Half of the world's esophageal cancer is in China, and listen to Professor Fu Junhui explain the key points of esophageal cancer treatment!

*For medical professionals only

Professor Fu Junhui: Breaking the "platform period" of esophageal cancer treatment, immunotherapy has a long way to go

Esophageal cancer is one of the most common cancers of the digestive system, according to the 2020 World Health Organization International Agency for Research on Cancer released data, the global incidence of esophageal cancer ranks among the top ten, more than half of the cases occur in China, and in 2020 alone, 300,000 people died of esophageal cancer, the fourth largest type of cancer death in China[1].


The vast majority of Chinese esophageal cancer patients are already in the advanced stage when they are diagnosed, so the treatment effect is not good
.
At the same time, the distribution of esophageal cancer in China is also uneven, and there are certain characteristics in gender and region, such as more male patients than women, and the high incidence
of Henan, Hebei, Shanxi and other areas such as the Taihang Mountains.

In the past, the treatment of esophageal cancer basically relied on chemotherapy, which was not effective
.
However, in recent years, with the addition of targeted drugs and immune drugs, the therapeutic effect of esophageal cancer has been significantly improved
.
In particular, the emergence and development of immune drugs has changed the fate of many patients, and after comprehensive treatment, some patients have achieved tumor survival and even clinical cure
.
How has the diagnosis and treatment of esophageal cancer changed? What does the addition of immunotherapy bring to patients with esophageal cancer? The Medical Cancer Channel sincerely invited Professor Fu Junhui of Shantou Central Hospital to share academic insights
.
Professor Fu Junhui interview videoProfessor Fu Junhui interview video

through the blockage,

New treatments offer new hope

In the past 30 years, China has made remarkable achievements in the early diagnosis, surgery and comprehensive treatment of esophageal cancer, but the long-term efficacy of esophageal cancer is still in the plateau period, and the average 5-year survival rate of resectable esophageal cancer patients has been hovering around 30%, while the vast majority of esophageal cancer patients are already in the advanced stage when diagnosed, and the survival rate is not optimistic, and the 5-year survival rate is less than 10%.

In general, esophageal cancer remains a major disease
that seriously threatens the health, economic development and social progress of our people.

Speaking of the treatment of esophageal cancer, Professor Fu Junhui introduced that in 1913, the world's first surgical resection of esophageal cancer was carried out in the United States, and in the 1940s, Professor Wu Yingkai carried out China's first esophageal cancer resection surgery in Beijing, and successfully removed the lower thoracic esophageal cancer, at this point, the curtain of surgical treatment of esophageal cancer in China was officially opened
。 In the following 70 years, after the unremitting efforts of the majority of clinical workers, China's esophageal cancer surgical skills have been continuously improved, anesthesia technology has been continuously improved, perioperative management has been continuously improved, the level of surgical treatment of esophageal cancer has made great progress, the surgical resection rate has risen from 75% in the 60s to the current 95%, and the perioperative mortality rate has also dropped from 30% to less than
1%.

Professor Fu Junhui said: "At the end of the 20th century, with the development of advanced instruments and minimally invasive surgical techniques, minimally invasive resection of esophageal cancer came into being and was widely carried out
worldwide.
Compared with traditional surgery, the incidence of minimally invasive surgical incisions, mild pain, shortened hospital stay, intraoperative bleeding and postoperative complications is also significantly reduced
.
Despite the continuation of treatments, we clinicians still face a real and cruel problem – these technological advances are still not enough to improve the long-term survival rate
of advanced esophageal cancer.
”

At the same time, many clinical experts at home and abroad have made continuous attempts to a variety of comprehensive treatment modes for esophageal cancer, but unfortunately they have not been able to achieve satisfactory treatment results
.
At present, chemotherapy is still the recommended first-line standard treatment plan for locally advanced or advanced esophageal cancer, but its effective rate is low, only about 38%-42%, the median survival is only about one year, and the incidence of ≥-level 3 side reactions is high, which adversely affects
the quality of life of patients.

"Overall, surgical treatment is still an important means of treating esophageal cancer, and standardized comprehensive treatment is an effective way to
improve the efficacy of esophageal cancer.
" As we enter the era of precision medicine, targeted and immunotherapy guided by molecular detection has brought new life
to patients with esophageal cancer.
Professor Fu Junhui said
.

Pain points, tiralizumab

Become a powerful treatment option

Immunotherapy has become an important choice in the treatment of esophageal cancer, and has been recommended by major guidelines, and corresponding drugs have been approved
.
In April 2022, the State Drug Administration of China (NMPA) approved the anti-PD-1 antibody drug tirelizumab injection for the treatment of patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have progressed or are intolerable after previous first-line standard therapy, providing patients with an effective and safe new option
for second-line treatment.

The approval of tiralizumab is mainly based on the significant benefit of the RATIONALE-302 study, which shows that tiralizumab brings long-term survival benefit, with a median overall survival (OS) of up to 8.
6 months and a 30% reduction in the risk of death; Second-line treatment with tirelizumab has a higher remission rate and a longer
duration of remission than chemotherapy.

At the same time, for patients with CPS≥10, the second-line treatment of tirelizumab was also better than chemotherapy (median OS 10.
3 months vs.
6.
8 months), and the 6-month OS rate was 67.
4% vs.
50.
8%, respectively, and the 12-month OS rate was 44.
0% vs.
27.
0%,
respectively 。 It is worth noting that this year, the American Society of Clinical Oncology (ASCO) released the Asian data of the RATIONALE-302 study, suggesting that the efficacy and safety data of ESCC patients in Asia are basically consistent with the world, which once again confirms the remarkable efficacy
of tirelizumab in the treatment of esophageal cancer.

Professor Fu Junhui added: "Tirelizumab from the essence of the drug mechanism determines that it has a certain therapeutic advantage, the Fab segment of the binding of terrelizumab and PD-1 has a unique binding epitope, and the binding surface on PD-1 overlaps with PD-L1 in a large range, which can completely block the binding of PD-1 and PD-L1, thus playing a role in low toxicity and high efficiency
.
" 。 From the perspective of the study design of the RATIONALE-302 study and the enrollment population, it is also very close to the real clinical practice in China - the study included in the population, about 50% of Chinese esophageal cancer patients, and the second-line chemotherapy regimen designed by the study includes three chemotherapy drugs
in international clinical practice.
Therefore, the study confirms that the second-line treatment of terrelimumab monotherapy in China and the world in patients with esophageal squamous cell carcinoma is universal, providing a promising option
for the current second-line treatment of esophageal cancer.
”

With hot spots, immunotherapy has a long way to go

As immunotherapy plays an increasingly important role, the identification of patients with the greatest clinical benefit and the selection of markers is becoming increasingly important
.
However, traditional PD-L1 expression does not seem to be a good predictor of immunotherapy in
patients with esophageal cancer.
How to further screen the beneficiary population? Where is the "perfect bio-marker" path for immunotherapy for esophageal cancer? In this regard, Professor Fu Junhui said: Looking back at a number of important clinical studies, PD-L1 expression level is still a reliable marker for screening most immunobeneficiary populations, and patients with higher CPS in the RATIONALE 302 study show better clinical benefits, but PD-L1 expression level is still relatively limited to the representation of the total population of esophageal cancer, and further research
is still needed in the future 。 In addition, there are some potential alternatives to bio-markers, such as tumor mutation load (TMB), microsatellite instability, HER2, NTRK, circulating tumor DNA (ctDNA), the clinical application value of these bio-markers still needs to be further verified
.

Although immunotherapy has made its mark in the field of esophageal cancer, it has not yet fundamentally changed the disease prognosis for all patients with esophageal cancer, and there is still a long way to go in the
future 。 At the same time, Professor Fu Junhui mentioned that the treatment mode of immuno + chemotherapy has the advantages of convenient administration, high patient acceptance, high tolerance, short treatment time, good downtime effect, etc.
in neoadjuvant therapy of esophageal cancer, and the new adjuvant therapy mode of immune + chemotherapy can make the patient's tissue space clearer, improve the aortic trachea, pericardial adhesion, etc.
, thereby reducing the difficulty of surgery and improving the resection rate, but the model still needs large-sample randomized controlled clinical studies to confirm its effectiveness and safety.
In practice, the patient's wishes should be fully respected and fully informed of the advantages and disadvantages
.
The application of the treatment mode of immune + chemotherapy in the perioperative period of esophageal cancer has certain application prospects, and it needs to be gradually explored
.

Finally, Professor Fu Junhui said: "Immunotherapy has made great progress in the field of esophageal cancer, with cross-era significance, but esophageal cancer immunotherapy still faces major breakthroughs and challenges, including how to accurately screen the advantages of immunotherapy, immunotherapy resistance treatment options, post-treatment strategies, etc.
For the majority of
clinicians and researchers, esophageal cancer diagnosis and treatment is still a long way to go.
" 。 It is believed that with the in-depth study of the human immune system, immunotherapy will play a more important role in the treatment of esophageal cancer in the future, bringing patients a prolongation of survival and the improvement
of quality of life.
"
Expert Profile
: Professor Fu Junhui Chief Physician and Master Supervisor

• Shantou City outstanding talents
• Nan Yue good doctor
• Director of Esophageal Surgery, National Center for Respiratory Medicine/First Affiliated Hospital of Guangzhou Medical University
• Director of the Department of Oncology of Shantou Central Hospital (Guangdong Provincial Clinical Key Specialty).
  
• Visiting Professor of Thoracic Surgery, Anyang Cancer Hospital
• Chairman of the Multidisciplinary Diagnosis and Treatment Committee of Esophageal Diseases of Guangdong Society of Chest Diseases
• Vice Chairman of the Oncology Surgeon Branch of Guangdong Medical Doctor Association
• Vice Chairman of Thoracic Surgery Management Branch of Guangdong Medical Industry Association
• Member of the Standing Committee of the Thoracic Surgery Branch of the Guangdong Medical Association / Deputy Head of the Esophageal Carcinoma Group
• Director of the Chinese Branch of the International Society of Esophageal Diseases
• Vice Chairman of the Lung Nodule Diagnosis and Treatment Committee of the Rehabilitation Branch of the Chinese Anti-Cancer Association
• Member of the Standing Committee of the Esophageal Cancer Committee of the Guangdong Anti-Cancer Association
• Scientific research:
• He has presided over a number of national, provincial and municipal scientific research projects
  .
  He has published more than 100 SCI and national academic papers
  .
  
• "Series of research on surgical treatment of esophageal cancer" won the first prize of Shantou Science and Technology Achievement Award 3 times in 2009, 2014 and 2015

References:

[1] IRAC Global Cancer Burden Report 2020

*This article is for the sole purpose of providing scientific information to medical professionals and does not represent the views of this platform