Neoadjuvant and Adjuvant Therapy for Gastric Cancer

SUMMARY

Gastric cancer is the fifth most common cancer worldwide, with the greatest incidence in East Asia. Survival outcomes are better in Asian countries when compared to the United States. This difference in survival may be related to the presence of mass screening programs in Asia, which allows for detection at an earlier stage and the use of a more extensive surgical approach (ie, D2 resection). Risk factors for developing gastric cancer include: diets high in salt/salt-preserved foods or processed meats, obesity, smoking, H. pylori infection, EBV, prior gastric surgery, radiation exposure, and positive family history.

According to the latest edition of TMN staging, gastric cancer includes tumors arising more than 5 cm distally of the GEJ or within 5 cm of the GEJ but without extension to the esophagus or GEJ. Diagnostic work-up includes: EGD with biopsy; basic labs; CT chest/abdomen/pelvis with oral and intravenous contrast; EUS if no M1 disease is identified; PET-CT if there is no M1 disease and if clinically indicated; and diagnostic laparoscopy with cytology for clinical stage T1b or higher.

The mainstay of treatment is surgical resection. Laparoscopic approach is preferred over open gastrectomy due to lower complication rates and similar survival outcomes. Current NCCN guidelines recommend a D1 or a modified D2 lymph node dissection with at least 15 lymph nodes removed for examination. Systemic chemotherapy is required in locally advanced gastric cancer (T3-T4 or node positive) and should be considered in T2N0 disease with high-risk features. Currently, there is no global consensus on the optimal treatment approach. Data from various trials have shown benefit for each approach. Regional preferences are: perioperative chemotherapy in Europe; adjuvant chemoradiotherapy in the United States; and adjuvant chemotherapy in Asia. In an effort to better define the optimal treatment approach, several randomized clinical trials are being conducted. According to the current NCCN guidelines, the following treatment approaches are acceptable and are supported by data in the trial listed in parentheses:

• Perioperative chemotherapy

° 5-FU/cisplatin (French FNLCC/FCCD trial)⁴⁴ or

° ECF (MAGIC trial)⁴² or

° ECF modifications: EOX, EOF, ECX (REAL-2 trial)⁴³

• Adjuvant chemoradiotherapy

° 5-FU/leucovorin sandwiched with 5-FU-based chemoradiation (INT-0116 trial)⁴⁵

• Adjuvant chemotherapy (after D2 resection)

° Capecitabine/oxaliplatin (CLASSIC trial)⁵² or

° Capecitabine/cisplatin (ARTIST trial)^48,49