Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis

Abstract

Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with "familial pancreatic cancer" (FPC) and specific syndromes are limited and heterogeneous.

Objective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs.

Methods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated.

Results: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years.

Conclusion: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.

Keywords: Pancreatic cancer; family history; meta-analysis; screening.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram of assessment of studies identified in the preset systematic review.

Figure 2.

Forest plot showing the pooled prevalence of pancreatic solid lesions (panel (a), on the left) diagnosed in high-risk individuals in all the 14 included studies and of the pooled prevalence of cystic lesions (panel (b), on the right) diagnosed in high-risk individuals in the 13 studies reporting this information. Random-effects model demonstrating a pooled prevalence of 5.8% (95% confidence interval (CI) 3%–8%) with moderate heterogeneity (I²= 77.5%) for solid lesions and a pooled prevalence of 20.2% (95% CI 14%–29%) with considerable heterogeneity (I²= 88.9%) for cystic ones.

Figure 3.

Forest plot showing the overall pooled prevalence of successful target lesions of the surveillance that is equal to 3.3% (95% confidence interval (CI) 2%–5%), with moderate heterogeneity (I²= 40.5%).

Figure 4.

Forest plot showing the pooled estimate rate of successful target lesions of the surveillance in the 11 studies that reported the follow-up length. The pooled estimate rate resulted of 5/1000 person years with moderate heterogeneity (I²= 56%).

Figure 5.

Summary of the pooled prevalence of pancreatic lesions (solid, cystic and successful target lesions of the surveillance) diagnosed either by endoscopic ultrasonography (EUS) or magnetic resonance imaging (MRI). CI: confidence interval.

Figure 6.

Pooled prevalence of lesions considered a successful target of surveillance in the different high-risk individual subgroups. The pooled prevalence of lesions considered a successful target of surveillance diagnosed in familial pancreatic cancer (FPC) was 3% (95% confidence interval (CI) 2%–5%) with moderate heterogeneity (I²= 22.2%). The pooled prevalence in familial atypical multi-mole melanoma syndrome (FAMMM) was 5% (95% CI 3%–9%), in hereditary pancreatitis (HP) was 4% (CI 1%–14%), in hereditary breast-ovarian cancer syndrome (HBOC) or BRCA1/BRCA2 or PALB2 mutation carriers was 6.3% (95% CI 3%–14%), and in Peutz-Jeghers syndrome (PJS) it was 12.2% (95% CI 4%–32%). Notably, in all these genetic syndromes but HP, there was no heterogeneity (I²= 0%).