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EDITORIAL |
From the University of Missouri—Ellis Fischel Cancer Center, Columbia, Missouri.
Correspondence: Dr. David M. Ota, University of Missouri—Ellis Fischel Cancer Center, 115 Business Loop 70 West, Columbia, MO 65203; Fax: 573-884-6054.
In this issue of the Annals of Surgical Oncology, Lowy et al. describe their phase II study of preoperative infusional 5-fluorouracil (5FU) and external beam radiation therapy (EBRT) for locally advanced gastric cancer.1 Twenty-three of 24 patients completed the planned preoperative course of therapy according to the protocol, demonstrating that the therapy is well-tolerated and the postoperative complication rate is acceptable. The authors have provided a rationale for preoperative chemoradiotherapy for patients who are appropriate candidates for surgical resection. The first reason is that the recent Intergroup gastric adjuvant trial INT-0116 has shown that postoperative adjuvant chemoradiotherapy produces a significant increase in 5-year survival compared with observation alone following gastric resection with curative intent.2 The second reason in favor of preoperative therapy is that patient tolerance is improved. According to Lowy et al., 88% of their patients received a full course of chemoradiotherapy, whereas the Intergroup Trial, in which therapy was given postoperatively, had a 65% completion rate. Postoperative adjuvant therapy depends on postoperative recovery after a major upper gastrointestinal surgery, and if 35% of patients cannot complete adjuvant therapy, another approach—such as preoperative therapy—should be considered.
There may be further advantages for preoperative chemoradiotherapy for gastric cancer. Surgical resection of gastrointestinal tumors should include complete removal of both macroscopic and microscopic disease. The desirability of an R0 resection vs. R1/R2 has been well described. An R0 resection is defined as one in which all margins are histologically free of tumor. An R1 resection is one in which microscopic residual disease been left behind. An R2 resection is defined as gross residual disease. An R0 resection is always preferred, and leads to improved survival. One of the main advantages of preoperative therapy is the possibility of increasing the R0 resection rate for gastric cancer. The recent Dutch randomized trial showed that without preoperative therapy, surgery resulted in an R1/2 resection rate of 11%.3 Because imaging studies will continue to improve, surgeons will be better able to determine preoperatively whether an R0 resection is feasible. If preoperative diagnostic testing can show that it is unlikely that an R0 resection can be done, then preoperative therapy should be considered. After complete surgical resection, then postoperative systemic chemotherapy can be considered.
Preoperative therapy for gastric cancer has many attractive advantages, but further investigations are needed to demonstrate that such an approach will improve survival. Improved preoperative staging methods are needed. Lowy et al. used endoscopic ultrasonography, CT scanning, and laparoscopy. Such a work-up is necessary for preoperative therapy because of the high incidence of systemic disease. Bonenkemp et al.3 reported that 29% of their eligible surgical patients were discovered at laparotomy to have peritoneal, hepatic, or distant lymph node metastases. These results point out the need for improved staging methods. In Lowy’s report, progression to stage IV disease occurred in 4 of 24 patients during local regional treatment, and it is unlikely that those patients would have benefitted from earlier surgical resection, because systemic disease developed so rapidly in those cases. For preoperative therapy to become the standard of care for resectable gastric cancer, a randomized trial is needed to show that it provides either improved tolerance to therapy or a survival benefit. Although the Intergroup postoperative adjuvant chemoradiotherapy adjuvant trial has shown that there is improved survival for resected adenocarcinoma of the stomach and gastroesophageal junction, further investigations are needed to improve tolerance to adjuvant therapy. The preoperative therapy described by Lowy et al. eventually may be an important strategy.
Received for publication April 17, 2001. Accepted for publication April 18, 2001.
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