Surgical resection followed by adjuvant chemotherapy remains the standard treatment for localized colon cancer. However, for patients with locally advanced colon cancer (LACC), neoadjuvant therapies—treatments given before surgery—are showing promise in improving outcomes. These therapies, particularly neoadjuvant chemotherapy, aim to shrink tumors before surgery, making them easier to remove and reducing the risk of recurrence. Recent clinical trials such as FOxTROT, OPTICAL, and NeoColr have demonstrated the potential benefits of this approach in enhancing tumor response and surgical success.
In light of these advances, a team of researchers led by Dr. Richard D Kim from the Department of Gastrointestinal Oncology at the Moffitt Cancer Center in the United States conducted a comprehensive review to examine the role of neoadjuvant therapies in colon cancer. Their article also highlights the use of neoadjuvant immunotherapy for patients with mismatch repair-deficient tumors, as seen in the NICHE trial, and discusses how MMR status can guide personalized treatment strategies. The review article was published in the Chinese Medical Journal on 5 September, 2025.
Neoadjuvant therapies are changing the treatment landscape for LACC, where chemotherapy or immunotherapy is given before surgery to shrink tumors and improve outcomes. The standard approach for colon cancer has long been surgery followed by chemotherapy, but for more advanced cases, this sequence may not be optimal. According to Dr. Kim, “ The treatment landscape for LACC is evolving as neoadjuvant therapies increasingly demonstrate their potential to transform clinical outcomes. ”
Anatomical and molecular differences between right colon cancer (RCC) and left colon cancer (LCC) further influence treatment strategies. RCC is associated with deficient mismatch repair (dMMR), BRAF and KRAS mutations, and challenging surgical access due to its location. Neoadjuvant chemotherapy can help shrink tumors preoperatively and improve surgical success. In contrast, LCC tends to occur in narrower anatomical spaces and features chromosomal instability and TP53 mutations, with oxaliplatin-based chemotherapy preferred.
Several trials have reported that neoadjuvant chemotherapy improves the survival outcomes and decreases cancer recurrence and metastasis in patients with LACC. Additionally, the neoadjuvant chemotherapy approach increases chemotherapy tolerance and mitigates the risk of postoperative complications. Neoadjuvant therapy also improves surgical outcomes, increasing the complete resection rate, decreasing the incidence of advanced-stage tumors, and promoting tumor regression. In some cases, neoadjuvant chemotherapy can prevent the need for surgery altogether.
Neoadjuvant chemotherapy has also been demonstrated to be effective in patients with MMR-proficient or MMR-deficient colon cancer, improving survival and surgical outcomes, mitigating surgical complications, achieving disease control, decreasing advanced-stage cancer incidence, and downstaging tumors.
However, neoadjuvant chemotherapy is associated with several challenges. For example, the disease can progress during treatment, leading to complications, such as obstruction or perforation, that may require emergency surgical interventions. The accurate staging of colon cancer for neoadjuvant chemotherapy is another major challenge, affecting the treatment decisions. Patients undergoing neoadjuvant chemotherapy may experience treatment-related toxicities, resulting in premature treatment discontinuation. Immune-related adverse events, such as pneumonia, thyroid dysfunction, and skin conditions are common during neoadjuvant chemotherapy. One trial found no significant difference in surgical complications between standard and neoadjuvant approaches. “ As research continues, the integration of neoadjuvant therapies will likely play a significant role in the personalized management of LACC, improving outcomes for selected patient populations,” said Dr. Kim.
To address current limitations, the authors advocate for the use of advanced imaging technologies, such as MRI and PET/CT, to improve staging accuracy. Radiomics and artificial intelligence may further help identify high-risk features and predict treatment responses. The study emphasizes the importance of multidisciplinary collaboration among oncologists, surgeons, radiologists, and pathologists to guide treatment decisions.
As evidence grows, neoadjuvant chemotherapy is poised to play a key role in the evolution of personalized cancer care, offering new hope for patients with LACC.
***
Reference
DOI: https://doi.org/10.1097/CM9.0000000000003756
Chinese Medical Journal
Literature review
Not applicable
Role of adjuvant therapies in locally advanced colon cancer
5-Sep-2025
Tiago Biachi de Castria receives an honorarium from Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme Corp., Ipsen, Moderna, AstraZeneca, and A2Bio. Richard D Kim receives an honorarium from AstraZeneca, Exelixis, Ipsen, Eisai, Roche, Pfizer (consulting/advisory role); Incyte, AstraZeneca (speaker’s bureau).