Several studies have supported what many clinicians are seeing: a steady increase in patients under age 50 being diagnosed with colorectal cancer. “In any given clinic day, my colleagues and I have two to three new patients under age 45. This is a striking and consistent theme. We rapidly need to rethink our approaches to screening and treatment,” says Nicholas DeVito, MD, GI medical oncologist and researcher. 

While some attribute the rise to risk factors linked to accelerated aging, such as ultraprocessed food, obesity, and sedentary lifestyles, Duke researchers are examining additional environmental or lifestyle factors. “This is an important body of work to go alongside other innovative treatment studies that will benefit younger patients diagnosed today,” says DeVito.

Because the current screening recommendations start at age 45, there’s a clear gap in screening access for younger patients. This leads to a delayed diagnosis, and at a more advanced stage. According to DeVito, primary care providers and gastroenterologists should think more often about the possibility of colorectal cancer in younger patients. “Younger, healthier bodies can take more insult, so symptoms might be nonspecific, or even not recognized until a patient has advanced disease,” he says. 

DeVito suggests providers lower the index of suspicion, switching to a “rule out” mentality rather than “rule in.” DeVito adds, “Colonoscopy is a very low threshold test, so for a young patient with even minor symptoms, ruling it out is my priority. If polyps are identified, there’s also an opportunity to remove them as an effective preventive measure. And if cancer is present, this approach leads to an earlier diagnosis and lower mortality for younger patients.”

DeVito is conducting trials that may change the standard of care treatment for microsatellite stable colorectal cancer, which accounts for more than 85% of all colorectal cancer. “At Duke, we have our sights set on discovering the next step in colon cancer management,” he says. That includes a unique first-line immunotherapy-only trial: BOT+BAL (botensilimab and balstilimab) for newly diagnosed metastatic or unresectable colorectal cancer.

The current standard of care for microsatellite stable colorectal cancer is four to five lines of traditional chemotherapy, followed by immunotherapy if refractory. Late-line immunotherapy with BOT+ BAL has a 20% to 30% response rate. Flipping the order, DeVito’s trial goes straight to immunotherapy, which has a promising advantage. “We don’t want patients to wait for what could deliver a durable response first, and with fewer side effects,” he explains. This is especially relevant for a young person, who may want to avoid short- and long-term side effects from chemo while having the potential to achieve better long-term disease control. Moreover, immunotherapy works better in other cancers when it is given before the tumor becomes resistant to chemotherapy or targeted therapy.

DeVito is also examining biomarkers in colon cancer. “Biomarker testing and tumor genetic testing are increasingly valuable resources to personalize patients’ treatments,” says DeVito. “Testing for microsatellite instability-high (MSI-high) colorectal cancer, tells us if a patient’s tumor has defective DNA repair, making them a better candidate for immunotherapy. Simply put, obtaining microsatellite status in colorectal cancer is part of the diagnosis. If we treat patients with MSI-H colorectal cancer with chemotherapy first, they might not achieve outcomes as positive compared to immunotherapy first,” says DeVito. 

Referring physicians can trust that their patients will receive the most promising options tailored to their needs, from screening protocols to diagnosis, tumor sequencing, and treatment plans that apply the most innovative approaches available for colorectal cancer. “We are our referring physicians’ partners; we’re here to consult on cases, screening plans, or treatment options to deliver the best possible care to our community,” says DeVito.