Editor’s Note: Although melanoma has a relatively low incidence among malignant tumors, its hidden onset and high malignancy make it a formidable disease. In recent years, targeted and immunotherapy treatments for solid tumors have developed rapidly, many of which began with melanoma and later extended to other cancers. However, there are significant biological differences between melanoma in Chinese and Western patients, necessitating the development of treatment protocols and standards tailored to Chinese and Asian patients. At the 2024 CSCO Conference, Dr. Jun Guo from Peking University Cancer Hospital, Dr. Xiaohui Niu from Beijing Jishuitan Hospital/National Center for Orthopedics, Dr. Di Wu from The First Bethune Hospital of Jilin University, and Dr. Lu Si from Peking University Cancer Hospital shared insights into the journey of melanoma diagnosis and treatment in China. They also reflected on the efforts of the CSCO Melanoma Expert Committee in establishing standardized treatment guidelines tailored to China’s needs.

Addressing East-West Differences and Finding Treatment Plans Suitable for Chinese Patients

Dr. Lu Si: In the vast family of tumors, melanoma might seem “unremarkable,” but it is definitely “difficult to deal with.” Dr. Jun Guo, you were one of the early experts in China to focus on the diagnosis and treatment of melanoma. What initially drew you to this “niche” tumor? How does melanoma in our country differ from that in Western countries?

Dr. Jun Guo: Globally, melanoma is considered a “leading tumor” in cancer treatment, particularly in the era of targeted therapies and immunotherapy. This reputation stems from melanoma’s central role in the development of new treatments, such as PD-1/PD-L1 inhibitors, CTLA-4 inhibitors, and LAG-3 inhibitors. These immunotherapies were initially explored in melanoma before expanding to other tumor types.

However, melanoma in China differs significantly from that in Western countries. From the perspectives of molecular subtyping and the immune microenvironment, Western melanomas—mostly skin melanomas—are characterized by lymphocytic infiltration and are often termed “hot tumors.” In contrast, the primary types of melanoma in China are acral and mucosal melanomas, which exhibit different biological characteristics. For example, mucosal melanomas are typically “cold tumors,” lacking lymphocytic infiltration within the tumor itself, though there is often significant infiltration around the tumor. Acral melanomas, on the other hand, show little lymphocytic infiltration both within the tumor and in the surrounding tissue.

Given these unique characteristics, we cannot simply apply Western treatment strategies to acral and mucosal melanomas in China. Therefore, we have conducted a series of clinical studies tailored to these specific melanoma types in Asia. Through these efforts, we have significantly improved the response rates for advanced melanoma, from about 14% to nearly 70% today. These achievements are the result of the collective efforts of the Chinese melanoma community.

Despite these advances, there is still room for improvement. In the future, colleagues in the Asian melanoma field must continue to collaborate, conducting more high-quality clinical studies to provide robust evidence for treating these unique subtypes of melanoma, thereby improving patient survival.

Melanoma as a “Benchmark” for Innovation: Leading the Development of Immunotherapy

Dr. Lu Si: As Professor Guo mentioned, melanoma is a “leading tumor” in the oncology field and a “testing ground” for many innovative treatments. Dr. Di Wu, could you elaborate on the biological or molecular characteristics of melanoma and how its treatment strategies have evolved?

Dr. Di Wu: As Professor Guo emphasized, melanoma, with its strong immunogenicity, has long been regarded as a model tumor in immunotherapy research. In discussing its biological characteristics, we must acknowledge the significant differences between melanoma in China and the West, particularly in terms of etiology. In Western countries, melanoma is primarily caused by UV exposure, with UV-induced genetic mutations being a major driver. However, this is not the case in China. Acral and mucosal melanomas account for more than 70% of melanomas in China, and their etiologies are markedly different. Acral melanoma may be associated with chronic irritation, inflammation, or even trauma, while the causes of mucosal melanoma are more complex, showing similarities to gastrointestinal tumors, with inflammation and adverse reactions playing roles.

These differences in etiology lead to distinct immune microenvironments and molecular drivers in Chinese and Western melanomas. For instance, BRAF V600 mutations are present in about 50% of Western patients with cutaneous melanoma, but the rate is significantly lower in China, at around 25%. Additionally, other genetic mutations, such as KIT, NRAS, and NF1, are more common in Chinese patients. Moreover, Chinese melanoma patients tend to have fewer point mutations, with copy number alterations being more prominent.

These molecular and pathological differences underscore the need for distinct treatment strategies in Chinese and Western melanomas. As some international experts have noted, acral and mucosal melanomas should be regarded as different diseases from cutaneous melanoma to some extent. Thus, treatment plans must be tailored to the specific circumstances of each patient to improve outcomes and survival rates.

Early Treatment for Melanoma: Evolving Strategies for Better Outcomes

Dr. Lu Si: In recent years, sentinel lymph node biopsy, neoadjuvant, and adjuvant therapies have added new dimensions to the surgical treatment of early-stage melanoma. Dr. Xiaohui Niu, could you share your experience and exploration of early-stage melanoma treatment?

Dr. Xiaohui Niu: The role of surgery in melanoma treatment has evolved alongside advancements in medical oncology. In the past, melanoma treatment mainly relied on systemic therapies, but now, with deeper understanding, early surgical intervention has become a critical treatment approach, sometimes on par with drug therapies. The emergence of neoadjuvant immunotherapy, in particular, has transformed our understanding of the nature of tumors and the direction of immunotherapy development.

Neoadjuvant therapy has become a standard treatment for cutaneous melanoma and is widely included in treatment guidelines. However, before implementing any treatment plan, accurate diagnosis and staging are crucial. This is not only important for research purposes but also directly affects the choice of treatment strategy and its effectiveness. Surgery’s role is not limited to tumor removal but extends to achieving precise staging through meticulous operations.

One of melanoma’s defining features is its tendency to metastasize early to the lymph nodes. This biological characteristic is key to assessing the tumor’s status and guiding treatment strategies. Therefore, sentinel lymph node biopsy remains an indispensable tool for precise diagnosis of melanoma metastasis and will continue to be vital in the coming years. This procedure allows us to better understand the tumor’s progression and develop more personalized treatment plans, thereby improving treatment outcomes and patient prognoses.

Forging Ahead to Establish a “China Standard” for Melanoma Diagnosis and Treatment

Dr. Lu Si: The CSCO Melanoma Expert Committee was the first expert committee established by CSCO in 2007. It introduced the first consensus guidelines in 2008 and has continued to update them. Dr. Jun Guo, could you tell us how China has gone “from zero to one” in building a standard for melanoma diagnosis and treatment?

Dr. Jun Guo: In 2007, under the guidance and care of President Shu-Kui Qin, CSCO established its first expert committee—the Melanoma Expert Committee. Although melanoma is a relatively niche cancer, the CSCO leadership, including Professor Jun Ma and Academician Yan Sun, among others, gave us tremendous support. Through the tireless efforts of multiple generations, the Melanoma Expert Committee has gradually grown, absorbing advanced experiences from abroad while also deeply exploring the differences between melanoma in China and the West. In both basic and clinical research, we’ve analyzed these differences at the molecular level, seeking breakthroughs.

Today, the CSCO Melanoma Expert Committee has achieved remarkable results. From the first set of guidelines to the current version, which has been revised nine times, the changes are significant. Over the past 17 years, we have accumulated a wealth of evidence-based medical data, particularly in the field of acral and mucosal melanoma, contributing the most global evidence in this area. This achievement is a source of pride for the CSCO Melanoma Expert Committee.

Looking ahead, we understand that the road is still long. With the support, unity, and pragmatic spirit of the CSCO family, we will continue to strive for more effective treatment models for melanoma patients in Asia and worldwide, ensuring every patient receives the best possible care.

Dr. Jun Guo

Peking University Cancer Hospital Chief Physician, Doctoral Supervisor, Professor Director of the Department of Medical Oncology for Melanoma and Sarcoma Vice President and Secretary General of CSCO Vice Chairman of the International Melanoma Association (MWS) Chairman of the Melanoma Expert Committee, National Cancer Center of China Chairman of the CSCO Melanoma Expert Committee Vice Chairman of the CSCO Renal Cancer Expert Committee Vice Chairman of the CSCO Immunotherapy Expert Committee Vice Chairman of the CSCO Urothelial Cancer Expert Committee Vice Chairman of the CSCO Prostate Cancer Expert Committee Expert on Drug Registration Review, CFDA Member of the National Health and Family Planning Commission’s Rational Drug Use Expert Committee (Anti-Tumor Drugs Group)

Dr. Xiaohui Niu

Beijing Jishuitan Hospital Chief Physician, Professor, Doctoral Supervisor Director of the Bone and Soft Tissue Tumor Diagnosis and Treatment Center, Beijing Jishuitan Hospital Director of CSCO Former Chairman of the CSCO Sarcoma Expert Committee Vice Chairman of the CSCO Melanoma Expert Committee Director of the CACA Sarcoma Professional Committee Honorary Director of the CACA Bone and Soft Tissue Tumor Rehabilitation Committee Standing Committee Member of the Chinese Medical Association Tumor Diagnosis and Treatment Professional Committee Vice Leader of the Bone Tumor Professional Group, Chinese Medical Association Orthopedics Branch Chairman of the Bone Tumor Group, Beijing Medical Association Orthopedics Branch The only Board Member from China for the International Society of Limb Salvage (ISOLS) Executive Director of the Asia-Pacific Musculoskeletal Tumor Society (APMSTS) Former Chairman and Executive Director of the East Asia Musculoskeletal Oncology Group (EAMOG) Deputy Editor-in-Chief of the Chinese Journal of Bone and Joint Reviewer for 34 SCI journals First or corresponding author of 262 papers, including 44 SCI articles

Dr. Di Wu

The First Bethune Hospital of Jilin University Doctoral Supervisor, Chief Physician, Professor Director of the Comprehensive Cancer Treatment Department at the First Hospital of Jilin University Director of CSCO Vice Chairman of the CSCO Melanoma Expert Committee Member of the CSCO Small Cell Lung Cancer Expert Committee Member of the CSCO Bone and Soft Tissue Sarcoma Expert Committee Member of the CACA Cancer Metastasis Professional Committee Standing Committee Member of the CSCO Cardio-Oncology Expert Committee

Dr. Lu Si

Peking University Cancer Hospital, Department of Medical Oncology for Melanoma and Sarcoma Chief Physician, Doctoral Supervisor Lead author of the CSCO Guidelines for Melanoma Diagnosis and Treatment Lead author of the CSCO Guidelines for the Management of Toxicity Related to Immune Checkpoint Inhibitors Vice Chairman of the CSCO Melanoma Expert Committee Vice Chairman of the CSCO Neuro-Oncology Expert Committee Deputy Editor of the Journal of Oncology Reviewer for Clinical Cancer Research