Differences in Skin Cancer Rates by Transplanted Organ Type and Patient Age After Organ Transplant in White Patients.

Importance: Although it is known that patients with thoracic organ transplants develop skin cancer more frequently than those who receive nonthoracic organ transplants, patterns of risk for subsequent skin cancers are unknown. Objective: To further characterize organ transplant recipients who develop multiple skin cancers and assess for patterns of development of additional skin cancers beyond the first skin cancer diagnosis by patient age and transplanted organ type. Design, Setting, and Participants: This cohort study used validated electronic health record-based data from a single tertiary care academic medical center to identify 5129 solid organ transplant recipients who underwent transplant surgery between 1992 and 2017 and were older than 18 years at the time of transplant. The cohort was limited to White patients because they have the highest skin cancer risk based on phenotype. The mean follow-up was 6.6 years. Data were analyzed June 9, 2021, to May 31, 2022. Main Outcomes and Measures: Differences in rates of skin cancer development for first and subsequent skin cancers were measured using t test or analysis of variance and χ2 tests for continuous and categorical variables. Rates of skin cancer development were compared based on organ type and patient age at transplant using Fine-Gray tests and cumulative incidence plots. Results: A total of 5129 organ transplant recipients (mean [SD] age, 51.3 [12.9] years; 3287 men [64.1%]) were included. Of these, 695 patients (13.6%) had development of at least 1 skin cancer, with 6842 skin cancers identified in the cohort overall. Compared with liver transplant recipients, heart, lung, or kidney recipients were more likely to develop at least 1 skin cancer (χ2 test, 25.6; df, 4; P < .001). There was no significant difference by transplanted organ type in the rate of developing a second or third skin cancer; however, the age at transplant was associated with the time to developing a second (χ2 test, 20.4; df, 4; P < .001) or third (χ2 test, 10.9; df, 4; P < .02) skin cancer. Conclusions and Relevance: This cohort study found that there was no difference by organ type for development of subsequent skin cancers in organ transplant recipients, and recipients of all organ types developed additional skin cancers at high rates after the initial skin cancer.

Validity of Using Billing Codes From Electronic Health Records to Estimate Skin Cancer Counts.

IMPORTANCE: Patients can develop multiple skin cancers, and their medical data can be spread over multiple health care systems. This fragmented care, combined with the lack of skin cancer registries, has limited our ability both to provide accurate estimates of incidence and to study the pathogenesis of multiple skin cancers. OBJECTIVE: To assess whether standard diagnostic and procedural codes present in the electronic health records at a single health care system are a valid proxy for estimating the number of overall skin cancers. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of patients seen at a single-center tertiary care hospital (ie, Vanderbilt University Medical Center) between July 1, 2008, and June 30, 2018. All patients with at least 1 electronic health record-based diagnostic or procedural code for any skin cancer and at least 1 pathology report of a skin cancer. EXPOSURE: The number of International Classification of Disease (ICD) or Current Procedural Terminology (CPT) codes relating to skin cancer. MAIN OUTCOMES AND MEASURES: Pearson correlation coefficient and R2 were calculated for the total number of ICD or CPT codes for skin cancer and histologically verified skin cancers. RESULTS: In this cohort study of 35 901 patients, the mean (SD) age was 70.4 (14.4) years, 20 404 (56.8%) were men, and 31 623 (88.1%) were White individuals. Of these patients, 6307 had at least 1 ICD or CPT code or pathology report for a skin cancer, of whom 5688 patients had both a CPT code related to skin malignancy and a histologically verified skin cancer. There was a strong linear correlation between the number of CPT codes and pathology records (r = 0.87). There was a poor correlation between the number of ICD codes and pathology records (r = 0.22). CONCLUSIONS AND RELEVANCE: This cohort study found that the use of ICD codes was a poor proxy measure for the number of skin cancers per patient. In contrast, CPT codes accounted for more than 75% of the variability in the number of skin cancers (R2 = 0.76) and were a better proxy measure for the total number of skin cancers per patient.

Development of a patient decision aid for the management of superficial basal cell carcinoma (BCC) in adults with a limited life expectancy.

BACKGROUND: Basal cell carcinoma (BCC) is a slow-growing, rarely lethal skin cancer that affects people 65 years or older. A range of treatment options exist for BCC, but there is little evidence available to guide patients and providers in selecting the best treatment options. OBJECTIVES: This study outlines the development of a patient decision aid (PDA) for low-risk BCC that can be used by patients and providers to assist in shared decision-making. METHODS: In accordance with the International Patient Decision Aids Standards (IPDAS) Collaboration framework, feedback from focus groups and semi-structured interviews with patients and providers, an initial prototype of the PDA was developed. This was tested using cognitive interviews and iteratively updated. RESULTS: We created eighteen different iterations using feedback from 24 patients and 34 providers. The key issues identified included: 1) Addressing fear of cancer; 2) Communicating risk and uncertainty; 3) Values clarification; and 4) Time lag to benefit. LIMITATIONS: The PDA does not include all possible treatment options and is currently paper based. CONCLUSIONS: Our PDA has been specifically adapted and designed to support patients with a limited life expectancy in making decisions about their low risk BCC together with their doctors.

Association between financial links to indoor tanning industry and conclusions of published studies on indoor tanning: systematic review.

OBJECTIVE: To assess whether an association exists between financial links to the indoor tanning industry and conclusions of indoor tanning literature. DESIGN: Systematic review. DATA SOURCES: PubMed, Embase, and Web of Science, up to 15 February 2019. STUDY SELECTION CRITERIA: Articles discussing indoor tanning and health were eligible for inclusion, with no article type restrictions (original research, systematic reviews, review articles, case reports, editorials, commentaries, and letters were all eligible). Basic science studies, articles describing only indoor tanning prevalence, non-English articles, and articles without full text available were excluded. RESULTS: 691 articles were included in analysis, including empiric articles (eg, original articles or systematic reviews) (357/691; 51.7%) and non-empiric articles letters (eg, commentaries, letters, or editorials) (334/691; 48.3%). Overall, 7.2% (50/691) of articles had financial links to the indoor tanning industry; 10.7% (74/691) articles favored indoor tanning, 3.9% (27/691) were neutral, and 85.4% (590/691) were critical of indoor tanning. Among the articles without industry funding, 4.4% (27/620) favored indoor tanning, 3.5% (22/620) were neutral, and 92.1% (571/620) were critical of indoor tanning. Among the articles with financial links to the indoor tanning industry, 78% (39/50) favored indoor tanning, 10% (5/50) were neutral, and 12% (6/50) were critical of indoor tanning. Support from the indoor tanning industry was significantly associated with favoring indoor tanning (risk ratio 14.3, 95% confidence interval 10.0 to 20.4). CONCLUSIONS: Although most articles in the indoor tanning literature are independent of industry funding, articles with financial links to the indoor tanning industry are more likely to favor indoor tanning. Public health practitioners and researchers need to be aware of and account for industry funding when interpreting the evidence related to indoor tanning. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019123617.

Effects of increased actinic keratosis count on skin-related quality of life: results from the Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial.

BACKGROUND: Actinic keratoses (AKs) are very common and it is therefore important to consider how morbidity of this disease impacts quality of life (QoL). Previous longitudinal studies of skin-related QoL in a high-risk population found no effect of increased AK counts on subsequent skin-related QoL, even though higher AK counts were associated with worse skin-related QoL cross-sectionally. OBJECTIVES: To determine if development of new actinic keratoses (AKs) are associated with worse skin-related QoL in those at high risk of keratinocyte carcinoma (KC). MATERIALS AND METHODS: A prospective analysis was performed using data from the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial, a randomized, double-blinded, placebo-controlled trial of topical 5-fluorouracil for chemoprevention of KC. We report correlates of skin-related quality of life, a secondary outcome of the trial. Demographic and health-related information were self-reported and AK multiplicity on the face/ears were noted on semi-annual skin exams. Skindex-29 and Skin Cancer Index instruments were used to assess skin-related QoL yearly. RESULTS: Participants with increased AK counts had worse skin-related QoL compared to those with unchanged or decreased counts, particularly in Year 1. CONCLUSION: Our findings of impaired skin-related QoL associated with AKs underscore the importance of appropriate management to reduce the burden of disease.

Outcomes and Risk Factors in Patients with Multiple Primary Melanomas.

The incidence and patient survival rates of melanoma have increased over the last several decades, with a growing population of patients who develop multiple primary melanomas (MPMs). To determine risk factors for developing MPMs and compare the survival of patients with MPMs to those with single primary melanomas, a prospective, multidisciplinary database of patients with melanoma at a single tertiary care institution was retrospectively reviewed. From 1985 to 2013, 6,963 patients with single primary melanomas and 305 patients with MPMs were identified. Mean follow-up was 8.3 ± 6.3 years for patients with single primary melanomas and 8.8 ± 5.9 years for patients with MPMs. Risk of developing multiple melanomas increased with age at diagnosis of first melanoma (hazard ratio [HR] = 1.20 for a 10-year increase in age, 95% confidence interval [CI] = 1.11-1.29, P < 0.001), male sex (HR = 1.44, 95% CI = 1.12-1.84, P = 0.005), and white race (HR = 3.07, 95% CI = 1.45-6.51). Patients with invasive MPMs had increased risk of melanoma-specific death both before (HR = 1.47, 95% CI = 1.0-2.2) and after adjusting for age, sex, site, race, family history of melanoma, personal history of other cancer, and Surveillance, Epidemiology, and End Results Program (SEER) stage (HR = 1.44, 95% CI = 0.95-2.2); however, this result did not reach statistical significance.

Comparative effectiveness of treatment of actinic keratosis with topical fluorouracil and imiquimod in the prevention of keratinocyte carcinoma: A cohort study.

BACKGROUND: The effectiveness of 5-fluorouracil compared with that of imiquimod for preventing keratinocyte carcinoma is unknown. OBJECTIVE: To compare the effectiveness of 5-fluorouracil and that of imiquimod in preventing keratinocyte carcinoma in a real-world practice setting. METHODS: We identified 5700 subjects who filled prescriptions for 5-fluorouracil or imiquimod for treatment of actinic keratosis in 2007. An intention-to-treat analysis controlling for potential confounding variables was used to calculate 2- and 5-year cumulative risk differences for subsequent keratinocyte carcinoma overall and in field-treated areas. RESULTS: 5-Fluorouracil was associated with a statistically significant decreased risk of any keratinocyte carcinoma compared with imiquimod (adjusted hazard ratio [aHR], 0.86; 95% confidence interval [CI], 0.76-0.97), but there were no significant differences in risk by tumor subtype (for squamous cell carcinoma: aHR, 0.89; 95% CI, 0.74-1.07; for basal cell carcinoma: aHR, 0.87; 95% CI, 0.74-1.03) or site-specific keratinocyte carcinoma (aHR, 0.96; 95% CI, 0.81-1.14). There were no significant differences in 2- or 5-year cumulative risk of keratinocyte carcinoma among those treated with 5-fluorouracil versus with imiquimod. LIMITATIONS: Generalizability to other practice settings may be limited. CONCLUSIONS: Whereas 5-fluorouracil was more effective in reducing keratinocyte carcinoma risk overall, we found no differences in the short- or long-term risk of subsequent site-specific keratinocyte carcinoma in a real-world practice setting.

Development of a Comprehensive Quality-of-Life Measure for Facial and Torso Acne.

Background Acne is a chronic skin disorder which generally presents in adolescence but continues into adulthood, and negatively affects both physical and psychosocial well-being. Presently, there are no validated acne-specific quality-of-life (QoL) measures that include dimensions for both facial and torso acne. OBJECTIVE: The objective of this study was to develop a QoL instrument for both facial and torso acne (CompAQ) in accordance with recommended standards. METHODS: A literature review and Delphi survey of patients and clinicians were used to develop the conceptual framework for outcomes perceived important to acne patients. An initial version of the measure was developed, CompAQ-v1, and pilot tested with patients via cognitive interviews. RESULTS: The Delphi survey generated 4 domains (physical, psychological, sociological, and treatment) and 54 items. These, along with a literature review and input from clinical experts, informed the development of the CompAQ-v1. Eleven cognitive interviews were conducted, resulting in the second version of the measure, CompAQ-v2. Psychometric validation resulted in the final 20-item CompAQ measure comprising 5 domains. An abbreviated 5-item measure was also developed (CompAQ-SF). CONCLUSION: CompAQ and CompAQ-SF are instruments intended to evaluate QoL in patients with acne on their face or torso. The former is a 21-item QoL intended for research, while the latter is intended for clinical practice.

A real-world, community-based cohort study comparing the effectiveness of topical fluorouracil versus topical imiquimod for the treatment of actinic keratosis.

BACKGROUND: The most widely used topical agents for the field-based treatment of multiple actinic keratoses (AKs) are 5-fluorouracil and imiquimod, but their comparative effectiveness has not been assessed in a real-world setting. OBJECTIVE: We compared the effectiveness of 5-fluorouracil and imiquimod in reducing risk for subsequent AKs in a large, integrated health care delivery system in northern California. METHODS: In this cohort study, we identified adult health plan members who had an AK diagnosed in 2007 and who subsequently filled a prescription for 5-fluorouracil or imiquimod (N = 5700). We followed subjects for subsequent AKs identified by the International Classification of Diseases codes and estimated the 2-year (short-term) and 5-year (long-term) differences in cumulative risk while controlling for potential confounding by pretreatment variables. RESULTS: 5-Fluorouracil reduced the short-term incidence of subsequent AKs (cumulative risk difference -4.54% [95% confidence interval, -7.91% to -1.17%]), but there was no statistically significant evidence of a long-term decreased risk (cumulative risk difference -1.43% [95% confidence interval, -3.43% to 0.05%]) compared with that with imiquimod. LIMITATIONS: This is a retrospective study with limited ascertainment of all relevant potential confounding variables. CONCLUSION: We found that 5-fluorouracil appeared to be significantly more effective than imiquimod in the short-term, but not long-term, prevention of subsequent AKs.

All-cause mortality in patients with basal and squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: There are varying reports of the association of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) with mortality. OBJECTIVE: To synthesize the available information on all-cause mortality after a diagnosis of BCC or SCC in the general population. METHODS: We searched PubMed (1966-present), Web of Science (1898-present), and Embase (1947-present) and hand-searched to identify additional records. All English articles that reported all-cause mortality in patients with BCC or SCC were eligible. We excluded case reports, case series, and studies in subpopulations of patients. Random effects model meta-analyses were performed separately for BCC and SCC. RESULTS: The searches yielded 6538 articles, and 156 were assessed in a full-text review. Twelve studies met the inclusion criteria, and 4 were included in the meta-analysis (encompassing 464,230 patients with BCC and with 175,849 SCC), yielding summary relative mortalities of 0.92 (95% confidence interval, 0.83-1.02) in BCC and 1.25 (95% confidence interval, 1.17-1.32) in SCC. LIMITATIONS: Only a minority of studies controlled for comorbidities. There was significant heterogeneity in meta-analysis (χ2P < .001, I2 > 98%), but studies of SCC were qualitatively concordant: all showed statistically significant increased relative mortality. CONCLUSIONS: We found that patients with SCC are at higher risk for death from any cause compared with the general population.

Risk of cutaneous squamous cell carcinoma after treatment of basal cell carcinoma with vismodegib.

BACKGROUND: Vismodegib is a first-in-class agent targeting the hedgehog signaling pathway for treatment of patients with locally advanced basal cell carcinoma (BCC) and metastatic BCC. There have been concerns about the development of squamous cell carcinoma (SCC) in patients treated with this drug. OBJECTIVE: We sought to determine whether treatment with vismodegib is associated with an increase in the risk of cutaneous SCC. METHODS: In this retrospective cohort study, patients treated with vismodegib as part of phase I and II clinical studies were compared with participants from the University of California, San Francisco, Nonmelanoma Skin Cancer Cohort who received standard therapy for primary BCC. In total, 1675 patients were included in the analysis, and the development of SCC after vismodegib exposure was assessed. RESULTS: The use of vismodegib was not associated with an increased risk of subsequent development of SCC (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28-1.16). Covariates including age, sex, history of previous nonmelanoma skin cancer, and number of visits per year were significantly associated with the development of SCC. LIMITATIONS: A limitation of the study was that a historic control cohort was used as a comparator. CONCLUSIONS: Vismodegib was not associated with an increased risk of subsequent SCC when compared with standard surgical treatment of BCC.

Teens, Tweets, and Tanning Beds: Rethinking the Use of Social Media for Skin Cancer Prevention.

The incidence of skin cancer is rising in the U.S., and melanoma, the deadliest form, is increasing disproportionately among young white women. Indoor tanning is a modifiable risk factor for all skin cancers and continues to be used at the highest rates in young white women. Adolescents and young adults report personal appearance-based reasons for using indoor tanning. Previous research has explored the influences on tanning bed use, including individual factors as well as relationships with peers, family, schools, media influences, legislation, and societal beauty norms. Adolescents and young adults also have high rates of social media usage, and research is emerging on how best to utilize these platforms for prevention. Social media has the potential to be a cost-effective way to reach large numbers of young people and target messages at characteristics of specific audiences. Recent prevention efforts have shown that comprehensive prevention campaigns that include technology and social media are promising in reducing rates of indoor tanning among young adults. This review examines the literature on psychosocial influences on indoor tanning among adolescents and young adults, and highlights ways in which technology and social media can be used for prevention efforts.

Tumor recurrence of keratinocyte carcinomas judged appropriate for Mohs micrographic surgery using Appropriate Use Criteria.

BACKGROUND: The use of Mohs micrographic surgery (MMS) has increased greatly to treat basal cell and cutaneous squamous cell carcinomas (keratinocyte carcinoma [KC]), and consensus-based Appropriate Use Criteria (AUC) were developed to identify tumors for which MMS is appropriate. OBJECTIVE: We sought to compare recurrence rates after different treatments in tumors judged appropriate for MMS. METHODS: We used data from an observational prospective cohort study and retrospectively categorized consecutive tumors as appropriate for MMS according to the AUC. Among appropriate tumors, we used survival analyses to compare 5-year recurrence rates after treatments. RESULTS: Among tumors appropriate for MMS (N = 1483), adjusted 5-year recurrence rates were 2.9% (range, 1.4-4.3%) after MMS, 5.5% (range, 3.1-7.9%) after excision, 4.0% (range, 0.6-7.2%) after destruction, and 5.9% (range, 1.5-10.2%) after other treatments. In tumors treated only with MMS or excision (the most similar subgroups), the adjusted hazard ratio of 5-year recurrence after MMS was 0.6 (95% confidence interval, 0.3-1.0; P = .06). LIMITATIONS: This study is limited by its uncertain generalizability, lack of randomization, and unmeasured characteristics. CONCLUSION: The AUC identified tumors for which recurrence would be less common after MMS than after excision, but the absolute difference in recurrence rates was small.

Comparing the Quality of Ambulatory Surgical Care for Skin Cancer in a Veterans Affairs Clinic and a Fee-For-Service Practice Using Clinical and Patient-Reported Measures.

The Institute of Medicine has identified serious deficiencies in the measurement of cancer care quality, including the effects on quality of life and patient experience. Moreover, comparisons of quality in Veterans Affairs Medical Centers (VA) and other sites are timely now that many Veterans can choose where to seek care. To compare quality of ambulatory surgical care for keratinocyte carcinoma (KC) between a VA and fee-for-service (FFS) practice, we used unique clinical and patient-reported data from a comparative effectiveness study. Patients were enrolled in 1999-2000 and followed for a median of 7.2 years. The practices differed in a few process measures (e.g., median time between biopsy and treatment was 7.5 days longer at VA) but there were no substantial or consistent differences in clinical outcomes or a broad range of patient-reported outcomes. For example, 5-year tumor recurrence rates were equally low (3.6% [2.3-5.5] at VA and 3.4% [2.3-5.1] at FFS), and similar proportions of patients reported overall satisfaction at one year (78% at VA and 80% at FFS, P = 0.69). These results suggest that the quality of care for KC can be compared comprehensively in different health care systems, and suggest that quality of care for KC was similar at a VA and FFS setting.