Lymph Node Surgery

To understand why the current NZ guidelines recommend that we sometimes perform a procedure called SNB, you need to understand a little of the history of how lymph spread of melanoma to lymph nodes was treated.  How to treat the regional lymph node basins (the first group of lymph nodes to which an area of skin drains lymphatic fluid, and therefore, the first place to which malignant melanoma or squamous cell carcinoma would be expected to spread), has been a contentious topic amongst surgeons for well over a century.

Broadly speaking, one school of thought believed that the regional lymph nodes should be removed en bloc at the same time that a tumour had been detected in the skin and removed – so you had your melanoma removed and then at the same time, or within a few weeks, you had the lymph nodes moved completely from your neck, arm or groin (which of those areas was stripped of lymph nodes depended on where your melanoma was – for example, if it was on your arm, then the nodes from your armpit were removed).

The other school of thought advocated waiting to see if the lymph nodes became involved (as judged by enlargement that could be felt on examination) and only then removing them at that stage. This they argued would prevent a proportion of patients undergoing radical surgery (which had an associated complication rate) unnecessarily.  On the other hand, by the time patients had palpable disease in their lymph nodes, their tumours had generally already spread beyond and into other organs, and could no longer be cured by lymph node removal alone, if at all.

There was scant evidence to choose between what were opinions, rather than evidence-based data, that divided the two schools of thought, although there was some evidence from retrospective studies that suggested patients with thick melanomas had better survival chances if they had their regional lymph nodes removed immediately (i.e. long before any symptoms developed in those nodes that would develop metastatic disease first).

Prospective randomized studies (which are much better evidence on which to base treatment decisions than retrospective studies) suggested less convincing evidence, if any, for electively removing regional nodes, but produced data suggesting benefit in some groups- such as patients with melanomas that are 1-2 mm thick; or who are under 60 years or who have malignant melanomas which have not ulcerated.

Even those who advocated electively clearing regional nodes, agreed that those patients whose melanomas had not metastasised, derived no benefit and suffered the morbidity and the complications of a major surgical procedure needlessly.

Ideally therefore, we needed to be able to select from within all melanoma patients, the group of patients who are most at risk of having melanoma that has spread silently to lymph nodes and treat only them by removing their regional nodes. It was this goal that underpinned the sentinel node concept, which is based on the hypothesis that lymphatic spread of melanoma proceeds as an orderly process which can be predicted by mapping the lymphatic drainage from a primary tumour to the first or ‘sentinel’ node in the regional lymphatic basin. This hypothesis was borne out in both animal and human studies for melanoma, and sentinel node biopsy to look for melanoma has been under evaluation as a therapeutic and prognostic tool for many years.

The melanoma team at Guys and St. Thomas’ Hospital in London was the only UK participant in the worldwide study of sentinel node biopsy called the “Multicenter Selective lymphadentectomy Trial – MSLT II for short.  I was one of the melanoma surgeons contributing data from SNB procedures that were randomised within the study and so my whole career as senior trainee and consultant has paralleled this debate and research into SNB.

The MSLT II Trial and how practice may change (but has not yet)

The New Zealand Care Standards were last revised in 2013 and published in 2014.  The UK’s National Institute for Clinical Excellence Guidelines “Melanoma: assessment and management” were published in July 2015.  Clinical Practice Guidelines for the Management of Melanoma in Australia and New Zealand, approved by the NZ Ministry of Health and various Australian Federal government bodies and the Australian Cancer Network, were published by the NZ Guidelines Group in 2008.

These documents are the only published evidence-based guidelines and the latter guides practice in New Zealand according to the Ministry of Health.  They advocate SNB for patients diagnosed with malignant melanoma of the skin that is thicker than 1mm.

However, a problem arises currently because the MSLT II published findings in 2017 that showed no survival benefit to people who underwent SNB.  So, our guidelines mandate one treatment, but more recent research suggests there is no benefit to the treatment in terms of survival and thus we may be subjecting people to surgery and complications, without being able to honestly say we are sure there is benefit.  In the absence of up-to-date guidance from the Ministry of Health, what should patients be offered?

I can point to two useful consensus publications since 2017 that address MSLT II.  First, the 2018 update of joint guidelines from the American Society of Clinical Oncology and Society of Surgical Oncology includes the following recommendations (Ann Surg Oncol 2018 Feb. 25 (2); 356-377), which say this about completion lymphadenectomy: In the case of a positive sentinel lymph node biopsy, completion lymph node dissection (CLND) or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathologic factors.  For higher-risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND.  So the American consensus view is that observation is only acceptable if patients are made fully aware of the risks (poor regional control and possibility of distant metastasis) and the benefits (less surgical morbidity – seroma formation, infection, skin flap problems) of not undergoing a groin dissection and removal of all lymph nodes.

The second publication is the “Melanoma Focus” document entitled “The current role of sentinel lymph node biopsy in the management of cutaneous Melanoma” – a UK consensus statement, which was based on a multi-disciplinary meeting held in Cambridge, UK on 17 May 2018.  This group was comprised of a mixture of general surgeons, histopathologists, medical oncologists, plastic surgeons, clinical nurse specialists, along with external reviewers from Italy and the Netherlands, and they met for the purpose of producing a consensus statement.  Their statement on completion lymphadenectomy (CLND), which has no official status or endorsement, goes as far as to suggest that CLND should not be recommended routinely for patients who have a positive sentinel node.

What to do?

The utility of sentinel node biopsy in appropriately selected patients is beyond doubt — with improvements in treatment outcomes for melanoma in specific survival, regional disease control, and surgical morbidity (this last is more particularly relevant for American practice which up until 10-15 years ago, had involved elective regional lymph node dissection, as opposed to the rest of the world, which practiced therapeutic regional lymph node dissection).

The experience from MSLT I, published in 2014, which randomised patients with primary melanoma to receive wide excision and SNB, or wide excision alone, showed that SNB and treatment of microscopic disease (that would not otherwise be clinically evident) improved patient outcomes, when compared with waiting until lymph node metastases became clinically evident.

In fact, MSLT II was one of two subsequent randomised trials which looked at completion lymph node dissection (CLND) — the other being the DeCOG SLT trial.  They were similar and they randomised SNB positive patients to undergo either CLND, or observation of the lymph node basis with ultrasound scans.

While MSLT II suggests there is no obvious survival benefit from CLND, on the other hand, nor was one likely to be found because the vast majority of SNB disease is purely that: disease in only one node at the time the melanoma was diagnosed – we have got much better at diagnosing melanoma early and so more is removed when spread to lymph nodes is still at an early stage, if present at all (and most likely, only in the first node it reached – “the sentinel node”).

To be clear, the SNB was therapeutic alone for those patients that had only single node disease at the time of initial diagnosis (which is the majority) and so, therefore, further lymphadenectomy, would only be beneficial for the very small group of patients in whom there was already spread beyond the sentinel node (a benefit unlikely to show with the design of MSLT II which wasn’t powered to find it).

If we can identify those patients who have metastatic spread beyond the sentinel node as early as possible, it would seem sensible to hypothesize that CLND for this group would improve survival.  How this group could be diagnosed optimally is what poses an ongoing question, with little evidence currently available on which to base opinions.

The relevant question for a surgeon to pose to themself when managing a patient with a melanoma thicker than 1.23mm is, I would suggest: ‘Is it my intention to offer the best opportunity for regional control of potentially lethal disease (bearing in mind the patient’s age and the tumour’s unique histology) or ‘Is my intention to offer my patient the most effective way of monitoring any progression of the melanoma, in the least invasive way possible’.

It is in addressing the latter question that MSLT II provides clinicians with useful evidence on which to base decisions.  Otherwise, until consensus guidance changes, my advice to a patient with SNB positive disease is if they are willing to accept the comorbidities and opt for CLND in the hands of an experienced surgeon, this still represents their best chance of gaining regional control of the disease and a long-term cure.  There is nothing in the MSLT II trial findings that contradicts this.