Search Results (457)

Background: There exists an unmet clinical need to define definitive management strategies for patients with locally advanced non-melanoma skin cancers (NMSC), particularly if not amenable to surgical resection. Methods: We retrospectively reviewed a case series of locally advanced unresectable NMSC treated with induction systemic treatment followed by response-adapted consolidative radiation. Results: We identified 15 patients who met study criteria, including seven with basal cell carcinoma (BCC), six with cutaneous squamous cell carcinoma (CSCC), and two with Merkel cell carcinoma (MCC). Clinical complete response (CR) by physical examination was observed in all 15 patients. No locoregional or distant recurrences were observed in any histologic subtype after completion of radiation (median follow-up from completion of radiation: 18.1 months BCC, 22.5 months CSCC, 22.7 months MCC). The median duration of observed response (DOOR), measured from first clinical response was 26.9 months (26.2 BCC, 29.4 CSCC, 27.1 MCC). Radiation treatment volumes were response-adapted with median gross tumor volume reduction of 55.3% (15.3%–100%). Median treatment-free response was 20.5 months. No unexpected systemic therapy related toxicities were identified. Conclusions: In this single-institution retrospective case series, induction systemic therapy followed by response-adapted consolidative radiation was feasible and associated with durable disease control in selected patients with locally advanced unresectable NMSC. Full article

Background/Objectives: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor, most commonly occurring on the head and neck. Incidence of MCC is rising with the aging population. Five-year overall survival (OS) for localized MCC is 50.6%; 5-year OS for patients with distant metastases is 13.5%. The purpose of this study is to determine if coordination of care for the treatment of MCC is logistically feasible, and provide a description of the patient population observed at this institution. Methods: All patients with MCC diagnosis from January 2012–June 2024 were identified at our tertiary care center. All patients with MCC were added to our non-melanoma skin cancer registry. Outcomes were compared between those treated with our “Merkel cell carcinoma in a day” (MIAD) protocol and those receiving the standard treatment protocol. Results: No significant differences were detected in the recurrence rate, transit metastasis, distant metastasis, and disease-specific death. Nodal metastasis was higher in the MIAD group (HR 4.94, 95% CI 1.08–22.6, p = 0.039, six events total). Both groups had similar times to treatment and treatment within 30 days of diagnosis. Conclusions: MCC is a rare and aggressive tumor, often exhibiting subclinical tumor spread. Mohs micrographic surgery ensures 100% peripheral and deep margin assessment, with potential for tissue sparing. With thoughtful coordination, lymphoscintigraphy can be completed on the same day as Mohs surgery followed by sentinel lymph node biopsy (SLNB) and reconstructive surgery. Full article

Electrochemotherapy (ECT) is a locoregional treatment that combines poorly permeable drugs, commonly bleomycin (BLM) or cisplatin (CDDP), with electric pulses that induce electroporation. By transiently increasing cell membrane permeability, ECT promotes intracellular drug accumulation, enhancing cytotoxic effects while minimizing undesirable systemic toxicity. Beyond its direct cytotoxic effects, ECT exerts additional antitumour mechanisms that contribute to tumour control. These include the induction of immunogenic cell death (ICD), leading to activation of innate and adaptive immune responses; the “abscopal effect”, achieved with the combination of ECT and immune checkpoint inhibitors; and the “vascular lock” phenomenon, promoting a transient local blood flow reduction and enhancing intratumoural drug retention; and a “vascular disrupting effect” that contributes to tumour vascular damage and secondary tumour cell death. ECT has demonstrated high objective response rates (ORR) across a wide range of cutaneous malignancies, including melanoma and non-melanoma skin cancers (NMSCs) and cutaneous dissemination of other tumours. Although predictive biomarkers capable of identifying patients who benefit from treatment are still lacking, substantial preclinical and clinical evidence supports the efficacy, safety and tolerability of ECT. Several ongoing clinical trials are currently evaluating ECT, particularly in advanced or non-resecable melanoma, aiming to investigate further biological effects and optimize therapeutic strategies. Furthermore, innovative approaches integrating ECT with gene electrotransfer and nanomedicine represent a promising avenue to enhance its therapeutic efficacy and expand its role in precision oncology. Full article

Background: Non-melanoma skin cancer (NMSC), principally basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), is incompletely captured by cancer surveillance. Objective: To synthesize European epidemiological evidence, with Poland considered in this context. Methods: PubMed/MEDLINE, Scopus, and Web of Science were searched for publications dated 1 January 2015–31 March 2026, supplemented by registry resources and reference-list searching. Additional eligibility checks during manuscript revision continued until 30 August 2026. The publication-date criterion was distinct from the observation periods of source data. Source-level methodological appraisal informed a descriptive synthesis. Results: The consolidated selection record comprised 198 records, 165 screened records, 61 full-text assessments, 37 full-text exclusions, and 24 included sources. Several registry-based studies reported increasing BCC or cSCC incidence in defined populations. Model-based age-standardized trends varied by geography, sex, age, and observation period. These results do not establish a uniform European increase. Polish estimates were affected by histological aggregation and incomplete ascertainment. Selected pandemic-period studies reported fewer diagnoses or changes in the treated case mix; these findings do not establish a Europe-wide decline in biological incidence or subsequent rebound. Conclusions: NMSC creates a substantial and incompletely measured European burden. Histology-specific registration, explicit multiple-primary counting rules, and improved outpatient capture are priorities for interpreting trends and planning care. Full article

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) treated with high-dose-rate (HDR) surface brachytherapy using patient-specific 3D-printed applicators lacks a validated non-invasive follow-up modality capable of resolving microscopic residual disease. Line-field confocal optical coherence tomography (LC-OCT) provides real-time, cellular resolution, three-dimensional imaging of the epidermis and superficial dermis and has been proposed as a candidate tool for post-radiotherapy monitoring. We evaluated the feasibility of LC-OCT for pre- and post-treatment imaging of cSCC and assessed whether an LC-OCT-defined remission phenotype, operationally defined a priori as the absence of all malignancy-associated LC-OCT criteria, can be documented after 3D-printed HDR surface brachytherapy. Methods: Eight consecutive patients with histologically confirmed cSCC, unsuitable for surgery, were treated with HDR surface brachytherapy delivered through patient-specific 3D-printed applicators. LC-OCT imaging was performed immediately before brachytherapy and at short-term follow-up (six months). Nineteen pre-treatment LC-OCT criteria derived from the Cinotti 2021 descriptive criterion set for cSCC were scored: seventeen malignancy-associated criteria, plus elastosis (scored as a background photodamage covariate, not counted towards remission) and fibrosis (scored post-treatment only). Presence/absence of each criterion was rated by two blinded dermatologists; inter-assessor agreement was quantified using percentage agreement and Cohen’s kappa. Results: Baseline LC-OCT showed a rich malignant signature: hyperkeratosis, parakeratosis, disarranged epidermal architecture, dyskeratotic keratinocytes, atypical and crowded nuclei, and dermoepidermal junction alterations were present in eight out of eight lesions (100%) under an inclusive two-reader rule. At short-term follow-up, six months after the final brachytherapy fraction, all seventeen malignancy-associated criteria constituting the pre-specified remission set were absent in all eight patients under the decision rule described in the article—which classifies isolated dilated linear vessels occurring in an otherwise criterion-negative, fibrotic dermis as post-radiation telangiectasia rather than residual tumour, yielding an LC-OCT-defined remission phenotype rate of 100% (eight out of eight; 95% exact binomial [Clopper–Pearson] CI 63.1–100%). Post-radiation fibrosis was observed in 8/8 patients (100%), and dilated linear vessels were observed in six out of eight patients (75%, evaluated under the same decision rule (Observer 1: 4/8; Observer 2: 6/8). Elastosis, a marker of background actinic photodamage present in eight out of eight lesions at baseline and excluded from the malignancy-associated criterion count, is distinct from post-treatment fibrosis, a radiation-induced dermal remodelling feature scored only at follow-up; the two should not be conflated. Conclusions: In this proof-of-concept cohort, LC-OCT was feasible for pre- and post-treatment imaging of cSCC after 3D-printed HDR surface brachytherapy, produced highly reproducible dual-observer readings (κ = 0.903), and documented, at a single short-term time point six months after the final fraction, an LC-OCT-defined remission phenotype in every treated lesion, with a consistent fibrosis signature. Persistent dilated linear vessels in a fibrotic, otherwise criterion-negative dermis were classified as a non-specific post-radiation vascular change and did not preclude LC-OCT-defined complete remission. Because this remission phenotype rests on a pre-specified but not externally validated imaging definition and was not anchored to post-treatment histopathology or reflectance confocal microscopy, it constitutes an imaging surrogate rather than a confirmed complete remission, and microscopic residual disease below the resolution limit of LC-OCT cannot be excluded. These hypothesis-generating findings support LC-OCT as a candidate non-invasive monitoring modality, requiring confirmation in larger, biopsy-anchored prospective studies with longer follow-up. Full article

Background and Objectives: Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer, and its global incidence rate constantly rises. However, there are no current epidemiological data for many regions, including Małopolska in southern Poland. This study aimed to characterize the clinical and histological profile of patients with BCC and to identify factors associated with local recurrence and the presence of multiple tumors. Materials and Methods: We performed a single-center, retrospective observational study consistent with STROBE guidelines at the Department of Dermatology and Allergology, University Hospital in Cracow. The included patients were adults with at least one histologically confirmed BCC treated between 2015 and 2025. Demographic, clinical, histopathological, and follow-up data were collected at patient and lesion levels. The results were evaluated using univariable tests, multivariable logistic regression, Kaplan–Meier survival analysis, and generalized estimating equations. Results: We included 108 patients (median age at first diagnosis, 73 years; 52% male) with 418 BCCs; the median follow-up duration was 84 months. Superficial BCC was the most common subtype among lesions with available histological subtype information (56%). The head and neck region was the most frequent anatomical site in this group (51%). Multiple BCCs were present in 62% of patients. Longer follow-up was independently associated with the presence of multiple BCCs. A history of actinic keratoses showed a positive but statistically nonsignificant association with multiple BCCs. Recurrence was observed in 15 lesions (3.6%). Female sex and H-zone involvement showed higher odds of recurrence. Conclusions: In this elderly cohort, multiple BCC tumors may reflect longer follow-up and cumulative actinic damage. Recurrence was relatively infrequent but associated with clinically relevant features, including H-zone involvement and female sex. These findings support an individualized, multifactorial approach to treatment and follow-up, taking into account age, sex, lesion burden, anatomical location, and histological subtype. Full article

Recurrent non-melanoma skin cancer (NMSC) may be accompanied by cosmetic, functional, and emotional consequences. Aims: To examine associations among psychological symptoms, quality of life, resilience, and religiosity and to compare psychological outcomes between patients treated once and patients with recurrent facial NMSC. Methods: This cross-sectional study included 160 patients after surgery for facial NMSC (63 treated once and 97 with recurrent disease). Data were collected with a sociodemographic questionnaire, the Symptom Checklist-90-R (SCL-90-R), the Connor–Davidson Resilience Scale 25 (CD-RISC-25), the World Health Organization Quality of Life Scale (WHOQOL-BREF) and DUREL. Results: Greater psychological symptom severity was consistently associated with poorer scores across all WHOQOL-BREF domains. The overall multivariate group effect was significant (Pillai’s Trace = 0.235, F(6.149) = 7.641, p < 0.001, partial eta squared = 0.235). After Bonferroni correction for six follow-up tests, patients with recurrent NMSC had a higher adjusted GSI and lower adjusted psychological health scores than patients treated once (both p < 0.001). Adjusted differences in physical health, social relationships, environment, and CD-RISC were not statistically significant. Conclusions: Recurrent NMSC status was associated with greater psychological symptom burden and poorer psychological quality of life. Routine psychological screening may help identify patients who require further assessment or support. Full article

Photodynamic therapy (PDT) is a promising minimally invasive treatment for non-melanoma skin cancer (NMSC). Still, its clinical efficacy is limited by light attenuation and drug distribution within tumor tissue, which restricts photosensitizer activation in deeper tumor regions. PDT with 5-aminolevulinic acid (ALA) is widely used as a precursor to induce accumulation of protoporphyrin IX (PpIX), followed by red light irradiation; it is effective for superficial lesions but often fails to achieve complete tumor control in thicker tumors, contributing to long-term lesion recurrence. To address this limitation, we investigated a two-photosensitizer, two-wavelength-PDT approach that combines ALA with indocyanine green (ICG), a near-infrared (NIR)-responsive photosensitizer that can be activated at greater tissue depths. This also promotes different cellular death targets, since ALA-mediated PDT mainly induces direct tumor cell killing through apoptosis and necrosis, whereas ICG-mediated PDT may contribute to treatment effects through deeper tissue activation and vascular-associated mechanisms. In this study, a preclinical model of cutaneous squamous cell carcinoma (SCC) was used, with animals assigned to control, single-photosensitizer PDT (ALA, ICG), and combined photosensitizer PDT treatment groups. The effect of photosensitizer administration and light irradiation sequence on therapeutic efficacy was also investigated, and tumor progression and survival outcomes were monitored over time. The results indicated that the combined ALA+ICG-PDT approach produced the most sustained suppression of tumor growth and significantly prolonged animal survival compared with single-photosensitizer PDT. Importantly, these findings demonstrated a strong dependence on the sequence in which the photosensitizer and light are applied. These findings indicate that integrating photosensitizers activated at complementary wavelengths may improve treatment coverage across the tumor and partially overcome depth-related limitations associated with PDT, representing a promising strategy to enhance PDT efficacy for NMSC and other solid tumors. Full article

Photodynamic therapy (PDT) is a minimally invasive anticancer modality based on the interaction of a photosensitizer, light of an appropriate wavelength, and molecular oxygen, resulting in reactive oxygen species (ROS)-mediated tumor injury. This review discusses PDT as a mechanism-dependent therapeutic platform and evaluates how photosensitizers, vitamin A, vitamin D, nanotechnology, and combination strategies may influence its efficacy. The article synthesizes mechanistic and translational evidence concerning photosensitizer activation, ROS generation, tumor cell death, vascular shutdown, immunogenic cell death, and clinically relevant PDT applications. Particular attention is given to the divergent roles of vitamin A and vitamin D. Mechanistic and limited experimental evidence indicates that the effects of vitamin A-related compounds on PDT are heterogeneous and context-dependent. Selected compounds may attenuate PDT through antioxidant or cytoprotective mechanisms, whereas enhancement has also been reported for specific retinoid–photosensitizer combinations; however, clinical evidence remains limited. In contrast, vitamin D may enhance ALA/MAL-PDT by increasing intracellular protoporphyrin IX accumulation through modulation of the heme biosynthetic pathway, especially in non-melanoma skin cancer contexts. Nanocarriers, targeted photosensitizers, oxygen-modulating platforms, chemotherapy, and immunotherapy may further improve PDT when selected according to mechanistic compatibility. Overall, PDT combination design should be guided by whether adjunctive agents support or undermine photosensitizer accumulation, oxygen availability, ROS-mediated cytotoxicity, and immune activation. Full article

Background/Objectives: Basal cell carcinoma (BCC) is the most common skin cancer and may negatively influence a patient’s well-being despite low mortality. This systematic review and exploratory meta-analysis evaluated dermatology-related quality of life, as measured exclusively by the Dermatology Life Quality Index (DLQI), in patients with BCC and other non-melanoma skin cancers (NMSC). Instruments other than the DLQI, including disease-specific measures of appearance, scarring, fear of recurrence and treatment satisfaction, were outside the scope of the quantitative synthesis. Methods: A systematic search of the PubMed, Scopus, and the Web of Science was conducted until 5 April 2026 following the PRISMA guidelines. Studies reporting DLQI outcomes in adult patients with BCC, squamous cell carcinoma (SCC), or NMSC were included. Pooled baseline DLQI scores and pre- to post-treatment changes were calculated using a random effects model. Results: Six studies were included. The pooled baseline DLQI score was 3.76 (95% CI: 2.18–5.33) in the BCC-only analysis and 4.07 (95% CI: 2.99–5.15) in an exploratory expanded analysis including SCC and broader NMSC populations; this estimate should be interpreted as a summary of heterogeneous keratinocyte cancer populations rather than as representative of BCC alone. None of the included studies had an untreated comparator group, so the pre–post results describe the change in DLQI score following treatment rather than a treatment effect. The pooled reduction was 2.38 points (95% CI: 0.56–4.19) in the BCC-only and 1.90 points (95% CI: 0.84–2.96) in the expanded pre–post analysis. Both fall below the minimal clinically important difference for the DLQI of approximately four points. Heterogeneity was very high throughout (I² > 95% for baseline analyses), so the pooled means summarize highly dispersed evidence and cannot be read as representative average values. Surgical treatment appeared to show a greater improvement in DLQI scores compared with the single available radiotherapy cohort. This comparison should be interpreted descriptively due to the inclusion of only one radiotherapy study. Conclusions: Patients with BCC and other NMSCs experience measurable impairment in dermatology-related quality of life before treatment, although the overall burden is generally mild. Treatment is associated with improvement in DLQI scores; however, the magnitude of change is modest and may not consistently exceed thresholds considered clinically meaningful. Evidence regarding differences between treatment modalities remains limited, particularly for radiotherapy, and further prospective studies using disease-specific quality-of-life instruments are needed. Full article

Background/Objectives: Metatypical basal cell carcinoma (MTBCC) is a rare and aggressive variant of non-melanoma skin cancer (NMSC) characterised by overlapping histological features of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Owing to its increased propensity for local invasion, recurrence, and metastasis, MTBCC poses diagnostic and therapeutic challenges. This study aimed to characterise the epidemiological, histopathological, and clinical features of MTBCC and to evaluate temporal changes in tumour characteristics and aggressiveness before, during, and after the COVID-19 pandemic. Methods: A retrospective cohort study was conducted on 129 histologically confirmed MTBCC lesions diagnosed in the Pathology Department of the Mures Clinical County Hospital, Targu Mures, Romania, between January 2017 and December 2025. Demographic data, tumour location, histological subtypes, differentiation of the squamous component, aggressiveness parameters, and volumetric measurements of tumours and excision specimens were analysed. Volumetric analyses were restricted to cases with complete three-dimensional measurements. Statistical comparisons were performed across demographic variables and the following three time periods: pre-pandemic, pandemic, and post-pandemic. Results: The median age at diagnosis was 71 years, with a slight male predominance (p = 0.25) and a significant predominance of patients from urban areas (p < 0.001). Most tumours were located in the head and neck region. Mixed-type MTBCC was significantly associated with higher tumour aggressiveness (p = 0.0019) and with high-risk histological subtypes, particularly micronodular and adenoid–cystic variants. Tumour volume showed a significant inverse correlation with year of diagnosis (p = 0.0139; r = (−) 0.50), whereas excision specimen volume differed significantly according to year of diagnosis (p = 0.0425). Neither tumour volume nor excision specimen volume was associated with histopathological aggressiveness. Conclusions: Metatypical basal cell carcinoma is a rare skin malignancy in which biological behaviour appears to be determined primarily by histopathological architecture rather than tumour size. Mixed-type lesions were associated with significantly higher aggressiveness, underscoring the need for accurate histopathological assessment. These findings support a pathology-driven approach to management and emphasise the importance of adequate surgical treatment and long-term follow-up in patients with MTBCC. Full article

Background: Long-term mortality trends for melanoma and non-melanoma skin cancer (NMSC) in Hungary have not been comprehensively assessed. Methods: We conducted a retrospective nationwide study of deaths registered in Hungary between 1980 and 2020 among individuals aged 35 years or older, where melanoma (ICD-10 C43) or NMSC (ICD-10 C44) was recorded as the primary cause of death. Annual crude death rates (CDRs; overall and age-specific 35–64 and ≥65 years) and age-standardised death rates (ASDRs) per 100,000 population were calculated by sex. Trends were analysed using Joinpoint regression. Results: Overall, 18,857 skin cancer deaths, including 12,026 melanoma and 6831 NMSC deaths, were identified. Melanoma mortality was consistently higher in men. Among men, melanoma ASDR increased until 1994 and then stabilised, while crude mortality among older men continued to increase. Among women, the ASDR of melanoma increased until 1994 and subsequently declined. Crude mortality decreased after 2005 in women aged 35–64 years. Although NMSC mortality was lower than melanoma mortality, NMSC accounted for 36.2% of skin cancer deaths. In both sexes, NMSC mortality was concentrated in adults ≥ 65 years. In older women, crude NMSC mortality increased again after the mid-2000s, whereas ASDR remained broadly stable. Conclusions: Melanoma mortality trends in Hungary partially stabilised or improved after the mid-1990s, particularly in age-standardised analyses, but mortality remained high among older adults, especially among men. NMSC represented a substantial proportion of skin cancer deaths, with the burden concentrated in adults ≥ 65 years, supporting the inclusion of NMSC in routine mortality surveillance and disease burden assessments. Full article

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer (NMSC) and represents the leading cause of NMSC-related deaths. Despite its growing global burden, comprehensive epidemiological and clinicopathological data from Easter Europe remains limited. This study aimed to evaluate the epidemiological, clinical, histopathological, and surgical characteristics of cSCC diagnosed before, during and after the COVID-19 pandemic. Methods: We conducted a retrospective, descriptive observational study including 332 lesions diagnosed between January 2017 and December 2025 at the Clinical Pathology Department of the Mureș Clinical County Hospital. Demographic, epidemiological, topographic, histopathologic, surgical, and volumetric parameters were analyzed. Tumours were stratified into low-, high-, and very-high-risk categories according to the National Comprehensive Cancer Network (NCCN) criteria. Results: The cohort demonstrated a significant male predominance (n = 193 vs. n = 139; p = 0.0355), with females presenting a higher median age (77 vs. 75; p = 0.0489). Lesions were predominantly located in the head and neck region (n = 216; p < 0.0001), which was significantly associated with very-high-risk tumours (p = 0.0051). Low-risk tumours accounted for 62.35% of cases, while high-risk and very-high-risk lesions comprised 19.88% and 17.77%, respectively (p < 0.0001). Ulcerations were strongly associated with very-high-risk tumours (p < 0.0001). Poor differentiation was more frequent outside the head and neck region (p < 0.0001) and varied significantly across the pandemic periods (p = 0.0349). Tumoral and excision volumes were higher in very-high-risk (p = 0.0070; p = 0.0004) and ulcerated tumours (p < 0.001), with a peak in volume during the COVID-19 period (p < 0.0001). A decrease through the years of diagnosis was observed in tumoral volumes (r = −0.2295; p < 0.0001) and patients showed a weak positive correlation with diagnosis year (r = +0.13; p = 0.019). Conclusions: The study provides an epidemiological and clinicopathological characterization of cSCC within one of the largest Romanian cohorts to date. Tumour aggressiveness was primarily driven by histopathological and topographical features rather than demographic factors. While the COVID-19 pandemic did not induce persistent changes in tumour risk profiles or surgical outcomes, it influenced diagnosis timing and tumour burden. These findings highlight the importance of incorporating temporal and emerging systemic factors, such as pandemics, and infectious events, into future epidemiological models to improve preparedness, early detection, future treatment schemes, and risk stratification in cSCC. Full article

Psoriasis is a chronic, autoimmune skin disease driven by persistent inflammation and immune dysfunction that severely impairs quality of life and is associated with serious comorbidities, including psoriatic arthritis, cardiovascular diseases (CVDs), and depression. Emerging epidemiological evidence suggests an association between psoriasis and an increased risk of certain malignancies, such as breast cancer (BC) and non-Hodgkin’s lymphoma (NHL), although the strength and consistency of these associations vary across study designs, and the underlying thrombo-inflammatory mechanisms remain incompletely understood. Several therapeutic approaches, including topical therapies, conventional systemic drugs (e.g., methotrexate and cyclosporine), and biological agents have been investigated for their potential associations with malignancy risk. However, the available evidence is heterogeneous and influenced by disease severity, treatment duration, cumulative exposure, and patient-related confounding factors. While some epidemiological studies have reported associations between conventional therapies and selected skin or hematological malignancies, combined or sequential treatment regimens further complicate the interpretation of treatment-related cancer risk. Similarly, Janus kinase (JAK) inhibitors have been associated with higher reported rates of lymphoma and non-melanoma skin cancer than tumor necrosis factor α inhibitors (TNFi-α) in some observational studies. Recent studies also highlight the clinical utility of inflammatory markers, specifically the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR) ratio, and systemic immune-inflammation index (SII), for monitoring systemic inflammation and treatment response, while certain therapies may additionally influence CVD risk. Despite these advances, substantial heterogeneity across observational studies, meta-analyses, and Mendelian randomization analyses preclude definitive conclusions regarding causality. Overall, this review synthesizes the current epidemiological and mechanistic evidence linking psoriasis, chronic inflammation, therapeutic interventions, cancer risk, and cardiovascular comorbidities, while highlighting the need for large prospective studies and standardized analytical approaches. Full article

Patients with inflammatory bowel disease (IBD) often require long-term immunosuppressive or advanced therapy, raising concerns about treatment-associated malignancy risk. This systematic review evaluated malignancy outcomes associated with biologic, advanced small-molecule, and thiopurine therapies in adults with IBD. PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception through June 2025, with supplementary screening of Google Scholar and reference lists. Eligible primary studies included randomized controlled trials and prospective or retrospective cohort studies evaluating malignancy outcomes. Thiopurines were included because they remain clinically important comparators and are central to combination-therapy risk. The Newcastle–Ottawa Scale and the Cochrane risk-of-bias tool were used for observational studies and randomized trials, respectively. Because of substantial clinical and methodological heterogeneity, we did not perform a de novo meta-analysis; pooled estimates from previously published meta-analyses are reported only as contextual evidence. Twenty-eight studies met the inclusion criteria. Thiopurines showed the most consistent malignancy associations, including lymphoma, non-melanoma skin cancer (NMSC), acute myeloid leukemia/myelodysplastic syndrome, and urinary tract cancer. Anti-tumor necrosis factor (anti-TNF) monotherapy was not associated with a clear increase in overall cancer incidence, although a modest lymphoma signal was reported in some datasets. Combination anti-TNF plus thiopurine therapy showed the strongest lymphoma signal. Current evidence has not demonstrated an increased malignancy risk with vedolizumab or ustekinumab, including in available cohorts of patients with prior malignancy; however, confidence is limited by observational designs, small event numbers, heterogeneous cancer histories, and limited follow-up. IBD-specific data for Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators remain comparatively immature, and long-term surveillance is required. Overall, treatment decisions should integrate absolute baseline risk, age, smoking, prior malignancy, prior NMSC, Epstein–Barr virus-related risk, disease-related cancer risk, and cumulative immunosuppressive exposure. Full article