¹Cancer Registry Saxony, Dresden, Germany

Text

Introduction: The introduction of immune checkpoint inhibitors (ICI) in 2011 symbolizes a paradigm shift in cancer treatment. Especially in metastatic malignant melanoma, the first cancer entity for which ICIs were approved [1], significant better treatment results have been described. However, these therapies are also associated with a new dimension of side effects [2], [3]. What developments can be derived from the cancer registry data for skin cancer treatment in Saxony?

Methods: The cancer registry data of the Free State of Saxony were analyzed for the occurrence and treatment of malignant melanoma of the outer skin. The first histologically confirmed tumor of each patient was included in the analyses. The study cohort includes all patients residing in Saxony who were 18 years or older at the time of diagnosis (≤18 years). For the period from 2005 to 2023, a total of N=18,121 patients were included (data status 04.04.2025). In addition to the cancer registry data, data from the Statistical Office of the Free State of Saxony on population figures were included. Besides descriptive statistics, chi-square tests and Fisher’s exact tests were used for bivariate comparisons. Cox regressions including log-rank tests were performed for overall survival in the individual cancer stages (UICC I-IV, ascending by disease progression) without and with ICI treatment.

Results: In the years 2005 to 2023, there was a 2.5-fold increase in the age-standardized incidence rate of malignant melanoma in Saxony (2005: N=607; 2023: N=1,547). The complexity of the treatment of malignant melanoma with advanced UICC stage increased (UICC I and II: primarily surgery, UICC III and IV: surgery + systemic therapy + radiotherapy of metastases and lymphatic drainage area if necessary). Since the introduction of ICI, this type of therapy has increasingly replaced chemotherapy and interferon therapy for UICC stage III and IV (each p=0.000). In addition, we have detected a shift in the reasons for discontinuation of treatment over the last five years. While 14% of therapies were discontinued due to side effects in 2019, this figure was 23% in 2023 (p=0.014). At the same time, the use of the effective but side-effect-rich combination ipilimumab+nivolumab has increased (2019: 33%; 2023: 40%; p=0.000). Treatment discontinuation due to side effects was more common among patients receiving ipilimumab+nivolumab treatment (30%), whereas other combination therapies (3%) and monotherapies (13%) less frequently resulted in discontinuation for this reason. It should be particularly emphasized that patients in UICC stage III with ICI therapy showed no significantly different survival to patients in UICC stage I (HR=1.13; CI: 0.8-1.6; p=0.485), but patients with UICC stage IV also benefited from ICI treatment (with ICI: HR=4.95; CI: 4.5-5.4; without ICI: HR=7.98; CI: 7.4-8.6).

Discussion: Early detection of malignant melanoma remains crucial for the prognosis and success of treatment. However, with the approval of ICI, a promising treatment option has also been developed for patients with advanced malignant melanoma, albeit with a considerable range of side effects.

Conclusion: The cancer registry data underline the success of ICI therapy, but also the need for intensive medical care in the treatment of patients.

The authors declare that they have no competing interests.

The authors declare that an ethics committee vote is not required.

Literatur

[1] Lamos C Hunger RE. Checkpoint inhibitors-indications and application in melanoma patients. Z Rheumatol. 2020;79(8):818-825. DOI: 10.1007/s00393-020-00870-8
[2] Almutairi AR, McBride A, Slack M, Erstad BL, Abraham I. Potential Immune-Related Adverse Events Associated With Monotherapy and Combination Therapy of Ipilimumab, Nivolumab, and Pembrolizumab for Advanced Melanoma: A Systematic Review and Meta-Analysis. Front Oncol. 2020;10:91. DOI: 10.3389/fonc.2020.00091
[3] Durbin SM, Zubiri L, Perlman K, Wu CY, Lim T, Grealish K, Hathaway N, LoPiccolo J, Wang M, Falade A, Molina G, Jacoby TV, Shah N, Mooradian MJ, Reynolds KL. Late-Onset Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy. JAMA Netw Open. 2025;8(3):e252668. DOI: 10.1001/jamanetworkopen.2025.2668