University of Groningen
Evolving treatment of locoregional metastatic melanoma
Faut, Marloes
DOI:
10.33612/diss.93011206
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from
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Publication date:
2019
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Faut, M. (2019). Evolving treatment of locoregional metastatic melanoma. University of Groningen.
https://doi.org/10.33612/diss.93011206
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As is apparent from this thesis, the treatment options of metastatic melanoma have expanded over the past decades and are constantly improving. Multidisciplinary teams the surgeon, medical oncologist, radiotherapist, radiologist, nuclear physician, dermatologist, neurologist and pathologist are now all part of, continuously cooperate to improve patient outcomes. As is also apparent from this thesis, improvement is needed on several aspects of melanoma care. These aspects are described below.
The future of diagnostics:
The MSLT II trial has shown that a completion lymph node dissection following a positive SLNB does not increase melanoma-specific survival. It provides prognostic information and slightly improves the rate of regional disease control.1 In the light of
the latter, a place for completion lymph node dissections in the future, seems limited. Lymph node dissections might be reserved for clinically evident nodal disease only. In guidelines, imaging methods, such as ultrasonography have to be included to ensure adequate follow-up of the draining lymph node basin.
In the light of the recent MSLT II trial results, the place of SLNB in the treatment of melanoma is uncertain, as a positive SLNB will not automatically lead to a CLND anymore.1 Therefore it seems logical to try and find new noninvasive diagnostic
tools, capable of predicting lymph node involvement. Stoffels et al. showed that multispectral optoacoustic tomography (MSOT) can adequately diagnose lymph node involvement in a noninvasive way. It can detect lymph node metastases of melanoma to a depth of 50mm, with a sensitivity of 100% and a false negative rate of 0%. Therefore it could be used as a first diagnostic tool to select those patients without nodal involvement, patients without nodal involvement can be spared an invasive procedure such as a SLNB.2 Possibly even patients with MSOT positive
lymph nodes will not undergo a regular SLNB procedure in the future as all stage III melanoma patients will be considered for adjuvant systemic treatment.
In breast carcinoma, a gene profile is already available that can aid to determine the risk for recurrent disease.3 In melanoma, genetic profiling might be able to predict
prognosis or response to therapy such as BRAF inhibitors or immunotherapy. Furthermore, melanoma specific gene mutations can be used to develop tumor specific targets which can be used in MSOT, or in melanoma-targeted PET-CT scans. This would help determine recurrent disease in an early stage and concurrently possibly aid in the initiation of early treatment.
The future of inguinal lymph node
dissections:
As most melanoma patients are treated with some form of surgery during their follow-up, surgeons should continuously pursue to improve existing therapies and their outcomes. A morbidity of 50% following ilio-inguinal lymph node dissections is simply unacceptable. As decades of attempts to reduce surgery induced morbidity have not led to satisfying results yet, it is time to focus on new surgical strategies such as videoscopic lymph node dissections. This procedure has promising results with a wound complication rate of 20% after completion of the learning curve4 and
adequate nodal yield.5 The implementation of videoscopic lymph node dissections in
patients with large, clinically evident, nodal metastasis seems feasible, as the largest resected lymph node in the UMCG was 60mm.
Personal note:
Immunotherapy is used in the treatment of various forms of cancer, such as renal cell carcinoma, breast carcinoma, lung carcinoma and melanoma. In melanoma, immunotherapy is applied in disseminated disease and in the (neo)adjuvant setting. All stage III melanoma patients already receive adjuvant treatment. This new era, where a shift will be made from surgery to systemic treatment of metastatic melanoma, presents new challenges. The risk of long term side effects of systemic therapy, devastating in a small percentage of patients, may be acceptable for stage IV but debatable for stage III patients. Also in case of failure or partial response
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to systemic therapy patients will present with metastasis that are surgically challenging due to location or size. In this new era, multidisciplinary treatment of melanoma patients will be even more important. Follow-up will likely be performed by medical oncologists, and decisions concerning a possible surgical procedure and resectability of metastasis is best judged by a surgeon. Therefore close collaboration remains important.
Furthermore, physicians have the obligation to be critical about every proposed medical treatment. In the case of the inescapable reality of death due to a malignant disease such as melanoma, even with increasing possibilities in systemic therapies, it seems even more important to realize when the boundaries of medical treatment have been reached.
References
1. Faries MB, Thompson JF, Cochran AJ, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med. 2017;376(23):2211-2222.
2. Stoffels I, Morscher S, Helfrich I, et al. Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imaging. Sci Transl Med. 2015;7(317):317ra199.
3. Cardoso F, van’t Veer LJ, Bogaerts J, et al. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717-729.
4. Sommariva A, Pasquali S, Cona C, et al. Videoscopic ilioinguinal lymphadenectomy for groin lymph node metastases from melanoma. Br J Surg. 2016;103(8):1026-1032.
5. Delman KA, Kooby DA, Ogan K, Hsiao W, Master V. Feasibility of a novel approach to inguinal lymphadenectomy: Minimally invasive groin dissection for melanoma. Ann Surg Oncol. 2010;17(3):731-737.
