Metastatic Gastric Cancer (Stage 4 Gastric Cancer)

Gastric cancer is the 5th most common type of cancer in the world. It has the potential to metastasize early and frequently due to its high vascularization and lymph drainage. In Eastern countries, it is diagnosed at an early stage thanks to screening programs. However, in western countries and especially in our country, the disease is usually at an advanced stage at the time of diagnosis. Gastric cancer metastasizes through lymph (lymphatic metastasis), blood (hematogenous metastasis) and/or direct spread (peritoneal spread, seeding).

Treatment of metastatic gastric cancer is generally chemotherapy, but despite advances in chemotherapy, the average survival is less than one year. Therefore, various studies have been and are still being conducted to achieve better outcomes in these patients. In current staging, all gastric cancers with distant metastases are defined as stage 4. However, the number and extent of metastases are not taken into account. As a result of advances in chemotherapy and targeted therapies, it has been observed that much better results can be obtained in patients with limited metastases. Patients with few metastases may benefit from an intensive multidisciplinary treatment including chemotherapy followed by surgery.The principles of endoscopic and surgical treatment of early and locally advanced gastric cancers are generally well defined. However, there are no clear recommendations in the guidelines regarding surgery for metastatic gastric cancer (stage 4 gastric cancer). Positive results have been obtained in many recent studies. It has been reported that very good results can be obtained with multidisciplinary treatment in well-selected patients and even complete recovery may be possible.

Surgery for Liver Metastases in Gastric Cancer

The most common site of gastric cancer metastasis is the liver. Due to the aggressive nature of gastric cancer, metastases may be widespread or other organs may be involved at the time of diagnosis. However, in cases where the involvement of the liver is limited and there is no other organ metastasis, surgical treatment for the liver lesions can be performed. Again, due to the aggressive nature of gastric cancer, meticulous patient selection is mandatory. Important criteria for patient selection are as follows:

No organ involvement other than the liver
No peritoneal involvement (peritoneal involvement)
Possibility of complete removal of liver metastases

The most suitable patients for surgery for liver metastases are those with a single metastatic lesion. Better results can be obtained from surgical treatment when the number of metastases does not exceed three, only one lobe of the liver is involved and the largest lesion is less than 5 cm in size. In addition to surgery, interventional radiologic procedures can also be applied for liver metastases.

The main ones are listed below:

Radiofrequency ablation (RFA)
Microwave ablation (MWA)
Transarterial chemoembolization) (TACE)
Transarterial radioembolization (TARE)

In patients with liver metastases, when a good response is obtained from preoperative chemotherapy immunotherapy, results of the surgical resection might be better.

The choice of surgery or interventional procedures should be based on a multidisciplinary approach with careful consideration of tumor and patient factors.

Surgery in Peritoneal Metastases (peritoneal metastases) in Gastric Cancer

Gastric cancer can metastasize through direct spread to the lining of the abdomen called peritoneum. Survival is generally low in this patient group. Response to chemotherapy is limited. The main reason for this is the presence of a tissue called the plasma-peritoneal barrier between the bloodstream and the peritoneum. Because of this tissue, drugs cannot reach the peritoneum in sufficient doses. For this reason, alternative treatments have been sought for patients with peritoneal involvement. Cytoreductive surgery + hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) application has come to the agenda in gastric cancer after good results in some other cancer types.

This application, popularly known as hot chemotherapy, has also been applied in gastric cancer and better results have been obtained compared to chemotherapy alone with good patient selection. In CRS-HIPEC, all tumor foci in the peritoneum are removed and then chemotherapy drugs are administered directly into the abdomen at 41-42 degrees for 60-90 minutes. In this way, the drugs affect the peritoneum at a much higher dose and for a longer period of time.

Gastric cancer is more aggressive than other cancer types for which hot chemotherapy is applied. Therefore, patient selection for hot chemotherapy must be meticulous. The main factors for the success of CRS-HIPEC (hot chemotherapy) are listed below:

Complete cytoreduction
Complete cytoreduction means complete removal of all tumor deposits. This is essential for treatment success.

Extent of peritoneal involvement
The extent of peritoneal involvement is expressed by a scoring system called the 'peritoneal cancer index'. This score ranges from 0 to 39. The best results in gastric cancer are obtained when this index is 6 or lower.

Response to chemotherapy
In patients with peritoneal involvement, patients who respond well to chemotherapy prior to CRS-HIPEC benefit more from CRS-HIPEC. In patients with peritoneal involvement, the preferred approach is to give chemotherapy first, re-evaluate the patient during this period and plan CRS-HIPEC according to the results.

Appropriate morphological characteristics of the tumor

Appropriate age and general performance status of the patient

Although there is no definite limit for age, it should be kept in mind that the risk of surgery increases at older ages. In addition, the patient's general performance and the presence of comorbidities should be taken into consideration.

Experience

In CRS-HIPEC treatment, major surgery of resection of the stomach is combined with the complete removal of tumors in the peritoneum and the administration of hot chemotherapy. Therefore, various complications related to both surgery and drug administration are possible. The patient should be carefully evaluated before surgery and informed about possible complications. When complications occur, they need to be managed appropriately.

Surgery in the Presence of Paraaortic (around the aorta) Lymph Nodes in Gastric Cancer

Tumor involvement in the lymph nodes around the aorta in gastric cancer is now considered distant metastasis. Removal of lymph nodes in this region is not included in standard gastric cancer surgery. However, in some patients, good results have been obtained with the combination of neoadjuvant chemotherapy and surgery in patients with peri-aortic lymph node involvement. In the Japanese gastric cancer guidelines, removal of these lymph nodes is recommended in cases where there is significant shrinkage of these lymph nodes after chemotherapy.