In the USA, a standard of care is postoperative chemoradiation for resected GEJ and gastric cancers based primarily on the results of the Intergroup 116 trial [11]. This trial randomized 556 patients to adjuvant chemotherapy and chemoradiation with bolus 5-FU/leucovorin versus observation alone following surgery. Patients who received adjuvant chemoradiation had an improvement in 3-year OS (51 vs. 40 %, p = 0.005).

Despite this positive result, this trial is frequently criticized because of the relatively suboptimal surgical resections that were performed—54 % of patients had less than a D1 or D2 resection, which is less than a complete dissection of the involved lymph nodes. It has been argued that radiation in this setting compensated for inadequate surgery because the greatest impact of adjuvant chemoradiation was a reduction in local recurrence of cancer. This is underscored by the observation that the major impact of postoperative chemoradiotherapy is to reduce local tumor recurrence. Such benefits may not be seen for radiotherapy if a more complete D1 or D2 surgical resection is undertaken.

Based on the results of the Intergroup trial, the Cancer and Leukemia Group B launched and completed the 80101 trial, a trial attempting to intensify the chemotherapy delivered as postoperative therapy. Five hundred and forty six gastric cancer patients were enrolled. The standard arm consisted of systemic bolus 5-FU/leucovorin preceding and following chemoradiation with infusional 5-FU while the experimental arm changed the systemic chemotherapy by replacing the bolus 5-FU/leucovorin with the ECF regimen. Results have been presented in abstract form and reveal no improvement in 3-year DFS (47 vs. 46 %) or OS (52 vs. 50 %) with the addition of an anthracycline and platinum compound to 5-FU [17]. These results are also virtually identical to the outcomes in the adjuvant chemoradiation arm of the Intergroup 116 trial. These results indicate that 5-FU monotherapy, combined with radiation, remains a standard of care, in particular in patients who have undergone less than a D1 or D2 resection. Adding cisplatin and epirubicin to adjuvant chemotherapy failed to improve survival. ECF should not be used as an adjuvant chemotherapy regimen, although pre- and postoperative ECF without radiation therapy remains a care standard. These results are summarized in Table 21.2.

An attempt to answer the question of whether there is a benefit for postoperative radiation in patients who have undergone a D2 gastrectomy was made by investigators of the Korean Adjuvant Chemoradiation Therapy in Stomach Cancer (ARTIST) trial. This study randomized 458 patients with stage IB-IV gastric cancer who had undergone D2 resections to either six cycles of adjuvant chemotherapy with the oral 5-FU pro-drug capecitabine and cisplatin or to two cycles of capecitabine/cisplatin before and after chemoradiation with capecitabine (Table 21.2; [18]). This study must of course be interpreted cautiously in a Western context but it does potentially offer insight into the benefit of radiation under these circumstances.