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Prognostic Value of the Preoperative Tumor Marker Index in Resected Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Institution Study

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The prediction of prognostic outcomes can provide the most suitable strategy for patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to evaluate the clinical value of the preoperative tumor marker index (pre-TI) in predicting prognostic outcomes after resection for PDAC.

Methods

For 183 patients who underwent pancreatic resection of PDAC, adjusted carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), pancreatic cancer-associated antigen-2 (DUpan-2), and s-pancreas-1 antigen (SPan-1) were retrospectively evaluated, and the positive number of these markers was scored as the pre-TI.

Results

A high pre-TI (≥ 2) was significantly associated with a larger tumor and lymph node metastases, and the patients with a high pre-TI had worse prognostic outcomes in terms of both relapse-free survival (RFS) (P < 0.0001, log-rank) and overall survival (OS) (P < 0.0001, Λlog-rank) than the patients with a low pre-TI. The pre-TI was one of the independent factors of a poor prognosis for RFS (hazard ratio [HR], 2.36; P < 0.0001) and OS (HR, 2.27; P < 0.0001). In addition, even for the patients with normal adjusted CA19-9 values (n = 74, 40.4%), those with the high pre-TI had a significantly poorer prognosis than those with a low pre-TI (RFS: P = 0.002, log-rank; OS: P = 0.031, log-rank).

Conclusions

The pre-TI could be a potent predictive marker of prognostic outcomes for patients with resections for PDAC. Patients with a high pre-TI may need additional strategies to improve their prognosis.

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References

  1. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014;371:1039–49.

    Article  CAS  Google Scholar 

  2. Uesaka K, Boku N, Fukutomi A, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016;388:248–57.

    Article  CAS  Google Scholar 

  3. Cloyd JM, Wang H, Egger ME, et al. Association of clinical factors with a major pathologic response following preoperative therapy for pancreatic ductal adenocarcinoma. JAMA Surg. 2017;152:1048–56.

    Article  Google Scholar 

  4. Mokdad AA, Minter RM, Zhu H, et al. Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score-matched analysis. J Clin Oncol. 2017;35:515–22.

    Article  Google Scholar 

  5. Maggino L, Malleo G, Marchegiani G, et al. Outcomes of primary chemotherapy for borderline resectable and locally advanced pancreatic ductal adenocarcinoma. JAMA Surg. 2019;154:932–42.

    Article  Google Scholar 

  6. Macedo FI, Ryon E, Maithel SK, et al. Survival outcomes associated with clinical and pathological response following neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel chemotherapy in resected pancreatic cancer. Ann Surg. 2019;270:400–13.

    Article  Google Scholar 

  7. Truty MJ, Kendrick ML, Nagorney DM, et al. Factors predicting response, perioperative outcomes, and survival following total neoadjuvant therapy for borderline/locally advanced pancreatic cancer. Ann Surg. 2019. https://doi.org/10.1097/SLA.0000000000003284.

    Article  Google Scholar 

  8. Hashimoto D, Arima K, Nakagawa S, et al. Pancreatic cancer arising from the remnant pancreas after pancreatectomy: a multicenter retrospective study by the Kyushu Study Group of Clinical Cancer. J Gastroenterol. 2019;54:437–48.

    Article  CAS  Google Scholar 

  9. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Pancreatic Adenocarcinoma NCCN Evidence BlocksTM Version 3. 2019.

  10. Zhou G, Liu X, Wang X, et al. Combination of preoperative CEA and CA19-9 improves prediction outcomes in patients with resectable pancreatic adenocarcinoma: results from a large follow-up cohort. Onco Targets Ther. 2017;10:1199–206.

    Article  CAS  Google Scholar 

  11. Kim YC, Kim HJ, Park JH, et al. Can preoperative CA19-9 and CEA levels predict the resectability of patients with pancreatic adenocarcinoma? J Gastroenterol Hepatol. 2009;24:1869–75.

    Article  CAS  Google Scholar 

  12. Hosokawa Y, Nagakawa Y, Sahara Y, et al. Serum SPan-1 is a significant risk factor for early recurrence of pancreatic cancer after curative resection. Dig Surg. 2017;34:125–32.

    Article  CAS  Google Scholar 

  13. Kawa S, Oguchi H, Kobayashi T, et al. Elevated serum levels of Dupan-2 in pancreatic cancer patients negative for Lewis blood group phenotype. Br J Cancer. 1991;64:899–902.

    Article  CAS  Google Scholar 

  14. Aoki S, Motoi F, Murakami Y, et al. Decreased serum carbohydrate antigen 19-9 levels after neoadjuvant therapy predict a better prognosis for patients with pancreatic adenocarcinoma: a multicenter case-control study of 240 patients. BMC Cancer. 2019;19:252.

    Article  Google Scholar 

  15. Rieser CJ, Zenati M, Hamad A, et al. CA19-9 on postoperative surveillance in pancreatic ductal adenocarcinoma: predicting recurrence and changing prognosis over time. Ann Surg Oncol. 2018;25:3483–91.

    Article  Google Scholar 

  16. Luo G, Liu C, Guo M, et al. Potential biomarkers in Lewis-negative patients with pancreatic cancer. Ann Surg. 2017;265:800–5.

    Article  Google Scholar 

  17. Nakagawa S, Yamashita YI, Umezaki N, et al. Serum marker score based on Prognostic Nutrition Index, carcinoembryonic antigen, and carbohydrate antigen 19-9 is associated with recurrence for patients undergoing surgery for pancreatic ductal adenocarcinoma. Pancreas. 2018;47:1130–4.

    Article  CAS  Google Scholar 

  18. Edge S, Byrd DR, Compton CC, et al. AJCC cancer staging manual. 7th ed. Springer, New York, NY, 2010.

    Google Scholar 

  19. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.

    Article  Google Scholar 

  20. Kang CM, Kim JY, Choi GH, et al. The use of adjusted preoperative CA 19-9 to predict the recurrence of resectable pancreatic cancer. J Surg Res. 2007;140:31–5.

    Article  CAS  Google Scholar 

  21. Neoptolemos JP, Palmer DH, Ghaneh P, 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;389:1011–24.

    Article  CAS  Google Scholar 

  22. Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–81.

    Article  CAS  Google Scholar 

  23. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366:2455–65.

    Article  CAS  Google Scholar 

  24. Knudsen ES, Vail P, Balaji U, et al. Stratification of pancreatic ductal adenocarcinoma: combinatorial genetic, stromal, and immunologic markers. Clin Cancer Res. 2017;23:4429–40.

    Article  CAS  Google Scholar 

  25. Mahajan UM, Langhoff E, Goni E, et al. Immune cell and stromal signature associated with progression-free survival of patients with resected pancreatic ductal adenocarcinoma. Gastroenterology. 2018;155:1625–39.e1622.

    Google Scholar 

  26. Tsukamoto M, Imai K, Ishimoto T, et al. PD-L1 expression enhancement by infiltrating macrophage-derived tumor necrosis factor-alpha leads to poor pancreatic cancer prognosis. Cancer Sci. 2019;110:310–20.

    CAS  PubMed  Google Scholar 

  27. Mace TA, Shakya R, Pitarresi JR, et al. IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer. Gut. 2018;67:320–32.

    Article  CAS  Google Scholar 

  28. Lu C, Paschall AV, Shi H, et al. The MLL1-H3K4me3 axis-mediated PD-L1 expression and pancreatic cancer immune evasion. J Natl Cancer Inst. 2017;109:djw283.

    Article  Google Scholar 

  29. Cassinotto C, Chong J, Zogopoulos G, et al. Resectable pancreatic adenocarcinoma: role of CT quantitative imaging biomarkers for predicting pathology and patient outcomes. Eur J Radiol. 2017;90:152–8.

    Article  Google Scholar 

  30. Cheng SH, Cheng YJ, Jin ZY, Xue HD. Unresectable pancreatic ductal adenocarcinoma: role of CT quantitative imaging biomarkers for predicting outcomes of patients treated with chemotherapy. Eur J Radiol. 2019;113:188–97.

    Article  Google Scholar 

  31. Xu HX, Chen T, Wang WQ, et al. Metabolic tumour burden assessed by 18F-FDG PET/CT associated with serum CA19-9 predicts pancreatic cancer outcome after resection. Eur J Nucl Med Mol Imaging. 2014;41:1093–102.

    Article  CAS  Google Scholar 

  32. Kauhanen SP, Komar G, Seppanen MP, et al. A prospective diagnostic accuracy study of 18F-fluorodeoxyglucose positron emission tomography/computed tomography, multidetector row computed tomography, and magnetic resonance imaging in primary diagnosis and staging of pancreatic cancer. Ann Surg. 2009;250:957–63.

    Article  Google Scholar 

  33. Kurahara H, Maemura K, Mataki Y, et al. Significance of 18F-fluorodeoxyglucose (FDG) uptake in response to chemoradiotherapy for pancreatic cancer. Ann Surg Oncol. 2019;26:644–51.

    Article  Google Scholar 

  34. Ramanathan RK, Goldstein D, Korn RL, et al. Positron emission tomography response evaluation from a randomized phase III trial of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas. Ann Oncol. 2016;27:648–53.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan

    Tatsunori Miyata MD, PhD, Hiromitsu Hayashi MD, PhD, Yo-ichi Yamashita MD, PhD, Kazuki Matsumura MD, Yosuke Nakao MD, Rumi Itoyama MD, Takanobu Yamao MD, PhD, Masayo Tsukamoto MD, PhD, Hirohisa Okabe MD, PhD, Katsunori Imai MD, PhD, Akira Chikamoto MD, PhD, Takatoshi Ishiko MD, PhD & Hideo Baba MD, PhD, FACS

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  1. Tatsunori Miyata MD, PhD
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  2. Hiromitsu Hayashi MD, PhD
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  3. Yo-ichi Yamashita MD, PhD
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Correspondence to Hideo Baba MD, PhD, FACS.

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Supplementary Figure 1

Figure shows the relapse-free survival (RFS) and overall survival (OS) curve in PDAC patients with pancreatic resection according to the Pre TI. The patients with a Pre TI score 2 and 3 demonstrated significantly poorer prognoses than that of patients with a Pre TI score 0 and 1 both for RFS and OS. We excluded patients with R2 (n=5) in RFS analysis (TIFF 19784 kb)

Supplementary Figure 2

Figure shows the ROC curves for recurrence in PDAC patients according to several tumor markers. The AUC value of the Pre TI was 0.6792, which was better than that of other tumor markers, including adjusted CA19-9 (AUC=0.6118). We excluded patients with R2 (n=5) in this analysis (TIFF 19784 kb)

Supplementary Figure 3

Figure shows the relapse-free survival (RFS) and overall survival (OS) curve in PDAC patients with normal adjusted CA19-9 values after curative pancreatic resection according to the Pre TI. The patients with a Pre TI score 2 and 3 demonstrated significantly worse prognosis than that of patients with a Pre TI score 0 both for RFS (Log-rank P=0.003) and OS (Log-rank P=0.043). We excluded patients with R2 (n=2) in RFS analysis (TIFF 19784 kb)

Supplementary material 4 (DOCX 18 kb)

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Miyata, T., Hayashi, H., Yamashita, Yi. et al. Prognostic Value of the Preoperative Tumor Marker Index in Resected Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Institution Study. Ann Surg Oncol 28, 1572–1580 (2021). https://doi.org/10.1245/s10434-020-09022-3

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  • DOI: https://doi.org/10.1245/s10434-020-09022-3

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