Few cancers have a worse prognosis than pancreatic cancer, but a recent study has concluded that the surveillance of certain patients detects most pancreatic ductal adenocarcinomas (PDACs) at a stage when they are still resectable. PDAC is the fifth leading cause of cancer death in the Western Hemisphere and has a dismal prognosis, with a 5-year survival rate of only 5%.1 Surgery is the only curative treatment, but in around 80% of patients, the tumour is unresectable at the time of diagnosis, since the majority of localised pancreatic tumours are asymptomatic and precursor lesions are difficult to detect with current imaging techniques. As a result, outcomes for patients have not significantly improved in over 50 years.2
Theoretically, surveillance for PDAC may be justified for some patient subgroups: in 3– 5% of cases of PDAC, hereditary factors – either an underlying gene defect3 or a family history of PDAC4 – are involved in the disease development. In addition, previous studies have concluded that the best chance for curing pancreatic cancer is the discovery of an adenocarcinoma that is small (ideally <1 cm in diameter) and confined to the ductal epithelium.5 However, no reliable screening tests are widely available for PDAC, and only a limited number of large institutions perform multimodality-screening protocols for high-risk individuals, based on genetic predisposition and strong family history. In this study, data was collected from three such European centres. The screening comprised annual magnetic resonance imaging, magnetic resonance cholangiopancreatography and/or endoscopic ultrasound. Although the latter is more invasive than magnetic resonance imaging, patients do not perceive it as more burdensome.6
The results of screening of 411 asymptomatic individuals were published online on April 25, 2016 in the Journal of Clinical Oncology.7 Among 178 patients with p16-Leiden mutations in the CDKN2A gene, PDAC was detected in 13 cases: five tumours were detected on the first screening and eight tumours were detected during follow-up. Nine of these patients underwent surgical resection; the others were ineligible for surgery, either because of the presence of metastases or extensive local disease. The resection rate of screening-detected PDAC in this group of patients was 75%, and the overall survival rate at 5 years was 24%. These are much higher rates than those seen in historical data.8 Precursor lesions were also found in in 26 additional patients in this group, two of whom also underwent surgery.
Among the 214 at risk of familial pancreatic cancer, the benefits of screening were less evident. The screening detected suspicious lesions in three patients and precursor lesions in 11 patients. Thirteen patients in this group underwent surgery, of whom 12 were still alive at 52-month follow-up. Suspicious lesions were diagnosed on the first screening in 38.5% of these patients and on follow-up visits in the remaining 61.5% of patients; however, only four lesions in this group were considered to be high-risk. A third group comprised 19 patients with either the BRCA1/2 or the PALB2 mutation. Only one patient with a BRCA2 mutation developed PDAC.
Overall, the detection rate for cancerous or precursor lesions in this surveillance study was 2–7% in the patients studied. In an accompanying editorial, Teresa Brentnall, MD, of the University of Washington Medical Center, in Seattle, commented that this detection rate is considered high enough to justify the cost of the surveillance program for individuals at high risk for PDAC.9 To put these figures into perspective, patients with Barrett’s oesophagus undergo endoscopic surveillance every 1–3 years, and the cancer incidence in this group of patients is approximately 1%. A 2003 cost-effectiveness analysis of pancreatic cancer surveillance in high-risk individuals, found that surveillance is cost-effective when the lifetime risk of pancreatic cancer approaches 15%.10 The patients with p16-Leiden mutations in the CDKN2A gene reached this benchmark. Dr Brentnall also recommended surveillance for individuals who carry the BRCA1/2 or PALB2 mutation and who have a family history of pancreatic cancer. However, she advised that any large-scale screening programmes of high-risk patients would have to be performed at specialist centres. Interpretation of imaging findings requires considerable expertise, particularly in the case of endoscopic ultrasound. In addition, pancreatic surgery is a high-risk procedure and also needs to be performed at expert centres.
Dr Brentnall concluded that these data “represent a remarkable and encouraging step forward for better management of PDAC, a disease that has not had a significant improvement in survival in the last 50 years.”9
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2. Carpelan-Holmstrom M, Nordling S, Pukkala E, et al., Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer Registry, Gut, 2005;54:385-7.
3. Vasen HF, Gruis NA, Frants RR, et al., Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden), Int J Cancer, 2000;87:809-11.
4. Shi C, Hruban RH, Klein AP, Familial pancreatic cancer, Arch Pathol Lab Med, 2009;133:365-74.
5. Ariyama J, Suyama M, Satoh K, et al., Imaging of small pancreatic ductal adenocarcinoma, Pancreas, 1998;16:396-401.
6. Harinck F, Nagtegaal T, Kluijt I, et al., Feasibility of a pancreatic cancer surveillance program from a psychological point of view, Genet Med, 2011;13:1015-24.
7. Vasen H, Ibrahim I, Ponce CG, et al., Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers, J Clin Oncol, 2016; Online first.
8. Vasen HF, Wasser M, van Mil A, et al., Magnetic resonance imaging surveillance detects early-stage pancreatic cancer in carriers of a p16-Leiden mutation, Gastroenterology, 2011;140:850-6.
9. Brentnall TA, Progress in the Earlier Detection of Pancreatic Cancer, J Clin Oncol, 2016; Online first.
10. Rulyak SJ, Kimmey MB, Veenstra DL, et al., Cost-effectiveness of pancreatic cancer screening in familial pancreatic cancer kindreds, Gastrointest Endosc, 2003;57:23-9.