An updated report on the incidence and epidemiological trends of keratinocyte cancers in the United Kingdom 2013-2018.

Introduction: The most common cancers in the UK are keratinocyte cancers (KCs): the combined term for basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs). Registration of KC is challenging due to high numbers and multiplicity of tumours per person. Methods: We provide an updated report on the descriptive epidemiology of trends in KC incidence for the resident populations of UK countries (England, Northern Ireland, Scotland and Wales) using population-based cancer registry and pathology report data, 2013-18. Results: Substantial increases in cSCC incidence in England, Scotland and Northern Ireland can be detected for the period of 2013-18, and the incidence of cSCC also increased in Wales from 2016 to 2018. In contrast, however, the pattern of annual change in the incidence of BCC across the nations differs. In England, the incidence of BCC declined slightly from 2016 to 2018, however, the overall trend across 2013-18 is not statistically significant. In Scotland, the incidence of BCC shows some variability, declining in 2017 before increasing in 2018, and the overall trend across 2013-18 was also not statistically significant. In Northern Ireland, the incidence of BCC increased significantly over the study period, and in Wales, the incidence of BCC increased from 2016 to 2018. One in five people will develop non-melanoma skin cancers (NMSC) in their lifetime in England. This estimate is much higher than the lifetime risk of melanoma (1 in 36 males and 1 in 47 females born after 1960 in the UK), which further highlights the burden of the disease and importance of early prevention strategies. Conclusions: We highlight how common these tumours are by publishing the first ever lifetime incidence of NMSC. Additionally, the first time reporting of the age standardised incidence of KC in Wales further confirms the scale of the disease burden posed by these cancers in the UK. With approximately one in five people developing NMSC in their lifetime, optimisation of skin cancer prevention, management and research are essential.

A 10-year review of surgical management of dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer. Standard treatment in the UK is either wide local excision (WLE) or Mohs micrographic surgery (MMS). It is unclear which approach has the lower recurrence rate. OBJECTIVES: We undertook a retrospective comparative review of surgical management of DFSP in the UK National Health Service in order to define (i) current surgical practice for primary and recurrent DFSP, (ii) local recurrence rates for primary DFSP and (iii) survival outcomes for DFSP. METHODS: A retrospective clinical case-note review of patients with histologically confirmed DFSP (January 2004 to December 2013) who have undergone surgical treatment. RESULTS: The surgical management of 483 primary and 64 recurrent DFSP in 11 plastic surgery and 15 dermatology departments was analysed. Almost 75% of primary DFSP (n = 362) were treated with WLE and 20% (n = 97) with MMS. For recurrent DFSP, 69% (n = 44) and 23% (n = 15) of patients underwent WLE and MMS, respectively. Recurrent primary DFSP occurred in six patients after WLE and none after MMS. The median follow-up time was 25·5 months (interquartile range 6·8-45·1) for new and 19·8 (IQR 4·5-44·5) for recurrent DFSP [Correction added on 1 Feb 2021, after first online publication: 4.8 years (interquartile range 3.5-5.8) was incorrect], with eight reported deaths during the follow-up analysis period (one confirmed to be DFSP related). CONCLUSIONS: WLE was the most common surgical modality used to treat DFSP across the UK. The local recurrence rate was very low, occurring only after WLE. Although a prospective randomized controlled trial may provide more definitive outcomes, in the absence of a clearly superior surgical modality, treatment decisions should be based on patient preference, clinical expertise and cost.

A feasibility study of microwave therapy for precancerous actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a common premalignant skin lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Microwave therapy is an established cancer treatment and has been used for plantar viral warts. OBJECTIVES: To evaluate the efficacy and feasibility of microwave as a treatment for AK. METHODS: Stage I was a dose-setting study, in which seven participants had the dielectric properties of 12 thick and 22 thin AKs assessed for optimization of the microwave dose used for treatment in Stage II. Stage II was a randomized, internally controlled trial evaluating 179 AKs in 11 patients (93 treated, 86 untreated controls) on the scalp/forehead or dorsal hand. Participants received one treatment initially and a repeat treatment to unresolved AKs at week 4. The response was assessed at six visits over 4 months. The primary outcome was partial or complete resolution of the treated AKs. RESULTS: A significantly higher proportion of treated AK areas responded than untreated (90% vs. 15%; P < 0·001). Thin AKs were more responsive than thick AKs. The site did not affect efficacy. Pain was severe, but brief (80% reported pain lasting 'a few seconds only'). Adverse effects were minimal (erythema, n = 6; flaking, n = 3; itch, n = 3). All participants who would chose microwave therapy over their current treatment cited the shorter discomfort period. CONCLUSIONS: Microwave therapy is a portable, safe and effective treatment for AK. An easy-to-deliver, acceptable therapy for AK is attractive as a prevention strategy. While these results are promising, a larger randomized controlled trial is needed against an effective comparator to confirm clinical efficacy and patient acceptability. What is already known about this topic? Actinic keratoses (AKs) are common precancerous skin lesions. Successful treatment of AK can prevent cutaneous squamous cell carcinoma (cSCC). Most topical therapies for AK require repeated application over weeks and drive local skin inflammation, leading to poor compliance. An easy-to-deliver and effective treatment for AK, suitable for use in primary care, could reduce cSCC. What does this study add? Microwave therapy is a feasible, effective treatment for AK. Ninety per cent of treated AKs showed full or partial resolution at 120 days post-treatment. Microwave therapy was painful, but the pain was short-lived (seconds) and this short discomfort period was cited as the main reason that microwave was preferred to their current treatment.

Treatment approaches in immunosuppressed patients with advanced cutaneous squamous cell carcinoma.

Immunosuppression, both iatrogenic and disease-related, is associated with a greatly increased incidence of cutaneous SCC (cSCC) and with aggressive cSCC and worse disease outcomes. Consequently, rapid access to skin cancer services and prudent surgical choices, such as circumferential margin assessment, is essential when treating advanced cSCC in an immunosuppressed patient. For high-risk cancers and control of cSCC multiplicity, additional strategies should be actively considered within the multidisciplinary clinical care team. These include minimization or revision of immunosuppressive medications, systemic chemoprevention (including retinoids, nicotinamide, capecitabine) and adjuvant therapies such as radiotherapy. Unfortunately, there is a relative paucity of good evidence for many of these treatments in the immunosuppressed. Systemic treatments for metastatic cSCC are often contraindicated in organ transplant recipients, notably checkpoint inhibitor immunotherapy. There are also toxicity concerns with some conventional chemotherapies and EGFR inhibitors. Until recently, clinical trials have largely excluded immunosuppressed individuals. Development of more effective treatment for advanced cSCC in this high-risk group and prospective clinical trials are now research priorities.

Achieving Self-Directed Integrated Cancer Aftercare (ASICA) in melanoma: protocol for a randomised patient-focused pilot trial of delivering the ASICA intervention as a means to earlier detection of recurrent and second primary melanoma.

BACKGROUND: Melanoma is common; 15,906 people in the UK were diagnosed with melanoma in 2015 and incidence has increased fivefold in 30 years. Melanoma affects old and young people, with poor prognosis once metastatic. UK guidelines recommend people treated for cutaneous melanoma receive extended outpatient, hospital follow up to detect recurrence or new primaries. Such follow up of the growing population of melanoma survivors is burdensome for both individuals and health services. Follow up is important since approximately 20% of patients with early-stage melanoma experience a recurrence and 4-8% develop a new primary; the risk of either is highest in the first 5 years. Achieving Self-directed Integrated Cancer Aftercare (ASICA) is a digital intervention to increase total-skin-self-examination (TSSE) by people treated for melanoma, with usual follow up. METHODS: We aim to recruit 240 adults with a previous first-stage 0-2C primary cutaneous melanoma, from secondary care in North-East Scotland and the East of England. Participants will be randomised to receive the ASICA intervention (a tablet-based digital intervention to prompt and support TSSE) or control group (treatment as usual). Patient-reported and clinical data will be collected at baseline, including the modified Melanoma Worry Scale (MWS), the Hospital Anxiety and Depression Scale (HADs), the EuroQoL 5-dimension 5-level questionnaire (EQ-5D-5 L), and questions about TSSE practice, intentions, self-efficacy and planning. Participants will be followed up by postal questionnaire at 3, 6 and 12 months following randomization, along with a 12-month review of clinical data. The primary timepoint for outcome analyses will be12 months after randomisation. DISCUSSION: If the ASICA intervention improves the practice of TSSE in those affected by melanoma, this may lead to improved psychological well-being and earlier detection of recurrent and new primary melanoma. This could impact both patients and National Health Service (NHS) resources. This study will determine if a full-scale randomised controlled trial can be undertaken in the UK NHS to provide the high-quality evidence needed to determine the effectiveness of the intervention. ASICA is a pilot study evaluating the effectiveness of the practice of digitally supported TSSE in those affected by melanoma. TRIAL REGISTRATION: Clinical Trials.gov, NCT03328247 . Registered on 1 November 2017.

Epidemiology of basal and cutaneous squamous cell carcinoma in the U.K. 2013-15: a cohort study.

BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together known as keratinocyte cancers (KCs), are the commonest cancer in white ethnic populations. Recent improvements to registry data collection in England has allowed more accurate analysis of the epidemiology of BCC and cSCC and for the first time we are able to provide an accurate (representative) tumour burden for KC in the U.K. OBJECTIVES: To estimate the incidence of BCC and cSCC in the U.K. METHODS: A cohort of patients with KCs between 2013 and 2015 were identified using linkage to diagnostic codes derived from pathology reports collected into the national cancer registry. Data from England's cancer registry were combined with data from Scotland, Northern Ireland and Wales. European age-standardized incidence rates (EASRs) of the first BCC and cSCC per patient per annum (PPPA) were calculated. RESULTS: In the U.K, the EASR of the first BCC and cSCC PPPA in 2013-15 were 285 and 77 per 100 000 person years, respectively (211 120 KCs total in 2015). The mean annual percentage increase was 5% between 2013 and 2015 for both BCC and cSCC. By counting the first KC PPPA, we include an additional 51% KCs compared with the previous reporting technique which counts only the first BCC and cSCC in a patient's lifetime, yet it represents a probable underestimation of 5-11% of the true tumour count. CONCLUSIONS: Based on an improved methodology, a more representative incidence of KC is presented, which is essential to healthcare planning and will lead to improved understanding of the epidemiology of KC. What's already known about this topic? Keratinocyte cancers (KCs) are the most common cancers affecting white ethnic populations. The incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) is increasing worldwide including the U.K., most commonly in elderly male Caucasian patients. These cancers are traditionally substantially underreported and frequently excluded from national cancer statistics. What does this study add? Using improved data collection methods in England and validated tumour-reporting techniques, we report the most accurate BCC and cSCC incidence data for the U.K. ever published. Identifying the first BCC and cSCC per patient per annum, the incidence of BCC and cSCC in the U.K. (excluding Wales) was 285 and 77 per 100 000 person years, respectively, between 2013 and 2015, with more than 210 000 KCs in the U.K. in 2015.

Patient preferences for topical treatment of actinic keratoses: a discrete-choice experiment.

BACKGROUND: The treatment of actinic keratosis (AK) is a potentially effective strategy for the prevention of cutaneous squamous cell carcinoma (cSCC). However, the patient perspective on potential benefits of AK treatment in terms of skin cancer reduction has received little attention to date. OBJECTIVES: (i) To investigate patient preferences for topical treatments for AK using a discrete-choice experiment (DCE); (ii) to evaluate patient willingness to trade between clinical benefit and medical burden. METHODS: The DCE was conducted as part of a study to establish the feasibility of a phase III randomized controlled trial evaluating the prevention of cSCC using currently available topical interventions. Preferences were elicited by asking patients to make a series of choices between treatment alternatives with different hypothetical combinations of attribute levels. Willingness to trade between treatment attributes was estimated using a flexible-choice model that allows for the heterogeneity of patient preferences. RESULTS: A total of 109 patients with AK completed the DCE. The majority of patients who expressed valid preferences were willing to accept some reduction in both prophylactic and cosmetic efficacy to reduce the burden of the treatment regimen, the severity of skin reaction and other adverse effects. Patients may reject treatment if the perceived therapeutic benefit is outweighed by the subjective burden of treatment. CONCLUSIONS: Evidence of significant variation in the perceived utility of treatments across patients highlights the importance of taking individual patient preferences into account to improve AK treatment acceptability and adherence.

The new 8th edition of TNM staging and its implications for skin cancer: a review by the British Association of Dermatologists and the Royal College of Pathologists, U.K.

The 8th edition of TNM (tumour, node and metastasis) has numerous and important changes compared with the 7th edition. Public Health England and the Royal College of Pathologists, U.K., have adopted the 8th edition of TNM (TNM8) published by the Union for International Cancer Control for skin cancer staging. These changes will have an impact on the management and commissioning of melanoma and nonmelanoma skin cancer (NMSC). The T1-T3 categories for NMSC staging require the clinician to measure the maximum dimension (usually diameter) of every potential invasive cancer. For squamous, basal and adnexal carcinomas, but not Merkel cell carcinoma (MCC), the T1-T3 categories are defined by new 20-mm and 40-mm divisions based on the maximum dimension of the lesion. In addition, new risk factors upstage T1 or T2 to T3. For melanoma, mitotic index no longer influences separation of pathological stage (pT1). There is a new, additional stratification level at 0·8-mm Breslow thickness. Subdivision pT1b, with a negative sentinel lymph node biopsy (SLNB) of pN0, is now stage IA compared with the previous IB. For MCC, SLNB is now included specifically in the pN staging system. The pT1 subdivision requires clinical information as to whether histologically involved nodes were clinically occult or detectable. For both melanoma and MCC the clinician must state whether the lymph nodes are occult or clinically detectable. Eyelid carcinoma continues to have a staging system different from that in general skin and the system is substantially revised in TNM8.

The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from patients with atopic dermatitis.

BACKGROUND: Carriage rates of Staphylococcus aureus on affected skin in atopic dermatitis (AD) are approximately 70%. Increasing disease severity during flares and overall disease severity correlate with increased burden of S. aureus. Treatment in AD therefore often targets S. aureus with topical and systemic antimicrobials. OBJECTIVES: To determine whether antimicrobial sensitivities and genetic determinants of resistance differed in S. aureus isolates from the skin of children with AD and healthy child nasal carriers. METHODS: In this case-control study, we compared S. aureus isolates from children with AD (n = 50) attending a hospital dermatology department against nasal carriage isolates from children without skin disease (n = 49) attending a hospital emergency department for noninfective conditions. Using whole genome sequencing we generated a phylogenetic framework for the isolates based on variation in the core genome, then compared antimicrobial resistance phenotypes and genotypes between disease groups. RESULTS: Staphylococcus aureus from cases and controls had on average similar numbers of phenotypic resistances per isolate. Case isolates differed in their resistance patterns, with fusidic acid resistance (FusR ) being significantly more frequent in AD (P = 0·009). The genetic basis of FusR also differentiated the populations, with chromosomal mutations in fusA predominating in AD (P = 0·049). Analysis revealed that FusR evolved multiple times and via multiple mechanism in the population. Carriage of plasmid-derived qac genes, which have been associated with reduced susceptibility to antiseptics, was eight times more frequent in AD (P = 0·016). CONCLUSIONS: The results suggest that strong selective pressure drives the emergence and maintenance of specific resistances in AD.

The pathogenesis of cutaneous squamous cell carcinoma in organ transplant recipients.

The pathogenesis of keratinocyte carcinoma following organ transplantation is multifactorial, and recent evidence suggests a complex and often synergistic interplay between the carcinogenic effects of ultraviolet radiation, compromised immune surveillance, direct pro- and anticarcinogenic effects of drugs, oncogenic viruses (in particular, beta-genus human papillomaviruses) and host genetic susceptibility factors. We present an overview of those factors for which there is currently the most convincing evidence and highlight important gaps in our knowledge. In particular, a clear understanding of the interdependence and relative contributions of these co-factors is currently lacking, yet has important implications for rational development of clinically relevant biomarkers and targeted strategies for treatment and prevention of post-transplant keratinocyte cancers.