Early Diagnosis of Pancreatic Cancer: Clinical Premonitions, Timely Precursor Detection and Increased Curative-Intent Surgery

Abstract

Background: The overall poor prognosis in pancreatic cancer is related to late clinical detection. Early diagnosis remains a considerable challenge in pancreatic cancer. Unfortunately, the onset of clinical symptoms in patients usually indicate advanced disease or presence of metastasis.

Analysis and results: Currently, there are no designated diagnostic or screening tests for pancreatic cancer in clinical use. Thus, identifying risk groups, preclinical risk factors or surveillance strategies to facilitate early detection is a target for ongoing research. Hereditary genetic syndromes are a obvious, but small group at risk, and warrants close surveillance as suggested by society guidelines. Screening for pancreatic cancer in asymptomatic individuals is currently associated with the risk of false positive tests and, thus, risk of harms that outweigh benefits. The promise of cancer biomarkers and use of 'omics' technology (genomic, transcriptomics, metabolomics etc.) has yet to see a clinical breakthrough. Several proposed biomarker studies for early cancer detection lack external validation or, when externally validated, have shown considerably lower accuracy than in the original data. Biopsies or tissues are often taken at the time of diagnosis in research studies, hence invalidating the value of a time-dependent lag of the biomarker to detect a pre-clinical, asymptomatic yet operable cancer. New technologies will be essential for early diagnosis, with emerging data from image-based radiomics approaches, artificial intelligence and machine learning suggesting avenues for improved detection.

Conclusions: Early detection may come from analytics of various body fluids (eg 'liquid biopsies' from blood or urine). In this review we present some the technological platforms that are explored for their ability to detect pancreatic cancer, some of which may eventually change the prospects and outcomes of patients with pancreatic cancer.

Keywords: biomarker; curative surgery; diagnosis; early detection; early diagnosis; liquid biopsy; prevention; radiology; screening.

Figure 1.

Proportion of patients presenting for potential curative treatment. Legend: Any given patient may be deemed inoperable at time of diagnosis or irresectable through clinical (image-based) staging. Definitions for borderline/locally advanced cancers are floating, with variation in management. More effective systemic therapy (eg FOLFIRINOX) is increasingly introduced in the pre-operative setting, with more resections offered after therapy, possibly influencing the pathological TNM-staging and interpretation of its prognostic role. Better predictive and prognostic biomarkers of cancer biology are needed. Reproduced with permission from Roalsø et al. Copyright © 2020 The Author(s). Published by Elsevier Ltd. All rights reserved.

Figure 2.

Window of opportunity for early detection of pancreatic cancer. Legend: The early detection of resectable disease or precursor lesions requires earlier detection at a time when no symptoms are present, yet biological signals (eg imaging, blood tests, biomarkers) are present for detection. Detection and treatment of high-grade dysplasia (HGD) before invasive cancer may provide cure (yellow zone); detection of early-stage cancer (green zone) may improve survival and cure rates.

Figure 3.

Relative risk for pancreatic cancer in the population. Legend: Highest risk is found in hereditary genetic syndromes, yet the majority present without specific risk factors.

Figure 4.

The Define-Enrich-Find strategy for early detection of pancreatic cancer. Legend: Screening for sporadic PDAC in the average risk general population is considered unrealistic because of the low incidence. An alternative to screening is a proposed DEF (Define, Enrich, Find) strategy that allows PDAC surveillance in a subset of higher risk asymptomatic patients where it might be most beneficial. New-onset diabetes or pancreatic cysts may be such targeted populations.