Gastric cancer, also known as stomach cancer, is one of the most common cancers worldwide, particularly in East Asia, Eastern Europe, and South America. The majority of gastric cancer cases are diagnosed at an advanced stage, where curative surgery is no longer a viable option. In such cases, the treatment focus shifts to systemic therapies aimed at controlling disease progression, improving survival, and enhancing the patient’s quality of life. This article explores the treatment options available for patients with advanced gastric cancer when surgery is not an option, with a focus on chemotherapy, targeted therapy, immunotherapy, and palliative care.
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The Role of Surgery in Gastric Cancer
Surgery is the primary treatment modality for early-stage gastric cancer and is curative in a significant proportion of patients. The standard surgical procedures include partial or total gastrectomy, where the tumor is surgically removed along with surrounding lymph nodes. However, only approximately 30% of gastric cancer cases are diagnosed at a resectable stage, and even fewer are eligible for surgery when the disease is advanced or metastatic (Baiocchi et al., 2021).
In patients with locally advanced or metastatic gastric cancer, surgery is often contraindicated due to the spread of the cancer to surrounding organs, distant metastases, or the patient’s inability to tolerate surgery due to comorbidities or poor general health. For these patients, systemic therapies become the cornerstone of treatment.
Chemotherapy: Standard Treatment for Advanced Gastric Cancer
Chemotherapy remains the primary treatment option for patients with advanced gastric cancer when surgery is not an option. Chemotherapy involves the use of drugs that target rapidly dividing cells, including cancer cells. The goal of chemotherapy in gastric cancer is to reduce tumor size, control disease progression, and improve the patient’s quality of life.
First-line chemotherapy regimens for advanced gastric cancer typically include a combination of drugs, most commonly fluorouracil (5-FU) or capecitabine, cisplatin, and docetaxel (Mishra et al., 2019). These regimens have been shown to significantly improve survival in metastatic gastric cancer, with overall survival (OS) benefits ranging from 9 to 12 months in clinical trials (Wagner et al., 2017).
However, chemotherapy is often associated with significant side effects, including nausea, vomiting, fatigue, neutropenia, and anemia. These side effects can lead to treatment discontinuation or dose reductions, which may impact the effectiveness of the treatment. Additionally, most patients eventually experience tumor resistance, and disease progression occurs despite continued chemotherapy.
Combining Chemotherapy with Targeted Therapy
To overcome the limitations of chemotherapy alone, targeted therapies have been introduced to enhance the effectiveness of treatment. Targeted therapies are designed to interfere with specific molecules that drive cancer cell growth and survival. In gastric cancer, HER2-positive tumors are a key target.
One of the most significant advances in the treatment of advanced gastric cancer is the addition of trastuzumab (Herceptin) to chemotherapy in patients with HER2-positive gastric cancer. Trastuzumab is a monoclonal antibody that binds to the HER2 receptor, a protein that is overexpressed in some gastric cancers, leading to uncontrolled cell growth. The ToGA trial demonstrated that adding trastuzumab to chemotherapy improved overall survival in patients with HER2-positive metastatic gastric cancer (Bang et al., 2010).
In addition to trastuzumab, other targeted therapies such as ramucirumab, an anti-angiogenic drug that blocks the VEGF receptor, have been evaluated in advanced gastric cancer. The RAINBOW trial showed that the combination of ramucirumab and paclitaxel improved progression-free survival (PFS) and overall survival compared to paclitaxel alone in patients with previously treated metastatic gastric cancer (Wilke et al., 2014).
Immunotherapy: An Emerging Treatment Option
Immunotherapy has become an exciting and promising option for many cancers, including gastric cancer. Immunotherapy works by stimulating the body’s immune system to recognize and attack cancer cells. In gastric cancer, immune checkpoint inhibitors (ICIs) have shown promise in clinical trials.
The Keynote-059 trial demonstrated the efficacy of pembrolizumab (Keytruda), an anti-PD-1 monoclonal antibody, in patients with advanced or metastatic gastric cancer. The trial found that pembrolizumab led to a durable response in some patients with tumors expressing PD-L1 (Fuchs et al., 2018). Pembrolizumab has since been approved for use in certain cases of advanced gastric cancer, particularly in patients with high PD-L1 expression and microsatellite instability-high (MSI-H) tumors.
Another immune checkpoint inhibitor, nivolumab (Opdivo), has been shown to improve survival in patients with advanced gastric cancer in the CheckMate-649 trial. This study demonstrated that nivolumab, when combined with chemotherapy, resulted in improved overall survival compared to chemotherapy alone in patients with advanced gastric cancer (Janjigian et al., 2021).
Immunotherapy is generally well tolerated, with side effects that include fatigue, rash, and immune-related adverse events, such as colitis and hepatitis. However, unlike traditional chemotherapy, immunotherapy has the potential to produce long-lasting responses in some patients, making it an exciting option for patients with advanced gastric cancer.
Read About Immunotherapy Success Rate For Gastric Cancer on OncoDaily
Palliative Care: Improving Quality of Life
For patients who are no longer responding to treatment or who are too ill to undergo chemotherapy, palliative care plays a crucial role in improving quality of life. Palliative care is focused on managing symptoms, reducing pain, and providing psychological support to patients and their families. It aims to help patients live as comfortably as possible, regardless of the cancer’s progression.
In advanced gastric cancer, palliative care may involve:
- Pain management, such as opioid medications or nerve blocks, to relieve cancer-related pain.
- Nutritional support, especially for patients who have difficulty swallowing due to tumor obstruction.
- Psychosocial support for patients and families to cope with the emotional burden of cancer.
- Palliative care is typically provided alongside other cancer treatments and is an integral part of comprehensive cancer care.
Conclusion: Treatment Choices When Surgery Is Not an Option
While surgery remains the most effective treatment for early-stage gastric cancer, many patients are diagnosed at advanced stages when surgery is no longer an option. For these patients, chemotherapy, targeted therapy, immunotherapy, and palliative care provide crucial alternatives to manage the disease and improve the quality of life.
Chemotherapy remains the mainstay of treatment for advanced gastric cancer, but new options like targeted therapies and immunotherapies are rapidly changing the treatment landscape. Drugs like trastuzumab, ramucirumab, pembrolizumab, and nivolumab offer new hope for patients with HER2-positive gastric cancer and those with PD-L1-positive or MSI-H tumors. Additionally, palliative care provides comfort and support for patients facing the final stages of the disease.
As research into gastric cancer continues, new treatments and clinical trials will undoubtedly improve outcomes for patients who are not candidates for surgery, offering more options and hope for survival and symptom control.
Patients facing advanced gastric cancer should discuss their options with a multidisciplinary team of specialists to determine the best treatment plan based on their specific condition, tumor characteristics, and overall health. New therapies and clinical trials offer hope, and ongoing research continues to advance the field, improving survival rates and the quality of life for many patients.
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Written by Armen Gevorgyan, MD