Regional Lymph-Node Surgery Does Not Improve Skin Cancer Survival

The benefits of sentinel lymph node biopsy in treating skin cancer (melanoma) is well established; however, the value of lymph-node dissection, a procedure in which all nodes located nearby metastasis-positive sentinel nodes are surgically removed, remains controversial. Recently, a phase III clinical trial demonstrated that immediate completion lymph-node dissection is not associated with increased melanoma-specific survival, although the procedure seems to confer better control over disease-progression at the expense of higher co-morbidities.

At a certain stage of disease progression, melanoma, or skin cancer, can form metastases that initially spread through nearby lymph nodes, referred to as sentinel nodes. For this reason, melanoma patients with clinical characteristics that suggest the primary tumor may have metastasized usually undergo a two-step procedure to 1) confirm whether or not the primary has the potential of spreading to a sentinel node and 2) surgically remove the sentinel node if it may indeed have been colonized by cancer cells and analyze the biopsy to infirm the presence of malignancy.

Melanoma patients diagnosed with metastasis-positive sentinel nodes are then usually recommended to undergo a procedure called immediate completion lymph-node dissection in which all nearby-located lymph nodes, called regional nodes, are surgically removed to prevent further metastases. However, the value of this procedure remains controversial as there is limited evidence to support its effectiveness and because the procedure increases the risks of several comorbidities including lymphedema.

Fortunately, a phase III randomized clinical trial resulting from a collaboration of several institutions located worldwide was recently performed to address this issue. The results were published in the prestigious New England Journal of Medicine. A total of 1939 patients between 18 and 75 years of age were randomized in a 1:1 ratio to an observation (i.e. regular office visits to monitor regional nodes state) or dissection group. After exclusion criteria were applied, data from 824 and 931 patients were analyzed for the dissection and observation groups, respectively. Patients in both groups were monitored every four months for the first two years, every three months between the third and fifth years and then annually. The primary outcome studied was melanoma-specific survival over 10 years and secondary outcomes included disease-free survival and the cumulative-rate of nonsentinel-node metastasis.

Overall, the data suggests that node dissection is not associated with better survival after three years (86% survival rate in both groups). However, disease-free survival and nodal-recurrence free survival rates were significantly higher for the dissection groups (P = 0.02 & P < 0.001, respectively), suggesting that although the procedure did not impart increased survival, it allowed patients to gain a better control over the progression of the disease. However, these benefits appear to come at the cost of adverse effects related to the procedure. In fact, lymphedema, a condition characterized by the localized swelling of a tissue following blockade of lymph flow, was four times more frequent among patients who underwent dissection. Thus, taken together, these results show that immediate completion lymph-node dissection does not impart better survival among melanoma-patients, but results in better disease control, at the expense of comorbidities such as lymphedema. To assess whether these comorbidities outweigh the benefits associated with better disease control as well as the economic costs related to the procedure, other health economics and outcome studies as well as patients’ quality of life assessments appear necessary.

Written By: Samuel Rochette, M.Sc