Lymphedema Laser Therapy Inches Closer to Clinical Utility

Low Level Laser Therapy (LLLT), also known as Photobiomodulation (PBM) therapy, has been investigated as a treatment for a very wide variety of conditions including musculoskeletal disorders, wound healing, and more recently lymphedema. Could lymphedema laser therapy offer real-world benefit to patients?

Despite decades of research and use, the clinical evidence supporting laser therapy is a mixed bag. This is primarily because:

1. There is little uniformity between clinical studies with respect to critical laser parameters (wavelength, energy density, number and location of treated points, and frequency and duration of treatment) which makes it difficult to compare results between studies.
2. Clinical studies are predominately small and poorly designed which makes it difficult to draw conclusions about efficacy, especially in light of #1 above.
3. There is a lack of clear understanding about how lasers might work to benefit cells and tissues which makes it more difficult to design, interpret, and trust clinical studies.

Thankfully, the state of laser therapy research is changing. The World Association for Laser Therapy (WALT) is promoting better research, and gradually more robust conclusions about laser therapy are being made. There are some clinical indications, such as short-term orthopaedic pain management, where data supporting the benefits of laser therapy is fairly strong.

Even though the available clinical data is largely insufficient to draw strong conclusions about its clinical utility, laser therapy continues to be used in the orthopaedic rehab setting. This is not surprising since the modality has few side effects, is relatively affordable, may offer at least temporary pain relief, and carries with it a certain ‘cachet’ with some patients. This also means that there is money being made both selling and using lasers, and so any discussion of laser and its merits can become entangled with financial interests. This is by no means exclusive to laser therapy, but it’s a good general point of caution for patients seeking out information about this modality.

Laser therapy for lymphedema – new data

In our 2013 review of the available data we concluded from our real-world clinical perspective that laser therapy as a treatment for lymphedema just isn’t justified. But I’m a bit of a self-confessed technophile, and so when a new lymphedema laser therapy systematic review appeared in my inbox I got a little excited – and for good reason: the authors of this latest paper conclude (ref 1):

“Based upon the current systematic review, LLLT (PBM) may be considered an effective treatment approach for women with BCRL.”

This sounds exciting. Of course, the authors do qualify this statement by saying that since their conclusion is drawn from a small number of clinical trials, there is a need for more and well-designed trials before we can be certain of its efficacy. From a real-world clinical application standpoint, they also point out that optimal treatment parameters have yet to be elucidated.

Putting these authors’ endorsement aside, has anything changed since we last reviewed the scientific literature that would make us change our minds about using it? A little. This new review primarily re-evaluates data that was previously reviewed by others, and that was mostly available to us when we did our own in-house examination a few years ago.  However, the cumulative data now provides a stronger argument that laser therapy has a beneficial effect on patients with breast cancer related lymphedema. So should it now be adopted in the clinical setting? Let’s dig in:

Lymphedema laser therapy appears to be more effective than ‘sham’ treatment

Based on three studies of breast cancer related lymphedema that were deemed “high quality” by the researchers of this latest systematic review, the authors drew the conclusion that Low Level Laser Therapy was more effective than sham treatment (fake treatment where the laser is made to appear to be working, but really isn’t) in reducing limb circumference in patients with BCRL, in the short term. The studies followed patients for one month after their treatment regimen completed, so conclusions can’t be made regarding potential longer-term benefit. One of these three studies also offered support to the possibility that laser could decrease pain in the short term – which makes sense given what we already know about laser – and two of the three studies supported a possible role for laser in improving arm range of motion.

Figure 1: Example of a Low Level Laser Therapy device (a) and application to the forearm (b). Figure modified from ref 1.

This looks both interesting and promising, but how do these results translate to the real world of patient care? Three concerns come to mind when considering the real world clinical utility of laser for lymphedema:

Real-world clinical concern #1

Laser therapy appears to be better than doing nothing, but that doesn’t mean it will add clinical value.

The clinical trials investigated in this recent review compared laser therapy to a control group of lymphedema patients that received sham (fake) laser. They did not compare laser against the gold standard treatment for lymphedema (Combined Decongestive Therapy, or ‘CDT’), nor did they evaluate laser in addition to CDT.

CDT is an effective treatment, and since laser does not appear to be better than conventional treatment (see below), there is no justification to replace current gold-standard practice with laser therapy. So, the obvious question is: will adding laser therapy to CDT improve patient outcomes over CDT alone? Unfortunately, we don’t have any data to answer this question, and it’s relatively common for a rehabilitation tool or technique to show benefit on its own, but to offer no additional benefit when added to the current standard of care.

Real-world Clinical concern #2

Laser therapy is not better than conventional treatments

The authors of this latest systematic review identified three other ‘high quality’ clinical trials that compared lymphedema laser therapy against conventional treatments for lymphedema, and combined these with results from a handful of lesser-quality studies. The data is conflicting and nuanced, and probably unnecessary to go into in detail here. Suffice it to say that the reviewers concluded that laser therapy for lymphedema is “not more effective than other conventional treatments”.

Real-world clinical concern #3

A considerable amount of treatment is required before a positive effect is observed

The largest and best designed of the three trials showed significant reductions in arm volume in only 1/3 of patients, and only after 18 treatments (but not 9 treatments). These treatments were delivered in 17-minute sessions performed 3 times per week. The second largest of the trials showed significant swelling reduction in 93% of participants after 24 treatments (but not 12) delivered in 20-minute sessions 3 times per week. The third trial looked at 18 treatments, but was a very small trial with some study limitations, and had inconclusive results.

Will we be using laser therapy to treat lymphedema patients in our clinics?

Not yet, but it’s looking more promising and we might do so in the future.

Why we don’t currently use lymphedema laser therapy:

1. Not currently shown to be better than current standard of care (CDT). Therefore, we should not use it in place of CDT.
2. Currently no evidence that it will improve patient symptoms when used in conjunction (as an ‘adjuvant’) with CDT. Therefore, we should only consider using it in conjunction with CDT if it doesn’t cost patients in terms of time and resources, and can be provided without sacrificing other evidence-based therapy. But this doesn’t appear to be the case:
3. The benefit of laser appears to require a considerable investment of time and resources – which looks to be perhaps 20 minute sessions 3x per week for 6 weeks. Patient time and financial resources are finite, and in our experience, many patients do not exhaust existing options for evidence-based symptom management, such as more frequent sessions with a CDT therapist, or better self-management through self-massage, self-compression and exercise.
4. Optimal Laser parameters for treating lymphedema are not clear (wavelength, energy density, size of the area, number of treatment points, frequency and duration, etc), and treatment efficacy will depend entirely on finding the right parameters. There are also scientifically-questionable therapeutic lasers for sale, such as lasers that function at wavelengths or energy densities that we would expect to poorly penetrate tissues, or that claim (incorrectly) to replicate the benefits of laser using inexpensive LEDs. Could there be a set of ideal laser parameters that truly unlocks a unique clinical benefit for lymphedema patients? Hopefully. Will using incorrect laser parameters still offer some benefit to patients? Not likely.
5. Proposed biological mechanism of action is unclear. If laser therapy was exceptionally effective at reducing lymphatic swelling then it wouldn’t bother me so much that it’s not clear as to how it’s supposed to work. But when you’ve got a novel therapy that shows only a modest benefit you should ask yourself if the observed benefit is truly real, or, could instead be an artifact of clinical trial design. Since there is no clear biological mechanism of action for how laser might benefit lymphedema patients, and because the positive effect is at best a modest one, we need to be skeptical of the data. There are some interesting hypotheses though. Scientists studying cells in the lab have observed laser stimulation to hijack cell function (likely via reactions that occur within the cell’s mitochondria) and promote cell behavior associated with new lymphatic vessel growth, lymphatic motility and decreased inflammation (among a whole host of other things). This is tantalizing, but having myself spent a LOT of time working with cells in a lab, I know first-hand that cells can respond very differently to stimuli when pulled from their complex three-dimensional home inside the body, and instead grown on a plastic surface in a lab. Plus, let’s assume that laser can activate these outwardly beneficial cell changes in real patients – should we expect these cellular changes to decrease patient symptoms? There is a drug called Ubenimex that appears to decrease inflammation and promote lymphatic vessel growth in animal models, but it’s potential benefit for humans remains in question.

Why we might still consider laser in the future:

1. It looks like it might have a real clinical effect, and so as an addition to the tried-and-true CDT approach, it might provide benefit. Or perhaps lymphedema laser therapy will offer unique benefit to a subsection of patients, limited perhaps to those with a specific state of disease progression. Hopefully new data will be published to guide us here.
2. Proposed mechanism of action is becoming more plausible. There is growing biological rationale for why it might be effective, which gives me more hope that it will become a clinically beneficial tool.

You may think we are being unfair to laser

Are we holding lymphedema laser therapy to a higher standard (from a clinical evidence perspective) than other tools / techniques / advice that we dispense daily in our clinics? Yes. But that doesn’t mean that we are unjustified in doing so, nor does this mean that we are biased against laser therapy. To the contrary, it would be advantageous for us to use laser therapy for lymphedema in our clinics.

If a tool / technique / advice has a plausible biological rationale for why it might benefit a patient, does the patient no harm, and can be offered to the patient in a way that is not at the expense of another known effective treatment, then we should use it.

Some of the less rigorously validated things we do in our clinics fit this bill, but laser does not. If a patient has an extra 20 minutes available 3 times per week and wishes to have additional therapy, we have a much stronger rationale for offering them additional CDT/lymphatic drainage during this extra time rather than introducing laser therapy. Alternatively, encouraging the patient to exercise 3 times per week for 20 minutes (if they are not already doing so) could also provide meaningful benefit for their lymphedema symptoms and their general health and wellness.

We want to find more ways to help our patients, so it would be great if we could justify the use of laser therapy for lymphedema, but so far we can’t. Hopefully one day soon we will be able to.

References

1. Baxter GD, Liu L, Petrich S, et al. Low level laser therapy (Photobiomodulation therapy) for breast cancer-related lymphedema: a systematic review. BMC Cancer. 2017 Dec 7;17(1):833.