Martin A. Weinstock

In Reply We appreciate the close scrutiny of our published work and the opportunity to elaborate on the end points we used for analysis of the trial data. The VAKCC Trial primary end point was the rate of occurrence of keratinocyte carcinoma (KC) over the course of the 4-year trial.¹ In the process of creating and executing this trial, however, the study team explicitly discussed that there were other important outcomes. In particular, while we did not have evidence to guide our estimation of the timing and duration of the effect of our intervention, if any, on the occurrence of KC, basal cell carcinoma, or squamous cell carcinoma (SCC), we realized that a short-term effect on risk (eg, during the first year) could be of considerable clinical importance even if the effect did not persist for the entire duration of the trial. We further recognized that even if there was a substantial effect in the first year, it could be lost in the 4-year results unless specifically examined. Hence, when analysis plans were discussed prior to unblinding the data, it was explicitly stated by the study chair, and summarized in the form of email guidance to the study statistician, that outcomes at 1 year were important to calculate and report. With the focus on completing the report, we chose not to officially amend the statistical analysis plan. This was an administrative decision that did not prevent appropriate analysis and should not prevent appropriate scientific interpretation. The final analyses, as reported,¹ revealed a clinically and statistically significant 75% reduction in SCC risk in the first year. It is appropriate for this finding to influence the clinical care of those at high risk of face and ear SCC.

Keratinocyte carcinoma (KC), often ambiguously termed nonmelanoma skin cancer (ie, cutaneous basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]), accounts for about three-quarters of all cancers in the United States.^1,2 Over 5 million KCs were diagnosed in 2012, and incidence is rising.³

BACKGROUND: Population‐based screening for the early detection of melanoma holds great promise for reducing melanoma mortality, but evidence is needed to determine whether benefits outweigh risks. Skin surgeries and dermatology visits after screening were assessed to indicate potential physical, psychological, and financial consequences.METHODS: Targeted primary care providers (PCPs) at the University of Pittsburgh Medical Center were trained to detect early melanoma using the INFORMED (INternet course FOR Melanoma Early Detection) program. The authors analyzed aggregated administrative data describing 3 groups of patients aged ≥35 years who had received an annual physical examination by PCPs: group A1 included patients of PCPs from the group with the highest percentage of INFORMED‐trained providers, group A2 included patients of PCPs from the group with a lower percentage of INFORMED‐trained providers, and group B included patients of PCPs without INFORMED training.RESULTS: INFORMED‐trained PCPs screened 1572 of 16,472 patients in groups A1 or A2 and none of the 56,261 patients in group B. In group A1, there was a 79% increase (95% confidence interval, 15%‐138%) in melanoma diagnoses noted; no increase was observed for the other groups, and no substantial increase in skin surgeries or dermatology visits occurred in any group.CONCLUSIONS: A large‐scale melanoma screening using the INFORMED program was conducted in Pennsylvania. To the best of the authors' knowledge, the current study is the first analysis of downstream results and the findings indicate increased melanoma diagnoses but little impact on skin surgeries or dermatology visits. This result provides some reassurance that such efforts can be conducted without major adverse consequences, at least as measured by these parameters, and therefore should be considered for more widespread use. Cancer 2016;122:3152–6. © 2016 American Cancer Society.

Detection and removal of melanoma, before it has metastasized, dramatically improves prognosis and survival. The purpose of this chapter is to (1) summarize current methods of melanoma detection and (2) review state-of-the-art detection methods and technologies that have the potential to reduce melanoma mortality. Current strategies for the detection of melanoma range from population-based educational campaigns and screening to the use of algorithm-driven imaging technologies and performance of assays that identify markers of transformation. This chapter will begin by describing state-of-the-art methods for educating and increasing awareness of at-risk individuals and for performing comprehensive screening examinations. Standard and advanced photographic methods designed to improve reliability and reproducibility of the clinical examination will also be reviewed. Devices that magnify and/or enhance malignant features of individual melanocytic lesions (and algorithms that are available to interpret the results obtained from these devices) will be compared and contrasted. In vivo confocal microscopy and other cellular-level in vivo technologies will be compared to traditional tissue biopsy, and the role of a noninvasive “optical biopsy” in the clinical setting will be discussed. Finally, cellular and molecular methods that have been applied to the diagnosis of melanoma, such as comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), will be discussed.

Primary care visits provide an opportunity for skin examinations with the potential to reduce melanoma mortality. The INFORMED (INternet curriculum FOR Melanoma Early Detection) Group developed a Web-based curriculum to improve primary care providers’ (PCPs’) skin cancer detection skills. This study details feedback obtained from participant focus groups, including the feasibility of implementing in other PCP practices. Practicing PCPs at Henry Ford Health System and Kaiser Permanente Northern California completed the curriculum. Feedback sessions were conducted with standardized questions focusing on four domains: (1) overall impressions of the curriculum, (2) recommendations for improvement, (3) current skin examination practices, and (4) suggestions for increasing skin screening by PCPs. Discussions at each site were audio recorded, transcribed verbatim, and de-identified. Providers (N = 54) had a positive impression of the Web-based curriculum, with suggestions to provide offline teaching aids and request assistance. Despite having improved confidence in diagnosing malignant lesions, many providers felt a lack of confidence in performing the screening and time constraints affected their current practices, as did institutional constraints. Providers intended to increase discussion with patients about skin cancer. The accessibility, effectiveness, and popularity of the curriculum indicate potential for implementation in the primary care setting. Participating providers noted that institutional barriers remain which must be addressed for successful dissemination and implementation.

The ability of medical practitioners to communicate risk estimates effectively to patients diagnosed with melanoma relies on accurate information about prognostic factors and their impact on survival. This study reports the development of one of the few melanoma prognostic models, called the Melanoma Severity Index (MSI), based on population-based cancer registry data. Data from the Queensland Cancer Registry for people (20–89 years) diagnosed with a single invasive melanoma between 1995 and 2008 (n = 28,654; 1,700 melanoma deaths). Additional clinical information about metastasis, ulceration and positive lymph nodes was manually extracted from pathology forms. Flexible parametric survival models were combined with multivariable fractional polynomial for selecting variables and transformations of continuous variables. Multiple imputation was used for missing covariate values. The MSI contained the variables thickness (transformed, explained 40.6% of variation in survival), body site (additional 1.9% in variation), metastasis (1.8%), positive nodes (0.7%), ulceration (1.3%), age (1.1%). Royston and Sauerbrei’s D statistic (measure of discrimination) was 1.50 (95% CI = 1.44, 1.56) and the corresponding RD2 (measure of explained variation) was 0.47 (0.45, 0.49), demonstrating strong explanatory performance. The Harrell-C statistic was 0.88 (0.88, 0.89). Lacking an external validation dataset, we applied internal-external cross validation to demonstrate the consistency of the prognostic information across geographically-defined subsets of the cohort. The MSI provides good ability to predict survival for melanoma patients. Beyond the immediate clinical use, the MSI may have important public health and research applications for evaluations of public health interventions aimed at reducing deaths from melanoma.

Although basal cell carcinoma (BCC) overall is less aggressive than other forms of skin cancer, the morpheaform subtype is particularly concerning because of its benign appearance and aggressive subclinical spread. We sought to evaluate risk factors for its development on the face or ears in a high-risk population of veterans with at least 2 prior keratinocyte carcinomas in the Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) Trial.

BACKGROUND AND OBJECTIVES: Primary care physicians (PCPs) are uniquely positioned to detect melanoma. Effective educational interventions targeted at PCPs may improve early melanoma detection. A previous in-person Basic Skin Cancer Triage (BSCT) 2-hour course demonstrated significant short-term improvement in provider practices, attitudes, ability, confidence, and knowledge. We conducted a randomized trial to test the efficacy of the BSCT course implemented as a web-based learning program, compared to a similar (control) web-based course on weight assessment. METHODS: We recruited a sample of 57 PCPs and 3,341 of their patients from four geographically diverse centers. Skin cancer control activities by PCPs were assessed by physician survey and by chart review and patient telephone interview about their recent visit to their PCP at baseline and at 1-2 months and 12 months after course completion. RESULTS: Some effect of intervention on skin cancer parameters was self-reported by physicians; this was not confirmed by patient survey or chart-extracted data. Rates of skin cancer control practices by PCPs were low across both groups before and after intervention. The positive changes in physician-reported behaviors (total body skin examination [TBSE]), intentions (discuss skin cancer detection), confidence (performing TBSE), office practices, and knowledge (58% skin versus 49% control) were neither matched by differences in practice reported by their patients, nor persisted in a longer term follow-up, hence may be attributable to physician recall bias due to the experience of the course or desire to please study investigators and were less dramatic as compared to our previously reported in-person BSCT intervention. Thus this approach by itself appears unlikely to result in improved PCP handling of skin cancer issues. CONCLUSIONS: Given previous success with our in-person course, the features required to make WBL a more effective tool for medical education must be further explored.