Early-stage melanoma can be cured by surgical resection, and undetected disease progression or relapse to advanced disease can be avoided when detected early. However, sensitive blood-based tools capable of detecting early-stage disease, residual disease or early disease recurrence are lacking. Circulating tumour-specific antibodies have shown promise as cancer biomarkers, particularly in melanoma. Unlike circulating tumour DNA, these antibodies do not rely on the presence and knowledge of tumour-specific mutations.
We utilize a custom cancer array capable of profiling 123 tumour-specific and associated antigens to determine if cognate antibodies can be used to detect early-stage melanoma. Upon successful detection of early disease onset, we further investigated if undetected residual disease following surgery led to detectable antibodies prior to clinically evident disease recurrence. Circulating tumour DNA (ctDNA) was measured in parallel for a subset of these patients with common BRAF and NRAS mutations.
Diagnostic blood samples from 200 stage I and II melanoma patients and 30 healthy individuals were screened on the array using separate Discovery (n=100) and Validation (n=100) cohorts. Univariate ROC analysis of our first cohort revealed that circulating antibodies against 4 tumour antigens resulted in AUC values ranging from 0.846 to 0.981, which was validated in our second cohort with antigen-matched AUC values from 0.824 to 0.985. Antibody kinetics were also investigated for 39 of the above early-stage melanoma patients with available follow-up blood, with regards to predicting disease recurrence by the detection of residual disease. Although ctDNA levels were elevated at disease recurrence, residual disease did not lead to detectable ctDNA.
Circulating tumour-specific antibodies may be used to detect melanoma at disease onset or early recurrence, and indicate if surgery was curative, thereby informing therapeutic decisions and improving patient outcomes