Non-melanoma skin cancer (NMSC) is a globally prevalent skin disease, with basal cell carcinoma and squamous cell carcinoma accounting for 99% of NMSC cases. While surgical excision is the most common approach, numerous non-surgical therapies have rapidly advanced in recent years. In cases of low-risk NMSC, alongside surgical excision, priority should be given to physical therapy and photodynamic therapy. Physical therapy modalities, exemplified by electrodessication and curettage, emerge as safe and efficacious alternatives. In juxtaposition, photodynamic therapy, albeit relatively more costly, assumes preference for patients exhibiting heightened cosmetic concerns owing to the scarring risks inherent to physical therapy and surgical excision. Notably, the combination of curettage and photodynamic therapy has exhibited remarkable efficacy in the treatment of nodular basal cell carcinoma. Additionally, for elderly patients who may be intolerant to stimulation, modified photodynamic therapy offers an almost painless option. When surgery is unavoidable, photodynamic therapy can be a valuable adjunct, allowing for a more conservative surgical approach, either before or after the procedure. Radiotherapy holds a prominent role in comprehensive treatment strategies, especially for patients ineligible for surgical intervention or those with lesions precluding further surgical measures. In cases of NMSC exhibiting perineural invasion or lymphovascular involvement, adjunctive radiotherapy is advised; however, potential adverse effects necessitate careful consideration. For advanced NMSC cases where surgery and physical therapy fall short, immunotherapy provide viable solutions. Systemic therapy employing Hedgehog pathway inhibitors can be considered for patients with distant metastatic basal cell carcinoma, despite its low incidence, or individuals with locally advanced lesions who are not surgical candidates, or those encountering recurrences after resection and radiotherapy. However, close monitoring of disease progression and adverse reactions is crucial. In this evolving landscape of NMSC treatment, personalized and multidisciplinary approaches are key, ensuring optimal outcomes while prioritizing patient safety and satisfaction.

Non-melanoma skin cancer (NMSC) is a prevalent skin malignancy. It has been indicated in many studies that trihalomethanes (THMs) exposure has a strong association with tumors but has not been associated with NMSC. Our investigation aims to explore the association between THMs exposure and NMSC.
Cross-sectional data from the 2011 to 2020 National Health and Nutrition Examination Survey (NHANES) was collected. Poisson regression and subgroup analyses were performed to evaluate the association between individual THMs components and NMSC. Fitted smoothing curves and generalized additive models were also used.
This study involved 5,715 individuals, 98 (1.7%) of whom self-reported NMSC. After adjusting for covariates, Poisson regression showed that higher blood TBM levels were associated with an increased likelihood of NMSC (OR = 1.03; 95% CI: 1.01-1.05, p = 0.002). However, the correlation between the blood levels of TCM, DBCM, and BDCM and the likelihood of NMSC was not statistically significant (all p > 0.05). Subgroup analysis and interaction tests showed no significant differences between blood TBM concentration and the likelihood of NMSC, indicating that age, gender, and race were significantly independent of this positive association (all p < 0.05).
Our results implied that among adults older than 65 years old in the U.S., elevated blood TBM concentrations were positively associated with NMSC. More prospective investigations are required to validate this relationship with the early prevention of NMSC.

OBJECTIVE: This study aimed to assess the cumulative incidences of Non-melanoma skin cancer (NMSC)-specific mortality (NMSC-SM) and develop a competing risk nomogram for NMSC-SM.
METHODS: Data on patients diagnosed with NMSC between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. To identify the independent prognostic factors, univariate and multivariate competing risk models were used, and a competing risk model was constructed. Based on the model, we developed a competing risk nomogram to predict the 1-, 3-, 5-, and 8-year cumulative probabilities of NMSC-SM. The precision and ability to discriminate of the nomogram were evaluated through the utilization of metrics, such as receiver-operating characteristic (ROC) area under the curve (AUC), concordance index (C-index), and a calibration curve. Decision curve analysis (DCA) was employed to assess the clinical usefulness of the nomogram.
RESULTS: Race, age, the primary site of the tumor, tumor grade, size, histological type, summary stage, stage group, order of radiation and surgery, and bone metastases were identified as independent risk factors. The prediction nomogram was constructed using the variables mentioned above. The ROC curves implied the good discrimination ability of the predictive model. The nomogram\'s C-index was 0.840 and 0.843 in the training and validation sets, respectively, and the calibration plots were well fitted. In addition, the competing risk nomogram demonstrated good clinical usefulness.
CONCLUSIONS: The competing risk nomogram displayed excellent discrimination and calibration for predicting NMSC-SM, which can be used in clinical contexts to help guide treatment decisions.

To assess the trends in non-melanoma skin cancer (NMSC) incidence in Hong Kong from 1990 to 2019 and the associations of age, calendar period, and birth cohort, to make projections to 2030, and to examine the drivers of NMSC incidence.
We assessed the age, calendar period, and birth cohort effects of NMSC incidence in Hong Kong between 1990 and 2019 using an age-period-cohort model. Using Bayesian age-period-cohort analysis with integrated nested Laplace approximations, we projected the incidence of NMSC in Hong Kong to 2030.
From 1990 to 2019, the age-standardized incidence rate of NMSC increased from 6.7 per 100,000 population to 8.6 per 100,000 population in men and from 5.4 per 100,000 to 5.9 per 100,000 population in women, among the 19,568 patients in the study (9812 male patients [50.14%]). The annual net drift was 2.00% (95% confidence interval [CI]: 1.50-2.50%) for men and 1.53% (95% CI: 0.95-2.11%) for women. Local drifts increased for both sexes above the 35-39-year age group. The period and cohort risk of developing NMSC tended to rise but slowed gradually in the most recent period and post-1975 birth cohort. From 2019 to 2030, it is projected that the number of newly diagnosed NMSC cases in Hong Kong will increase from 564 to 829 in men and from 517 to 863 in women. Population aging, population growth, and epidemiologic changes contributed to the increase in incident NMSCs, with population aging being the most significant contributor.
The slowing of the period and cohort effects suggests that the rising incidence of NMSC is partly attributable to increased awareness and diagnosis. The increasing prevalence of NMSC among the elderly and an aging population will significantly impact the clinical workload associated with NMSC for the foreseeable future.

BACKGROUND: The disease burden of non-melanoma skin cancer (NMSC) has become a significant public health threat. We aimed to conduct a comprehensive analysis to mitigate the health hazards of NMSC.
METHODS: This study had three objectives. First, we reported the NMSC-related disease burden globally and for different subgroups (sex, socio-demographic index (SDI), etiology, and countries) in 2019. Second, we examined the temporal trend of the disease burden from 1990 to 2019. Finally, we used the Bayesian age-period-cohort (BAPC) model integrated nested Laplacian approximation to predict the disease burden in the coming 25 years. The Norpred age-period-cohort (APC) model and the Autoregressive Integrated Moving Average (ARIMA) model were used for sensitivity analysis.
RESULTS: The disease burden was significantly higher in males than in females in 2019. The results showed significant differences in disease burden in different SDI regions. The better the socio-economic development, the heavier the disease burden of NMSC. The number of new cases and the ASIR of basal cell carcinoma (BCC) were higher than that of squamous cell carcinoma (SCC) in 2019 globally. However, the number of DALYs and the age-standardized DALYs rate were the opposite. There were statistically significant differences among different countries. The age-standardized incidence rate (ASIR) of NMSC increased from 54.08/100,000 (95% uncertainty interval (UI): 46.97, 62.08) in 1990 to 79.10/100,000 (95% UI: 72.29, 86.63) in 2019, with an estimated annual percentage change (EAPC) of 1.78. Other indicators (the number of new cases, the number of deaths, the number of disability-adjusted life years (DALYs), the age-standardized mortality rate (ASMR), and the age-standardized DALYs rate) showed the same trend. Our predictions suggested that the number of new cases, deaths, and DALYs attributable to NMSC would increase by at least 1.5 times from 2020 to 2044.
CONCLUSIONS: The disease burden attributable to NMSC will continue to increase or remain stable at high levels. Therefore, relevant policies should be developed to manage NMSC, and measures should be taken to target risk factors and high-risk groups.

Photodynamic therapy (PDT) is an effective treatment for some non-melanoma skin cancers (NMSC) and actinic keratosis. To compare recurrence-free survival (RFS) rates between surgery alone and surgery with postoperative PDT in patients with NMSC in China. This retrospective cohort study included patients with pathologically confirmed NMSC or actinic keratosis treated by surgical excision with/without PDT. A total of 125 patients were included, including 72 patients (43 females) aged 57-75 years in the surgery alone group and 53 patients (32 females) aged 61-76 years in the surgery+PDT group. The most common NMSC types were squamous cell carcinoma and basal cell carcinoma, the most common lesion site was the head and neck, and the vast majority of patients had a primary disease and solitary lesions. There were no significant differences between groups in baseline characteristics. RFS rates in the surgery alone and surgery+PDT groups were, respectively, 100.0% and 98.1% at 1 week, 98.6% and 98.1% at 4 weeks, 97.2% and 98.1% at 8 weeks, 97.2% and 98.1% at 12 weeks, and 90.3% and 90.4% at 24 weeks, with no significant differences between groups. Adjuvant PDT after surgical excision of NMSC or actinic keratosis does not provide short-term improvement in RFS, but the results need to be confirmed by a formal randomized controlled trial.

BACKGROUND: Most previous studies compared the risk for non-melanoma skin cancer (NMSC) in biologic-treated common inflammatory diseases with the general population. Whether the increased NMSC risk is caused by the disease itself, the biologics, or both remains unknown.
METHODS: We systematically searched PubMed, Embase, Medline, Web of Science, and Cochrane Library from inception to May 2021. Studies were included if they assessed the risk of NMSC for rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis patients treated with biologics compared with patients not receiving biologics. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the fixed- or random-effects model.
RESULTS: The current meta-analysis included 12 studies. Compared with patients with the inflammatory disease without biologics, patients receiving biological therapy were associated with an increased risk for NMSC (RR 1.25, 95% CI 1.14 to 1.37), especially in patients with RA (RR 1.24, 95% CI 1.13 to 1.36) and psoriasis (RR 1.28, 95% CI 1.07 to 1.52), but not in patients with IBD (RR 1.49, 95% CI 0.46 to 4.91). The risks for squamous cell skin cancer and basal cell skin cancer were both increased for patients receiving biologics. However, the risk of NMSC did not increase in patients treated with biologics less than 2 years.
CONCLUSIONS: Current evidence suggests that increased risk of NMSC was identified in RA and psoriasis treated with biologics compared with patients not receiving biologics, but not in patients with IBD. The inner cause for the increased risk of NMSC in IBD patients should be further discussed.

Non-melanoma skin cancer (NMSC) is the most common malignancy. Photodynamic therapy (PDT) is effective for the treatment of certain NMSCs. However, the clinical response rates of some NMSCs to single PDT are still far from ideal. The reason may be that PDT has shown limited efficacy in managing thicker NMSCs. To explore the efficacy and safety of dermabrasion combined with PDT (D-PDT) for the treatment of NMSCs. This was a retrospective, single-arm, multi-centre study. In total, 172 tumours from 40 patients were treated with D-PDT during the study period. The mean follow-up period was 40 months (range 15-110 months). D-PDT was performed with 633-nm red light at 80 m W/cm2 after lesion dermabrasion and 4 h of photosensitizer exposure. Six nodular basal cell carcinomas (nBCCs) from 6 patients, 9 squamous cell carcinomas (SCCs) from 9 patients, 17 Bowen diseases (BDs) from 10 patients and 140 actinic keratoses (AKs) from 15 patients treated with D-PDT were examined in this study. Only two patients with three AKs experienced recurrence over 12 months. The mean final follow-up periods of patients with AKs, BDs, nBCCs and SCCs were 30, 33, 45 and 60 months, respectively. Thirty-four of the 40 patients treated with D-PDT reported excellent or good cosmetic results. The mean Dermatology Life Quality Index (DLQI) scores of the patients improved significantly after treatment (estimated MD 9.72 [95% CI 8.69 to 10.75]; p < 0.001). D-PDT is a safe, cosmetic and effective treatment that could be a new candidate therapeutic for NMSC.

UNASSIGNED: 5-aminolevulinic acid through a needle-free, plum-blossom needle or conventional needle followed by photodynamic therapy are available options for non-melanoma skin cancer treatment.
UNASSIGNED: To compare these three techniques of injection of 5-aminolevulinic, regarding treatment response and adverse effects in patients with non-melanoma skin cancer.
UNASSIGNED: Non-melanoma skin cancer patients have received six cycles of 0.5 mL intralesional 20% w/v 5-aminolevulinic acid through a conventional needle (CPT cohort, n = 158), or plum-blossom needle (BPT cohort, n = 118), or needle-free injection (NPT cohort, n = 105) followed by irradiation with a red light. Data regarding treatment response and adverse effects were collected and analyzed.
UNASSIGNED: The treatment response was higher among patients of NPT cohort than those of CPT (p = .012, q = 3.981) and BPT (p = .012, q = 3.472) cohorts. Conventional and plum-blossom needle injections therapies were reported scar, local redness, and worse cosmetic appearance in the follow-up period.
UNASSIGNED: Needle-free injection of intralesional 5-aminolevulinic acid followed by irradiation with red light therapy were reported high treatment response with manageable adverse effects for non-melanoma skin cancer patients than that of conventional and plum-blossom needle injections.
UNASSIGNED: III.

OBJECTIVE: Tumor necrosis factor inhibitors (anti-TNF) have become the standard treatment for rheumatoid arthritis (RA). However, evidence is inconsistent as to whether RA patients with anti-TNF are associated with an increased risk of non-melanoma skin cancer (NMSC) compared with those without anti-TNF. We performed a systematic review and meta-analysis to evaluate the risk of NMSC in patients with anti-TNF drugs compared with those without anti-TNF.
METHODS: We did a systematic literature search with PubMed, EMBASE, and the Cochrane Library from inception to April 1, 2019. Prospective observational studies were eligible for inclusion if they included any of the approved anti-TNF drugs and reported the risk estimates and 95% confidence interval (95% CI) of NMSC associated with anti-TNF in RA patients. Pooled relative risks (RRs) and 95% CIs were calculated using a fixed-effects model. To assess the heterogeneity and risk of publication bias, we respectively conducted the subgroup and sensitivity analysis, funnel plot, Begg\'s and Egger\'s test.
RESULTS: The present meta-analysis included six studies with 123,031 patients. Compared with RA patients without anti-TNF, patients with anti-TNF drugs were associated with an increased risk of NMSC (RR 1.28, 95% CI 1.19 to 1.38; I2 = 45.6%, P = 0.056), especially squamous cell skin cancer (SCC) (RR 1.30, 95% CI 1.09 to 1.54; I2 = 0%, P = 0.854), but not basal cell skin cancer (RR 1.13, 95% CI 0.97 to 1.31; I2 = 0%, P = 0.555). Sensitivity and subgroup analysis confirmed the robustness of the primacy results. There was no evidence of publication bias with Begg\'s and Egger\'s test or by inspection of the funnel plot.
CONCLUSIONS: These results suggest that RA patients treated with anti-TNF are at an increased risk of NMSC, especially SCC. However, this association in RA urgently needs the more clinical studies and basic researches to further validate.Key Points• Rheumatoid arthritis patients treated with tumor necrosis factor inhibitors are associated with a higher risk of non-melanoma skin cancer compared to those patients treated without tumor necrosis factor inhibitors. Hence, tumor necrosis factor inhibitors may be avoided in rheumatoid arthritis patients who are at high risk of non-melanoma skin cancer.• Of note, rheumatoid arthritis patients who were treated for tumor necrosis factor inhibitors compared with patients who were not treated for tumor necrosis factor inhibitors were at significantly increased risk of squamous cell skin cancer, but were not at increased risk of basal cell skin cancer. Therefore, use of tumor necrosis factor inhibitors in rheumatoid arthritis patients should be paid attention to the occurrence of squamous cell skin cancer.