In patients with branch-duct intraductal papillary mucinous neoplasm (BD IPMN), understanding which neoplasms are the precursors to pancreatic cancer has been the aim of surveillance in order to avoid unnecessary surgery. An international retrospective cohort study suggests that changes in some of these risk factors or the development of a high-risk stigmata (HRS) may help identify which patients are at the highest risk of developing high-grade dysplasia (HGD).
“The ultimate goal in the surveillance of IPMNs is to understand which neoplasms will eventually evolve into malignant neoplasms and to avoid the risks of unnecessary pancreatic surgery for patients who will never develop malignant neoplasms in their lifetime,” Giovanni Marchegiani, MD, PhD, University of Verona Hospital Trust, Verona, Italy, and colleagues reported in JAMA Surgery. “The dynamic interpretation of risk factors over time seems to be the most effective way to select patients for surgery after surveillance before they develop an invasive component.”
The study authors noted that those patients whose initial diagnosis was presumed BD IPMN and who developed HRS, “namely, obstructive jaundice and enhancing mural nodules of at least 5mm, and those with an MPD measuring at least 10 mm, were considered for resection if they met requirements for surgery,” they wrote.
Worrisome features included “acute pancreatitis, cyst of at least 30 mm, thickened/enhancing cyst wall main pancreatic duct (MPD) measuring 5.0 to 9.9 mm, enhancing mural nodules smaller than 5 mm, abrupt change in MPD caliber with distal atrophy of the pancreatic gland, an increased level of carbohydrate antigen 19-9, and cyst growth of at least 5 mm in 2 years,” the study authors wrote.
Finally, they defined BD IPMN “as the presence of a pancreatic cyst with a connection with the main pancreatic duct (MPD) through a secondary duct, without MPD dilatation detected using abdominal magnetic resonance imaging with and without contrast enhancement and with cholangiopancreatography or with abdominal computerized tomographic imaging with and without contrast enhancement.”
In a cohort of 292 patients with BD IPMNs, developing an additional worrisome feature during a year-long surveillance was associated with a greater than 3-fold increased risk of progressing to HGD at the final pathological evaluation at time of surgery at an odds ratio [OR] of 3.24 (95% CI, 1.38-7.60; P=0.007), Marchegiani and colleagues wrote.
Similarly, the development of a HRS from a baseline worrisome feature was associated with an almost 3-fold greater risk of having HGD at final pathological evaluation at an OR of 2.87 (95% CI, 1.01-8.17; P=0.048), investigators added. However, among HRS, only the development of obstructive jaundice was associated with the presence of invasive cancer at the same follow-up evaluation.
All patients undergoing surgical resection for BD IPMN between January 2000 and December 2019 following a surveillance interval of at least one year were eligible for inclusion in the current study. The median age at diagnosis was 64 years (interquartile range (IQR), 56-71 years) and the median length of surveillance was 37 months (IQR, 20-68 months).
At baseline, 39.7% of patients had a worrisome feature; 5.5% harbored a HRS, while slightly over half at 54.8% had neither a worrisome feature nor a HRS at diagnosis. After a median surveillance of 33 months (IQR, 15-62 months), 58% of patients who did not have a worrisome feature or HRS at diagnosis developed a worrisome feature.
It is noteworthy that 9.2% of the same group of patients developed a worrisome feature after 5 years of surveillance.
Of those who did not have a HRS at diagnosis, 16.7% developed a HRS during surveillance after a median of 28 months (IQR, 11-64 months) from baseline. Furthermore, the rate of HGD or invasive cancer increased from 27.3% among those with low-risk IPMNs that exhibited complete stability up until the point of surgery to 61.9% of patients who progressed from having a worrisome feature at baseline to a HRS during surveillance (P<0.001), the researchers noted.
Progression from a low-risk cyst to the development of a HRS was also significantly associated with an over 4-fold risk of harboring invasive cancer at the final pathologic examination at an OR of 4.20 (95% CI, 1.61-10.93; P=0.003).
“In contrast, patients with a baseline worrisome feature showing cyst stability until surgical resection had an 84% lower risk of having invasive cancer at the same follow-up examination at an OR of 0.16 (95% CI, 0.03-0.87; P=0.03), the authors added.
As the authors pointed out, most patients underwent pancreaticoduodenectomy following the surveillance interval where 36.6% of patients had malignant disease, 21.6% of them having HGD.
Both the development of additional worrisome features during surveillance in patients with worrisome features at diagnosis, as well as progression from worrisome features to HRS during the same surveillance interval were independently associated with a greater risk of harboring HGD at the final pathological examination.
Once an additional worrisome feature is found in addition to a previous one, surgery is indicated based on the current data, the authors emphasized.
“The goal of surgery for IPMNs should be to identify those lesions that have the potential to progress to invasive cancer and to resect them before an invasive component develops,” the investigators noted. “[T]he use of the known worrisome features and HRS helps the clinician select patients who are at higher risk for harboring HGD,” they reemphasized.
Commenting on the findings, editorialists Patricia Conroy, MD, and Eric Nakakura MD, PhD, both from the University of California, San Francisco, agreed with the authors that because most patients with BD IPMN will not go on to develop invasive cancer, “patient selection is paramount.”
Currently both clinical and imaging-based guidelines aim at identifying patients for whom continued surveillance is safe have a low specificity, which often leads to unnecessary surgery, they pointed out. Results from the current study are “not surprising,” as they suggested, but they do provide insight into the progression of BD IPMNs and reinforce expected outcomes from surveillance, namely intervention after progression.
However, the results also demonstrate that current guidelines fail to meet the goals of surveillance even at centers of excellence where the study took place, Conroy and Nakakura noted. They also pointed out that the majority of the cohort at 63.4% had low-grade dysplasia and thus were overtreated although the authors do not explain why patients with low-risk lesions underwent surgery. At the same time, 15.1% of patients had invasive cancer and were thus undertreated with surveillance.
Again, the authors do not explain who made up this group and whether it may have included patients with HRS at baseline: If so, why did these patients not undergo surgery for more than 1 year after diagnosis?” Conroy and Nakakura wrote. “There is no doubt that identifying HGD before surgery is incredibly difficult,” the editorialists confirmed. “As such, future efforts by Marchegiani et al and others are desperately needed.”
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In patients with branch-duct intraductal papillary mucinous neoplasm (BD IPMN), understanding which neoplasms are the precursors to pancreatic cancer has been the aim of surveillance in order to avoid unnecessary surgery.
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This international retrospective cohort study suggests that changes in some of these risk factors or the development of a high-risk stigmata (HRS) carried the highest risk of developing high-grade dysplasia (HGD).
Pam Harrison, Contributing Writer, BreakingMED™
Neither the authors nor the editorialists had any conflicts of interest to declare.
Cat ID: 120
Topic ID: 78,120,112,188,120,935,925
