Efficacy of Lymphedema Treatment Protocols

Comments on Technology Assessment "Diagnosis and Treatment of Secondary Lymphedema".
Robert Weiss, MS, Lymphedema Patient Advocate

General Observations

• The treatment of lymphedema is a multimodal, multi-phase therapy which comprises manual lymph drainage to reduce swelling by stimulating the lymphatics, compression to prevent re-swelling, exercise with compression to facilitate decongestion and skin care to maintain skin integrity. Any attempt to select one modality to the exclusion of the others will result in a partial and ineffective treatment for this chronic, ever changing, and progressive medical condition.
• Current Medicare coverage fails the lymphedema patient because it does not cover compression therapy, places fixed limits on the intensive phase treatment and has no requirements on the competency of the therapists providing therapy services. Many of the necessary treatment elements are not addressed or billable, such as measurement, compression bandaging, patient instruction, garment measurement and fitting. Pumps are covered for treatment of lymphedema but criteria for coverage are not coordinated with the primary lymphedema treatment services and results. The generalized criteria for selection of lymphedema pumps often downgrade the pumps to provide a medically incorrect type of pump.
• Any assessment of the efficacy of the protocols for lymphedema treatment must consider the natural history of the lymphedema and the required combination of protocols for any given patient at given time. Assessment of published clinical trials must take into account the characteristics of the trial cohort and the stage, extent and nature of their lymphedema before any conclusions can be made as to the efficacy of any treatment protocol, and the measured efficacy cannot be extended to other populations or disease stages.
• Selection of the proper combination of treatment protocols for the treatment of an individual patient is the responsibility of the treating physician and trained therapist on the basis of the patient's medical needs at the moment. Medicare must provide a selection of covered protocols shown to be effective in treating some subset of lymphedema stages, types, body sites, etiology, duration, co-conditions, etc.
• There is no evidence that treatment protocols for primary and secondary lymphedema are different, and so excluding trials that may have contained mixed cohorts may not be appropriate, and may result in discarding valuable evidence of the efficacy of treating any lymphedema. On the contrary, recent research seems to be leading to the idea that genetic differences determine the inherent susceptibility to lymphedema, and some "secondary" cases may actually be "primary" (genetically susceptible because of a marginally functional lymphatic system) with a precipitating trauma or event causing it to be classified as "secondary" [Rockson 2008, Stanton 2009]. Clinical studies on diagnosed breast cancer patients purport to be able to determine, prior to breast surgery and radiation, which patient will develop lymphedema [Campisi 2002] based on pre-surgical lymphatic transport measurements.
• Early detection of lymphatic changes and early intervention is being shown to prevent fibro-sclerotic tissue changes and infections that are responsible for the progression of lymphedema. There is no current Medicare coverage for the early detection of pre-clinical lymphedema or for its preventive treatment, in spite of the preventive potential.

The Many Faces of Lymphedema

• There is no best treatment modality because of the variety of lymphatic presentations, affected sites and the temporal evolution of the condition. What is "best" today for a given patient may not be "best" as the condition either worsens or improves. Nor is a single selected modality or treatment appropriate for the heterogeneous population of lymphedema patients.
  
  "The question arises, has Evidence Based Medicine (EBM) got a role to play in lymphoedema treatment? It probably has but with the acknowledgement that EBM generally deals with group response and then generally with the quantitative aspects of it. Lymphoedema is multi-faceted, each patient is strongly unique in the presentation and often in the combination of symptoms and associated sequelae, each patient responds to an intervention differently and each has different treatment and management preferences either forced on them by finances or the availability of treating staff. Often then there is a gulf between what might be able to be done optimally and what can be done in reality." [Manual Lymphatic Drainage – an effective treatment for lymphoedemas By Neil B Piller and Jan Douglass, ca. 2003]
• There is an infinite variety of lymphedema manifestations as functions of:
  Affected body site(s)
  Amount of swelling
  Patency of lymphatic network
  Tissue fibrosis
  Lymphangion autonomous functionality
  Skin integrity
  Skin elasticity
  Patency and functionality of venous system
  Co-morbidities
• Lymphedema patient individuality forces the treating physician to perform a differential diagnosis before determining treatment modalities. It also requires the evidence analyst to be careful to determine whether there is patient bias in a given study, whether the intervention is being applied to the correct lymphedema patient subset and whether the conclusions are extrapolatable to a general population. Given this variability between patients, it may be prudent for the analyst to highlight the characteristics of the trial cohort for which favorable results accrued and allow the physician and lymphedema therapist, familiar with the patient's lymphedema etiology, co-morbidities and specific health status, to prescribe the combination of protocols most likely to have a positive outcome for the specific patient.
• For example, in a recent study by Olszewski, the patient population comprised Stage 3 lower limb lymphedema patients with "obliterated lymphatics". Fluid flow in this case is not through a patent network of lymphangions and nodes, but through the affected limb tissue space. The study concluded that MLD was ineffective, and that a sequential pump was designed to emulate MLD in stimulating lymphangion contractions was ineffective. These results are hardly applicable to the lymphedema of a recent breast cancer survivor. Reviewers must be very careful that the patient population involves lymphedema, and not venous insufficiency, lipedema, myxedema, or other causes of swollen limbs.
• As another example of how differences in individual patient conditions have a great effect on the effectiveness of a given modality arises in the randomized study of the effectiveness of MLD when added to compression bandaging [McNeely 2004]. A sub-analysis of the trial data showed that the MLD was effective in patients with early stage lymphedema whereas it was not effective in longer-standing cases. The author postulated that in the "early" lymphedema the lymphangions were still functional and were stimulated by MLD to increase lymphatic flow and establish collateral flow, whereas in the late chronic or severe cases the lymphatic system was more compromised and compression was the dominant mode of tissue fluid drainage. In these older chronic lymphedema cases the compression bandaging effects dominated in both arms of the trial, and the addition of MLD was not productive. This result is substantiated in Johansson 1999 in a cohort of recent breast cancer survivors.
• How differences in the nature of the lymphedema can affect the efficacy of a treatment modality can be found in François 1989 [François A, Richaud C, Bouchet JY, Franco A & Comet M: "Does medical treatment of lymphedema act by increasing lymph flow?" Vasa 1989;18(4):281-6]. In this paper François observes two MLD response groups among his lower limb cohort undergoing an 8-day trial of MLD, leg elevation and exercises while under double compression bandaging--those whose lymph flow responds immediately to MLD (n=16) and those whose lymph flow did not increase (n=9) in spite of a decrease in their leg edema. The author postulates that there must be another mechanism other than increased lymph flow, such as an increase in fluid resorption in the venous capillaries.
• There is no evidence that treatment protocols for primary and secondary lymphedema are different, and so excluding trials that may have contained mixed cohorts may not be appropriate, and may result in discarding valuable evidence of the efficacy of treating any lymphedema. Szuba 2000 concluded in his "Decongestive Lymphatic Therapy for Patients with Cancer-related or Primary Lymphedema":
  "The results of this investigation suggest that manual lymphatic therapy provides measurable therapeutic benefits in all subgroups of our lymphedema patients. Decongestive lymphatic therapy was effective both in the acute, intensive phase of limb volume reduction, when performed by trained therapists in the institutional setting, as well as in the maintenance phase, where it helped to promote effective self-management of edema." The cohort for this trial included patients with lymphedema after breast cancer (43), pelvic cancer (12), infection (2), injury (1), metastatic cancer (4) and primary lymphedema (16).

Technology Assessments and Systematic Reviews

• Technology assessments designed to determine whether one treatment modality is "better" than another may be significantly distorting the issue of whether Combined Decongestive Therapy (CDT) is effective in the treatment of lymphedema. CDT is a multimodal therapy recognized as the standard of lymphedema care. It makes no more sense asking the question "Is MLD better than exercise?" than to ask in the treatment of breast cancer "Is radiotherapy better than chemotherapy?" The selection of the modalities to treat lymphedema or breast cancer is the responsibility of the treating physician based on the individual patient's medical needs. It is not a decision to be made by Medicare. It could be that the conclusions of lack of effectiveness of MLD in some studies [Andersen 2000 and McNeely 2004] are only artifacts of the analytic goals or the questions asked.
  "In an attempt to reduce the oedema developing after mastectomy in 39 breast cancer patients, a number of physiotherapy techniques were applied in various combinations over 6 months. The techniques included massage, isometric exercises and an elastic sleeve. In the first week of the daily treatment a decrease of 11-13% in the volume of oedema was recorded, but in the next 3 weeks the benefit achieved declined sharply. To maintain the reduction in volume of the swollen arm, an elastic sleeve was applied. During the 4 weeks that the sleeve was worn there was no significant increase in volume. There was a correlation between an objective reduction in the volume of the arm and the patient's rating of the improvement." [Swedborg I: "Effectiveness of combined methods of physiotherapy for post-mastectomy lymphoedema" Scand J Rehabil Med. 1980;12(2):77-85.]
• There are many studies that have shown the effectiveness of MLD in reducing swelling [e.g. Moseley 2007, Sitzia 2002, Williams 2002, Zanolla 1984]. There are many studies that demonstrate the efficacy of compression garments [e.g. Andersen 2000, Badger 2000, Bertelli 1991, Johansson 1998]. And some studies show that the combination of these modalities may be better than each used singly [e.g. Johansson 1999, McNeely 2004]. Each therapeutic modality has a unique physiological action on the lymphedematous site, and their effects have different temporal effectiveness. For full and lasting treatment of lymphedema for a given patient, acombination of modalities is appropriate.
• A number of systematic reviews of lymphedema treatment protocols have been performed over the last decade. In essence, the conclusions of these systematic studies was that, although there is a paucity of high-level evidence, ALL of the considered physical therapy interventions (MLD, SLD, compression bandages, compression garments, decompression exercise) were effective in the treatment of lymphedema on some subset of the tested population.

Randomized Clinical Trials Document Efficacy of Treatment Protocols

The following randomized clinical trials RCTs have been accepted for review by one or another of the systematic reviews listed above. There is credible evidence to show that every manual modality can benefit some population subset. Shown on the following table are the lead author and date of the RCT, the systematic review which used the RCT, characteristics of the trial cohort, modalities employed, summary results in terms of edema reduction and comments on the length of the trial or follow-up.

* The review or systematic study which identified the RCT: C=CHBRP 2005; Erickson 2001; H=Hayes 2008; K=Kligman 2003; M= Megens 1998; T=Technology Assessment-McMasters;
** BCRL=breast cancer-related lymphedema; LLLE=lower-limb lymphedema; RC=recurrent cellulitis
*** CB=compression bandaging; CDT=complex decongestive therapy; CG=compression garment; CGE=compression garment plus exercise; DO=Deep Oscillation; E=exercise; ESLD=electrically-stimulated lymph drainage; HT=home therapy; IPC=intermittent pneumatic compression; MLD=manual lymph drainage; SM=simple massage; SP=standard physiotherapy; WR=weight reduction
† DLA=Dermatolymphangioadenitis; GLE=genital lymphedema; NS=not significant

Cohort Studies Show Efficacy of Combined Decongestive Therapy

• In view of the paucity of high-level evidence, we must rely on the vast number of cohort studies which demonstrate the efficacy of the multimodal protocol of CDT in the treatment of lymphedema [Boris 1997, Bunce 1994, Casley-Smith 1992, Ferrandez 1992, Földi 1989, Hamner 2007, Hinrichs 2004, Karadibak 2008, Ko 1998, Szuba 2000, Vignes 2006, Wozniewski 2001, Yamamoto 2007] Together these references document an almost 50% reduction of the volumes of the lymphedematous limbs of over 2,200 patients.
• In 1995 E. Földi commented in an editorial in Lymphology "Combined physiotherapy which we employ in the treatment of lymphedema is a tetrad phenomenon consisting of skin care, manual lymphedema treatment (MLT), remedial exercises and compression therapy. Compression is applied as long as edema prevails by circumferential wrapping or "bandaging" and, after the evacuation of edema fluid, by elastic stockings and sleeves. It is not my aim to comment on combined physiotherapy further. I wish only to stress that MLT performed as an isolated therapeutic application has little or no beneficial effect in the treatment of peripheral lymphedema."
• Bertelli comments [Bertelli 1991] on single modality treatments for lymphedema "Clearly, neither ESD nor the elastic sleeve are the definitive answer to the problem of post-mastectomy lymphedema: on the basis of this study and on our previous experience with ESD as single therapy, they can both be considered as moderately effective treatments which will benefit a given subset of patients. In the present study the combination of the two did not result in an increase of effectiveness. Wearing an elastic sleeve is a simple and economical treatment of post-mastectomy lymphedema: however, not all patients will be able or willing to use it with the same regularity as the women enrolled in this study. Such patients could benefit from ambulatory sessions of ESD or other treatments."

Value of Repeated Intensive Course of Treatment

• There are indications in some references of the additional value of a repeated intensive course of lymphedema after an initial course and many months of home maintenance treatment [Casley-Smith 1992]. Lifetime limitations of treatment of this chronic medical condition are not medically sound.

Prevention of Lymphedema

• A few randomized controlled trials addressed the question of whether early intervention can prevent or delay the development of lymphedema [Box 2002, Stout 2008]. Coupled with patient education in detecting early signs of lymphedema and arm volume measurement, these preliminary trials confirm that lymphedema can be prevented by early intervention with exercises or simple wearing of compression garments. The use of pre-operative and post-operative lymphoscintigraphy to detect lymphatic system deficiencies before appearance of swelling allowed the early intervention with CDT to prevent the appearance of clinical lymphedema [Campisi 2002].

Initiation and Termination of Lymphedema Treatment

• In view of the early indications that prevention of or retarding progression of lymphedema may be a highly beneficial medical strategy, the question of initiation and termination of treatment of this chronic and progressive medical condition may have lost its meaning. Lymphedema brings with it a heightened risk of infection, which in turn has been determined to worsen the lymphedema and make it more difficult to treat. The answer is to detect lymphedema in its pre-clinical stage in the at-risk patient population, and apply conservative preventive measures to prevent progression. This places the stress on developing more sensitive methods of detection than the "gold standard" of volumetry to enable earlier pre-clinical detection and early intervention.
• Termination of treatment is an interesting question when applied to a chronic disease. When do we terminate treatment of diabetes, or asthma, or congestive heart failure? The stated aim of lymphedema intense phase treatment is to reduce swelling to a plateau that can be maintained by the patient through home self-treatment. Part of the intense training phase is patient education on self bandaging, wearing and care of compression garments and devices, self-MLD or simple decongestion, use of an ancillary pneumatic sequential pump, skin care and awareness of infection. The required intense phase treatment plan, developed by the patient's therapist and treating physician, defines the treatment goals and the criteria for determining termination point. This is partly a function of when the patient is ready to assume self-treatment. Periodic evaluations and perhaps additional intense courses of treatment may be expected for refitting new garments, modifying treatment goals or protocols, and integration of home treatment with co-morbidities.

Lymphedema of the Head and Neck and Trunk

• Few randomized studies have been performed on the measurement or treatment of lymphedema of the breast, back, trunk and genitalia. Commonly used methods of lymphedema measurement for the limbs by measuring or calculating limb volume or limb circumference are not appropriate for measurement of lymphedema of the trunk, head, neck and genitalia. Other properties of the skin such as skin thickness or skin fluid content have been employed in a research setting, such as ultrasonic detection of skin thickness, MRI measurement of skin thickness and sub-facial structure, inference of fluid content from skin bioelectric impedance [Ward 2009] or tissue dielectric constant [Mayrovitz 2007]. It is unfortunate that in the studies of efficacy of treatment of lymphedema of the limbs, researchers seldom account for the displacement of lymphatic fluid from the limb to the adjacent body quadrant, where lymphedema may be created in areas it didn't exist before, and we have no way of measurement. This issue is addressed in Williams 2002.

Intermittent Sequential Pneumatic Pumps

• The efficacy of an intermittent pneumatic compression pump will be a strong function of not only the individual patient and lymphedema etiology, but on the construction and operational details of the device. [Mayrovitz HN: "Interface pressures produced by two different types of lymphedema therapy devices" Phys Ther. 2007;87:1379-88.] In view of the diversity of lymphedema etiology and presentation, and the diversity of pump configurations and operational principles, future studies of the efficacy of intermittent sequential pneumatic pumps must better select and describe the trial cohort and the pump details before conclusions can be made about the use and efficacy of pumps.
• Medicare coverage policy currently requires trial and failure of a simple pump before an appropriate segmental gradient pump will be covered in spite of ample evidence that the simple pumps are not effective for early stage lymphedema. [Bergan JJ, Sparks S, Angle N: "A comparison of compression pumps in the treatment of lymphedema"
  Vasc Surg.1998(32):455-62.] The generalized Medicare criteria for selection of lymphedema pumps often downgrade the pumps to provide a medically incorrect type of pump. It is important that the type of pump appropriate to treat a particular patient be determined by the prescribing physician and not determined by a non-medical Medicare Contractor clerk on the basis of an interpretation of a policy.

Lymphedema Treatment Provider Qualifications

• The provider of CDT lymphedema treatment must have training and experience in the specialized techniques of manual lymph drainage, compression bandaging, garment fitting and decongestive exercises. These are not generally a part of the curriculum for a Physical Therapist (PT) or an Occupational Therapist (OT) degree, nor is it a part of the testing for a license in these fields even though lymphedema treatment is within the scope of license of a licensed PT or OT. The Technology Assessment wisely notes the training of the physiotherapist in MLD for each RCT, for this is an important factor in evaluating the trial results. Medicare policies have no requirement on the provider of MLD and CDT except that they be licensed PTs or OTs. A training and competency requirement on therapists providing CDT might improve the efficacy of Medicare lymphedema treatment.

Summation

The conclusions of the Technology Assessment are in essential agreement with the others performed over the last decade. Although there is a lack of high-level evidence in support of the de facto lymphedema treatment protocol of complex decongestive therapy, this multi-modal multi-phasic treatment has been found to be effective in treating tens of thousands of patients in the U.S., Europe and Australia over the last 50 years. It is important for Medicare to cover a variety of measurement and treatment modalities and to allow the treating physicians and treating therapists to determine which combination of modalities are indicated for each patient, to arrive at a written plan of treatment and to select the appropriate measurements to measure progress against that plan.

December 7, 2009

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Lymphedema Treatment is Good Business as well as Good Medicine
© 2002 Robert Weiss, Porter Ranch, CA