[Ask the Specialist: Disease A to Z] Stage 4 Colorectal Cancer Can Still Be Operated On — How Cetuximab Widened the 'Chance of a Cure'
< Interest in health has grown significantly since the COVID-19 pandemic. The problem is that as information channels have diversified, indiscriminate health information is clouding public understanding. Health Kyunghyang selects leading specialists based on the number of SCIE-indexed papers published, awards received, and academic society activities, and is running the series "Ask the Specialist: Disease A to Z" to accurately explain each disease through real multidisciplinary treatment cases. >"Even metastatic colorectal cancer can be cured if aggressive drug therapy is combined with surgery," said Dr. Jeong Eun Kim,Professor of Oncology at Asan Medical Center.Colorectal cancer is the third most common cancer in Korea, after thyroid and lung cancer. When caught early, however, it has an excellent cure rate of over 90%. The problem is that early-stage symptoms are barely noticeable — about 25% of patients are first diagnosed only after the cancer has already reached stage 4, having spread to other organs such as the liver or lungs.Treatment for metastatic colorectal cancer, however, is changing rapidly. In the past, chemotherapy focused mainly on extending life; today, the new goal is "conversion therapy" — shrinking the tumor enough to make surgery possible. In particular, for RAS wild-type metastatic colorectal cancer, the EGFR-targeted therapy cetuximab is reshaping the treatment paradigm by rapidly shrinking tumors and expanding surgical opportunities. Health Kyunghyang met with Dr. Jeong Eun Kim, Professor of Oncology at Asan Medical Center, to learn about the changing landscape of metastatic colorectal cancer treatment and a real patient case. ■ The Patient's Condition at the TimeA 55-year-old man, referred to here as Mr. Kim, visited the hospital with pain in the upper right abdomen. Tests revealed ascending colon cancer that had spread to two-thirds of his liver. At the time, the extent of liver metastasis was so large that surgery seemed practically impossible. But the medical team did not give up. Through multidisciplinary care involving oncology, hepatobiliary-pancreatic surgery and radiology, they decided to first shrink the tumor and then reassess whether surgery would be feasible."Unlike other cancers, colorectal cancer is one of the few cancers where a cure can still be expected even with metastasis, as long as all lesions can be completely removed," said Dr. Kim. "What matters most, in the end, isn't only finding patients who are operable from the start — it's determining, through multidisciplinary care, how to bring a patient to an operable state." ■ The Course of TreatmentGenetic testing confirmed the patient had RAS wild-type metastatic colorectal cancer. To shrink the tumor as quickly as possible and improve the odds of surgery, the medical team started combination therapy with cetuximab and FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin). About four months later, imaging showed the tumor had shrunk by more than 60%. After reassessment through multidisciplinary care, surgery became possible — removing both the primary tumor and the liver metastases in a single operation."The key to treating metastatic colorectal cancer isn't simply shrinking the tumor — it's bringing the patient to an 'operable state,'" Dr. Kim explained. "Cetuximab plays an important role in conversion therapy through its high tumor response rate and rapid tumor shrinkage."Cetuximab, an anti-EGFR agent, has been used as a standard first-line option for metastatic colorectal cancer for nearly 20 years. In particular, in RAS wild-type patients, it has repeatedly demonstrated long-term survival benefits and rapid tumor shrinkage, and has become a leading example of biomarker-based treatment in the era of precision medicine."In the past, the concept of biomarkers wasn't clearly defined, but now we can identify patients likely to benefit from treatment based on RAS mutation status," said Dr. Kim. "By selecting patients more precisely, the clinical value of cetuximab has also become clearer." ■ The Patient's Condition TodayThe patient underwent additional chemotherapy after surgery. During follow-up, a small liver metastasis was found but was treated with additional resection. About nine years after his initial diagnosis, he remains stable with no recurrence. ■ Why Surgery Is a Viable Strategy Even for Stage 4 Colorectal CancerTreatment strategy for colorectal cancer varies depending on where the tumor is located. For colon cancer, location itself doesn't significantly affect outcomes, but for rectal cancer, the distance from the anus determines the extent of surgery and whether radiation therapy is needed. Right-sided colon cancer, which often shows symptoms later, is also known to have a relatively worse prognosis than left-sided colon cancer.What sets colorectal cancer apart from other solid tumors is that a cure can still be expected through surgery even at stage 4. If metastatic lesions in the liver or lungs can be completely removed, long-term survival — and in some patients, a full cure — becomes possible. Because blood from the intestines travels to the liver through the portal vein, colorectal cancer metastases can, in some cases, be relatively limited, creating an opportunity for surgery.Of course, not every patient with metastatic colorectal cancer is a candidate for surgery. Whether surgery is possible is determined by comprehensively evaluating the location, size, number and extent of the metastatic lesions. For liver metastases, MRI is used to assess the lesions and remaining liver volume; for lung metastases, the number, distribution and location of lesions determine resectability. This process requires multidisciplinary care involving oncology, surgery and radiology."Since colorectal cancer is difficult to cure with drug therapy alone, the principle is to actively consider resection whenever surgery is feasible," said Dr. Kim. "Recently, research into liver transplantation for patients with liver metastases is also underway, gradually expanding the scope of surgical treatment." ■ The Era of Precision Medicine: 'Who the Patient Is' Determines TreatmentThe biggest recent shift in metastatic colorectal cancer treatment is precision medicine tailored to each patient's genetic profile.In the past, most patients received the same chemotherapy. Today, treatment strategy is determined after analyzing various biomarkers — RAS/BRAF mutations, MSI/MMR status, HER2 amplification, and NTRK fusion genes.Cetuximab, too, is not a treatment used for every patient. It is a leading EGFR-targeted therapy proven effective specifically in RAS wild-type metastatic colorectal cancer. Recently, the BREAKWATER trial has broadened its potential use, suggesting new combination therapy options even for patients with BRAF V600E mutations."Recent real-world data studies are moving beyond simply confirming the effect of a particular drug — they're now integrating diverse clinical and molecular biological information to find the optimal treatment strategy and sequence for each patient," said Dr. Kim. "In Korea, following the expansion of insurance coverage for NGS testing, major institutions such as the National Cancer Center and Asan Medical Center are actively conducting research analyzing real-world treatment data, including cetuximab, to identify the optimal treatment sequence." ■ Colorectal Cancer Is Striking Younger Patients — Screening Age Should Change TooDr. Kim said one of the points she explains most often in her clinic is that "stage 4 is not the same as terminal."Stage 4 simply means the cancer has spread to other organs — it doesn't mean the final stage of life. In particular, metastatic colorectal cancer can often be controlled with long-term drug therapy, or shrunk enough to make surgery possible.Globally, the number of colorectal cancer patients under 50 has been rising. Korea, along with Australia, has one of the highest rates of early-onset colorectal cancer in the world — its rate among people under 50 stands at 12.9 per 100,000, among the highest globally. The proportion of colorectal cancer cases in Korea occurring in people under 50 is 14.3%, also among the highest after Australia, the United States and New Zealand.Dr. Kim pointed to expanding national screening programs as the most realistic way to reduce metastatic colorectal cancer cases. As early-onset colorectal cancer continues to rise steadily, she said, the screening age should be lowered and access to colonoscopy should be expanded."The United States has already lowered its recommended colorectal cancer screening age to 45, and Japan is moving in the same direction," said Dr. Kim. "Lowering the screening age and improving screening rates will be the most effective way to reduce colorectal cancer mortality in Korea as well."
