Screening/surveillance programs for pancreatic cancer in familial high-risk individuals: A systematic review and proportion meta-analysis of screening results
Introduction
Pancreatic cancer (PC) remains one of the deadliest solid tumors. In 2017 PC is the third leading cause of cancer-death in USA and by 2030 it is predicted to be the second leading cause [1,2]. PC is considered micrometastatic at the time of diagnosis because most patients eventually experience a recurrence (local and/or systemic) after radical surgery. In fact, it has been estimated that the chances of harboring a metastatic disease are 23% and 78% when the tumor is 1 or 2 cm, respectively [3]. The aggressive biology of PC raises the question whether an early diagnosis is not only possible but also worthwhile. However, several efforts have been made to define categories of individuals at high-risk (HRI) of developing PC to enroll in proper screening/surveillance programs.
Precursor lesions of pancreatic malignancy such as intraductal papillary mucinous neoplasm (IPMN) and pancreatic intraepithelial neoplasia (PanIN) have been identified, and their recognition should be the goal of any screening/surveillance program directed to HRI. There are two well-known categories of HRI—familial pancreatic cancer (FPC)-HRI and syndromic-HRI. The first group encompasses subjects with various degrees of kinship (until the third) with patients diagnosed with PC. The second group includes subjects suffering from genetic conditions in whom PC could be a clinical epiphenomenon such as Hereditary Breast-Ovarian Cancer Syndrome (HBOC), Familial Atypical Multiple Mole Melanoma Syndrome, Hereditary Pancreatitis (HP), or Peutz-Jeghers Syndrome (PJS) [4]. In 2009, a meta-analysis calculated that having an affected relative increases pancreatic cancer risk with an overall relative risk of 1.80 [5]. In 2015, Pandharipande et al. developed a simulation model of PC and demonstrated that an MRI-based screening/surveillance program conducted on a hypothetical 50-year-old subject with one first-degree relative (FDR) affected (called “modestly elevated-risk individual”) can lead to a gain in life expectancy [6]. According to the Cancer of the Pancreas Screening (CAPS) Consortium, the goal of any screening/surveillance program for HRI should be T1N0M0 margin-negative PC, high-grade dysplasia/carcinoma in situ (HGD)-IPMNs, and pancreatic intraepithelial neoplasia (PanIN)-3 [7]. Participating in a screening/surveillance program implies a certain inherent risk to receive surgery—even unnecessary. Thus, unnecessary surgery for a presumed malignant or pre-malignant lesion should be strictly avoided due to the high perioperative morbidity and mortality rates of pancreatic surgery and long-term complications following pancreatic resection. The aim of this study was to assess the proportion of screening/surveillance goal achievement as well as the overall and unnecessary surgery in studies reporting FPC-HRI screening/surveillance.
Section snippets
Data sources and study selection
We searched MEDLINE, Embase, PubMed, and the Cochrane Library database from January 2000 to December 2016. Any study reporting results of screening/surveillance programs including cohorts of FPC-HRI were considered. The terms “screening” and “surveillance” were intentionally used interchangeably similar to the published manuscripts. Only English-language studies and full-text papers were considered. When considered together in a study, syndromic-HRI was excluded; only the FPC-HRI subpopulation
Results
The PRISMA® diagram (Fig. 1) summarizes the systematic literature search results. Briefly, the sum of the four queries generated 17,097 abstracts; 82 papers were retrieved for full-text examination, and 16 of them were ultimately included in the meta-analysis [[17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31]].
Discussion
The possibility of diagnosing small PC or pre-malignant lesions is extremely intriguing yet very difficult. An expert panel in 2013 established a goal for PC screening/surveillance programs: T1N0M0 R0 PC, HGD-IPMNs, or PanIN3. Clinically, the detection of such lesions is difficult and anecdotic. However, screening/surveillance programs on FPC-HRI allow the community to concentrate all diagnostic efforts on a category of otherwise asymptomatic and healthy subjects at high risk of PC due to
Conclusions
Our study underlines the importance and the efficacy of submitting FPC-HRI to screening/surveillance programs. It is likely that being enrolled in a screening/surveillance program due to familiarity with PC means inherently accepting a certain risk of receiving surgery for a benign (serous cystadenoma, focal fibrosis, PanIN1, Incipient IPMN, etc.) or an undefined-risk lesion (MGD-IPMN, PanIN2). A strict observance of FPC-HRI criteria, a multidisciplinary evaluation of each subject enrolled and
Acknowledgements
We acknowledge the Associazione Italiana Ricerca sul Cancro (AIRC program 12182). The funding source had no role in study design, data collection, data analysis, data interpretation or writing of the manuscript. All authors declare no conflicts of interest.
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