Association of Pathologic Response and Adjuvant Chemotherapy with Survival in Resected Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Therapy
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Study Population
2.2. Treatment Evaluation and Outcome Definitions
2.3. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Prognostic Factors Associated with Survival Outcomes
3.3. Subgroup Analyses by Pathologic Response
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Cai, J.; Chen, H.; Lu, M.; Zhang, Y.; Lu, B.; You, L.; Zhang, T.; Dai, M.; Zhao, Y. Advances in the epidemiology of pancreatic cancer: Trends, risk factors, screening, and prognosis. Cancer Lett. 2021, 520, 1–11. [Google Scholar] [CrossRef] [PubMed]
- SEER. Cancer of the Pancreas—Cancer Stat Facts. Available online: https://seer.cancer.gov/statfacts/html/pancreas.html (accessed on 1 May 2025).
- Mizrahi, J.D.; Surana, R.; Valle, J.W.; Shroff, R.T. Pancreatic cancer. Lancet 2020, 395, 2008–2020. [Google Scholar] [CrossRef] [PubMed]
- Sohal, D.P.S.; Willingham, F.F.; Falconi, M.; Raphael, K.L.; Crippa, S. Pancreatic Adenocarcinoma: Improving Prevention and Survivorship. Am. Soc. Clin. Oncol. Educ. Book 2017, 37, 301–310. [Google Scholar] [CrossRef] [PubMed]
- Kommalapati, A.; Tella, S.H.; Goyal, G.; Ma, W.W.; Mahipal, A. Contemporary Management of Localized Resectable Pancreatic Cancer. Cancers 2018, 10, 24. [Google Scholar] [CrossRef]
- Strobel, O.; Neoptolemos, J.; Jäger, D.; Büchler, M.W. Optimizing the outcomes of pancreatic cancer surgery. Nat. Rev. Clin. Oncol. 2019, 16, 11–26. [Google Scholar] [CrossRef]
- Versteijne, E.; Vogel, J.A.; Besselink, M.G.; Busch, O.R.C.; Wilmink, J.W.; Daams, J.G.; van Eijck, C.H.J.; Groot Koerkamp, B.; Rasch, C.R.N.; van Tienhoven, G.; et al. Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br. J. Surg. 2018, 105, 946–958. [Google Scholar] [CrossRef]
- Gillen, S.; Schuster, T.; Meyer zum Büschenfelde, C.; Friess, H.; Kleeff, J. Preoperative/Neoadjuvant Therapy in Pancreatic Cancer: A Systematic Review and Meta-Analysis of Response and Resection Percentages. PLoS Med. 2010, 7, e1000267. [Google Scholar] [CrossRef]
- Versteijne, E.; Suker, M.; Groothuis, K.; Akkermans-Vogelaar, J.M.; Besselink, M.G.; Bonsing, B.A.; Buijsen, J.; Busch, O.R.; Creemers, G.J.; van Dam, R.M.; 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, 1763–1773. [Google Scholar] [CrossRef]
- Springfeld, C.; Ferrone, C.R.; Katz, M.H.G.; Philip, P.A.; Hong, T.S.; Hackert, T.; Büchler, M.W.; Neoptolemos, J. Neoadjuvant therapy for pancreatic cancer. Nat. Rev. Clin. Oncol. 2023, 20, 318–337. [Google Scholar] [CrossRef]
- NCCN Guidelines Panel. NCCN Clinical Practice Guidelines in Oncology; Pancreatic Adenocarcinoma; Version 1.2025; National Comprehensive Cancer Network: Plymouth Meeting, PA, USA, 2025. [Google Scholar]
- van Roessel, S.; van Veldhuisen, E.; Klompmaker, S.; Janssen, Q.P.; Abu Hilal, M.; Alseidi, A.; Balduzzi, A.; Balzano, G.; Bassi, C.; Berrevoet, F.; et al. Evaluation of Adjuvant Chemotherapy in Patients With Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX Treatment. JAMA Oncol. 2020, 6, 1733–1740. [Google Scholar] [CrossRef]
- Sugawara, T.; Rodriguez Franco, S.; Sherman, S.; Kirsch, M.J.; Colborn, K.; Ishida, J.; Grandi, S.; Al-Musawi, M.H.; Gleisner, A.; Schulick, R.D.; et al. Association of Adjuvant Chemotherapy in Patients with Resected Pancreatic Adenocarcinoma After Multiagent Neoadjuvant Chemotherapy. JAMA Oncol. 2023, 9, 316–323. [Google Scholar] [CrossRef]
- Choi, J.H.; Kim, M.K.; Lee, S.H.; Park, J.W.; Park, N.; Cho, I.R.; Ryu, J.K.; Kim, Y.-T.; Jang, J.-Y.; Kwon, W.; et al. Proper adjuvant therapy in patients with borderline resectable and locally advanced pancreatic cancer who had received neoadjuvant FOLFIRINOX. Front. Oncol. 2022, 12, 945829. [Google Scholar] [CrossRef] [PubMed]
- College of American Pathologists. Protocol for the Examination of Specimens from Patients with Carcinoma of the Pancreas; College of American Pathologists: Northfield, IL, USA, 2021; Available online: https://documents.cap.org/protocols/Panc.Exo_4.2.0.2.REL_CAPCP.pdf (accessed on 1 April 2025).
- van Roessel, S.; Janssen, B.V.; Soer, E.C.; Fariña Sarasqueta, A.; Verbeke, C.S.; Luchini, C.; Brosens, L.A.A.; Verheij, J.; Besselink, M.G. Scoring of tumour response after neoadjuvant therapy in resected pancreatic cancer: Systematic review. Br. J. Surg. 2021, 108, 119–127. [Google Scholar] [CrossRef]
- Amin, M.B.; Edge, S.; Greene, F.; Byrd, D.R.; Brookland, R.K.; Washington, M.K. AJCC Cancer Staging Manual, 8th ed.; Springer: New York, NY, USA, 2017. [Google Scholar]
- Bao, Q.R.; Frigerio, I.; Tripepi, M.; Marletta, S.; Martignoni, G.; Giardino, A.; Regi, P.; Scopelliti, F.; Allegrini, V.; Girelli, R.; et al. Prognostic value of major pathological response following neoadjuvant therapy for non resectable pancreatic ductal adenocarcinoma. Pancreatology 2023, 23, 266–274. [Google Scholar] [CrossRef] [PubMed]
- Conroy, T.; Pfeiffer, P.; Vilgrain, V.; Lamarca, A.; Seufferlein, T.; O’Reilly, E.M.; Hackert, T.; Golan, T.; Prager, G.; Haustermans, K.; et al. Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up☆. Ann. Oncol. 2023, 34, 987–1002. [Google Scholar] [CrossRef]
- Khorana, A.A.; Mangu, P.B.; Berlin, J.; Engebretson, A.; Hong, T.S.; Maitra, A.; Mohile, S.G.; Mumber, M.; Schulick, R.; Shapiro, M.; et al. Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J. Clin. Oncol. 2017, 35, 2324–2328. [Google Scholar] [CrossRef] [PubMed]
- Groot, V.P.; Blair, A.B.; Gemenetzis, G.; Ding, D.; Burkhart, R.A.; Yu, J.; Borel Rinkes, I.H.M.; Molenaar, I.Q.; Cameron, J.L.; Weiss, M.J.; et al. Recurrence after neoadjuvant therapy and resection of borderline resectable and locally advanced pancreatic cancer. Eur. J. Surg. Oncol. 2019, 45, 1674–1683. [Google Scholar] [CrossRef]
- Shimizu, T.; Maeda, S.; Link, J.; Deranteriassian, A.; Premji, A.; Verma, A.; Chervu, N.; Park, J.; Girgis, M.; Benharash, P.; et al. Clinical and pathological factors associated with survival in patients with pancreatic cancer who receive adjuvant therapy after neoadjuvant therapy: A retrospective multi-institutional analysis. Surgery 2024, 175, 1377–1385. [Google Scholar] [CrossRef]
- He, J.; Blair, A.B.; Groot, V.P.; Javed, A.A.; Burkhart, R.A.; Gemenetzis, G.; Hruban, R.H.; Waters, K.M.; Poling, J.; Zheng, L.; et al. Is a Pathological Complete Response Following Neoadjuvant Chemoradiation Associated With Prolonged Survival in Patients With Pancreatic Cancer? Ann. Surg. 2018, 268, 1–8. [Google Scholar] [CrossRef]
- Kim, S.S.; Ko, A.H.; Nakakura, E.K.; Wang, Z.J.; Corvera, C.U.; Harris, H.W.; Kirkwood, K.S.; Hirose, R.; Tempero, M.A.; Kim, G.E. Comparison of Tumor Regression Grading of Residual Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Chemotherapy Without Radiation: Would Fewer Tier-Stratification Be Favorable Toward Standardization? Am. J. Surg. Pathol. 2019, 43, 334–340. [Google Scholar] [CrossRef]
- Tummers, W.S.; Groen, J.V.; Sibinga Mulder, B.G.; Farina-Sarasqueta, A.; Morreau, J.; Putter, H.; van de Velde, C.J.; Vahrmeijer, A.L.; Bonsing, B.A.; Mieog, J.S.; et al. Impact of resection margin status on recurrence and survival in pancreatic cancer surgery. Br. J. Surg. 2019, 106, 1055–1065. [Google Scholar] [CrossRef] [PubMed]
- Ghaneh, P.; Kleeff, J.; Halloran, C.M.; Raraty, M.; Jackson, R.; Melling, J.; Jones, O.; Palmer, D.H.; Cox, T.F.; Smith, C.J.; et al. The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma. Ann. Surg. 2019, 269, 520–529. [Google Scholar] [CrossRef] [PubMed]
- Morales-Oyarvide, V.; Rubinson, D.A.; Dunne, R.F.; Kozak, M.M.; Bui, J.L.; Yuan, C.; Qian, Z.R.; Babic, A.; Da Silva, A.; Nowak, J.A.; et al. Lymph node metastases in resected pancreatic ductal adenocarcinoma: Predictors of disease recurrence and survival. Br. J. Cancer 2017, 117, 1874–1882. [Google Scholar] [CrossRef] [PubMed]
- Van Cutsem, E.; Cervantes, A.; Adam, R.; Sobrero, A.; Van Krieken, J.H.; Aderka, D.; Aranda Aguilar, E.; Bardelli, A.; Benson, A.; Bodoky, G.; et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann. Oncol. 2016, 27, 1386–1422. [Google Scholar] [CrossRef]
- Yoshino, T.; Arnold, D.; Taniguchi, H.; Pentheroudakis, G.; Yamazaki, K.; Xu, R.H.; Kim, T.W.; Ismail, F.; Tan, I.B.; Yeh, K.H.; et al. Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: A JSMO–ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS. Ann. Oncol. 2018, 29, 44–70. [Google Scholar] [CrossRef]
- Riesco-Martinez, M.C.; Modrego, A.; Espinosa-Olarte, P.; La Salvia, A.; Garcia-Carbonero, R. Perioperative Chemotherapy for Liver Metastasis of Colorectal Cancer: Lessons Learned and Future Perspectives. Curr. Treat. Options Oncol. 2022, 23, 1320–1337. [Google Scholar] [CrossRef]
Characteristics | N = 230 | % or IQR | |
---|---|---|---|
Age (years) | Median | 68 | 62–72 |
Gender | Male | 117 | 51 |
Female | 113 | 49 | |
Race | Black | 11 | 5 |
White | 216 | 94 | |
Other | 2 | 1 | |
Not Available | 1 | 0 | |
NACT Regimen | mFOLFIRINOX | 96 | 42 |
GEM-NAB | 34 | 15 | |
GTX | 100 | 43 | |
Duration of NACT | ≤2 months | 97 | 42 |
>2 to ≤4 months | 25 | 11 | |
>4 months | 108 | 47 | |
Neoadjuvant RT | No | 6 | 3 |
Yes | 224 | 97 | |
Path T-Stage | 0 | 13 | 6 |
1 | 59 | 26 | |
2 | 82 | 36 | |
3 | 74 | 32 | |
4 | 2 | 1 | |
Path N-Stage | 0 | 136 | 59 |
1 | 81 | 35 | |
2 | 13 | 6 | |
Surgical Margin Status | R0 | 216 | 94 |
R1 | 14 | 6 | |
Histologic Grade | 1 | 15 | 7 |
2 | 142 | 62 | |
3 | 54 | 23 | |
N/A | 19 | 8 | |
TRG-CAP | 0–1 | 67 | 29 |
2–3 | 163 | 71 | |
Receipt of ACT | No | 75 | 33 |
Yes | 155 | 67 | |
NACT vs. ACT * | De-escalate | 86 | 56 |
Same | 39 | 25 | |
Conversion | 30 | 19 | |
Duration of Perioperative chemotherapy | <6 months | 180 | 78 |
6 months | 50 | 22 | |
Recurred | No | 115 | 50 |
Yes | 115 | 50 | |
Died | No | 109 | 47 |
Yes | 121 | 52 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Yu, J.; Laborde, J.M.; Park, R.; Shahzad, M.; Kim, Y.; Cheon, J.; Imanirad, I.; Kim, R.D.; Biachi de Castria, T.; Nardella, N.L.; et al. Association of Pathologic Response and Adjuvant Chemotherapy with Survival in Resected Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Therapy. Cancers 2025, 17, 1797. https://doi.org/10.3390/cancers17111797
Yu J, Laborde JM, Park R, Shahzad M, Kim Y, Cheon J, Imanirad I, Kim RD, Biachi de Castria T, Nardella NL, et al. Association of Pathologic Response and Adjuvant Chemotherapy with Survival in Resected Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Therapy. Cancers. 2025; 17(11):1797. https://doi.org/10.3390/cancers17111797
Chicago/Turabian StyleYu, James, Jose M. Laborde, Robin Park, Moazzam Shahzad, Youngchul Kim, Jaekyung Cheon, Iman Imanirad, Richard D. Kim, Tiago Biachi de Castria, Nicole L. Nardella, and et al. 2025. "Association of Pathologic Response and Adjuvant Chemotherapy with Survival in Resected Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Therapy" Cancers 17, no. 11: 1797. https://doi.org/10.3390/cancers17111797
APA StyleYu, J., Laborde, J. M., Park, R., Shahzad, M., Kim, Y., Cheon, J., Imanirad, I., Kim, R. D., Biachi de Castria, T., Nardella, N. L., Malafa, M., Denbo, J. W., Fleming, J. B., Hoffe, S. E., Frakes, J. M., Sinnamon, A. J., Pimiento, J. M., Hodul, P. J., & Kim, D. W. (2025). Association of Pathologic Response and Adjuvant Chemotherapy with Survival in Resected Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Therapy. Cancers, 17(11), 1797. https://doi.org/10.3390/cancers17111797