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Randomized Controlled Trial
. 2023 Feb;43(2):257-275.
doi: 10.1002/cac2.12399. Epub 2022 Dec 29.

Standard pancreatoduodenectomy versus extended pancreatoduodenectomy with modified retroperitoneal nerve resection in patients with pancreatic head cancer: a multicenter randomized controlled trial

Qing Lin  1   2   3 , Shangyou Zheng  1   2   3 , Xianjun Yu  4 , Meifu Chen  5 , Yu Zhou  1 , Quanbo Zhou  2   3 , Chonghui Hu  1   2   3 , Jing Gu  6 , Zhongdong Xu  3   7 , Lin Wang  3   8 , Yimin Liu  3   9 , Qingyu Liu  3   10 , Min Wang  11 , Guolin Li  12 , He Cheng  4 , Dongkai Zhou  13 , Guodong Liu  14 , Zhiqiang Fu  2   3 , Yu Long  2   3 , Yixiong Li  14 , Weilin Wang  13   15   16 , Renyi Qin  11 , Zhihua Li  3   9 , Rufu Chen  1   2   3
Affiliations
Randomized Controlled Trial

Standard pancreatoduodenectomy versus extended pancreatoduodenectomy with modified retroperitoneal nerve resection in patients with pancreatic head cancer: a multicenter randomized controlled trial

Qing Lin et al. Cancer Commun (Lond). 2023 Feb.

Abstract

Background: The extent of pancreatoduodenectomy for pancreatic head cancer remains controversial, and more high-level clinical evidence is needed. This study aimed to evaluate the outcome of extended pancreatoduodenectomy (EPD) with retroperitoneal nerve resection in pancreatic head cancer.

Methods: This multicenter randomized trial was performed at 6 Chinese high-volume hospitals that enrolled patients between October 3, 2012, and September 21, 2017. Four hundred patients with stage I or II pancreatic head cancer and without specific pancreatic cancer treatments (preoperative chemotherapy or chemoradiation) within three months were randomly assigned to undergo standard pancreatoduodenectomy (SPD) or EPD, with the latter followed by dissection of additional lymph nodes (LNs), nerves and soft tissues 270° on the right side surrounding the superior mesenteric artery and celiac axis. The primary endpoint was overall survival (OS) by intention-to-treat (ITT). The secondary endpoints were disease-free survival (DFS), mortality, morbidity, and postoperative pain intensity.

Results: The R1 rate was slightly lower with EPD (8.46%) than with SPD (12.56%). The morbidity and mortality rates were similar between the two groups. The median OS was similar in the EPD and SPD groups by ITT in the whole study cohort (23.0 vs. 20.2 months, P = 0.100), while the median DFS was superior in the EPD group (16.1 vs. 13.2 months, P = 0.031). Patients with preoperative CA19-9 < 200.0 U/mL had significantly improved OS and DFS with EPD (EPD vs. SPD, 30.8 vs. 20.9 months, P = 0.009; 23.4 vs. 13.5 months, P < 0.001). The EPD group exhibited significantly lower locoregional (16.48% vs. 35.20%, P < 0.001) and mesenteric LN recurrence rates (3.98% vs. 10.06%, P = 0.022). The EPD group exhibited less back pain 6 months postoperation than the SPD group.

Conclusions: EPD for pancreatic head cancer did not significantly improve OS, but patients with EPD treatment had significantly improved DFS. In the subgroup analysis, improvements in both OS and DFS in the EPD arm were observed in patients with preoperative CA19-9 < 200.0 U/mL. EPD could be used as an effective surgical procedure for patients with pancreatic head cancer, especially those with preoperative CA19-9 < 200.0 U/mL.

Keywords: disease-free survival; extended; lymph nodes; nerve resection; overall survival; pancreatic head cancer; pancreatoduodenectomy; standard.

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Conflict of interest statement

We declare no competing interests.

Figures

FIGURE 1
FIGURE 1
Schematic diagram of the dissection of surgery. Abbreviations: LN, lymph node.
FIGURE 2
FIGURE 2
Study flowchart illustrating patients’ randomization and group allocation for treatments with SPD and EPD. Abbreviations: SPD, standard pancreatoduodenectomy; EPD, extended pancreatoduodenectomy; CRF, case report form.
FIGURE 3
FIGURE 3
The outcome of the SPD and EPD groups in the ITT population. (A) OS and (B) DFS in the ITT population. (C) OS and (D) DFS in the ITT population for the prespecified subgroup of preoperative CA19–9 < 200.0 U/mL. (E) OS and (F) DFS in the ITT population for the prespecified subgroup of preoperative CA19–9 ≥ 200.0 U/mL. Abbreviations: SPD, standard pancreatoduodenectomy; EPD, extended pancreatoduodenectomy; OS, overall survival; DFS, disease‐free survival; ITT, intention‐to‐treat; CA19–9, carbohydrate antigen 19–9; HR, hazard ratio; CI, confidence interval.
FIGURE 4
FIGURE 4
Analysis for the best cutoff value of preoperative CA19–9. (A) ROC curve for preoperative CA19–9. The red diagonal represents sensitivity plus specificity = 1. The blue polyline represents the ROC curve of preoperative CA 19–9 in predicting DFS. (B) The cutoff value of preoperative CA19–9 from ROC analysis. (C) Relationship between preoperative CA19–9 levels and DFS by RCS model. The red curve represents the result of RCS, which indicates the HR value of CA19–9 on DFS. The black vertical dotted line indicates the zero value of CA19–9; the black horizontal dotted line represents the reference HR value of 1.0; the red vertical dotted line indicates the position of CA19–9 of 200.0 U/mL. Abbreviations: CA19–9, carbohydrate antigen 19–9; ROC, receiver operating characteristic; AUC, area under the curve; DFS, disease‐free survival; RCS, restricted cubic splines; HR, hazard ratio; CI, confidence interval.
FIGURE 5
FIGURE 5
A flow chart of treatment options for patients with TNM stage I and II pancreatic cancer. Abbreviations: CA19–9, carbohydrate antigen 19–9.
See this image and copyright information in PMC

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