Interventions for Lower Limb Lymphedema Following Gynecological Cancer: A Systematic Review and Meta-Analysis

Interventions for Lower Limb Lymphedema Following Gynecological Cancer: A Systematic Review and Meta-Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Interventions for Lower Limb Lymphedema Following Gynecological Cancer: A Systematic Review and Meta-Analysis Chaonan Zhang, Soh Kim Lam, Putri binti Yubbu, Lizhi Yang, Yingying Chen, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7083022/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose To evaluate the effectiveness of interventions for managing lower limb lymphedema (LLL) in women following gynecological cancer treatment. Methods A review of randomized controlled trials and quasi-experimental studies was conducted, covering literature up to November 2024 across six databases: Web of Science, PubMed, Cochrane Library, Medline, CINAHL, and Scopus. Meta-analyses were performed using Stata 17.0 with a random effects model. Results Nine studies (four RCTs and five quasi-experimental) involving 307 participants were included. Risk of bias was generally low, based on RoB 2 and ROBINS-I assessments, though some domains showed high risk. Interventions, exercise, compression therapy, and their combination, yielded improvements in limb volume, pain, and quality of life in several studies. However, meta-analysis found no significant overall effect on limb volume (SMD = 0.07, 95% CI: -0.96 to 1.09, p = 0.90), with high heterogeneity (I² = 96.25%). Meta-regression identified mean age as a significant moderator (p = 0.025). No serious adverse effects were reported, and no publication bias was detected. Conclusions While the meta-analysis did not show a significant reduction in limb volume, the findings support exercise combined with compression therapy as a safe, practical, and potentially effective strategy for managing LLL and its symptoms. Biological sciences/Cancer Health sciences/Diseases Health sciences/Health care Health sciences/Medical research Health sciences/Oncology Gynecology Lower Limb Lymphedema Therapeutics Meta-analysis Systematic review Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Gynecological cancers, including cervical, ovarian, uterine, vulvar, vaginal, and other malignancies of the female reproductive system, are among the most common cancers in women globally[ 1 , 2 ]. While treatments such as surgery and radiation aim to control the disease, they can also lead to long-term complications, with lower limb lymphedema (LLL) being one of the most prevalent [ 3 , 4 ]. As survival rates improve, rising from 64.3–72.3% for cervical, 64.2–78.9% for uterine, and 44.7–50.8% for ovarian cancers [ 5 ], the need for effective management of treatment-related sequelae like LLL becomes increasingly important. LLL is a frequent but often under-recognized complication after gynecologic cancer treatment, with its prevalence varying by cancer type [ 6 ]. Treatment-related damage to lymphatic vessels, such as stenosis, occlusion, or fibrosis, can impair lymph flow, resulting in fluid accumulation in lower limb tissues [ 7 , 8 ]. Compared to upper limb lymphedema, which is more extensively studied in breast cancer survivors, LLL progresses more rapidly due to gravitational forces and the legs weight-bearing function. Early stages involve extracellular fluid buildup in the lower limbs, including ankles, feet, and genital or pelvic regions. As the condition progresses, visible swelling and fibrotic tissue changes develop [ 9 ]. LLL can significantly impair mobility and daily functioning [ 10 ], while also affecting body image, quality of life, and psychosocial well-being [ 11 , 12 ]. Given its chronic nature and impact on survivorship, identifying effective, evidence-based interventions for LLL is crucial. Once developed, lymphedema becomes a chronic and difficult condition to manage [ 8 ]. Current treatment options for LLL include surgical, pharmacological, and conservative approaches. While surgical methods have advanced, they are not curative and are generally reserved for severe cases. Their applicability is limited for patients with mild to moderate lymphedema, and inconsistent study outcomes hinder the creation of standardized surgical guidelines [ 13 , 14 ]. Pharmacological treatments are used occasionally but offer limited long-term benefits and may carry risks such as renal impairment, making them unsuitable for routine care [ 15 ]. Conservative management is the preferred approach, with complex decongestive therapy (CDT) regarded as the gold standard non-surgical intervention by the International Lymphatic Society [ 8 ]. CDT, also known as combined physical therapy, includes manual lymphatic drainage (MLD), compression therapy, exercise, and skin care. It is generally safe, effective, and helps reduce swelling, pain, and improve mobility [ 16 ]. However, CDT is resource-intensive, time-consuming, and expensive, placing a financial burden on patients [ 17 – 20 ]. Despite its benefits, CDT is rarely integrated into standard gynecologic cancer care [ 9 ]. Its complexity and the need for adherence to multiple components often make consistent application difficult in real-world settings [ 21 ]. CDT outcomes can vary significantly between individuals, and full adherence to its multi-component regimen is rarely achieved [ 22 ]. These challenges underscore the need for simpler, accessible, and cost-effective strategies to manage LLL. Identifying the most effective components of CDT is key to developing practical, sustainable treatments. LLL management after gynecological cancer remains difficult due to limited systematic reviews on effective interventions. While upper limb lymphedema has been widely studied in breast cancer, LLL remains underexplored. This systematic review and meta-analysis address this gap by evaluating CDT-based interventions for LLL in women treated for gynecological cancer. The goal is to identify optimal, evidence-based treatment combinations that improve quality of life, reduce financial burden, and support long-term management. This review followed the PICO framework to assess whether CDT-based interventions (I) effectively reduce limb volume and circumference and alleviate symptoms (O) in women with LLL after gynecological cancer treatment (P). Materials and Methods Eligibility criteria This review included studies that met the following conditions: participants were women aged 18 years or older who had received treatment for gynecological cancer; the studies evaluated interventions specifically targeting LLL and assessed symptoms such as limb volume, pain, heaviness, tightness, or functional limitations. Eligible interventions were those based on components of CDT, including MLD, compression therapy, exercise, skin care, patient education (delivered or supervised by nurses), or case management. Studies were required to use either a randomized controlled trial (RCT) or a quasi-experimental design. Studies were excluded if they did not focus on secondary lymphedema, were not published in English, lacked full-text availability, were not peer-reviewed, or fell under grey literature such as theses, dissertations, books, or government reports. Search strategies A comprehensive electronic search was conducted across six databases, Web of Science, PubMed, Cochrane Library, Medline, CINAHL, and Scopus, from their inception to November 2024. The aim was to identify studies related to gynecologic cancer, interventions, and LLL. Two independent investigators (CNZ and YYC), with support from a health science librarian, performed the search using Boolean logic. The specific search terms and strategies are detailed in Supplementary File 1 . Study Selection All citations identified through the database search were imported into Rayyan for reference management [ 23 ]. A total of 1,045 articles were retrieved, and 522 duplicates were removed. Two investigators (CNZ and YYC) independently screened the remaining titles and abstracts for relevance. Articles deemed potentially eligible were then assessed in full-text form. Any disagreements were resolved through discussion with the research team to reach consensus. Following the screening process, 479 articles were excluded based on title and abstract, 20 full texts could not be retrieved, and 15 were excluded after full-text review. Ultimately, nine studies met the inclusion criteria for this review. The study selection process adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Data extraction Data were independently extracted by two investigators (LZY and JW) from the studies that met the inclusion criteria. Extracted information included study characteristics, participant demographics, details of the interventions, and the outcome measures used. After completing the extraction process separately, the two investigators compared and consolidated their findings into a single data table through discussion and consensus. Appraisal of Study Quality and Risk of Bias To evaluate the risk of bias in the included studies, two investigators (YYC and LZY) conducted independent assessments. For randomized controlled trials (RCTs), the Revised Cochrane risk-of-bias tool (RoB 2) [ 24 ] was applied. This tool assesses five key domains: bias arising from the randomization process, deviations from intended interventions, missing outcome data, outcome measurement, and selection of the reported results. Each domain is rated as "low risk," "some concerns," or "high risk," with an overall judgment reflecting the study’s validity. For quasi-experimental studies, the Cochrane Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) [ 25 ] was used. This tool evaluates seven domains: confounding, participant selection, intervention classification, deviations from intended interventions, missing data, outcome measurement, and selection of the reported results. Each domain is rated as “low,” “moderate,” “serious,” “critical” risk of bias, or “no information,” leading to an overall risk of bias judgment for each study. Data Synthesis Following a narrative synthesis, meta-analyses were conducted using Stata version 17.0 (StataCorp LP, College Station, TX, USA). Effect sizes for outcome measures were pooled using standardized mean differences (SMDs). Study heterogeneity was assessed with the I² statistic, categorized as low (0%-40%), moderate (30%-60%), substantial (50%-90%), or considerable (75%-100%) [ 26 ]. The I² in this analysis was 96.25%, indicating considerable heterogeneity. Consequently, a random-effects model was applied to account for variability within and between studies [ 26 ]. Forest plots illustrated pooled effect sizes with 95% confidence intervals, while funnel plots and Egger’s regression test assessed potential publication bias. Meta-regression identified age as a significant moderator of heterogeneity (p < 0.05), prompting subgroup analyses stratified by age (< 60 years versus ≥ 60 years) to explore its impact on outcomes. Sensitivity analyses were also performed by removing individual studies sequentially to evaluate the stability of the results and detect influential outliers. All statistical tests were two-sided, with significance set at p < 0.05. Results A total of 1,045 articles were retrieved through the database search. Of these, nine studies met the inclusion criteria, comprising four RCTs [ 27 – 30 ] and five quasi-experimental studies [ 31 – 35 ] (Fig. 1 ). Characteristics of included studies The nine studies, summarized in Table 1 , were published between 2008 and 2024. Sample sizes varied from 12 to 60 participants, with a combined total of 307 women affected by LLL following gynecological cancers such as cervical, endometrial, or ovarian cancer. The studies investigated a range of interventions for managing LLL, including active exercise combined with compression therapy [ 27 , 28 ], complex rehabilitation paired with complex decongestive therapy [ 29 ], diaphragmatic breathing with limb coordination training [ 30 ], and fluoroscopy-guided manual lymph drainage as part of complex decongestive therapy [ 35 ]. Additional approaches included vascular gymnastics (involving external compression using multilayer bandages, sleeves, or Mobiderm Autofit), hydrotherapy, and patient education on lifelong management strategies [ 32 ]. Table 1 Main characteristics of included studies (n = 9) Author(Year)/ Cuontry Subjects(n) Design Interventions Outcomes & evaluation time Results Interventions Comparators Abe, K et al. (2021)/ Japan women with secondary lower limb lymphedema (LLL) after gynecological cancer surgery (n = 18) RCTs 1.Active exercise with compression therapy (AECT) in a supine position using a bicycle ergometer. 2. AECT in a seated position using a bicycle ergometer. AECT: Performed using a bicycle ergometer for 15 minutes with the affected limb wrapped in multilayered elastic compression bandages. Compression-only therapy (CT) in a supine position Outcomes : Primary : Lower-limb volume Secondary : Pain, heaviness, skin stiffness, pitting edema Time : Before and after each intervention 1.Supine AECT showed the greatest reduction in limb volume (2.03% ± 1.24%), better than seated AECT (1.19% ± 1.32%) and CT (0.99% ± 0.83%). 2.Supine AECT significantly reduced pain (71.0% ± 22.4%) and heaviness (62.3% ± 26.2%) compared to seated AECT. 3.No significant changes in skin stiffness or pitting edema. Fukushima, T et al. (2017)/Japan women with lower limb lymphedema (LLL) following gynecological cancer treatment (n = 22) RCTs 1. High-load AECT (Active Exercise with Compression Therapy) using a bicycle ergometer: Bicycle ergometer at 10% of the participant's maximum leg extension strength, 15 minutes of pedaling at 50 revolutions/min, lower limb wrapped in short-stretch compression bandages. 2. Low-load AECT using a bicycle ergometer༚Bicycle ergometer at 5% of the participant's maximum leg extension strength, 15 minutes of pedaling at 50 revolutions/min, lower limb wrapped in short-stretch compression bandages. only therapy (CT): Participants sat for 15 minutes, with lower limbs wrapped in short-stretch compression bandages. Outcomes : Primary : Lower-limb volume Secondary : Pain, heaviness, skin stiffness, pitting edema Time : Before and after each intervention 1.High-load AECT had the greatest effect on lower-limb volume reduction (62.5 ± 15.3 mL), significantly better than CT (18.5 ± 15.0 mL, P = 0.02). 2.Pain and heaviness improved significantly for all interventions, but no significant difference was found between them. 3.Skin stiffness did not improve significantly, but pitting edema improved across all interventions. Hwa, J et al. (2017)/South Korea women with unilateral lower limb lymphedema (LLL) after gynecological cancer surgery (n = 40) RCTs 1. Complex rehabilitation (CR) combined with complex decongestive therapy (CDT) (CRCDT) for 4 weeks. — Complex Decongestive Therapy (CDT): Manual lymph drainage (MLD), pneumatic compression, compression bandages, skin care, and remedial exercises. — Complex Rehabilitation (CR) Program: 40 minutes of stretching, strengthening, core stability, and aerobic exercise (15 minutes on a cycle and 15 minutes on a treadmill) for 5 days per week over 4 weeks. The first 2 weeks were supervised, and the last 2 weeks were home exercises with a diary log. Complex Decongestive therapy (CDT) only: participants received 10 sessions of CDT over 4 weeks, but no additional rehabilitation exercises. Outcomes : Primary : Edema status, physical function, and quality of life (QoL) Secondary : Fatigue, pain, bioimpedance, GCLQ-K score, 30-second chair stand test, muscular strength Time : Baseline and 4 weeks 1.The CRCDT group showed significant improvements in physical function, fatigue, and muscular strength (P < 0.05) compared to CDT alone. 2.Both groups showed improvement in leg volume, fatigue, and pain. 3.The CRCDT group had higher physical function and fatigue improvements than the CDT group. Wang, J et al. (2024)/China patients with lower limb lymphedema following gynecologic cancer surgery (n = 60) RCTs Diaphragmatic breathing combined with limb coordination training plus CDT — Diaphragmatic breathing: Resistance diaphragmatic breathing exercises, 10 minutes per session, two sets of five breaths before CDT treatment. — Limb coordination training: Using a device called LoopGO, 20 minutes per session, once daily for 4 weeks. Comparators: Complex Decongestive Therapy (CDT) alone — CDT includes Manual Lymphatic Drainage (MLD), Pressure Therapy (Intermittent Pneumatic Compression and Bandaging Pressure Therapy), Skin care, and Edema exercise. Complex Decongestive Therapy (CDT) alone Outcomes : Primary : GCLQ scores; Bilateral lower limb circumference measurements Secondary : Hospital Anxiety and Depression Scale (HADS) scores Time : Before and after the 4-week treatment 1.The treatment group experienced notable reductions in GCLQ scores, bilateral lower limb circumference, and anxiety and depression scores compared to the control group. 2.The treatment group showed significantly lower GCLQ scores at both 2 weeks (p < 0.001) and 4 weeks (p < 0.001) after treatment. 3.The treatment group showed significantly lower bilateral lower limb circumference measurements at both 2 weeks (p = 0.006) and 4 weeks (p < 0.001) after treatment. 4.The treatment group showed significantly lower HADS scores at both 2 weeks (p < 0.001) and 4 weeks (p < 0.001) after treatment. Kim, S et al. (2008)/South Korea gynecological cancer patients with unilateral lymphedema (n = 57) Quasi-Experimental Design Complex decongestive physiotherapy (CDP) which includes: Manual lymphatic drainage (MLD); Compression bandaging; Remedial exercise; Skin care —— Outcomes : Primary : % excess volume Secondary : Quality of Life (QOL) assessed using the SF-36 questionnaire Time : Before CDP and 1 month after CDP 1.% excess volume was significantly decreased after CDP (P < 0.05). QOL scores were significantly higher than at baseline, indicating an improvement in QOL (P < 0.05). 2. The change in % excess volume was associated with changes in physical functioning, social functioning, role-physical, bodily pain, and general health at baseline and 1 month (P < 0.05). Zeng, Y et al. (2023)/China patients with secondary bilateral lower limb lymphedema after comprehensive treatment for gynecological malignant tumors (n = 18) Quasi-Experimental Design 1. Complex decongestive therapy (CDT) based on fluoroscopy-guided manual lymph drainage (FG-MLD) combined with intermittent pneumatic compression (IPC). 2. Treatment course included manual drainage, IPC, bandaging, functional exercise, and skincare, performed once a day for a total of 18 times. —— Outcomes : Primary : Reduction in bilateral lower limb circumference; Reduction in extracellular water (ECW) content༛ Reduction in lower limb segment ECW ratio Secondary : Improvement in 50-kHz bioelectrical impedance༛ Improvement in quality of life (QoL) scores༛ Improvement in subjective symptoms Time : Before treatment and after 18 treatments 1. Significant reduction in bilateral lower limb circumference (p < 0.05) 2. Significant reduction in ECW content and lower limb segment ECW ratio (p < 0.05) 3.Significantly higher 50-kHz bioelectrical impedance and QoL scores after treatment (p < 0.05) 4.Significant improvement in subjective symptoms except for local swelling (p < 0.05) Freyne, A et al. (2021)/Ireland patients with severe lower limb lymphoedema following gynaecological cancer treatment (n = 12) Quasi-Experimental Design Home compression pneumatic devices (PCD) for at least one hour per day. —— Outcomes : Primary : Quality of life (QoL) assessed using EORTC QLQ-C30 Version 3.0 and a supplementary gynaecological cancer-specific lymphoedema questionnaire. Secondary : Improvement in functional and symptom scores, except for sexual function. Time : Before treatment and after at least 8 weeks of home compression treatment. 1.Improvement in all participants' functional and symptom scores with compression therapy, except for sexual function. 2.Significantly higher mean global health score after compression pump therapy (p < 0.01). 3.Significant improvement in physical, role, emotional, cognitive, and social functioning, as well as pain and fatigue (p < 0.01). 4.The gynaecological cancer-related lymphoedema questionnaire identified body image as the scale which improved most after therapy (p < 0.05). Kim, Y et al.(2022)/South Korea patients with stage 3 chronic secondary unilateral leg lymphedema after gynecological cancer treatment (n = 30) Quasi-Experimental Design Home-based intermittent pneumatic compression (IPC) device with a unique mode designed to mimic manual lymphatic drainage (MLD) technique. Participants used the IPC device for 1 hour twice a day for 4 weeks, including 30 minutes of MLD-mimicking mode and 30 minutes of conventional mode. —— Outcomes : Primary : Inter-limb volume; difference ratio (Vratio) Secondary : Quality of life (QOL) assessed using the modified Lymph-ICF-LL questionnaire, participant satisfaction. Time : Baseline (T0), post-intervention (T1), one-month follow-up (T2), and two-month follow-up (T3). 1.No significant time-dependent interactions in the inter-limb volume difference ratio (Vratio). 2.Participants who maintained their routine self-maintenance program of short-stretch bandages (group B) showed a more significant decline in Vratio than those who did not (group A). 3.All scores of QOL decreased significantly after the intervention without subgroup difference. 4.All participants were satisfied with the 4-week intervention. Kendrová, L et al. (2020)/Slovak patients diagnosed with secondary lymphedema of the lower extremities after gynecological cancer and radiotherapy (n = 50) Quasi-Experimental Design Comprehensive Decongestive Therapy (CDT) including manual lymphatic drainage, instrumental lymphatic drainage, multilayer bandage, vascular gymnastics, hydrotherapy, and patient education. —— Outcomes : Primary : Reduction in lymphedema volume. Secondary : Quality of Life (QoL) assessed using the LYMQOL LEG questionnaire and pain assessed using the Visual Analogue Scale (VAS). Time : Before and after treatment. 1.Reduction in lymphedema (P < 0.001), increase in QoL (P < 0.001), and reduction in pain (P < 0.001). 2.Significant relationship between QoL change and pain in the domains of symptoms, function, and overall QoL (P 0.001). Additional interventions included home-based pneumatic compression devices [ 31 ] and intermittent pneumatic compression systems designed to simulate manual lymphatic drainage [ 34 ]. Exercise sessions ranged in duration from 15 minutes to one hour, with frequencies varying between once and five times per week over periods spanning four weeks to six months. Control groups received various forms of standard care, such as compression-only therapy [ 27 ], complex decongestive therapy alone [ 29 , 30 ], or no additional intervention beyond the assigned treatment [ 35 ]. Lower extremity volume was the most commonly assessed outcome across the studies. Measurement methods included perometry [ 27 , 28 , 30 ] and, in two studies, bioelectrical impedance to evaluate both limb volume and extracellular water content [ 29 , 35 ]. The water displacement method was not explicitly mentioned but was implied in one study [ 34 ]. Secondary outcomes assessed across the studies included pain, heaviness, skin stiffness, pitting edema, and quality of life. These were evaluated using a variety of instruments, including the Global Cancer Lymphedema Questionnaire (GCLQ) [ 29 ], the LYMQOL LEG questionnaire [ 32 ], the Visual Analogue Scale (VAS) [ 32 ], and bioelectrical impedance analysis [ 35 ]. Quality of appraisal in included studies The quality of the RCTs was assessed using the Revised Cochrane Risk of Bias tool for randomized trials (RoB 2), as shown in Fig. 2 . Of the four RCTs, three (75%) [ 27 – 29 ] demonstrated a low risk of bias related to the randomization process (Domain 1, D1). All four studies (100%) showed a low risk of bias regarding deviations from intended interventions (Domain 2, D2). However, only two studies (50%) [ 27 , 28 ] were rated as having a low risk of bias due to missing outcome data (Domain 3, D3). For the measurement of outcomes (Domain 4, D4), three studies (75%) [ 27 – 29 ] had a low risk of bias, whereas one study [ 30 ] was rated as having a high risk due to concerns in this area. Regarding bias in the selection of the reported result (Domain 5, D5), three studies (75%) [ 27 – 29 ] were assessed as low risk, while Wang et al. [ 30 ] was rated as high risk. Notably, this study [ 30 ] was classified as having a high risk of bias in both the measurement of the outcome (D4) and the selection of the reported result (D5), which substantially impacts its overall quality. None of the RCTs were found to have a high risk of bias related to deviations from intended interventions (D2). However, Abe et al. [ 27 ] was the only study identified as having some concerns regarding missing outcome data (D3), potentially affecting the reliability of its findings. Overall, the quality of the included studies was considered acceptable, with most demonstrating a low risk of bias across the assessed domains. Nonetheless, the high-risk ratings observed in specific areas for Wang et al. [ 30 ] warrant caution in interpreting its results. In contrast, the remaining three RCTs generally exhibited strong methodological rigor with low risks of bias. The quality of the quasi-experimental studies was assessed using the Cochrane Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I), as illustrated in Fig. 3 . Among the five studies, three (60%) [ 31 , 34 , 35 ] demonstrated a low risk of bias due to confounding (D1). All studies, except those by Kendrová et al. [ 32 ] and Kim et al. [ 33 ], exhibited a low risk of bias related to the selection of participants (D2). In terms of bias in the classification of interventions (D3), three studies (60%) [ 31 , 34 , 35 ] were rated as low risk. Only two studies (40%) [ 31 , 34 ] had a low risk of bias due to deviations from intended interventions (D4). Regarding missing data (Domain 5), three studies (60%) [ 31 , 34 , 35 ] were assessed as low risk. Similarly, three studies (60%) [ 31 , 34 , 35 ] showed a low risk of bias in the measurement of outcomes (Domain 6), while Kendrová et al. [ 32 ] and Kim et al. [ 33 ] were rated as high risk in this domain. For the selection of the reported result (Domain 7), three studies (60%) [ 31 , 33 , 35 ] were assessed as low risk, whereas the remaining two [ 32 , 33 ] showed high risk. Notably, Kendrová et al. [ 32 ] and Kim et al. [ 33 ] were categorized as having a high risk of bias in both the selection of participants (D2) and the selection of the reported result (D7), which significantly undermines their overall methodological quality. In summary, while many of the included quasi-experimental studies demonstrated a low risk of bias in several domains, the high-risk assessments in specific areas for Kendrová et al. [ 32 ] and Kim et al. [ 33 ] highlight the need for cautious interpretation of their findings. The remaining three studies were generally methodologically sound, with low risk of bias across most evaluated domains. Effect of inventions on lower limb lymphedema Nine studies examined the effects of various interventions, such as exercise, compression therapy, and combined approaches, on LLL. While improvements in limb volume, pain, heaviness, and quality of life were consistently reported, the extent of these benefits varied depending on the type of intervention and study design. Importantly, no severe adverse events were documented, supporting the overall safety of these interventions. Seven studies specifically evaluated changes in limb volume following physical activity interventions or combined strategies incorporating compression and rehabilitation. For instance, Abe et al. [ 27 ] reported that supine active exercise combined with compression therapy (AECT) led to the greatest reduction in limb volume (2.03% ± 1.24%), outperforming both seated AECT (1.19% ± 1.32%) and compression therapy alone (0.99% ± 0.83%). Similarly, Fukushima et al. [ 28 ] reported a significant reduction in limb volume with high-load AECT (62.5 ± 15.3 mL), which was notably greater than that observed with compression therapy alone (18.5 ± 15.0 mL, p = 0.02). Hwa et al. [ 29 ] demonstrated that comprehensive rehabilitation combined with compression therapy (CRCDT) significantly reduced leg volume and led to improvements in fatigue, physical function, and muscle strength (p < 0.05). Zeng et al. [ 35 ] found notable decreases in both extracellular water content and limb circumference (p < 0.05) following fluoroscopy-guided manual lymph drainage combined with pneumatic compression. Results regarding pain and heaviness were mixed. Significant improvements were reported in some studies. Abe et al. [ 27 ] observed reductions in both parameters, whereas others, such as Fukushima et al. [ 28 ], reported non-significant changes. Kendrová et al. [ 32 ] found substantial reductions in pain (p < 0.001) and significant improvements in quality of life scores (p < 0.005). Similarly, Kim et al. [ 33 ] reported meaningful enhancements in physical and social functioning following complete decongestive physiotherapy (CDP) (p < 0.05). Additionally, Kendrová et al. [ 32 ] observed significant improvements in quality of life (QOL) scores, noting a positive correlation between pain reduction and QOL in areas such as symptoms and functional capacity. Freyne et al. [ 31 ] similarly reported higher global health scores alongside significant improvements in physical, emotional, and social functioning (p < 0.01). Effect size of inventions on lower limb lymphedema Of the nine studies included in the systematic review, four RCTs [ 27 – 30 ] and three quasi-experimental studies [ 32 , 33 , 35 ] were selected for inclusion in the meta-analysis. Outcomes such as pain, quality of life, and heaviness were excluded from the quantitative synthesis due to variability in assessment tools across studies. The meta-analysis therefore focused solely on changes in lower limb volume, comparing measurements before and after interventions. The analysis revealed that the interventions did not produce a significant effect on lower limb volume (standardized mean difference [SMD] = 0.07, 95% confidence interval [CI] − 0.96 to 1.09, p = 0.90), with substantial heterogeneity observed (I² = 96.25%), as shown in Fig. 4 . To explore the impact of potential outliers, a sensitivity analysis was performed ( Supplementary Fig. 1 ), which indicated that excluding individual studies did not meaningfully change the overall effect size, supporting the robustness of these findings. Meta-regression analyses were conducted to explore potential sources of heterogeneity, examining sample size, intervention duration, study quality rating, and mean age. The results showed that mean age was significantly associated with changes in lower limb volume (z = 2.24, p = 0.025), whereas sample size (z = -1.33, p = 0.184), intervention time (z = -1.03, p = 0.303), and study quality rating (z = -1.10, p = 0.272) were not significantly related to the effect size. Following this, subgroup analyses based on mean age were performed. Studies with a mean age ≥ 60 years demonstrated a significant effect size (SMD = 1.49, 95% CI 0.36 to 2.62, I² = 90.09%), while those with a mean age < 60 years showed a non-significant effect (SMD = -1.05, 95% CI − 2.11 to 0.00, I² = 94.79%). The difference between these groups was statistically significant (p < 0.001), suggesting that mean age may be a key moderator driving heterogeneity in outcomes. Specifically, interventions appeared more effective in populations with a mean age of 60 years or older, indicating a potential age-related response to treatment, as illustrated in Fig. 5 . Publication bias was assessed using a funnel plot and Egger’s regression test, with detailed results presented in Supplementary Fig. 2 . Both analyses found no significant evidence of publication bias, reinforcing the reliability of the findings. Discussion This systematic review and meta-analysis underscore the potential effectiveness of interventions for improving clinical outcomes in LLL following gynecological cancer. Although the review includes nine studies involving 307 participants that met strict inclusion criteria, it is important to recognize the relatively small number of studies available in this specialized area. The existing focus on upper limb lymphedema has resulted in a notable evidence gap for LLL, an issue this analysis aims to address, yet this focus naturally limits the number of eligible studies. The meta-analysis of seven qualifying studies offers several important insights that advance the current understanding of lymphedema management. Systematic reviews have highlighted the promising effectiveness of various interventions for managing LLL. Specifically, exercise combined with compression therapy, particularly supine active exercise, has demonstrated greater efficacy in reducing limb volume compared to compression therapy alone [ 27 ]. Despite this, previous research suggests that women with LLL may avoid physical exercise due to fears of worsening their condition [ 36 ]. However, the findings of this systematic review provide strong evidence supporting the beneficial role of exercise in alleviating LLL and its related symptoms. Additionally, these interventions have been shown to improve physical symptoms and quality of life measures. Importantly, their positive effects extend beyond volume reduction to include pain relief, decreased sensations of heaviness, and enhanced functional capacity. This highlights the importance of adopting a comprehensive outcome framework that includes patient-reported symptom relief and quality of life measures. Moreover, the reported feasibility of these interventions across multiple studies indicates that such treatment approaches, including exercise, are generally well-tolerated by patients. Integrating exercise into the management of lLLL following gynecological cancer may therefore enhance patient engagement and adherence to therapy. However, the meta-analysis of seven studies found no significant overall effect on lower limb volume reduction (SMD = 0.07, 95% CI − 0.96 to 1.09), with considerable heterogeneity present (I² = 96.25%), underscoring the complexity and variability of treatment responses. Importantly, subgroup analysis identified age as a key moderator of treatment efficacy, with interventions proving significantly more effective in populations with a mean age of 60 years or older (SMD = 1.49, 95% CI 0.36 to 2.62). This suggests that, despite the typical decline in lymphatic function associated with aging [ 37 ], older adults may experience greater benefits from specific lymphedema treatments. One possible explanation is that older individuals may have lived with lymphedema for a longer duration, potentially reaching a more stable or chronic phase in which interventions produce more consistent and predictable effects. Additionally, older adults are generally less likely to participate in high-intensity exercise or strenuous activities, which may complement and enhance the effectiveness of therapeutic protocols [ 38 ]. Together, these factors could help explain the age-related differences observed in treatment responsiveness. Future research should aim to clarify the mechanisms driving these variations, with a focus on both biological and behavioral factors that improve treatment outcomes in older populations. Such insights will be essential for optimizing lymphedema management tailored to different age groups. These findings carry important implications for both clinical practice and future research. The systematic review suggests that combined interventions, particularly those integrating exercise with compression therapy, may offer greater effectiveness. The observed age-related differences in treatment response highlight the need for personalized approaches; older patients appear to benefit more from current interventions, while younger patients may require additional or tailored strategies to address their more dynamic, long-term responses. Moreover, this study emphasizes the value of adopting a comprehensive outcome assessment framework that goes beyond volume reduction to include critical measures such as pain relief, decreased heaviness, and improved functional ability. Embracing this multifaceted approach will provide a more holistic understanding of treatment efficacy and guide the development of optimized therapeutic strategies tailored to diverse patient needs. This review has several limitations that should be acknowledged. First, the substantial heterogeneity and risk of bias present in some studies necessitate cautious interpretation of the findings. Second, the relatively small sample sizes reflect the current scarcity of focused research on LLL following gynecological cancers, which may limit the statistical power to detect more subtle intervention effects. Third, although meta-regression identified age as a significant moderator, other potential influencing factors may have gone undetected due to the limited number and scope of the primary studies included. Conclusion In conclusion, this systematic review and meta-analysis highlight exercise combined with compression therapy as a key and effective component of CDT for managing LLL following gynecological cancer. This suggests that a more targeted and refined approach to CDT could improve patient outcomes. Although the meta-analysis did not show a statistically significant reduction in limb volume, the evidence supports that exercise with compression therapy is a feasible, safe, and beneficial strategy for alleviating LLL and its related symptoms. The observed age-dependent effects emphasize the importance of personalized treatment approaches: older patients may experience greater benefits from existing interventions, whereas younger patients might need additional strategies to address their longer-term, dynamic responses. Future research should focus on large-scale randomized controlled trials with extended follow-up periods, using standardized outcome measures and reporting practices to further optimize lymphedema management. Moreover, understanding the mechanisms behind age-related differences in treatment efficacy, as well as exploring the biological and behavioral factors that enhance responsiveness in older populations, will be critical. By addressing these gaps, healthcare providers can offer evidence-based, tailored interventions that ultimately improve patient outcomes and quality of life. Declarations Contributions: CNZ, LZY, and YYC made significant contributions to the conception and design of the study, data acquisition, or data analysis and interpretation. KLS, JW, and KGS were involved in drafting the manuscript or critically revising it for important intellectual content. CNZ, LZY, YYC, KLS, JW, and KGS provided final approval for the version to be published. Each author has participated sufficiently in the work to take public responsibility for the appropriate portions of the content. CNZ, LZY, YYC, KLS, JW, and KGS are accountable for all aspects of the work, ensuring that any questions regarding the accuracy or integrity of any part of the work are properly investigated and resolved. Acknowledgments We sincerely thank all the participants who contributed to this study. Data Statement: The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Funding information Chaonan Zhang is supported by Health Commission of Zhejiang Province (2023KY142), Project of Wenzhou Science and Technology Bureau(Y20220157), Project of Wenzhou Science and Technology Bureau(Y2023742), Project of the Nursing Department of the First Affiliated Hospital of Wenzhou Medical University (HLKY202202). Competing interests The authors declare no competing interests. References Duan, R., et al., Temporal trends and projections of gynecological cancers in China, 2007-2030. BMC Womens Health, 2023. 23 (1): p. 346. Keyvani, V., et al., Epidemiological trends and risk factors of gynecological cancers: an update. Med Oncol, 2023. 40 (3): p. 93. Hu, H., et al., Risk factors for lower extremity lymphedema after cervical cancer treatment: a systematic review and meta-analysis. Transl Cancer Res, 2022. 11 (6): p. 1713-1721. Kunitake, T., T. Kakuma, and K. Ushijima, Risk factors for lower limb lymphedema in gynecologic cancer patients after initial treatment. Int J Clin Oncol, 2020. 25 (5): p. 963-971. Deng, S., et al., Survival analysis of gynecological cancers in Southeast China, 2011-2020: A population-based study. Cancer Epidemiol, 2024. 92 : p. 102641. Dessources, K., E. Aviki, and M.M. Leitao, Jr., Lower extremity lymphedema in patients with gynecologic malignancies. Int J Gynecol Cancer, 2020. 30 (2): p. 252-260. Sakkuru, R.K., et al., "Incidence of Lower Limb Lymphedema in Post therapeutic Gynaecological Malignancies". International Journal of Physiotherapy, 2023. 10 (2). Executive Committee of the International Society of, L., The diagnosis and treatment of peripheral lymphedema: 2020 Consensus Document of the International Society of Lymphology. Lymphology, 2020. 53 (1): p. 3-19. Plinsinga, M.L., et al., Mild symptoms matter: Results from a prospective, longitudinal study on the relationship between symptoms, lymphedema and health-related outcomes post-gynecological cancer. Gynecol Oncol, 2024. 191 : p. 158-164. Eidenberger, M., Patient-Reported Outcome Measures With Secondary Lower Limb Lymphedemas: A Systematic Review. J Adv Pract Oncol, 2021. 12 (2): p. 174-187. Lau, K., et al., Cancer-Related Lymphedema and Psychological Distress. Curr Psychiatry Rep, 2024. 26 (11): p. 635-642. Russo, S., et al., Standardization of lower extremity quantitative lymphedema measurements and associated patient-reported outcomes in gynecologic cancers. Gynecol Oncol, 2021. 160 (2): p. 625-632. Chang, D.W., et al., Surgical Treatment of Lymphedema: A Systematic Review and Meta-Analysis of Controlled Trials. Results of a Consensus Conference. Plast Reconstr Surg, 2021. 147 (4): p. 975-993. Mackie, H., et al., Outcome of Liposuction for Limb Lymphedema in Men Compared with Women. J Plast Reconstr Surg, 2025. 4 (1): p. 1-6. Donahue, P.M.C., et al., Advances in the prevention and treatment of breast cancer-related lymphedema. Breast Cancer Res Treat, 2023. 200 (1): p. 1-14. Choi, J.E. and M.C. Chang, Management of lymphedema is really a matter in patients with breast cancer. World J Clin Cases, 2024. 12 (15): p. 2482-2486. Rockson, S.G., et al., A non-randomized, open-label study of the safety and effectiveness of a novel non-pneumatic compression device (NPCD) for lower limb lymphedema. Sci Rep, 2022. 12 (1): p. 14005. Rockson, S.G., et al., Author Correction: A non-randomized, open-label study of the safety and effectiveness of a novel non-pneumatic compression device (NPCD) for lower limb lymphedema. Sci Rep, 2023. 13 (1): p. 911. Weiss, R., Cost of a lymphedema treatment mandate - 16 years of experience in the Commonwealth of Virginia. Health Econ Rev, 2022. 12 (1): p. 40. Rajan, S. and H. Venkatramani, Recent advances in management of lymphedema. Journal of Skin and Sexually Transmitted Diseases, 2021. 3 : p. 26-32. Bergmann, A., J.M.T. Baiocchi, and M.F.C. de Andrade, Conservative treatment of lymphedema: the state of the art. J Vasc Bras, 2021. 20 : p. e20200091. Vo, T.T., et al., Effect of Complex Decongestive Therapy Program on Volume and Functioning in Breast Cancer-Related Lymphedema: Global Effect and Predicting Factors. Lymphat Res Biol, 2024. 22 (6): p. 271-277. Ouzzani, M., et al., Rayyan-a web and mobile app for systematic reviews. Syst Rev, 2016. 5 (1): p. 210. Sterne, J.A.C., et al., RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 2019. 366 : p. l4898. Sterne, J.A., et al., ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ, 2016. 355 : p. i4919. Higgins, J.P.T., et al., Cochrane Handbook for Systematic Reviews of Interventions . 2019. Abe, K., et al., Postural differences in the immediate effects of active exercise with compression therapy on lower limb lymphedema. Support Care Cancer, 2021. 29 (11): p. 6535-6543. Fukushima, T., et al., Immediate effects of active exercise with compression therapy on lower-limb lymphedema. Support Care Cancer, 2017. 25 (8): p. 2603-2610. Hwa, J., DO, Choi, K. H., Ahn, J. S., & Jeon, J. Y. (2017). Effects of a complex rehabilitation program on edema status, physical function, and quality of life in lower-limb lymphedema after gynecological cancer surgery. Gynecologic Oncology, 147(2), 450–455. https://doi.org/10.1016/j.ygyno.2017.09.003. Wang, J., et al., The rehabilitation efficacy of diaphragmatic breathing combined with limb coordination training for lower limb lymphedema following gynecologic cancer surgery. Front Bioeng Biotechnol, 2024. 12 : p. 1392824. Freyne, A., et al., Severe lymphoedema in gynaecological cancers: Impact of pneumatic compression on quality of life. Gynecol Oncol Rep, 2022. 39 : p. 100902. Kendrova, L., et al., Comprehensive Decongestive Therapy as a Treatment for Secondary Lymphedema of the Lower Extremity and Quality of Life of Women After Gynecological Cancer Surgery. Med Sci Monit, 2020. 26 : p. e924071. Kim, S.J. and Y.D. Park, Effects of complex decongestive physiotherapy on the oedema and the quality of life of lower unilateral lymphoedema following treatment for gynecological cancer. Eur J Cancer Care (Engl), 2008. 17 (5): p. 463-8. Kim, Y., et al., Home-Based Intermittent Pneumatic Compression Therapy: The Impact in Chronic Leg Lymphedema in Patients Treated for Gynecologic Cancer. Healthcare (Basel), 2022. 10 (4). Zeng, Y., et al., Application of Complete Decongestive Therapy in Patients with Secondary Bilateral Lower Limb Lymphedema after Comprehensive Treatment of Gynecological Malignant Tumor. Lymphat Res Biol, 2024. 22 (1): p. 60-65. Abakay, H., et al., Association of lower extremity lymphedema with pelvic floor functions, sleep quality, kinesiophobia, body image in patients with gynecological cancers. Women Health, 2023. 63 (1): p. 27-34. Yoshihara, M., et al., Risk factors for late-onset lower limb lymphedema after gynecological cancer treatment: A multi-institutional retrospective study. Eur J Surg Oncol, 2020. 46 (7): p. 1334-1338. Hida, M., et al., Investigation of factors influencing low physical activity levels in community-dwelling older adults with chronic pain: a cross-sectional study. Sci Rep, 2023. 13 (1): p. 14062. Additional Declarations No competing interests reported. Supplementary Files SupplementaryFiles1.docx SupplementaryFiles2.docx Supplementary Figure 1.Sensitivity analysis for the Effect of interventions on lower limb volume. Supplementary Figure 2.A funnel plot for the Effect of interventions on lower limb volume. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7083022","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":496749561,"identity":"b8b68f35-9f4d-44eb-92b0-73393b74aa76","order_by":0,"name":"Chaonan Zhang","email":"","orcid":"","institution":"Universiti Putra Malaysia","correspondingAuthor":false,"prefix":"","firstName":"Chaonan","middleName":"","lastName":"Zhang","suffix":""},{"id":496749562,"identity":"6377daf7-0b81-45f4-acb3-8d6064714578","order_by":1,"name":"Soh Kim Lam","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuklEQVRIiWNgGAWjYDACHuYGBoYKCFuCSC2MQC1nSNbC2EaKFvmeg42fbs47nKfbwHzwNg/DtsQGQloMzjY2S+duO1xsdoAt2ZqH4TYRWvgZG0BaErcd4DGTJkqLfD9j8+/cOSAt/N+I08JwtrFNOrcBbAsbcVoMzhxss845ll5sdpjN2HKOwW1jwg7rST58O6fGOs/sePPDG28qbssSdhgUJDAwgy1lcCRBCxTYE6tjFIyCUTAKRg4AAOItQH4OpgcDAAAAAElFTkSuQmCC","orcid":"","institution":"Universiti Putra Malaysia","correspondingAuthor":true,"prefix":"","firstName":"Soh","middleName":"Kim","lastName":"Lam","suffix":""},{"id":496749563,"identity":"11b15576-2819-4870-8d79-b0770bed65ae","order_by":2,"name":"Putri binti Yubbu","email":"","orcid":"","institution":"Universiti Putra Malaysia","correspondingAuthor":false,"prefix":"","firstName":"Putri","middleName":"binti","lastName":"Yubbu","suffix":""},{"id":496749564,"identity":"150e2726-b8d3-42e5-a1ac-1746ad5f949b","order_by":3,"name":"Lizhi Yang","email":"","orcid":"","institution":"Health Medical College, Zhejiang DongFang Polytechnic","correspondingAuthor":false,"prefix":"","firstName":"Lizhi","middleName":"","lastName":"Yang","suffix":""},{"id":496749565,"identity":"d9e053b6-89d5-4385-9dea-785c14f98ba1","order_by":4,"name":"Yingying Chen","email":"","orcid":"","institution":"Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yingying","middleName":"","lastName":"Chen","suffix":""},{"id":496749566,"identity":"b2a528f8-5f2a-4ae4-a308-d94f38d01a8a","order_by":5,"name":"Jian Chen","email":"","orcid":"","institution":"Universiti Putra Malaysia","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Chen","suffix":""},{"id":496749567,"identity":"41d0b093-223b-4bd7-877e-36b99e97e649","order_by":6,"name":"Jing Wu","email":"","orcid":"","institution":"The First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Wu","suffix":""}],"badges":[],"createdAt":"2025-07-09 10:53:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7083022/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7083022/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89861204,"identity":"48e7f017-13f5-4f3e-9ef8-8614ceeb9cae","added_by":"auto","created_at":"2025-08-25 20:57:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1021179,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA Flowchart of the study selection.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7083022/v1/4eb2026698b33c512979c5c1.png"},{"id":89861924,"identity":"616baa77-6f08-4606-b273-04310a5fc310","added_by":"auto","created_at":"2025-08-25 21:13:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1899259,"visible":true,"origin":"","legend":"\u003cp\u003eRisk of bias for included RCTs.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7083022/v1/8f0d6c3429daddf6322ec29d.png"},{"id":89861535,"identity":"e4681541-9883-4edd-b2d2-e890f1141720","added_by":"auto","created_at":"2025-08-25 21:05:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":271150,"visible":true,"origin":"","legend":"\u003cp\u003eRisk of bias for included Quasi-Experimental.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7083022/v1/46e69ae6f32b274f2a97541a.png"},{"id":89861206,"identity":"1a942577-7fef-4da0-ada2-a59065f28ce0","added_by":"auto","created_at":"2025-08-25 20:57:43","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":186799,"visible":true,"origin":"","legend":"\u003cp\u003eForest Plots for the Effect of interventions on lower limb volume.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7083022/v1/9fa852f746f8b662d2485169.png"},{"id":89861213,"identity":"dab1a300-c403-44b9-a2bf-c79e290cf396","added_by":"auto","created_at":"2025-08-25 20:57:43","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":229951,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analyses based on mean age.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7083022/v1/bc3cead0a958dc2de9bb29a3.png"},{"id":95654801,"identity":"25ce9878-648e-4c2b-b41c-3d593f199105","added_by":"auto","created_at":"2025-11-11 16:13:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4820347,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7083022/v1/9e3f4160-300e-4290-a00f-50841044cd15.pdf"},{"id":89861923,"identity":"cd92e8d8-c854-4c1c-aa12-79f90b2074ae","added_by":"auto","created_at":"2025-08-25 21:13:43","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":27213,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFiles1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7083022/v1/fc38f6fbcb49af9a6203a8e5.docx"},{"id":89861536,"identity":"f9038910-bfd8-469d-b6fa-cc4eb948516b","added_by":"auto","created_at":"2025-08-25 21:05:43","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":195452,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Figure 1.\u003c/strong\u003eSensitivity analysis for the Effect of interventions on lower limb volume.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Figure 2.\u003c/strong\u003eA funnel plot for the Effect of interventions on lower limb volume.\u003c/p\u003e","description":"","filename":"SupplementaryFiles2.docx","url":"https://assets-eu.researchsquare.com/files/rs-7083022/v1/4beb72945f307f8276b9c783.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Interventions for Lower Limb Lymphedema Following Gynecological Cancer: A Systematic Review and Meta-Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGynecological cancers, including cervical, ovarian, uterine, vulvar, vaginal, and other malignancies of the female reproductive system, are among the most common cancers in women globally[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. While treatments such as surgery and radiation aim to control the disease, they can also lead to long-term complications, with lower limb lymphedema (LLL) being one of the most prevalent [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. As survival rates improve, rising from 64.3\u0026ndash;72.3% for cervical, 64.2\u0026ndash;78.9% for uterine, and 44.7\u0026ndash;50.8% for ovarian cancers [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], the need for effective management of treatment-related sequelae like LLL becomes increasingly important. LLL is a frequent but often under-recognized complication after gynecologic cancer treatment, with its prevalence varying by cancer type [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Treatment-related damage to lymphatic vessels, such as stenosis, occlusion, or fibrosis, can impair lymph flow, resulting in fluid accumulation in lower limb tissues [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Compared to upper limb lymphedema, which is more extensively studied in breast cancer survivors, LLL progresses more rapidly due to gravitational forces and the legs weight-bearing function. Early stages involve extracellular fluid buildup in the lower limbs, including ankles, feet, and genital or pelvic regions. As the condition progresses, visible swelling and fibrotic tissue changes develop [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. LLL can significantly impair mobility and daily functioning [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], while also affecting body image, quality of life, and psychosocial well-being [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Given its chronic nature and impact on survivorship, identifying effective, evidence-based interventions for LLL is crucial. Once developed, lymphedema becomes a chronic and difficult condition to manage [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Current treatment options for LLL include surgical, pharmacological, and conservative approaches. While surgical methods have advanced, they are not curative and are generally reserved for severe cases. Their applicability is limited for patients with mild to moderate lymphedema, and inconsistent study outcomes hinder the creation of standardized surgical guidelines [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Pharmacological treatments are used occasionally but offer limited long-term benefits and may carry risks such as renal impairment, making them unsuitable for routine care [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Conservative management is the preferred approach, with complex decongestive therapy (CDT) regarded as the gold standard non-surgical intervention by the International Lymphatic Society [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. CDT, also known as combined physical therapy, includes manual lymphatic drainage (MLD), compression therapy, exercise, and skin care. It is generally safe, effective, and helps reduce swelling, pain, and improve mobility [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, CDT is resource-intensive, time-consuming, and expensive, placing a financial burden on patients [\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Despite its benefits, CDT is rarely integrated into standard gynecologic cancer care [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Its complexity and the need for adherence to multiple components often make consistent application difficult in real-world settings [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. CDT outcomes can vary significantly between individuals, and full adherence to its multi-component regimen is rarely achieved [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. These challenges underscore the need for simpler, accessible, and cost-effective strategies to manage LLL. Identifying the most effective components of CDT is key to developing practical, sustainable treatments. LLL management after gynecological cancer remains difficult due to limited systematic reviews on effective interventions. While upper limb lymphedema has been widely studied in breast cancer, LLL remains underexplored. This systematic review and meta-analysis address this gap by evaluating CDT-based interventions for LLL in women treated for gynecological cancer. The goal is to identify optimal, evidence-based treatment combinations that improve quality of life, reduce financial burden, and support long-term management. This review followed the PICO framework to assess whether CDT-based interventions (I) effectively reduce limb volume and circumference and alleviate symptoms (O) in women with LLL after gynecological cancer treatment (P).\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cb\u003eEligibility criteria\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis review included studies that met the following conditions: participants were women aged 18 years or older who had received treatment for gynecological cancer; the studies evaluated interventions specifically targeting LLL and assessed symptoms such as limb volume, pain, heaviness, tightness, or functional limitations. Eligible interventions were those based on components of CDT, including MLD, compression therapy, exercise, skin care, patient education (delivered or supervised by nurses), or case management. Studies were required to use either a randomized controlled trial (RCT) or a quasi-experimental design. Studies were excluded if they did not focus on secondary lymphedema, were not published in English, lacked full-text availability, were not peer-reviewed, or fell under grey literature such as theses, dissertations, books, or government reports.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSearch strategies\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA comprehensive electronic search was conducted across six databases, Web of Science, PubMed, Cochrane Library, Medline, CINAHL, and Scopus, from their inception to November 2024. The aim was to identify studies related to gynecologic cancer, interventions, and LLL. Two independent investigators (CNZ and YYC), with support from a health science librarian, performed the search using Boolean logic. The specific search terms and strategies are detailed in \u003cb\u003eSupplementary File 1\u003c/b\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStudy Selection\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAll citations identified through the database search were imported into Rayyan for reference management [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. A total of 1,045 articles were retrieved, and 522 duplicates were removed. Two investigators (CNZ and YYC) independently screened the remaining titles and abstracts for relevance. Articles deemed potentially eligible were then assessed in full-text form. Any disagreements were resolved through discussion with the research team to reach consensus. Following the screening process, 479 articles were excluded based on title and abstract, 20 full texts could not be retrieved, and 15 were excluded after full-text review. Ultimately, nine studies met the inclusion criteria for this review. The study selection process adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData extraction\u003c/b\u003e\u003c/p\u003e\u003cp\u003eData were independently extracted by two investigators (LZY and JW) from the studies that met the inclusion criteria. Extracted information included study characteristics, participant demographics, details of the interventions, and the outcome measures used. After completing the extraction process separately, the two investigators compared and consolidated their findings into a single data table through discussion and consensus.\u003c/p\u003e\u003cp\u003e\u003cb\u003eAppraisal of Study Quality and Risk of Bias\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTo evaluate the risk of bias in the included studies, two investigators (YYC and LZY) conducted independent assessments. For randomized controlled trials (RCTs), the Revised Cochrane risk-of-bias tool (RoB 2) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] was applied. This tool assesses five key domains: bias arising from the randomization process, deviations from intended interventions, missing outcome data, outcome measurement, and selection of the reported results. Each domain is rated as \"low risk,\" \"some concerns,\" or \"high risk,\" with an overall judgment reflecting the study\u0026rsquo;s validity. For quasi-experimental studies, the Cochrane Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] was used. This tool evaluates seven domains: confounding, participant selection, intervention classification, deviations from intended interventions, missing data, outcome measurement, and selection of the reported results. Each domain is rated as \u0026ldquo;low,\u0026rdquo; \u0026ldquo;moderate,\u0026rdquo; \u0026ldquo;serious,\u0026rdquo; \u0026ldquo;critical\u0026rdquo; risk of bias, or \u0026ldquo;no information,\u0026rdquo; leading to an overall risk of bias judgment for each study.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData Synthesis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFollowing a narrative synthesis, meta-analyses were conducted using Stata version 17.0 (StataCorp LP, College Station, TX, USA). Effect sizes for outcome measures were pooled using standardized mean differences (SMDs). Study heterogeneity was assessed with the I\u0026sup2; statistic, categorized as low (0%-40%), moderate (30%-60%), substantial (50%-90%), or considerable (75%-100%) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The I\u0026sup2; in this analysis was 96.25%, indicating considerable heterogeneity. Consequently, a random-effects model was applied to account for variability within and between studies [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Forest plots illustrated pooled effect sizes with 95% confidence intervals, while funnel plots and Egger\u0026rsquo;s regression test assessed potential publication bias. Meta-regression identified age as a significant moderator of heterogeneity (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), prompting subgroup analyses stratified by age (\u0026lt;\u0026thinsp;60 years \u003cem\u003eversus\u003c/em\u003e \u0026ge;\u0026thinsp;60 years) to explore its impact on outcomes. Sensitivity analyses were also performed by removing individual studies sequentially to evaluate the stability of the results and detect influential outliers. All statistical tests were two-sided, with significance set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 1,045 articles were retrieved through the database search. Of these, nine studies met the inclusion criteria, comprising four RCTs [\u003cspan additionalcitationids=\"CR28 CR29\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] and five quasi-experimental studies [\u003cspan additionalcitationids=\"CR32 CR33 CR34\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eCharacteristics of included studies\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe nine studies, summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, were published between 2008 and 2024. Sample sizes varied from 12 to 60 participants, with a combined total of 307 women affected by LLL following gynecological cancers such as cervical, endometrial, or ovarian cancer. The studies investigated a range of interventions for managing LLL, including active exercise combined with compression therapy [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], complex rehabilitation paired with complex decongestive therapy [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], diaphragmatic breathing with limb coordination training [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], and fluoroscopy-guided manual lymph drainage as part of complex decongestive therapy [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Additional approaches included vascular gymnastics (involving external compression using multilayer bandages, sleeves, or Mobiderm Autofit), hydrotherapy, and patient education on lifelong management strategies [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMain characteristics of included studies (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAuthor(Year)/\u003c/p\u003e\u003cp\u003eCuontry\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSubjects(n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eDesign\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eInterventions\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eOutcomes \u0026amp; evaluation time\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eResults\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eInterventions\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eComparators\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbe, K et al. (2021)/ Japan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ewomen with secondary lower limb lymphedema (LLL) after gynecological cancer surgery (n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRCTs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.Active exercise with compression therapy (AECT) in a supine position using a bicycle ergometer.\u003c/p\u003e\u003cp\u003e2. AECT in a seated position using a bicycle ergometer.\u003c/p\u003e\u003cp\u003eAECT: Performed using a bicycle ergometer for 15 minutes with the affected limb wrapped in multilayered elastic compression bandages.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCompression-only therapy (CT) in a supine position\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003ePrimary\u003c/b\u003e: Lower-limb volume\u003c/p\u003e\u003cp\u003e\u003cb\u003eSecondary\u003c/b\u003e: Pain, heaviness, skin stiffness, pitting edema\u003c/p\u003e\u003cp\u003e\u003cb\u003eTime\u003c/b\u003e: Before and after each intervention\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.Supine AECT showed the greatest reduction in limb volume (2.03% \u0026plusmn; 1.24%), better than seated AECT (1.19% \u0026plusmn; 1.32%) and CT (0.99% \u0026plusmn; 0.83%). \u003c/p\u003e\u003cp\u003e2.Supine AECT significantly reduced pain (71.0% \u0026plusmn; 22.4%) and heaviness (62.3% \u0026plusmn; 26.2%) compared to seated AECT. \u003c/p\u003e\u003cp\u003e3.No significant changes in skin stiffness or pitting edema.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFukushima, T et al. (2017)/Japan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ewomen with lower limb lymphedema (LLL) following gynecological cancer treatment (n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRCTs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1. High-load AECT (Active Exercise with Compression Therapy) using a bicycle ergometer: Bicycle ergometer at 10% of the participant's maximum leg extension strength, 15 minutes of pedaling at 50 revolutions/min, lower limb wrapped in short-stretch compression bandages.\u003c/p\u003e\u003cp\u003e2. Low-load AECT using a bicycle ergometer༚Bicycle ergometer at 5% of the participant's maximum leg extension strength, 15 minutes of pedaling at 50 revolutions/min, lower limb wrapped in short-stretch compression bandages.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eonly therapy (CT): Participants sat for 15 minutes, with lower limbs wrapped in short-stretch compression bandages.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003ePrimary\u003c/b\u003e: Lower-limb volume \u003c/p\u003e\u003cp\u003e \u003cb\u003eSecondary\u003c/b\u003e: Pain, heaviness, skin stiffness, pitting edema\u003c/p\u003e\u003cp\u003e\u003cb\u003eTime\u003c/b\u003e: Before and after each intervention\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.High-load AECT had the greatest effect on lower-limb volume reduction (62.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3 mL), significantly better than CT (18.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.0 mL, P\u0026thinsp;=\u0026thinsp;0.02).\u003c/p\u003e\u003cp\u003e2.Pain and heaviness improved significantly for all interventions, but no significant difference was found between them.\u003c/p\u003e\u003cp\u003e3.Skin stiffness did not improve significantly, but pitting edema improved across all interventions.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHwa, J et al. (2017)/South Korea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ewomen with unilateral lower limb lymphedema (LLL) after gynecological cancer surgery (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRCTs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1. Complex rehabilitation (CR) combined with complex decongestive therapy (CDT) (CRCDT) for 4 weeks. \u003c/p\u003e\u003cp\u003e\u0026mdash; Complex Decongestive Therapy (CDT): Manual lymph drainage (MLD), pneumatic compression, compression bandages, skin care, and remedial exercises.\u003c/p\u003e\u003cp\u003e\u0026mdash; Complex Rehabilitation (CR) Program: 40 minutes of stretching, strengthening, core stability, and aerobic exercise (15 minutes on a cycle and 15 minutes on a treadmill) for 5 days per week over 4 weeks. The first 2 weeks were supervised, and the last 2 weeks were home exercises with a diary log.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eComplex Decongestive therapy (CDT) only: participants received 10 sessions of CDT over 4 weeks, but no additional rehabilitation exercises.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003ePrimary\u003c/b\u003e: Edema status, physical function, and quality of life (QoL) \u003c/p\u003e\u003cp\u003e\u003cb\u003eSecondary\u003c/b\u003e: Fatigue, pain, bioimpedance, GCLQ-K score, 30-second chair stand test, muscular strength\u003c/p\u003e\u003cp\u003e\u003cb\u003eTime\u003c/b\u003e: Baseline and 4 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.The CRCDT group showed significant improvements in physical function, fatigue, and muscular strength (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) compared to CDT alone. 2.Both groups showed improvement in leg volume, fatigue, and pain.\u003c/p\u003e\u003cp\u003e3.The CRCDT group had higher physical function and fatigue improvements than the CDT group.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWang, J et al. (2024)/China\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epatients with lower limb lymphedema following gynecologic cancer surgery (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRCTs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDiaphragmatic breathing combined with limb coordination training plus CDT\u003c/p\u003e\u003cp\u003e\u0026mdash; Diaphragmatic breathing: Resistance diaphragmatic breathing exercises, 10 minutes per session, two sets of five breaths before CDT treatment.\u003c/p\u003e\u003cp\u003e\u0026mdash; Limb coordination training: Using a device called LoopGO, 20 minutes per session, once daily for 4 weeks. Comparators: Complex Decongestive Therapy (CDT) alone\u003c/p\u003e\u003cp\u003e\u0026mdash; CDT includes Manual Lymphatic Drainage (MLD), Pressure Therapy (Intermittent Pneumatic Compression and Bandaging Pressure Therapy), Skin care, and Edema exercise.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eComplex Decongestive Therapy (CDT) alone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003ePrimary\u003c/b\u003e: GCLQ scores; Bilateral lower limb circumference measurements\u003c/p\u003e\u003cp\u003e\u003cb\u003eSecondary\u003c/b\u003e: Hospital Anxiety and Depression Scale (HADS) scores\u003c/p\u003e\u003cp\u003e\u003cb\u003eTime\u003c/b\u003e: Before and after the 4-week treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.The treatment group experienced notable reductions in GCLQ scores, bilateral lower limb circumference, and anxiety and depression scores compared to the control group.\u003c/p\u003e\u003cp\u003e2.The treatment group showed significantly lower GCLQ scores at both 2 weeks (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 4 weeks (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) after treatment.\u003c/p\u003e\u003cp\u003e3.The treatment group showed significantly lower bilateral lower limb circumference measurements at both 2 weeks (p\u0026thinsp;=\u0026thinsp;0.006) and 4 weeks (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) after treatment.\u003c/p\u003e\u003cp\u003e4.The treatment group showed significantly lower HADS scores at both 2 weeks (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 4 weeks (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) after treatment.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKim, S et al. (2008)/South Korea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003egynecological cancer patients with unilateral lymphedema (n\u0026thinsp;=\u0026thinsp;57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eQuasi-Experimental Design\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eComplex decongestive physiotherapy (CDP) which includes: Manual lymphatic drainage (MLD); Compression bandaging; Remedial exercise; Skin care\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026mdash;\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003ePrimary\u003c/b\u003e: % excess volume\u003c/p\u003e\u003cp\u003e\u003cb\u003eSecondary\u003c/b\u003e: Quality of Life (QOL) assessed using the SF-36 questionnaire\u003c/p\u003e\u003cp\u003e\u003cb\u003eTime\u003c/b\u003e: Before CDP and 1 month after CDP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.% excess volume was significantly decreased after CDP (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eQOL scores were significantly higher than at baseline, indicating an improvement in QOL (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e2. The change in % excess volume was associated with changes in physical functioning, social functioning, role-physical, bodily pain, and general health at baseline and 1 month (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eZeng, Y et al. (2023)/China\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epatients with secondary bilateral lower limb lymphedema after comprehensive treatment for gynecological malignant tumors (n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eQuasi-Experimental Design\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1. Complex decongestive therapy (CDT) based on fluoroscopy-guided manual lymph drainage (FG-MLD) combined with intermittent pneumatic compression (IPC).\u003c/p\u003e\u003cp\u003e2. Treatment course included manual drainage, IPC, bandaging, functional exercise, and skincare, performed once a day for a total of 18 times.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026mdash;\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003ePrimary\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eReduction in bilateral lower limb circumference;\u003c/p\u003e\u003cp\u003eReduction in extracellular water (ECW) content༛\u003c/p\u003e\u003cp\u003eReduction in lower limb segment ECW ratio\u003c/p\u003e\u003cp\u003e\u003cb\u003eSecondary\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eImprovement in 50-kHz bioelectrical impedance༛\u003c/p\u003e\u003cp\u003eImprovement in quality of life (QoL) scores༛\u003c/p\u003e\u003cp\u003eImprovement in subjective symptoms\u003c/p\u003e\u003cp\u003e\u003cb\u003eTime\u003c/b\u003e: Before treatment and after 18 treatments\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1. Significant reduction in bilateral lower limb circumference (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/p\u003e\u003cp\u003e2. Significant reduction in ECW content and lower limb segment ECW ratio (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/p\u003e\u003cp\u003e3.Significantly higher 50-kHz bioelectrical impedance and QoL scores after treatment (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/p\u003e\u003cp\u003e4.Significant improvement in subjective symptoms except for local swelling (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFreyne, A et al. (2021)/Ireland\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epatients with severe lower limb lymphoedema following gynaecological cancer treatment (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eQuasi-Experimental Design\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHome compression pneumatic devices (PCD) for at least one hour per day.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026mdash;\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003ePrimary\u003c/b\u003e: Quality of life (QoL) assessed using EORTC QLQ-C30 Version 3.0 and a supplementary gynaecological cancer-specific lymphoedema questionnaire.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSecondary\u003c/b\u003e: Improvement in functional and symptom scores, except for sexual function.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTime\u003c/b\u003e: Before treatment and after at least 8 weeks of home compression treatment.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.Improvement in all participants' functional and symptom scores with compression therapy, except for sexual function.\u003c/p\u003e\u003cp\u003e2.Significantly higher mean global health score after compression pump therapy (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e\u003cp\u003e3.Significant improvement in physical, role, emotional, cognitive, and social functioning, as well as pain and fatigue (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e\u003cp\u003e4.The gynaecological cancer-related lymphoedema questionnaire identified body image as the scale which improved most after therapy (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKim, Y et al.(2022)/South Korea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epatients with stage 3 chronic secondary unilateral leg lymphedema after gynecological cancer treatment (n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eQuasi-Experimental Design\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHome-based intermittent pneumatic compression (IPC) device with a unique mode designed to mimic manual lymphatic drainage (MLD) technique.\u003c/p\u003e\u003cp\u003eParticipants used the IPC device for 1 hour twice a day for 4 weeks, including 30 minutes of MLD-mimicking mode and 30 minutes of conventional mode.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026mdash;\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003ePrimary\u003c/b\u003e: Inter-limb volume; difference ratio (Vratio)\u003c/p\u003e\u003cp\u003e\u003cb\u003eSecondary\u003c/b\u003e: Quality of life (QOL) assessed using the modified Lymph-ICF-LL questionnaire, participant satisfaction.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTime\u003c/b\u003e: Baseline (T0), post-intervention (T1), one-month follow-up (T2), and two-month follow-up (T3).\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.No significant time-dependent interactions in the inter-limb volume difference ratio (Vratio).\u003c/p\u003e\u003cp\u003e2.Participants who maintained their routine self-maintenance program of short-stretch bandages (group B) showed a more significant decline in Vratio than those who did not (group A).\u003c/p\u003e\u003cp\u003e3.All scores of QOL decreased significantly after the intervention without subgroup difference.\u003c/p\u003e\u003cp\u003e4.All participants were satisfied with the 4-week intervention.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKendrov\u0026aacute;, L et al. (2020)/Slovak\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epatients diagnosed with secondary lymphedema of the lower extremities after gynecological cancer and radiotherapy (n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eQuasi-Experimental Design\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eComprehensive Decongestive Therapy (CDT) including manual lymphatic drainage, instrumental lymphatic drainage, multilayer bandage, vascular gymnastics, hydrotherapy, and patient education.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026mdash;\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003ePrimary\u003c/b\u003e: Reduction in lymphedema volume.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSecondary\u003c/b\u003e: Quality of Life (QoL) assessed using the LYMQOL LEG questionnaire and pain assessed using the Visual Analogue Scale (VAS).\u003c/p\u003e\u003cp\u003e\u003cb\u003eTime\u003c/b\u003e: Before and after treatment.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.Reduction in lymphedema (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), increase in QoL (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and reduction in pain (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e2.Significant relationship between QoL change and pain in the domains of symptoms, function, and overall QoL (P\u0026thinsp;\u0026lt;\u0026thinsp;0.005).\u003c/p\u003e\u003cp\u003e3.Reduction of lymphedema was not a significant predictor of QoL (P\u0026thinsp;\u0026gt;\u0026thinsp;0.001).\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAdditional interventions included home-based pneumatic compression devices [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] and intermittent pneumatic compression systems designed to simulate manual lymphatic drainage [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Exercise sessions ranged in duration from 15 minutes to one hour, with frequencies varying between once and five times per week over periods spanning four weeks to six months. Control groups received various forms of standard care, such as compression-only therapy [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], complex decongestive therapy alone [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], or no additional intervention beyond the assigned treatment [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Lower extremity volume was the most commonly assessed outcome across the studies. Measurement methods included perometry [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] and, in two studies, bioelectrical impedance to evaluate both limb volume and extracellular water content [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. The water displacement method was not explicitly mentioned but was implied in one study [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Secondary outcomes assessed across the studies included pain, heaviness, skin stiffness, pitting edema, and quality of life. These were evaluated using a variety of instruments, including the Global Cancer Lymphedema Questionnaire (GCLQ) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], the LYMQOL LEG questionnaire [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], the Visual Analogue Scale (VAS) [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], and bioelectrical impedance analysis [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cb\u003eQuality of appraisal in included studies\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe quality of the RCTs was assessed using the Revised Cochrane Risk of Bias tool for randomized trials (RoB 2), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Of the four RCTs, three (75%) [\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] demonstrated a low risk of bias related to the randomization process (Domain 1, D1). All four studies (100%) showed a low risk of bias regarding deviations from intended interventions (Domain 2, D2). However, only two studies (50%) [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] were rated as having a low risk of bias due to missing outcome data (Domain 3, D3). For the measurement of outcomes (Domain 4, D4), three studies (75%) [\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] had a low risk of bias, whereas one study [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] was rated as having a high risk due to concerns in this area. Regarding bias in the selection of the reported result (Domain 5, D5), three studies (75%) [\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] were assessed as low risk, while Wang et al. [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] was rated as high risk. Notably, this study [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] was classified as having a high risk of bias in both the measurement of the outcome (D4) and the selection of the reported result (D5), which substantially impacts its overall quality. None of the RCTs were found to have a high risk of bias related to deviations from intended interventions (D2). However, Abe et al. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] was the only study identified as having some concerns regarding missing outcome data (D3), potentially affecting the reliability of its findings. Overall, the quality of the included studies was considered acceptable, with most demonstrating a low risk of bias across the assessed domains. Nonetheless, the high-risk ratings observed in specific areas for Wang et al. [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] warrant caution in interpreting its results. In contrast, the remaining three RCTs generally exhibited strong methodological rigor with low risks of bias. The quality of the quasi-experimental studies was assessed using the Cochrane Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I), as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Among the five studies, three (60%) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] demonstrated a low risk of bias due to confounding (D1). All studies, except those by Kendrov\u0026aacute; et al. [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] and Kim et al. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], exhibited a low risk of bias related to the selection of participants (D2). In terms of bias in the classification of interventions (D3), three studies (60%) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] were rated as low risk. Only two studies (40%) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] had a low risk of bias due to deviations from intended interventions (D4). Regarding missing data (Domain 5), three studies (60%) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] were assessed as low risk. Similarly, three studies (60%) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] showed a low risk of bias in the measurement of outcomes (Domain 6), while Kendrov\u0026aacute; et al. [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] and Kim et al. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] were rated as high risk in this domain. For the selection of the reported result (Domain 7), three studies (60%) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] were assessed as low risk, whereas the remaining two [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] showed high risk. Notably, Kendrov\u0026aacute; et al. [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] and Kim et al. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] were categorized as having a high risk of bias in both the selection of participants (D2) and the selection of the reported result (D7), which significantly undermines their overall methodological quality. In summary, while many of the included quasi-experimental studies demonstrated a low risk of bias in several domains, the high-risk assessments in specific areas for Kendrov\u0026aacute; et al. [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] and Kim et al. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] highlight the need for cautious interpretation of their findings. The remaining three studies were generally methodologically sound, with low risk of bias across most evaluated domains.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eEffect of inventions on lower limb lymphedema\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNine studies examined the effects of various interventions, such as exercise, compression therapy, and combined approaches, on LLL. While improvements in limb volume, pain, heaviness, and quality of life were consistently reported, the extent of these benefits varied depending on the type of intervention and study design. Importantly, no severe adverse events were documented, supporting the overall safety of these interventions.\u003c/p\u003e\u003cp\u003eSeven studies specifically evaluated changes in limb volume following physical activity interventions or combined strategies incorporating compression and rehabilitation. For instance, Abe et al. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] reported that supine active exercise combined with compression therapy (AECT) led to the greatest reduction in limb volume (2.03% \u0026plusmn; 1.24%), outperforming both seated AECT (1.19% \u0026plusmn; 1.32%) and compression therapy alone (0.99% \u0026plusmn; 0.83%).\u003c/p\u003e\u003cp\u003eSimilarly, Fukushima et al. [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] reported a significant reduction in limb volume with high-load AECT (62.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3 mL), which was notably greater than that observed with compression therapy alone (18.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.0 mL, p\u0026thinsp;=\u0026thinsp;0.02). Hwa et al. [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] demonstrated that comprehensive rehabilitation combined with compression therapy (CRCDT) significantly reduced leg volume and led to improvements in fatigue, physical function, and muscle strength (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Zeng et al. [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] found notable decreases in both extracellular water content and limb circumference (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) following fluoroscopy-guided manual lymph drainage combined with pneumatic compression.\u003c/p\u003e\u003cp\u003eResults regarding pain and heaviness were mixed. Significant improvements were reported in some studies. Abe et al. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] observed reductions in both parameters, whereas others, such as Fukushima et al. [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], reported non-significant changes. Kendrov\u0026aacute; et al. [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] found substantial reductions in pain (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and significant improvements in quality of life scores (p\u0026thinsp;\u0026lt;\u0026thinsp;0.005). Similarly, Kim et al. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] reported meaningful enhancements in physical and social functioning following complete decongestive physiotherapy (CDP) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eAdditionally, Kendrov\u0026aacute; et al. [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] observed significant improvements in quality of life (QOL) scores, noting a positive correlation between pain reduction and QOL in areas such as symptoms and functional capacity. Freyne et al. [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] similarly reported higher global health scores alongside significant improvements in physical, emotional, and social functioning (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e\u003cp\u003e\u003cb\u003eEffect size of inventions on lower limb lymphedema\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOf the nine studies included in the systematic review, four RCTs [\u003cspan additionalcitationids=\"CR28 CR29\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] and three quasi-experimental studies [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] were selected for inclusion in the meta-analysis. Outcomes such as pain, quality of life, and heaviness were excluded from the quantitative synthesis due to variability in assessment tools across studies. The meta-analysis therefore focused solely on changes in lower limb volume, comparing measurements before and after interventions. The analysis revealed that the interventions did not produce a significant effect on lower limb volume (standardized mean difference [SMD]\u0026thinsp;=\u0026thinsp;0.07, 95% confidence interval [CI]\u0026thinsp;\u0026minus;\u0026thinsp;0.96 to 1.09, p\u0026thinsp;=\u0026thinsp;0.90), with substantial heterogeneity observed (I\u0026sup2; = 96.25%), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. To explore the impact of potential outliers, a sensitivity analysis was performed (\u003cb\u003eSupplementary Fig.\u0026nbsp;1\u003c/b\u003e), which indicated that excluding individual studies did not meaningfully change the overall effect size, supporting the robustness of these findings. Meta-regression analyses were conducted to explore potential sources of heterogeneity, examining sample size, intervention duration, study quality rating, and mean age. The results showed that mean age was significantly associated with changes in lower limb volume (z\u0026thinsp;=\u0026thinsp;2.24, p\u0026thinsp;=\u0026thinsp;0.025), whereas sample size (z = -1.33, p\u0026thinsp;=\u0026thinsp;0.184), intervention time (z = -1.03, p\u0026thinsp;=\u0026thinsp;0.303), and study quality rating (z = -1.10, p\u0026thinsp;=\u0026thinsp;0.272) were not significantly related to the effect size. Following this, subgroup analyses based on mean age were performed. Studies with a mean age\u0026thinsp;\u0026ge;\u0026thinsp;60 years demonstrated a significant effect size (SMD\u0026thinsp;=\u0026thinsp;1.49, 95% CI 0.36 to 2.62, I\u0026sup2; = 90.09%), while those with a mean age\u0026thinsp;\u0026lt;\u0026thinsp;60 years showed a non-significant effect (SMD = -1.05, 95% CI \u0026minus;\u0026thinsp;2.11 to 0.00, I\u0026sup2; = 94.79%). The difference between these groups was statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), suggesting that mean age may be a key moderator driving heterogeneity in outcomes. Specifically, interventions appeared more effective in populations with a mean age of 60 years or older, indicating a potential age-related response to treatment, as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ePublication bias was assessed using a funnel plot and Egger\u0026rsquo;s regression test, with detailed results presented in \u003cb\u003eSupplementary Fig.\u0026nbsp;2\u003c/b\u003e. Both analyses found no significant evidence of publication bias, reinforcing the reliability of the findings.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis systematic review and meta-analysis underscore the potential effectiveness of interventions for improving clinical outcomes in LLL following gynecological cancer. Although the review includes nine studies involving 307 participants that met strict inclusion criteria, it is important to recognize the relatively small number of studies available in this specialized area. The existing focus on upper limb lymphedema has resulted in a notable evidence gap for LLL, an issue this analysis aims to address, yet this focus naturally limits the number of eligible studies. The meta-analysis of seven qualifying studies offers several important insights that advance the current understanding of lymphedema management. Systematic reviews have highlighted the promising effectiveness of various interventions for managing LLL. Specifically, exercise combined with compression therapy, particularly supine active exercise, has demonstrated greater efficacy in reducing limb volume compared to compression therapy alone [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Despite this, previous research suggests that women with LLL may avoid physical exercise due to fears of worsening their condition [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. However, the findings of this systematic review provide strong evidence supporting the beneficial role of exercise in alleviating LLL and its related symptoms. Additionally, these interventions have been shown to improve physical symptoms and quality of life measures. Importantly, their positive effects extend beyond volume reduction to include pain relief, decreased sensations of heaviness, and enhanced functional capacity. This highlights the importance of adopting a comprehensive outcome framework that includes patient-reported symptom relief and quality of life measures. Moreover, the reported feasibility of these interventions across multiple studies indicates that such treatment approaches, including exercise, are generally well-tolerated by patients. Integrating exercise into the management of lLLL following gynecological cancer may therefore enhance patient engagement and adherence to therapy. However, the meta-analysis of seven studies found no significant overall effect on lower limb volume reduction (SMD\u0026thinsp;=\u0026thinsp;0.07, 95% CI \u0026minus;\u0026thinsp;0.96 to 1.09), with considerable heterogeneity present (I\u0026sup2; = 96.25%), underscoring the complexity and variability of treatment responses. Importantly, subgroup analysis identified age as a key moderator of treatment efficacy, with interventions proving significantly more effective in populations with a mean age of 60 years or older (SMD\u0026thinsp;=\u0026thinsp;1.49, 95% CI 0.36 to 2.62). This suggests that, despite the typical decline in lymphatic function associated with aging [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], older adults may experience greater benefits from specific lymphedema treatments. One possible explanation is that older individuals may have lived with lymphedema for a longer duration, potentially reaching a more stable or chronic phase in which interventions produce more consistent and predictable effects. Additionally, older adults are generally less likely to participate in high-intensity exercise or strenuous activities, which may complement and enhance the effectiveness of therapeutic protocols [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Together, these factors could help explain the age-related differences observed in treatment responsiveness. Future research should aim to clarify the mechanisms driving these variations, with a focus on both biological and behavioral factors that improve treatment outcomes in older populations. Such insights will be essential for optimizing lymphedema management tailored to different age groups.\u003c/p\u003e\u003cp\u003eThese findings carry important implications for both clinical practice and future research. The systematic review suggests that combined interventions, particularly those integrating exercise with compression therapy, may offer greater effectiveness. The observed age-related differences in treatment response highlight the need for personalized approaches; older patients appear to benefit more from current interventions, while younger patients may require additional or tailored strategies to address their more dynamic, long-term responses. Moreover, this study emphasizes the value of adopting a comprehensive outcome assessment framework that goes beyond volume reduction to include critical measures such as pain relief, decreased heaviness, and improved functional ability. Embracing this multifaceted approach will provide a more holistic understanding of treatment efficacy and guide the development of optimized therapeutic strategies tailored to diverse patient needs.\u003c/p\u003e\u003cp\u003eThis review has several limitations that should be acknowledged. First, the substantial heterogeneity and risk of bias present in some studies necessitate cautious interpretation of the findings. Second, the relatively small sample sizes reflect the current scarcity of focused research on LLL following gynecological cancers, which may limit the statistical power to detect more subtle intervention effects. Third, although meta-regression identified age as a significant moderator, other potential influencing factors may have gone undetected due to the limited number and scope of the primary studies included.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this systematic review and meta-analysis highlight exercise combined with compression therapy as a key and effective component of CDT for managing LLL following gynecological cancer. This suggests that a more targeted and refined approach to CDT could improve patient outcomes. Although the meta-analysis did not show a statistically significant reduction in limb volume, the evidence supports that exercise with compression therapy is a feasible, safe, and beneficial strategy for alleviating LLL and its related symptoms. The observed age-dependent effects emphasize the importance of personalized treatment approaches: older patients may experience greater benefits from existing interventions, whereas younger patients might need additional strategies to address their longer-term, dynamic responses. Future research should focus on large-scale randomized controlled trials with extended follow-up periods, using standardized outcome measures and reporting practices to further optimize lymphedema management.\u003c/p\u003e\u003cp\u003eMoreover, understanding the mechanisms behind age-related differences in treatment efficacy, as well as exploring the biological and behavioral factors that enhance responsiveness in older populations, will be critical. By addressing these gaps, healthcare providers can offer evidence-based, tailored interventions that ultimately improve patient outcomes and quality of life.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eContributions:\u0026nbsp;\u003c/strong\u003eCNZ, LZY, and YYC made significant contributions to the conception and design of the study, data acquisition, or data analysis and interpretation. KLS, JW, and KGS were involved in drafting the manuscript or critically revising it for important intellectual content. CNZ, LZY, YYC, KLS, JW, and KGS provided final approval for the version to be published. Each author has participated sufficiently in the work to take public responsibility for the appropriate portions of the content. CNZ, LZY, YYC, KLS, JW, and KGS are accountable for all aspects of the work, ensuring that any questions regarding the accuracy or integrity of any part of the work are properly investigated and resolved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe sincerely thank all the participants who contributed to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChaonan Zhang is supported by Health Commission of Zhejiang Province (2023KY142), Project of Wenzhou Science and Technology Bureau(Y20220157), Project of Wenzhou Science and Technology Bureau(Y2023742), Project of the Nursing Department of the First Affiliated Hospital of Wenzhou Medical University (HLKY202202).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDuan, R., et al., \u003cem\u003eTemporal trends and projections of gynecological cancers in China, 2007-2030.\u003c/em\u003e BMC Womens Health, 2023. \u003cstrong\u003e23\u003c/strong\u003e(1): p. 346.\u003c/li\u003e\n\u003cli\u003eKeyvani, V., et al., \u003cem\u003eEpidemiological trends and risk factors of gynecological cancers: an update.\u003c/em\u003e Med Oncol, 2023. \u003cstrong\u003e40\u003c/strong\u003e(3): p. 93.\u003c/li\u003e\n\u003cli\u003eHu, H., et al., \u003cem\u003eRisk factors for lower extremity lymphedema after cervical cancer treatment: a systematic review and meta-analysis.\u003c/em\u003e Transl Cancer Res, 2022. \u003cstrong\u003e11\u003c/strong\u003e(6): p. 1713-1721.\u003c/li\u003e\n\u003cli\u003eKunitake, T., T. Kakuma, and K. Ushijima, \u003cem\u003eRisk factors for lower limb lymphedema in gynecologic cancer patients after initial treatment.\u003c/em\u003e Int J Clin Oncol, 2020. \u003cstrong\u003e25\u003c/strong\u003e(5): p. 963-971.\u003c/li\u003e\n\u003cli\u003eDeng, S., et al., \u003cem\u003eSurvival analysis of gynecological cancers in Southeast China, 2011-2020: A population-based study.\u003c/em\u003e Cancer Epidemiol, 2024. \u003cstrong\u003e92\u003c/strong\u003e: p. 102641.\u003c/li\u003e\n\u003cli\u003eDessources, K., E. Aviki, and M.M. Leitao, Jr., \u003cem\u003eLower extremity lymphedema in patients with gynecologic malignancies.\u003c/em\u003e Int J Gynecol Cancer, 2020. \u003cstrong\u003e30\u003c/strong\u003e(2): p. 252-260.\u003c/li\u003e\n\u003cli\u003eSakkuru, R.K., et al., \u003cem\u003e\u0026quot;Incidence of Lower Limb Lymphedema in Post therapeutic Gynaecological Malignancies\u0026quot;.\u003c/em\u003e International Journal of Physiotherapy, 2023. \u003cstrong\u003e10\u003c/strong\u003e(2).\u003c/li\u003e\n\u003cli\u003eExecutive Committee of the International Society of, L., \u003cem\u003eThe diagnosis and treatment of peripheral lymphedema: 2020 Consensus Document of the International Society of Lymphology.\u003c/em\u003e Lymphology, 2020. \u003cstrong\u003e53\u003c/strong\u003e(1): p. 3-19.\u003c/li\u003e\n\u003cli\u003ePlinsinga, M.L., et al., \u003cem\u003eMild symptoms matter: Results from a prospective, longitudinal study on the relationship between symptoms, lymphedema and health-related outcomes post-gynecological cancer.\u003c/em\u003e Gynecol Oncol, 2024. \u003cstrong\u003e191\u003c/strong\u003e: p. 158-164.\u003c/li\u003e\n\u003cli\u003eEidenberger, M., \u003cem\u003ePatient-Reported Outcome Measures With Secondary Lower Limb Lymphedemas: A Systematic Review.\u003c/em\u003e J Adv Pract Oncol, 2021. \u003cstrong\u003e12\u003c/strong\u003e(2): p. 174-187.\u003c/li\u003e\n\u003cli\u003eLau, K., et al., \u003cem\u003eCancer-Related Lymphedema and Psychological Distress.\u003c/em\u003e Curr Psychiatry Rep, 2024. \u003cstrong\u003e26\u003c/strong\u003e(11): p. 635-642.\u003c/li\u003e\n\u003cli\u003eRusso, S., et al., \u003cem\u003eStandardization of lower extremity quantitative lymphedema measurements and associated patient-reported outcomes in gynecologic cancers.\u003c/em\u003e Gynecol Oncol, 2021. \u003cstrong\u003e160\u003c/strong\u003e(2): p. 625-632.\u003c/li\u003e\n\u003cli\u003eChang, D.W., et al., \u003cem\u003eSurgical Treatment of Lymphedema: A Systematic Review and Meta-Analysis of Controlled Trials. Results of a Consensus Conference.\u003c/em\u003e Plast Reconstr Surg, 2021. \u003cstrong\u003e147\u003c/strong\u003e(4): p. 975-993.\u003c/li\u003e\n\u003cli\u003eMackie, H., et al., \u003cem\u003eOutcome of Liposuction for Limb Lymphedema in Men Compared with Women.\u003c/em\u003e J Plast Reconstr Surg, 2025. \u003cstrong\u003e4\u003c/strong\u003e(1): p. 1-6.\u003c/li\u003e\n\u003cli\u003eDonahue, P.M.C., et al., \u003cem\u003eAdvances in the prevention and treatment of breast cancer-related lymphedema.\u003c/em\u003e Breast Cancer Res Treat, 2023. \u003cstrong\u003e200\u003c/strong\u003e(1): p. 1-14.\u003c/li\u003e\n\u003cli\u003eChoi, J.E. and M.C. Chang, \u003cem\u003eManagement of lymphedema is really a matter in patients with breast cancer.\u003c/em\u003e World J Clin Cases, 2024. \u003cstrong\u003e12\u003c/strong\u003e(15): p. 2482-2486.\u003c/li\u003e\n\u003cli\u003eRockson, S.G., et al., \u003cem\u003eA non-randomized, open-label study of the safety and effectiveness of a novel non-pneumatic compression device (NPCD) for lower limb lymphedema.\u003c/em\u003e Sci Rep, 2022. \u003cstrong\u003e12\u003c/strong\u003e(1): p. 14005.\u003c/li\u003e\n\u003cli\u003eRockson, S.G., et al., \u003cem\u003eAuthor Correction: A non-randomized, open-label study of the safety and effectiveness of a novel non-pneumatic compression device (NPCD) for lower limb lymphedema.\u003c/em\u003e Sci Rep, 2023. \u003cstrong\u003e13\u003c/strong\u003e(1): p. 911.\u003c/li\u003e\n\u003cli\u003eWeiss, R., \u003cem\u003eCost of a lymphedema treatment mandate - 16 years of experience in the Commonwealth of Virginia.\u003c/em\u003e Health Econ Rev, 2022. \u003cstrong\u003e12\u003c/strong\u003e(1): p. 40.\u003c/li\u003e\n\u003cli\u003eRajan, S. and H. Venkatramani, \u003cem\u003eRecent advances in management of lymphedema.\u003c/em\u003e Journal of Skin and Sexually Transmitted Diseases, 2021. \u003cstrong\u003e3\u003c/strong\u003e: p. 26-32.\u003c/li\u003e\n\u003cli\u003eBergmann, A., J.M.T. Baiocchi, and M.F.C. de Andrade, \u003cem\u003eConservative treatment of lymphedema: the state of the art.\u003c/em\u003e J Vasc Bras, 2021. \u003cstrong\u003e20\u003c/strong\u003e: p. e20200091.\u003c/li\u003e\n\u003cli\u003eVo, T.T., et al., \u003cem\u003eEffect of Complex Decongestive Therapy Program on Volume and Functioning in Breast Cancer-Related Lymphedema: Global Effect and Predicting Factors.\u003c/em\u003e Lymphat Res Biol, 2024. \u003cstrong\u003e22\u003c/strong\u003e(6): p. 271-277.\u003c/li\u003e\n\u003cli\u003eOuzzani, M., et al., \u003cem\u003eRayyan-a web and mobile app for systematic reviews.\u003c/em\u003e Syst Rev, 2016. \u003cstrong\u003e5\u003c/strong\u003e(1): p. 210.\u003c/li\u003e\n\u003cli\u003eSterne, J.A.C., et al., \u003cem\u003eRoB 2: a revised tool for assessing risk of bias in randomised trials.\u003c/em\u003e BMJ, 2019. \u003cstrong\u003e366\u003c/strong\u003e: p. l4898.\u003c/li\u003e\n\u003cli\u003eSterne, J.A., et al., \u003cem\u003eROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions.\u003c/em\u003e BMJ, 2016. \u003cstrong\u003e355\u003c/strong\u003e: p. i4919.\u003c/li\u003e\n\u003cli\u003eHiggins, J.P.T., et al., \u003cem\u003eCochrane Handbook for Systematic Reviews of Interventions\u003c/em\u003e. 2019.\u003c/li\u003e\n\u003cli\u003eAbe, K., et al., \u003cem\u003ePostural differences in the immediate effects of active exercise with compression therapy on lower limb lymphedema.\u003c/em\u003e Support Care Cancer, 2021. \u003cstrong\u003e29\u003c/strong\u003e(11): p. 6535-6543.\u003c/li\u003e\n\u003cli\u003eFukushima, T., et al., \u003cem\u003eImmediate effects of active exercise with compression therapy on lower-limb lymphedema.\u003c/em\u003e Support Care Cancer, 2017. \u003cstrong\u003e25\u003c/strong\u003e(8): p. 2603-2610.\u003c/li\u003e\n\u003cli\u003eHwa, J., DO, Choi, K. H., Ahn, J. S., \u0026amp; Jeon, J. Y. (2017). Effects of a complex rehabilitation program on edema status, physical function, and quality of life in lower-limb lymphedema after gynecological cancer surgery. Gynecologic Oncology, 147(2), 450\u0026ndash;455. https://doi.org/10.1016/j.ygyno.2017.09.003.\u003c/li\u003e\n\u003cli\u003eWang, J., et al., \u003cem\u003eThe rehabilitation efficacy of diaphragmatic breathing combined with limb coordination training for lower limb lymphedema following gynecologic cancer surgery.\u003c/em\u003e Front Bioeng Biotechnol, 2024. \u003cstrong\u003e12\u003c/strong\u003e: p. 1392824.\u003c/li\u003e\n\u003cli\u003eFreyne, A., et al., \u003cem\u003eSevere lymphoedema in gynaecological cancers: Impact of pneumatic compression on quality of life.\u003c/em\u003e Gynecol Oncol Rep, 2022. \u003cstrong\u003e39\u003c/strong\u003e: p. 100902.\u003c/li\u003e\n\u003cli\u003eKendrova, L., et al., \u003cem\u003eComprehensive Decongestive Therapy as a Treatment for Secondary Lymphedema of the Lower Extremity and Quality of Life of Women After Gynecological Cancer Surgery.\u003c/em\u003e Med Sci Monit, 2020. \u003cstrong\u003e26\u003c/strong\u003e: p. e924071.\u003c/li\u003e\n\u003cli\u003eKim, S.J. and Y.D. Park, \u003cem\u003eEffects of complex decongestive physiotherapy on the oedema and the quality of life of lower unilateral lymphoedema following treatment for gynecological cancer.\u003c/em\u003e Eur J Cancer Care (Engl), 2008. \u003cstrong\u003e17\u003c/strong\u003e(5): p. 463-8.\u003c/li\u003e\n\u003cli\u003eKim, Y., et al., \u003cem\u003eHome-Based Intermittent Pneumatic Compression Therapy: The Impact in Chronic Leg Lymphedema in Patients Treated for Gynecologic Cancer.\u003c/em\u003e Healthcare (Basel), 2022. \u003cstrong\u003e10\u003c/strong\u003e(4).\u003c/li\u003e\n\u003cli\u003eZeng, Y., et al., \u003cem\u003eApplication of Complete Decongestive Therapy in Patients with Secondary Bilateral Lower Limb Lymphedema after Comprehensive Treatment of Gynecological Malignant Tumor.\u003c/em\u003e Lymphat Res Biol, 2024. \u003cstrong\u003e22\u003c/strong\u003e(1): p. 60-65.\u003c/li\u003e\n\u003cli\u003eAbakay, H., et al., \u003cem\u003eAssociation of lower extremity lymphedema with pelvic floor functions, sleep quality, kinesiophobia, body image in patients with gynecological cancers.\u003c/em\u003e Women Health, 2023. \u003cstrong\u003e63\u003c/strong\u003e(1): p. 27-34.\u003c/li\u003e\n\u003cli\u003eYoshihara, M., et al., \u003cem\u003eRisk factors for late-onset lower limb lymphedema after gynecological cancer treatment: A multi-institutional retrospective study.\u003c/em\u003e Eur J Surg Oncol, 2020. \u003cstrong\u003e46\u003c/strong\u003e(7): p. 1334-1338.\u003c/li\u003e\n\u003cli\u003eHida, M., et al., \u003cem\u003eInvestigation of factors influencing low physical activity levels in community-dwelling older adults with chronic pain: a cross-sectional study.\u003c/em\u003e Sci Rep, 2023. \u003cstrong\u003e13\u003c/strong\u003e(1): p. 14062.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Gynecology, Lower Limb Lymphedema, Therapeutics, Meta-analysis, Systematic review","lastPublishedDoi":"10.21203/rs.3.rs-7083022/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7083022/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eTo evaluate the effectiveness of interventions for managing lower limb lymphedema (LLL) in women following gynecological cancer treatment.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA review of randomized controlled trials and quasi-experimental studies was conducted, covering literature up to November 2024 across six databases: Web of Science, PubMed, Cochrane Library, Medline, CINAHL, and Scopus. Meta-analyses were performed using Stata 17.0 with a random effects model.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eNine studies (four RCTs and five quasi-experimental) involving 307 participants were included. Risk of bias was generally low, based on RoB 2 and ROBINS-I assessments, though some domains showed high risk. Interventions, exercise, compression therapy, and their combination, yielded improvements in limb volume, pain, and quality of life in several studies. However, meta-analysis found no significant overall effect on limb volume (SMD\u0026thinsp;=\u0026thinsp;0.07, 95% CI: -0.96 to 1.09, p\u0026thinsp;=\u0026thinsp;0.90), with high heterogeneity (I\u0026sup2; = 96.25%). Meta-regression identified mean age as a significant moderator (p\u0026thinsp;=\u0026thinsp;0.025). No serious adverse effects were reported, and no publication bias was detected.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eWhile the meta-analysis did not show a significant reduction in limb volume, the findings support exercise combined with compression therapy as a safe, practical, and potentially effective strategy for managing LLL and its symptoms.\u003c/p\u003e","manuscriptTitle":"Interventions for Lower Limb Lymphedema Following Gynecological Cancer: A Systematic Review and Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-25 20:57:38","doi":"10.21203/rs.3.rs-7083022/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4a3b0212-a376-464e-8a00-477861349946","owner":[],"postedDate":"August 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":52767243,"name":"Biological sciences/Cancer"},{"id":52767244,"name":"Health sciences/Diseases"},{"id":52767245,"name":"Health sciences/Health care"},{"id":52767246,"name":"Health sciences/Medical research"},{"id":52767247,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2025-11-10T14:53:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-25 20:57:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7083022","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7083022","identity":"rs-7083022","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}