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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 6/2021

01-06-2021 | Pancreatic Tumors

Comparative Effectiveness of Neoadjuvant Therapy and Upfront Resection for Patients with Resectable Pancreatic Adenocarcinoma: An Instrumental Variable Analysis

Authors: Wilson Luiz da Costa Jr., MD, MPH, PhD, Hop S. Tran Cao, MD, Kyle H. Sheetz, MD, MSc, Xiangjun Gu, PhD, Edward C. Norton, PhD, Nader N. Massarweh, MD, MPH

Published in: Annals of Surgical Oncology | Issue 6/2021

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Abstract

Background

Neoadjuvant therapy (NAT) is increasingly being used in the management of patients with resectable pancreatic ductal adenocarcinoma (PDAC); however, there is a lack of evidence regarding the benefit among these patients.

Objective

The aim of this study was to evaluate overall survival (OS) in PDAC patients with resectable disease treated with NAT or upfront resection through instrumental variable (IV) analysis.

Design

A national cohort study of resectable PDAC patients in the National Cancer Data Base (2007–2015) treated with either upfront surgery or resection after NAT. Using multivariable modeling and IV methods, OS was compared between those treated with NAT and upfront resection. The IV was hospital-level NAT utilization in the most recent year prior to treatment.

Results

The cohort included 16,666 patients (14,012 upfront resection; 2654 NAT) treated at 779 hospitals. Among those treated with upfront resection, 59.9% received any adjuvant therapy. NAT patients had higher median (27.9 months, 95% confidence interval [CI] 26.2–29.1) and 5-year OS (24.1%, 95% CI 21.9–26.3%) compared with those treated with upfront surgery (median 21.2 months, 95% CI 20.7–21.6; 5-year survival 20.9%, 95% CI 20.1–21.7%). After multivariable modeling, NAT was associated with an approximately 20% decrease in the risk of death (hazard ratio [HR] 0.78, 95% CI 0.73–0.84), and this effect was magnified in the IV analysis (HR 0.61, 95% CI 0.47–0.79).

Conclusions

In patients with resectable PDAC, NAT is associated with improved survival relative to upfront resection. Given the benefits of multimodality therapy and the challenges in receiving adjuvant therapy, consideration should be given to treating all PDAC patients with NAT.
Literature
1.
2.
3.
Khorana AA, McKernin SE, Berlin J, Hong TS, Maitra A, Moravek C, et al. Potentially curable pancreatic adenocarcinoma: ASCO clinical practice guideline update. J Clin Oncol. 2019;37(23):2082–8.CrossRef
4.
Youngwirth LM, Nussbaum DP, Thomas S, Adam MA, Blazer DG, 3rd, Roman SA, et al. Nationwide trends and outcomes associated with neoadjuvant therapy in pancreatic cancer: an analysis of 18 243 patients. J Surg Oncol. 2017;116(2):127–32.CrossRef
5.
Mirkin KA, Hollenbeak CS, Gusani NJ, Wong J. Trends in utilization of neoadjuvant therapy and short-term outcomes in resected pancreatic cancer. Am J Surg. 2017;214(1):80–8.CrossRef
6.
Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, et al. FOLFIRINOX or Gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379(25):2395–406.CrossRef
7.
Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310(14):1473–81.CrossRef
8.
Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011–24.CrossRef
9.
Mayo SC, Gilson MM, Herman JM, Cameron JL, Nathan H, Edil BH, et al. Management of patients with pancreatic adenocarcinoma: national trends in patient selection, operative management, and use of adjuvant therapy. J Am Coll Surg. 2012;214(1):33–45.CrossRef
10.
Tran Cao HS, Zhang Q, Sada YH, Silberfein EJ, Hsu C, Van Buren G, 2nd, et al. Value of lymph node positivity in treatment planning for early stage pancreatic cancer. Surgery. 2017;162(3):557–67.CrossRef
11.
Nathan H, Atoria CL, Bach PB, Elkin EB. Hospital volume, complications, and cost of cancer surgery in the elderly. J Clin Oncol. 2015;33(1):107–14.CrossRef
12.
Merkow RP, Bilimoria KY, Tomlinson JS, Paruch JL, Fleming JB, Talamonti MS, et al. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg. 2014;260(2):372–7.CrossRef
13.
14.
Mokdad AA, Minter RM, Zhu H, Augustine MM, Porembka MR, Wang SC, et al. Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score matched analysis. J Clin Oncol. 2017;35(5):515–22.CrossRef
15.
Murphy JE, Wo JY, Ryan DP, Jiang W, Yeap BY, Drapek LC, et al. Total neoadjuvant therapy With FOLFIRINOX followed by individualized chemoradiotherapy for borderline resectable pancreatic adenocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2018;4(7):963–9.CrossRef
16.
Versteijne E, Vogel JA, Besselink MG, Busch ORC, Wilmink JW, Daams JG, et al. Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg. 2018;105(8):946–58.CrossRef
17.
18.
Fisher AV, Abbott DE, Venkatesh M, Leverson GE, Campbell-Flohr SA, Ronnekleiv-Kelly SM, et al. The impact of hospital neoadjuvant therapy utilization on survival outcomes for pancreatic cancer. Ann Surg Oncol. 2018;25(9):2661–8.CrossRef
19.
da Costa WL Jr, Tran Cao HS, Massarweh NN. Neoadjuvant treatment for patients with localized pancreatic adenocarcinoma—are we there yet? JAMA Oncol. 2020;6(8):1163–4.CrossRef
20.
Satoi SUM, Motoi F, Matsuyama Y, Matsumoto I, Aosasa S, et al. The effect of neoadjuvant chemotherapy with gemcitabine and S-1 for resectable pancreatic cancer (randomized phase II/III trial; Prep-02/JSAP-05). J. Clin. Oncol. 2019;37(15 Suppl):4126.CrossRef
21.
Versteijne E, Suker M, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: results of the dutch randomized phase III PREOPANC trial. J Clin Oncol. 2020;38(16):1763–73.CrossRef
22.
Newhouse JP, McClellan M. Econometrics in outcomes research: the use of instrumental variables. Annu Rev Public Health. 1998;19:17–34.CrossRef
23.
Stukel TA, Fisher ES, Wennberg DE, Alter DA, Gottlieb DJ, Vermeulen MJ. Analysis of observational studies in the presence of treatment selection bias: effects of invasive cardiac management on AMI survival using propensity score and instrumental variable methods. JAMA. 2007;297(3):278–85.CrossRef
24.
Urbach DR. Pledging to eliminate low-volume surgery. N Engl J Med. 2015;373(15):1388-90.CrossRef
25.
Terza JV, Basu A, Rathouz PJ. Two-stage residual inclusion estimation: addressing endogeneity in health econometric modeling. J Health Econ. 2008;27(3):531–43.CrossRef
26.
Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.CrossRef
27.
Neoptolemos JP, Moore MJ, Cox TF, Valle JW, Palmer DH, McDonald AC, et al. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012;308(2):147–56.CrossRef
28.
Janssen QP, Buettner S, Suker M, Beumer BR, Addeo P, Bachellier P, et al. Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: a systematic review and patient-level meta-analysis. J Natl Cancer Inst. 2019;111(8):782–94.CrossRef
29.
Tzeng CW, Fleming JB, Lee JE, Xiao L, Pisters PW, Vauthey JN, et al. Defined clinical classifications are associated with outcome of patients with anatomically resectable pancreatic adenocarcinoma treated with neoadjuvant therapy. Ann Surg Oncol. 2012;19(6):2045–53.CrossRef
30.
Finks JF, Osborne NH, Birkmeyer JD. Trends in hospital volume and operative mortality for high-risk surgery. N Engl J Med. 2011;364(22):2128–37.CrossRef
31.
El Amrani M, Clement G, Lenne X, Farges O, Delpero JR, Theis D, et al. Failure-to-rescue in patients undergoing pancreatectomy: is hospital volume a standard for quality improvement programs? Nationwide analysis of 12,333 patients. Ann Surg. 2018;268(5):799–807.CrossRef
32.
Amini N, Spolverato G, Kim Y, Pawlik TM. Trends in hospital volume and failure to rescue for pancreatic surgery. J Gastrointest Surg. 2015;19(9):1581–92.CrossRef
33.
Sheetz KH, Dimick JB, Nathan H. Centralization of high-risk cancer surgery within existing hospital systems. J Clin Oncol. 2019;37(34):3234–42.CrossRef
34.
Jacobs RC, Groth S, Farjah F, Wilson MA, Petersen LA, Massarweh NN. Potential impact of “take the volume pledge” on access and outcomes for gastrointestinal cancer surgery. Ann Surg. 2019;270(6):1079–89.CrossRef
35.
Du L, Wang-Gillam A. Trends in neoadjuvant approaches in pancreatic cancer. J Natl Compr Cancer Netw. 2017;15(8):1070–7.CrossRef
36.
Baugh KA, Tran Cao HS, van Buren G 2nd, Silberfein EJ, Hsu C, Chai C, et al. Understaging of clinical stage I pancreatic cancer and the impact of multimodality therapy. Surgery. 2019;165(2):307–14.CrossRef
37.
Sinn M, Bahra M, Liersch T, Gellert K, Messmann H, Bechstein W, et al. CONKO-005: Adjuvant chemotherapy with gemcitabine plus erlotinib versus gemcitabine alone in patients after R0 resection of pancreatic cancer: a multicenter randomized phase III trial. J Clin Oncol. 2017;35(29):3330–7.CrossRef
Metadata
Title
Comparative Effectiveness of Neoadjuvant Therapy and Upfront Resection for Patients with Resectable Pancreatic Adenocarcinoma: An Instrumental Variable Analysis
Authors
Wilson Luiz da Costa Jr., MD, MPH, PhD
Hop S. Tran Cao, MD
Kyle H. Sheetz, MD, MSc
Xiangjun Gu, PhD
Edward C. Norton, PhD
Nader N. Massarweh, MD, MPH
Publication date
01-06-2021
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 6/2021
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-09327-3

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