Postoperative Chemotherapy vs Chemoradiotherapy in Resectable Gastric Cancer


Key Points

  • No significant difference in overall survival was observed with postoperative chemotherapy vs chemoradiotherapy.
  • Postoperative treatment was started by 59% of the chemotherapy group and 62% of the chemoradiotherapy group.

In the Scandinavian phase III CRITICS trial reported in The Lancet Oncology, Cats et al found no benefit of postoperative chemoradiotherapy vs chemotherapy among patients with gastric cancer who had received neoadjuvant chemotherapy. Compliance with postoperative regimens was poor in both groups.

Study Details

In the open-label investigator-initiated trial, 788 patients with stage IB to IVA resectable gastric or gastroesophageal adenocarcinoma from 56 sites in the Netherlands, Sweden, and Denmark were randomized between January 2007 and April 2015 to receive postoperative chemoradiotherapy (n = 395) or chemotherapy (n = 393). Randomization was performed prior to preoperative chemotherapy and was stratified by histologic subtype, tumor location, and study site.

Surgery consisted of radical resection of the primary tumor and at least a D1+ lymph node dissection (ie, dissection of the suprapancreatic lymph nodes along the common hepatic artery and around the celiac axis in addition to D1 lymph node dissection, which entails dissection of the perigastric lymph nodes en bloc with the stomach). Postoperative treatment started within 4 to 12 weeks after surgery.

Chemotherapy consisted of 3 preoperative 21-day cycles and 3 postoperative cycles of epirubicin (50 mg/m² on day 1), cisplatin (60 mg/m² on day 1), or oxaliplatin (130 mg/m² on day 1), and capecitabine (1,000 mg/m² twice daily for 14 days in combination with epirubicin and cisplatin or 625 mg/m² twice daily for 21 days in combination with epirubicin and oxaliplatin) given once every 3 weeks. Chemoradiotherapy consisted of 45 Gy in 25 fractions of 1.8 Gy for 5 weeks with 5 daily fractions per week combined with capecitabine (575 mg/m² twice daily on radiotherapy days) and cisplatin (20 mg/m² on day 1 of each 5 weeks of radiotherapy).

The primary endpoint was overall survival in the intention-to-treat population.

Survival Outcomes

After preoperative chemotherapy, 369 (93%) of 395 patients in the chemoradiotherapy group and 372 (95%) of 393 patients in the chemotherapy group underwent surgery, with potentially curative resection being completed in 326 patients (83%) in the chemoradiotherapy group and 310 patients (79%) in the chemotherapy group. Overall, 245 patients (62%) started postoperative chemoradiotherapy and 233 patients (59%) started postoperative chemotherapy.

At a median follow-up of 61.4 months, median overall survival was 37 months in the chemoradiotherapy group vs 43 months in the chemotherapy group (stratified hazard ratio [HR] = 1.01, P = .90). Overall survival at 5 years was 40% vs 42%. Median event-free survival was 25 months vs 28 months (stratified HR = 0.99, P = .92).

Adverse Events

During preoperative chemotherapy, among all patients, grade 3 adverse events occurred in 47% and grade 4 adverse events occurred in 17%. Death occurred in 13 patients (2%), with causes consisting of diarrhea (n = 2), dihydropyrimidine deficiency (n = 1), sudden death (n = 1), cardiovascular events (n = 8), and functional bowel obstruction (n = 1).

During postoperative treatment, grade 3 and 4 adverse events occurred in 101 (41%) and 10 (4%) of 245 patients in the chemoradiotherapy group and 113 (48%) and 22 (9%) of 233 patients in the chemotherapy group. Nonfebrile neutropenia was more common in the chemotherapy group (34% vs 11%). No deaths were reported during postoperative treatment.

The investigators concluded, “Postoperative chemoradiotherapy did not improve overall survival compared with postoperative chemotherapy in patients with resectable gastric cancer treated with adequate preoperative chemotherapy and surgery. In view of the poor postoperative patient compliance in both treatment groups, future studies should focus on optimising preoperative treatment strategies.”

The study was supported by the Dutch Cancer Society, Dutch Colorectal Cancer Group, and Hoffmann-La Roche.

Edwin Jansen, MD, of the Netherlands Cancer Institute, is the corresponding author for The Lancet Oncology article. 

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