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Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Cytostatic Therapy | Research article

Comparative effectiveness of primary tumor resection in patients with stage III pancreatic adenocarcinoma

Authors: Ke Sun, Wei Li, Jun Han, Hong Wu

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Previous studies comparing primary tumor resection (PTR) to palliative treatment for advanced-stage pancreatic ductal adenocarcinoma (PDA) were limited by strong selection bias. We used multiple methods to control for confounding and selection bias to estimate the effect of PTR on survival for late-stage PDA.

Methods

Surveillance, Epidemiology, and End Results (SEER) 18 registry database for 2004 through 2014 was retrieved for the present study. A total of 4322 patients with stage III (AJCC, 6th) PDA were included in this study. Propensity score matching (PSM) was performed to eliminate possible bias. In addition, instrumental variable (IV) analysis was utilized to adjust for both measured and unmeasured confounders.

Results

A total of 4322 patients with stage III PDA including 552 (12.8%) who underwent PTR, 3770 (87.2%) without PTR, were identified. In the multivariable cohort, a clear prognostic advantage of PTR was observed in overall survival (OS) (P < 0.001) and disease-specific survival (DSS) (P < 0.001) compared to patients after non-surgery therapy. In the PSM cohort, patients in PTR group showed a better OS and DSS (both P values < 0.001) compared to patients in non-surgery group. The survival benefit of PTR for stage III PDA was not observed in the two-stage residual inclusion (2SRI) model. Estimates based on this instrument indicated that patients treated with PTR had similar OS (P = 0.448) and DSS (P = 0.719). In IV analyses stratified by chemotherapy and tumor location, patients undergoing PTR had similar OS and DSS compared to patients in non-surgery group across all subgroups.

Conclusions

Survival with PTR did not differ significantly from palliative treatment in marginal patients with stage III pancreatic adenocarcinoma. High-quality randomized trials are needed to validate these results.
Appendix
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Literature
1.
go back to reference Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.CrossRef Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.CrossRef
2.
go back to reference Tempero MA, Malafa MP, Al-Hawary M, Asbun H, Bain A, Behrman SW, Benson AB 3rd, Binder E, Cardin DB, Cha C, et al. Pancreatic adenocarcinoma, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2017;15(8):1028–61.CrossRef Tempero MA, Malafa MP, Al-Hawary M, Asbun H, Bain A, Behrman SW, Benson AB 3rd, Binder E, Cardin DB, Cha C, et al. Pancreatic adenocarcinoma, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2017;15(8):1028–61.CrossRef
3.
go back to reference Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, Zahurak ML, Dooley WC, Coleman J, Sauter PK, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg. 1997;225(5):621–33 discussion 633-626.CrossRef Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, Zahurak ML, Dooley WC, Coleman J, Sauter PK, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg. 1997;225(5):621–33 discussion 633-626.CrossRef
4.
go back to reference Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. Jama. 2010;304(10):1073–81.CrossRef Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. Jama. 2010;304(10):1073–81.CrossRef
5.
go back to reference Sabater L, Munoz E, Rosello S, Dorcaratto D, Garces-Albir M, Huerta M, Roda D, Gomez-Mateo MC, Ferrandez-Izquierdo A, Darder A, et al. Borderline resectable pancreatic cancer. Challenges and controversies. Cancer Treat Rev. 2018;68:124–35.CrossRef Sabater L, Munoz E, Rosello S, Dorcaratto D, Garces-Albir M, Huerta M, Roda D, Gomez-Mateo MC, Ferrandez-Izquierdo A, Darder A, et al. Borderline resectable pancreatic cancer. Challenges and controversies. Cancer Treat Rev. 2018;68:124–35.CrossRef
6.
go back to reference Lopez NE, Prendergast C, Lowy AM. Borderline resectable pancreatic cancer: definitions and management. World J Gastroenterol. 2014;20(31):10740–51.CrossRef Lopez NE, Prendergast C, Lowy AM. Borderline resectable pancreatic cancer: definitions and management. World J Gastroenterol. 2014;20(31):10740–51.CrossRef
7.
go back to reference Varadhachary GR, Tamm EP, Abbruzzese JL, Xiong HQ, Crane CH, Wang H, Lee JE, Pisters PW, Evans DB, Wolff RA. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006;13(8):1035–46.CrossRef Varadhachary GR, Tamm EP, Abbruzzese JL, Xiong HQ, Crane CH, Wang H, Lee JE, Pisters PW, Evans DB, Wolff RA. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006;13(8):1035–46.CrossRef
8.
go back to reference Springett GM, Hoffe SE. Borderline resectable pancreatic cancer: on the edge of survival. Cancer control : journal of the Moffitt Cancer Center. 2008;15(4):295–307.CrossRef Springett GM, Hoffe SE. Borderline resectable pancreatic cancer: on the edge of survival. Cancer control : journal of the Moffitt Cancer Center. 2008;15(4):295–307.CrossRef
9.
go back to reference Chin V, Nagrial A, Sjoquist K, O'Connor CA, Chantrill L, Biankin AV, Scholten RJ, Yip D. Chemotherapy and radiotherapy for advanced pancreatic cancer. Cochrane Database Syst Rev. 2018;3:Cd011044.PubMed Chin V, Nagrial A, Sjoquist K, O'Connor CA, Chantrill L, Biankin AV, Scholten RJ, Yip D. Chemotherapy and radiotherapy for advanced pancreatic cancer. Cochrane Database Syst Rev. 2018;3:Cd011044.PubMed
10.
go back to reference Vaccaro V, Sperduti I, Milella M. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;365(8):768–9 author reply 769.CrossRef Vaccaro V, Sperduti I, Milella M. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;365(8):768–9 author reply 769.CrossRef
11.
go back to reference Sadot E, Doussot A, O'Reilly EM, Lowery MA, Goodman KA, Do RK, Tang LH, Gonen M, D'Angelica MI, DeMatteo RP, et al. FOLFIRINOX induction therapy for stage 3 pancreatic adenocarcinoma. Ann Surg Oncol. 2015;22(11):3512–21.CrossRef Sadot E, Doussot A, O'Reilly EM, Lowery MA, Goodman KA, Do RK, Tang LH, Gonen M, D'Angelica MI, DeMatteo RP, et al. FOLFIRINOX induction therapy for stage 3 pancreatic adenocarcinoma. Ann Surg Oncol. 2015;22(11):3512–21.CrossRef
12.
go back to reference Luu AM, Herzog T, Hoehn P, Reinacher-Schick A, Munding J, Uhl W, Braumann C. FOLFIRINOX treatment leading to pathologic complete response of a locally advanced pancreatic cancer. J Gastrointest Oncol. 2018;9(2):E9–e12.CrossRef Luu AM, Herzog T, Hoehn P, Reinacher-Schick A, Munding J, Uhl W, Braumann C. FOLFIRINOX treatment leading to pathologic complete response of a locally advanced pancreatic cancer. J Gastrointest Oncol. 2018;9(2):E9–e12.CrossRef
13.
go back to reference Nitsche U, Wenzel P, Siveke JT, Braren R, Holzapfel K, Schlitter AM, Stoss C, Kong B, Esposito I, Erkan M, et al. Resectability after first-line FOLFIRINOX in initially Unresectable locally advanced pancreatic Cancer: a single-center experience. Ann Surg Oncol. 2015;22(Suppl 3):S1212–20.CrossRef Nitsche U, Wenzel P, Siveke JT, Braren R, Holzapfel K, Schlitter AM, Stoss C, Kong B, Esposito I, Erkan M, et al. Resectability after first-line FOLFIRINOX in initially Unresectable locally advanced pancreatic Cancer: a single-center experience. Ann Surg Oncol. 2015;22(Suppl 3):S1212–20.CrossRef
14.
go back to reference Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261(1):12–7.CrossRef Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261(1):12–7.CrossRef
15.
go back to reference Wang L, Cheng CS, Chen L, Chen Z. Benefit from the inclusion of surgery in the treatment of patients with stage III pancreatic cancer: a propensity-adjusted, population-based SEER analysis. Cancer Manag Res. 2018;10:1907–18.CrossRef Wang L, Cheng CS, Chen L, Chen Z. Benefit from the inclusion of surgery in the treatment of patients with stage III pancreatic cancer: a propensity-adjusted, population-based SEER analysis. Cancer Manag Res. 2018;10:1907–18.CrossRef
16.
go back to reference Beane JD, House MG, Pitt SC, Kilbane EM, Hall BL, Parmar AD, Riall TS, Pitt HA. Distal pancreatectomy with celiac axis resection: what are the added risks? HPB (Oxford). 2015;17(9):777–84.CrossRef Beane JD, House MG, Pitt SC, Kilbane EM, Hall BL, Parmar AD, Riall TS, Pitt HA. Distal pancreatectomy with celiac axis resection: what are the added risks? HPB (Oxford). 2015;17(9):777–84.CrossRef
17.
go back to reference Denecke T, Andreou A, Podrabsky P, Grieser C, Warnick P, Bahra M, Klein F, Hamm B, Neuhaus P, Glanemann M. Distal pancreatectomy with en bloc resection of the celiac trunk for extended pancreatic tumor disease: an interdisciplinary approach. Cardiovasc Intervent Radiol. 2011;34(5):1058–64.CrossRef Denecke T, Andreou A, Podrabsky P, Grieser C, Warnick P, Bahra M, Klein F, Hamm B, Neuhaus P, Glanemann M. Distal pancreatectomy with en bloc resection of the celiac trunk for extended pancreatic tumor disease: an interdisciplinary approach. Cardiovasc Intervent Radiol. 2011;34(5):1058–64.CrossRef
18.
go back to reference Klompmaker S, de Rooij T, Korteweg JJ, van Dieren S, van Lienden KP, van Gulik TM, Busch OR, Besselink MG. Systematic review of outcomes after distal pancreatectomy with coeliac axis resection for locally advanced pancreatic cancer. Br J Surg. 2016;103(8):941–9.CrossRef Klompmaker S, de Rooij T, Korteweg JJ, van Dieren S, van Lienden KP, van Gulik TM, Busch OR, Besselink MG. Systematic review of outcomes after distal pancreatectomy with coeliac axis resection for locally advanced pancreatic cancer. Br J Surg. 2016;103(8):941–9.CrossRef
19.
go back to reference McDowell BD, Chapman CG, Smith BJ, Button AM, Chrischilles EA, Mezhir JJ. Pancreatectomy predicts improved survival for pancreatic adenocarcinoma: results of an instrumental variable analysis. Ann Surg. 2015;261(4):740–5.CrossRef McDowell BD, Chapman CG, Smith BJ, Button AM, Chrischilles EA, Mezhir JJ. Pancreatectomy predicts improved survival for pancreatic adenocarcinoma: results of an instrumental variable analysis. Ann Surg. 2015;261(4):740–5.CrossRef
20.
go back to reference Baiocchi M, Cheng J, Small DS. Instrumental variable methods for causal inference. Stat Med. 2014;33(13):2297–340.CrossRef Baiocchi M, Cheng J, Small DS. Instrumental variable methods for causal inference. Stat Med. 2014;33(13):2297–340.CrossRef
21.
go back to reference Valley TS, Sjoding MW, Ryan AM, Iwashyna TJ, Cooke CR. Association of Intensive Care Unit Admission with Mortality among Older Patients with Pneumonia. Jama. 2015;314(12):1272–9.CrossRef Valley TS, Sjoding MW, Ryan AM, Iwashyna TJ, Cooke CR. Association of Intensive Care Unit Admission with Mortality among Older Patients with Pneumonia. Jama. 2015;314(12):1272–9.CrossRef
22.
go back to reference Tan HJ, Norton EC, Ye Z, Hafez KS, Gore JL, Miller DC. Long-term survival following partial vs radical nephrectomy among older patients with early-stage kidney cancer. Jama. 2012;307(15):1629–35.CrossRef Tan HJ, Norton EC, Ye Z, Hafez KS, Gore JL, Miller DC. Long-term survival following partial vs radical nephrectomy among older patients with early-stage kidney cancer. Jama. 2012;307(15):1629–35.CrossRef
23.
go back to reference Zhao J, Mao J, Li W. Association of Tumor Grade with Long-Term Survival in patients with hepatocellular carcinoma after liver transplantation. Transplant Proc. 2019;51(3):813–9.CrossRef Zhao J, Mao J, Li W. Association of Tumor Grade with Long-Term Survival in patients with hepatocellular carcinoma after liver transplantation. Transplant Proc. 2019;51(3):813–9.CrossRef
24.
go back to reference Xu H, Xia Z, Jia X, Chen K, Li D, Dai Y, Tao M, Mao Y. Primary tumor resection is associated with improved survival in stage IV colorectal Cancer: an instrumental variable analysis. Sci Rep. 2015;5:16516.CrossRef Xu H, Xia Z, Jia X, Chen K, Li D, Dai Y, Tao M, Mao Y. Primary tumor resection is associated with improved survival in stage IV colorectal Cancer: an instrumental variable analysis. Sci Rep. 2015;5:16516.CrossRef
25.
go back to reference Gore JL, Litwin MS, Lai J, Yano EM, Madison R, Setodji C, Adams JL, Saigal CS. Use of radical cystectomy for patients with invasive bladder cancer. J Natl Cancer Inst. 2010;102(11):802–11.CrossRef Gore JL, Litwin MS, Lai J, Yano EM, Madison R, Setodji C, Adams JL, Saigal CS. Use of radical cystectomy for patients with invasive bladder cancer. J Natl Cancer Inst. 2010;102(11):802–11.CrossRef
26.
go back to reference 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 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
27.
go back to reference Mohammed S, Van Buren G 2nd, Fisher WE. Pancreatic cancer: advances in treatment. World J Gastroenterol. 2014;20(28):9354–60.PubMedPubMedCentral Mohammed S, Van Buren G 2nd, Fisher WE. Pancreatic cancer: advances in treatment. World J Gastroenterol. 2014;20(28):9354–60.PubMedPubMedCentral
28.
go back to reference Doi R, Imamura M, Hosotani R, Imaizumi T, Hatori T, Takasaki K, Funakoshi A, Wakasugi H, Asano T, Hishinuma S, et al. Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial. Surg Today. 2008;38(11):1021–8.CrossRef Doi R, Imamura M, Hosotani R, Imaizumi T, Hatori T, Takasaki K, Funakoshi A, Wakasugi H, Asano T, Hishinuma S, et al. Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial. Surg Today. 2008;38(11):1021–8.CrossRef
29.
go back to reference Lygidakis NJ, Singh G, Bardaxoglou E, Dedemadi G, Sgourakis G, Nestoridis J, Malliotakis A, Pedonomou M, Solomou EK, Safioleas M, et al. Mono-bloc total spleno-pancreaticoduodenectomy for pancreatic head carcinoma with portal-mesenteric venous invasion. A prospective randomized study. Hepato-gastroenterology. 2004;51(56):427–33.PubMed Lygidakis NJ, Singh G, Bardaxoglou E, Dedemadi G, Sgourakis G, Nestoridis J, Malliotakis A, Pedonomou M, Solomou EK, Safioleas M, et al. Mono-bloc total spleno-pancreaticoduodenectomy for pancreatic head carcinoma with portal-mesenteric venous invasion. A prospective randomized study. Hepato-gastroenterology. 2004;51(56):427–33.PubMed
30.
go back to reference Scemama U, Birnbaum DJ, Ouaissi M, Turrini O, Moutardier V, Soussan J. Portal vein stent placement in five patients with chronic portal vein thrombosis prior to pancreatic surgery. J Vasc Interv Radiol. 2016;27(6):889–94.CrossRef Scemama U, Birnbaum DJ, Ouaissi M, Turrini O, Moutardier V, Soussan J. Portal vein stent placement in five patients with chronic portal vein thrombosis prior to pancreatic surgery. J Vasc Interv Radiol. 2016;27(6):889–94.CrossRef
31.
go back to reference Wan F, Small D. Bias in estimating the causal hazard ratio when using two-stage instrumental variable methods. Stat Med. 2015;34(14):2235–65.CrossRef Wan F, Small D. Bias in estimating the causal hazard ratio when using two-stage instrumental variable methods. Stat Med. 2015;34(14):2235–65.CrossRef
Metadata
Title
Comparative effectiveness of primary tumor resection in patients with stage III pancreatic adenocarcinoma
Authors
Ke Sun
Wei Li
Jun Han
Hong Wu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5966-9

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