Reflectance Confocal Microscopy Improves Skin Cancer Diagnosis in New Trial

Findings from the randomized NET-DAM trial (Advanced Non-invasive Diagnostics for Early Cutaneous Tumor Diagnosis, Clinical-therapeutic and Economic Management) show that benefits to reflectance confocal microscopy (RCM) are 2-fold for in vivo skin cancer diagnoses: The diagnostic method both reduces unnecessary lesion excision and identifies invasive melanomas at baseline.

Findings were published recently in JAMA Dermatology.

The investigation encompassed 3165 patients undergoing care at 3 dermatology centers in Italy—the Department of Dermatology of the University of Modena and Reggio Emilia, the Skin Cancer Unit of IRCCS Reggio Emilia, and the Skin Cancer Unit of IRCCS IRST Romagna—and enrolled between January 2017 and December 2019. Prior to data analyzation, which took place from April to September 2021, these patients were randomized 1:1 to either standard therapeutic care only (the control group; n = 1582) or standard care plus adjunctive RCM (the study group; n = 1583). Most of the patients were male (50.8%), and the overall mean (SD) age was 49.3 (14.9) years.

“Previous systematic reviews and meta-analyses have concluded that given data paucity, a comparison of RCM with dermoscopy is complex,” the authors wrote. “They recommend comparative prospective studies in a real-world setting of suspect lesions.”

Over a mean follow-up of 9.6 (6.9) months (range, 1.9-37.0) months, 48 patients were lost to follow-up and 39 refused lesion excision. Among those included in the final analysis, adjunctive RCM was shown to have a higher positive predictive value, a lower benign to malignant ratio, and a significantly reduced number needed to excise vs standard treatment:

• Positive predictive value: 33.3 vs 18.9
• Benign to malignant ratio: 1.8:1.0 vs 3.7:1.0
• Number needed to excise: 3.0 vs 5.3

Of note, the authors highlighted, the number needed to excise findings represents a 43.4% reduction with use of RCM—which is almost 14 percentage points higher than the 30% they predicted before their study. They noted that RCM appears more accurate than dermoscopy alone.

The authors had also hypothesized before their study that for clinicians who requested dermoscopy digital follow-up of lesions, RCM would lead to a melanoma positive rate in less than 2% of lesions with a Breslow thickness of 0.5 mm or less. All of the lesions identified in their study that had a delayed diagnosis were 0.5 mm or thinner.

The most common site of lesions was the trunk, in 67.7% of the study group and 69.3% of the control group. Phototypes 2 and 3 were the most common types among the entire study population (50.5% and 39.3%, respectively), as well as the study (51.8% and 39.0%) and control (49.1% and 39.6%) groups, respectively. In addition, 72.2% of each patient cohort had fewer than 3 atypical nevi and only 44.9% of all lesions “had photodamage immediately around the suspected lesion.”

Additional study analyses showed the following results:

• In the study group, just 45.5% of patients had been sent for immediate excision
• Short-term follow-up in the study group led to more excisions vs long-term follow-up: 17.9% vs 7.2%
• A melanoma positivity rate of 33.2% was seen among the study group following lesion excision and adjunctive RCM vs 18.6% diagnosed through histopathology alone
• In the control group, 99.8% of patients were assigned excision
• More lesions in the control group were classified as melanoma in situ vs the study group: 60.5% vs 51.8%

“This randomized interventional trial assessed the applicability of adjunctive RCM for equivocal lesions suspected of melanoma in a clinical setting and proves that unnecessary excisions can be reduced by almost half,” the authors concluded, “with greater accuracy of in vivo identification of benign lesions. Furthermore, delayed diagnosis included thin melanomas only.”

They note their data can help aid in ongoing discussions around the use of advanced technologies for routine melanoma detection, because before their study, “most estimates of NNE calculations were based on retrospective analyses.

Reference

Pellacani G, Fernetani F, Ciardo S, et al. Effect of reflectance confocal microscopy for suspect lesions on diagnostic accuracy in melanoma: a randomized clinical trial. JAMA Dermatol. Published online June 1, 2022. doi:10.1001/jamadermatol.2022.1570