New Insights in Lymphedema after Cancer to Enhance Clinical Practice

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 October 2022) | Viewed by 20451

Special Issue Editors


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Guest Editor
1. Department of Rehabilitation Sciences, KU Leuven - University of Leuven, 3000 Leuven, Belgium
2. Department of Vascular Surgery and Department of Physical Medicine and Rehabilitation, Centre for Lymphedema, University Hospitals Leuven, 3000 Leuven, Belgium
Interests: lymphedema; upper or lower limb; evaluation; prevention; conservative treatment; evaluation lymphatic transport

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Guest Editor
1. Department of Rehabilitation Sciences, KU Leuven - University of Leuven, 3000 Leuven, Belgium
2. Department of Rehabilitation Sciences (MOVANT), University of Antwerp, 2000 Antwerpen, Belgium
Interests: cancer rehabilitation; upper limb dysfunctions (including lymphedema); pain

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Guest Editor
1. Department of Vascular Surgery, University Hospitals Leuven, 3000 Leuven, Belgium
2. Department of Cardiovascular Sciences, Research Unit Vascular Surgery, KU Leuven - University of Leuven, 3000 Leuven, Belgium
Interests: lymphedema; lymphatic disorders; phlebology

Special Issue Information

Dear Colleagues,

Lymphoedema is the most feared complication after the treatment of cancer. Lymphoedema can cause functional impairments and psychosocial morbidities and may lead to diminished health-related quality of life. Cancer survivors may develop lymphoedema of the arm and/or trunk, leg and/or midline or head/ neck, depending on the type of cancer (such as breast cancer, melanoma, gynecological cancer, urogenital cancer).

Much research is performed in the domain of breast cancer-related lymphoedema. In contrast, little research is performed on the evaluation, prevention, and treatment of cancer-related lymphoedema developed after head and neck cancer, melanoma, urogenital and gynecological cancer.

In this Special Issue, we will discuss new insights related to the evaluation, prevention, and (conservative or surgical) treatment of cancer-related lymphoedema of the arm, leg, and/or midline. We only accept original clinical research that can impact daily clinical practice.

Prof. Dr. Nele Devoogdt
Prof. Dr. An De Groef
Dr. Sarah Thomis
Guest Editors

Manuscript Submission Information

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Keywords

  • lymphedema
  • breast cancer
  • urogenital cancer
  • head and neck cancer
  • melanoma
  • gynecological cancer
  • evaluation
  • prevention
  • treatment
  • clinical research

Published Papers (10 papers)

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Research

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14 pages, 913 KiB  
Article
Early Intervention with a Compression Sleeve in Mild Breast Cancer-Related Arm Lymphedema: A 12-Month Prospective Observational Study
by Karin Johansson, Katarina Blom, Lena Nilsson-Wikmar and Christina Brogårdh
Cancers 2023, 15(10), 2674; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15102674 - 09 May 2023
Cited by 2 | Viewed by 1673
Abstract
Background: In our previous randomized controlled trial (RCT), the progression/no progression of mild breast cancer-related arm lymphedema (BCRL) was examined among women randomized to a compression group (CG) with a compression sleeve (compression class (ccl) 1) or not (NCG) for 6 months. In [...] Read more.
Background: In our previous randomized controlled trial (RCT), the progression/no progression of mild breast cancer-related arm lymphedema (BCRL) was examined among women randomized to a compression group (CG) with a compression sleeve (compression class (ccl) 1) or not (NCG) for 6 months. In the present prospective study, BCRL in the CG and NCG was followed for 12 months. Methods: At the end of the RCT, 33 women with mild BCRL were eligible in the CG and 37 in the NCG. The proportional differences in no progression/progression of BCRL were defined as a >2% increase from start of RCT or exceeding 10% in the lymphedema relative volume as measured by the water displacement method. In addition, changes in the lymphedema relative volume and tissue dielectric constant ratio, which measures local tissue water, were examined. At the end of the RCT (i.e., after 6 months), a one-month break of the compression treatment was made in the CG. If the lymphedema relative volume progressed by definition, the compression treatment was resumed and continued, with follow-up of all women at 9 and 12 months. Results: A larger proportion of women in the NCG showed progression (57%, 61%, 67%) compared to the CG (16%, 22%, 31%) at 6, 9, and 12 months (p < 0.001, 0.005, 0.012), respectively. Twelve (33%) women in the NCG did not progress at all. No changes of the lymphedema relative volume and local tissue water were found over time at any follow-ups, but were stable on a low level. Conclusions: To avoid the progression of mild BCRL into a chronic issue in the long-term, compression sleeve ccl 1 may be applied immediately after early diagnosis of mild BCRL. Full article
(This article belongs to the Special Issue New Insights in Lymphedema after Cancer to Enhance Clinical Practice)
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14 pages, 665 KiB  
Article
Early Disturbance of Lymphatic Transport as a Risk Factor for the Development of Breast-Cancer-Related Lymphedema
by Sarah Thomis, Nele Devoogdt, Beate Bechter-Hugl and Inge Fourneau
Cancers 2023, 15(6), 1774; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15061774 - 15 Mar 2023
Viewed by 1458
Abstract
Introduction: Breast-cancer-related lymphedema (BCRL) is a frequently occurring and debilitating condition. When lymphedema is diagnosed late, treatment can be expected to be less effective. Lymphofluoroscopy can provide details about the superficial lymphatic architecture and can detect an early disturbance of lymphatic transport (i.e., [...] Read more.
Introduction: Breast-cancer-related lymphedema (BCRL) is a frequently occurring and debilitating condition. When lymphedema is diagnosed late, treatment can be expected to be less effective. Lymphofluoroscopy can provide details about the superficial lymphatic architecture and can detect an early disturbance of lymphatic transport (i.e., dermal backflow) before the lymphedema is clinically visible. The main objective of this study is to investigate whether this early disturbance of lymphatic transport visualized by lymphofluoroscopy is a risk factor for the development of BCRL. Methodology: All patients scheduled for unilateral breast cancer surgery with axillary lymph node dissection or sentinel node biopsy were considered. Patients were assessed at baseline and 1, 3, 6, 9, 12, 18, 24 and 36 months postoperatively. During each visit, a clinical assessment was performed to determine the volume difference between both arms and hands (through circumference measurements and water displacement). Clinical BCRL was defined as a ≥5% increase in relative arm volume difference compared to the baseline value. Variables related to (1) the disturbance of lymphatic transport (through lymphofluoroscopy), (2) the demographics and general health of the patient and (3) the breast cancer and treatment of the patient were collected. Results: We included data of 118 patients in the present study. Thirty-eight patients (39.8%) developed BCRL. Early disturbance of lymphatic transport was identified as a risk factor for the development of clinical BCRL (HR 2.808). Breast-cancer- and treatment-related variables such as axillary lymph node dissection (ALND) (HR 15.127), tumor stage (HR 1.745), mastectomy (HR 0.186), number of positive lymph nodes (HR 1.121), number of removed lymph nodes (HR 1.055), radiotherapy of the axilla (HR 2.715), adjuvant taxanes (HR 3.220) and postsurgical complications (HR 2.590) were identified as significant risk factors for the development of BCRL. In the multivariate analysis, age and ALND were withheld as independent risk factors for the development of BCRL. Conclusion: Lymphofluoroscopy can identify an early disturbance of lymphatic transport after breast cancer treatment. Patients with an early disturbance of lymphatic transport are considered to be a high-risk group for the development of BCRL. This study also confirms that age and ALND are predictors for the development of BCRL. Therefore, a surveillance program of these patients with lymphofluoroscopy could be useful to identify lymphedema in subclinical stages. Full article
(This article belongs to the Special Issue New Insights in Lymphedema after Cancer to Enhance Clinical Practice)
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15 pages, 718 KiB  
Article
Improving the Assessment and Diagnosis of Breast Lymphedema after Treatment for Breast Cancer
by Katie Riches, Kwok-Leung Cheung and Vaughan Keeley
Cancers 2023, 15(6), 1758; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15061758 - 14 Mar 2023
Cited by 1 | Viewed by 1771
Abstract
Lymphedema can develop after treatment for breast cancer (BCRL). Lymphedema of the breast is not well studied. Currently, the main techniques used to diagnose and monitor the effectiveness of treatment are subjective clinician assessment and patient reports. Eighty-nine women who had undergone breast [...] Read more.
Lymphedema can develop after treatment for breast cancer (BCRL). Lymphedema of the breast is not well studied. Currently, the main techniques used to diagnose and monitor the effectiveness of treatment are subjective clinician assessment and patient reports. Eighty-nine women who had undergone breast cancer treatment were recruited with and without breast lymphedema. Blinded clinical assessment determined the presence or absence of breast lymphedema. Measurement of skin thickness by ultrasound scanning, local tissue water by tissue dielectric constant (TDC) and tissue indentation by tonometry was recorded. Breast cancer treatment and demographic details were documented. Descriptive statistics were undertaken to compare sample characteristics, including the Chi-squared test, Odds Ratio (OR) and Relative Risks (RR) calculated. Increased body mass index (BMI), larger bra size, increased number of positive lymph nodes, axillary surgery, chemotherapy and increased Nottingham Prognostic Index (NPI) were all associated with breast lymphedema (p < 0.05). Ultrasound and TDC measurements were significantly higher in the lymphedema group (p < 0.05). Receiver Operator Characteristic (ROC) curves demonstrated that ultrasound and TDC measurements could distinguish between edematous and non-edematous breasts. Threshold levels were produced, which demonstrated good levels of sensitivity and specificity. These findings have the potential to improve the diagnosis of breast lymphedema. Full article
(This article belongs to the Special Issue New Insights in Lymphedema after Cancer to Enhance Clinical Practice)
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13 pages, 688 KiB  
Article
The Effectiveness of Fluoroscopy-Guided Manual Lymph Drainage as Part of Decongestive Lymphatic Therapy on the Superficial Lymphatic Architecture in Patients with Breast Cancer-Related Lymphoedema: A Randomised Controlled Trial
by Nele Devoogdt, Sarah Thomis, An De Groef, An-Kathleen Heroes, Ines Nevelsteen, Nick Gebruers, Wiebren A. A. Tjalma, Jean-Paul Belgrado, Chris Monten, Marianne Hanssens and Tessa De Vrieze
Cancers 2023, 15(5), 1545; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15051545 - 28 Feb 2023
Cited by 2 | Viewed by 2609
Abstract
The objective of this trial was to investigate the effectiveness of fluoroscopy-guided manual lymph drainage (MLD), as part of decongestive lymphatic therapy (DLT), on the superficial lymphatic architecture in patients with chronic mild to moderate breast cancer-related lymphoedema (BCRL). This trial was a [...] Read more.
The objective of this trial was to investigate the effectiveness of fluoroscopy-guided manual lymph drainage (MLD), as part of decongestive lymphatic therapy (DLT), on the superficial lymphatic architecture in patients with chronic mild to moderate breast cancer-related lymphoedema (BCRL). This trial was a multicentre, double-blind, randomised controlled trial involving 194 participants with BCRL. Participants were randomised into (1) DLT with fluoroscopy-guided MLD (intervention group), (2) DLT with traditional MLD (control group), or (3) DLT with placebo MLD (placebo group). Superficial lymphatic architecture was evaluated as a secondary outcome, visualised by ICG lymphofluoroscopy at the baseline (B0), post-intensive (P), and post-maintenance phases (P6). Variables were (1) number of efferent superficial lymphatic vessels leaving the dermal backflow region, (2) total dermal backflow score, and (3) number of superficial lymph nodes. The traditional MLD group showed a significant decrease in the number of efferent superficial lymphatic vessels at P (p = 0.026), and of the total dermal backflow score at P6 (p = 0.042). The fluoroscopy-guided MLD and placebo group showed significant decreases in the total dermal backflow score at P (p < 0.001 and p = 0.044, respectively) and at P6 (p < 0.001 and p = 0.007, respectively); the placebo MLD group showed a significant decrease in the total number of lymph nodes at P (p = 0.008). However, there were no significant between-group differences for the changes in these variables. In conclusion, based on lymphatic architecture outcomes, the added value of MLD, in addition to the other parts of DLT, could not be demonstrated in patients with chronic mild to moderate BCRL. Full article
(This article belongs to the Special Issue New Insights in Lymphedema after Cancer to Enhance Clinical Practice)
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13 pages, 782 KiB  
Article
The Lymphatic System, Lymphoedema, and Medical Curricula–Survey of Australian Medical Graduates
by Natalie Kruger, Melanie L. Plinsinga, Rhian Noble-Jones, Neil Piller, Vaughan Keeley and Sandra C. Hayes
Cancers 2022, 14(24), 6219; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14246219 - 16 Dec 2022
Cited by 2 | Viewed by 1531
Abstract
The aim of this study was to survey the perceptions of recent (i.e., within the past 12 months) Australian medical graduates regarding (i) their understanding of the lymphatic system and lymphoedema, and (ii) the extent to which the lymphatic system and lymphoedema were [...] Read more.
The aim of this study was to survey the perceptions of recent (i.e., within the past 12 months) Australian medical graduates regarding (i) their understanding of the lymphatic system and lymphoedema, and (ii) the extent to which the lymphatic system and lymphoedema were covered as part of their medical degree. Medical graduates were invited to participate in a 17-item online survey that asked respondents to rate their level of agreement (using a 5-point Likert scale; higher scores = higher agreement) to statements that explored their understanding and comprehensiveness of their medical degree. Responses to each item were described using n (%). Subscale scores for understanding and medical degree were computed by summing scores of individual items, described using means (SD) and compared by participant characteristics. Medical graduates (n = 230) perceived their understanding of the lymphatic system and lymphoedema to be low, and comprehensiveness of medical curricula specific to the lymphatic system and lymphoedema to be lacking. Subscale scores did not differ by participant characteristics. Improvement of medical graduates understanding of lymphoedema may facilitate greater awareness of lymphoedema, thus optimizing the timeliness of diagnosis and access to treatment. Full article
(This article belongs to the Special Issue New Insights in Lymphedema after Cancer to Enhance Clinical Practice)
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12 pages, 564 KiB  
Article
Early Referral for Breast-Cancer-Related Lymphedema: Do We Follow the Evidence? A Two-Year Prospective Multicenter Cohort Study
by Ad A. Hendrickx, Saskia W. Küthe, Cees P. van der Schans, Wim P. Krijnen, Chantal M. Mouës-Vink and Robert J. Damstra
Cancers 2022, 14(23), 6016; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14236016 - 06 Dec 2022
Viewed by 1306
Abstract
The early detection of breast-cancer-related lymphedema and referral for therapy has the potential to reduce lymphedema-related morbidity. Although research shows the benefits, a gap is observed between evidence and daily practice. We aimed to determine whether the early detection of lymphedema and referral [...] Read more.
The early detection of breast-cancer-related lymphedema and referral for therapy has the potential to reduce lymphedema-related morbidity. Although research shows the benefits, a gap is observed between evidence and daily practice. We aimed to determine whether the early detection of lymphedema and referral for treatment is adequate following the current guidelines. Women with primary breast cancer treated with breast-conserving therapy or ablative treatment were included. Demographic-, general health-, tumor-, and treatment-related data were recorded. Bilateral arm volume measurements were performed preoperatively and 3, 6, 12, and 24 months post-surgery. A 5% or greater Relative Volume Change was considered the cutoff point for lymphedema and as an indication for therapy referral. After 24 months post-surgery, the main outcomes show that among the patients with early signs of lymphedema, based on a Relative Volume Change ≥5%, a nonreferral for therapy was noted in 83%. Additionally, we observed a significant improvement of the mean Relative Volume Change at 24 months within this group, which might implicate that nonreferral was an adequate choice and that watchful waiting is appropriate when lymphedema is detected within the first year post-surgery. Full article
(This article belongs to the Special Issue New Insights in Lymphedema after Cancer to Enhance Clinical Practice)
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14 pages, 273 KiB  
Article
Do Patient-Reported Upper-Body Symptoms Predict Breast Cancer-Related Lymphoedema: Results from a Population-Based, Longitudinal Breast Cancer Cohort Study
by Sandra C. Hayes, Matthew Dunn, Melanie L. Plinsinga, Hildegard Reul-Hirche, Yumeng Ren, E-Liisa Laakso and Melissa A. Troester
Cancers 2022, 14(23), 5998; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14235998 - 05 Dec 2022
Cited by 2 | Viewed by 1633
Abstract
The objectives of this work were to (i) describe upper-body symptoms post-breast cancer; (ii) explore the relationship between symptoms and upper-body function, breast cancer-related lymphoedema (BCRL), physical activity levels, and quality of life; and (iii) determine whether the presence of upper-body symptoms predicts [...] Read more.
The objectives of this work were to (i) describe upper-body symptoms post-breast cancer; (ii) explore the relationship between symptoms and upper-body function, breast cancer-related lymphoedema (BCRL), physical activity levels, and quality of life; and (iii) determine whether the presence of upper-body symptoms predicts BCRL. Nine symptoms, upper-body function, lymphoedema, physical activity, and quality of life were assessed in women with invasive breast cancer at baseline (2- to 9-months post-diagnosis; n = 2442), and at 2- and 7-years post-diagnosis. Mann–Whitney tests, unpaired t-tests, and chi-squared analyses were used to assess cross-sectional relationships, while regression analyses were used to assess the predictive relationships between symptoms at baseline, and BCRL at 2- and 7-years post-diagnosis. Symptoms are common post-breast cancer and persist at 2- and 7-years post-diagnosis. Approximately two in three women, and one in three women, reported >2 symptoms of at least mild severity, and of at least moderate severity, respectively. The presence of symptoms is associated with poorer upper-body function, and lower physical activity levels and quality of life. One or more symptoms of at least moderate severity increases the odds of developing BCRL by 2- and 7-years post-diagnosis (p < 0.05). Consequently, improved monitoring and management of symptoms following breast cancer have the potential to improve health outcomes. Full article
(This article belongs to the Special Issue New Insights in Lymphedema after Cancer to Enhance Clinical Practice)
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10 pages, 6598 KiB  
Article
Acoustic Radiation Force Impulse Elastography Assessment of Lymphoedema Tissue: An Insight into Tissue Stiffness
by Jennifer Sanderson, Neil Tuttle and Liisa Laakso
Cancers 2022, 14(21), 5281; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14215281 - 27 Oct 2022
Cited by 1 | Viewed by 1746
Abstract
Palpation remains essential for evaluating lymphoedema to detect subtle changes that may indicate progression. As palpation sense is not quantifiable, this study investigates the utility of ultrasound elastography to quantify stiffness of lymphoedema tissue and explore the influence of the pitting test on [...] Read more.
Palpation remains essential for evaluating lymphoedema to detect subtle changes that may indicate progression. As palpation sense is not quantifiable, this study investigates the utility of ultrasound elastography to quantify stiffness of lymphoedema tissue and explore the influence of the pitting test on tissue stiffness. Fifteen women with unilateral arm lymphoedema were scanned using a Siemens S3000 Acuson ultrasound (Siemens, Germany) with 18 MHz and 9 MHz linear transducers to assess tissue structure and tissue stiffness with Acoustic Radiation Force Impulse elastography. Ninety sites were assessed, three on each of the lymphoedema-affected and contralateral unaffected arms. A subgroup of seven lymphoedema-affected sites included additional elastography imaging after a 60-s pitting test. Dermal tissue stiffness was greater than subcutaneous tissue stiffness regardless of the presence of pathology (p < 0.001). Lymphoedematous tissue exhibited a higher dermal to subcutaneous tissue stiffness ratio than contralateral sites (p = 0.005). Subgroup analysis indicated that the pitting test reduces dermal tissue stiffness (p = 0.018) and may alter the stiffness of the subcutaneous tissue layer. Elastography demonstrates potential as a complement to lymphoedema palpation assessment. The novel pre-test and post-pitting elastography imaging protocol yielded information representative of lymphoedema tissue characteristics that could not be ascertained from pre-test elastography images alone. Full article
(This article belongs to the Special Issue New Insights in Lymphedema after Cancer to Enhance Clinical Practice)
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Review

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12 pages, 4257 KiB  
Review
Genital Lymphedema after Cancer Treatment: A Narrative Review
by Stéphane Vignes
Cancers 2022, 14(23), 5809; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14235809 - 25 Nov 2022
Viewed by 3063
Abstract
Genital lymphedema may affect males and females after cancer treatment (gynecological, such as cervical, uterine or ovarian, melanoma, prostate, anus…). It is frequently associated with lower limb lymphedema, and is responsible for discomfort, cosmetic disfigurement and functional disturbances. Impacts on body image, sexual [...] Read more.
Genital lymphedema may affect males and females after cancer treatment (gynecological, such as cervical, uterine or ovarian, melanoma, prostate, anus…). It is frequently associated with lower limb lymphedema, and is responsible for discomfort, cosmetic disfigurement and functional disturbances. Impacts on body image, sexual function and quality of life are major, and difficult to explore because cancer treatment itself and lymphedema are so closely interwoven. Local complications, e.g., papillomatosis, warty growth, lymph vesicles with embarrassing lymph oozing and cellulitis, may occur. Usual lymphedema therapies, like bandaging and elastic compression, are poorly adapted to these sites. Surgery, essentially based on cutaneous resection techniques, is the primary symptomatic treatment; it achieves good efficacy, in adults and children, with possible recurrence requiring reintervention. Full article
(This article belongs to the Special Issue New Insights in Lymphedema after Cancer to Enhance Clinical Practice)
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Other

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17 pages, 915 KiB  
Systematic Review
The Prevalence of Lower Limb and Genital Lymphedema after Prostate Cancer Treatment: A Systematic Review
by Andries Clinckaert, Klaas Callens, Anne Cooreman, Annabel Bijnens, Lisa Moris, Charlotte Van Calster, Inge Geraerts, Steven Joniau and Wouter Everaerts
Cancers 2022, 14(22), 5667; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14225667 - 18 Nov 2022
Cited by 11 | Viewed by 2844
Abstract
(1) Background: Secondary lymphedema is a chronic, progressive, and debilitating condition with an important impact on quality of life. Lymphedema is a frequently reported complication in oncological surgery but has not been systematically studied in the setting of prostate cancer. (2) Methods: Pubmed/MEDLINE [...] Read more.
(1) Background: Secondary lymphedema is a chronic, progressive, and debilitating condition with an important impact on quality of life. Lymphedema is a frequently reported complication in oncological surgery but has not been systematically studied in the setting of prostate cancer. (2) Methods: Pubmed/MEDLINE and Embase were systematically searched to identify articles reporting on lower limb or genital lymphedema after primary treatment (surgery of radiation therapy) of the prostate and the pelvic lymph nodes in men with prostate cancer. Primary outcome was the prevalence of lower limb and genital lymphedema. (3) Results: Eighteen articles were eligible for qualitative synthesis. Risk of bias was high in all included studies, with only one study providing a prespecified definition of secondary lymphedema. Eleven studies report the prevalence of lower limb (0–14%) and genital (0–1%) lymphedema after radical prostatectomy with pelvic lymph node dissection (PLND) Seven studies report a low prevalence of lower limb (0–9%) and genital (0–8%) lymphedema after irradiation of the pelvic lymph nodes. However, in the patient subgroups that underwent pelvic irradiation after staging pelvic lymph node dissections, the prevalence of lower limb (18–29%) and genital (2–22%) lymphedema is substantially elevated. (4) Conclusion: Prostate cancer patients undergoing surgery or irradiation of the pelvic lymph nodes are at risk of developing secondary lymphedema in the lower limbs and the genital region. Patients receiving pelvic radiation after pelvic lymph node dissection have the highest prevalence of lymphedema. The lack of a uniform definition and standardized diagnostic criteria for lower limb and genital lymphedema hampers the accurate estimation of their true prevalence. Future clinicals trials are needed to specifically evaluate secondary lymphedema in patients undergoing prostate cancer treatments, to identify potential risk factors and to determine the impact on quality of life. Full article
(This article belongs to the Special Issue New Insights in Lymphedema after Cancer to Enhance Clinical Practice)
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