Effect Of Ulceration On The Therapeutic Benefit Of Surgery In Patients With Stage Ⅳ Skin Melanoma

Background:Dermal melanoma is a kind of skin cancer which is invasive and lethal.The morbidity increased by years,patients were diagnosed with stage Ⅳ melanoma when tumor presents with distant metastasis.A study on stage Ⅳ skin malignant melanoma patients demonstrated the poor prognosis,1-year survival rate was 33%–62%,5-year survival rate only was 19%.Despite improvements in survival,largely attributed to the new progress of targeted therapy and immunotherapy.However,there is no standard method for the treatment of distant metastatic melanoma,and there is no consensus on the role of surgery.Surgery still plays a major role in stage Ⅳ melanoma treatment based on the experience of multidisciplinary treatment.In this new era of systemic therapies,to the best of our knowledge,the existing guideline lacks informative analyses regarding different surgical interventions associated with survival in newly diagnosed stage Ⅳ melanoma patients.In addition,only anatomic sites and serum lactate dehydrogenase level are prognostic criteria for stage Ⅳ melanoma in AJCC guideline.It cannot meet clinical diagnosis and treatment practice.Some literature reported ulceration of melanoma is associated with tumor development,matastasis and prognostic.However,the guideline didn’t evaluate the potential of melanoma ulceration as prognostic marker and the effect on the therapeutic benefit of surgery in patients with stage Ⅳ malignant melanoma.Objective:The aim of this population-based,large sample,multicenter retrospective study is to analyze the clinicopathological characteristics of patients with different surgical treatments and different ulceration status of melanoma,to evaluate the prognostic factors of stage Ⅳ skin melanoma,to explore the impact of tumor ulceration status on surgical options and postoperative survival and provide a basis for clinical diagnosis and treatment.Method:We screened stage Ⅳ skin malignant melanoma patients who were diagnosed in 2004–2015 from the SEER datasets.The patients were divided into four groups:the R0 group（resection of all malignant lesions）,the primary tumor resection group,the metastasectomy group,and the no-resection group.The patients were subdivided into different categories according to different ulceration status of melanoma.The balance of categorical covariates in the patient characteristics between the groups was evaluated using the Chi-square（χ2）test.We used the log-rank test and Kaplan–Meier curves to compare the overall survival,melanoma-specific survival in the resection cohorts.Logistic regression was used to evaluate the influence of ulceration status on patients’choice of surgery.We assessed survival factors utilizing the Cox proportional hazards regression.In order to study the prognosis of different operation groups under different ulceration status,patients were divided into groups according to ulceration status,and each group was further subdivided into R0 group,the primary tumor resection group,the metastasectomy group,and the no-resection group.Similarly,log-rank test was used to compare the prognosis of patients within different treatment groups under different ulceration status,and the survival curve was constructed by Kaplan-Meier method.Result:We identified 5760 eligible patients that were initially diagnosed with stage Ⅳ malignant melanoma.The R₀,primary tumor resection,metastasectomy,and no-resection groups had median survival times of 11,13,20,and 4 months,respectively（P<0.001）.Cox proportional hazards regression models estimated that patients in the R₀,primary tumor resection,and metastasectomy groups had longer survival benefits,with hazard ratios of 0.396（95%CI,0.347–0.453）,0.509（95%CI,0.465–0.556）,and0.481（95%CI,0.447–0.519）,respectively.Ulceration will predict poor overall survival compare with non-ulcerated melanoma,with hazard ratio of 1.378（95%CI 1.249-1.521,P<0.001）.The logistic regression analysis revealed that ulceration was a significant independent factor of surgical intervention.In the non-ulcerated melanoma subgroup,the R0 resection group,primary excision group and metastasectomy group showed distinctly longer survival time compared to the no-resection group,respectively.In the ulcerated melanoma subgroup,both the R0 group and primary site excision group showed an improved overall survival when compared with the no-resection group,no additional survival benefit was detected when the metastasectomy group was compared with the no-resection group.Conclusion:We highlight the importance of surgery in newly diagnosed metastatic melanoma,each surgical group in this study is independently correlated with increased survival.Patients with melanoma ulceration showed significantly poor survival and outcome.In addition,the patient’s ulceration status are able to predict surgical treatment.In the non-ulcerated melanoma cases,the surgical treatment groups have longer survival outcome compared to the no-resection group.In the ulcerated melanoma cohorts,the survival outcomes were distinctly improved in patients who underwent R0resection and primary site excision when compared with the no-resection,however,caution should be exercised when only considering a metastasectomy.