Stage 4 Gastric Stomach Cancer

Stage 4 Gastric Stomach Cancer: Current Research and Treatment Insights

Introduction to Stage 4 Gastric Cancer

Stage 4 gastric cancer, also known as advanced gastric cancer, is characterized by the spread of cancer beyond the stomach to other parts of the body. This stage is associated with a very poor prognosis, with a 5-year survival rate of approximately 4%. The management of stage 4 gastric cancer involves a combination of chemotherapy, targeted therapy, immunotherapy, and, in some cases, palliative surgery.

Chemotherapy and Survival Trends

Impact of Chemotherapy on Prognosis

Recent studies have shown that the introduction of new chemotherapeutic agents has led to an improvement in the overall survival rates of patients with stage 4 gastric cancer. A population-based study in Japan observed that the 3-year survival rate for stage 4 gastric cancer improved from 11.4% to 13.2% following the approval of several new oncologic drugs since 2009. Younger patients, particularly those under 60 years old, showed the most significant improvement in survival rates.

Neoadjuvant Chemotherapy

Neoadjuvant chemotherapy (NAC) has been explored as a treatment option for specific subtypes of gastric cancer, such as type 4 or large type 3 gastric cancer. However, a phase III trial (JCOG0501) found that NAC with S-1 plus cisplatin did not demonstrate a survival benefit compared to surgery followed by adjuvant chemotherapy with S-1 . Despite this, NAC was associated with significant downstaging of tumors, indicating its potential role in reducing tumor burden before surgery.

Molecular Testing and Targeted Therapy

HER2/neu and Immunotherapy

Molecular profiling has become a standard practice in the treatment of stage 4 gastric cancer. Testing for HER2/neu, mismatch repair (MMR)/microsatellite instability (MSI), and programmed death ligand 1 (PDL-1) status is crucial for determining eligibility for targeted therapies and immunotherapy. In a study conducted in India, 16.16% of stage 4 gastric cancer patients tested positive for HER2/neu and were treated with trastuzumab, which has been shown to improve survival. Additionally, 8.8% of patients had d-MMR/MSI high status, and 32.7% had a PDL-1 tumor proportion score greater than 1%, making them candidates for immune checkpoint inhibitors.

Role of Surgery in Stage 4 Gastric Cancer

Palliative Surgery

While stage 4 gastric cancer is generally considered incurable, palliative surgery can provide symptomatic relief and potentially improve prognosis when combined with chemotherapy and/or radiotherapy. However, surgery should not be offered as a standard first-line treatment and should be considered on a case-by-case basis after thorough multidisciplinary discussions. Factors such as the patient's overall health, tumor characteristics, and expected quality of life post-surgery must be carefully evaluated.

Conclusion

The management of stage 4 gastric cancer continues to evolve with advancements in chemotherapy, targeted therapy, and immunotherapy. While new chemotherapeutic agents have improved survival rates, the role of neoadjuvant chemotherapy remains uncertain for certain subtypes. Molecular testing is essential for guiding targeted and immunotherapy treatments. Palliative surgery may offer benefits in selected cases, but its use should be carefully considered. Ongoing research and clinical trials will further refine these treatment strategies, offering hope for better outcomes in the future.

Summary

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