Note: In patients with early-stage melanoma of the skin, delaying surgery after biopsy (tissue removal) potentially increased mortality (death rate): patients who did not have surgery until between 90 and 119 days after biopsy or even later had an increased risk of mortality (hazard ratio [HR]: 1.09 and 1.12, respectively): compared with patients who had surgery within four weeks. Surgical Interventions
Malignant melanoma should primarily be excised completely with a small safety margin. The S3 guideline details that “a lateral safety margin of approximately 2 mm is recommended for excision; for depth, excision should be performed down to the fat tissue.”
| Excision in toto | Tumor thickness according to Breslow | Safety distance |
| ≤ 2 mm | 1 cm | |
| > 2 mm | 2 cm |
Note: In R1 and R2 situations (residual tumor/residual tumor detected microscopically and macroscopically, respectively) of the primary tumor region, a resection should always be performed if an R0 situation (no residual tumor) can be achieved by doing so.Note: In the case of in situ melanoma or lentigo maligna (intraepidermal (located in the epidermis) neoplastic proliferation of atypical melanocytes), the safety distance should be greater than 3 mm. Further notes
- Melanoma in situ are completely incised and removed with a safety distance of 10 mm.
- A safety distance of 1 cm at primary excision seems to be sufficient even for thicker melanomas. So far, thicker melanomas are still removed with a safety margin of 2 cm and thin melanomas up to 2 mm tumor thickness with 1 cm safety margin.In multicenter studies must be investigated in the future, whether a safety margin of 1 cm is actually sufficient for thicker melanomas.
- A study with almost 20 years of follow-up was able to demonstrate that if cutaneous melanomas with a thickness greater than 2 mm are removed with a 2 cm resection margin, this guarantees a similar good prognosis as a more extensive excision.
- Note: The safety margin avoids, only local recurrences. It has no influence on overall survival and the development of metastases.
- According to the currently valid German S3 guideline on malignant melanoma, a safety distance of > 3 mm is expected to have a recurrence rate of 0.5%.
- When comparing excision (surgical removal) with a safety distance of more than 3 mm with micrographically controlled Mohs surgery with 3-D histology in the presence of melanoma in situs, 94%, 86%, and 76% of patients were still alive after five, ten, and 15 years after further excision and 92%, 81%, and 73% of patients after Mohs surgery; differences in overall survival were as insignificant as those in cancer-specific survival.
Sentinel lymph node (sentinel lymph node)
Timing of sentinel lymph node biopsy: Biopsy (tissue removal) of sentinel lymph nodes early, that is, within 30 days of the first diagnostic skin biopsy (tissue removal from the skin), and thereafter, showed no difference in survival rates at 10 years 64.4 ± 4.5% versus 65.6 ± 3.4%. Sentinel lymph node biopsy (Sentinel node biopsy, SNB) [S3 guideline]:
- For staging purposes, sentinel lymph node biopsy (tissue sampling) should be performed when tumor thickness is 1.0 mm or greater and there is no evidence of locoregional or distant metastasis (spread of tumor cells from the site of origin via the blood/lymphatic system to a distant site in the body and growth of new tumor tissue there).
- If there are additional risk factors for a positive sentinel lymph node, sentinel lymph node biopsy should also be performed for thinner primary tumors (0.75-1 mm), including ulceration (ulceration) and/or increased mitotic rate and/or younger age (< 40 years).
Further notes
- Do not perform sentinel lymph node biopsy or other diagnostic tests for melanoma in situ, T1a or T1b melanomas ≤ 0.5 mm (see classification below), as it does not improve survival. Here, the risk of spread is very low; the 5-year survival rate of patients is 97%.Otherwise, disease-free survival is significantly prolonged by sentinel lymph node biopsy.Another study also proved that there is a significant prolongation of progression-free time:
- Patients with dissection of the sentinel lymph node: tumor-specific survival 102.7 months; 10-year survival 74.9%.
- Comparison group: 97 months and 66.9% survival, respectively.
According to the current S3 guideline, the patient should be offered sentinel lymph node biopsy if the tumor thickness is > 1.0 mm.
- With histologic evidence of partial regression in the primary tumor (= neoplastic cells have disappeared within the tumor or are reduced to at least in the dermis; incidence: approximately 10 to 30% of cases), a meta-analysis of all studies showed that the probability of biopsy detection of micrometastases in the sentinel lymph node was reduced by 44% (odds ratio [OR]: 0.56; 95% confidence interval between 0.41 and 0.77). This was associated with a significant prolongation of progression-free and cancer-specific survival.
Approach to locally metastatic stage (stage III)
Elective lymphadenectomy (LAD; lymph node removal) after primary diagnosis is not recommended. However, in cases of clinically and sonographically or imaging manifest lymph node metastases and exclusion of distant metastases, therapeutic LAD der should be performed. This leads to the avoidance of regional recurrences and at the same time pursues a curative approach. Further notes
- Completer lymph node dissection in patients with malignant melanoma and involvement of sentinel lymph nodes: this did not improve patient prognosis in a large randomized controlled trial.
- Interval between primary excision and diagnosis of first distant recurrence (variable: 12-24 months vs > 24 months) showed no significant association with either progression-free or overall survival. Here, the analysis was based on 638 cohort participants diagnosed with inoperable stage III or IV melanoma between 2013 and 2017.
Operative approach
1st order
- Primary tumor – excision (surgical removal) in toto with sufficient safety margin; if necessary, with sentinel lymph node biopsy* (Sentinel Node Dissection, SLND) – in case of micrometastases in the sentinel lymph node (sentinel lymph node), the further procedure depends on the diameter of the metastases:
- Diameter < 0.1 mm or single cells in the sentinel lymph node: a completion lymph node dissection can be omitted (LoE 2b)
- Diameter 0.1-1 mm: a completion lymph node dissection (surgical removal of the lymph nodes) may be offered, although other risk factors should be considered (LoE 2b). Relevant are mainly capsular infiltration, depth extension in the sentinel lymph node and number of affected sentinel lymph nodes as well as thickness and ulceration of the primary tumor.
- Diameter > 1 mm: Should-Recommendation for completion lymph node dissection (see “Further notes” below)Possible complications: Disruption of lymphatic drainage
- Locoregional metastases → intratumoral injection of interleukin-2 and intratumoral electrochemotherapy with bleomycin or cisplatin or oncolytic immunotherapy.
- Distant metastases (distant metastatic daughter tumors): resection (surgical removal) of distant metastases should be considered if technically feasible as R0 resection (microscopic no evidence of residual tumor) [S3 guideline] and
- Is not expected to result in an unacceptable functional deficit
- Positive predictive factors for local approach are present (low metastatic number, long duration of metastasis-free interval),
- Other therapeutic procedures are exhausted or less promising.
* Using MSOT method (“Multispectral Optoacoustic Tomography”), the sentinel lymph node can be examined noninvasively for metastasis.
