More Controversy than Ever – Challenges and Promises Towards Personalized Treatment of Gastric Cancer

Clinical decisions for the treatment of localized gastric cancer have become much more sophisticated and complicated than ever. Two recent large-scale trials published in NEJM for East Asian 1 and Western patients 2 strongly support the routine use of adjuvant chemotherapy. However, differences in design, extent of surgery, kind of chemotherapy timing of administration, and survival results in the two trials as well as potential differences in genetic background of Asian and Western gastric caner patients raise critical questions and grow confusion and uncertainty. Which is the optimum update treatment for Western patients? Is the Japanese model with standardized D2 surgery followed by one year S-1 chemotherapy applicable in the West and can it produce similar excellent results or should treatment decisions be based on Western patients data from the UK MAGIC trial 2 and the USA INT-0116 trial? 3 This editorial approaches this critical question towards a live-saving decision. Emphasis is given to current advances in network biology, 4 cancer genome and functional studies 5–10 as well as a current comprehensive benchto-bedside genomic-based protocol for biomarkersbased personalized treatment of gastric cancer. 11 The landmark ACTS-GC Japanese study demonstrated excellent survival results with primary standardized D2 surgery followed by S-1 chemotherapy for advanced stages II and III. 1 Most patients (89%) had node-positive disease; these advanced tumor stages are associated with poor prognosis in the West. 12 Despite this advanced disease, the overall 3year survival rate was 70% after D2 surgery alone and 80% in the S-1 chemotherapy group. The hazard ratio for death in the S-1 group, as compared with the surgery-only group, was 0.68 (95% CI, 0.52–0.87; p = 0.003). Because of this significant survival difference the trial was stopped. Local control is now increasingly recognized to have a crucial role in the treatment strategy not only of gastric cancer 13–15 but also for many other solid tumor including breast cancer despite the use of adjuvant treatment. 16,17 Appropriate surgery alone