Intraductal Radiofrequency Ablation (RFA) for Pancreatic Cancer: Getting in Under the Wire?

Abstract

Since pancreatic carcinoma, an aggressive cancer often unresectable at initial diagnosis, is curable by complete surgical removal in only 10–20 % of cases [1], palliative therapy, primarily chemotherapy, is therefore the mainstay of treatment. Newer regimens combining chemotherapy with either external beam or stereotactic body radiation therapy (SBRT) and more intense regimens such as 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) are ongoing. Nevertheless, even with the best care, survival is dismal, especially in those with unresectable disease [2, 3]. Although biliary obstruction, commonly complicating disease involving the pancreatic head, can be stented successfully during endoscopic retrograde cholangiopancreatography (ERCP), stent occlusion is a frequent problem, even with the newer metallic stents, whether covered or uncovered. Stent occlusion can be complicated by jaundice, cholangitis, and delay in chemotherapy or other treatments. Since the prognosis for survival with locally advanced or metastatic pancreatic carcinoma is poor, endoscopic therapy of advanced disease is merely palliative. Radiofrequency ablation (RFA) delivered primarily by the intraoperative and percutaneous routes has been used for years to treat a variety of tumors. The development of new ‘‘over-the-wire’’ endobiliary RFA catheters compatible with existing electrosurgical units eases the application of RFA while reducing its cost [4]. The endobiliary RFA device was originally designed to be applied to malignant biliary strictures to slow intraductal growth and improve stent patency. In this issue of Digestive Diseases and Sciences, Kallis et al. [5] sought to determine whether endoscopically delivered RFA prolongs stent patency and survival in patients with pancreatic carcinoma. In a large-volume center routinely performing RFA for pancreatic carcinoma, the authors compared, using a retrospective case–control analysis, 23 patients with biliary obstruction due to unresectable pancreatic cancer undergoing endoscopic RFA/SEMS with 46 controls undergoing SEMS alone. The authors’ uniform approach to all study subjects, including use of the same stent type and the same chemotherapy regimens, provides a reasonable basis for comparison. The primary endpoint was patient survival with secondary endpoints stent patency and procedure-related safety and tolerability. A significant survival benefit was observed in patients treated with RFA and SEMS (226 vs 123.5 days, p = 0.01), although no difference in stent patency was observed (median 472 vs 324 days, p = 0.669). RFA was independently predictive of survival at 90 and 180 days. In both groups, patients died primarily from disease progression and carcinomatosis, but not from the direct effects of stent occlusion. What is the mechanism by which RFA prolongs survival? Although it has been postulated that RFA decreases intimal hyperplasia [6], this does not explain increased survival in the absence of increased stent patency. Hansler et al. [7] reported in a study of 10 patients with primary or secondary liver tumors undergoing RFA increased cytologic tumorspecific T cell stimulation suggestive of an immunological mechanism for increased survival. den Brok et al. [8] also reported increased immune response to RFA in a mouse model, suggesting that immune activation by RFA may enhance tumor suppression. Although enhanced immunogenicity may very well explain the increased survival, this & Brian C. Brauer Brian.brauer@ucdenver.edu