Metastatic melanoma to the small bowel is a disease traditionally associated with dismal prognosis and is accompanied by substantial adverse events, such as obstruction, abdominal pain, perforation and chronic GI bleeding. In the context of these symptomatic indications, small bowel metastasectomy is often performed. This series provides the accounts of 15 patients treated at our institution who underwent small bowel resection for metastatic melanoma and received perioperative immunotherapy or targeted therapy. To our knowledge, this is largest case series of patients who underwent surgical resection for GI melanoma metastases that all received perioperative immunotherapy and presents an updated perspective of the utility of metastasectomy for small bowel metastasis in the age of novel immunotherapeutic agents as standard systemic treatment.

Most notably, the median survival following operative intervention observed in this case series (overall 30.1 months, curative 48.5 months, palliative 23.7 months) greatly surpasses those reported in prior studies concerning patients receiving surgical resection of metastatic melanoma to the gastrointestinal tract [10,11,12]. In a cohort of 68 patients with metastatic melanoma to the GI tract, Agrawal et al. cited a median overall survival of 8.2 months, with the majority of patients (61.4%) treated in the adjuvant setting receiving chemotherapy [10]. Similarly, Mantas et al. reported a median overall survival of 14 months in patients with metastatic melanoma to visceral surfaces that all had received neoadjuvant palliative chemotherapy. Lastly, an investigation by Sanki et al. of 117 patients who underwent surgical resection for GI melanoma metastases yielded a median overall survival of 16.4 months, but adjuvant therapy was only administered to a portion of patients (chemotherapy: 29.1%, immunotherapy: 17.1% )[12]. The survival differences between this present case series and prior reports is that these studies were conducted before the implementation of immunotherapies as standard treatment regimen, whereas the timeframe of our patients encompasses the efficacy of checkpoint inhibitors in the context of metastatic melanoma.

Surgical resection for stage IV melanoma to the small bowel continues to be debated, as some have reported that elective surgery can improve quality of life but does not confer to survival benefits [11]. Conversely, proponents for surgery have found that metastasectomy is an independent predictor of survival compared to patients who were ineligible for surgery and others managed conservatively [11, 12]. These findings were less consistent for patients undergoing palliative-intent resections, as there still remains questions about whether surgery can prolong overall survival in addition to improvements in quality of life [12].

However, the utility of small bowel metastasectomy has not been previously investigated in the setting of immune checkpoint inhibitors. In this case series, all patients received checkpoint blockade therapy, with the most common being anti-PD-1 and anti-CTLA-4 inhibitors, or a combination of both. This represents a shift in the standard of treatment for metastatic melanoma from chemotherapies, like Dacarbazine, to immunotherapeutic options. The efficacy of immunotherapies, namely immune checkpoint inhibitors, in advanced melanoma furthers the rationale for pursuing metastasectomy, especially since the surgery can be performed with low morbidity and mortality [10], as seen in our case series.

Overall, our study demonstrates that small bowel resection for well selected patients with metastatic melanoma in the era of immune systemic therapy is safe and appears to promote long-term survival and enhanced quality of life. Thus, small bowel metastasectomy should be offered to appropriately selected Stage IV melanoma patients in this setting.