Editor’s Note: From September 25 to 29, 2024, the much-anticipated 27th Annual Chinese Society of Clinical Oncology (CSCO) conference was held successfully in Xiamen. This prominent event gathered top experts from China's oncology community, focusing on standardized pathways and cutting-edge advancements in the diagnosis and treatment of malignant tumors.During the conference, Dr. Gong Chen from the Sun Yat-sen University Cancer Center delivered a well-received presentation titled "The Evolving Treatment Paradigm for Locally Advanced Colorectal Cancer." In this golden moment of academic exchange, Oncology Frontier conducted a deep interview with Professor Chen. The discussion centered around the latest advancements in the treatment of locally advanced colorectal cancer and his long-standing academic connection with CSCO, offering an insightful blend of professional wisdom and personal emotion.

Oncology Frontier: In your lecture, you discussed the significant changes in the treatment paradigm for locally advanced colorectal cancer. Could you elaborate on these shifts and the driving factors behind them?

Dr. Gong Chen: The treatment paradigm for locally advanced colorectal cancer is undergoing profound transformation, and this wave of change will likely impact the treatment of all solid tumors in the future. In the past, surgery was seen as the sole curative option for colorectal cancer. However, with medical advancements, we now recognize the importance of multiple treatment modalities. From the introduction of postoperative adjuvant therapies to the rise of neoadjuvant treatments, some patients can even achieve non-surgical cures. This evolution signifies the advent of a multi-modality treatment era, reflecting deeper understanding of cancer and aligning with the growing influence of precision medicine.

Historically, before the 1990s, colorectal cancer treatment primarily relied on surgical intervention due to limited therapeutic options. The application of 5-fluorouracil (5-FU) chemotherapy in the following years opened a new chapter in adjuvant treatment, significantly improving survival rates. In the early 21st century, the addition of oxaliplatin propelled adjuvant therapy to new heights, though the accompanying neurotoxicity issues pushed us to continuously seek better solutions. By 2017, the success of the IDEA trial marked the entry of oxaliplatin into an era of precision stratification, tailoring treatment duration based on risk to find the optimal balance between efficacy and toxicity. Yet, precision medicine’s momentum hasn’t stopped. Recent breakthroughs in molecular biomarkers and minimal residual disease (MRD) detection have enabled us to more accurately determine patient needs, ushering colorectal cancer treatment into a new era of individualized therapy.

In the realm of neoadjuvant therapy, while it hasn’t become standard for colon cancer, its potential cannot be ignored. Given the high surgical resection rates for colon cancer and the limitations of CT staging, future clinical research must focus more on precise stratification to guide treatment decisions. In contrast, neoadjuvant treatment for rectal cancer has made significant progress. With high-resolution MRI, we can now precisely evaluate the risk of tumor recurrence, allowing for the customization of treatment plans, which has notably improved both sphincter preservation rates and quality of life. Particularly worth mentioning is the emergence of the Total Neoadjuvant Therapy (TNT) model, which provides an effective treatment pathway for high-risk rectal cancer patients. By front-loading radiotherapy and chemotherapy and continuing treatment during the waiting period for surgery, the TNT model not only increases sphincter preservation rates but also reduces distant metastasis risk, ultimately improving the overall survival rates of patients with locally advanced rectal cancer. The successful application of this model marks a new era of precision treatment for locally advanced rectal cancer.

As precision medicine advances, the accuracy of imaging assessments in clinical practice becomes increasingly critical, and refined patient stratification is key to success. However, the most essential precision comes from the molecular biology level, particularly with the accurate assessment of microsatellite instability (MSI). For colorectal cancer, the microsatellite status is a crucial biomarker, closely linked to how tumors respond to treatment. Since 2015, we have observed extraordinary efficacy in MSI-H colorectal cancer patients treated with immunotherapy. This discovery prompted us to innovatively apply experiences from metastatic colorectal cancer treatment to the neoadjuvant setting. From 2018 to 2019, we became the first to explore neoadjuvant immunotherapy in MSI-H locally advanced colorectal cancer. By 2021, the CSCO guidelines became the first in the world to recommend neoadjuvant immunotherapy for T4b MSI-H colorectal cancer, significantly improving surgical resection rates and treatment outcomes. Following this, the National Comprehensive Cancer Network (NCCN) guidelines adopted a similar recommendation the following year. As CSCO guideline developers, we felt an immense sense of pride in leading international standards in this field.

Supported by extensive clinical research and data, including a groundbreaking study led by former CSCO President Dr. Xu Ruihua, we achieved a 75% complete response rate (pCR + cCR) for MSI-H rectal cancer with neoadjuvant immunotherapy, sparing a large proportion of patients from surgery. International validation has confirmed these results, establishing a new paradigm for MSI-H rectal cancer treatment—prioritizing immunotherapy over traditional chemoradiotherapy. In the field of MSI-H colon cancer, neoadjuvant immunotherapy research is also flourishing. Under Dr. Xu’s leadership, the NeoShot study (combining PD-1 and CTLA-4 inhibitors) has shown remarkable efficacy, with a pathological complete response (pCR) rate as high as 80% in MSI-H colon cancer, signaling a significant improvement in outcomes and possibly sparing surgery for some patients in the future.

In conclusion, the shift toward precision medicine has profoundly impacted colorectal cancer treatment strategies, with microsatellite status emerging as the core determinant of treatment pathways. For locally advanced colorectal cancer, we advocate for stratification based on microsatellite status: MSI-H patients should prioritize neoadjuvant immunotherapy, while MSS patients should follow traditional approaches, combining surgery, neoadjuvant chemotherapy, or chemoradiotherapy depending on individual needs. This signifies the dawn of an individualized treatment era driven by molecular markers, patient-centered care, and goal-oriented multi-modal approaches.

Oncology Frontier: Could you share your personal story with CSCO?

Dr. Gong Chen: This year, the CSCO organizing committee introduced the heartwarming topic “My Story with CSCO,” and I am deeply honored to share my long-standing connection with CSCO. Since its establishment in 1997, CSCO has played a pivotal role in the development of China’s oncology field, and I have had the privilege of being part of its journey since 2009. That year, I participated in the first National Young Doctor Speech Contest hosted by CSCO and was fortunate enough to win the top prize. Professor Li Jin, who was the Secretary-General at the time, presented the award to me personally. I vividly remember the excitement and honor of that moment. Professor Li jokingly suggested that I use the 5,000 RMB prize to enroll in a Mandarin class to improve my accent. When we recently met again, we reminisced about those days, and while my accent may not have changed, the deep bond formed through CSCO remains as strong as ever. That competition marked the beginning of my unbreakable connection with CSCO, and since then, I have actively participated and grown alongside this esteemed organization.

With the guidance and support of esteemed leaders such as Academician Sun Yan, Professor Liao Meilin, Professor Guan Zhongzhen, Professor Wu Yilong, Professor Qin Shukui, and Professor Li Jin, CSCO has not only upheld its academic excellence but also provided young oncologists with a broad platform for growth. In 2013, at the suggestion of Professor Qin Shukui, we established “CSCO Young” (now the CSCO Youth Expert Committee), and I was honored to serve as its first chairperson. Today, CSCO Young has become an integral part of CSCO, contributing significantly to annual reviews, progress assessments, and conference translations. Many members have since grown into rising stars within CSCO’s various expert committees.

I feel privileged to have witnessed and participated in CSCO’s remarkable journey, which has been driven by the foresight and selfless dedication of its leadership. Their mentorship has nurtured young talents, providing continuous energy for CSCO’s ongoing development. Today, CSCO stands as one of the most influential and widely respected academic organizations in China, welcomed by clinicians across all levels. With everyone’s collective efforts, I am confident that CSCO’s future will be even brighter. I extend my heartfelt wishes for its continued growth and hope to contribute more to this vibrant community, working together to create an even more promising future.

Dr. Gong Chen

• Chief Physician, Doctoral Supervisor

• Deputy Director, Colorectal Surgery Department, Sun Yat-sen University Cancer Center

• Vice Secretary-General and Executive Council Member, CSCO

• Former Committee Member, Academic Committee, American Society of Clinical Oncology (ASCO)

• Former Chair, Colorectal Cancer Committee, Guangdong Anti-Cancer Association

• 2019 “National Famous Doctor – Excellent Role Model” Award Winner

• Vice Chair and Secretary-General, CSCO Colorectal Cancer Committee

• Co-lead Author, CSCO Colorectal Cancer Guidelines

• Vice Chair, CSCO Minimally Invasive Surgery Committee and CSCO Elderly Oncology Committee

• Executive Member, Colorectal Cancer Committee, Chinese Medical Doctor Association

• Vice Chair, Colorectal Tumor Liver Metastasis Subcommittee, Chinese Medical Doctor Association