Second malignancies after a gastrectomy for gastric cancers: the effects of adjuvant therapies

Second malignancy after gastrectomy has become one of the important issues in the management of gastric cancer patients. However, the effect of adjuvant therapies has never been surveyed, although there have been many reports on second malignancy after chemotherapy of other malignancies. Between 1979 and 1995, 574 patients with gastric cancer underwent gastrectomies in our department. 563 patients (98.1%) were completely followed-up, and the incidence of second malignancy after gastrectomy was assessed with special emphasis on the effect of adjuvant therapies, namely benefits versus carcinogenesis. The overall postsurgical survival rate was 62.5%, and the survival rate of patients with stage 2-4 cancer was significantly higher in the adjuvant therapy groups than in the surgery alone group. The overall incidence rate of a second malignancy was 3.20% (18/563), including 4 colorectal, 3 liver, 3 head and neck, and 8 other malignancies, and 3.90% (9/231) for the surgery alone group, 1.94% (3/155) for the chemotherapy group, 3.68% (6/163) for the chemoimmunotherapy group, and 0% (0/14) for the immunotherapy alone group. There were no statistical differences in the incidence rates between these 4 groups. The mean duration until the occurrence of second malignancy was 5.1 years for the surgery alone group, 8.6 years for the adjuvant therapy group (9.3 years for chemotherapy and 8.1 years for chemoimmunotherapy; p < 0.1, surgery alone vs. adjuvant therapy). The overall mean actuarial risk of developing a second malignancy was 6% at 5 years and 18% at 10 years. Multivariate analysis demonstrated that chemotherapy decreased the risk of death due to gastric cancer (risk ratio = 0.67, p = 0.017) and the risk of a second malignancy (risk ratio = 0.52, p = 0.261). Oral fluoropyrimidines were found to be particularly effective at decreasing the risk of death due to gastric cancer (risk ratio = 0.66, p = 0.012) and a second malignancy (risk ratio = 0.38, p = 0.136). However, intravenous chemotherapy was demonstrated to have no influence on survival (risk ratio = 0.93, p = 0.692) or a second malignancy (risk ratio = 0.58, p = 0.500). There was no evidence of an increased risk for a second malignancy following adjuvant chemotherapy. Adjuvant chemotherapy with oral fluoropyrimidines was suggested to contribute to the improved survival of patients with stage 2-4 gastric cancer, and to have a decreased the risk of a second malignancy.