Defining and modeling 'cure' in early-stage melanoma: perspectives from a systematic literature review

Defining "cure" in oncology remains conceptually and methodologically challenging, particularly in early-stage melanoma treated with curative intent. Recent advances in adjuvant and neoadjuvant immunotherapy have improved relapse-free and event-free survival, raising questions about how and when recurrence-free patients can be considered cured. This review aimed to clarify how "cure" is defined, identified, and modeled in early-stage melanoma and to describe the clinical and methodological evidence supporting cure assumptions.

A systematic literature review (SLR) was conducted in MEDLINE and Embase from January 2014 to July 2024 using a predefined PICOTS framework. Eligible studies described definitions of "cure," criteria for identifying cure, or quantitative modeling of long-term outcomes in solid tumors, with a focus on melanoma. Data were screened and extracted using a hybrid AI-assisted process consistent with PRISMA standards.

Twenty-six publications were included and grouped into analytical, data driven review, and expert-opinion categories. Most defined cure statistically, based on survival plateaus or estimated cure fractions (CFs), which ranged widely from 28% in cases with nodal category 3, to 99% for cases with localized disease according to summary stage at diagnosis. Cure estimates varied by disease stage, age, gender, and tumor site. Few studies compared cure across treatment modalities, reflecting ongoing methodological challenges with overall survival data maturity and confounding, as well as uncertainty about progression-free survival (PFS) or relapse free survival (RFS) as reliable surrogates for cure.

Cure in early-stage melanoma remains variably defined across clinical and statistical contexts. Standardized terminology, biologically grounded definitions, and mature long-term datasets are needed to support consistent and credible modeling of curative outcomes.