麻豆传媒

In a recent issue of the Journal of Clinical Oncology, explored the effects of prospective surveillance over a period of 20 years on the detection of pancreatic adenocarcinomas in individuals with germline variants in CDKN2A. In general, it is estimated that 10-15% of sporadic cases are resectable in the general population, with a dismal overall survival rate of 5% at 5 years. Therefore, the purpose of this study was to examine whether an imaging-based surveillance program in this highly selected population, with 342 high-risk patients, could improve outcomes in terms of lower disease stage, greater resectability, and improved survival.

In this cohort, surveillance was offered at age 45 (lowered later to 40), or 10 years prior to the youngest family member with a history of pancreatic cancer. The imaging-based program allowed every 6-month alternating magnetic resonance imaging/magnetic resonance cholangiopancreatography and an optional endoscopic ultrasound

Patients were followed for a median of about 5.5 years, leading to a diagnosis of pancreatic cancer in 36 cases by a median age of 60 years old. In fact, this high-risk population had a cumulative incidence of pancreatic cancer of almost 21% by age 70. Remarkably, 30 of these cases were considered resectable and 12 of these were diagnosed with early stage I disease. Those who underwent resection (20 of the patients) had a nearly 12% improved survival as compared with the overall 5-year survival rate. Of note, nine of these patients who underwent surgery ended up having no malignant lesion.

The authors concluded that prospective, long-term surveillance in this high-risk population resulted in the detection of a greater number of early-stage, resectable patients, thereby improving survival. Carriers of CDKN2A (also known as p16-Leiden) pathologic variants were chosen as the high-risk cohort, which apparently have an estimated 15-20% risk of pancreatic cancer in their lifetime. It was humbling, however, to see that the overall 5-year survival rate was still only 32.4% in this highly selected, large cohort that was very closely monitored.

This is one of the largest prospective studies to my knowledge that investigated this topic in a very systematic fashion over 20 years with a robust multidisciplinary team. In any case, some of the limitations of this study include: enrollment in a single center in the Netherlands, study of a predominantly homogeneous Dutch population, the major potential for lead-time bias due to the study design, lack of prospective surveillance and follow-up for other types of cancers that developed in this population, lack of long-term survival data, and a major change in outcomes during more recent phases (i.e., the last decade) of the long-term study period. The latter issue was ascribed to potentially improved imaging technology by the authors, but it also brings up the evolving nature of modern cancer diagnostics and therapies. For instance, today we treat a far higher proportion of patients with early-stage pancreatic cancer with neoadjuvant chemotherapy, which drastically improves outcomes.

We know there are no standard guidelines for population-based screening for pancreatic cancer in the general population. This is likely due to numerous factors including lack of an evidence-based screening modality that can be applied to the entire population (whether it be imaging, tumor markers, or circulating tumor DNA), costs of and equal access to such population-wide screening, the low incidence overall of pancreatic adenocarcinoma, and the risks of false positives and unnecessary additional testing and procedures.

The goal of an effective surveillance program, therefore, should be to increase both the yield (i.e., increased rate of diagnosis) and the early-detection rate, thereby ultimately having an impact on outcomes such as survival.

Some of the challenges of implementing such a program include:

• Identifying how to conduct effective surveillance (which has an impact on outcomes) on the "average" population without high-risk genetic variants
• Detection and management of non-cancerous precursor lesions such as dysplasia
• Minimizing overtreatment
• Recognizing direct and indirect signs of pancreatic cancer in between screening
• Identifying relevant genetic variants population-wide in each region and implementing dedicated and multidisciplinary teams throughout the region
• Monitoring for all types of cancers (including secondary cancers) that can develop
• Changing the frequency and modality of detection when interval cancers are suspected

In addition to addressing some of the challenges above, future studies should focus on the development and validation of biomarkers that correlate with stage/grade/outcomes to risk-stratify patients, investigation of other well-known genetic variants such as BRCA, longer follow-up periods to decrease lead time bias, and potential implementation of algorithms/artificial intelligence to further enhance surveillance.

, is a physician-scientist, educator, author, and speaker, who is involved with cancer care, personalized medicine, and innovation in healthcare. At Palomar Health Medical Group in San Diego, he is the Director of Oncology and Chief Medical Officer of Physician Wellness. He also serves as Alumni Specialty Director at the Cleveland Clinic Lerner College of Medicine and as Clinical Instructor at the University of California San Diego. You can also find him on and .

Read the study here and an interview about it here.