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Page 6 of 9 Ida et al. J Cancer Metastasis Treat 2018;4:22 I http://dx.doi.org/10.20517/2394-4722.2017.75

of patients who did not undergo conversion surgery [30,32,34,35] . Furthermore, whether R0 resection is performed
may greatly affect the prognosis. Yamaguchi et al. analyzed the treatment outcomes of 259 patients with
[30]
stage IV gastric cancer and found that the MST of those who underwent R0 resection (41.3 months) was
significantly better than that of patients who underwent R1 and R2 resection (21.2 months). Sato et al.
[32]
evaluated the treatment outcomes of initially unresectable gastric cancer treated with docetaxel, cisplatin, and
S-1 (DCS) chemotherapy in a clinical trial. Conversion therapy was achieved in 33 of 100 patients (33%), and
R0 resection was performed in 28 (84.8%) patients. The authors focused on the pathological response of the
primary tumor, and the pathological response rate was 78.8%. Furthermore, multivariate analysis showed that
pathological response was the only independent prognostic factor for conversion therapy (P = 0.009). These
findings suggest the clinical significance of performing conversion surgery for stage IV gastric cancer.

VOLUME REDUCTION SURGERY
The JCOG and Korea Gastric Cancer Association conducted an open-label, randomized phase III trial
(JCOG0705/KGCA01) comparing gastrectomy plus chemotherapy vs. chemotherapy alone in patients with
advanced gastric cancer with a single noncurative factor. The patients were randomly assigned to gastrectomy
followed by chemotherapy or chemotherapy alone. The chemotherapy regimen was S-1 plus cisplatin, which is
a standard treatment for advanced gastric cancer. The 2-year OS rate was 31.7% (95% CI, 21.7-42.2) for patients
assigned to chemotherapy alone compared with 25.1% (95% CI, 16.2-34.9) for those assigned to gastrectomy
plus chemotherapy. The median OS was 16.6 months (95% CI, 13.7-19.8) for patients assigned to chemotherapy
alone and 14.3 months (95% CI, 11.8-16.3) for those assigned to gastrectomy plus chemotherapy (HR, 1.09; 95%
CI, 0.78-1.52; P = 0.70). Thus, no evidence in support of volume reduction surgery was found for patients with
advanced gastric cancer, even those with a single noncurative factor .
[36]
The German AIO study group conducted the RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy
alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with
limited metastatic adenocarcinoma of the stomach or esophagogastric junction. This trial is a prospective,
multicenter, randomized, investigator-initiated phase III trial aimed to evaluate the effects of perioperative
chemotherapy with FLOT (5-flourouracil, leucovorin, oxaliplatin, and docetaxel) in chemo naive patients
with limited metastatic disease . If the RENAISSANCE concept proves to be effective, this could potentially
[37]
lead to a new standard therapy for metastatic gastric cancer.

CONCLUSION
Long-term survivors exist among patients who have undergone conversion surgery with R0 resection
for stage IV gastric cancer. Adequate selection of patients with stage IV gastric cancer for conversion
therapy is very important to increase the likelihood of long-term survival. Furthermore, even with
surgery, the prognosis of patients with other involvement of other organs in addition to peritoneal
dissemination is poor. Therefore, surgical intervention in such patients should be performed cautiously.
Further cooperation of specialists, such as surgeons and physicians, is necessary to allow for the
establishment of diagnostic methods, surgery with fewer complications, and development of more
effective agents. In the future, an approach applying the concept of conversion surgery might expand
the eligibility for surgery with curative intent to include even patients with currently considered
unresectable for metastases.

DECLARATIONS
Authors’ contributions
Concept, design, literature search and manuscript preparation: Ida S
Manuscript editing and review: Watanabe M