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Background The role of surveillance imaging in high-risk stage III melanoma patients after complete surgical resection remains controversial, and with the advent of adjuvant therapy, it may also be expanded. Therefore, we evaluated two fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) protocols in two cohorts. Methods Cohort 1 (n = 35) focused on surveillance in asymptomatic patients (before approval and reimbursement of adjuvant therapy) and was assigned to 5x FDG-PET/CT's after surgery: one every 6 months for 2 years, with one final scan after 3 years. Cohort 2 (n = 42) was assigned to one screening FDG-PET/CT, which took place in between surgery and the start of adjuvant treatment. Results In cohort 1 (median follow-up: 33 months), 12 patients (34.3%) developed recurrence detected by FDG-PET/CT, of which 7 (20.0%) were detected with the first scan. Sensitivity and specificity were 92.3% and 100%, respectively. In cohort 2, recurrence was suspected on nine scans (21.4%) and four (9.5%) were true positive. The number of scans needed to find one asymptomatic recurrence were 8.8 and 10.5 in cohort 1 and 2, respectively. Conclusions FDG-PET/CT is a valuable imaging tool to detect recurrence in stage III melanoma, even shortly after surgery. A surveillance FDG-PET/CT protocol after surgery or a screening PET/CT before adjuvant therapy should be considered.

Measures of prognosis are typically estimated from the time of diagnosis. However, these estimates become less relevant as the time from diagnosis increases for a patient. Conditional survival measures the probability that a cancer patient will survive some additional number of years, given that the patient has already survived for a certain number of years. In the current study, the authors analyzed data regarding patients with stage III melanoma to demonstrate that survival estimates from the time of diagnosis underestimate long-term survival as the patient is followed over time. The probability of surviving to year 5 for patients at the time of presentation compared with patients who had already survived for 4 years increased from 72% to 95%, 48% to 90%, and 29% to 86%, respectively, for patients with substage IIIA, IIIB, and IIIC disease. Considering the major role played by survival estimates during follow-up in patient counseling and the development of survivorship programs, the authors strongly recommend the routine use of conditional survival estimates.

Melanoma patients in stage III have a considerable recurrence rate. The 10-year survival in this stage depends on the number and size of affected nodes. Currently, there is no optimal serum marker for early detection of relapse available. The goal of the study was to assess the utility of melanoma inhibitory activity (MIA) serum marker in the follow up and primary diagnosis of stage III melanoma patients. One hundred and thirty-eight melanoma patients in stage III at time of primary diagnosis were analyzed at time of primary diagnosis and during periodical routine follow up both for serum MIA using an enzyme-linked immunosorbent assay and for serum lactate dehydrogenase (LDH). Results were correlated with the positivity of the sentinel lymph node (SLN) and the number of lymph node metastases in the completion lymph node dissection at time of primary diagnosis. During follow up, the overall survival time was assessed using the Kaplan-Meier method in terms of elevated MIA (>12 ng/mL) values. Regarding SLN status, significant differences of MIA values (P = 0.024) and LDH (P = 0.007) were found, both within the normal cut-off. Having lymph node metastases in the completion lymph node dissection, significantly higher MIA values (12.55 ng/mL [±0.48], P < 0.0001) were found. In patients with three or more tumor-positive nodes, MIA values were significantly higher when compared to patients with one or two affected nodes (P = 0.024). In the routine follow-up, stage III patients with an MIA value of more than 12 ng/mL had a five times higher risk for developing recurrences (P < 0.0001). Patients with relapsing disease had a significantly (P < 0.0001) higher mean MIA value (13.76 ng/mL) compared to patients without relapse (7.52 ng/mL). The MIA serum marker can be helpful in patients undergoing lymph node dissection. Furthermore, during follow up, patients showing relapsing diseases can have an elevated MIA value.

BACKGROUND Prognostic factors for patients with stage III melanoma are still controversial. METHODS Two hundred eighty-six patients with solitary cutaneous malignant melanoma of the skin in Stage III (International Union Against Cancer [UICC]) were followed up for as long as 11 years. RESULTS Patients in risk group pT 4a, pN O (primary tumor thickness of more than 4 mm or invasion of subcutis and absence of regional lymph node metastasis in elective lymph node specimen) have a 5-year survival rate of 72.8%. If regional metastases are excluded clinically (pT 4a, NO), the 5-year survival rate is 62.8%. Patients with regional lymph node metastases have an average 5-year survival rate of 39%, depending mainly on the number of involved lymph nodes and the depth infiltration of the primary tumor. The number of involved lymph nodes reflects the grade of dissemination. It shows a stronger correlation with the prognosis than does the size of metastases. CONCLUSIONS The authors recommend that revisions of the UICC classification should distinguish Stage IIIA and IIIB based on the presence or absence of regional metastases and that a clearer distinction should be made between regional cutaneous or subcutaneous metastases and regional lymph node metastases.

Radiation therapy has several roles in the management of stage III melanoma. Perhaps the most controversial is in the post-operative setting where several retrospective studies and one prospective trial have suggested that radiation therapy results in a reduction in regional recurrence. On the basis of this and the fact that late toxicity is not increased, many cancer centres have adopted the use of radiation therapy in “high risk” patients with large nodes, multiple node involvement and the presence of extracapsular extension. The benefit of radiation therapy for this indication remains to be proven in a randomised trial and the outcome of the Trans Tasman Radiation Oncology group/Australian and New Zealand Melanoma Trials Group in settling this question is awaited. At the present time the only clear indications for post-operative radiation therapy are in those patients where the dissection may reveal an inadequate number of dissected nodes, those with positive margins, tumour spill at surgery or where disease has already recurred after a previous dissection. The area which is gaining more interest is the role of radiation therapy in the pre-operative setting for bulky, tethered or fixed nodal disease where the use of such therapy can not only result in significant reduction in tumour volume, thus aiding resection, but also separate out patients at high risk of metastatic disease where a major operation may be counterproductive to quality of life. If patients having this approach do develop distant metastases during or shortly after receiving radiation therapy, they may still obtain reasonable palliation with the use of such local therapy.

Lymphocytes from 16 stage I, 6 stage II and 31 stage III melanoma patients (MP) and 51 healthy donors (HD) were tested as far as possible in parallel on a melanoma cell line (NKI-4), a bladder carcinoma cell line (T 24) and 18 different short-term melanoma cultures. Lymphocytes from MP and HD showed cytotoxic effects towards all three types of target cells. Lymphocytes from HD showed the strongest "spontaneous" cytotoxic effects on NKI-4 cells whereas, in general, weak cytotoxic effects were seen on short-term cultured melanoma cells. Within the different lymphocyte donor groups an enormous variation in cytotoxic effects was observed. However, the overall cytotoxic effects of stage I and II MP were significantly higher than those of the HD-group. Stage I MP showed significantly stronger cytotoxic effects on NKI-4 cells than on T 24 cells, indicating that tumour-associated lymphocyte cytotoxicity was superimposed on spontaneous cytotoxicity.