By the time your patient visited the dermatologist, the dark spot on her back had grown to the size of a dime. She calls you, her long-term doctor, panicked by the biopsy results: melanoma.
As you talk her through the diagnosis and what to expect, certain things are clear. Her surgeons will cut out the melanoma and enough surrounding tissue to ensure safe, clean margins. But after this, the plans grow murkier. Should her surgeons go on to sample a nearby lymph node – the so-called sentinel node – and then, if that node is positive for microscopic signs of cancer, perform a complete lymph node dissection? Or would your patient be just as well served by an approach of watchful waiting, whereby lymph nodes would only be removed if they show clinical evidence of disease?
On one hand, it would seem that complete lymph node dissection could save your patient the risk of cancer spread later on. On the other hand, the procedure brings with it potential complications such as bleeding, infection and nerve damage. In theory, it would be ideal to only pursue complete lymph node dissection for patients with positive sentinel nodes as a way to maximize benefit while limiting harm. That approach makes intuitive sense, but does it work in practice?
This was the question that drove the Multicenter Selective Lymphadenectomy Trial (MSLT-1), which began in 1994, enrolling patients with melanoma and randomly assigning them to have the melanoma excised and then to undergo either sentinel node biopsy with removal of lymph nodes if positive or observation (and removal of lymph nodes if disease developed). Patients were further separated into three groups based on the depth of invasion of melanoma – thin melanoma, intermediate thickness, and thick.
In 2006, after following more than 1,000 patients for five years, investigators published their first study results. Overall, those with and without sentinel node biopsy actually had similar rates of survival due to melanoma. But in patients with an intermediate level of melanoma thickness – greater than 1.2 mm – and positive nodes, immediate dissection did yield a survival benefit.
The jury was still out, and the MSLT-1 investigators continued to collect data on their cohort of patients. In this week’s issue of NEJM, they publish results that follow these patients for 10 years. The authors show that patients with intermediate thickness of melanoma will live longer without recurrent disease if they undergo immediate lymph node dissection prompted by sentinel node biopsy.
Of note, the findings for patients with intermediate thickness melanoma didn’t hold true for the subset of patients with thin melanoma – the authors note that there were too few of these patients in their trial to allow them to draw conclusions. It also did not hold true for patients with thicker melanomas; probably because they were more likely to already harbor metastatic disease that could not be cured by removing lymph nodes.
In an accompanying editorial, melanoma researchers and surgeons Charles Balch and Jeffrey Gershenwald note, “This practice-changing trial demonstrates the important role of early identification and surgical removal of regional metastases, both for staging value and for improved survival in defined cohorts of melanoma patients.”
With this study, your advice to your recently diagnosed patient has become clearer.