Time to progression of pancreatic ductal adenocarcinoma from low-to-high tumour stages

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Abstract

Objective

Although pancreatic ductal adenocarcinoma is considered a rapidly progressive disease, mathematical models estimate that it takes many years for an initiating pancreatic cancer cell to grow into an advanced stage cancer. In order to estimate the time it takes for a pancreatic cancer to progress through different tumor, node, metastasis (TNM) stages, we compared the mean age of patients with pancreatic cancers of different sizes and stages.

Design

Patient age, tumour size, stage and demographic information were analysed for 13 131 patients with pancreatic ductal adenocarcinoma entered into the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database. Multiple linear regression models for age were generated, adjusting for patient ethnicity, gender, tumour location and neoplastic grades.

Results

African-American ethnicity and male gender were associated with an earlier age at diagnosis. Patients with stage I cancers (mean age 64.8 years) were on average 1.3 adjusted years younger at diagnosis than those with stage IV cancers (p=0.001). Among patients without distant metastases, those with T1 stage cancers were on average 1.06 and 1.19 adjusted years younger, respectively, than patients with T3 or T4 cancers (p=0.03 for both). Among patients with stage IIB cancers, those with T1/T2 cancers were 0.79 adjusted years younger than those with T3 cancers (p=0.06). There was no significant difference in the mean adjusted age of patients with stage IA versus stage IB cancers.

Conclusions

These results are consistent with the hypothesis that once pancreatic ductal adenocarcinomas become detectable clinically progression from low-stage to advanced-stage disease is rapid.

Related collections

Most cited references 28

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1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience.

Jordan Winter, John L. Cameron, Kurtis A. Campbell … (2006)

Pancreaticoduodenectomy (PD) with the possible addition of neoadjuvant or adjuvant therapy is the standard of care in the United States for adenocarcinoma originating in the pancreatic head, neck, and uncinate process. We reviewed 1423 patients who underwent a PD for a malignancy originating in the pancreas at our institution between 1970 and 2006. We examined 1175 PDs for ductal adenocarcinomas in greater detail. Eighteen different histological types of pancreatic cancer were identified; the most common diagnoses included ductal adenocarcinoma, neuroendocrine carcinoma, and IPMN with invasive cancer. Patients with ductal adenocarcinoma were analyzed in detail. The median age was 66 years, with patients in the present decade significantly older (68 years), on average, than patients in the three prior decades (e.g., 60 years in 1970, P = 0.02). The median tumor diameter was 3 cm; 42% of the resections had positive margins and 78% had positive lymph nodes. The perioperative morbidity was 38%. The median postoperative stay declined over time, from 16 days in the 1980s to 8 days in the 2000s (P < 0.001). The perioperative mortality declined from 30% in the 1970s to 1% in the 2000s (P < 0.001). The median survival for all patients with ductal adenocarcinoma was 18 months (1-year survival = 65 %, 2-year survival = 37%, 5-year survival = 18%). In a Cox proportional hazards model, pathological factors having a significant impact on survival included tumor diameter, resection margin status, lymph node status, and histologic grade. This is the largest single-institution experience with PD for pancreatic cancer. Patients who have cancers with favorable pathological features have a statistically significant improved long-term survival.

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International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer

Marcia Irene Canto, Femme Harinck, Ralph H. Hruban … (2012)

Background Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. Objective To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. Methods A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥75% agreed or disagreed. Results There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz–Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screening abnormalities were of sufficient concern to for surgery to be recommended. Conclusions Screening is recommended for high-risk individuals, but more evidence is needed, particularly for how to manage patients with detected lesions. Screening and subsequent management should take place at high-volume centres with multidisciplinary teams, preferably within research protocols.

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Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators.

T Sohn, Darren Yeo, J L Cameron … (2015)

This large-volume, single-institution review examines factors influencing long-term survival after resection in patients with adenocarcinoma of the head, neck, uncinate process, body, or tail of the pancreas. Between January 1984 and July 1999 inclusive, 616 patients with adenocarcinoma of the pancreas underwent surgical resection. A retrospective analysis of a prospectively collected database was performed. Both univariate and multivariate models were used to determine the factors influencing survival. Of the 616 patients, 526 (85%) underwent pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas, 52 (9%) underwent distal pancreatectomy for adenocarcinoma of the body or tail, and 38 (6%) underwent total pancreatectomy for adenocarcinoma extensively involving the gland. The mean age of the patients was 64.3 years, with 54% being male and 91% being white. The overall perioperative mortality rate was 2.3%, whereas the incidence of postoperative complications was 30%. The median postoperative length of stay was 11 days. The mean tumor diameter was 3.2 cm, with 72% of patients having positive lymph nodes, 30% having positive resection margins, and 36% having poorly differentiated tumors. Patients undergoing distal pancreatectomy for left-sided lesions had larger tumors (4.7 vs. 3.1 cm, P < 0.0001), but fewer node-positive resections (59% vs. 73%, P = 0.03) and fewer poorly differentiated tumors (29% vs. 36%, P < 0.001), as compared to those undergoing pancreaticoduodenectomy for right-sided lesions. The overall survival of the entire cohort was 63% at 1 year and 17% at 5 years, with a median survival of 17 months. For right-sided lesions the 1- and 5-year survival rates were 64% and 17%, respectively, compared to 50% and 15% for left-sided lesions. Factors shown to have favorable independent prognostic significance by multivariate analysis were negative resection margins (hazard ratio [HR] = 0.64, confidence interval [CI] = 0.50 to 0.82, P = 0.0004), tumor diameter less than 3 cm (HR = 0.72, CI = 0.57 to 0.90, P = 0.004), estimated blood loss less than 750 ml (HR = 0.75, CI = 0.58 to 0.96, P = 0.02), well/moderate tumor differentiation (HR = 0.71, CI = 0.56 to 0.90, P = 0.005), and postoperative chemoradiation (HR = 0.50, CI = 0.39 to 0.64, P < 0.0001). Tumor location in head, neck, or uncinate process approached significance in the final multivariate model (HR = 0.60, CI = 0.35 to 1.0, P = 0.06). Pancreatic resection remains the only hope for long-term survival in patients with adenocarcinoma of the pancreas. Completeness of resection and tumor characteristics including tumor size and degree of differentiation are important independent prognostic indicators. Adjuvant chemoradiation is a strong predictor of outcome and likely decreases the independent significance of tumor location and nodal status.

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Author and article information

Journal

Journal ID (nlm-ta): Gut

Journal ID (iso-abbrev): Gut

Journal ID (hwp): gutjnl

Journal ID (publisher-id): gut

Title: Gut

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Print): 0017-5749

ISSN (Electronic): 1468-3288

Publication date (Print): November 2015

Publication date (Electronic): 30 January 2015

Volume: 64

Issue: 11

Pages: 1783-1789

Affiliations

[1 ]Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine , Baltimore, Maryland, USA

[2 ]Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine , Baltimore, Maryland, USA

[3 ]Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine , Baltimore, Maryland, USA

[4 ]Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine , Baltimore, Maryland, USA

Author notes

[Correspondence to ] Dr Michael Goggins, Johns Hopkins Medical Institutions, Department of Pathology, 1550 Orleans Street, Baltimore, MD 21231, USA; mgoggins@ 123456jhmi.edu

Article

Publisher ID: GUTJNL-2014-308653

DOI: 10.1136/gutjnl-2014-308653

PMC ID: 4520782

PubMed ID: 25636698

SO-VID: 8d948a2f-7d23-4b8c-81c9-f5f0668876d2

License:

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/