Background
Phase III RCT (CRITICS). 788 patients with resectable gastric or gastroesophageal adenocarcinoma (stage IB–IVA) enrolled at 56 centers in the Netherlands, Sweden, and Denmark. All patients received 3 preoperative ECX/EOX cycles + D1+ gastrectomy. Randomized 1:1 to postoperative chemotherapy (3 more ECX/EOX cycles) vs chemoradiotherapy (45 Gy + capecitabine + cisplatin). First head-to-head comparison of these two strategies.
Interventions and follow up
Arm A: Perioperative chemotherapy — 3 preop cycles ECX/EOX + D1+ surgery + 3 postop cycles ECX/EOX (total 6 cycles)
Arm B: Preoperative chemotherapy + CRT — 3 preop cycles ECX/EOX + D1+ surgery + 45 Gy/25 fr + capecitabine 575 mg/m² BID (radiation days) + cisplatin 20 mg/m² weekly
Primary endpoint: Overall survival
mFollow up: 61.4 month
Arm B: Preoperative chemotherapy + CRT — 3 preop cycles ECX/EOX + D1+ surgery + 45 Gy/25 fr + capecitabine 575 mg/m² BID (radiation days) + cisplatin 20 mg/m² weekly
Primary endpoint: Overall survival
mFollow up: 61.4 month
Results
OS: 43 vs 37 months, HR 1.01 (95% CI 0.84–1.22), P=.90 — not significant
Postoperative treatment completion: 59% (chemo arm) vs 62% (CRT arm) started postoperative treatment
Postoperative treatment completion: 59% (chemo arm) vs 62% (CRT arm) started postoperative treatment
Adverse events
Main adverse events: Grade 3/4 postoperative (chemo): neutropenia 34% vs 4% (CRT); overall grade 3/4: ~57% (chemo) vs ~45% (CRT). No treatment deaths during postoperative treatment. CRT associated with less hematologic toxicity but similar GI toxicity.
Conclusions
Postoperative chemoradiotherapy did not improve OS compared to postoperative chemotherapy in resectable gastric cancer treated with adequate preoperative chemotherapy and surgery, suggesting perioperative chemotherapy alone is sufficient and addition of postoperative radiation provides no survival benefit.
Key Limitations
Key Limitations: Poor postoperative treatment compliance in both arms (~40% did not complete planned postoperative therapy) — underpowering and diluting any potential benefit. Only D1+ (not D2) dissection was mandated; true D2 rate unknown. ECX/EOX chemotherapy backbone is now largely replaced by FLOT. The trial cannot answer whether CRT improves outcomes after FLOT-based perioperative therapy, which is the current standard.
Clinical Context
CRITICS, together with ARTIST, provides strong evidence against routine postoperative CRT after adequate perioperative chemotherapy and surgery. These results have largely confined adjuvant CRT to scenarios with inadequate lymph node dissection (≤D1) or incomplete resection. Ongoing investigations focus on adding immunotherapy (CheckMate 577, KEYNOTE-585) to perioperative strategies.
References
References: Cats A et al, Lancet Oncol 2018 (CRITICS)