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Cited by 247Pancreatic and Hepatic Oncology ResearchGlobal Cancer Incidence and ScreeningPancreatitis Pathology and Treatment

The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival

Open access
Dbouk, Mohamad, Katona, Bryson W., Brand, Randall E., Chak, Amitabh, Syngal, Sapna, Farrell, James J., Kastrinos, Fay, Stoffel, Elena M. +15 more·2022·Journal of Clinical Oncology
DOI 10.1200/jco.22.00298PMC PMC9553376
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Abstract

PURPOSE: To report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies. METHODS: Individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and 2021. The primary end point was the stage distribution of pancreatic ductal adenocarcinoma (PDAC) detected (stage I v higher-stage). Overall survival was determined using the Kaplan-Meier method. RESULTS: Of 1,461 high-risk individuals enrolled into CAPS5, 48.5% had a pathogenic variant in a PDAC-susceptibility gene. Ten patients were diagnosed with PDAC, one of whom was diagnosed with metastatic PDAC 4 years after dropping out of surveillance. Of the remaining nine, seven (77.8%) had a stage I PDAC (by surgical pathology) detected during surveillance; one had stage II, and one had stage III disease. Seven of these nine patients with PDAC were alive after a median follow-up of 2.6 years. Eight additional patients underwent surgical resection for worrisome lesions; three had high-grade and five had low-grade dysplasia in their resected specimens. In the entire CAPS cohort (CAPS1-5 studies, 1,731 patients), 26 PDAC cases have been diagnosed, 19 within surveillance, 57.9% of whom had stage I and 5.2% had stage IV disease. By contrast, six of the seven PDACs (85.7%) detected outside surveillance were stage IV. Five-year survival to date of the patients with a screen-detected PDAC is 73.3%, and median overall survival is 9.8 years, compared with 1.5 years for patients diagnosed with PDAC outside surveillance (hazard ratio [95% CI]; 0.13 [0.03 to 0.50], P = .003). CONCLUSION: Most pancreatic cancers diagnosed within the CAPS high-risk cohort in the recent years have had stage I disease with long-term survival.

AI snapshot

Written from the paper’s full text.

TL;DR

In the multicenter CAPS5 prospective cohort of 1,461 high-risk individuals, 9 screen-detected pancreatic ductal adenocarcinomas (PDACs) were diagnosed, and 7/9 (77.8%) were stage I by surgical pathology. In the combined CAPS1-5 cohort, screen-detected PDACs had 57.9% stage I disease and 73.3% 5-year survival, with median overall survival of 9.8 years versus 1.5 years for PDACs diagnosed outside surveillance.

Key findings

  • Among 1,461 CAPS5 high-risk individuals enrolled 2014-2021, 48.5% had a pathogenic variant in a PDAC-susceptibility gene; 10 patients were diagnosed with PDAC, 9 during surveillance. Of the 9 screen-detected PDACs, 7 (77.8%) were stage I by surgical pathology (4 stage IA, 3 stage IB), 1 was stage IIB, and 1 was stage III; 8/9 (88.9%) were resectable. Seven of these 9 patients were alive after a median follow-up of 2.6 years, with median overall survival to date of 3.84 years.
  • Eight additional CAPS5 patients underwent surgical resection for worrisome lesions; 3 had high-grade dysplasia and 5 had low-grade dysplasia. Overall, 10 of 18 patients with PDAC or resection had pathology meeting recommended surveillance goals (7 stage I PDAC and 3 high-grade dysplasia).
  • In the combined CAPS1-5 cohort of 1,731 high-risk individuals, 26 PDACs were diagnosed; 19 were detected during surveillance, with 57.9% stage I, 15.8% stage II, 21.1% stage III, and 5.2% stage IV. Six of 7 PDACs (85.7%) detected outside surveillance were stage IV.
  • Screen-detected PDACs had 5-year survival of 73.3% and median overall survival of 9.8 years, compared with 1.5 years for PDACs diagnosed outside surveillance (unadjusted HR 0.13 [95% CI, 0.03 to 0.50], P = .003; adjusted HR 0.04 [95% CI, 0.004 to 0.32], P = .003). The CAPS1-5 detection rate was 5.15 PDACs per 1,000 person-years of surveillance, or one PDAC per year for every 194 screened.

Methods

  • CAPS5 is a multicenter, prospective cohort study at eight US academic medical centers, enrolling high-risk individuals recommended for pancreas surveillance from 2014 until June 2021; the report also updates the Johns Hopkins CAPS1-4 single-center experience since 1998 and combines data as CAPS1-5.
  • Eligible participants were high-risk individuals recommended for surveillance per CAPS international consensus guidelines, including those with familial/inherited risk; surveillance used magnetic resonance imaging and endoscopic ultrasound, typically annually.
  • The primary endpoint was stage I PDAC or noninvasive neoplasm with high-grade dysplasia, reported descriptively; overall survival was estimated by Kaplan-Meier, and screen-detected versus outside-surveillance PDAC survival was compared with Cox proportional hazards models, unadjusted and adjusted for age at diagnosis and risk group.

Limitations

  • The paper states that CAPS5 follow-up is relatively short, that long-term survival outcomes are needed to minimize confounding from lead-time bias, and that few PDACs have been diagnosed to date, especially outside surveillance, limiting precision.
  • The paper notes that a larger cohort with longer follow-up would generate better precision estimates for the proportion of stage I PDACs diagnosable with surveillance.
  • Evident from the text: this is an observational surveillance cohort without a randomized control group, and five resections for low-grade dysplasia highlight limitations of current EUS and MRI to characterize concerning lesions.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1200/jco.22.00298

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 26 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    One CAPS5 patient was diagnosed with metastatic PDAC 4 years after dropping out of surveillance.

    “one of whom was diagnosed with metastatic PDAC 4 years after dropping out of surveillance.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Of 1,461 high-risk individuals enrolled in CAPS5, 48.5% had a pathogenic variant in a PDAC-susceptibility gene.

    “Of 1,461 high-risk individuals enrolled into CAPS5, 48.5% had a pathogenic variant in a PDAC-susceptibility gene.”
    • Also stated in: § Study Population · plain
      “48.5% of participants had a pathogenic germline variant, including 18.4% with a BRCA2 and 6.4% with an ATM variant.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Ten patients in CAPS5 were diagnosed with PDAC.

    “Ten patients were diagnosed with PDAC”
    • Also stated in: § Pancreatic Cancers and Other Resected Lesions · plain
      “During the CAPS5 study surveillance period, nine patients were diagnosed with a screen-detected PDAC (either at baseline or at subsequent surveillance visits). One additional patient presented with symptomatic metastatic PDAC 4 years after their baseline and only surveillance (Table 2).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Screen-detected PDAC in CAPS1-5 is associated with significantly longer survival than PDAC diagnosed outside surveillance (unadjusted HR 0.13 [95% CI, 0.03 to 0.50], P = .003).

    “hazard ratio [95% CI]; 0.13 [0.03 to 0.50], P = .003”
    • Also stated in: § CAPS1-5 Combined Cohort · plain
      “HR unadjusted: 0.13 [95% CI, 0.03 to 0.50], P = .003”
    Quote in the paperSubstantial claim
  • Findingown data

    Of the 13 patients with HGD in IPMN or PanIN who underwent resection, 12 (92%) were alive at last follow-up.

    “Overall, of the 13 patients with HGD in IPMN or pancreatic intraepithelial neoplasias who underwent resection, 12 (92%) were alive at last follow-up”
    Quote in the paperNot a substantial claim
  • May combine two claims. 15
  • Classified as probably not a substantial claim. 7

  • May combine two claims.

    Findingown data

    Median overall survival of patients with screen-detected PDAC in CAPS is 9.8 years, compared with 1.5 years for patients diagnosed outside surveillance.

    “median overall survival is 9.8 years, compared with 1.5 years for patients diagnosed with PDAC outside surveillance”
    • Also stated in: § CAPS1-5 Combined Cohort · plain
      “The median survival for the patients with a screen-detected PDAC was 9.8 years (95% CI, 5.2 to ∼ years, ∼; small sample size precludes upper survival limit estimate), compared with 1.5 years (0.50 to ∼ years) for patients whose PDACs were diagnosed outside surveillance”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In CAPS1-5, 10 patients had resections of IPMN with HGD, and none of the resected PDACs were associated with an IPMN by surgical pathology.

    “Regarding management of IPMN, 10 patients had resections of IPMN with HGD, but none of the resected PDACs were associated with an IPMN by surgical pathology.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Eight additional CAPS5 patients underwent surgical resection for worrisome lesions; three had high-grade dysplasia and five had low-grade dysplasia.

    “Eight additional patients underwent surgical resection for worrisome lesions; three had high-grade and five had low-grade dysplasia in their resected specimens.”
    • Also stated in: § Pancreatic Cancers and Other Resected Lesions · plain
      “In addition, eight patients had pancreatic resections for concerning cystic lesions detected during surveillance; three were found to have HGD (in high-grade pancreatic intraepithelial neoplasia or IPMN; summarized in Table 2). The remaining five patients who underwent surgical resection for worrisome lesions had only low-grade dysplasia”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Of the 19 screen-detected PDACs in CAPS1-5, 57.9% had stage I disease and 5.2% had stage IV disease.

    “57.9% of whom had stage I and 5.2% had stage IV disease.”
    • Also stated in: § CAPS1-5 Combined Cohort · plain
      “57.9% of whom had stage I disease, 15.8% stage II, 21.1% stage III, and 5.2% stage IV”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Of the nine screen-detected PDACs in CAPS5, one was stage II and one was stage III.

    “one had stage II, and one had stage III disease.”
    • Also stated in: § Pancreatic Cancers and Other Resected Lesions · plain
      “one patient had stage IIB cancer (case 8), and one (case 9) had a stage III cancer (clinically staged) with superior mesenteric artery involvement”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The results support current CAPS surveillance recommendations and argue against limiting pancreatic surveillance to high-risk individuals with known pathogenic mutations.

    “Our results support current CAPS surveillance recommendations and argue against the notion of limiting pancreatic surveillance to those high-risk individuals with known pathogenic mutations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The CAPS5 study has relatively short follow-up, and few PDACs have been diagnosed to date, limiting precision.

    “Some limitations to our study include our relatively short follow-up of the CAPS5 study cohort included in this study”
    • Also stated in: § DISCUSSION · plain
      “Few PDACs have been diagnosed-to-date in the CAPS program; a larger cohort with longer follow-up would generate better precision estimates for the proportion of stage I PDACs diagnosable with surveillance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The risk of PDAC increases with the number of affected first-degree relatives with pancreatic cancer and in those who carry a pathogenic germline variant in a pancreatic cancer susceptibility gene.

    “The risk increases with the number of affected first-degree relatives with pancreatic cancer and in those who carry a pathogenic germline variant in a pancreatic cancer susceptibility gene.9-11”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [9] source

      Not checked in the free run.

    • cites [10] source

      Not checked in the free run.

    • cites [11] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Most pancreatic cancers diagnosed within the CAPS high-risk cohort in recent years have had stage I disease with long-term survival.

    “Most pancreatic cancers diagnosed within the CAPS high-risk cohort in the recent years have had stage I disease with long-term survival.”
    • Also stated in: § DISCUSSION · plain
      “most of the patients with PDACs diagnosed in the multicenter CAPS5 study to date had stage I disease.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Stage I PDAC is the stage when pancreatic cancer is most curable.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The survival comparison was adjusted for age at diagnosis and risk group.

    “We report hazard ratios (HRs) both unadjusted and adjusted for age at diagnosis and whether patients were enrolled for family history or pathogenic variant in a PDAC susceptibility gene.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    In 2019, the US Preventative Services Task Force recommended against pancreas screening of asymptomatic average-risk adults and those with a family history, but it did not address the role of surveillance in germline mutation carriers.

    “In 2019, the US Preventative Services Task Force recommended against pancreas screening of asymptomatic average-risk adults and those with a family history, but it did not address the role of surveillance in germline mutation carriers.12,13”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12] source

      Not checked in the free run.

    • cites [13] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Pancreas surveillance has been recommended for individuals estimated to be at high risk of developing PDAC (5% or higher estimated lifetime risk).

    “Pancreas surveillance has been recommended for individuals estimated to be at high risk of developing PDAC (5% or higher estimated lifetime risk).5-8”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [5] source

      Not checked in the free run.

    • cites [6] source

      Not checked in the free run.

    • cites [7] source

      Not checked in the free run.

    • cites [8] source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    The comparison of outcomes between screen-detected PDAC and PDAC diagnosed after dropping out of surveillance is worthwhile because these groups have similar demographic/risk characteristics, but the number of such cases was small.

    “Comparing outcomes of those diagnosed with a screen-detected PDAC to those whose PDAC was diagnosed after dropping out of surveillance is worthwhile because these groups have similar demographic/risk characteristics, and for whom data on pancreatic cancer outcomes is limited,41-43 but the number of such cases was small.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [41] source

      Not checked in the free run.

    • cites [42] source

      Not checked in the free run.

    • cites [43] source

      Not checked in the free run.

    • Rests on an assumption: The screen-detected PDAC and PDAC diagnosed after dropping out of surveillance groups have similar demographic/risk characteristics.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The study was approved by institutional review boards and all participants provided written informed consent.

    “CAPS5 was approved by the Johns Hopkins Institutional Review Board and the institutional review boards at each of the CAPS sites with written informed consent provided by all participants.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    The low diagnostic yield of PDACs in the CAPS cohort highlights the need to develop more refined estimates of pancreatic cancer risk.

    “At the same time, the low diagnostic yield of PDACs in our cohort highlights the need to develop more refined estimates of pancreatic cancer risk.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Study design and conductnone given

    Long-term survival outcomes are needed to minimize confounding from lead-time bias.

    “Long-term survival outcomes are needed to minimize confounding from lead-time bias.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The CAPS5 study results differ from the Dutch Familial Pancreatic Cancer Surveillance Study Group report, which had a PDAC resectability rate of only 60%, possibly due to predominance of CDKN2A mutation carriers.

    “The CAPS5 study results differ in some respects from the recent report of the Dutch Familial Pancreatic Cancer Surveillance Study Group.16 This study reported a PDAC resectability rate of only 60%, which may be a function of the predominance of CDKN2A mutation carriers in their high-risk cohort”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] source

      Not checked in the free run.

    • cites [24] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The five CAPS5 pancreatic resections for worrisome findings that harbored low-grade dysplasia only represent a smaller proportion of resections for low-grade lesions than reported in prior studies, likely due to better selection of patients for surgery.

    “it is notable that these five cases represent a smaller proportion of resections for low-grade lesions than has been reported in prior studies14,15,29,30 and likely results from better selection of patients for surgery.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [14] source

      Not checked in the free run.

    • cites [15] source

      Not checked in the free run.

    • cites [29] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Recent evidence indicates that pancreas surveillance can downstage pancreatic cancers diagnosed in high-risk individuals, though based on few studies.

    “Recent evidence indicates that pancreas surveillance can downstage pancreatic cancers diagnosed in high-risk individuals (HRIs), although this is based upon only a few studies,12,14-16 with relatively few PDACs diagnosed, and only a small percentage of which were diagnosed with stage I disease.17”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [12] source

      Not checked in the free run.

    • cites [14] source

      Not checked in the free run.

    • cites [15] source

      Not checked in the free run.

    • cites [16] source

      Not checked in the free run.

    • cites [17] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    The improvement in surveillance outcomes reported here compared with previous reports is likely the combined effect of multiple factors, including case mix, diagnostic performance, and cumulative experience.

    “The improvement in surveillance outcomes reported here compared with previous reports is likely the combined effect of multiple factors, including our case mix (CDKN2A carriers appear to have more aggressive disease), the diagnostic performance of our study team, and the cumulative experience gained from undertaking pancreatic screening studies over more than 20 years.”
    Quote in the paperNot a substantial claim
20 of 20

  • The paper relies on this without support.

    The screen-detected PDAC and PDAC diagnosed after dropping out of surveillance groups have similar demographic/risk characteristics.

    “these groups have similar demographic/risk characteristics”

  • The paper relies on this without support.

    Stage I PDAC is the stage when pancreatic cancer is most curable.

    “at a stage when the disease is most curable (stage I PDAC)”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Patients with pancreatic cancer detected by screening had a 5-year survival rate of 73.3% and a median survival time of 9.8 years, compared with 1.5 years for patients with PC seen by non-screening.

    “A multicenter study demonstrated that patients with PC detected by screening had a 5-year survival rate of 73.3% and a median survival time of 9.8 years, compared with 1.5 years for patients with PC seen by non-screening 14.”

    From Artificial intelligence in pancreatic cancer (2022) · cites this paper as [14]

  • In a large multi-center international trial of high-risk cohorts, almost three-fourths of patients diagnosed with PDAC on active surveillance had Stage I disease, and an equal proportion were alive at five years.

    “almost three-fourths of patients who were diagnosed with PDAC on active surveillance had Stage I disease, and an equal proportion were still alive at five years”

    From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [21]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • CAPS5 median survival conflicts with its reported result

    Major

    The discussion attributes a 9.8-year median survival to CAPS5, but the CAPS5 results state 3.84 years. The results attribute 9.8 years to the combined CAPS1-5 cohort instead.

1 of 1

The citation lists haven’t been fetched yet

References 44 · Cited by 247

Research works printed but not linked: 3

  1. Brune K, 2006, Am J Surg Pathol, 30, 1067
  2. Canto MI, 2019, J Gastrointest Surg, 115, 1
  3. Tanaka H, Clin Gastroenterol Hepatol

Authors
Dbouk, M., Katona, B. W., Brand, R. E., Chak, A., Syngal, S., Farrell, J. J., Kastrinos, F., Stoffel, E. M., Blackford, A. L., Rustgi, A. K., Dudley, B., Lee, L. S., Chhoda, A., Kwon, R., Ginsberg, G. G., Klein, A. P., Kamel, I., Hruban, R. H., He, J., Shin, E. J., Lennon, A. M., Canto, M. I., & Goggins, M.
Affiliations
  • Johns Hopkins University (US)
  • Abramson Cancer Center (US)
  • University of Pittsburgh Medical Center (US)
  • University Hospitals of Cleveland (US)
  • Brigham and Women's Hospital (US)
  • Yale University (US)
  • Columbia University Irving Medical Center (US)
  • University of Michigan (US)
Corresponding author
Goggins, Michael
ORCID
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2022-10-01
Volume
40
Issue
28
Pages
3257-3266
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.22.00298
PMC
PMC9553376
OpenAlex
W4282963663
Semantic Scholar
df60386bbc317043038f94ab2190585d12e7ac91
Cited by
247
References
44
Citations by year
2026: 50 · 2025: 64 · 2024: 71 · 2023: 50 · 2022: 12
FWCI
20.61
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of Clinical Oncology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (UL1TR001863)
  • National Cancer Institute (P50CA062924, R01CA176828, U01CA210170, P30CA013696)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK132710)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Health Sciences › Medicine › Oncology › Global Cancer Incidence and Screening
  • Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
Keywords
pancreatic ductal adenocarcinoma, pancreatic cancer screening, early-stage cancer detection, stage at diagnosis, overall survival, high-risk individuals, hereditary cancer predisposition, pathogenic variants, pancreatic dysplasia
MeSH terms
Humans, Pancreas, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Early Detection of Cancer

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