Sentinel Node Biopsy

For people with a stage 2 melanoma, it is important to examine and stage lymph nodes. What cancer staging means, is, determining how much cancer is present in the body, and to what areas it has spread. In melanoma, the depth of invasion of the primary tumour (the Breslow thickness) is related to the risk of spread of melanoma to the local lymph nodes.

When a primary melanoma has a Breslow thickness of >1mm (or sometimes 0.8mm with some adverse other features) there is a small risk of lymph node spread, which increases proportionally with the tumour thickness. Therefore it is important to assess the local lymph nodes for melanoma involvement.

There are three ways used to assess the local nodes: clinical examination, ultrasound and sentinel node biopsy.

Ultrasound is a good way to identify abnormal nodes and can identify an area of melanoma from about 4-5mm large, and some centres offer serial ultrasounds to monitor the lymph nodes.

Sentinel node biopsy is a procedure that takes place at the same time as a wide local excision for melanoma. Usually, a blue dye is injected into the scar from the original melanoma excision, as is technetium, a radioactive isotope. Both the dye and the isotope will drain to the first lymph node the lymphatic channels from the area ok skin harbouring the melanoma. If melanoma is going to spread via the lymph nodes it usually will go to this first or ‘sentinel’ node in the first instance.

Lymph nodes are small globes of tissue that harbour immune cells, hence the analogy to a sentinel – they are like barracks for the different types of immune cells that fight cancer and infection. The radioisotope allows us to identify the node (or nodes) before operating, and we can map (identify) the particular node on 2 types of scans (SPECT – a type of CT, and lymphoscintigraphy). Using a gamma-probe to pick up the radioactive signal and identifying the blue dye allows us to identify the sentinel node after making a very small incision over the node (this may also be marked by an ultrasound).

The procedure is straightforward, but does have complications – allergy to the blue dye, sometimes the sentinel node cannot be identified, one can get infections or seroma in the wound, and a small percentage of people may develop lymphoedema or numbness in the region of surgery.

One to three nodes are usually examined, to a fine level of details, which can take up to 2 weeks to process fully. If the node is positive, then the melanoma is staged as Stage IIIA or B depending on tumour thickness. This may have relevance for being eligible for clinical trials of adjuvant treatment which aim to reduce the risk of melanoma recurrence after clearing disease with surgery, and in the near future, eligibility for adjuvant treatment regimens, as they are more clearly defined.

Recent updates on Sentinel Node Biopsy

Until recently, if the sentinel was positive for melanoma, most centres would recommend a dissection (surgical removal) of all of the lymph nodes in the region – usually the axilla (armpit) or the groin. The rationale of this approach was to clear out any other nodes that may have the disease (‘non-sentinel nodes’) which could progress in future (around 10-15% of other nodes may have melanoma present) to gain control of the melanoma, and also because finding other nodes would give useful prognostic information – indicating a higher risk of spread elsewhere.

A major international randomised trial, MSLT-1 (Multicenter Selective Lymphadenectomy Trial) was set up to test whether performing a sentinel node biopsy and removing all of the nodes early if a positive node was identified would improve survival, when compared to clinical examination and taking out the nodes if they became clinically apparent (usually swollen).

Although people have argued that removing all nodes when the sentinel node is positive, the trial did not show improved survival in these patients (http://www.nejm.org/doi/full/10.1056/NEJMoa1310460). That was a very important finding, as a lymph node dissection can have significant morbidity (surgical side-effects) – up to 15% of people may develop lymphoedema, and in the groin 30-40 of people develop wound complications such as infection, wound breakdown and seromas.

Two recent trials, the follow up MSLT trial (MSLT-2) and the German DeCOG-SLT have further informed our approach to sentinel node biopsy. Both were randomised trials that examined whether there was a difference in survival when monitoring patients with ultrasound after a positive sentinel node biopsy, in comparison with dissecting all of the lymph nodes.

Both trials found that there was no difference in survival, but the majority of patients could avoid a further operation and complications. If lymph nodes were identified during follow up, they could be safely removed. The number of patients in MSLT-2 who had a recurrence of melanoma in the lymph nodes only was 6.4% higher in the ultrasound group. Although one can consider a node dissection, in particular, if there is no facility for ultrasound surveillance at your treating centre, or if it is a personal preference, in general, it need not be performed, which is good news for many melanoma patients.

A recent interesting study from Australia looked at the potential benefit from sunscreen, by asking whether use in childhood or early adulthood reduces the future risk of melanoma. This was a case-control study looking at over 600 patients who regularly used sunscreen in the Australian Melanoma Family Study comparison to a larger control group outside the study.

The main finding of this research is that regular sunscreen use is associated with a reduced risk of melanoma in young adults who regularly use sunscreen.

A previous randomised trial from Australia demonstrated a major reduction in melanoma in people using daily sunscreen compared to discretionary use (11 melanomas in those using daily sunscreen compared to 22 in those using is at their discretion) aged 22-75 years old.

Taken together with other population-based studies – which examine what happens in real-world conditions – there is quality evidence that appropriate use of sunscreen may prevent the development of melanoma.

There are many good sources of melanoma advice regarding sunscreen including the British Association of Dermatology and Melanoma UK

Lymphoedema, in the context of surgery for melanoma, is swelling in a limb due to the excision of lymph glands and disruption of lymphatic vessels. It can occur when someone has either a dissection (removal) of all lymph nodes in a basin (as in the axilla or armpit) or the groin (inguinal nodes); or a sentinel lymph node biopsy (SLNB).

Although lymphoedema can occur with either a sentinel node biopsy or node dissection, it is more frequent in those having a node dissection.

For example, in trials of SLNB, the rate of lymphoedema range from 4.6-7.2% in the Sunbelt Trial (1) and the MSLT-I (2) trials respectively, with a rate of 12.5% for those having a node dissection in MSLT-I. However, in case series and other studies, higher rates have been described, with a higher risk of lymphoedema associated with higher body mass index, co-morbidities such as diabetes, and in the groin, whether the deep (iliac nodes) are also dissected as part of the operation.

After lymph node surgery, you should be assessed for lymphoedema, and if it occurs, referred on for appropriate management. Although there is no definitive cure if it occurs, it can be successfully controlled with methods to reduce the accumulation of fluid and improve drainage.

Treatment for Lymphoedema after surgery for melanoma

Approaches include compression dressings and garments, massage and exercise as part of a supervised regime. There are many people living well with lymphoedema, and if you have been affected, it may be helpful to contact the Lymphoedema Support Network, to access more information and gain support.

References:

1. Faries MB, Thompson JF, Cochran A, et al. The impact on morbidity and length of stay of early versus delayed complete lymphadenectomy in melanoma: results of the multicenter selective lymphadenectomy trial (I). Ann Surg Oncol.2010;17:3324–9.
2. Wrightson WR, Wong SL, Edwards MJ, et al. Complications associated with sentinel lymph node biopsy for melanoma. Ann Surg Oncol. 2003;10:676–80.
3. https://www.nhs.uk/conditions/lymphoedema/
4. http://www.lymphoedema.org/

The main aim of wide excision of melanoma after a diagnostic excision is to prevent the cancer recurring at the site of origin, and to maximize long-term survival. The functional and cosmetic impact of surgery on an individual patient, are major secondary considerations when planning a further excision.

Our current theory of how further surgery helps control melanoma is that a wider excision will likely remove any residual tumour cells at the site of origin of the tumour and any microsatellites of disease that may exist in the skin near the tumour, or in the local lymphatic system.

Although there is consensus that after a diagnostic (usually 2mm wide margin) excision, a further excision is beneficial in reducing the risk of local recurrence, the optimal width of a further excision has long been debated. The Scottish Physician, William Handley studied the lymphatic drainage of breast cancer and melanoma, and in the early 1900s suggested performing an approximately 5cm wide excision of melanoma with removal of the draining lymph nodes.

The contemporary approach to wide excision is based on good quality randomised trials of different margin widths, which tested the benefit of different margins of excision of the primary melanoma guided by the Breslow thickness of the primary tumour (i.e. testing with many patients randomly assigned to different excision margins to see if the recurrence rate of a melanoma is the same for a given Breslow thickness melanoma).

For example, the MSG/BAPS randomized trial, recently presented and subsequently published in the Lancet Oncology by my colleague Mr Andrew Hayes of the Royal Marsden, on behalf of his trial colleagues asked the question of whether a 1cm or 3cm excision margin is best for a 2mm Breslow (Stage II) melanoma. Long-term follow up of the 900 patients with Stage II melanoma recruited throughout the UK and randomly assigned either a 1cm or 3cm excision demonstrated no difference in overall survival with a wider excision of 3cm.

The current NICE guidelines recommend a margin of at least 1cm to people with a diagnosis of stage I melanoma (Breslow depth 1-2mm), and margin of at least 2cm to people with stage II melanoma (Breslow depth 1-2mm). For melanoma in situ, a 0.5cm margin is sufficient. Occasionally, in a cosmetically sensitive area, close clinical surveillance after a narrow excision may be considered.

The procedure may be performed by a Dermatologist, General Surgeon, GP or Plastic Surgeon, often as a day case under local anaesthetic. Usually, the wound can be closed primarily with sutures (beneath the skin sometimes) or skin clips; however, if the area is difficult to close, a skin graft or other Plastic surgical procedure may be required to close the excision site. If reconstruction, a 2cm excision, or a sentinel node biopsy is being performed at the same time, a general anaesthetic is generally required. It is important to realise that the excisions may be quite long, as one needs to make the length of the incision longer than the width to close the wound neatly and ensure it is apposed.

Usually, the wound is covered for 24-48 hours, and sutures or clips removed between 5-14 days later depending on the location of the wound, and you will be scheduled a follow-up appointment to ensure good wound healing, removal of sutures and discussion of the pathology examination of the specimen.

References/further reading:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303163/

https://www.skincancer.org/skin-cancer-information/melanoma/the-stages-of-melanoma/guide-to-staging-melanoma

http://www.nejm.org/doi/full/10.1056/NEJMoa030681

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00482-9/abstract

https://www.royalmarsden.nhs.uk/our-consultants-units-and-wards/clinical-units/skin-unit

https://www.royalmarsden.nhs.uk/private-care-magazine/skin-cancer-below-surface