IMPORTANCEUntil now, most studies on cutaneous squamous cell carcinoma (cSCC) incidence rates concerned only the first cSCC per patient. Given the increase in incidence rates and the frequent occurrence of subsequent cSCCs per patient, population-based data on the incidence rates of both first and multiple cSCCs are needed.OBJECTIVES To calculate annual age-standardized incidence rates for histopathologically confirmed first and multiple cSCCs per patient and to estimate future cSCC incidence rates up to 2027. DESIGN, SETTING, AND PARTICIPANTS A nationwide population-based epidemiologic cohort study used cancer registry data on 145 618 patients with a first histopathologically confirmed cSCC diagnosed between January 1, 1989, and December 31, 2017, from the Netherlands Cancer Registry and all patients with multiple cSCCs diagnosed in 2017. MAIN OUTCOMES AND MEASURES Age-standardized incidence rates for cSCC-standardized to the European Standard Population 2013 and United States Standard Population 2000-were calculated per sex, age group, body site, and disease stage. A regression model with positive slope was fitted to estimate cSCC incidence rates up to 2027. RESULTS A total of 145 618 patients in the Dutch population (84 572 male patients [58.1%]; mean [SD] age, 74.5 [11.5] years) received a diagnosis of a first cSCC between 1989 and 2017.Based on incident data, European Standardized Rates (ESRs) increased substantially, with the highest increase found among female patients from 2002 to 2017, at 8.2% (95% CI, 7.6%-8.8%) per year. The ESRs for first cSCC per patient in 2017 were 107.6 per 100 000 person-years (PY) for male patients, an increase from 40.0 per 100 000 PY in 1989, and 68.7 per 100 000 PY for female patients, an increase from 13.9 per 100 000 PY in 1989, which corresponds with a US Standardized Rate of 71.4 per 100 000 PY in 2017 for men and 46.4 per 100 000 PY in 2017 for women. Considering multiple cSCCs per patient, ESRs increased by 58.4% for men (from 107.6 per 100 000 PY to 170.4 per 100 000 PY) and 34.8% for women (from 68.7 per 100 000 PY to 92.6 per 100 000 PY). Estimation of ESRs for the next decade show a further increase of 23.0% for male patients (ESR up to 132.4 per 100 000 PY [95% prediction interval, 125.8-139.0 per 100 000 PY]) and 29.4% for female patients (ESR up to 88.9 per 100 000 PY [95% prediction interval, 84.3-93.5 per 100 000 PY]).CONCLUSIONS AND RELEVANCE This nationwide epidemiologic cohort study suggests that incidence rates of cSCC keep increasing, especially among female patients, and that the occurrence of multiple cSCCs per patient significantly adds to the current and future burden on dermatologic health care. Revision of skin cancer policies are needed to halt this increasing trend.

Background: Cutaneous squamous cell carcinoma (cSCC) represents the most serious form of keratinocyte cancers because of its metastatic potential. Studies on nationwide incidence and diseasespecific survival rates of metastatic cSCC (mcSCC) are lacking.Objective: To investigate the cumulative incidence and disease-specific survival of patients with mcSCC in the Dutch population and assess patient-based risk factors.Methods: We conducted a nationwide cancer registry study including all patients with the first cSCC in 2007 or 2008, using data from the Netherlands Cancer Registry, the nationwide network and registry of histopathology and cytopathology, and Statistics Netherlands. Cumulative incidence and Kaplan-Meier curves were calculated, and time-dependent Cox proportional hazards regression analyses were used.Results: Of the 11,137 patients, metastases developed in 1.9% (n = 217). The median time to metastasis was 1.5 years (interquartile range 0.6-3.8 years). The risk factors were age (adjusted hazard ratio [aHR] 1.03, 95% CI 1.02-1.05), male sex (aHR 1.7, 95% CI 1.3-2.3), and immunosuppression (aHR [organ transplant recipient] 5.0, 95% CI 2.5-10.0; aHR [hematologic malignancy] 2.7, 95% CI 1.6-4.6). The 5-year diseasespecific survival for patients with mcSCC was 79.1%.Limitations: Only histopathologically confirmed mcSCCs were included.Conclusion: About 2% of cSCCs metastasize, with higher risk for men, increasing age, and immunocompromised patients. Disease-specific survival for patients with mcSCC is high.

Summary Background Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer worldwide with relatively low metastatic potential (2–5%). Developments in therapeutic options have highlighted the need to better identify high‐risk patients who could benefit from closer surveillance, adjuvant therapies and baseline/follow‐up imaging, while at the same time safely omitting low‐risk patients from further follow‐up. Controversy remains regarding the predictive performance of current cSCC staging systems and which methodology to adopt. Objectives To validate the performance of four cSCC staging systems [American Joint Committee on Cancer 8th edition (AJCC8), Brigham and Women’s Hospital (BWH), Tübingen and Salamanca T3 refinement] in predicting metastasis using a nationwide cohort. Methods A nested case–control study using data from the National Disease Registration Service, England, 2013–2015 was conducted. Metastatic cSCC cases were identified using an algorithm to identify all potential cases for manual review. These were 1 : 1 matched on follow‐up time to nonmetastatic controls randomly selected from 2013. Staging systems were analysed for distinctiveness, homogeneity, monotonicity, specificity, positive predictive value (PPV), negative predictive value (NPV) and c‐index. Results We included 887 metastatic cSCC cases and 887 nonmetastatic cSCC controls. The BWH system showed the highest specificity [92.8%, 95% confidence interval (CI) 90.8–94.3%, PPV (13.2%, 95% CI 10.6–16.2) and c‐index (0.84, 95% CI 0.82–0.86). The AJCC8 showed superior NPV (99.2%, 95% CI 99.2–99.3), homogeneity and monotonicity compared with the BWH and Tübingen diameter and thickness classifications (P < 0.001). Salamanca refinement did not show any improvement in AJCC8 T3 cSCC staging. Conclusions We validated four cSCC staging systems using the largest nationwide dataset of metastatic cSCC so far. Although the BWH system showed the highest overall discriminative ability, PPV was low for all staging systems, which shows the need for further improvement and refining of current cSCC staging systems.

The incidence rates of keratinocyte cancer are increasing globally; however, the incidence rates of cutaneous squamous cell carcinoma (cSCC) in situ and the risk of developing subsequent invasive cSCC remain unknown. OBJECTIVE To estimate annual population-based age-standardized incidence rates of histopathologically confirmed cSCC in situ stratified by sex, age, and body site and to assess the risk of developing invasive cSCC among patients with cSCC in situ compared with the general population. DESIGN, SETTING, AND PARTICIPANTSThis nationwide epidemiological population-based cohort study used cancer registry data to identify all patients with a first incident of histopathologically confirmed cSCC in situ between January 1, 1989, and December 31, 2017. In addition, all patients with cSCC in situ who subsequently had a first incident of invasive cSCC were identified up to June 11, 2019. Data were analyzed between March 18 and November 12, 2019. MAIN OUTCOMES AND MEASURESAge-standardized incidence rates per year for cSCC in situ, standardized to the 2013 edition of the European Standard Population, were calculated by sex, age, and body site. Cumulative risks, standardized incidence ratios, and absolute excess risks were calculated to assess the risk of invasive cSCC in patients with cSCC in situ compared with the general population. RESULTSIn this population-based cohort study of 88 754 patients with a first incident of cSCC in situ between January 1, 1989, and December 31, 2017, 58.8% were women; the median age was 75 years (interquartile range [IQR], 67-82 years) for women and 73 years (IQR, 65-80 years) for men. Increasing incidence rates were observed, with the highest incidence rates in 2017 among women in general (71.7 cases per 100 000 person-years) and among men 80 years and older (540.9 cases per 100 000 person-years). The most common body site among women was the face (15.9 cases per 100 000 person-years) and among men was the scalp and/or neck (12.3 cases per 100 000 person-years). After 5 years of follow-up, among patients with cSCC in situ, the cumulative risk of developing an invasive cSCC at any anatomic location was 11.7% (95% CI, 11.6%-11.9%) in men and 6.9% (95% CI, 6.8%-7.0%) in women (P < .001). The standardized incidence ratio was highest in the first year of follow-up among both men (16.6; 95% CI, 15.7-17.5) and women (15.1; 95% CI, 14.2-16.1). CONCLUSIONS AND RELEVANCEThis study reports the first nationwide incidence rates of cSCC in situ to date. The increasing incidence rates of cSCC in situ and the high risk of developing invasive cSCC among patients with cSCC in situ may increase the health care burden associated with precursors of keratinocyte cancer and highlight the need to include cutaneous skin cancer precursor lesions when exploring policies to address skin cancer care.

Summary Background Patients with actinic keratosis (AK) are at increased risk for developing keratinocyte carcinoma (KC) but predictive factors and their risk rates are unknown. Objectives To develop and internally validate a prediction model to calculate the absolute risk of a first KC in patients with AK. Methods The risk‐prediction model was based on the prospective population‐based Rotterdam Study cohort. We hereto analysed the data of participants with at least one AK lesion at cohort baseline using a multivariable Cox proportional hazards model and included 13 a priori defined candidate predictor variables considering phenotypic, genetic and lifestyle risk factors. KCs were identified by linkage of the data with the Dutch Pathology Registry. Results Of the 1169 AK participants at baseline, 176 (15·1%) developed a KC after a median follow‐up of 1·8 years. The final model with significant predictors was obtained after backward stepwise selection and comprised the presence of four to nine AKs [hazard ratio (HR) 1·68, 95% confidence interval (CI) 1·17–2·42], 10 or more AKs (HR 2·44, 95% CI 1·65–3·61), AK localization on the upper extremities (HR 0·75, 95% CI 0·52–1·08) or elsewhere except the head (HR 1·40, 95% CI 0·98–2·01) and coffee consumption (HR 0·92, 95% CI 0·84–1·01). Evaluation of the discriminative ability of the model showed a bootstrap validated concordance index (c‐index) of 0·60. Conclusions We showed that the risk of KC in patients with AK can be calculated with the use of four easily assessable predictor variables. Given the c‐index, extension of the model with additional, currently unknown predictor variables is desirable. Linked Comment: Kim et al. Br J Dermatol 2020; 183:415–416.