Pancreatic Cancer: Yearly Monitoring of Cystic Lesions in Doubt

Vincent Richeux

March 31, 2022

PARIS, France — Fewer than 1% of patients with intraductal papillary mucinous neoplasms (IPMNs) of the branch ducts develop adenocarcinoma after 5 years of follow-up monitoring, according to a French observational study. These findings were presented during the Francophone Days of Hepato-gastroenterology and Gastrointestinal Oncology (JFHOD 2022). This rate of adenocarcinoma falls well below those reported in previous studies, which is leading to a reconsideration of recommendations of yearly imaging-based monitoring.

"I'm astonished by the low number of cancers observed after this follow-up," stated Vinciane Rebours, MD, PhD, the study's lead author and professor of pancreatology and digestive oncology at Beaujon Hospital in Clichy, France, during a press conference. According to the gastroenterologist, this study may contribute toward modifying the most recent European recommendations for monitoring patients with IPMN, which are slated for renewal "sometime in the upcoming 2 to 3 years."

Given the low number of patients who developed adenocarcinoma among the cohort, "it is difficult to ascertain the predictive factors for degeneration" of cystic lesions, said Rebours. Further work resulting from this study should be able to help fine-tune the criteria. "Monitoring every other year could be sufficient in case of smaller lesions (<10 mm)."

Common Cystic Lesions

IPMNs are common precancerous lesions of the pancreas that generally are discovered by chance during an imaging exam (MRI or endoscopic ultrasound). Estimated at 7% among the general adult population, the prevalence of these cystic lesions goes up with age, reaching nearly 15% among individuals over 70 years of age. Such lesions are purportedly responsible for 10% of pancreatic cancer cases.

The risk of degenerating into adenocarcinoma varies depending on the nature of the lesions. Several primarily morphologic criteria have been established to stratify the risk of cancer at 5 years. This risk is greater than 50% when high-risk criteria for malignancy (involvement of the main duct with dilatation >10 mm, budding >5 mm, etc) are present and is greater than 4% when so-called red flags (acute pancreatitis, de novo diabetes, cyst >40 mm, etc) arise.

When such criteria for degeneration are not present, as in most cases of IPMN, the risk of cancer is poorly understood. According to the literature, it may range between 0 to 10% and may be higher over the long term. One recent Japanese study that monitored more than 1000 patients with branch-duct IPMN determined that the risk of pancreatic cancer after 5 years was 3.3%. This risk went up over the course of follow-up, reaching 12% after 15 years.

In consideration of the potential risk of cancer, monitoring should be offered whenever patients with IPMN do not meet any of the criteria, in keeping with the most recent 2018 expert guidance from the European Study Group on Cystic Tumors of the Pancreas. Follow-up monitoring should be yearly and based primarily on imaging.

Low Carcinoma Incidence

In the TEAM-P prospective observational study, Rebours sought to evaluate the applicability of such follow-up monitoring by ascertaining the medium-term risk of degeneration for cases of branch-duct (BD) IPMN in which high-risk criteria and red flags are not present. The study likewise aimed to define predictive criteria for these patients.

In total, 1817 patients with BD-IPMN, a majority of whom were women (70%), were enrolled at 58 French sites. The average age of these patients was 65.2 years. Cases of IPMN that were free of signs of degeneration were mainly discovered by chance (78%) or during a bout of acute pancreatitis (13%). Upon enrollment, the lesions measured 11 mm in diameter on average (for two thirds of lesions, the diameter was <10 mm).

On the basis of international guidance, monitoring regimens were offered according to cystic lesion size, with combined use of MRI, CT, and endoscopic ultrasound, at the physician's discretion.

During follow-up monitoring, the average duration of which was 4.29 years, 38 patients underwent procedures, for a rate of 2.1%. This amounts to an incidence of four procedures per 1000 person-years. Procedures were chosen upon involvement of the main pancreatic duct (n = 14), recurrence of acute pancreatitis (n = 13), rapid increase in lesion size (n = 13), onset of budding (n = 9) or appearance of a mass (n = 3).

The researchers reported 25 cases of low- or medium-grade dysplasia, nine cases of high-grade dysplasia, and four cases of invasive carcinoma, including one case that developed remotely from the lesion. This finding corresponds to an incidence rate for high-grade or invasive lesions of 1.6 cases per 1000 person-years.

A Representative Cohort

Among patients monitored for fewer than 5 years, the rate of high-grade or invasive lesions was 0.6%. Beyond 5 years, this rate went up to 0.9%. Patients who presented with these lesions were slightly overweight (median body mass index, 25.5) and were nonsmokers.

"All told, there was an extremely low rate of degeneration. This remains well below the figures published in the literature," said Rebours. To explain this discrepancy, she pointed out that the cohorts from published studies were taken from expert centers, whereas in the French cohort, one third of patients were also being monitored by private-practice practitioners.

European experts advise yearly monitoring for patients who can undergo an MRI or endoscopic ultrasound. "In light of these numbers, one might think this is excessive," said Rebours. From her viewpoint, monitoring could possibly be switched over to checkups every other year for cysts measuring <10 mm, as previously suggested by international experts.

Other studies will be performed using the data obtained from this study, in particular to determine the best follow-up strategies and to ascertain the cost of IPMN monitoring recommended by European expert guidance, "to determine how much should be spent on preventing pancreatic cancer development," said Rebours.

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