Impact of the changes in the completion lymph node dissection criteria and approval of adjuvant therapies on the real-world outcomes of Japanese stage III melanoma patients.

BACKGROUND: Completion lymph node dissection (CLND) has long been the standard treatment for stage III melanomas identified as metastasis on the sentinel node (SN-positive). Two major changes occurred in 2017 and 2018, the change in the CLND criteria for SN-positive patients and the approval of several adjuvant therapies could revolutionize such management approach. However, their effects have not been fully investigated on the real-world outcomes of stage III melanoma patients. Therefore, we investigated the impact of these changes on the prognosis of Japanese stage III melanoma patients. METHODS: Totally, 119 stage III, SN-positive melanoma patients were included. They were categorized into those diagnosed as SN-positive between January 2015 and June 2017 (pre-June 2017 group) and between July 2017 and December 2019 (post-July 2017 group). Recurrence-free survival (RFS), overall survival, and prognostic factors were analyzed. RESULTS: The frequency of patients who received CLND was significantly higher in the pre-June 2017 group (p = 0.001), and those who received adjuvant therapy were significantly higher in the post-July 2017 group (p < 0.001). The 2-year RFS was 50.1% and 68.5% in the pre-June and post-July 2017 groups, respectively (p = 0.049). Cox proportional hazards model analysis for RFS showed that adjuvant therapies reduce the risk of recurrence (hazard ratio 0.37; 95% confidence interval 0.14-0.99; p = 0.047). CONCLUSION: Changes in the CLND criteria in SN-positive patients and the approval of adjuvant therapies for stage III melanomas have significantly impacted Japanese melanoma medicine. Adjuvant therapy tended to prolong patient's RFS while omitting immediate CLND had no significant negative influence on it.

Systemic treatment of patients with advanced cutaneous squamous cell carcinoma: response rates and outcomes of the regimes used.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer. Few patients with cSCC experience metastases, but the prognosis of advanced cSCC (acSCC) is dismal. Evidence regarding systemic therapy for acSCC is limited. Therefore, we aimed to determine the most effective systemic treatment for acSCC. PATIENTS AND METHODS: This retrospective study involved 16 Japanese institutions. We documented patient and tumour characteristics and disease course of patients with acSCC who received systemic therapy between 1st January 2006 and 31st December 2015. We compared the overall survival (OS) and progression-free survival (PFS) for (1) platinum versus non-platinum groups, (2) radiation plus chemotherapy first-line therapy (RCT) versus non-RCT groups and (3) platinum-based RCT versus non-platinum-based RCT groups. RESULTS: Although the use of platinum-based systemic therapy was not associated with statistically significant improvements in PFS and OS, there were significant differences between the RCT and non-RCT groups (PFS: p < 0.001, OS: p = 0.003). In the subgroup analysis, RCT significantly prolonged PFS and OS in the nodal SCC (nSCC) group. For the RCT and non-RCT groups, the median OS was 110 and 14 months, respectively, and the 5-year OS rate was 54% and 21%, respectively. CONCLUSION: RCT could improve OS in patients with nSCC. However, further multicenter prospective studies are needed to establish evidence for superiority of RCT.

Usefulness of sentinel lymph node biopsy for prognostic prediction in extramammary Paget's disease.

Complete excision of the primary lesion has long been considered the standard treatment for extramammary Paget's disease (EMPD). However, the presence of lymph node metastases has been reported as an important prognostic factor. We evaluated the association between lymph node metastasis and prognosis for EMPD using sentinel lymph node (SLN) biopsy. This retrospective study included 59 patients with histopathologically-confirmed primary EMPD. A total of 45 patients with microinvasion to the papillary dermis and deep invasion into the reticular dermis or subcutaneous tissue were included in the analysis. The survival curves of the SLN-negative group and the SLN-positive group were compared and we examined the risk factors for SLN positivity. A total of 139 SLNs were excised from one (28 patients) or both inguinal regions (31 patients). The average number of detected SLNs was 2.4. The incidence of SLN metastases was 16.9%. SLN positivity rates according to level of invasion were 0% for intraepithelial lesions, 4.1% for microinvasion, and 42.8% for dermal invasion. The five-year survival rates were 100% in the SLN-negative and 24% in the SLN-positive groups (p = 0.0001). Reticular dermis or subcutaneous tissue invasion was a significant independent risk factor for SLN positivity according to multivariate analysis. The result of SLN biopsy affected prognosis. It is extremely important to accurately ascertain the presence, i.e. the number, or absence of regional lymph node metastases in patients with EMPD. We conclude that SLN biopsy may be appropriate for cases where invasion is suspected.

[Sentinel node navigation surgery in melanoma and non-melanoma malignant skin tumor].

Sentinel node biopsy (SNB) has been performed for melanomas by many researchers since Morton's report in 1992. The technique has been well discussed, however, there have been only few reports about the application of SNB for treatment strategy of melanoma patients. Besides, we have not yet enough information of the clinical significance of SNB for non-melanoma malignant skin tumors. In this paper, we report two new findings of SNB for melanoma patients from the results of a multi-institutional study of SNB in 203 cases of melanoma. Firstly, the incidence of metastasis in non-sentinel node (non-SN) is less than 1% if no metastasis in SN; the identification rate of SN was 97.5%, the false negative rate was 0.98%, and correct diagnosis rate was 99.0%. Secondly, the incidence of metastasis in non-SN is less than 36.4% when patients had pSN 1 or pSN 2 metastasis. That means total removal of lymphnode metastasis can be achieved in 63.6% patients with lymphnode metastasis through SNB. Finally, we studied the usefulness of SNB on 71 cases of non-melanoma malignant skin tumors, and found the SN concept was also applicable for squamous cell carcinoma or invasive case of genital Paget's disease (Paget's carcinoma). Especially, we believe SNB for patients with Paget's carcinoma is as useful as for melanoma patients according our results of 25 cases; the identification rate of SN was 97.6%, the false negative rate was 0%, and correct diagnosis rate was 100%. SNB should be applied for patients with Paget's carcinoma as a diagnostic method of lymphnode metastasis and to determine the indication of lymphnode dissection, and its usefulness must be analyzed in the near future.