Does Resection Prolong Survival in Patients with Neuroendocrine Tumors with Isol
Does Resection Prolong Survival in Patients with Neuroendocrine Tumors with Isolated Hepatic Metastases?
ABSTRACT & COMMENTARY
Synopsis: In this series of 38 patients with isolated hepatic metastases treated at Johns Hopkins, 15 had resectable lesions and 23 did not. Using actuarial analysis, the five-year survival was 73% for the resected group compared to 29% for the unresected group. Hepatic resection in selected patients with isolated liver metastases from neuroendocrine tumors may prolong survival.
Source: Chen H, et al. Isolated liver metastases from neuroendocrine tumors: Does resection prolong survival? J Am Coll Surg 1998;187:88-92.
Neuroendocrine tumors are uncommon, but one typical feature is their predisposition to metastasize to the liver. In this report of the experience at a single institution (Johns Hopkins), the data from 38 patients with isolated liver metastases from carcinoid, islet cell, or other neuroendocrine tumors was examined in the context of whether surgical resection of the isolated liver metastasis resulted in prolonged survival. Of these patients, 15 underwent complete resection. The remaining 23 were considered unresectable, either by CT scan or by surgical exploration. The groups (resected vs non-resected) were comparable with regard to volume of hepatic metastasis and other clinical features including age, pathology, primary tumor site, and percentage of liver involved. All resections were complete (lobectomy, n = 3; segmentectomy, n = 1; wedge resection, n = 11) and there were no operative deaths. Patients who underwent resection had a significantly longer survival than those who did not. By actuarial survival analysis, those who underwent liver resection had a higher five-year survival (73% vs 29%).
Of the 15 resected patients, 10 developed recurrence (9 in the remaining liver tissue and 1 in the mesentery). The median time to recurrence was 21 months. Four of those with hepatic recurrence were re-resected, and one of these had yet another recurrence that was once again resected.
COMMENTARY
Surgical management of solitary hepatic metastases has become more widely accepted as potentially curative in patients with colorectal carcinoma as new surgical techniques have developed.1,2 The strategy is based upon the biology of colorectal cancers that tend to spread to the liver before disseminating more generally. Neuroendocrine tumors share this property, and, theoretically, patients with hepatic metastases might also be cured by surgical resection. Neuroendocrine tumors are thought to have more indolent growth characteristics than colorectal cancers, and, thus, even a non-curative resection might be expected to enhance survival. Furthermore, neuroendocrine tumors that produce hormones such as insulin or glucagon, or other biologically active peptides, might have significant reduction in the production of these hormones by debulking, and a surgical approach might offer palliation. However, these tumors are so uncommon that it is difficult to demonstrate that such an approach actually results in greater survival.
This series highlights the problems. A total of 38 patients with neuroendocrine tumors metastatic to the liver were seen within a 10-year period at a major cancer center. In these patients, the primary had already been resected and the only known disease was in the liver. Thus, each patient was considered a candidate for curative surgery. However, only 15 had resectable lesions, and the other 23 could not, for one reason or another, have their tumor resected. Chen and colleagues make a case that because most of the demographic and prognostic features (such as the size of the hepatic metastasis) were comparable in the two groups, a survival difference could be attributed to the surgical approach. However, despite the comparable tumor burdens, unresected patients might fall into a less favorable category for the same reasons that they have unresectable tumors (e.g., central location, tumors that extend into two lobes, etc.). Thus, the preoperative evaluation might have defined two different prognostic groups, independent of the hepatic resection. This is highlighted by the fact that two-thirds of the resected patients had disease recurrence and only five remained disease free.
This, however, does not diminish the importance of the series. First of all, because neuroendocrine tumors are uncommon, it is unlikely that a prospective, randomized trial could be accomplished, even by a large cooperative group. Yet, despite the uncommon occurrence of these tumors, when they do present, it is not uncommon to be faced with just this question. How do you manage metastatic disease?
Chemotherapy, such as with streptozocin and doxorubicin, have been modestly effective,3 but responses are of limited duration and the drugs may produce unacceptable toxicity. Radiolabeled somatostatin analogs (such as 111In-pentetreotide) have proven effective at reducing symptoms, but have not yet been shown to prolong survival.4 Interferon-a can palliate symptoms, but generally does so without inducing a dramatic antitumor effect. Thus, if surgical intervention is possible, it remains a reasonable approach to offer palliation, and even possibly a chance for cure. However, one cannot conclude from the current paper that surgery provides a survival advantage for patients with metastatic neuroendocrine tumors. More accurately, patients who have surgically resectable lesions are more likely to live longer than those who don't.
References
1. Rosen CB, et al. Ann Surg 1992;216:492-505.
2. Scheele J, et al. Surgery 1991;110:13-29.
3. Moertel CG, et al. N Engl J Med 1992;326:519-523.
4. McCarthy KE, et al. Cancer J Sci Am 1998;4: 94-102.
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