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Aggressive Surgical Therapy for Metastatic Disease Is Appropriate in the Current Management of Melanoma

Aggressive Surgical Therapy for Metastatic Disease Is Appropriate in the Current Management of Melanoma

Small bowel metastases from melanoma are uncommon. While the authors reference two studies that reported a large proportion of patients with small bowel metastases, the true incidence of gastrointestinal (GI) lesions in melanoma patients is much lower. The two reports referenced[1,2] were autopsy studies, and thus reflect a specific subset of patients: those who died of their disease. In clinical series, the actual reported incidence of intestinal metastases is less than 10%.[3-5] Patients with disseminated metastases have a much higher incidence of GI involvement, and it is this subset of patients to whom the authors refer.

Rise in Aggressive Surgery

The management of stage IV melanoma has undergone a paradigm shift in recent years, particularly in patients with oligometastatic disease. In the past, patients with visceral metastases were considered surgically unresectable and referred for systemic therapy or palliative care. Median survival in patients with best known systemic treatment and visceral metastases is currently between 6 and 9 months, and there has been minimal improvement in systemic treatment options in the past 20 years. Recently, as the by-product of a number of trials mandating that patients be rendered stage IV no evidence of disease€ prior to treatment, it has become evident that a subset of patients can have a markedly prolonged survivalas much as 40 monthsafter complete surgical resection alone.

The difference between the patient reported and the truly extirpative approach to surgical therapy is that this patient presented with bleeding, and therefore resection was palliative in his case. Palliative surgery for melanoma has been reported for decades, and few would argue against its use. Surgical intervention to relieve symptoms is the genesis of aggressive, potentially curative surgical therapy, since anecdotal evidence from patients treated for palliation identified individuals with relatively long-term survival.

The result of these anecdotal findings has been to increase the number of patients undergoing aggressive surgery for limited, surgically resectable, metastatic disease. The authors report a patient who, in some respects, characterizes this aggressive surgical approach. Although the acute need in this patient was to manage blood loss induced anemia, the small bowel was the only site of residual disease. Whether it was the authors intent or not, the surgical intervention apparently rendered the patient clinically disease-free. A growing body of literature argues that this approach offers a survival benefit in well-selected patients.[4-8] Similarly, additional recent studies have demonstrated that surgical resection of disease limited to the adrenal glands or the lung can improve survival compared to best systemic therapy.[9,10]

Characterizing Disease Burden

Data have demonstrated that the number of metastases present does not influence outcome as long as disease is completely resected.[7] This approach, however, should be mitigated by a consideration of biologic behavior and appropriate patient selection. As with hepatic metastases from colorectal carcinoma, long disease-free intervals and minimal or no progression over time implies a more indolent course and therefore a patient more likely to benefit from aggressive surgical intervention.

An important consideration is to utilize the best radiographic staging available to characterize the true extent of a patients disease burden. Among a litany of radiographic techniques, the authors allude to small bowel series as a possible tool for the evaluation of patients with GI disease. As they mention, high-quality CT scan, magnetic resonance imaging, capsule endoscopy, and perhaps most importantly, positron-emission tomography (PET)/CT fusion scanning have replaced this cumbersome method of radiographic evaluation.

PET/CT scanning is rapidly evolving into the standard of care for staging patients with melanoma, with recent data indicating an ability to detect lesions greater than 1 cm in size in 98% of patients, compared to 70% for dynamic CT scan.[11] The criticism of PET/CT scanning generally focuses on the false-positive rate, which has been reported to be as high as 60%,[12] although most studies report a much lower percentage. Regardless, with modern imaging, the role of a small bowel series in these patients is essentially obsolete.

Genetic Finding

Park and colleagues offer an extensive discussion regarding new insights into the genetic underpinnings of the propensity for melanoma to metastasize to the small intestine. While these insights may offer little by way of therapeutic opportunities, they contribute enormously to our understanding of the disease. Although these initial findings have not led to improvements in therapy, it is clear that recent advances in our understanding of cancer genetics and targeted therapy have resulted in considerable progress in other diseases, and we can be hopeful that a better understanding of melanoma will lead to similar progress. In fact, genetic analysis has shown that mucosal lesions such as anorectal and vaginal lesions harbor mutations in c-kit up to 40% of the time, indicating a possible therapeutic target in these patients.[13]

The authors acknowledge the difficulty in many instances of differentiating primary melanomas of the small bowel from metastatic lesions. Nevertheless, for patients with limited disease, these genetic insights offer another indication for surgical resection. Resecting these lesions will allow for genetic profiling of the tumors, potentially increasing the number of therapeutic options for these patients, and certainly eliminating particular approaches for those in whom targeted genetic abnormalities are not present.

Concluding Thoughts

The current management of patients with limited disease of the small intestine does not necessarily mandate the determination of primary vs metastatic origin before considering surgical extirpation. While systemic treatment choices may be directed by this differentiation, the benefit of surgical resection in appropriately selected patients currently warrants aggressive intervention for either, as survival may be enhanced regardless of the nature of the disease. Furthermore, genetic profiling and histologic characterization may provide additional information to help guide therapeutic options. As such, the current algorithm for patients with limited disease, minimal surgical risk, and technically resectable lesions should include surgical extirpation as a major component for consideration.

Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References

1. Blecker D, Abraham S, Furth EE, et al: Melanoma in the gastrointestinal tract. Am J Gastroenterol 94:3427-3433, 1999.
2. DasGupta T, Brasfield R: Metastatic melanoma of the gastrointestinal tract. Arch Surg 88:969-973, 1964.
3. Balch CM, Soong SJ, Murad TM, et al: A multifactorial analysis of melanoma. IV. Prognostic factors in 200 melanoma patients with distant metastases (stage III). J Clin Oncol 1:126-134, 1983.
4. Ollila DW: Complete metastasectomy in patients with stage IV metastatic melanoma. Lancet Oncol 7:919-24, 2006.
5. Meyer T, Merkel S, Goehl J, et al: Surgical therapy for distant metastases of malignant melanoma. Cancer 89:1983-1991, 2000.
6. Morton DL, Mozzillo N, Thompson JF, et al: An international, randomized, double-blind, phase 3 study of the specific active immunotherapy agent, onamelatucel-L (Canvaxin™) compared to placebo as a post-surgical adjuvant in AJCC stage IV melanoma. Presented at the Society of Surgical Oncology 59th Annual Cancer Symposium; San Diego, Calif; March 23–26, 2006.
7. Ollila DW, Essner R, Wanek LA, et al: Surgical resection for melanoma metastatic to the gastrointestinal tract. Arch Surg 131:975-980, 1996.
8. Agrawal S, Yao T, Coit DG: Surgery for melanoma metastatic to the gastrointestinal tract. Ann Surg Oncol 6:336-344, 1999.
9. Neuman HB, Patel A, Hanlon C, et al: Stage IV melanoma and pulmonary metastases: Factors predictive of survival. Ann Surg Oncol 14:2847-2853, 2007.
10. Mittendorf EA, Lim SJ, Schacherer CW, et al: Melanoma adrenal metastasis: Natural history and surgical management. Am J Surg 195:363-369, 2008.
11. Reinhardt MJ, Joe AY, Jaeger U, et al: Diagnostic performance of whole body dual modality 18F-FDG PET/CT imaging for N- and M-staging of malignant melanoma: Experience with 250 consecutive patients. J Clin Oncol 24:1178-1187, 2006.
12. Yancovitz M, Finelt N, Warycha MA, et al: Role of radiologic imaging at the time of initial diagnosis of stage T1b-T3b melanoma. Cancer 110:1107-1114, 2007.
13. Curtin JA, Busam K, Pinkel D, et al: Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 24:4340-4346, 2006.
 
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