Screening for Pancreatic Cancer Results in Early Detection and Improved Overall Survival

SUMMARY: The American Cancer Society’s estimates that in 2022, about 62,210 people will be diagnosed with pancreatic cancer and 49,830 people will die of the disease. Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States and Western Europe. Unfortunately, unlike other malignancies, very little progress has been made and outcome for patients with advanced pancreatic cancer has been dismal, with a 5-year survival rate for metastatic pancreatic cancer of approximately 10%. Pancreatic cancer has surpassed breast cancer as the third leading cause of cancer death in the United States and is on track to surpass colorectal cancer, to move to the second leading cause of cancer related deaths in the United States

Detecting cancer at early stages can significantly increase survival rates and outcomes. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, and is typically detected when the disease is advanced. Even though serum CA19-9 is intended as an aid in the management of patients with confirmed pancreatic cancer for serial monitoring of their response to therapy and disease progression, it is not recommended by the FDA for screening, as it may be elevated in several benign conditions.

NCCN guideline recommends that germline testing should be considered for all patients with pancreatic cancer and is especially recommended for those with a personal history of cancer, family history or clinical suspicion of a family history of pancreatic cancer. Approximately 10% of pancreatic cancer cases have a familial component. When hereditary cancer syndrome is suspected in patients with pancreatic cancer, genetic counseling should be considered.

Screening for pancreatic cancer has been recommended for individuals considered to be at high risk of developing pancreatic ductal adenocarcinoma (5% or higher estimated lifetime risk). The risk increases with the number of affected first-degree relatives with pancreatic cancer and in those who carry a pathogenic germline variant in a pancreatic cancer susceptibility gene. The goals of screening for pancreatic cancer are to reduce mortality from pancreatic cancer through early detection, at a stage when the disease is most curable (Stage I), or when there is only a noninvasive neoplasm with high-grade dysplasia.

The Cancer of the Pancreas Screening Study (CAPS) is a research program developed at Johns Hopkins in 1998, to evaluate the effectiveness of early detection screening in high risk individuals of pancreatic cancer, and to progress the discovery of new biomarkers to improve early detection. The screening consortium agreed that to be successful, a screening program should detect and treat T1N0M0 margin-negative pancreatic cancer and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). CAPS 1–4 studies were single-institution studies, whereas CAPS 5 is a multicenter, prospective cohort study involving eight academic medical centers in the United States that opened to enrollment in 2014. The goal of CAPS 5 was to report pancreas surveillance outcomes of high-risk individuals within the CAPS 5 study, and to update outcomes of patients enrolled in prior CAPS studies, initiated more than 20 years ago. .

CAPS 5 prospectively enrolled 1,461 high-risk individuals for pancreas surveillance. High Risk Individuals included those with hereditary syndromes or germline variant carriers such as BRCA2, ATM, BRCA1, PALB2 or Lynch syndrome associated genes with a family history of pancreatic ductal adenocarcinoma, FAMMM-Familial Atypical Multiple mole Melanoma (CDKN2A) and Peutz-Jeghers syndrome (STK11). Also included in the high risk group were individuals with a family history of at least one first-degree and one second-degree relative with pancreatic ductal adenocarcinoma. High risk individuals should have met age criteria for surveillance. Surveillance protocol included annual surveillance with endoscopic ultrasound and or MRI/MRCP, often alternating between these two methods. Surveillance interval was modified when suspicious lesions were detected.

The Primary outcome of this study was the early detection of Stage I pancreatic duct adenocarcinoma or a noninvasive neoplasm with high grade dysplasia among high risk individuals undergoing surveillance. The study’s secondary outcome was Overall Survival after a diagnosis of pancreatic ductal adenocarcinoma or high grade dysplasia for high risk individuals enrolled in all CAPS studies (CAPS1-5), estimated using the Kaplan-Meier method.

Among the 1461 high risk individuals undergoing surveillance in the CAPS 5 study, 77.8% of pancreatic cancers were surgical pathology Stage I at diagnosis, 88.9% had resectable disease and the median survival for these patients was 9.8 years. This is in contrast to pancreatic ductal adenocarcinoma diagnosed outside surveillance where more than 50% present with metastatic disease, less than 20% have localized resectable disease and less than 5% have surgical Stage I disease.

In the entire CAPS cohort (CAPS 1-5) to date, the 5-year Overall Survival among screen-detected pancreatic ductal adenocarcinoma was 73.3%. The patients who progressed to pancreatic ductal adenocarcinoma in this study included carriers with germline pathogenic variants and those who met familial-risk criteria only. These results support current CAPS surveillance recommendations and argue against limiting pancreatic surveillance to those high-risk individuals with known pathogenic mutations. The median survival in the entire CAPS cohort for the patients with a screen-detected pancreatic ductal adenocarcinoma was 9.8 years, compared with 1.5 years for patients whose pancreatic ductal adenocarcinoma were diagnosed outside surveillance (HR=0.13; P=0.003).

The researchers concluded that screening for pancreatic cancer in high risk individuals can result in early detection, at a stage when the disease is most curable (Stage I).

The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival. Dbouk M, Katona BW, Brand RE, et al., J Clin Oncol. 2022 Jun 15;JCO2200298. doi: 10.1200/JCO.22.00298. Online ahead of print.