Abstract
BackgroundThe clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools.MethodsSixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).ResultsThe panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively associated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected <1 and >1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone.ConclusionsMost biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combinations offered advantage over CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis. However, the efficacy of biomarker-based tools remains limited at present. Several biomarkers demonstrated significant velocity related to time to diagnosis, an observation which may offer considerable potential for enhancements in early detection.
Highlights
Pancreatic cancer is the fourth leading cause of cancer death in the United States
In the current study we investigated the efficacy of a large group of serum biomarkers, including several combinations shown previously to be effective in a retrospective case/control cohort, in pre-diagnostic samples collected from patients diagnosed with pancreatic ductal adenocarcinomas (PDAC) who were enrolled in the large Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)
We previously reported the performance of several biomarker combinations in the discrimination of PDAC cases from healthy control subjects in a large retrospective case/ control study [8]
Summary
In 2013, an estimated 43,924 people will be diagnosed with pancreatic cancer and 37,390 will perish from the disease [1]. The high lethality associated with pancreatic ductal adenocarcinomas (PDAC), which constitute 85–90% of pancreatic cancer diagnoses, can be largely attributed to the presence of advanced disease at the time of diagnosis. PDAC is characterized by clinical manifestations which present late in the natural history of the disease at a stage when metastasis is a common finding, leading to a median survival of 6 months and an overall 5-year survival of ,5% [2]. Outcomes are significantly improved in the minority of patients who present with small, surgically-resectable cancers for which there is a realistic chance of cure and a 5-year survival rate of 20–30% [3]. The clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools
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