The article by Drs. Jackson, Mochlinski, and Cunningham is a timely review of the current state of practice in the adjuvant treatment of gastric cancer, a common and deadly disease. Unlike breast and colon cancer, where early detection has a significant impact on outcome, few patients with gastric cancer are actually cured by surgery alone. The data for gastric cancer suggest that even early-stage disease has a poor prognosis.
The concept of using additional therapies to improve both local control and management of systemic metastasis in gastric cancer is obviously attractive. After decades of clinical research, we finally have two positive clinical trials that demonstrate a clinically significant benefit to patients with localized gastric cancer. The problem is that these trials give us conflicting clinical strategies to follow and leave us in the clinic with some confusion as to an optimum approach. This article does a nice job of explaining the two approaches but is somewhat lacking in terms of recommendations on how to proceed from here.
As in any adjuvant setting, it would be most valuable for us to understand which patients actually need adjuvant therapy. Following surgical resection, a subgroup of patients clearly is cured by the surgery alone and, therefore, cannot benefit from adjuvant therapy. If we could develop techniques to define this population, then we would make immediate progress by preventing patients from undergoing unnecessary chemotherapy and radiation.
On the other hand, it would be equally useful (although much more difficult) if we could define a subpopulation of patients who, despite receiving standard adjuvant chemotherapy or radiation, would fail to benefit due to resistance. Thus, one of the goals that remains lost is the definition of the population who will respond to chemotherapy and radiation. When we look at these two clinical trials, only a small subgroup is seen to benefit. By predefining this group, our progress will be much more rapid.
Sorting Out the Data
The two clinical trials presented in this review suggest that both chemotherapy and radiation have a role in the perioperative setting. The problem is that the trials give us two different regimens and dramatically different strategies, both yielding positive results. While the radiation therapy used in the intergroup trial may be making up for less than optimal surgery, no study has clearly demonstrated that radiation is required in the postoperative adjuvant setting. Likewise, the European MRC Adjuvant Gastric Infusional Chemotherapy (MAGIC) study does not incorporate radiation at all, but uses multiagent chemotherapy.
So what are we to do when faced with a gastric cancer patient? Just this week I saw one such patient seeking a third opinion. He had been given recommendations ranging from no further therapy, to fluorouracil (5-FU) alone, to ECF (epirubicin [Ellence], cisplatin, 5-FU) postchemoradiation and surgery, and I was supposed to sort it all out.
If we add the results of the two trials together, they suggest there may be a role for neoadjuvant chemotherapy and possibly for neoadjuvant radiation therapy, as in other gastrointestinal cancers such as those of the esophagus and rectum. Unfortunately, the currently ongoing randomized clinical trial does not address this issue, as all patients are being treated postoperatively. A study evaluating neoadjuvant chemotherapy and radiation therapy followed by surgery and more chemotherapy would seem to be ideal, given the results of these two clinical trials.