Risk factors for late-onset lower limb lymphedema after gynecological cancer treatment: A multi-institutional retrospective study
Introduction
Lower limb lymphedema (LLL) is one of the most disabling and debilitating complications of treatment for gynecological cancer [1]. It is characterized by lymphatic fluid accumulation in the interstitium, resulting from an injury to the lymphatic vessels or the obstruction of lymphatic channels or nodes caused by treatment, such as surgical procedures involving lymphadenectomy [2]. The prevalence of LLL after gynecological cancer treatment reportedly ranges from 5% to 58% [[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]]. The marked variation in the prevalence of LLL after gynecological cancer treatment is caused by differences in the observational period among studies and the absence of standard diagnostic criteria. The clinical presentations of LLL are usually chronic and progressive, and LLL ultimately leads to a reduction in quality of life [[12], [13], [14]].
Focusing on the period from treatment to the onset of LLL, it has been reported that some patients developed LLL ≥10 years after receiving treatment for gynecological cancer [5,7]. In contrast, most of the literature focuses on LLL that develops early in the follow-up period; however, late-onset LLL is a significant clinical challenge for physicians that deal with patients that undergo surgery involving the pelvic cavity. In ordinary clinical practice, most patients that do not exhibit any evidence of cancer recurrence stop visiting healthcare institutions after 5–10 years of follow-up. Therefore, a substantial number of cases of late-onset LLL might be missed due to the current clinical situation. To detect as many cases of LLL as possible, even after post-cancer-treatment follow-up, we need to be able to identify high-risk patients and inform them of the possibility of late-onset LLL to implement possible interventions such as lymphaticovenular anastomosis [15,16], and creating perforator flap [17]. In this study, we aimed to evaluate the prevalence of and risk factors for late-onset LLL after gynecological cancer treatment and to assess the associations between clinical variables and the timing of LLL onset.
Section snippets
Materials and methods
We conducted a multicenter retrospective study using the records of 7 medical institutions (Toyota Memorial Hospital, Hirota Internal Medicine Clinic, Nagumo Clinic Fukuoka, Northern Fukushima Medical Center, Limbs Tokushima Clinic, Iwate Prefectural Miyako Hospital, and the Cancer Institute Hospital of the Japanese Foundation for Cancer Research) for the period from April 2002 to November 2014. Every institution follows the recommendations of the National Lymphedema Network who require a
Results
In total, 711 patients with LLL who visited one of the 7 institutions during the study period fulfilled the required criteria. The mean age of the patients was 50.2 years old. ISL stages I, II, late in II, and III were noted in 6 (0.8%), 634 (89.2%), 65 (9.1%) and 6 (0.8%) patients, respectively. One hundred and ninety-five (27.4%) patients received radiotherapy. The baseline characteristics of the eligible cases are listed in Table 1. The patients’ characteristics were also stratified into
Discussion
In the present study, more than half of the examined cases of LLL were categorized as late-onset LLL. Moreover, approximately 30% of LLL developed ≥10 years after treatment for gynecological cancer. This indicates that a substantial number of patients develop LLL 5–10 years after undergoing treatment for gynecological cancer. We also confirmed that being aged <50 years, having a history of cervical cancer rather than endometrial or ovarian cancer, and receiving radiotherapy were independent
Funding sources
This study was supported by JSPS KAKENHI, Grant Number 26293463.
Declaration of competing interest
None declared.
Acknowledgment
We express our appreciation to the seven medical institutions that contributed to our study. We also express our sincere gratitude to Dr. Koji Tamakoshi, who contributed to the design of this study and the statistical analysis with patience and knowledge.
References (27)
- et al.
Lymphedema following gynecological cancer: results from a prospective, longitudinal cohort study on prevalence, incidence and risk factors
Gynecol Oncol
(2017) - et al.
Australian National Endometrial Cancer Study Group. Incidence, risk factors and estimates of a woman's risk of developing secondary lower limb lymphedema and lymphedema-specific supportive care needs in women treated for endometrial cancer
Gynecol Oncol
(2015) - et al.
The incidence of symptomatic lower-extremity lymphedema following treatment of uterine corpus malignancies: a 12-year experience at Memorial Sloan-Kettering Cancer Center
Gynecol Oncol
(2006) - et al.
Impact of lower limb lymphedema on quality of life in gynecologic cancer survivors after pelvic lymph node dissection
Eur J Obstet Gynecol Reprod Biol
(2015) - et al.
Australian National Endometrial Cancer Study Group. Quality of life of women with lower limb swelling or lymphedema 3-5 years following endometrial cancer
Gynecol Oncol
(2014) - et al.
Risk factors for lymphoedema in women with breast cancer: a large prospective cohort
Breast
(2016) - et al.
Lymphedema after gynecological cancer treatment: prevalence, correlates, and supportive care needs
Cancer
(2007) - et al.
Prevalence, classification, and risk factors for postoperative lower extremity lymphedema in women with gynecologic malignancies: a retrospective study
Int J Gynecol Canc
(2015) - et al.
Risk factors and a prediction model for lower limb lymphedema following lymphadenectomy in gynecologic cancer: a hospital-based retrospective cohort study
BMC Wom Health
(2017) - et al.
Frequency and risk factors of lower limb lymphedema following lymphadenectomy in patients with gynecological malignancies
Eur J Gynaecol Oncol
(2013)
Risk factors for lower-limb lymphedema after surgery for cervical cancer
Int J Clin Oncol
Incidence and risk factors of lower-extremity lymphedema after radical surgery with or without adjuvant radiotherapy in patients with FIGO stage I to stage IIA cervical cancer
Int J Gynecol Canc
Incidence and risk factors of lower extremity lymphedema after gynecologic surgery in ovarian cancer
Int J Gynecol Canc
Cited by (13)
Conservative treatment versus lymphaticovenular anastomosis for early-stage lower extremity lymphedema
2023, Journal of Vascular Surgery: Venous and Lymphatic DisordersChallenges in lower limb lymphoedema assessment based on limb volume change: Lessons learnt from the SENTIX prospective multicentre study
2022, Gynecologic OncologyCitation Excerpt :This morbidity can limit patients' mobility and have a substantial impact on quality of life [3,4]. The incidence of LLL in patients after surgical treatment of cervical cancer is reported in a wide range of 0–62% [5–7]. The main reason for such a wide variation in LLL observation is the lack of assessment standards, including the use of different classification systems and, most importantly, the method of the assessment [8].
A machine learning-based prediction model of pelvic lymph node metastasis in women with early-stage cervical cancer
2024, Journal of Gynecologic OncologyRisk factors for lymphedema and method of assessment in endometrial cancer: A prospective longitudinal multicenter study
2023, International Journal of Gynecological Cancer