Abstract P5-07-04: Postoperative upper Limb Edema and Dysfunction Generated by axillary nodes Excision in breast cancer patients with high or low proportion of upper limb venous reflux(PLEDGE-Reflux): a multicenter, prospective cohort study

Abstract Background: The purpose of this study was to explore the influence of the proportion of axillary venous reflux(PVR) on the incidence of upper limb edema and dysfunction in patients with breast cancer after axillary lymph node dissection. Methods: The study was designed as a multicentre, prospective cohort study, which was carried out in Shanghai Sixth People's Hospital, Shanghai Fengxian Central Hospital, and Zhejiang Cancer Hospital in China. The patient cohort consisted of patients who met the PLEDGE-Surgery study(NCT05120180) inclusion criteria and were ultimately randomly assigned to undergo ALND surgery with or without preservation of axillary vein branches.The primary endpoint was the short-term(1-month, 6-month and 12-month) incidence of postoperative upper limb lymphedema and dysfunction on the affected side. The secondary endpoints were tumor-free survival and the incidence of upper limb lymphedema and dysfunction at 5 years postoperatively. Preoperative ultrasound measurement was used to calculate the PVR for each patient. After surgery, arm circumference and DASH score were measured at 1 month, 6 months, 12 months, and 5 years. Patients were divided into Preponderant venous reflux group and Preponderant lymphatic reflux group based on the high or low PVR. Chi square test was used to compare the differences in the incidence of upper limb edema/dysfunction between two groups, and least absolute shrinkage and selection operator (LASSO) regression was performed to screen for risk factors of upper limb edema/dysfunction and establish an optimized model nomogram. The discrimination, calibration, and clinical validity of the model were evaluated. AUC value>0.7 is considered a good discrimination of the model. The Bootstrap method (repeated self-sampling 1000 times) was used to verify the constructed model internally to evaluate the accuracy of the constructed model. Data collection and initial analysis were conducted 3 months after patient recruitment was closed. All patients were included in the final analysis per protocol. The trial was registered with ClinicalTrials.gov, NCT05246592. Findings: From January 3rd, 2022 to April 1st, 2024, a total of 258 female patients were randomly assigned to the PLEDGE-Surgery study, all of whom were included in the analysis of this study. The median age was 53 years(IQR 47-59). The median follow-up was 14.2 months(IQR 10.6-17.6). The average upper limb PVR was 25.94%±18.87%. The optimal cutpoint for the PVR was determined to be 15.223% using the ROC curve. Based on this, patients were divided into a Preponderant venous reflux group(PVR>15.223%) and a Preponderant lymphatic reflux group(PVR<15.223%). The Fisher's exact test showed that there was no significant difference in the incidence of upper limb edema between the two groups at 1 month after surgery(3/151 vs. 0/78, ARR 1.99%, P=0.553, OR was not available), but there were significant differences at 6(1/110 vs. 10/51, ARR 18.7%, P=0.000, OR 26.585, 95% CI [3.299, 214.244]) and 12 months after surgery(1/75 vs. 11/35, ARR 30.10%, P=0.000, OR 33.917, 95% CI [4.161, 276.485]). The incidence of upper limb edema in the Preponderant venous reflux group(RR: 0.125[0.019, 0.813] at 6-month, 0.110[0.017, 0.723] at 12-month) was significantly lower than that in the Preponderant lymphatic reflux group(RR: 3.326[2.413, 4.585] at 6-month, 3.743[2.541, 5.513] at 12-month). The predictive model we developed for diagnosing postoperative upper limb edema achieved an area under the curve (AUC) of 0.919(95%CI: 0.778-1.000) in the cohort. The model concluded the variables selected by as preponderant lymphatic reflux group, ALND without axillary vein branches preservation, level 3 lymphadenectomy, and post-surgical wound infections. The AUC of the optimized model obtained by internal validation were 0.910. Interpretation: Proportion of upper limb venous reflux, a previously understudied factor significantly associated with postoperative upper limb edema, has been incorporated into a nomogram predictive model in this study. The constructed model demonstrates a robust predictive value and effectively anticipates the occurrence of postoperative upper limb edema in breast cancer patients. Funding: This project was supported by the Science and Technology Commission of Shanghai Municipality medical program (grant number: 22Y11912900). Citation Format: Qianrui Xu, Xiangyun Zong, Xue Peng, Qianrui Xu, Fen Tang, Yang Yu, Hongjian Yang, Wei Zhang, Ziwei Sun, Junhong Zhou, Fang Cheng, Kewei Sun, Qi Shao, Weiyun Pan, Yurong Zheng, Jiejie Hu, Chengdong Qin. Postoperative upper Limb Edema and Dysfunction Generated by axillary nodes Excision in breast cancer patients with high or low proportion of upper limb venous reflux(PLEDGE-Reflux): a multicenter, prospective cohort study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-07-04.