​2021 version of CSCO gastric cancer guidelines update: neoadjuvant chemotherapy for stage Ⅲ patients becomes grade Ⅰ recommendation

*Only for medical professionals to read and reference.
In this guide, the update of non-metastatic gastric cancer has no major breakthrough in the treatment plan, which is mainly reflected in the adjustment of the level of evidence; the update of metastatic gastric cancer is mainly reflected in the improvement of the status of immunotherapy.

The 2021 Chinese Society of Clinical Oncology (CSCO) Guidelines Conference will be held in Beijing from April 23 to 24 in a combination of online and offline methods.

At the conference, Professor Zhang Xiaotian from Peking University Cancer Hospital and Professor Wang Fenghua from the Cancer Center of Sun Yat-sen University interpreted the non-metastatic and metastatic gastric cancer parts of the "2021 CSCO Guidelines for Gastric Cancer Diagnosis and Treatment".

The 2021CSCO gastric cancer guidelines update is mainly reflected in the following aspects: diagnosis, comprehensive treatment and neoadjuvant treatment of non-metastatic gastric cancer, and immunotherapy for metastatic gastric cancer.

Non-metastatic gastric cancer 1 Diagnosis of gastric cancer 1) Remarks for imaging endoscopy diagnosis: Replace “recommend abdominal MRI as a means of further examination when CT suspects liver metastasis, and recommend the use of hepatocyte-specific contrast agents for those with conditions, which can improve the diagnosis of liver metastasis "Sensitivity" is "When clinical or CT suspects liver metastasis, the first choice is liver MRI plain scan + enhanced examination, and hepatocyte-specific contrast agents can be used according to clinical needs"; "The efficacy evaluation of immunotherapy can refer to the iRECIST standard".

Replace "imaging functional imaging parameters" with "imaging volumetric measurement and functional imaging parameters".

2) Update on CT staging signs of gastric cancer: In particular, it is proposed that the "Siewert classification of esophageal gastric junction cancer should be reported" to determine whether to stage the gastric cancer or esophageal cancer according to the standard, which may affect the patient's admission to thoracic surgery (esophageal cancer) or General surgery (gastric cancer).

Regarding the number and characterization of lymph nodes, a new "group report based on the Gastric Cancer Treatment Protocol of the Japanese Society of Gastric Cancer" was added.

3) Pathological diagnosis update: "Specifications for pathological diagnosis of specimens after endoscopic mucosal resection/endoscopic submucosal dissection (EMR/ESD)" has been added.

2 Comprehensive treatment of gastric cancer 1) The overall treatment strategy Table 1 The overall treatment strategy for the comprehensive treatment of non-metastatic gastric cancer recommends that patients with stage III (cT3-4aN1-3M0) non-esophageal gastric junction cancer (cT3-4aN1-3M0) suitable for surgery will be treated as "laparoscopic exploration (Class 1B) Evidence), neoadjuvant chemotherapy + gastrectomy D2 + adjuvant chemotherapy (Class 1B evidence)" changed from level II recommendation to level I recommendation.

The source of evidence is the RESOLVE study.
The results show that perioperative SOX chemotherapy can improve the 3-year disease-free survival rate compared with postoperative XELOX adjuvant.

2) Perioperative treatment of locally advanced gastric cancer Although some progress has been made in the perioperative treatment of locally advanced gastric cancer, due to the relatively limited evidence, it has not been formally written into the guideline.
4 new annotations are added.
Early gastric cancer CLASS02: endoscopic exploration compared to whole stomach Resection has clear efficacy and safety.

The long-term efficacy has not been confirmed, and research exploration can be carried out in a center with rich experience.

Advanced gastric cancer KLASS-02: It is confirmed that laparoscopic distal gastrectomy combined with D2 lymph node dissection is safe.

Robotic surgery: Robotic distal gastrectomy (RDG) has lower complications than laparoscopic distal gastrectomy (LDG), and can remove more perigastric lymph nodes, but the long-term survival advantage needs more evidence to confirm.

Increase operation specimens for laparoscopic exploration: For clinical stage III patients, the 3-perforation method should be used for laparoscopic exploration.

First assess whether there is peritoneal metastasis.
If there is peritoneal metastasis, it should be sent for a clear diagnosis and tested for HER2, MMR protein to guide treatment; if there is no obvious peritoneal metastasis, lavage with normal saline and retain peritoneal lavage for ascites Cytological testing.

3) Neoadjuvant Therapy Table 2 The neoadjuvant treatment for non-metastatic gastric cancer recommends non-esophageal gastric junction cancer.
The SOX neoadjuvant chemotherapy" is changed from level II recommendation to level I recommendation, and level III recommendation is to delete "ECF and its modified plan".

For esophagogastric junction cancer, “SOX neoadjuvant chemotherapy” (1A evidence) was added to the grade I recommendation, and the “FLOT4 regimen” (1B evidence) was added to the grade II recommendation.
The
update is mainly based on the FLOT4 study, and the results indicate that it is in perioperative In the period, the FLOT program significantly improved the OS compared with the ECF or ECX program.

Many attempts have been made in neoadjuvant precision drug treatment, only HER2-positive gastric cancer has made progress, but the evidence to become a standard treatment is not yet mature.

Added note: HER2-positive gastric cancer: perioperative chemotherapy combined with anti-HER2 therapy.

NEOHX study: preoperative and postoperative XELOX-T regimen, trastuzumab maintenance; HERFLOT study: FLOT + trastuzumab, trastuzumab maintenance; PETRARCA study: FLOT + trastuzumab + Pertuzumab anti.

4) Postoperative adjuvant treatment Table 3 Recommendations for postoperative adjuvant treatment of non-metastatic gastric cancer In the level III recommendation for patients with stage III D2R0 resection, the "postoperative concurrent radiotherapy and chemotherapy" is deleted.

5) Two revised comments have been added for conversion therapy for unresectable gastric cancer: Retrospective studies have shown that even for patients who cannot be surgically removed, chemotherapy and radiotherapy have a survival benefit compared to chemotherapy alone; for patients who are expected to be unresectable, the dose of radical radiation therapy: DT 50-60Gy.

For those who are frail and have extensive tumors and do not consider surgery, it is recommended that only the visible tumor is included in the radiation field of radiotherapy, and preventive irradiation of the lymph node area is not performed.

Metastatic gastric cancer 1) First-line treatment Table 4 Recommended first-line treatment for advanced metastatic gastric cancer In the recommended first-line treatment, the renewal point of HER2-negative population is reflected in the improvement of immunotherapy status; HE2-positive population comment adds anti-HER2 and antibody-conjugated drugs (ADC) biosimilar Elaboration of the drug.

In last year's CSCO guidelines, the status of the first-line treatment of immune checkpoint inhibitors has not been established, and patients are only encouraged to participate in relevant research.

In this guideline, for HER2-negative patients, it is recommended that people with PD-L1 CPS≥5 use chemotherapy combined with nivolumab (Class 1A evidence, level I recommendation); for people with PD-L1 CPS≥1, use pembrolizumab ( Type 1B evidence, grade III recommendation).

The status of first-line immune therapy has been significantly improved, mainly based on the results of the CheckMate 649 study, the ATTRACTION-4 study, and the KEYNOTE-062 study.

2) Second-line treatment Table 5 Recommendations for second-line treatment of advanced metastatic gastric cancer.
Second-line treatment is newly recommended for "Pembrolizumab as a single agent in people with high microsatellite instability (MSI-H)" (Class 2A evidence, Class II recommendation) ).

3) In the third-line treatment, the recommendation of "nivolumab single-agent" (1A evidence, level I recommendation) was newly added, and the "two-drug chemotherapy" was deleted.

Summary: On the basis of the 2020 CSCO Gastric Cancer Guidelines, the 2021 CSCO Gastric Cancer Guidelines integrate the latest clinical advances at home and abroad more quickly, pay attention to the research data of the Chinese population, and be close to the clinical practice of the country.

The survival improvement of non-metastatic gastric cancer depends on perioperative clinical precision staging and advanced precision drug treatment.
In this guideline update, the diagnosis of gastric cancer is more reflected in clinical staging services.

The status of immunotherapy for metastatic gastric cancer has gradually increased from the third-line to the first-line, and from single-agent therapy to combination therapy, more treatment models have yet to be unlocked.