Commentary (Coia): Management of Small Bowel Adenocarcinoma

Dr. Kummar and her coauthors have tackled the difficult task of reviewing small bowel adenocarcinoma so that we might have a better understanding of this uncommonly encountered malignancy. The task is unusually difficult, not because of the need to critically review reams of publications on the topic, but rather because so little literature exists on the topic of optimal management. Nonetheless, the authors have succeeded in educating the reader on several important issues, including the need for close follow-up of patients with small bowel adenocarcinoma, who are not only at risk for recurrence but also have a relatively high risk of other gastrointestinal tumors. Additionally, the authors identify factors associated with poor prognosis, including age > 75 years, lack of surgical resection, advanced disease stage, and tumor arising in the duodenum.

Pancreatic vs Duodenal Cancer

In a section entitled "Preoperative Chemoradiation," Dr. Kummar and colleagues present the results of a study that Dr. John Hoffman and I, along with others at the Fox Chase Cancer Center, published in 1994. In that study, patients with adenocarcinoma of the pancreas or duodenum were treated with preoperative chemoradiation followed by surgical resection. Only 4 of the 31 patients in that pilot study had duodenal adenocarcinoma.

Two things were remarkable about these four patients with duodenal (mostly periampullary) cancer. First, following resection it was found that all four had a pathologic complete response to 50 Gy and concurrent chemotherapy (fluorouracil [5-FU] and mitomycin [Mutamycin]). In contrast, none of the 13 patients with pancreatic cancer who underwent resection following chemoradiation had a pathologic complete response. In fact, over 60 patients with pancreatic cancer have been treated with chemoradiation followed by resection at the Fox Chase Cancer Center, and none has had a pathologic complete response. It is therefore likely that adenocarcinoma of the duodenum (particularly the periampullary region) is much more sensitive to chemoradiation than adenocarcinoma of the pancreas.

Second, at the time of that publication, all patients were alive, with a median follow-up of 4.5 years. In fact, at a minimum follow-up of over 8 years and a median follow-up of more than 12.5 years, all four patients remain alive without recurrence. Certainly this excellent survival is not seen with pancreatic adenocarcinoma and is better than that reported in the studies reviewed by Kummar et al for duodenal adenocarcinoma managed by surgery alone or surgery followed by chemoradiation.

Treatment Recommendations

Although we cannot draw conclusions from such a small number of patients treated with preoperative chemoradiation, I would offer the following opinions regarding management: The primary management of small bowel adenocarcinoma is surgical resection. Chemoradiation should be a treatment option for patients with adenocarcinoma of the duodenum-especially the periampullary region or ampulla-who are medically inoperable or have surgically unresectable lesions. Patients managed with chemoradiation are likely to have an objective tumor response along with palliation of symptoms (eg, relief of pain or jaundice due to obstruction). Furthermore, some operable patients with unresectable lesions may have significant tumor response to chemoradiation, which may render the lesion resectable. Resection should then be performed when possible.

I would also encourage consideration of preoperative chemoradiation for resectable lesions in a study setting. With further confirmation of the value of preoperative chemoradiation, one might contemplate a registry-type study of patients treated with preoperative chemoradiation, postoperative chemoradiation, or surgery alone for duodenal adenocarcinoma. (A randomized study with sufficient patients could never be completed.)

Conclusions

The rarity of this cancer is quite fortunate. Nevertheless, let us be prepared to optimally treat the unfortunate patient with this diagnosis. The article by Kummar et al gives the clinician the background to recognize that we have work to do in improving outcome for patients with small bowel adenocarcinoma and gives us some direction to achieve this goal.