The Evolving Role of Surgery in Stage IV Gastric Cancer

From Palliation to Potential Cure

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Introduction: Redefining the Boundaries

For decades, stage IV gastric cancer—characterized by distant metastasis or peritoneal involvement—was considered uniformly terminal. Treatment focused solely on palliative chemotherapy and symptom management, with surgery reserved for emergencies like bleeding or obstruction. This fatalistic outlook is now changing dramatically. Groundbreaking research reveals that select patients with advanced disease may achieve meaningful survival benefits through aggressive, treatment-oriented surgical approaches combined with systemic therapy 1 4 . This paradigm shift stems from sophisticated biological classifications, advanced surgical techniques, and novel therapies that convert previously inoperable cases into resectable ones.

Key Concepts: Decoding Stage IV Complexity

Biological Subtypes Matter

Stage IV gastric cancer is not a monolithic entity. Researchers classify it into distinct subtypes with different surgical implications:

  1. CY+ (Positive Peritoneal Cytology): Microscopic cancer cells in abdominal fluid without visible tumors.
  2. Limited Peritoneal Carcinomatosis: Visible abdominal implants.
  3. Distant Lymph Node Metastases: Involvement beyond regional nodes.
  4. Hematogenous Metastases: Isolated liver/lung lesions.
The Conversion Therapy Revolution

The most significant advance is conversion therapy—using chemotherapy, targeted drugs, or immunotherapy to shrink tumors enough to enable radical surgery.

Success depends on:

  • Patient Selection
  • Systemic Therapy Response
  • Radical Resection

Oligometastatic Disease

Patients with ≤3 metastatic lesions in one organ ("oligometastatic") show superior outcomes with aggressive local therapy. The median survival for this group can reach 31 months—double that of polymetastatic disease 5 .

In-Depth Look: The Landmark SEER-Matched Analysis

A pivotal 2022 study interrogated the U.S. National Cancer Institute's SEER database to quantify surgery's impact on stage IV gastric cancer 8 .

Methodology: Precision Through Matching
  1. Cohort Identification: 6,284 stage IV gastric adenocarcinoma patients (2010–2015).
  2. Propensity Score Matching (PSM): 514 surgical patients matched 1:1 with non-surgical controls.
  3. Groups Compared: Cancer-directed surgery vs. Chemotherapy/palliative procedures only.
  4. Outcome Measured: Overall survival (OS).
Table 1: Patient Characteristics After Matching
Variable CDS Group (n=432) No-CDS Group (n=432)
Median Age 64.5 years 64.6 years
Liver Metastasis 27.2% 28.1%
Peritoneal Mets 23.1% 24.0%
Chemotherapy Use 69.1% 68.3%
Results: Surgery's Survival Signal
  • Median OS: 10 months (CDS) vs. 6 months (no-CDS) (p<0.001)
  • 2-Year Survival: 18.2% (CDS) vs. 4.1% (no-CDS)
  • Key Predictors: Poor tumor differentiation and chemotherapy omission worsened survival
Analysis: Contextualizing the Findings

This study provided real-world validation that surgery can extend life in stage IV gastric cancer. However, the modest absolute gain (4 months) underscores critical nuances:

  • Benefit was strongest in patients receiving chemotherapy
  • The 2-year survival gap suggests surgery enables a durable remission subset

Surgical Approaches: Precision Tactics for Advanced Disease

Conversion Surgery Protocol

1

Induction Therapy

2

Reassessment

3

Radical Resection

4

Adjuvant Therapy

Table 2: Survival by Metastatic Subtype After Aggressive Therapy
Subtype Median OS (Months) 5-Year Survival
CY1 Converted to CY0 31.6 25.3%
Liver Mets (Resected) 21.4 20.1%
Peritoneal PCI <7 + HIPEC 18.9 15.8%
Unresectable Metastasis 10.2 0%

The Scientist's Toolkit: Key Innovations Enabling Progress

Table 3: Essential Technologies Driving Surgical Advances
Tool Function Impact
Staging Laparoscopy Detects occult peritoneal cells (CY+) Avoids futile laparotomy; guides therapy
HIPEC Heated chemotherapy baths during surgery Kills microscopic peritoneal residues
Liquid Biopsies Tracks circulating tumor DNA (ctDNA) Monitors treatment response; predicts relapse
CLDN18.2 Biomarker Identifies tumors for zolbetuximab targeting Enables targeted conversion therapy
AI-Powered CT Analysis Predicts occult metastasis (AUC=0.92) Improves patient selection

Future Directions: The Road Ahead

Molecular Personalization

The 2025 approval of zolbetuximab (targeting CLDN18.2) marked a turning point. Emerging targets like FGFR2b (bemarituzumab) and HER2 (trastuzumab deruxtecan) promise further gains.

Trials Poised to Reshape Care
  • MATTERHORN (NCT04592913): Testing perioperative durvalumab + FLOT chemotherapy.
  • KUNLUN (NCT04550260): Immunotherapy for esophageal/gastric junction tumors.
  • DANTE/ESOPEC: Refining multimodal protocols for oligometastatic disease .

Conclusion: A Cautious but Hopeful Shift

Treatment-oriented surgery in stage IV gastric cancer is no longer an oxymoron. Rigorous patient selection, biomarker-driven therapy, and radical resection can yield survival previously deemed unattainable. As Korean consensus guidelines emphasize: "Conversion therapy provides survival benefit for selected metastatic GC patients responding to systemic therapy and achieving R0 resection" 2 . While cure remains elusive for most, the goalposts have moved—from palliation toward durable control, and for a subset, long-term remission.

This article is dedicated to the patients and clinical researchers pioneering this new frontier in gastric cancer care.

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