Adding radiotherapy to chemotherapy after curative resection with D2 lymph node dissection improved disease-free survival in node-positive patients.

Despite poor overall long-term survival in patients with gastric cancer, adjuvant therapy improves survival after gastrectomy. Adjuvant approaches include postoperative 5-fluorouracil chemotherapy and radiotherapy in the U.S., pre- and postoperative chemotherapy in Europe, and adjuvant chemotherapy in Asia. The role of postoperative radiotherapy in adjuvant management has been controversial, given that the quality of surgery varies between Eastern and Western countries. Also, some argue that the superior survival associated with systematic D2 lymph node resection — comprising removal of greater and lesser curvature, gastrohepatic, splenic, and celiac nodes — negates any potential benefit for postoperative radiotherapy.

To investigate this issue, researchers in Korea conducted the phase III, multicenter, randomized, ARTIST trial, which compared adjuvant capecitabine and cisplatin with or without radiotherapy in 458 patients with gastric cancer after curative resection with D2 lymph node dissection. Most patients (88.3%) were node positive, 57.8% had stage I–II disease, and 42.2% had stage III–IV disease. One group of patients received six, 3-week cycles of capecitabine (2000 mg/m² daily on days 1–14) and cisplatin (60 mg/m² on day 1). The other group received 2 cycles of the same chemotherapy, followed by 5 weeks of capecitabine (1650 mg/m² daily) plus radiotherapy (4500 cGy in 180 daily cGy fractions) and 2 more cycles of chemotherapy. The primary endpoint was 3-year disease-free survival (DFS).

Among all patients, DFS was similar with radiotherapy plus chemotherapy or chemotherapy alone (78.2% and 74.2%). However, among node-positive patients, DFS was improved with radiotherapy plus chemotherapy versus chemotherapy alone (77.5% vs. 72.3%; P=0.0365); this improvement was retained in multivariate analysis (hazard ratio, 0.6865; P=0.0471). Rates of therapy completion were comparable with radiotherapy plus chemotherapy or chemotherapy alone (81.7% and 75.4%).

Comment: Adjuvant therapy improves survival in gastric cancer and is standard therapy. Asian and European trials demonstrate a survival benefit for chemotherapy alone, even without postoperative radiotherapy. The current trial now reopens the debate that, even after D2 gastrectomy, node-positive patients might benefit from adjuvant chemotherapy and radiotherapy. These data suggest that the benefit of radiotherapy seen in U.S. trials might not merely be a function of inadequate surgery performed in the U.S. Whether or not the overall 5% difference in DFS is meaningful and holds up under further study awaits completion of the authors’ follow-up trial, which will compare chemotherapy with or without radiotherapy in node-positive patients only.

Source: Journal Watch Oncology and Hematology