Young Adults

The AYA ACCESS study (NCT07091617) evaluates whether a digital chatbot-enabled genetic service model can improve access to genetic counseling and testing among adolescents and young adults with cancer. AACR

Conclusion

The diverse portfolio of Alliance trials highlights the ongoing commitment to advancing prevention, improving treatments, and shaping the future of care for patients with gastrointestinal cancers. Current research extends beyond treatment efficacy to address prevention, care delivery, and clinical decision-making. Full details are available on the Alliance for Clinical Trials in Oncology website.