What have new treatments of gastric cancer been added into ESMO guidelines?

1. If a familial cancer syndrome is suspected , evaluation by a geneticist is recommended  [V, A] .

2. Population-based asymptomatic individual endoscopic screening is only suitable for use in areas with a very high incidence of gastric cancer  [V, B] .
   
   

1. Endoscopic biopsies should be obtained from multiple sites (5-8) to ensure adequate tumor coverage  [IV, B] .

2. Pathology should be reported according to  WHO standards  [V, B] .

3. Immunohistochemistry (IHC) and/or in situ hybridization amplification can be used to detect HER2 expression  [I, A; ESCAT score: IA] , IHC to detect PD-L1 expression CPS score  [I, A]  and  MSI-H/dMMR  [ II, A; ESCAT score: IB] , these are predictive markers of effective drug therapy.

1. Initial staging and risk assessment should include physical examination, blood count and classification, liver and kidney function, endoscopy, and contrast-enhanced CT scan of chest, abdomen ± pelvis  [V, A] .

2. FDG-PET-CT is not routinely recommended  [III, C] .

3. Diagnostic laparoscopy and peritoneal lavage cytology are recommended in operable patients who are also candidates for perioperative chemotherapy  [III, B] . Surgical resection is uncertain for patients with positive lavage cytology.

4. TNM staging should refer to the 8th edition of the AJCC/UICC Grading Manual  [IV, A] .

Treatment of local disease: Multidisciplinary diagnosis and treatment (MDT) is required before any treatment decision  [IV, B] .

Resections:

1. Pure endoscopic or surgical resection is only suitable for very early stage disease (stage IA) [III, B] .

2. Perioperative treatment and radical surgical resection are recommended for patients with  stage IB-III gastric cancer [I, A] . 

3. D2 radical mastectomy can be performed in patients with larger surgical volumes   [II, B] .

Perioperative chemotherapy:

1. Perioperative chemotherapy (preoperative and postoperative) is recommended for  patients with resectable gastric cancer of stage IB or higher [I, A] .

2. A 3-drug combination regimen  containing fluorouracil , platinum compounds , and docetaxel is recommended when possible [I, A] .

3. The FLOT regimen is the standard treatment regimen for perioperative chemotherapy, provided that chemotherapy toxicity can be tolerated [I, A; ESMO-MCBS version 1.1 score: A] . 

4. For patients who are not suitable for 3-drug chemotherapy, fluorouracil combined with cisplatin or oxaliplatin is recommended as a perioperative chemotherapy regimen  [II, B] .

Adjuvant therapy:

1. Adjuvant chemotherapy is strongly recommended for patients with stage IB and above if they have not received preoperative chemotherapy before surgery  [I, A] .

2. In patients with negative margins (R0 resection), postoperative radiotherapy has shown no additional benefit and is not recommended  [I, D] .

3. In patients who have received preoperative or postoperative chemotherapy, postoperative radiotherapy has shown no benefit and is not recommended  [I, E] .

4. Adjuvant chemoradiation should be considered in patients not receiving perioperative chemotherapy and without D2 lymph node dissection [I, C] .   

5. For patients with positive margins (R1 resection), adjuvant radiotherapy or chemoradiation may be performed on an individual basis, but is not recommended as standard treatment [IV, C] . 

6. Postoperative adjuvant chemotherapy is not recommended for patients with MSI-H after radical gastrectomy  [IV, D] . However, if the tumor needs to be downstaged before surgery,  FLOT chemotherapy is recommended.

    

Treatment of locally advanced and metastatic patients: Treatment modalities include chemotherapy, targeted therapy, and immunotherapy .

First-line treatment   :

1. The platinum-based combination with fluorouracil is recommended as the first-line regimen. Oxaliplatin is preferred, especially in elderly patients  [I, A] . S-1 is only recommended for Asian patients  [I, A] .

2. Considering the high toxicity and uncertainty of efficacy, paclitaxel -based three-drug chemotherapy regimen is not recommended as standard in first-line therapy  [I, C] .

3. Irinotecan + 5-FU  regimen can be used as a first-line alternative for  patients with platinum complex toxicity intolerance  [II, B] .

4. Trastuzumab combined with chemotherapy is recommended for  patients with HER2-positive gastric cancer  [I, A; ESMO-MCBS v1.1 score: 3; ESCAT score: IA] .

5. Nivolumab combined with chemotherapy is recommended for advanced, untreated, PD-L1 expression CPS ≥ 5 patients with esophagogastric junction and esophageal cancer   [I, A; ESMO-MCBS v1.1 score: 4] .

6. Pembrolizumab is approved for patients with esophageal or gastroesophageal junction adenocarcinoma with PD-L1 expression CPS ≥ 10  [II, C; ESMO-MCBS v1.1 score: 4] .

Second-line and later-line treatments:

1. Ramucirumab combined with paclitaxel is the standard second-line treatment regimen for  gastric cancer  [I, A; ESMO-MCBS v1.1 score: 2] . Ramucirumab monotherapy is also an option  [I, B; ESMO-MCBS v1.1 score: 1] .

2. In areas where ramucirumab is not available, single-agent paclitaxel , docetaxel  [I, A],  or  F OLFIRI chemotherapy   [I, B]  is the recommended second-line regimen . 

3. After progression on first-line trastuzumab in HER2-positive patients, continuation of second-line trastuzumab is not recommended   [I, D] , but desiccated trastuzumab (DS8201) may be considered [II, B; ESMO-MCBS v1.1 Score: 4; FDA approved, EMA not approved] .

4. Pembrolizumab is recommended for second-line treatment of MSI-H/dMMR patients [  II, A; ESMO-MCBS v1.1 score: 3; ESCAT score: IB] . 

5. Trifluridine /tipiramidine (TAS-102) is recommended for patients who have failed second-line therapy  [I, A; ESMO-MCBS v1.1 score: 3] . Taxanes or irinotecan are also available as alternatives   [II, B] .

• Surgical treatment of metastatic gastric cancer:

1. Surgery is not recommended for patients with metastatic gastric cancer unless surgery is required for symptomatic relief  [I, D] .

2. In general, resection of metastatic tumors is not recommended , but it can be used as a treatment for some patients with highly selective oligometastases and effective chemotherapy  [V, C] .