Disparities in the Use of Neoadjuvant Therapy for Resectable Pancreatic Ductal Adenocarcinoma

Restricted access

Background: Current guidelines support either immediate surgical resection or neoadjuvant therapy (NT) for patients with resectable pancreatic ductal adenocarcinoma (PDAC). However, which patients are selected for NT and whether disparities exist in the use of NT for PDAC are not well understood. Methods: Using the National Cancer Database from 2004 through 2016, the clinical, demographic, socioeconomic, and hospital-related characteristics of patients with stage I/II PDAC who underwent immediate surgery versus NT followed by surgery were compared. Results: Among 58,124 patients who underwent pancreatectomy, 8,124 (14.0%) received NT whereas 50,000 (86.0%) did not. Use of NT increased significantly throughout the study period (from 3.5% in 2004 to 26.4% in 2016). Multivariable logistic regression analysis showed that travel distance, education level, hospital facility type, clinical T stage, tumor size, and year of diagnosis were associated with increased use of NT, whereas comorbidities, uninsured/Medicaid status, South/West geography, left-sided tumor location, and increasing age were associated with immediate surgery (all P<.001). Based on logistic regression–derived interaction factors, the association between NT use and median income, education level, Midwest location, clinical T stage, and clinical N stage significantly increased over time (all P<.01). Conclusions: In addition to traditional clinicopathologic factors, several demographic, socioeconomic, and hospital-related factors are associated with use of NT for PDAC. Because NT is used increasingly for PDAC, efforts to reduce disparities will be critical in improving outcomes for all patients with pancreatic cancer.

Submitted September 13, 2019; accepted for publication November 25, 2019.

Author contributions: Study concept: Cloyd, Santry, Bridges, Dillhoff, Ejaz, Pawlik, Tsung. Methodology: Cloyd, Shen, Tsung. Investigation: Cloyd. Visualization: Cloyd. Supervision: Cloyd, Tsung. Formal analysis: Shen. Validation: Tsung. Resources: Tsung. Writing–original draft: Cloyd. Writing–review and editing: All authors. Project administration: Tsung.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Jordan M. Cloyd, MD, Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, 410 West 10th Avenue, N-907 Doan Hall, Columbus, OH 43210. Email: jordan.cloyd@osumc.edu
  • 1.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:734.

  • 2.

    Neoptolemos JP, Stocken DD, Friess H, . A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004;350:12001210.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Oettle H, Post S, Neuhaus P, . Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007;297:267277.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Bilimoria KY, Bentrem DJ, Ko CY, . Multimodality therapy for pancreatic cancer in the U.S.: utilization, outcomes, and the effect of hospital volume. Cancer 2007;110:12271234.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Mayo SC, Gilson MM, Herman JM, . Management of patients with pancreatic adenocarcinoma: national trends in patient selection, operative management, and use of adjuvant therapy. J Am Coll Surg 2012;214:3345.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Simons JP, Ng SC, McDade TP, . Progress for resectable pancreatic [corrected] cancer?: a population-based assessment of US practices [published correction appears in Cancer 2010;116:2503]. Cancer 2010;116:16811690.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Valle JW, Palmer D, Jackson R, . Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. J Clin Oncol 2014;32:504512.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Altman AM, Wirth K, Marmor S, . Completion of adjuvant chemotherapy after upfront surgical resection for pancreatic cancer is uncommon yet associated with improved survival. Ann Surg Oncol 2019;26:41084116.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Cloyd JM, Katz MHG, Prakash L, . Preoperative therapy and pancreatoduodenectomy for pancreatic ductal adenocarcinoma: a 25-year single-institution experience. J Gastrointest Surg 2017;21:164174.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Youngwirth LM, Nussbaum DP, Thomas S, . Nationwide trends and outcomes associated with neoadjuvant therapy in pancreatic cancer: an analysis of 18,243 patients. J Surg Oncol 2017;116:127132.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Cloyd JM, Wang H, Egger ME, . Association of clinical factors with a major pathologic response following preoperative therapy for pancreatic ductal adenocarcinoma. JAMA Surg 2017;152:10481056.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Mokdad AA, Minter RM, Zhu H, . Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score matched analysis. J Clin Oncol 2017;35:515522.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Estrella JS, Rashid A, Fleming JB, . Post-therapy pathologic stage and survival in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant chemoradiation. Cancer 2012;118:268277.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Sugimoto M, Takahashi N, Farnell MB, . Survival benefit of neoadjuvant therapy in patients with non-metastatic pancreatic ductal adenocarcinoma: a propensity matching and intention-to-treat analysis. J Surg Oncol 2019;120:976984.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Versteijne E, Vogel JA, Besselink MG, . Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg 2018;105:946958.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Bradley A, Van Der Meer R. Upfront surgery versus neoadjuvant therapy for resectable pancreatic cancer: systematic review and bayesian network meta-analysis. Sci Rep 2019;9:4354.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Unno M, Hata T, Motoi F. Long-term outcome following neoadjuvant therapy for resectable and borderline resectable pancreatic cancer compared to upfront surgery: a meta-analysis of comparative studies by intention-to-treat analysis. Surg Today 2019;49:295299.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    de Geus SWL, Evans DB, Bliss LA, . Neoadjuvant therapy versus upfront surgical strategies in resectable pancreatic cancer: a Markov decision analysis. Eur J Surg Oncol 2016;42:15521560.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Ren X, Wei X, Ding Y, . Comparison of neoadjuvant therapy and upfront surgery in resectable pancreatic cancer: a meta-analysis and systematic review. OncoTargets Ther 2019;12:733744.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Van Tienhoven G, Versteijne E, Suker M, . Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): a randomized, controlled, multicenter phase III trial [abstract]. J Clin Oncol 2018;36(Suppl):Abstract LBA4002.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Jang JY, Han Y, Lee H, . Oncological benefits of neoadjuvant chemoradiation with gemcitabine versus upfront surgery in patients with borderline resectable pancreatic cancer: a prospective, randomized, open-label, multicenter phase 2/3 trial. Ann Surg 2018;268:215222.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Khorana AA, Mangu PB, Berlin J, . Potentially curable pancreatic cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2016;34:25412556.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Tempero MA, Malafa MP, Al-Hawary M, . NCCN Clinical Practice Guidelines in Oncology: Pancreatic Adenocarcinoma. Version 3.2019. Accessed November 13, 2019. To view the most recent version, visit NCCN.org.

  • 24.

    Raval MV, Bilimoria KY, Stewart AK, . Using the NCDB for cancer care improvement: an introduction to available quality assessment tools. J Surg Oncol 2009;99:488490.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Boffa DJ, Rosen JE, Mallin K, . Using the National Cancer Database for outcomes research: a review. JAMA Oncol 2017;3:17221728.

  • 26.

    Hashmi A, Kozick Z, Fluck M, . Neoadjuvant versus adjuvant chemotherapy for resectable pancreatic adenocarcinoma: a National Cancer Database analysis. Am Surg 2018;84:14391445.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Cunningham D, Allum WH, Stenning SP, . Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:1120.

  • 28.

    van Hagen P, Hulshof MCCM, van Lanschot JJB, . Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012;366:20742084.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Kapiteijn E, Marijnen CAM, Nagtegaal ID, . Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345:638646.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    van der Hage JA, van de Velde CJ, Julien JP, . Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 2001;19:42244237.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Abraham A, Al-Refaie WB, Parsons HM, . Disparities in pancreas cancer care. Ann Surg Oncol 2013;20:20782087.

  • 32.

    Boevers E, McDowell BD, Mott SL, . Insurance status is related to receipt of therapy and survival in patients with early-stage pancreatic exocrine carcinoma. J Cancer Epidemiol 2017;2017:4354592.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Davila JA, Chiao EY, Hasche JC, . Utilization and determinants of adjuvant therapy among older patients who receive curative surgery for pancreatic cancer. Pancreas 2009;38:e1825.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Jindal M, Zheng C, Quadri HS, . Why do long-distance travelers have improved pancreatectomy outcomes? J Am Coll Surg 2017;225:216225.

  • 35.

    Makar M, Worple E, Dove J, . Disparities in care: impact of socioeconomic factors on pancreatic surgery: exploring the National Cancer Database. Am Surg 2019;85:327334.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Fisher AV, Abbott DE, Venkatesh M, . The impact of hospital neoadjuvant therapy utilization on survival outcomes for pancreatic cancer. Ann Surg Oncol 2018;25:26612668.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Christians KK, Heimler JW, George B, . Survival of patients with resectable pancreatic cancer who received neoadjuvant therapy. Surgery 2016;159:893900.

  • 38.

    Tzeng C-WD, Fleming JB, Lee JE, . Defined clinical classifications are associated with outcome of patients with anatomically resectable pancreatic adenocarcinoma treated with neoadjuvant therapy. Ann Surg Oncol 2012;19:20452053.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 1381 1381 1044
PDF Downloads 266 266 197
EPUB Downloads 0 0 0