Adjuvant S-1 Chemotherapy for Gastric Cancer and Peritoneal Wash John Spiliotis • Odysseas Zoras Published online: 21 September 2010 Ó Socie ´te ´ Internationale de Chirurgie 2010 In the September issue of the World Journal of Surgery, Ito and colleagues evaluated the efficacy of postoperative S-1 chemotherapy in patients with stage II/III gastric cancer with detection by a real-time reverse transcription poly- merase chain reaction (RT-PCR) of free intraperitoneal cancer cells [1]. Based on the results of a large-scale, appropriately designed, multicenter, Japanese, Phase III, randomized controlled trial (RCT) [2], postoperative S-1 chemotherapy has become a standard adjuvant treatment in Japanese patients with stage II/III gastric cancer after standardized gastrectomy with D2 lymphadenectomy. In this changing treatment study, adjuvant S-1 chemotherapy reduced peri- toneal recurrence in the subgroup analysis. However, that trial was not designed to evaluate the efficacy of S-1 treatment in stage II/III patients with a positive peritoneal wash on RT-PCR. Ito and colleagues [1] looked at whether adjuvant S-1 treatment was effective also in the subgroup of patients with molecular detection of peritoneal micrometastases in patients with gastric cancer by quantifying carcinoembry- onic antigen (CEA) mRNA in peritoneal washes. From a total of 32 patients with CEA mRNA(?) gastric cancer, 20 patients (37.5%) relapsed, 10 of whom showed peritoneal relapse. The authors compared these findings with those of historical controls and found that the 3-year survival rates for the study population and the controls were similar (67.3% vs. 67.1%, respectively). The authors concluded that S-1 monotherapy seems not to be effective in eradi- cating free cancer cells in the abdominal cavity. If this is true, all patients with stage II/III should undergo a peritoneal wash during D2 surgery because CEA mRNA(?) may influence the decision-making about post- operative adjuvant S-1 treatment. However, this is a small retrospective comparison study with historical controls, which suggests major limitations in terms of drawing con- clusions. The authors might better have performed a Phase II trial to assess a potential role of CEA mRNA. If such a study had positive results, a Phase III RCT could then be satisfied. Current efforts to improve oncologic outcomes of patients with stage II/III disease have focused on the addition of adjuvant radiotherapy to S-1 or cisplatin-based combination chemotherapy. Moreover, the positive results of a Phase III trial adding trastuzumab to HER2-positive patients with advanced or metastatic gastric cancer [3] drive new clinical trials of adjuvant treatment with trast- uzumab plus combination chemotherapy. Exciting emerg- ing research explores other mutated genes that influence other signaling pathways, such as HER1 and HER3 downstream pathways as well as signaling pathway net- works important for gastric cancer metastasis. The advent of the latest DNA sequencing technology raises rational optimism for improving outcomes of patients with gastric cancer or other solid cancers [4–15]. Conflict of interest None. References 1. Ito S, Kodera Y, Mochizuki Y et al (2010) Phase II clinical trial of postoperative S-1 monotherapy for gastric cancer patients with J. Spiliotis (&) Department of Surgery (B Unit), ‘‘METAXA’’ Cancer Memorial Hospital, Piraeus, Greece e-mail: jspil@in.gr O. Zoras Department of General Surgery, University Hospital of Heraklion, Medical School, University of Crete, Heraklion, Crete, Greece 123 World J Surg (2011) 35:468–469 DOI 10.1007/s00268-010-0807-7