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"[The original diagnosis] was based on the [findings of a] local pathologist. [The stage of the diagnosis] can be very impactful for patients who might receive management based on the decision of the local pathologist [to call] call it a metastatic melanoma. [Corresponding treatment] could be systemic therapy or surgery, and [there are] potential complications and toxicities associated with that."

Alexander C.J. Van Akkooi, MD, PhD, FRACS, chair, Melanoma Surgery, Melanoma Institute Australia; associate professor, University of Sydney, discusses findings from the prospective EORTC-1208-MG registry study (NCT01942603), which, in addition to evaluating the outcomes of patients with minimal sentinel node tumor burden who were managed without complete lymph node dissection, evaluated the accuracy of local pathological review in diagnosing metastatic melanoma.

In this multicenter registry study, van Akkooi notes that investigators conducted central pathological reviews of lesions initially classified as metastatic melanoma by local pathologists. The analysis confirmed that 11% of lesions diagnosed as metastatic melanoma were nonmetastatic upon central review. This misclassification could lead to unnecessary systemic therapy or surgery, exposing patients to potential toxicities and complications associated with overtreatment.

This discrepancy highlights the need for improved diagnostic accuracy, van Akkooi emphasizes, noting the importance of educating pathologists on the challenges of diagnosing small or ambiguous lesions. He also recommended implementing a secondary review board for cases by independent pathologists to ensure diagnostic precision and reduce the likelihood of overtreatment. These measures could improve patient outcomes by preventing unnecessary therapies and interventions, he notes.

The EORTC-1208-MG registry study also established a biobank of tissue, plasma, and serum samples for future translational research. These biospecimens will enable the investigation of biomarkers and molecular characteristics associated with melanoma, potentially enhancing diagnostic and therapeutic strategies.

Van Akkooi notes that ongoing collaborative efforts are focused on evaluating whether insights from the study can be incorporated into the forthcoming 9th edition of the American Joint Committee on Cancer staging system.

Videos

Alexander C.J. Van Akkooi, MD, PhD, FRACS, discusses how discrepancies in local and central pathologic review can expose patients to potential toxicities associated with overtreatment for metastatic melanoma.

Dr Akkooi on Pathologic Review Discrepancies and Overtreatment Risks in Metastatic Melanoma

Alexander C. Van Akkooi, MD, PhD, FRACS, discusses the prognostic value of minimal sentinel node tumor burden in melanoma.

Dr Van Akkooi on the Prognostic Value of Minimal Sentinel Node Tumor Burden in Melanoma

Alexander C. Van Akkooi, MD, PhD, FRACS, chair, Melanoma Surgery, Melanoma Institute Australia; associate professor, the University of Sydney, Australia, discusses the prognostic value of minimal sentinel node tumor burden in melanoma, as evaluated in the prospective EORTC-1208-MG registry study (NCT01942603).

The aim of the trial was to evaluate the outcomes of patients with minimal sentinel node tumor burden who were managed without complete lymph node dissection. Investigators hypothesized that the cumulative incidence of distant metastasis at 5 years would be less than 20% in patients with pT2-pT3 tumors. The primary analysis revealed that the cumulative distant metastasis free survival (DMFS) rate in this cohort was 15% (90% CI, 10%-21%) at a median follow-up of 4.5 years, though this result did not meet the study’s primary end point of statistical significance, Van Akkooi reports. The subgroup of patients with AJCC stage IIIA tumors and minimal tumor burden who chose observation had a 5-year DMFS rate of 8.2% (95% CI, 2.8%-17.4%), he notes.

A notable finding was the high rate of discrepancy upon central pathology review, which indicated significant overdiagnosis of sentinel node metastasis in many cases, Van Akkooi continues. Patients who were reclassified following the central review demonstrated a high DMFS rate at 5 years, suggesting that the central pathology review was accurate and that some patients initially diagnosed with minimal tumor burden had an even more favorable prognosis than anticipated, he adds.

The study further identified that sentinel tumor burden, along with AJCC stage, were independent prognostic factors, suggesting the possibility of refining future staging systems, Van Akkooi says. Incorporating these factors may allow for better prognostication and may potentially spare low-risk stage III patients from the toxicity associated with adjuvant therapies, he explains. These findings could influence future clinical guidelines by shifting management strategies for patients with minimal tumor burden towards less invasive approaches, especially for those in earlier stages of disease, Van Akkooi concludes.

Alexander van Akkooi, MD, PhD, FRACS

Articles

Dr Akkooi on Pathologic Review Discrepancies and Overtreatment Risks in Metastatic Melanoma

Dr Van Akkooi on the Prognostic Value of Minimal Sentinel Node Tumor Burden in Melanoma