What is my risk of lymphedema after melanoma, and can I decrease it?

Lymphedema is a common complication of lymphadenectomy (lymph node removal), a routine practice used for cancer staging and the treatment of a variety of cancer types including melanoma. But not everyone who has lymph nodes removed gets lymphedema, and the incidence of lymphedema differs between cancer types. So what is my risk of getting lymphedema after melanoma treatment, and how can I decrease this risk?

Lymphedema in melanoma patients vs breast cancer patients

The majority of online information and clinical research on lymphedema focuses on breast cancer patients. This may give other cancer patients the impression that lymphedema is a special complication of breast cancer treatment only. So how does lymphedema risk in melanoma compare with breast cancer?

Authors of a new paper published last month explored this very question (ref1). They compared the risk of lymphedema following sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND), in a population of breast cancer patients and upper-extremity melanoma patients. Their conclusion? Of the 205 breast cancer patients, 36.5% developed lymphedema, while 35% of 144 melanoma patients developed lymphedema. But when the authors did a statistical analysis that controlled for confounding variables, the risk of lymphedema in melanoma patients was found to be roughly half of that observed for breast cancer patients undergoing identical lymph node procedures.

While their study suffers from a number of limitations (not the least of which was observing patients only as late as 18 months post-surgery), it suggests that the incidence of lymphedema in breast cancer and melanoma cancer patients differs considerably despite identical lymph node procedures. This highlights a significant role for other non-surgical factors in the development of lymphedema.

So what additional factors might modify a patient’s risk of developing lymphedema? In the author’s multivariate analysis, three additional factors appeared to increase the risk of lymphedema: high body mass index (>30), longer time since surgery (not surprisingly), and number of lymph nodes removed (although they found this increased risk marginally). The patients’ age did not appear to influence risk. Although they offered no data to support it, the authors suggested that breast cancer patients may have twice the risk of lymphedema as compared to melanoma patients due to other treatments they may receive including radiation therapy, which is typically less common and less extensive in melanoma patients. All the risk factors they identified and a number of others have been found to be risk factors in previous studies of breast cancer related lymphedema (see our posts on genetic predisposition for secondary lymphedema, lymphedema risks from cancer treatment, chemotherapy and lymphedema, and obesity-related lymphedema).

Are there lymphedema risk factors unique to melanoma patients?

Compared to breast cancer patients, melanoma patients typically present at a later stage of their disease process, undergo more extensive lymph node dissection surgery, receive fewer adjuvant therapies like radiation, and in the case of lower extremity melanoma, undergo inguinal (groin) lymph node dissection (ILND) instead of ALND. As a result of these differences, the list of factors that increase a patient’s risk of lymphedema likely differs between breast cancer patients and melanoma patients. Indeed, as we saw above, even when we compare identical lymph node surgeries, the risk of lymphedema between breast cancer and melanoma patients differed considerably.

All that we have learned about lymphedema risk factors in breast cancer patients may not apply to melanoma patients, and additional risk factors unique to melanoma patients surely exist.

What are they?

Another new study in press by a different group sheds further light on lymphedema risk factors specific to melanoma. In particular, the authors examined the difference in lymphedema risk between ALND (for upper extremity melanoma), and ILND (for lower extremity melanoma) (ref2). In their study of 269 patients who underwent lymphadenectomy at their centre, 20.8% developed lymphedema overall. The authors found that both ALND and ILND surgical procedures increased the risk of developing lymphedema, but ILND was a much greater determinant of risk. Whereas 32.1% of patients who underwent ILND developed lymphedema, only 10.9% of ALND patients did so. These rates are in line with at least one previous study (ref3).

Interestingly (but perhaps not surprisingly), the presence of peripheral vascular disease (PVD) was also a very significant lymphedema risk factor. The authors observed that peripheral vascular disease doubles the risk of lymphedema in patients who underwent ILND and triples it in patients who underwent ALND. So the incidence of lymphedema in ALND rose from 10.5% in patients without PVD to 31.9% with, and from 32.1% in ILND patients without PVD to 63.9% with.

The authors also examined the role of body mass in risk determination, and found that it “approached” statistical significance (meaning that it was close to passing the statistical test of significance used, but didn’t quite do so). So unlike numerous other studies, the authors of this study couldn’t conclude that a higher BMI increases lymphedema risk melanoma patients. Furthermore, the authors found no relationship between lymphedema and patient age, previous same-limb operations including sentinel lymph node biopsy, number of nodes removed, or use of radiation therapy or other postoperative adjuvant treatment.

Summary of lymphedema risk factors specific to melanoma patients:

The studies examined above are single-center studies, and each had their limitations, so broad strokes should be applied when interpreting their results. However, some tentative conclusions can be drawn:

Factors that likely increase the risk of lymphedema after melanoma:

1. Presence of peripheral vascular disease.
2. Type of lymphadenectomy (SLND / ALND / ILND)
   • Greater risk for ILND than ALND
   • Greater risk for ALND than SLND
3. High body mass index. This was found to be a factor or nearly a factor in both studies, and there is significant support in the literature relating body mass with lymphedema risk. Furthermore, high BMI is a lymphedema risk factor even in the absence of cancer.
4. Number of lymph nodes removed. But this may only marginally increase risk. The first study suggested that risk increases 5% for each additional node removed, but the second study did not agree. Number of lymph nodes removed is believed to play a more significant role in breast cancer-related lymphedema, than melanoma-related lymphedema.

Factors that likely don’t significantly increase the risk of lymphedema after melanoma:

1. Patient age.
2. Previous same-limb operations.
3. Use of radiation and post-operative adjuvant treatments (including interferon and other immunotherapies). However, radiation therapy is a known risk factor for lymphedema in breast cancer patients, and is likely to add some risk here as well. A link between radiation therapy and lymphedema may have been masked in the above study by the relatively small number of patients who underwent radiation. Radiation therapy is not as frequently used or as effective as a treatment for melanoma.
4. Severe post-operative complications including infection and blood loss.

So what should I do/not do, as a melanoma patient, to modify my personal risk of lymphedema?

1. Be diligent in managing any peripheral vascular disease.
2. If you have a high BMI (at least 30 or above), ask your physician to help you devise a weight-loss strategy.
3. Do not avoid recommended cancer treatment procedures for fear of developing lymphedema. This includes limiting the number of lymph nodes dissected, or forgoing post-operative treatments. Discuss your fears with your physician.

References

1. Voss R.K., Cromwell K.D., Chiang Y.J., et al. The long-term risk of upper-extremity lymphedema is two-fold higher in breast cancer patients than in melanoma patients. J Surg Oncol. 2015 Oct 18. [Epub ahead of print].
2. Friedman J.F., Sunkara B., Jehnsen J.S., et al. Risk factors associated with lymphedema after lymph node dissection in melanoma patients. Am J Surg. 2015 Sep 28. [Epub ahead of print].
3. Faries M.B., Thompson J.F., Cochran A., et al. The impact on morbidity and length of stay of early versus delayed complete lymphandectomy in melanoma: results of the Multicenter Selective Lymphandectomy Trial (I). Ann Surg Oncol. 2010; 17:3324-9.