Journal of Cancer Survivorship
https://doi.org/10.1007/s11764-020-00928-1
REVIEW
Manual lymphatic drainage treatment for lymphedema: a systematic
review of the literature
Belinda Thompson 1
1
2
1
& Katrina Gaitatzis & Xanne Janse de Jonge & Robbie Blackwell & Louise A. Koelmeyer
1
Received: 3 June 2020 / Accepted: 7 August 2020
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
Purpose Manual lymphatic drainage (MLD) massage is widely accepted as a conservative treatment for lymphedema. This
systematic review aims to examine the methodologies used in recent research and evaluate the effectiveness of MLD for those atrisk of or living with lymphedema.
Methods The electronic databases Embase, PubMed, CINAHL Complete and Cochrane Central Register of Controlled Trials
were searched using relevant terms. Studies comparing MLD with another intervention or control in patients at-risk of or with
lymphedema were included. Studies were critically appraised with the PEDro scale.
Results Seventeen studies with a total of 867 female and two male participants were included. Only studies examining breast
cancer-related lymphedema were identified. Some studies reported positive effects of MLD on volume reduction, quality of life
and symptom-related outcomes compared with other treatments, while other studies reported no additional benefit of MLD as a
component of complex decongestive therapy. In patients at-risk, MLD was reported to reduce incidence of lymphedema in some
studies, while others reported no such benefits.
Conclusions The reviewed articles reported conflicting findings and were often limited by methodological issues. This review
highlights the need for further experimental studies on the effectiveness of MLD in lymphedema.
Implications for Cancer Survivors There is some evidence that MLD in early stages following breast cancer surgery may help
prevent progression to clinical lymphedema. MLD may also provide additional benefits in volume reduction for mild lymphedema. However, in moderate to severe lymphedema, MLD may not provide additional benefit when combined with complex
decongestive therapy.
Keywords Manual lymphatic drainage . Breast cancer . Lymphedema . Lymphatic therapy
Introduction
Lymphedema arises from impairment of the lymphatic system
and results in progressive swelling due to an accumulation of
protein-rich fluid in the interstitial spaces [1, 2]. Lymphedema
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s11764-020-00928-1) contains supplementary
material, which is available to authorized users.
* Belinda Thompson
belinda.thompson@mq.edu.au
1
Australian Lymphoedema Education, Research & Treatment
(ALERT) Program, Department of Clinical Medicine, Faculty of
Medicine, Health and Human Sciences, Macquarie University, Level
1, 75 Talavera Road, Sydney, NSW 2109, Australia
2
School of Environmental & Life Sciences, Faculty of Science, The
University of Newcastle, Ourimbah, NSW, Australia
can cause significant psycho-social, physical, functional and
financial hardship [3]. Although the cause of lymphedema can
vary, typically research tends to focus on secondary lymphedema following cancer treatment. In 2018, there were an
estimated 17 million new cancer diagnoses worldwide [4].
With increased cancer incidence and survival rates, management of chronic treatment related complications, such as
lymphedema, should be prioritized.
Complex decongestive therapy (CDT) has been widely accepted as a conservative treatment strategy for lymphedema [5, 6].
CDT commonly consists of a two-stage program. Phase one,
known as the intensive phase, includes education, skin care, manual lymphatic drainage (MLD) massage, exercise and multilayered
compression bandaging and usually lasts between 2 and 4 weeks.
Phase two, the maintenance phase, aims to optimize and retain
changes obtained in the intensive phase, typically through the
use of compression garments, skin care, self-MLD and a home
exercise program [5]. As a component of CDT, MLD is thought to
J Cancer Surviv
soften fibrosis and increase lymph drainage into venous circulation
by stimulating superficial lymphatic contraction and rerouting
lymphatic fluid into adjacent functioning lymphatic systems [7,
8]. Historically, several MLD schools have been founded, with
the most recognized and widely used including Vodder, Földi,
Casley-Smith and Leduc [9]. Qualified lymphedema therapists
use specialized slow repetitive hand movements, gently massaging
along anatomical lymphatic pathways over affected areas,
attempting to stimulate lymphatic flow and drainage [8, 9].
Firmer movements over areas of fibrosclerosis may be used, with
MLD generally starting proximally and centrally, before moving
distally in segments with massage performed in the direction of
lymphatic flow [10]. However, the effect MLD has on lymphedema management is still poorly understood, partly due to limitations
in establishing valid and reliable measures to assess lymphatic flow
changes and difficulties in distinguishing the effect MLD has on
lymphedema outcomes from other interventions, such as compression therapy [9].
To date, there have been contradictory findings from systematic reviews examining the effect of MLD on lymphedema outcomes ranging from no benefit [7], to small benefits in mild-tomoderate lymphedema [8], to inconclusive findings when using
MLD both as a lymphedema preventative modality [11] and for
improvements in health-related quality of life (QOL) outcomes
[11, 12]. In addition to the highly variable short-term effect of
MLD on lymphedema, long-term outcomes of MLD treatment
are inconsistent. With the chronicity of lymphedema, the effectiveness of MLD interventions as part of the maintenance phase
of treatment also needs to be established. Moreover, MLD is
generally examined in the context of a multi-modal CDT program, and therefore the effectiveness of MLD as a stand-alone
modality needs to be evaluated [8]. Furthermore, reviews examining the effect of MLD as a preventative or management technique for lymphedema have focused mostly on breast cancerrelated lymphedema (BCRL) [7, 8, 11]; consequently, further
exploration of the literature to evaluate the effect MLD has on
other forms of lymphedema is warranted. Therefore, the objectives of this manuscript were to firstly investigate, by way of
systematic review of RCTs, the effectiveness of MLD as a treatment for various forms of lymphedema. Secondly, this manuscript aims to examine the methodologies used in recent MLD
research on patients at-risk of or living with lymphedema. It is
envisaged that the results of this review will assist in the formulation of recommendations for MLD therapy and further methodological considerations to assist future research.
Complete and Cochrane Central Register of Controlled
Trials was conducted on 28 February 2020. Search terms used
were lymphoedema, lymphedema, oedema, edema,
lymphedematous, manual lymphatic drainage, complete decongestive therapy, decongestive lymphatic therapy, lymphatic drainage, complex lymphedema therapy, manual lymph
drainage, massage, complex decongestive therapy, decongestive physiotherapy and congestive lymphatic therapy
(Online Resource 1). The search was restricted to humans
and the English language; however, no date restrictions were
used. A manual search of current reviews and the reference
lists of included articles was also performed.
Study selection
Only published full-text RCTs that compared MLD as a treatment for lymphedema with another intervention or a control
intervention were included. Studies were also included if they
compared the effect of MLD on lymphedema incidence in
patients at-risk of lymphedema with another intervention or
a control intervention. Trials were also required to report
changes in limb volume or circumference measurements as
outcome measures. Studies were excluded if the effects of
MLD could not be isolated due to the presence of mixed
treatments or when comparisons could not be made due to
all treatment arms describing an MLD component. Studies
were also excluded if MLD was not provided by a therapist
(self-MLD).
Data extraction and quality assessment
The electronic searches were performed by one reviewer
(BT). Titles and abstracts were assessed independently by
two reviewers (BT and KG). Any disagreement about the
inclusion of trials was resolved by consensus or a third reviewer (LK) where necessary. Population characteristics, trial inclusion and exclusion criteria, intervention details, outcome
data and overall conclusions from each trial were extracted
using a standardized data extraction form.
The PEDro scale was used independently by two reviewers
(BT and KG) to assess the methodological quality of the included trials [14]. Scores were compared, and any disagreements were resolved by a third reviewer (LK). The PEDro
scores range from 0 to 10 with a score of 6 or more are considered to be of high methodological quality, and studies scoring 5 or less are considered to be of low methodological quality [15].
Methods
Data synthesis and analysis
Data sources and searches
Following PRISMA guidelines [13], an electronic database
search of title and abstract in Embase, PubMed, CINAHL
Data analyses were performed using Review Manager [16].
The studies were classified into two groups: patients with
lymphedema and patients at-risk of lymphedema. As excess
J Cancer Surviv
limb volume was the primary outcome in the majority of studies for patients with lymphedema, standard mean difference
(SMD) (Hedges g) was calculated to compare the treatment
effect of MLD on excess limb volume or limb circumference
with the treatment effect of the control or comparison intervention. An effect size of greater than or equal to 0.8 was
considered a large effect, 0.5 a moderate effect, 0.2 a small
effect and less than 0.2 a trivial effect [17]. Where the mean
and SD of the change from baseline to endpoint were not
reported in the original articles, the appropriate equation was
used for calculation when possible following recommendations from the Cochrane Handbook for Systematic Reviews
of Interventions [18].
Results
Study selection
The initial database search produced a total of 1786 articles.
After removing 371 duplicate articles, the remaining 1415
articles were screened, of which 31 were deemed potentially
eligible based on title and abstract (Fig. 1). After a full-text
review, 14 articles were excluded (Online Resource 2). A total
of 17 studies remained for inclusion in the qualitative analysis.
Due to the large variation in study design, interventions, comparisons and outcomes, quantitative analysis was not deemed
appropriate, and therefore the results have been presented in a
narrative form.
Methodological quality
The PEDro scores ranged from 3 to 8 with a mean score of
5.35 (Table 1). Nine of the studies scored 6 or more and were
deemed to be of good methodological quality, while the remaining eight studies scored 5 or less. All studies randomly
allocated participants, and most provided sufficient results and
analysis. Thirteen studies failed to conceal allocation [19,
21–24, 26–32, 35], two studies did not report baseline comparability [23, 24], and twelve studies did not use intention-totreat analysis [20–27, 29, 30, 32, 35]. Therapists and participants were not blinded in any of the trials as is to be expected
for MLD intervention studies, and only eight studies reported
blinding of the assessors [20, 22, 25, 28, 30, 32–34].
Study characteristics
The characteristics of the included studies are summarized in
Table 2. The 17 studies examining the effect of MLD on
lymphedema or incidence of lymphedema included a total of
867 female and two male participants with a mean age range
of 46.0 to 71.0 years. The individual studies included between
27 and 160 participants. Trials included patients with BCRL
(n = 13) or at-risk of developing BCRL (n = 4). No RCTs
investigating the effect of MLD on other types of lymphedema were identified. The trials included between five and 54
MLD sessions performed by a trained therapist over 1 to
22 weeks. Sessions were between 15 and 80 min in length.
Follow-up beyond the post-intervention period was only reported by four studies at 6 months [22], 7 months [30],
12 months [33] and 60 months [34]. Comparisons against
MLD included simplified lymphatic drainage, self-MLD, proprioceptive neuromuscular facilitation (PNF), intermittent
pneumatic compression (IPC), low-level laser therapy
(LLLT) and low-frequency low-intensity electrotherapy
(LFLIE). Standard therapy, CDT, exercise and compression
bandaging with or without the inclusion of MLD were also
compared. Only one of the studies that included patients with
lymphedema did not report the use of compression bandaging
or a compression sleeve/garment [26]; all other studies including patients with lymphedema reported the use of compression bandaging or a compression sleeve/garment in all treatment arms.
Method of manual lymphatic drainage
Two studies reported using the Vodder method of MLD as
their only description provided [21, 32], while a further three
studies reported using the Vodder method and provided additional information regarding the MLD sequence or technique
[24, 25, 31]. One study reported using a method similar to the
Vodder method with some additional information [26]. One
study reported using the Vodder II method and provided detailed information regarding the MLD sequence used [22].
Another study reported using the Leduc method and also included specific details relating to the MLD sequence [29]. The
therapists providing the MLD intervention for two articles
(with the same participants) were reported as being trained
in the Leduc or Vodder methods with additional information
regarding the specific sequence provided [33, 34]. Two studies reported using the Földi method with no additional information [27, 30]. One further study reported using a modified
version of the Földi technique. Although it was not specified
how the technique had been modified, a brief description of
the method was provided [35]. Four studies provided no information or description of the MLD used [19, 20, 23, 28].
Of the nine studies that provided additional information
regarding the specific MLD sequence used, one reported only
applying MLD to the affected side of the body, draining in a
proximal direction towards the ipsilateral axilla in patients atrisk of BCRL [35]. Devoogdt et al. report emptying the neck
and axilla before massaging axillo-axillary anastomoses at the
breast and back (connections between the ipsilateral and contralateral axilla) and the lateral side of the shoulder, followed
by draining the arm and hand in patients at-risk for BCRL [33,
34]. For the studies that included patients with lymphedema,
J Cancer Surviv
Fig. 1 Flow chart showing
screening process and search
results. MLD manual lymphatic
drainage, RCT randomized
controlled trial
11
Records
through
database search (n = 1,786)
EMBASE: 335, PubMed: 867,
CINAHL: 166, Cochrane Central
Register of Controlled Trials: 418
Addional records
through other sources (n = 0)
Records screened
(n = 1,415)
Records excluded
(n = 1,384)
Eligibility
Full text arcles assessed for
eligibility (n = 31)
Full-text arcles excluded
(n = 14)
Unable to isolate the effect of
MLD (n = 3)
Not an RCT (n = 5)
No comparison for MLD (n = 1)
Both groups received MLD (n = 4)
MLD was not provided by a
therapist (n = 1)
Included
Screening
Records aer duplicates removed (n = 1,415)
Studies included in
synthesis
(n = 17)
MLD: manual lymphatic drainage, RCT: randomized controlled trial
one study reported using a low pressure in a proximal direction, starting with the trunk, and working in segments ending
with the hand [24]. Another study described a gentle pressure
with massage initiated in the contralateral and ipsilateral upper
quadrants before progressing to the affected arm [25]. A similar sequence is described in another study with patients who
have more advanced lymphedema; however, this study reported using slower movements and high pressure [22]. Odebiyi
et al. described a slow deep effleurage, kneading and frictional
massage of the affected limb with the arm at a 45° angle to
assist with drainage [26]. Williams et al. reported the removal
of fluid from the neck, posterior and anterior trunk and affected arm, with fluid always being moved to the unaffected
(contralateral) side of the body [31]. Sitzia et al. provided
detailed information regarding the sequence performed on patients with moderate to severe lymphedema. In this study,
MLD commenced at the base of the neck, subclavian areas
and both axilla before draining the posterior thoracic pathways
(MLD performed on the back of the patient) and finishing by
draining the affected arm [29]. Finally, although Sanal-Toprak
et al. did not provide a description of the MLD provided, they
did describe a pressure applied with the hands and fingers of
30–45 mmHg; however, there is no information on how this
pressure was measured [28].
Methods for measuring volume changes in patients
with or at-risk of lymphedema
Six of the 17 included studies measured limb volume with
water displacement [24, 25, 30, 33–35]. Of the six studies that
used water displacement, two studies (with the same participants) also included circumferential measurements spaced
Eligibility
criteria
1
1
1
1
1
1
1
1
1
1
1
0
0
0
1
0
0
0
0
0
0
0
1
1
0
1
1
Johansson et al. Yes
1
[24]
McNeely et al. Yes
1
[25]
Odebiyi et al. Yes
1
[26]
Ridner et al.
Yes
1
[27]
Sanal-Toprak Yes
1
et al. [28]
Sitzia et al. [29] Yes
1
Tambour et al. Yes
1
[30]
Williams et al. Yes
1
[31]
Patients at-risk for lymphedema
Cho et al. [32] Yes
1
1
Devoogdt et al. Yes
[33]
Devoogdt et al. Yes
1
[34]
Zimmerman
No
1
et al. [35]
High quality shown in italics
0
0
1
0
1
1
1
1
1
1
Baseline
comparability
0
Concealed
allocation
1
Random
allocation
PEDro scores for the included articles
Patients with lymphedema
Anderson et al. Yes
[19]
Belmonte et al. Yes
[20]
Bergman et al. Yes
[21]
Gradalski et al. No
[22]
Ha et al. [23]
No
Author
Table 1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Blinded
participants
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Blinded
therapists
0
1
1
1
0
0
1
1
0
0
1
0
0
1
0
1
0
Blinded
assessors
0
1
1
1
0
1
1
1
1
0
1
1
0
1
0
0
1
Adequate
follow-up
0
1
0
1
1
0
0
1
0
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
Intention-to-treat Between group
analysis
comparisons
1
1
1
1
0
1
1
1
1
1
1
1
1
1
0
1
1
4/10
8/10
6/10
8/10
3/10
5/10
6/10
7/10
5/10
4/10
7/10
4/10
3/10
6/10
3/10
6/10
6/10
Point estimates and Total
variability
score
J Cancer Surviv
J Cancer Surviv
Table 2
Summary of included studies
Author
Population
ISL Participants
stage
Patients with lymphedema
Andersen
Patients with unilateral
NR
et al.
BCRL min 4 months
(2000)
post-surgery, vol diff
Denmark [19]
> 200 ml or circ diff
> 2 cm, recruited from
outpatient lymphedema
clinic
Belmonte
et al.
(2011)
Spain [20]
Patients with chronic
NR
BCRL who were in the
maintenance phase of
CDT for > 12 months,
recruited from
outpatient hospital
rehabilitation setting
Bergmann
et al.
(2014)
Brazil [21]
Patients with unilateral
NR
BCRL, circ diff > 3 cm,
recruited from
outpatient clinic
Gradalski
et al.
(2015)
Poland [32]
Patients with unilateral
BCRL
post-mastectomy, vol
diff > 20%
Ha et al.
(2017)
South Korea
[23]
Patients with unilateral
NR
BCRL, circ diff > 2 cm
Johansson
et al.
(1998)
Sweden [24]
Patients with unilateral
NR
BCRL and ALND, vol
diff > 10%, recruited
from university hospital
McNeely
et al.
(2004)
Sweden [25]
Patients with unilateral
BCRL and ALND, vol
diff > 150 ml, referred
to rehabilitation
II
NR
Intervention and
comparison
MLD
components
PEDro Results/conclusions
score
44 females, 0 Standard therapy
Total
6/10
males
(compression sleeve and
sessions: 8
Age: 56 and
education) vs standard
Weeks: 2
53
therapy + MLD (no
Mins/session:
Randomizspecific details given
60
ed: 44
regarding MLD method)
Analysed: 42
Significant reduction in
volume and symptoms in
both groups, no
additional benefit of
MLD above standard
therapy for reduction in
volume or lymphedema
symptoms
36 females, 0
males
Age:
67.8 ± 11.3
Randomized:
36
Analysed: 30
66 females, 0
males
Age:
62.2 ± 9.1
and
63.6 ± 11.0
Randomized:
66
Analysed: 57
60 females, 0
males
Age:
62.0 ± 12.2
and
61.2 ± 9.2
Randomized:
60
Analysed: 51
55 females, 0
males
Age:
50.8 ± 0.9,
54.1 ± 0.9
and
53.4 ± 0.8
Randomized:
55
Analysed: 55
28 females, 0
males
Age: 64.0 and
57.5
Randomized:
28
Analysed: 24
No difference in treatment
outcomes (volume
reduction, QOL and
symptoms) between
interventions, no
reduction in volume
reported for either group
Significant volume and
symptom reductions in
both groups, no
significant difference
between groups, MLD
did not increase
therapeutic response in
BCRL
Low-frequency
low-intensity electrotherapy vs MLD (no
specific details given regarding MLD method);
both groups received
compression garments
Physical treatment (skin
care, CB, and remedial)
exercises vs physical
treatment + MLD
(Vodder technique)
Total
6/10
sessions:
10
Weeks: 2
Mins/session:
NR
Total
3/10
sessions:
9–12
Weeks: avg 3
Mins/session:
30
CDT (CB, aerobic exercise Total
6/10
and deep breathing) vs
sessions:
CDT + MLD (Vodder II
10
method)
Weeks: 2
Mins/session:
30
Similar volume reductions
and improvement in
QOL scores were
reported for both groups,
no additional benefit of
MLD above CDT
MLD (performed by a
Total
3/10
certified technician but
sessions:
no specific information
48
given) vs PNF
Weeks: 16
(performed by a certified Mins/session:
technician) vs PNF +
30
MLD (all participants
were given lymph pads
and CB)
Significant reductions in
volume, pain and
depression in all groups,
larger response in
combined group
Sequential pneumatic
Total
4/10
compression (pressure
sessions:
40–60 mmHg applied
10
for 2 h each session) vs Weeks: 2
MLD (Vodder method, Mins/session:
all patients were given a
45
compression sleeve)
Significant volume
reductions observed in
both groups, no
differences were
reported between
intervention groups,
significant
improvements in tension
and heaviness in MLD
group
Significant reduction in
volume in both groups
with no difference
between groups,
sub-analysis revealed
50 females, 0 Compression bandage
Total
males
(short stretch bandage)
sessions:
Age: 58 ± 13
vs compression bandage
20
and
+ MLD (Vodder
Weeks: 4
63 ± 13
method)
7/10
J Cancer Surviv
Table 2 (continued)
Author
Population
ISL Participants
stage
department at cancer
institute
Odebiyi et al. Patients with stage II and
(2014)
III breast cancer and
Portugal [26]
BCRL, recruited from
outpatient unit of
university teaching
hospital
Randomized:
50
Analysed: 45
27 females, 0
males
Age:
46.0 ± 8.4
and
54.0 ± 14.0
Randomized:
30
Analysed: 27
Ridner et al. Patients with BCRL,
I or 46 females, 0
(2013)
recruited through
II
males
USA [27]
advertisement and
Age:
private medical practice
66.6 ± 10.4
Randomized:
46
Analysed: 46
Sanal-Toprak Patients with BCRL
II or 46 females, 0
et al.
minimum 3 months
III
males
(2019)
post-surgery, recruited
Age:
Turkey [28]
from oncologic
55.4 ± 10.3
rehabilitation clinic
and
59.0 ± 2.83
Randomized:
46
Analysed: 46
Sitzia et al.
Patients with moderate to NR 28 females, 0
(2002)
severe unilateral BCRL,
males
UK [29]
vol diff > 20%, recruited
Age:
from hospital
71.0 ± 10.8
lymphedema clinic
Randomized:
28
Analysed: 27
Tambour
Patients with unilateral
II–III 77 females, 0
et al.
BCRL, min circ diff
males
(2018)
2 cm, min 6 weeks post
Age:
Denmark [30]
cancer treatment,
61.5 ± 11.1
recruited from
Randomized:
oncologists or breast
77
surgeons
Analysed: 73
Williams
et al.
(2002)
UK [31]
Patients with unilateral
BCRL > 3 months, vol
diff > 10%, min
12 months post cancer
treatment, recruited
from hospital
lymphedema clinic
Patients at-risk for lymphedema
Cho et al.
Patients with
(2016)
AWS > 4 weeks
South Korea
post-surgery for breast
[32]
cancer, recruited from
Intervention and
comparison
NR
MLD
components
PEDro Results/conclusions
score
Mins/session:
45
possible additional benefit of MLD above CB
alone in patients with
mild lymphedema
Exercise (stretching and
Total
4/10
aerobic exercise) vs
sessions:
exercise + MLD (similar
12
to the Vodder method
Weeks: 6
with arm held at a 45°
Mins/session:
angle)
15
MLD (Földi method
Total
5/10
(international standards))
sessions:
vs LLLT (20 mins laser
avg 8
therapy) vs LLLT +
Weeks: NR
MLD (all treatments
Mins/session:
included CB)
40
IPC + CB (30 mins IPC
followed by CB) vs
MLD + CB (MLD
performed by massage
therapist (30–45 mmHg
pressure applied with
hands during MLD)
followed by CB)
Significantly higher change
in limb girth with
exercise + MLD
compared with exercise
alone, combined
exercise and MLD
improved QOL and LOF
scores compared with
exercise alone
All groups had significant
reduction in volume, no
differences between
groups in psychological
or physical symptoms
Total
7/10
sessions:
15
Weeks: 5
Mins/session:
30
Both groups had significant
reductions in arm
circumference, shoulder
ROM, pain, tightness
and heaviness, no
differences were
observed between
groups
MLD (Leduc method
Total
5/10
(detail given)) vs SLD
sessions:
(simplified version of
10
MLD in a set sequence); Weeks: 2
both groups received CB Mins/session:
40–80
Results suggest that MLD
is more effective than
SLD in treating BCRL;
however, differences
between groups were
insignificant
CDT + MLD (Földi
method, CB, skin care
and exercise) vs CDT
(CB, skin care and
exercise)
Both groups had significant
volume reductions with
no differences between
groups, significantly
greater reduction in
shoulder tension in MLD
group, MLD added no
further volume reduction
beyond CDT in BCRL
Significant reduction in
excess limb volume, pain
and heaviness with
MLD, trend towards
significant differences
between groups, MLD
improves symptoms of
BCRL
Total
6/10
sessions: 6
Weeks: 3
Mins/session:
30–60
NR
3/10
31 females, 0 MLD (Vodder method) vs Total
SLD (set sequence
sessions:
males
performed by
15
Age:
59.7 ± 2.1
participants on
Weeks: 3
and
themselves—cross-over Mins/session:
59.3 ± 2.4
design); both groups
45
Randomized:
received both treatments,
31
all participants were
Analysed: 29
fitted with compression
garments
NA
48 females, 0 Physical therapy (stretching Total
males
and strengthening
sessions: 5
Age:
exercises and manual
Weeks: 1
46.6 ± 6.8
therapy) vs physical
6/10
Physical therapy combined
with MLD decreases arm
lymphedema incidence
over the short term
J Cancer Surviv
Table 2 (continued)
Author
Population
ISL Participants
stage
rehabilitation medicine
department
Devoogdt
et al.
(2011)
Belgium [33]
Patients with unilateral
NA
breast cancer and
ALND, 5 weeks
post-surgery, recruited
from university hospital
Devoogdt
et al.
(2018)
Belgium [34]
Patients with unilateral
NA
breast cancer and
ALND, 5 weeks
post-surgery, recruited
from university hospital
Zimmermann Patients who had
et al.
undergone surgery for
(2012)
breast cancer
Germany [35]
NA
Intervention and
comparison
and
therapy combined with
50.7 ± 9.6
MLD (Vodder method
Randomized:
during week 1 (5
48
sessions), self MLD for
Analysed: 41
weeks 2–4)
158 females, Guidelines and exercise
2 males
therapy (stretching,
Age:
mobility and
55.8 ± 12.5
strengthening exercises)
and
vs guidelines, exercise
54.5 ± 11.1
therapy and MLD
Randomized:
(standardized lymph
160
drainage (1 therapist
Analysed:
trained in Vodder
154 at
method))
12 months
158 females, Guidelines and exercise
2 males
therapy (stretching,
Age:
mobility and
55.8 ± 12.5
strengthening exercises)
and
vs guidelines, exercise
54.5 ± 11.1
therapy and MLD
Randomized:
(standardized lymph
160
drainage (2 therapists
Analysed:
trained in Vodder
133 at
method, 2 trained in
60 months
Leduc method))
67 females, 0 MLD (modified Földi
males
technique) vs
Age:
self-drainage
59.4 ± 10.4
Randomized:
67
Analysed: 67
MLD
components
PEDro Results/conclusions
score
Mins/session:
30
(4 weeks) and reduces
pain scores compared
with physical therapy
alone in patients with
AWS
Total
8/10
sessions:
23–35+
Weeks: 20
Mins/session:
30
No additional benefit of
MLD above guidelines
combined with exercise
therapy for decreasing
lymphedema incidence
in patients who have had
ALND over the short
term (12 months)
8/10
Total
sessions:
23–35+
Weeks: 20
Mins/session:
30
No difference in
lymphedema incidence
between groups at 60month follow-up, poorer
scores for functioning
with MLD, MLD may
not have a preventative
effect on BCRL in the
long term (60 months)
Total
4/10
sessions:
54
Weeks: 24
Followed by:
5 sessions per
week for
2 weeks,
followed
by 2 per
week for
6 months
Mins/session:
NR
Significant increase in arm
volume in patients
without MLD, no
increase in volume in
patients who received
MLD following
6 months of
intervention, early
administration of MLD
post-surgery beneficial
for lymphedema prevention
ALND axillary lymph node dissection, avg average, AWS axillary web syndrome, BCRL breast cancer-related lymphedema, CB compression bandaging,
CDT complex decongestive therapy, circ circumference, diff difference, ISL International Society of Lymphology, IPC intermittent pneumatic compression, LLLT low-level laser therapy, LOF level of fatigue, min minimum, MLD manual lymphatic drainage, NA not applicable, NR not reported, PNF
proprioceptive neuromuscular facilitation, QOL quality of life, ROM range of motion, SLD simple lymphatic drainage, vol volume
4 cm apart using a stainless steel bar with a tapeline [33] or a
perometer [34], one study used the sum of seven circumferential measurements from pre-determined sites [30], and one
study included volume measurement using the truncated cone
formula from circumferential measurements spaced 4 cm
apart [25]. A further three of the 17 included studies also
calculated volume using the truncated cone formula and
circumferential measurements at 4-cm intervals [22, 29, 32].
Studies also reported using the truncated cone formula to calculate volume from five circumferential measurements spaced
7 cm apart [21] and four segments identified by using anatomical landmarks [20]. One study performed circumferential
measurements spaced 4 cm apart; however, the formula for
calculating the volume of a cylinder was used to estimate arm
J Cancer Surviv
volume [31]. Another study performed eight circumferential
measurements spaced 5 cm apart and used the Simpson’s rule
of integration to calculate arm volume [19]. One further study
also estimated arm volume from circumferential measurements spaced 4 cm apart; however, it is unclear which formula
was used in the volume calculation [27]. In addition to circumferential volume measurement, Ridner et al. also used
bioimpedance spectroscopy (BIS) to compare the ratio of extracellular fluid in the affected arm to the unaffected arm (LDex score) and was the only study of the seventeen included
studies to utilize this method [27]. Three studies only used
circumference measurements: at one site, 13 cm from the ulna
olecranon process [26]; two sites, one 10 cm proximal and one
10 cm distal to the ulna olecranon process [23]; and at five
sites on the arm [28] to assess changes in arm swelling. Only
one study calculated effect sizes to assess the magnitude of
change in volume from baseline [27], and none of the included
studies defined the amount of volume reduction required to be
considered clinically meaningful.
The effect of manual lymphatic drainage on volume
reduction in patients with lymphedema
Thirteen of the seventeen included studies examined the effect
of MLD on patients with BCRL. MLD with compression
bandaging was reported to be as effective in reducing arm
volume as IPC with compression bandaging in patients with
International Society of Lymphology (ISL) stage II or III
BCRL [28] and LLLT with compression bandaging in patients with ISL stage I or II BCRL [27]. MLD in addition to
a compression sleeve was reported to be as effective in decreasing arm volume as treatment with sequential pneumatic
compression and a compression sleeve with a small effect
(SMD = 0.41) in favour of MLD [24]. MLD was also reported
to be as effective as PNF for reducing arm circumference in
patients with BCRL, and additional reductions were observed
when MLD and PNF were combined suggesting a synergistic
effect of the two treatments [23]. Four studies reported significant arm volume reductions with 2 weeks [19, 22] and
3 weeks [21, 30] of CDT consisting of skin care, exercise
and bandaging; however, the addition of MLD to CDT did
not provide any further volume reductions in any of the four
studies [19, 21, 22, 30]. Furthermore, calculation of the effect
sizes for the difference in treatment effect between groups
revealed a small effect in favour of CDT without MLD in
one study (SMD = − 0.31) [19], while in the other three studies, effect sizes were trivial (SMD = − 0.04 to 0.09) [21, 22,
30]. One cross-over study compared the effect of 10 sessions
of MLD over 2 weeks on arm volume with the same number
of sessions of LFLIE in patients with chronic BCRL who were
in the maintenance phase of CDT (compression garment, exercise and skin care) and reported no volume reductions in
response to either treatment [20]. In addition, the effect size
for the treatment effect of MLD compared with LFLIE in this
study was trivial (SMD = 0.12).
One study compared compression bandaging alone with
compression bandaging with the addition of 20 sessions over
4 weeks of MLD in patients with BCRL [25]. Significant
volume reductions were observed in both groups, with no
differences and trivial effects (SMD = 0.07) between groups.
However, sub-group analysis based on limb volume difference at commencement of the study (mild, moderate and severe lymphedema) revealed a significantly greater relative
volume reduction with the addition of MLD to compression
bandaging in patients with mild lymphedema (< 15% volume
difference between limbs) compared with all the other subgroups. This suggests an additional benefit of MLD above
compression bandaging alone for patients with mild BCRL
[25]. One study reported significantly greater reductions in
arm girth (at one measurement point) in patients with BCRL
who undertook 12 sessions over 6 weeks of stretching and
aerobic exercise combined with MLD compared with patients
in the exercise only group. Furthermore, calculation of the
effect size revealed a large effect (SMD = 1.51), suggesting
an additional benefit of MLD above exercise alone [26].
Finally, one study compared a traditional form of MLD provided by a therapist with a simplified version of MLD also
provided by a therapist with both groups receiving compression bandaging [29]. Although greater volume reductions with
a moderate effect (SMD = 0.58) with the traditional style of
MLD compared with the simplified version of MLD in patients with moderate to severe BCRL were observed, the between group differences were not significant [29]. One crossover study compared traditional MLD with self-MLD for 15
sessions over 3 weeks combined with compression garment.
They reported significant excess volume reductions with traditional MLD but not with self-MLD. Although the difference
between MLD and self-MLD just failed to achieve significance (p = 0.053), calculation of the effect size showed a small
effect in favour of MLD (SMD = 0.27) [31].
The effect of manual lymphatic drainage on
lymphedema incidence in patients at-risk for breast
cancer-related lymphedema
Four of the seventeen studies examined the effect of MLD on
lymphedema incidence in patients at-risk for BCRL. One
study compared the effect of exercise and manual therapy with
and without the addition of MLD on patients with axillary
web syndrome following axillary dissection [32]. The authors
reported arm volume to be significantly lower in the group
that received MLD compared with the group without MLD.
Additionally, lymphedema, defined as a 3% or greater volume
increase from baseline of the affected arm, was developed in
six of the 20 patients (30%) in the non-MLD group and none
of the 21 patients in the MLD group. However, patient
J Cancer Surviv
outcomes were only reported following 4 weeks of treatment
with no additional long-term data [32]. One study compared
the effect of MLD with self-MLD on lymphedema incidence
in patients at-risk of BCRL [35]. Treatment commenced from
day 2 post-surgery. Following 6 months of treatment, 70.6%
of patients who did not receive MLD developed lymphedema
(defined as a 5% or greater volume difference between the
affected and unaffected arm), while none of the patients who
received MLD had developed lymphedema, suggesting that
MLD applied early after surgery for breast cancer has a preventative effect on lymphedema development [35]. In contrast, Devoogdt et al. compared a 6-month treatment program
consisting of guidelines for lymphedema prevention (education), exercise and MLD with the same treatment program
without MLD in patients at-risk for developing BCRL with
follow-up reported at 12 months [33] and 60 months postsurgery [34]. The intervention commenced approximately
5 weeks post-surgery; however, no difference in lymphedema
incidence (defined as a volume increase of 200 mL or greater
of the affected arm) between groups was reported at any timepoint [33, 34].
The effect of manual lymphatic drainage on quality of
life and symptoms in patients with lymphedema or
at-risk for lymphedema
Eleven of the included studies examined the effect of MLD on
QOL and lymphedema-related symptoms in patients with
BCRL. One of these studies reported improvements in
oedema-related QOL and treatment satisfaction with CDT;
however, the addition of MLD did not appear to provide any
further improvements in these outcomes [22]. Similarly,
Andersen et al. and Bergmann et al. reported improvements
in subjective symptoms related to lymphedema following
CDT with no further benefits provided by the addition of
MLD to the treatment program [19, 21]. Tambour et al. reported a significantly higher reduction in heaviness of the
affected arm in patients who received MLD in addition to
CDT compared with patients who received CDT without
MLD at 1-month follow-up. However, no differences between
groups were reported in QOL scores or any other symptom
scores, and at a follow-up of 6 months post-intervention, the
difference between groups in arm heaviness was no longer
apparent [30]. In contrast, significantly greater improvements
in QOL and level of fatigue were observed following an intervention of MLD combined with exercise compared to exercise alone [26]. One further study reported improvements in
QOL and lymphedema symptoms, such as pain and heaviness, in patients receiving MLD, but no improvements in
these outcomes were observed in the patients performing
self-MLD [31].
When comparing MLD with IPC for reducing
lymphedema-related symptoms, Sanal-Toprak et al. reported
improvements in pain, tightness and heaviness for both treatments with no difference between treatments [28]. However,
Johansson et al. reported improvements in tension and heaviness in the affected arm of patients who received MLD, but
not in patients receiving IPC [24]. Together, these studies
suggest that MLD is as effective or more effective than IPC
in reducing lymphedema-related symptoms such as tension
and heaviness. One study reported MLD to be as effective
as LLLT for reducing symptom burden in patients with
BCRL [27]. In contrast, another study observed significant
reductions in pain, heaviness and tightness and significant
improvements in health-related QOL with LFLIE, but no significant reductions in these outcomes were observed with
MLD. However, no significant differences between groups
were reported in all outcomes except for reduction in pain
(LFLIE > MLD, p = 0.05) [20]. One further study observed
significant reductions in pain and depression with MLD only,
and when combined with PNF, even greater reductions in pain
and depression were reported [23].
Finally, in patients at-risk for lymphedema, Devoogdt et al.
reported comparable results for health-related QOL at 12- and
60-month follow-up between physical therapy with and without MLD [33, 34]. However, the participants who received
MLD had significantly higher (worse) scores for problems in
functioning than those in the control group at a 60-month
follow-up [34]. In contrast, Cho et al. reported significant
improvements in QOL and arm disability in patients with
axillary web syndrome with physical therapy with and without
MLD with no differences between groups. However, significantly greater improvements in pain were reported in the
MLD with physical therapy group compared with physical
therapy alone [32].
Discussion
Despite limited evidence to support its use, MLD is widely
accepted as a conservative treatment for lymphedema. The
aim of this manuscript was to investigate, by way of systematic review of RCTs, the effectiveness of MLD as a treatment
for lymphedema or as a preventative therapy in patients at-risk
for lymphedema. Only 17 studies met the inclusion criteria for
this review and 13 of these studies included patients with
BCRL, while four studies focussed on patients at-risk for
BCRL. The 17 studies often reported conflicting results,
which may be related to the wide range of different MLD
techniques used and outcome measurement tools employed.
Conventional methods of MLD aim to treat healthy lymph
nodes, for example, in unilateral upper limb lymphedema; the
contralateral axilla and ipsilateral inguinal nodes are massaged
[9]. The theory behind this is that MLD will potentially influence the creation of collateral pathways to the healthy lymph
nodes [9]. Of the nine studies in this review which described
J Cancer Surviv
the MLD technique used, six studies specifically mentioned
massaging the contralateral axilla [22, 25, 29, 31, 33, 34]. An
early lymphangiography study demonstrated that 68% (13 out
of 19) patients with BCRL had patent lymphatic vessels passing through the ipsilateral axilla [36]. Similarly, a recent indocyanine green fluorescence (ICG) lymphography study in 100
patients with BCRL reported that lymphatic drainage to the
ipsilateral axilla occurred in 67% of cases [37]. Furthermore, a
sub-analysis revealed that for patients with mild lymphedema
(MD Anderson Cancer Centre (MDACC) ICG lymphedema
stage one), the percentage of patients with drainage pathways
towards the ipsilateral axilla increased to 95% [37]. This suggests that the ipsilateral axilla remains an important drainage
pathway, particularly with mild BCRL. Zimmerman et al.
used a modified MLD technique which only focussed on the
affected side of the body and reported MLD to be effective for
reducing the incidence of BCRL in patients at-risk for lymphedema following surgery for breast cancer [35]. In contrast, in
high-quality studies in patients at-risk for lymphedema,
Devoogdt et al. reported no additional benefit of MLD in
reducing incidence of BCRL compared with education guidelines and exercise therapy [33, 34]. However, the MLD applied in these studies included massage of collateral drainage
pathways at the breast and back towards the contralateral axilla and the lateral side of the shoulder (Mascagni pathway)
prior to draining the affected limb from proximal to distal, in
the direction of lymphatic flow. As MLD was only provided
for 30 min each session, modifying the MLD technique to
focus on drainage towards the ipsilateral axilla, such as that
provided by Zimmerman et al. [35], may be a more efficient
use of time in patients who are at-risk of BCRL.
For patients with more severe lymphedema (MDACC IGC
stage 4), the recent ICG lymphography study by Suami et al.
reported that only 50% of cases had drainage pathways to the
ipsilateral axilla, while 41% had drainage pathways to the
clavicular nodes, 17% had drainage pathways to parasternal
nodes, and 17% had drainage pathways to the contralateral
axilla [37]. Therefore, in patients with more severe lymphedema, massage of the collateral pathways may remain an important component of MLD. When examining the effect of MLD
on volume changes in patients with moderate to severe unilateral BCRL, Sitzia et al. performed MLD commencing with
the neck, subclavian areas and both axilla and concluded that
MLD was effective for reducing excess limb volume [29].
However, Sitzia et al. also showed that when MLD was compared with a simplified version of lymphatic drainage, the
between group differences in volume reduction were not significant (p = 0.34). Despite this, calculation of the effect size
for the between groups differences in treatment effect revealed
a moderate effect in favour of MLD (SMD = 0.58). The authors concluded that the failure of the between group differences to reach significance may be due to the low participant
numbers (n = 27) and recommended that the study should
therefore be replicated on a larger scale. The duration of each
MLD session in this study was 40 to 80 min. Williams et al.
also described stimulation of the contralateral pathways with
MLD applied to the neck, and anterior and posterior trunk,
with the aim of moving fluid to the unaffected side of the body
in patients with moderate to severe BCRL [31]. Each session
was 45 min in duration and resulted in significant reduction in
excess limb volume, pain and heaviness. When MLD was
compared with self-MLD, there was a trend towards a significance difference in volume reduction between groups (p =
0.053), and calculation of the effect size revealed a small effect in favour of MLD (SMD = 0.27). Together, the outcomes
of these studies suggest that in patients with moderate to severe lymphedema, a longer session (> 40 min) of MLD with
massage to the collateral pathways may be beneficial.
Pressure applied during MLD is difficult to quantify, and
most of the included studies provided little or no description of
the pressure applied. Although one study reported pressure
applied by the hands of 30–45 mmHg, it is unclear how this
pressure was measured and therefore very difficult for therapists to replicate [28]. Traditionally, MLD is applied gently
and superficially [10, 38]. It has been suggested that MLD
applied too firmly will cause spasm in the surrounding smooth
muscle sheath of the superficial lymphatic vessels or damage
to the fine anchoring filaments [5]. Two studies reported using
a traditional method with a low or gentle pressure [24, 25]. It is
interesting to note that one of these studies reported greater
benefits from MLD in patients who had mild lymphedema
compared with patients who had moderate or severe lymphedema [25]. Although the other study to describe low pressure
MLD reported an inclusion criterion of > 10% volume difference between the affected and non-affected limbs, lymphedema severity was not reported. However, these authors also
reported positive effects of MLD on lymphedema volume
and symptom-related outcomes [24]. MLD under ICG lymphography shows that a slow firm MLD technique is required
to move the lymphatic fluid through areas of superficial dermal lymphatic congestion (dermal backflow) [37]. Therefore,
particularly in patients with more severe lymphedema, it may
be that a firmer and slower MLD technique will produce superior results. Odebiyi et al. describe a slow, deep massage
with the affected limb at a 45° angle to assist with drainage in
patients with ISL stage II and III lymphedema [26]. These
authors reported a significantly higher change in limb girth
together with improved QOL and fatigue scores when MLD
was combined with exercise compared with exercise alone.
Although the results from this study showed a large treatment
effect for reduction in limb girth in favour of MLD (SMD =
1.51), it should be noted that the measurement was only recorded for one site on the arm and so care should be taken
when interpreting these results. In contrast, in a high-quality
study, Gradalski et al. also described a slow deep massage in
patients with ISL stage II lymphedema and reported no
J Cancer Surviv
additional benefit of MLD when combined with CDT
(SMD = − 0.03) [22]. Although difficult to quantify, further
research examining the effect of various levels of speed and
pressure applied during MLD appears to be warranted.
Another difficulty in establishing the effect of MLD on
lymphedema outcomes is the presence of combined treatments. To separate the effect of MLD on lymphedema from
the other components of CDT, one low-quality and three highquality studies examined CDT with and without MLD. All
four studies reported no additional benefit of MLD in reducing
arm volume compared with CDT without MLD [19, 21, 22,
30]. No additional benefit of MLD was also reported for improving oedema-related QOL and treatment satisfaction [22]
or improving subjective symptoms related to lymphedema
[19, 21]. However, it should be noted that MLD in these
studies was only applied for two [19, 22] and 3 weeks [21,
30]. Therefore, it is not known whether MLD performed beyond the initial 3 weeks of CDT would provide additional
benefits. McNeely et al. reported the greatest reductions in
excess volume to occur during the first week of treatment with
compression bandaging with and without MLD, with a slower
reduction in excess volume occurring over the following
2 weeks, and a slightly greater reduction in excess volume in
the fourth week of treatment [25]. Furthermore, Yamamoto
et al. reported the largest volume reductions in patients with
upper extremity lymphedema to occur within the first 2 days
of commencing CDT with greatly reduced volume changes
occurring after day 3 of treatment [39]. Therefore, given the
expected decrease in improvements in volume over time with
CDT, it could be that MLD may need to be applied for a
longer timeframe than 2 to 3 weeks for the benefit of MLD
in addition to CDT to become apparent. However, this notion
requires further research with long-term follow-up.
As lymphedema is a chronic condition, the effectiveness of
MLD interventions beyond the post-intervention period also
needs to be established. As only two studies provided followup beyond the post-intervention period at 6 months [22] and
7 months [30] in patients with moderate to severe lymphedema, it is difficult to draw clear conclusions regarding the longterm effects of MLD on lymphedema outcomes. However,
both studies reported that improvements in volume reductions
in response to two [22] and three [30] weeks of CDT with and
without MLD remained at follow-up; however, no differences
between groups with small to trivial effect sizes were observed. Similarly, as the risk for BCRL has been reported to
peak between 12 and 30 months postoperatively [40], the
success of MLD interventions in preventing lymphedema also
needs to be established beyond the post-intervention period.
Only two studies (with the same participants) examined the
long-term effect of MLD on the incidence of lymphedema in
patients at-risk for BCRL. These authors reported comparable
incidence rates between groups at 12 months [33] and
60 months [34] following 20 weeks (2 sessions per week) of
education and exercise with and without the addition of MLD.
Although these studies highlight the positive effect of CDT on
excess limb volume for patients with moderate to severe
lymphedema, and exercise therapies for patients at-risk for
BCRL, it appears that the addition of MLD to these modalities
did not provide any additional benefit over the long-term.
In a cross-over study design, a trial with high quality investigated the effect of MLD compared with LFLIE on arm volume in patients with chronic BCRL [20]. The patients in this
study had previously completed the intensive phase of CDT
and had been in the maintenance phase of therapy (compression garment, exercise and skin care) for a minimum of
12 months. Interestingly, the authors reported no significant
volume reductions in response to either treatment; however, in
their results table, a paired t-test comparing pre- and posttreatment means for volume showed a significant treatment
effect for MLD (p = 0.048). It is unclear why this has been
reported by the authors as non-significant and it is not
discussed any further in the manuscript. However, when the
treatment effect of MLD was compared with the treatment
effect of LFLIE, the differences were not significant (p =
0.608), and the effect size was trivial (SMD = 0.12).
Additionally, although the authors observed significant reductions in pain, heaviness and tightness with LFLIE but not with
MLD, no significant differences between the groups were
reported for all outcomes except for pain. As the interventions
in this study were only delivered in 10 sessions over 2 weeks
in patients with chronic BCRL, and the patients had completed CDT and were in the maintenance phase of treatment, it is
expected that large volume reductions in response to either
intervention would be unlikely. In contrast, in a pilot trial,
Ridner et al. reported MLD combined with compression bandaging to be as effective with comparable moderate effect
sizes as LLLT combined with compression bandaging for
reducing arm volume and symptom burden in patients with
ISL stage I or II BCRL [27]. However, as there was no control
group that received compression bandaging alone, the authors
acknowledge that it is possible that the reductions in volume
may have been largely due to the compression bandaging.
Only one of the included studies compared compression
bandaging with and without the addition of MLD [25]. In this
high-quality study, the authors reported significant volume
reductions in both groups with no significant differences and
trivial effect between groups. However, when allowing for
lymphedema severity, significantly greater relative volume
reductions were observed for patients with mild lymphedema
who received MLD compared with all other sub-groups [25].
The authors suggested that this may be partly due to patients
with mild lymphedema having better functioning lymphatics
which allows MLD to work more effectively in stimulating
lymphatic flow and in forming collateral drainage routes.
However, the presence of collateral drainage routes and lymphatic flow was not investigated in this study. With new
J Cancer Surviv
imaging technologies emerging, such as ICG, research examining the effect of MLD on the formation of collateral pathways and lymphatic flow may provide further insight into the
mechanisms behind the therapeutic effect of MLD on lymphedema outcomes.
A further difficulty in establishing the effectiveness of MLD
on lymphedema outcomes is that there is no accepted definition
for lymphedema with regard to girth and volume measures and
no set standards for measuring changes in girth or volume.
Although water displacement volumetry is often recognized
as the gold standard for measuring limb volume [41, 42], only
six of the 17 included studies (35%) used water displacement
volumetry to assess volume changes [20, 24, 30, 33–35].
Furthermore, this method is not suitable for patients with skin
ulcers, limited shoulder range of motion or in the immediate
post-operative period [43]. It is also time-consuming to fill,
clean and empty the volumeter; several litres of water are required; and it can be difficult to move the volumeter when filled
[41]. Therefore, estimation of limb volume using circumferential measurements is widely used in both research and clinical
practice. Nine of the 17 included studies (53%) calculated limb
volume from circumferential measurements [19–22, 25, 27, 29,
31, 32]; however, three different formulas were used. Previous
research investigating the use of geometric volume formulae to
calculate limb volume from circumferential measurements
compared with water displacement reports the truncated cone
formula to be most accurate [42, 44, 45]. The majority of studies included in this review that calculated volume using circumferential measurements (67%) reported using the truncated cone
formula [20–22, 25, 29, 32]. Therefore, to standardize limb
volume measurements in future research, we recommend that
at a minimum, the truncated cone formula be used with measurements taken at a maximum of 4 cm intervals. An earlier
review on MLD for the treatment of BCRL emphasized the
need for the development and validation of sensitive testing
instruments such as BIS and tissue dielectric constant for the
detection of early changes in subcutaneous tissue fluid [8].
Despite this recommendation and the development of new technologies, only one of the included studies assessed volume
changes using BIS measurements [27]. Future research should
focus on validation of these newer technologies to further our
understanding of extracellular fluid changes following treatments for lymphedema. Additionally, only one of the included
studies calculated effect sizes for change in limb volume from
pre- to post-treatment to assess the magnitude of treatment effect [27]. Most of the included studies reported significant reductions in limb volume in response to treatment; however,
there was little indication of whether the reductions in volume
or differences in treatment effect between modalities were considered clinically meaningful. Future research should also include a definition of, and discussion surrounding, clinically
meaningful volume reductions to better inform the effectiveness of lymphedema treatment modalities.
Although the current review sought to include all types of
lymphedema, only RCTs investigating the effect of MLD on
patients with breast cancer were identified and included.
Therefore, the findings of this review may be biased towards
BCRL and cannot necessarily be generalized to other groups
of patients such as those with primary lymphedema or secondary lymphedema of the breast, torso or leg. Further RCTs are
required that include patients with other forms of lymphedema
to be able to make recommendations regarding MLD as a
treatment for patients with lymphedema not related to breast
cancer treatment.
Conclusion
This systematic review highlights the limited high-quality research investigating the effect of MLD on outcomes in patients at-risk of or living with lymphedema. Although we did
not seek to restrict our search to patients with BCRL, this was
the only patient group investigated in the included studies.
Due to the many different study designs, it is difficult to draw
clear conclusions regarding the effect of MLD on BCRL.
Additionally, poor description of methods of MLD, combining MLD with other treatments and lack of control groups,
adds to the ambiguity surrounding the benefits of MLD on
lymphedema outcomes.
There is some evidence from low-quality studies that MLD
in the early stages following surgery for breast cancer may
help prevent progression to clinical lymphedema and that
using a modified technique that focuses on the affected side
of the body may be beneficial. However, evidence from highquality studies suggests that there is no further benefit of MLD
beyond education combined with exercise therapy in reducing
lymphedema incidence over the long-term. There is some evidence from a high-quality study that MLD provides additional benefits in volume reduction above compression bandaging
for patients with mild lymphedema but not for patients with
moderate to severe lymphedema. In addition, there is evidence
from low- and high-quality studies that MLD as part of a CDT
program does not provide any additional benefit over CDT
without MLD when applied for 2–3 weeks in patients with
moderate to severe lymphedema. Furthermore, the current evidence does not support the addition of 2–3 weeks of MLD to
a CDT program for achieving long-term benefits; however, it
is not known whether MLD provided over a longer treatment
period would produce different results. The level of pressure,
speed and technique required during MLD also needs further
investigation.
To improve the quality of future MLD research, we recommend authors to provide a detailed description of the method
of MLD, including information regarding speed, pressure and
drainage direction and destination, as well as time spent on
MLD. Additionally, the use of standardized assessment
J Cancer Surviv
methods is also recommended. At a minimum, we recommend that segmental circumferential measurements with a
maximum of 4-cm increments be used with the truncated cone
formula to calculate limb volume and that clinically meaningful volume changes are defined and discussed. Further research of MLD in lymphedema is warranted in validating
newer technologies for the assessment of lymphedema as well
as understanding whether MLD assists with the formation of
collateral pathways and increased lymphatic flow. Finally,
further research should incorporate other forms of lymphedema, and not focus solely on BCRL.
Authors’ contributions All authors contributed to the conception and
design of the systematic review. The literature search, data extraction
and data synthesis were performed by Belinda Thompson and Katrina
Gaitatzis. The first draft of the manuscript was written by Belinda
Thompson, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Data availability All data generated for this review are included in the
manuscript and/or the supplementary files.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
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