Editor’s Note: The 2024 update of the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Colorectal Cancer has been released. The new edition incorporates the latest evidence-based medical developments, adds new biomarkers for colorectal cancer, enriches clinical treatment strategy options, and adjusts the recommendation levels for various treatment protocols. Oncology Frontier interviewed Professor Ying Yuan from The Second Affiliated Hospital of Zhejiang University School of Medicine, one of the guideline’s authors, to discuss the key updates and their clinical significance.

Oncology Frontier: Since the first edition of the CSCO Guidelines for Colorectal Cancer was released seven years ago, how have you experienced its evolution as both a participant and a clinical user?

Professor Ying Yuan: Since the release of the CSCO Guidelines for Colorectal Cancer in 2017, we have updated it annually based on the latest clinical research results, new drug approvals, and the availability of medications in China. Over the past seven years, I have been involved every year. My strongest impression is that the expert team, under the leadership of senior figures like Professors Suzhang Zhang and Sanjun Cai, has developed guidelines that are highly rigorous and objectively tailored to domestic clinical practice. Consequently, the CSCO Guidelines for Colorectal Cancer are highly regarded among clinicians.

Oncology Frontier: What are the major updates in the 2024 CSCO Guidelines for Colorectal Cancer?

Professor Ying Yuan: This year’s updates are relatively minor, focusing on pathology, conversion therapy, palliative care, and radiotherapy for rectal cancer. In pathology, in addition to the previously recommended tests for RAS, BRAF, MSI-H, dMMR, and HER2 and NTRK after standard treatment failure, this year’s guidelines add POLE/POLD1 mutation testing.

For conversion therapy, the recommendation level for the triplet regimen combined with bevacizumab for patients with potentially resectable metastases, suitable for strong therapeutic regimens, has been upgraded from grade 1, 2A evidence to grade 1. This applies to all patients with RAS and BRAF wild-type or mutant tumors, regardless of whether the lesions are in the left or right colon. Additionally, the TRICE study showed that the triplet regimen combined with cetuximab did not offer better conversion efficiency compared to the doublet regimen combined with cetuximab. Therefore, the new guidelines have removed the grade 3 recommendation for the triplet regimen combined with cetuximab.

In palliative care, TAS-102 was approved in China in 2019, and the guidelines recommend it as a first-level option for third-line treatment of advanced colorectal cancer after standard treatments have failed. Based on the SUNLIGHT study published at the 2023 ASCO GI meeting and in the New England Journal of Medicine, the new guidelines now first-level recommend TAS-102±bevacizumab for third-line palliative treatment.

In rectal cancer radiotherapy, the 2023 ASCO meeting presented the PROSPECT study, which showed that for rectal cancer patients with low recurrence risk who could undergo sphincter-preserving surgery, adding pelvic radiotherapy for those who are chemotherapy-resistant or intolerant after neoadjuvant chemotherapy can be beneficial. The study’s significance is underscored by its simultaneous publication in the New England Journal of Medicine, indicating its potential to change clinical practice. The new guidelines reflect this treatment strategy based on these results.

Oncology Frontier: Can you elaborate on the important updates in the new guidelines for advanced treatment and their evidence?

Professor Ying Yuan: As previously mentioned, in the field of advanced colorectal cancer treatment:

• First, the evidence level for the triplet regimen combined with bevacizumab for potentially resectable metastases has been upgraded to the highest level, grade 1.
• Second, the triplet regimen combined with cetuximab has been removed from the grade 3 recommendation.
• Third, based on the SUNLIGHT study, TAS-102 combined with bevacizumab improves progression-free survival (PFS) and overall survival (OS), making it a first-level recommendation for third-line palliative treatment in advanced patients.

Moreover, some updates are included in the annotations due to insufficient or inadequate evidence. During the guideline drafting process, Dean Ruihua Xu emphasized that mentioning these topics in the guidelines, even if they are not included in the main tables, shows that the expert group has recognized these issues and aims to inspire clinical practice. For instance, there is considerable interest in whether immunotherapy can be used for patients with pMMR and MSS colorectal cancer. The phase II CAPability-01 study showed that combining chidamide with bevacizumab and sintilimab resulted in a 44% objective response rate (ORR) in pMMR and MSS advanced colorectal cancer patients who failed standard treatments. Although current data is not sufficient to be included in the main table, ongoing phase III clinical studies may validate these findings, and the annotation highlights this potential.

For the first-line palliative treatment of pMMR and MSS advanced colorectal cancer patients, there are ongoing studies exploring standard chemotherapy combined with anti-angiogenesis therapy and immunotherapy, such as the international AtezoTRIBE and CheckMate 9X8 studies and the domestic BBCAPX study led by our center. Although current data is insufficient for inclusion in the main guidelines, these explorations are noted in the annotations. We look forward to the results of these phase III clinical studies in 2-3 years to further guide clinical practice.

Oncology Frontier: What are the significant recent and future research advances in the field of colorectal cancer, and how will they impact clinical practice?

Professor Ying Yuan: One of the most notable issues in the future colorectal cancer field is how to apply immunotherapy to the over 90% of patients with pMMR and MSS colorectal cancer. Determining how to select the optimal patient population for immunotherapy will benefit a large number of patients.

Additionally, as our comprehensive clinical treatment capabilities improve, we are exploring the potential to avoid surgery or radiotherapy in certain cases. For instance, in the future, treatment plans for locally advanced rectal cancer will likely depend on molecular subtyping or responses to initial induction therapy, rather than the current standard concurrent chemoradiotherapy. Personalized precision treatment will be the inevitable development trend for all tumors, including colorectal cancer.

Professor Ying Yuan:

• Director and Professor, Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine
• Chief Physician and Doctoral Supervisor
• Deputy Director, Key Laboratory of Early Warning and Intervention of Malignant Tumors, Ministry of Education
• Executive Deputy Editor-in-Chief and Editorial Director, Journal of Practical Oncology
• Recipient of the First China Young Scientist Award in Oncology
• Winner of the Third National Famous Doctor Excellence Model Award
• Board Member, Chinese Society of Clinical Oncology (CSCO)
• Deputy Chair, CSCO Colorectal Cancer Expert Committee
• Standing Member, CSCO Gastric Cancer Expert Committee
• Deputy Chair, Chinese Anti-Cancer Association Family Hereditary Tumor Committee
• Standing Member, Chinese Anti-Cancer Association Clinical Chemotherapy Committee
• Standing Member and Genetics Group Leader, Chinese Anti-Cancer Association Colorectal Cancer Committee
• Vice Chair, Zhejiang Medical Association Oncology Branch
• Chair, Zhejiang Anti-Cancer Association Family Hereditary Tumor Committee
• Vice Chair, Zhejiang Anti-Cancer Association Oncology Committee