The superior patency of metal biliary stents over their plastic counterparts among the spectrum pancreatic cancer cohorts with biliary obstruction has been firmly established in a number of prior studies. A recent retrospective study by Decker et al
. examined the rate of repeat endoscopic intervention in 29 pancreatic cancer patients who underwent biliary stent placement prior to pancreaticoduodenectomy (10
). This study was not limited to the neoadjuvant treatment population, but found that 39% (7 of 18) of patients in the plastic stent group required pre-operative stent intervention, while no patients in the metal stent group (11 patients) required re-intervention. However, there is a paucity of information available regarding the rates of re-intervention in the specific subset of pancreatic cancer patients who are candidates for neoadjuvant therapy in anticipation of later surgical resection.
A recent retrospective study by Boulay et al
. evaluated 49 patients with resectable or locally advanced pancreatic cancer who had plastic stents placed for malignant biliary obstruction, and then underwent neoadjuvant therapy (11
). The majority of patients (55%) underwent repeat endoscopic intervention with stent exchange due to plastic stent complications including, most commonly, stent occlusion and cholangitis. The study concluded that plastic stents were not advisable in this subset of patients because they do not remain patent for the amount of time necessary for most patients to complete neoadjuvant therapy, which often lasts 2 to 4 months. While their report did include 7 metal stent patients, showing a 14% rate of repeat intervention, it represented too small a sample population to allow statistical comparison (11
). The expanded cohort size in our study has facilitated meaningful comparisons, allowing conclusions that may guide clinical decision making. No published randomized controlled trials exist currently to examine this issue.
While, in theory, patients undergoing chemotherapy may be more susceptible to stent complications for reasons set forth earlier, at least some studies refute this conclusion. In one retrospective analysis of 80 patients with plastic stents, the rate of stent occlusion was not found to be significantly different between those exposed to chemotherapy (37%) and those unexposed (39%), and mean duration of patency was not shortened by chemotherapy (12
). A later Japanese study of 147 patients, also retrospective, showed that the rate of biliary infectious complications in metal stents was unchanged by administration of chemotherapy (13
). However, the treatments may not be directly comparable. The key consideration is that for patients undergoing neoadjuvant therapy, a stent complication may render disease unresectable due to local complications or delay surgery to the point that disease progression renders the patient inoperable.
It is also important to recognize, as demonstrated by our data, that neoadjuvant therapy is not a complete solution to the challenge of treating pancreatic cancer, which has an extremely poor 5-year survival rate. Of the patients in our study, over a quarter either had progression of disease or no improvement in tumor burden after neoadjuvant therapy, such that they were not ultimately operative candidates despite the neoadjuvant therapy. Furthermore, of those patients who underwent surgery, roughly one third were not successfully resected due to progression of disease discovered during surgical exploration. This confirms earlier estimates that neoadjuvant therapy is able to convert approximately 33% of borderline resectable patients to resectable candidates, but may not improve overall outcome (11
). We were unable to accurately estimate overall survival outcome in our study, due to the high number of patients who were lost to follow-up (local care), either prior to or following surgical resection.
One argument against routine use of metal stents has been their increased cost as compared to their plastic counterparts. However, our data supports the conclusion that it is actually more economically sound to use metal stents for two reasons. First, since metal stents remain in place substantially longer without complication, they do not need to be exchanged like plastic stents, which must be routinely exchanged roughly every 3 months based on the known median time to occlusion. Our data shows that the mean time from initial stent placement to surgery is roughly 4.5 months, and up to 7.5 months, such that a plastic stent would have to be exchanged at least once prior to surgery. This overall mean duration of stent patency is consistent with that elucidated in prior published studies (14
). One meta-analysis concluded that a metal stent would be cost-effective if future re-interventions cost greater than $1,820, representative of a patient expected to have at least a 4 to 6 month survival following initial stent placement (14
). Furthermore, our data shows that patients who receive plastic stents have a roughly 3-fold greater rate of hospitalization for stent-related complications than patients receiving metal stents. The extra cost of a metal stent pales in comparison to the economic cost of even a short hospital stay.
Our data expands the literature in this unique and growing patient population by including a formal metal stent comparison group, and demonstrating a statistically significant difference in stent patency and complication rate in the metal stent group. Metal stents not only have a 7-fold lower absolute complication rate, they also remain in place approximately 5 times longer without complication as indicated by our Kaplan-Meier analysis. Recent data have shown that metal stents neither interfere with surgical margins, nor obscure tumor imaging pre-operatively. The importance of successful neoadjuvant therapy has been recently emphasized by evidence of its association with improved outcomes for this lethal malignancy (4
In terms of our study’s practical application for the interventional endoscopist, our group reserves ERCP for palliation of jaundice after a pancreatic protocol CT provides staging information. A tissue diagnosis may be confirmed by EUS-FNA and/or on-site review of ERCP brushings followed by metal stent placement. Many of the patients in our study cohort had stenting performed at initial presentation, often with plastic stents of small caliber and typically prior to referral. Therefore, the choice of plastic versus metal stent at initial presentation depended in large part on the level of suspicion and/or confirmation of malignancy versus benign causes of biliary obstruction. For cases of confirmed malignant obstruction, our data supports the clear improved efficacy of metal stents due to their longevity without complications both in patients who are destined for surgical resection, as well as those who are ultimately poor candidates for resection due to the extent of their disease. The presence of a metal stent is no longer considered the barrier to surgery it once was.
We acknowledge several important limitations to our study. First, the comparatively small number of patients in our metal stent group limits the power of the study. Second, for purposes of statistical analysis, we chose to look at stents independently, rather than individual patients, in order to account for the fact that an individual patient may have multiple stents placed during their course of treatment. While this made some elements of our analysis easier, it may have obscured other factors. Finally, given the retrospective nature of our study, factors other than stent choice may have impacted the clinical outcomes of each cohort.
In summary, our compelling evidence indicates that self-expanding metal, not plastic stents should be used for malignant biliary obstruction in patients undergoing neoadjuvant therapy for pancreatic cancer, due to lower rates of complication, hospitalizations, and longer stent patency.