KEY POINTS
- This multicenter retrospective study included 670 patients with cT2–4/N+ M0 gastric or gastroesophageal junction adenocarcinoma treated between 2012 and 2022 with neoadjuvant therapy followed by R0 gastrectomy and D2 lymphadenectomy. Patients received chemotherapy alone (n=339), chemoimmunotherapy (n=233), or chemoradiotherapy (n=98).
- The chemoradiotherapy group received IMRT or VMAT to the primary tumor and regional lymphatics to 45 Gy in 25 fractions, usually with concurrent oral S-1; 57/98 patients (58.2%) also received 2–6 cycles of induction or consolidation chemotherapy.
- Pathological complete response was highest after chemoradiotherapy at 26.5%, compared with 16.3% after chemoimmunotherapy and 7.4% after chemotherapy alone (P<.001). All 670 patients ultimately underwent R0 resection.
- At a median follow-up of 40.7 months, five-year overall survival was 80.4% with chemoradiotherapy versus 57.3% with chemotherapy and 50.8% with chemoimmunotherapy; both comparisons with chemoradiotherapy were significant at P<.001.
- Five-year disease-free survival was likewise higher after chemoradiotherapy at 63.9%, versus 50.0% with chemotherapy (P=.019) and 44.0% with chemoimmunotherapy (P=.034). Five-year distant metastasis-free survival was 77.9%, 59.3%, and 53.1%, respectively.
- The apparent advantage was not driven by superior local control: three-year local control was 87.4% with chemoradiotherapy, 90.2% with chemotherapy, and 91.6% with chemoimmunotherapy, with no significant intergroup differences. This makes the strong distant-control and survival associations particularly difficult to interpret causally in a retrospective dataset.
- Grade ≥3 treatment-related toxicity was similar across groups: 15.3% with chemoradiotherapy, 12.1% with chemotherapy, and 12.5% with chemoimmunotherapy (P=.69), with no treatment-related deaths. Chemoradiotherapy caused more low-grade gastrointestinal toxicity, while severe events were predominantly hematologic.
CLINICAL TAKEAWAY
Neoadjuvant chemoradiotherapy produced the highest pathological response rate and was associated with markedly better long-term survival than chemotherapy or chemoimmunotherapy in this cohort. The magnitude of the survival difference is clinically interesting, but retrospective treatment selection, heterogeneous systemic regimens, era effects and baseline imbalances make prospective randomized confirmation essential, particularly given prior randomized gastric cancer data.