Initial Stage of Cutaneous Primary Melanoma Plays a Key Role in the Pattern and Timing of Disease Recurrence

Ertekin, Sümeyre Seda; Podlipnik, Sebastián; Loughlin, Constanza Riquelme‐Mc; Barreiro-Capurro, Alicia; Arance, Ana; Carrera, Cristina; Malvehy, Josep; Puig, Susana

doi:10.2340/00015555-3832

Cited by 16 publications

(24 citation statements)

References 35 publications

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“…In our study, 56.6% of first recurrences were distant, which is considerably higher than rates reported a decade ago but close to the 49.9% recently reported for patients with stage IIB to III melanoma, followed up with routine CT and magnetic resonance imaging . This high proportion of distant recurrences indicates that hematogenous dissemination is a more common metastatic pathway in melanoma than previously assumed and suggests a potential benefit of functional/cross-sectional imaging in surveillance .…”

Section: Discussionsupporting

confidence: 71%

Stage-Specific Risk of Recurrence and Death From Melanoma in Denmark, 2008-2021

Helvind,

Brinch-Møller Weitemeyer,

Chakera

et al. 2023

JAMA Dermatol

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ImportanceTo ensure optimal treatment and surveillance of patients with melanoma, knowledge of the clinical stage-specific risk of recurrence, mortality, and recurrence patterns across the American Joint Committee on Cancer Eighth Edition (AJCC8) substages is needed.ObjectiveTo estimate stage-specific recurrence and melanoma-specific mortality rates, assess absolute stage-specific risks of recurrence and mortality, and describe stage-specific recurrence patterns, including conditional rates.DesignRetrospective cohort study of prospectively collected nationwide population-based registry data.SettingNationwide, population-based cohort study.ParticipantsThe 25 720 Danish patients, 18 years or older, diagnosed with first-time stage IA to IV cutaneous melanoma between January 1, 2008, and December 31, 2019, were included and followed up from time of primary treatment until December 31, 2021.ExposuresFirst diagnosis of stage IA to IV cutaneous melanoma.Main OutcomesStage-specific cumulative incidence of recurrence and melanoma-specific mortality, melanoma-specific recurrence-free survival, and assessed absolute stage-specific risks of recurrence and melanoma-specific mortality. Secondary outcomes were stage-specific recurrence patterns, including conditional rates, and melanoma-specific survival.ResultsWe followed up 25 720 patients for a median of 5.9 years (95% CI, 58.9-59.3 years). Mean age was 59.1 years (95% CI, 58.9-59.3 years). Patients with stage IIB to IIC melanoma were older, had more comorbidities at diagnosis, and had the lowest rate of pathologic staging by sentinel node biopsy (81.6%-87.4%). A total of 10.6% of patients developed recurrence; first recurrence included distant recurrence, alone or with synchronous locoregional recurrence, in 56.6% of patients. We found a comparable risk of recurrence in stages IIIA and IIB (29.7% vs 33.2%) and in stages IIIB and IIC (35.9% vs 36.8%), respectively. Melanoma-specific mortality was comparable between stages IIIA and IIA (13.0% vs 13.6%) and between stages IIIB and IIB (18.4% vs 22.0%), respectively. These risk patterns persisted in cause-specific hazards models.Conclusions and RelevanceThis nationwide, population-based cohort study found that the increasing stages of the current AJCC8 staging system do not accurately reflect an increasing risk of recurrence and mortality in melanoma. The high proportion of distant recurrences suggests that hematogenous spread is a more common metastatic pathway than previously assumed, and surveillance with routine functional/cross-sectional imaging should be considered for stages IIB to IV. Future efforts should be put toward developing new tools for risk stratification and determining the survival effect of routine imaging in surveillance.

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Section: Discussionsupporting

confidence: 71%

Stage-Specific Risk of Recurrence and Death From Melanoma in Denmark, 2008-2021

Helvind,

Brinch-Møller Weitemeyer,

Chakera

et al. 2023

JAMA Dermatol

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“…Compared with thicker melanomas, they have a greater propensity for locoregional metastasis and are less likely to spread to distant sites [21]. Our results, however, indicate the presence of synchronous regional and distant metastasis in thin melanoma, which would explain the absence of a significant survival benefit for SLNB in this setting [23][24][25].…”

Section: Discussionmentioning

confidence: 52%

Sentinel Lymph Node Biopsy vs. Observation in Thin Melanoma: A Multicenter Propensity Score Matching Study

Tejera‐Vaquerizo¹,

Boada

Ribero

et al. 2021

JCM

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The therapeutic value of sentinel lymph node biopsy (SLNB) in thin melanoma remains controversial. The aim of this study is to determine the role of SLNB in the survival of thin melanomas (≤1 mm). A multicenter retrospective observational study was designed. A propensity score matching was performed to compare patients who underwent SLNB vs. observation. A multivariate Cox regression was used. A total of 1438 patients were matched by propensity score. There were no significant differences in melanoma-specific survival (MSS) between the SLNB and observation groups. Predictors of MSS in the multivariate model were age, tumor thickness, ulceration, and interferon treatment. Results were similar for disease-free survival and overall survival. The 5- and 10-year MSS rates for SLN-negative and -positive patients were 98.5% vs. 77.3% (p < 0.001) and 97.3% vs. 68.7% (p < 0.001), respectively. SLNB does not improve MSS in patients with thin melanoma. It also had no impact on DSF or OS. However, a considerable difference in MSS, DFS, and OS between SLN-positive and -negative patients exists, confirming its value as a prognostic procedure and therefore we recommend discussing the option of SLNB with patients.

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“…Bioinformatics tools have been widely used to analyze Next Generation Sequencing (NGS) data in order to identify gene mutations potentially associated with the etiopathogenesis of melanoma [ 30 , 31 , 32 ]. Moreover, the study of the integrated properties of melanoma, its tissue microenvironment, and immune invasion is guided by classical histopathology, while the profiling of protein or RNA expression in particular has revealed some molecular features associated with tumor development that involve paracrine cytokine signaling [ 33 , 34 ]. Thus, the spatial landscape of primary melanoma progression is being enhanced by the use of multiplex analyses [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, adjuvant treatment is not usually recommended for stage I and II melanoma, even though the mortality rate at 10 years may be relatively high [ 37 ]. Indeed, in an analysis of the gene expression profiles of 523 primary melanomas, 70% of stage I and II patients developed distant metastasis [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Along with the Breslow thickness, the Melanoma CDSS includes features such as the relative number of tumors infiltrating L-BCL2 + and serum levels of IL-4 or IL-6, all of which have been reported to be important risk factors for melanoma progression [ 9 ]. The Breslow thickness alone has been considered a malignant risk factor [ 34 ], but an important increase in the predictive power of the Breslow Index was achieved by combining it with data regarding infiltrating L-BCL2 + and serum levels of IL-4 and GM-CSF. Models obtained using RapidMiner DTs show that the Breslow index, infiltrating L-BCL2 + , and IL-4 levels are associated with a poor prognosis, whereas a decrease in GM-CSF serum levels directly identifies early-stage melanoma patients in whom the disease-free survival is less than 21.5 months.…”

Section: Discussionmentioning

confidence: 99%

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Melanoma Clinical Decision Support System: An Artificial Intelligence-Based Tool to Diagnose and Predict Disease Outcome in Early-Stage Melanoma Patients

Díaz-Ramón

Gardeazábal

Izu

et al. 2023

Cancers

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This study set out to assess the performance of an artificial intelligence (AI) algorithm based on clinical data and dermatoscopic imaging for the early diagnosis of melanoma, and its capacity to define the metastatic progression of melanoma through serological and histopathological biomarkers, enabling dermatologists to make more informed decisions about patient management. Integrated analysis of demographic data, images of the skin lesions, and serum and histopathological markers were analyzed in a group of 196 patients with melanoma. The interleukins (ILs) IL-4, IL-6, IL-10, and IL-17A as well as IFNγ (interferon), GM-CSF (granulocyte and macrophage colony-stimulating factor), TGFβ (transforming growth factor), and the protein DCD (dermcidin) were quantified in the serum of melanoma patients at the time of diagnosis, and the expression of the RKIP, PIRIN, BCL2, BCL3, MITF, and ANXA5 proteins was detected by immunohistochemistry (IHC) in melanoma biopsies. An AI algorithm was used to improve the early diagnosis of melanoma and to predict the risk of metastasis and of disease-free survival. Two models were obtained to predict metastasis (including “all patients” or only patients “at early stages of melanoma”), and a series of attributes were seen to predict the progression of metastasis: Breslow thickness, infiltrating BCL-2 expressing lymphocytes, and IL-4 and IL-6 serum levels. Importantly, a decrease in serum GM-CSF seems to be a marker of poor prognosis in patients with early-stage melanomas.

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Initial Stage of Cutaneous Primary Melanoma Plays a Key Role in the Pattern and Timing of Disease Recurrence

Cited by 16 publications

References 35 publications

Stage-Specific Risk of Recurrence and Death From Melanoma in Denmark, 2008-2021

Stage-Specific Risk of Recurrence and Death From Melanoma in Denmark, 2008-2021

Sentinel Lymph Node Biopsy vs. Observation in Thin Melanoma: A Multicenter Propensity Score Matching Study

Melanoma Clinical Decision Support System: An Artificial Intelligence-Based Tool to Diagnose and Predict Disease Outcome in Early-Stage Melanoma Patients

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