Screening for Pancreatic Cancer in CDKN2A Mutation Carriers

Although population-wide screening for pancreatic cancer is not recommended, data are emerging to support surveillance of high-risk individuals to identify disease at an early stage (NEJM JW Oncol Hematol Dec 2022 and J Clin Oncol 2022; 40:3257). Among individuals with significantly increased risk for pancreatic cancer who may be candidates for screening include those with a germline pathogenic variant in CDKN2A.

To address the potential benefit of screening in this population, investigators in the Netherlands now report results of a prospective, 20-year, pancreatic cancer surveillance program (initiated in 2000) involving 347 germline CDKN2A pathogenic variant carriers. Of this cohort, the median age was 49, 58% were female, 38% had a first-degree relative with pancreatic cancer, 35% had a second-degree relative with pancreatic cancer, and 55% had a personal history of melanoma. Testing consisted of annual MRI cholangiopancreatography and, since 2012, inclusion of optional endoscopic ultrasound annually, alternating with MRI every 6 months.

Results at a median follow-up of 5.6 years were as follows:

• 36 cases of pancreatic cancer were detected in 31 patients (9%).
• 23% of cancers were diagnosed at first screening, and 81% were detected by MRI.
• 16% of patients had a second primary pancreatic cancer up to 9 years after the first diagnosis.
• 75% of cancers were resected, and 33% were stage I.
• 5-year overall survival (OS) was 32% among all patients and 44% among resected patients.
• Patients with stage I resectable disease had a 3-year OS of 83%.
• 3% had surgery for suspected malignancy but were found not to have pancreatic cancer.