High-risk melanoma patients - identification, surgical management and follow-up

This thesis concerns the identification of these patients with high-risk melanoma, their surgical management, and follow-up.
Patients with stage III melanoma are frequently identified through sentinel node biopsy (SNB). Lymph from most of the skin drains to lymph nodes in the axilla, groin and neck. Lymph can also drain to smaller regions like the epitrochlear fossa and the popliteal fossa. Our study established lymphatic drainage to the popliteal fossa in 176 of 3902 patients with a melanoma below the knee (4.5%). SNB was attempted in only 96 of them(55%). A SN was retrieved in 79, while the procedure failed in 17 (18%). The SN was positive in 13 of the 79 patients with a successful popliteal SNB (17%) and in eight (10%) this was the only positive SN. Although SNs in the popliteal fossa are uncommon, they have a similar positivity rate and prognostic value as SNs in more common node fields. It is worthwhile to pursue these SNs, although the procedure can be challenging.
In June 2017, two large prospective trials of SN-positive patients had shown that survival of those who underwent CLND and those who were observed was similar. The pros and cons of dissection are discussed in the literature review. Advantages of immediate CLND are the reduced risk of nodal recurrence, improved staging with additional prognostic information from the tumor status of non-SNs, smaller risk of morbidity compared to delayed CLND for a recurrence and a less demanding follow-up schedule. These advantages of early CLND rarely outweigh the potential morbidity to which all these patients are exposed and the lack of a significant survival benefit. This was illustrated by our study on the management of SN-positive patients. At Melanoma Institute Australia, 59 of the 61 SN-positive patients (97%) were observed with regular ultrasound examinations. Two patients requested CLND because of anxiety about observation in view of unfavorable characteristics of the primary tumor and SNs. 46 of the 57 SN-positive patients (81%) presenting after November 2017 were seen by a medical oncologist to discuss adjuvant systemic treatment, and 32 chose to receive such treatment.
Of all melanoma patients, 2 to 5% will develop a local recurrence and some 4% an in-transit metastasis (ITM). The value of SNB in 128 such patients is discussed in this thesis. A SN could be identified in all patients. Metastases were found in 16 of them (13%). Patients with a positive SN had a 5-year survival rate of 54% and in patients with a negative SN this was 81% (P=0.01). Four patients with a negative SN (4%) and seven patients with a positive SN (44%) developed their first subsequent metastasis at a distant site. This prognostic information can be useful in the discussion on adjuvant systemic therapy and follow-up management.
This thesis also describes the potential use of ultrasound assessment of the lymphatic drainage area. Thirty patients with an in-transit recurrence are described, in more than half of them additional lesions were found with ultrasound examination.
Research on surveillance imaging is usually focused on the detection of metastases (true-positive findings). We researched false-positive and incidental findings in a group of 154 asymptomatic patients, who underwent a total of 1022 scans, with a median follow-up duration of seven years. False-positive and/or incidental findings led to additional healthcare activities in 81 of them (53%). The lesions proved to be benign in 109 of the 124 findings (88%). The additional healthcare usage resulting from of these findings was substantial. Awareness of both the benefits and downsides of surveillance imaging enables a balanced follow-up strategy, which is important with the increasing use of imaging in asymptomatic patients.