Improved cutaneous melanoma survival stratification through integration of 31-gene expression profile testing with the American Joint Committee on Cancer 8th Edition Staging.

Cutaneous melanoma (CM) survival is assessed using averaged data from the American Joint Committee on Cancer 8th edition (AJCC8). However, subsets of AJCC8 stages I-III have better or worse survival than the predicted average value. The objective of this study was to determine if the 31-gene expression profile (31-GEP) test for CM can further risk-stratify melanoma-specific mortality within each AJCC8 stage. This retrospective multicenter study of 901 archival CM samples obtained from patients with stages I-III CM assessed 31-GEP test predictions of 5-year melanoma-specific survival (MSS) using Kaplan-Meier and Cox proportional hazards. In stage I-III CM population, patients with a Class 2B result had a lower 5-year MSS (77.8%) than patients with a Class 1A result (98.7%) and log-rank testing demonstrated significant stratification of MSS [χ2 (2df, n = 901) = 99.7, P < 0.001). Within each stage, 31-GEP data provided additional risk stratification, including in stage I [χ2 (2df, n = 415) = 11.3, P = 0.004]. Cox regression multivariable analysis showed that the 31-GEP test was a significant predictor of melanoma-specific mortality (MSM) in patients with stage I-III CM [hazard ratio: 6.44 (95% confidence interval: 2.61-15.85), P < 0.001]. This retrospective study focuses on Class 1A versus Class 2B results. Intermediate results (Class 1B/2A) comprised 21.6% of cases with survival rates between Class 1A and 2B, and similar to 5-year MSS AJCC stage values. Data from the 31-GEP test significantly differentiates MSM into lower (Class 1A) and higher risk (Class 2B) groups within each AJCC8 stage. Incorporating 31-GEP results into AJCC8 survival calculations has the potential to more precisely assess survival and enhance management guidance.

Expert Consensus on the Use of Prognostic Gene Expression Profiling Tests for the Management of Cutaneous Melanoma: Consensus from the Skin Cancer Prevention Working Group.

BACKGROUND: Prognostic assessment of cutaneous melanoma relies on historical, clinicopathological, and phenotypic risk factors according to American Joint Committee on Cancer(AJCC) and National Comprehensive Cancer Network (NCCN) guidelines but may not account for a patient's individual additional genetic risk factors. OBJECTIVE: To review the available literature regarding commercially available gene expression profile (GEP) tests and their use in the management of cutaneous melanoma. METHODS: A literature search was conducted for original, English-language studies or meta-analyses published between 2010 and 2021 on commercially available GEP tests in cutaneous melanoma prognosis, clinical decision-making regarding sentinel lymph node biopsy, and real-world efficacy. After the literature review, the Skin Cancer Prevention Working Group, an expert panel of dermatologists with specialized training in melanoma and non-melanoma skin cancer diagnosis and management, utilized a modified Delphi technique to develop consensus statements regarding prognostic gene expression profile tests. Statements were only adopted with a supermajority vote of > 80%. RESULTS: The initial search identified 1064 studies/meta-analyses that met the search criteria. Of these, we included 21 original articles and meta-analyses that studied the 31-GEP test (DecisionDx-Melanoma; Castle Biosciences, Inc.), five original articles that studied the 11-GEP test (Melagenix; NeraCare GmbH), and four original articles that studied the 8-GEP test with clinicopathological factors (Merlin; 8-GEP + CP; SkylineDx B.V.) in this review. Six statements received supermajority approval and were adopted by the panel. CONCLUSION: GEP tests provide additional, reproducible information for dermatologists to consider within the larger framework of the eighth edition of the AJCC and NCCN cutaneous melanoma guidelines when counseling regarding prognosis and when considering a sentinel lymph node biopsy.

Enhanced melanoma diagnosis with multispectral digital skin lesion analysis.

Multispectral digital skin lesion analysis (MSDSLA) is both sensitive and specific in the detection of malignant melanoma by dermatologists and nondermatologists, and data have shown that MSDSLA can be a valuable tool in the evaluation of pigmented skin lesions (PSLs). This study aimed to aggregate data from 7 prior studies to provide a comprehensive overview and evaluate the consistency of the effects of MSDSLA when used in conjunction with clinical examination and dermoscopy to evaluate PSLs.

Clinical Diagnosis of Skin Cancer: Enhancing Inspection and Early Recognition.

The annual incidence rate for melanoma and nonmelanoma skin cancer continues to rise and morbidity and deaths from skin cancer are increasing. Despite advances in therapeutics, the factors that most impact prognosis remain early recognition and removal of neoplasms before deep invasion or metastatic disease can occur. There are numerous public health and screening initiatives that have been introduced to help recognize disease earlier and to increase patients' awareness of signs or changes of lesions that may represent skin cancers. Early recognition and removal of suspicious lesions remains critical in significantly reducing morbidity and mortality associated with skin cancers.

Noninvasive Technologies for the Diagnosis of Cutaneous Melanoma.

Multispectral analysis devices assess pigmented lesion disorganization at different levels using variable wavelengths of light. Computerized algorithms measure morphologic disorganization of the pigmented skin lesion. Aggregated data of 855 participants investigating the influence of multispectral digital skin lesion analysis (MSDSLA) on practitioner decisions to biopsy pigmented skin lesions revealed the overall sensitivity for detection of melanoma improved from 70% to 88%. Participant specificity increased from 52% to 58% after MSDSLA. Five studies using spectrophotometric intracutaneous analysis scope to evaluate suspicious pigmented skin lesions demonstrated an overall sensitivity and specificity of 85% and 81%, respectively, for the detection of melanoma.

Assessing Genetic Expression Profiles in Melanoma Prognosis.

A 31-genetic expression profile (31-GEP) test (DecisionDx-Melanoma, Castle Biosciences Inc, Friendswood, TX, USA) was developed as a diagnostic test to assist physicians in the management of cutaneous malignant melanoma. Based on a patient's primary tumor expression levels of a panel of genes (28 discriminating genes and 3 control genes), a lesion is classified as "low risk" (class 1) or "high risk" (class 2) for metastasis. Studies evaluating the clinical utility and impact of the 31-GEP test showed it positively influenced clinical management and patient care, as clinicians incorporated the additional data to modify their clinical recommendations in a risk-appropriate manner.

Integrating Skin Cancer-Related Technologies into Clinical Practice.

Early diagnosis and treatment of melanoma improve survival. New technologies are emerging that may augment the diagnosis, assessment, and management of melanoma but penetrance into everyday practice is low. In the current health care climate, greater emphasis will be placed on the incorporation of technology for clinically suspicious pigmented lesions to facilitate better, more cost-effective management.

Quantitative ABCD parameters measured by a multispectral digital skin lesion analysis device for evaluation of suspicious pigmented skin lesions strongly correlate with clinical ABCD observations.

Background/Study Aim: A multispectral digital skin lesion analysis (MSDSLA) device has proven to be sensitive and specific for malignant melanoma (MM) detection by dermatologists and may have other useful applications. This study aimed to develop and test objective quantitative Asymmetry, Border irregularity, Color, and Diameter (qABCD) parameters for MSDSLA and correlate them with the presence of clinical ABCD features to aid the decision to biopsy a suspicious pigmented skin lesions (PSLs). METHODS: 1632 benign and malignant [175 MM/High Grade Dysplastic Nevi (HGDN)] were evaluated for their qABCD parameters. Quantitative characteristics were correlated with the presence of clinical ABCD features identified by independent dermatologists. RESULTS: qA, qB, qC, and qD had correlations of 78%, 73%, 76%, and 86%, respectively, for non-MM/HGDN lesions. The correlations for qA, qB, qC, and qD for MM/HGDN lesions was 86.3%, 83%, 89%, and 89%, respectively. All repeatability parameters were statistically significant. CONCLUSIONS: This study demonstrates qABCD values are repeatable and strongly correlate with the clinical ABCD features. qABCD characteristics provide an additional objective and reliable means of identifying PSLs that need further evaluation to rule out MM and, in combination with the clinical ABCDs, may allow for improved assessment when evaluating the malignant potential of PSLs.

The Impact of Quantitative Data Provided by a Multi-spectral Digital Skin Lesion Analysis Device on Dermatologists'Decisions to Biopsy Pigmented Lesions.

BACKGROUND: Early diagnosis of melanoma is critical to survival. New technologies, such as a multi-spectral digital skin lesion analysis (MSDSLA) device [MelaFind, STRATA Skin Sciences, Horsham, Pennsylvania] may be useful to enhance clinician evaluation of concerning pigmented skin lesions. Previous studies evaluated the effect of only the binary output. OBJECTIVE: The objective of this study was to determine how decisions dermatologists make regarding pigmented lesion biopsies are impacted by providing both the underlying classifier score (CS) and associated probability risk provided by multi-spectral digital skin lesion analysis. This outcome was also compared against the improvement reported with the provision of only the binary output. METHODS: Dermatologists attending an educational conference evaluated 50 pigmented lesions (25 melanomas and 25 benign lesions). Participants were asked if they would biopsy the lesion based on clinical images, and were asked this question again after being shown multi-spectral digital skin lesion analysis data that included the probability graphs and classifier score. RESULTS: Data were analyzed from a total of 160 United States board-certified dermatologists. Biopsy sensitivity for melanoma improved from 76 percent following clinical evaluation to 92 percent after quantitative multi-spectral digital skin lesion analysis information was provided (p<0.0001). Specificity improved from 52 percent to 79 percent (p<0.0001). The positive predictive value increased from 61 percent to 81 percent (p<0.01) when the quantitative data were provided. Negative predictive value also increased (68% vs. 91%, p<0.01), and overall biopsy accuracy was greater with multi-spectral digital skin lesion analysis (64% vs. 86%, p<0.001). Interrater reliability improved (intraclass correlation 0.466 before, 0.559 after). CONCLUSION: Incorporating the classifier score and probability data into physician evaluation of pigmented lesions led to both increased sensitivity and specificity, thereby resulting in more accurate biopsy decisions.

Enhancement of International Dermatologists' Pigmented Skin Lesion Biopsy Decisions Following Dermoscopy with Subsequent Integration of Multispectral Digital Skin Lesion Analysis.

BACKGROUND: Early detection and subsequent management of melanoma are critical for patient survival. New technologies have been developed to augment clinician analysis of suspicious pigmented skin lesions. OBJECTIVE: To determine how information provided by a multispectral digital skin lesion analysis device affects the biopsy decisions of international dermatologists following clinical and dermoscopic pigmented skin lesion evaluation. METHODS: Participants at a dermoscopy conference in Vienna, Austria, were shown 12 clinical and dermoscopic images of pigmented skin lesions (2 melanomas in situ, 3 invasive melanomas, and 7 low-grade dysplastic nevi) previously analyzed by multispectral digital skin lesion analysis. Participants were asked if they would biopsy the lesion based on clinical images, again after observing high-resolution dermoscopy images, and again when subsequently shown multispectral digital skin lesion analysis information. RESULTS: Data were analyzed from a total of 70 international dermatologists. Overall, sensitivity was 58 percent after clinical evaluation (C) and 59 percent post-dermoscopy (D), but 74 percent after multispectral digital skin lesion analysis. Participant specificity was 56 percent (C) decreasing to 51 percent (D), but increasing to 61 percent with multispectral digital skin lesion analysis. Diagnostic accuracy was 57 percent (C) decreasing to 54 percent (D), but increasing to 67 percent for dermatologists after integrating the multispectral digital skin lesion analysis data into the biopsy decision. The overall number of lesions biopsied increased from 50 percent (C) to 53 percent (D), rising to 54 percent after multispectral digital skin lesion analysis. CONCLUSION: Decisions to biopsy melanocytic lesions were more sensitive and specific when multispectral digital skin lesion analysis information was provided with no significant increase in the number of biopsies recommended. Providing multispectral digital skin lesion analysis data may lead to additional improvement in biopsy accuracy with a concomitant decrease in the number of nonessential biopsies for pigmented skin lesions even after dermoscopic evaluation.

Correlation Between the Evaluation of Pigmented Lesions by a Multi-spectral Digital Skin Lesion Analysis Device and the Clinical and Histological Features of Melanoma.

OBJECTIVE: To correlate Multi-spectral Digital Skin Lesion Analysis classifier scores with histopathological severity of pigmented lesions and clinical features of melanoma. DESIGN: Classifier scores were computed for 1,632 skin lesions. Dermatologists evaluated the same lesions for Asymmetry, Border Irregularity, Color variegation, Diameter >6mm, Evolution, Patient's Concern, Regression, and/or "Ugly Duckling" sign. Classifier scores were correlated to the number of clinical risk features and for six histopathological severity levels of pigmented lesions. MEASUREMENTS: Average classifier score, Welch's t-test, and chi-square analysis. RESULTS: Melanomas had higher mean classifier scores (3.5) than high-grade dysplastic nevi (2.7, p=0.002), low-grade dysplastic nevi (1.7, p<0.0001), non-dysplastic nevi (1.6, p<0.0001), and benign non-melanocytic lesions (2.0, p<0.0001). Classifier score and the number of clinical risk characteristics directly correlated (Pearson coefficient 0.32, p<0.0001). CONCLUSION: Correlation of classifier scores to clinical and histological melanoma features supports the effectiveness of Multi-spectral Digital Skin Lesion Analysis in assessing the risk of pigmented lesions requiring biopsy. Optimizing outcomes of dermatologist decisions to biopsy suspicious pigmented lesions may be enhanced utilizing Multi-spectral Digital Skin Lesion Analysis.

The Impact of Multispectral Digital Skin Lesion Analysis on German Dermatologist Decisions to Biopsy Atypical Pigmented Lesions with Clinical Characteristics of Melanoma.

OBJECTIVE: To determine the impact of multispectral digital skin lesion analysis on German dermatologist biopsy decisions of atypical pigmented skin lesions. DESIGN: Participants were shown high-resolution clinical images of 12 atypical pigmented skin lesions previously analyzed by multispectral digital skin lesion analysis. Participants were asked if they would biopsy the lesion based on clinical images and high-resolution dermoscopy images and again when subsequently shown multispectral digital skin lesion analysis probability information. SETTING/PARTICIPANTS: Forty-one dermatologists at a skin cancer conference in Germany in September 2014. MEASUREMENTS: Sensitivity, specificity, diagnostic accuracy, percent biopsying all melanomas, and overall biopsy rates. RESULTS: Sensitivity for the detection of melanoma following clinical evaluation was 64 percent. After receipt of multispectral digital skin lesion analysis probability information, sensitivity decreased nonsignificantly to 62 percent. Specificity with clinical evaluation was 57 percent and increased to 73 percent using multispectral digital skin lesion analysis. Overall biopsy accuracy increased from 60 percent with clinical evaluation to 68 percent with multispectral digital skin lesion analysis. The percentage of low-grade dysplastic nevi chosen for biopsy decreased from 43 percent after clinical evaluation to 27 percent with multispectral digital skin lesion analysis. Finally, the overall percentage of lesions biopsied decreased from 52 percent with clinical evaluation to 42 percent after multispectral digital skin lesion analysis. CONCLUSION: Multispectral digital skin lesion analysis can be used reliably to detect melanoma as well as clinical evaluation. Dermatologists can confidently use multispectral digital skin lesion analysis to significantly improve specificity and reduce their overall number of biopsies while increasing overall diagnostic accuracy.

Pigmented Skin Lesion Biopsies After Computer-Aided Multispectral Digital Skin Lesion Analysis.

BACKGROUND: The incidence of melanoma has been rising over the past century. With 37% of patients presenting to their primary care physician with at least 1 skin problem, primary care physicians and other nondermatologist practitioners have substantial opportunity to make an impact at the forefront of the disease process. New diagnostic aids have been developed to augment physician analysis of suspicious pigmented skin lesions (PSLs). OBJECTIVE: To determine the effects of computer-aided multispectral digital skin lesion analysis (MSDSLA) on dermatologists' and nondermatologist clinicians' decisions to biopsy suspicious PSLs after clinical and dermatoscopic evaluation. METHODS: Participants were shown 6 images of PSLs. For each PSL, participants were asked 3 times if they would biopsy the lesion: first after reviewing a clinical image of the PSL, again after reviewing a high-resolution dermatoscopic image, and again after reviewing MSDSLA probability findings. An answer was right if a melanoma or high-risk lesion was selected for biopsy or a low-risk lesion was not selected for biopsy. An answer was wrong if a melanoma or high-risk lesion was not selected for biopsy or a low-risk lesion was selected for biopsy. Clinicians' decisions to biopsy were evaluated using χ² analysis for proportions. RESULTS: Data were analyzed from a total of 212 participants, 177 of whom were dermatologists. Overall, sensitivity of clinical image review was 63%; dermatoscopic image review, 5%; and MSDSLA, 83%. Specificity of clinical image review was 59%; dermatoscopic image review, 40%; and MSDSLA, 76%. Biopsy decision accuracy was 61% after review of clinical images, 52% after review of dermatoscopic images, and 80% after review of MSDSLA findings. The number of lesions participants indicated that they would biopsy increased significantly, from 52% after reviewing clinical images to 63% after reviewing dermatoscopic images (P<.001). However, the overall number of specimens that participants indicated they would biopsy did not change significantly after they reviewed MSDSLA findings (53%). CONCLUSION: Sensitivity, specificity, and biopsy decision accuracy increased after clinicians reviewed MSDSLA findings. The use of objective, computer-based diagnostic aids such as MSDSLA during clinical evaluations of ambiguous PSLs could aid clinicians' decisions to biopsy such lesions.

Impact of Guidance Provided by a Multispectral Digital Skin Lesion Analysis Device Following Dermoscopy on Decisions to Biopsy Atypical Melanocytic Lesions.

OBJECTIVE: To determine how a multispectral digital skin lesion analysis (MSDSLA) device data affects the biopsy performance of dermatologists and non-dermatologist practitioners following clinical and dermoscopic pigmented lesion evaluation. DESIGN: MSDSLA employs near infrared light to image and analyze pigmented skin lesions. MSDSLA generates a "classifier score" based on morphological disorganization. Using a logistical regression model, 1) a probability of being melanoma and, 2) a probability of being melanoma, atypical melanocytic hyperplasia, or a high grade dysplastic nevus is computed. PARTICIPANTS were shown clinical images of 12 lesions (2 melanomas in situ, 3 invasive melanomas, and 7 low grade DNs). They were asked first if they would biopsy the lesion based on clinical images, again after observing dermoscopy images, and once more when presented with MSDSLA probability information. SETTING: National dermoscopy conference. PARTICIPANTS: Sixty-four healthcare providers; 30 dermatologists and 34 non-dermatologist practitioners. MEASUREMENTS: Sensitivity, specificity, diagnostic accuracy, biopsy rates Results: For the 30 dermatologists, sensitivity was 65 percent after clinical evaluation (C) and 65% post-dermoscopy (D) but improved to 91% after MSDSLA. For the 34 non-dermatologist practitioners, sensitivity improved from 66 percent (C) to 70 percent (D) to 95 percent after MSDSLA. With MSDSLA information, dermatologist specificity increased from 40 percent (D) to 58 percent while non-dermatologist practitioners specificity increased from 34 percent (D) to 55 percent. Diagnostic accuracy of malignant and benign lesions decreased for both groups 55 percent (C) to 51 percent (D) for dermatologists and 54 percent (C) to 49 percent (D) for non-dermatologist practitioners. However, diagnostic accuracy increased to 72 percent for dermatologists and 72 percent for non-dermatologist practitioners with MSDSLA data. Non-melanoma biopsy percentages by dermatologists increased from 53 percent (C) to 60 percent (D), but decreased to 42 percent when provided with MSDSLA data. Similarly, non-dermatologist practitioners' biopsy percentages of nonmelanomas increased from 55 percent (C) to 66 percent (D) and decreased to 45 percent with MSDSLA. CONCLUSION: Decisions to biopsy atypical melanocytic lesions were more sensitive and specific when MSDSLA information was provided for both dermatologists and nondermatologist practitioners. Both groups were also less likely to biopsy nonmelanomas after MSDSLA evaluation. The authors' results suggest providing practitioners with MSDSLA data leads to improved biopsy accuracy decreasing the number of nonessential biopsies for nonmelanocytic lesions even after dermoscopic evaluation.

Negative predictive value of pigmented lesion evaluation by multispectral digital skin lesion analysis in a community practice setting.

OBJECTIVE: To determine if the high negative predictive value of a multispectral digital skin lesion analysis that has been previously found in an academic-based trial would be similar in a community-based setting with its expected different distribution of pigmented lesions. DESIGN: Data were collected from patients undergoing routine skin examinations over a one-year period at a community-based practice in Florida. All lesions that were selected for biopsy to rule out melanoma were also imaged with multispectral digital skin lesion analysis prior to biopsy. Histopathological diagnoses and multispectral digital skin lesion analysis results were reviewed and compared with findings from a prior primarily academic center-based multispectral digital skin lesion analysis trial. SETTING/PARTICIPANTS: Community-based clinical setting in Florida. MEASUREMENTS: Negative predictive value, sensitivity, and specificity. RESULTS: One hundred thirty-seven consecutive lesions were selected for biopsy and also analyzed via multispectral digital skin lesion analysis. All 21 cases with multispectral digital skin lesion analysis "Low Disorganization" readings were all histologically benign (100% negative predictive value, 95% lower confidence boundary = 96.9%). The negative predictive value and the sensitivity were not significantly different than what was found in the prior academic-based multispectral digital skin lesion analysis trial. Multispectral digital skin lesion analysis also correctly identified all high-risk lesions, which were subsequently confirmed via histology to be one invasive melanoma and 15 moderately dysplastic nevi (100% sensitivity). Specificity with multispectral digital skin lesion analysis was significantly higher than reported in the academic-based multispectral digital skin lesion analysis trial (18% vs. 10%, p=0.02). CONCLUSION: Because of the high negative predictive value achieved by multispectral digital skin lesion analysis, lesions with readings of "Low Disorganization" may be considered for observation versus biopsy. Similar to what was noted in the academic center setting, multispectral digital skin lesion analysis may help dermatologists reduce the number of unnecessary biopsies while improving diagnostic accuracy.

Comparison of the Distribution of Morphological Disorganization of Pigmented Lesions in a Community-based Practice versus a University-based Clinical Setting as Measured by a Multispectral Digital Skin Lesion Analysis Device: Impact on Diagnosis.

OBJECTIVE: To observe how a multispectral digital skin lesion analysis device was used by dermatologists in a community-based clinical setting and determine differences from a university-based environment. DESIGN: Use of multispectral digital skin lesion analysis was incorporated into a community-based practice by 12 dermatologists across six clinics over seven consecutive days with the data provided by the device integrated as an adjuvant to their clinical evaluation for their pigmented lesion management decisions. Multispectral digital skin lesion analysis results were collected electronically for lesions prior to biopsy, and histopathological evaluation was performed for the biopsied lesions. Multispectral digital skin lesion analysis and pathology results were then compared to assess the degree of morphological disorganization. SETTING/PARTICIPANTS: Study of 160 consecutive patients in community-based clinical setting. MEASUREMENTS: Proportion of "low" and "high" disorganization lesions identified by multispectral digital skin lesion analysis. RESULTS: Of the 344 pigmented skin lesions analyzed by multispectral digital skin lesion analysis, 255 were high disorganization, 113 of which were biopsied. Of the 89 lesions evaluated by multispectral digital skin lesion analysis to be low disorganization, seven were biopsied and all pathology was benign. Data demonstrate a higher rate of multispectral digital skin lesion analysis low disorganization readings for pigmented skin lesions (32% for single use per patient lesions, p<0.0001; 26% for all lesions, p<0.0001) than observed in the pigmented lesions clinics providing data for the university-based clinical study (10%). CONCLUSION: Multispectral digital skin lesion analysis in the community-based clinical setting may outperform specificity results from the university-based clinical trial study, perhaps because of a higher proportion of subtle lesions encountered at high-risk pigmented lesion clinics of participating major academic centers as compared with those in a community-based practice setting.