Screening for pancreatic cancer has the potential to save lives, but is it practical?

Mazer, Benjamin L.; Lee, Jae Woo; Roberts, Nicholas J.; Chu, Linda C.; Lennon, Anne Marie; Klein, Alison P.; Eshleman, James R.; Fishman, Elliot K.; Canto, Marcia Irene; Goggins, Michael; Hruban, Ralph H.

doi:10.1080/17474124.2023.2217354

Cited by 13 publications

(9 citation statements)

References 224 publications

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“…Recent studies have indicated that surveillance among such individuals increased the percentage of PDAC patients diagnosed with early-stage disease with concomitantly improved outcomes [20–22]. Among additional elevated-risk groups, such as those with chronic pancreatitis, sudden-onset diabetes [19], or PDAC-associated clinical histories [23], surveillance by radiographic imaging would not be sustainable owing to a lower prevalence of PDAC [3,7]. However, a blood test could be a cost-effective way to identify patients who could be further evaluated by radiographic imaging.…”

Section: Discussionmentioning

confidence: 99%

“…The best-known blood biomarker for PDAC, CA19-9, is elevated in the majority of PDAC patients but is not highly specific for PDAC, yielding 0.70-0.75 sensitivity and 0.70-0.75 specificity for distinguishing PDAC from non-cancer conditions [4,5]. Such performance is insufficient for surveillance for PDAC [3,6].…”

Section: Introductionmentioning

confidence: 99%

“…Remarkably, such patients have an ∼ 3-fold higher 5-year survival rate (44%) than patients with node positive (regional stage) PDAC (16%) [1,2], supporting the goal of pursuing strategies to identify PDAC patients when their disease is at an earlier, localized stage. This goal, however, has been constrained by the lack of a low-cost and convenient blood test that would perform well enough for surveillance of elevated-risk populations [3]. The best-known blood biomarker for PDAC, CA19-9, is elevated in the majority of PDAC patients but is not highly specific for PDAC, yielding 0.70-0.75 sensitivity and 0.70-0.75 specificity for distinguishing PDAC from non-cancer conditions [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have identified many candidate biomarkers for PDAC, although the best individual biomarkers identify PDAC patients with sensitivity and specificity no better than CA19-9 (see reviews [3,7,8]). Such biomarkers potentially identify separate subsets patients without a complementary identification of non-PDAC subjects, thus yielding superior performance if used in combination.…”

Section: Introductionmentioning

confidence: 99%

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A Rigorous Multi-Laboratory Study of Known PDAC Biomarkers Identifies Increased Sensitivity and Specificity Over CA19-9 Alone

Haab,

Qian,

Staal

et al. 2024

Preprint

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A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs. We analyzed the training set to identify candidate biomarker combination panels using biomarkers across laboratories, and we applied the fixed panels to the validation set. The panels identified in the training set, CA19-9 with CA199.STRA, LRG1, TIMP-1, TGM2, THSP2, ANG, and MUC16.STRA, achieved consistent performance in the validation set. The panel of CA19-9 with the glycan biomarker CA199.STRA improved sensitivity from 0.44 with 0.98 specificity for CA19-9 alone to 0.71 with 0.98 specificity (p < 0.001, 1000-fold bootstrap). Similarly, CA19-9 combined with the protein biomarker LRG1 and CA199.STRA improved specificity from 0.16 with 0.94 sensitivity for CA19-9 to 0.65 with 0.89 sensitivity (p < 0.001, 1000-fold bootstrap). We further validated significantly improved performance using biomarker panels that did not include CA19-9. This study establishes the effectiveness of a coordinated study of previously discovered biomarkers and identified panels of those biomarkers that significantly increased the sensitivity and specificity of early-stage PDAC detection in a rigorous validation trial.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Rigorous Multi-Laboratory Study of Known PDAC Biomarkers Identifies Increased Sensitivity and Specificity Over CA19-9 Alone

Haab,

Qian,

Staal

et al. 2024

Preprint

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“…1-3 A major hurdle in confronting this aggressive disease is that there is no effective screening test for PDAC or its precursor lesions. 4 As such, PDAC is often diagnosed late when distant metastases are present and few clinical options remain. Only 15% of patients present with localized disease at the time of diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Power-law growth models explain incidences and sizes of pancreatic cancer precursor lesions and confirm spatial genomic findings

Kiemen,

Wu,

Braxton

et al. 2023

Preprint

Self Cite

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Pancreatic ductal adenocarcinoma is a rare but lethal cancer. Recent evidence reveals that pancreatic intraepithelial neoplasms (PanINs), the microscopic precursor lesions in the pancreatic ducts that can give rise to invasive pancreatic cancer, are significantly larger and more prevalent than previously believed. Better understanding of the growth law dynamics of PanINs may improve our ability to understand how a miniscule fraction of these lesions makes the transition to invasive cancer. Here, using artificial intelligence (AI)-based three-dimensional (3D) tissue mapping method, we measured the volumes of >1,000 PanIN and found that lesion size is distributed according to a power law with a fitted exponent of -1.7 over > 3 orders of magnitude. Our data also suggest that PanIN growth is not very sensitive to the pancreatic microenvironment or an individual’s age, family history, and lifestyle, and is rather shaped by general growth behavior. We analyze several models of PanIN growth and fit the predicted size distributions to the observed data. The best fitting models suggest that both intraductal spread of PanIN lesions and fusing of multiple lesions into large, highly branched structures drive PanIN growth patterns. This work lays the groundwork for future mathematical modeling efforts integrating PanIN incidence, morphology, genomic, and transcriptomic features to understand pancreas tumorigenesis, and demonstrates the utility of combining experimental measurement of human tissues with dynamic modeling for understanding cancer tumorigenesis.

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Pancreatic Cancer Surveillance and Survival of High-Risk Individuals

Blackford,

Canto,

Dbouk

et al. 2024

JAMA Oncol

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ImportancePancreatic ductal adenocarcinoma (PDAC) is a deadly disease with increasing incidence. The majority of PDACs are incurable at presentation, but population-based screening is not recommended. Surveillance of high-risk individuals for PDAC may lead to early detection, but the survival benefit is unproven.ObjectiveTo compare the survival of patients with surveillance-detected PDAC with US national data.Design, Setting, and ParticipantsThis comparative cohort study was conducted in multiple US academic medical centers participating in the Cancer of the Pancreas Screening program, which screens high-risk individuals with a familial or genetic predisposition for PDAC. The comparison cohort comprised patients with PDAC matched for age, sex, and year of diagnosis from the Surveillance, Epidemiology, and End Results (SEER) program. The Cancer of the Pancreas Screening program originated in 1998, and data collection was done through 2021. The data analysis was performed from April 29, 2022, through April 10, 2023.ExposuresEndoscopic ultrasonography or magnetic resonance imaging performed annually and standard-of-care surgical and/or oncologic treatment.Main Outcomes and MeasuresStage of PDAC at diagnosis, overall survival (OS), and PDAC mortality were compared using descriptive statistics and conditional logistic regression, Cox proportional hazards regression, and competing risk regression models. Sensitivity analyses and adjustment for lead-time bias were also conducted.ResultsA total of 26 high-risk individuals (mean [SD] age at diagnosis, 65.8 [9.5] years; 15 female [57.7%]) with PDAC were compared with 1504 SEER control patients with PDAC (mean [SD] age at diagnosis, 66.8 [7.9] years; 771 female [51.3%]). The median primary tumor diameter of the 26 high-risk individuals was smaller than in the control patients (2.5 [range, 0.6-5.0] vs 3.6 [range, 0.2-8.0] cm, respectively; P &lt; .001). The high-risk individuals were more likely to be diagnosed with a lower stage (stage I, 10 [38.5%]; stage II, 8 [30.8%]) than matched control patients (stage I, 155 [10.3%]; stage II, 377 [25.1%]; P &lt; .001). The PDAC mortality rate at 5 years was lower for high-risk individuals than control patients (43% vs 86%; hazard ratio, 3.58; 95% CI, 2.01-6.39; P &lt; .001), and high-risk individuals lived longer than matched control patients (median OS, 61.7 [range, 1.9-147.3] vs 8.0 [range, 1.0-131.0] months; 5-year OS rate, 50% [95% CI, 32%-80%] vs 9% [95% CI, 7%-11%]).Conclusions and RelevanceThese findings suggest that surveillance of high-risk individuals may lead to detection of smaller, lower-stage PDACs and improved survival.

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Screening for pancreatic cancer has the potential to save lives, but is it practical?

Cited by 13 publications

References 224 publications

A Rigorous Multi-Laboratory Study of Known PDAC Biomarkers Identifies Increased Sensitivity and Specificity Over CA19-9 Alone

A Rigorous Multi-Laboratory Study of Known PDAC Biomarkers Identifies Increased Sensitivity and Specificity Over CA19-9 Alone

Power-law growth models explain incidences and sizes of pancreatic cancer precursor lesions and confirm spatial genomic findings

Pancreatic Cancer Surveillance and Survival of High-Risk Individuals

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