Preoperative Treatment of Advanced Colorectal Cancer: Can Chemotherapy Before Surgical Resection Improve Treatment Outcomes?

Colorectal cancer (colon cancer) is one of the most common types of cancer worldwide. It usually develops from benign growths, known as polyps, that form primarily in the large intestine (colon) or the rectum. If these polyps change over the course of several years, they can develop into cancer. The exact causes are not fully understood, but there are various factors that can increase the risk, such as age, family history, an unhealthy diet, chronic intestinal diseases, smoking, excessive alcohol consumption, and lack of physical activity. In the early stages, colorectal cancer often causes no symptoms. In advanced stages, however, abdominal pain, changes in bowel habits such as frequent diarrhea or constipation, blood in the stool, weight loss, and fatigue may occur. In advanced stages, colorectal cancer has already spread through all layers of the intestinal mucosa. In addition, lymph nodes may be affected, and tumor metastases may be present in other organs, most commonly the liver or lungs. In such cases, it is often no longer possible to remove all tumor cells from the body through surgery alone. Therefore, chemoradiotherapy and targeted therapies are also used. In addition, neoadjuvant therapies offer promising opportunities for tumor reduction and improved surgical outcomes. Neoadjuvant therapies are treatments administered before surgery. Their goal is to shrink or stabilize the tumor in order to facilitate surgical removal or improve the chances of success.

The goal of the PROTECTOR/FIRE-10 study is to compare the effectiveness of such neoadjuvant chemotherapy followed by surgery with the standard approach, in which additional treatment based on the cancer stage is administered after surgery. The primary objective is to investigate whether preoperative chemotherapy can extend the time during which patients remain free of the disease, which is referred to as disease-free survival. To this end, patients are randomly assigned to two groups. The treatment group will receive neoadjuvant chemotherapy for 12 weeks before surgery. The control group will undergo surgery according to current standard practice. This will be followed by adjuvant therapy appropriate for the cancer stage, which is not specific to this study. The study will last approximately 2 years. During this time, patients will receive treatment and be monitored.

Eligible participants are adult patients aged 18 and older with colorectal cancer (adenocarcinoma of the colon or rectum) that is at an advanced stage (stage T3–4), and/or positive lymph node findings, as determined by CT or MRI imaging. However, the cancer must not have spread to distant parts of the body (metastases). The tumor must exhibit certain genetic characteristics, such as mismatch repair proficiency or microsatellite stability, and surgery with curative intent must be feasible.

Study Details:

1. Disease: advanced colorectal cancer (adenocarcinoma of the colon or upper rectum)
2. Cancer characteristics: Stage T3–4, positive lymph node status (N+), microsatellite stability (MSS), no distant metastases
3. What the study investigates: neoadjuvant chemotherapy before surgery vs. standard therapy after surgery
4. Study objective: To prolong disease-free survival through neoadjuvant chemotherapy
5. Study duration: Up to approximately 2 years
6. Study characteristics: Phase 3 study, randomized, two study arms