Melanoma: Treatment

SURGICAL TREATMENT

MARGINS

Wide Local Excision

For lentigo maligna melanoma, margin status of positive or close (<3mm) is independently predictive of recurrence/progression. 37454699

Mohs Surgery

There have been numerous studies that have demonstrated that head and neck melanoma in situ requires wider margins than the 5-10mm margins recommended by most guidelines.

Tate JA, Matsumoto A, Greif C, Lim J, Nijhawan RI, Srivastava D. Excision margins for melanoma in situ on the head and neck-A single-center 10-year retrospective review of treatment with Mohs micrographic surgery. J Am Acad Dermatol. 2024. PMID: 38253130.

10mm margins would be required to clear 90%, 15mm margins to clear 97%
They indicated that preoperative size correlated with the requirement for >5mm margins but did not break this down.

Melanoma in situ

For melanoma in situ less than 10mm on the trunk and extremities, a 5mm margin carried a 0.9% recurrence rate after 7 years median follow up. Of recurrences, all were local. 1.7% of cases had positive margins requiring re-excision. 30% of cases were LM subtype, and histologic subtype did not predict recurrence. 38922604

MOHS SURGERY

There does not appear to be a difference in overall survival when comparing wide local excision to Mohs surgery for in situ and invasive melanoma of the trunk and extremities. 33084853 This study did not parse out MIS from invasive melanoma in a clear way, and also may have been underpowered given the relatively low number of cases treated with MMS (~2% of entire cohort).
There does seem to be improved disease specific survival in lentigo maligna melanoma patients treated with Mohs vs WLE (38969012), although a letter in response brought up some serious methodological problems with this analysis which may invalidate these findings. 39647704

WIDE LOCAL EXCISION AND SLNBx

No basis for delaying WLE until SLNBx

Tassavor M, Bland M, Goldenberg O, Tassavor B, Coldiron B. Wide Local Excision Before Sentinel Lymph Node Biopsy in Melanoma. Dermatol Surg. 2024. PMID: 38810277.

This article reviews the literature in search of evidence that performing WLE prior to SLNBx leads to an increased rate for false negative sentinel node biopsies, and reports that there is not substantial evidence that this is the case. One caveat is that large rotation flaps could potentially impact lymphatic flow patterns and increase false negative rates, but the evidence for this is also minimal.
There is some data that suggests that delay of WLE could lead to worsening melanoma survival (35787410, 32711092), specifically when performed 30 days or more after diagnosis.
From MSLT-1, nearly half of patients waiting for SLNBx to have WLE receive their WLE after 30 days.

ADJUVANT THERAPIES

IMMUNE CHECKPOINT INHIBITORS

Incidence of new primary melanoma not changed by ICI therapy

The incidence of new primary melanomas does not seem to be attenuated by use of immune checkpoint inhibition. In one single-center study, the cumulative 5-year incidence of new primary cutaneous melanoma in patients being treated with immune checkpoint inhibitors for metastatic melanoma was ~5%. 32936222

Treatment when disease burden is lower may improve response

Ribas A, Hamid O, Daud A, et al. Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. JAMA. 2016. PMID: 27092830.

This study looked at patients with advanced melanoma who were treated with pembrolizumab with or without prior ipilimumab, and assessed safety and tumor response. There was no placebo or other control group.
Patients with baseline below median tumor size had higher objective response rates (~43% vs 28% for below median vs above median).

FOLLOW-UP/MONITORING

Surveillance of patients with early stage (I or II) melanoma

NCCN guidelines recommend routine imaging for patients with stage IIB or greater melanoma.

Early routine imaging may lead to earlier detection of melanoma recurrence

Dhillon S, Duarte-Bateman D, Fowler G, et al. Routine imaging guided by a 31-gene expression profile assay results in earlier detection of melanoma with decreased metastatic tumor burden compared to patients without surveillance imaging studies. Arch Dermatol Res. 2023. PMID: 36977840.

Assumptions (assumptions are things stated by a paper that I have not independently verified): ICI improves overall survival (cit 1-3). Trials have shown that there is greater efficacy when administered with an initial tumor burden (cit 4-8). Routine imaging can effectively detect early relapse when there is a lower tumor burden (cit 9-11).
Design: retrospective, patients with stage I or II melanoma who had a negative SLNBx AND a 31-GEP class 2A or 2B. The control were patients with stage I/II melanoma and negative SLNBx without a GEP test result and without scheduled routine imaging (only received symptom or exam finding-driven imaging). They excluded patients in the control group with recurrent melanoma who had routine imaging, and in the experimental group with recurrent melanoma who did not have routine imaging. The intervention seems to be early scheduled imaging vs not. They looked at the tumor burden at recurrence of those in the experimental group compared to the control group. Routine imaging consisted of chest and pelvic CT and brain MRI.
Results: recurrence in experimental group was detected earlier (~25mo vs 35mo), with a lower tumor burden (~27mm vs 73mm). Survival was similar when looking at identical follow up periods (at 45 mo, ~87% vs 75%).
Limitations: there were many. Like many publications, the authors leap to conclusions that are favorable to the intervention they are supporting. In this case, mentioning in the abstract that patients receiving routing imaging after high-risk GEP test scores have better clinical outcomes. This is premature on 2 accounts: 1) they did not compare routine imaging in patients with high-risk vs low risk GEP test scores, and 2) overall survival was not statistically significant between the two groups when looking at similar follow up times (it was better in the experimental group but follow up was nearly 18mo shorter in the experimental group. Also, this wasn't really GEP-guided imaging. First, it was retrospective, so the use of GEP to determine whether imaging would be done was not an established protocol. They also did not compare detection rates of patients with low risk GEP scores vs high risk GEP scores to determine if imaging was more valuable in patients with high risk GEP scores.

Adherence to yearly dermatology visits improves survival

An Ontario-based study found that patients who were at least 75% adherent to at least a yearly follow up regimen after the diagnosis of their first melanoma had a decreased melanoma-specific mortality (HR 0.64, 95% CI 0.52-0.78). In the discussion the authors say, "mortality reduction seen with annual follow-up was further enhanced by shorter follow-up intervals of 3 and 6 months". However, in the supplemental tables the HR for annual, 6mo, and 3mo follow ups were 0.63, 0.62, and 0.61, respectively. My interpretation of this is that more frequent follow up does NOT seem to add an appreciable mortality benefit. In correspondence with one of the authors, he confirmed that the interpretation published in the paper was based on these figures. 38368952