Background/Objectives: Despite demonstrated mortality benefits, annual low-dose computed tomography (LDCT) screening faces challenges in real-world adoption due to low uptake and poor longitudinal adherence. This review evaluates patient- and provider-level factors that influence screening participation and highlights strategies to strengthen equitable engagement throughout the screening pathway. Methods: A structured literature search of PubMed and Web of Science was performed to identify studies published between 2013 and November 2025 (search conducted on 25 November 2025). Eligible publications included qualitative and quantitative studies, study protocols, and reviews examining LDCT screening uptake, adherence, and follow-up practices. Extracted evidence was synthesized, with particular attention being paid to patient- and provider-level determinants. Results: The evidence demonstrates that both patient- and provider-level factors substantially influence screening participation and continuity. At the patient level, limited awareness of screening, misconceptions regarding asymptomatic disease, and psychosocial factors such as fear, fatalism, stigma, and medical mistrust were consistently associated with reduced uptake and adherence. At the provider level, gaps in guideline familiarity, time constraints, and challenges in delivering high-quality shared decision-making limited referrals and follow-up. Conclusions: Improving real-world effectiveness of LDCT lung cancer screening requires reframing screening as a longitudinal program of care. Strategies that support patient navigation, enhance provider capacity for sustained engagement, and integrate tobacco dependence treatment into screening pathways are central to improving adherence and reducing disparities.

Background/Objectives: The advent of immune checkpoint inhibitors (ICIs) and targeted therapies has revolutionized advanced cutaneous melanoma care, shifting it from an acutely fatal illness to a chronic, manageable condition. While extending survival, these modern therapies introduce a new spectrum of persistent immune-related adverse events (irAEs) and long-term toxicities. This study aims to explore the “Toxicity-HRQoL Paradox” to comprehensively evaluate the true price of survival across the melanoma treatment continuum. Methods: This narrative review, based on a systematic database search, synthesizes quantitative patient-reported outcomes, health-related quality of life (HRQoL) trajectories, and health-economic data. It evaluates the impact of surgical, regional, and modern systemic therapies utilizing data derived from validated instruments, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), EuroQol 5 Dimensions (EQ-5D), Functional Assessment of Cancer Therapy-Melanoma (FACT-M), and comprehensive score for financial toxicity (COST). Results: Historically, extensive locoregional surgeries and high-dose interferons caused profound, debilitating drops in physical and overall QoL. Today, modern systemic therapies are associated with high rates of severe (Grade ≥ 3) acute toxicities and irreversible chronic conditions, such as permanent endocrinopathies. Despite this, global HRQoL frequently remains stable or even improves. This “toxicity-HRQoL paradox” occurs because the profound psychological relief of durable disease control effectively offsets the physical symptom burden. Furthermore, neoadjuvant ICI approaches demonstrate superior long-term HRQoL by enabling tailored surgical de-escalation. Ultimately, extended survivorship unmasks hidden burdens, revealing high prevalences of fear of cancer recurrence (FCR) (81–86%) and substantial financial toxicity. Conclusions: Despite the severe physical toxicities of modern melanoma treatments, the psychological benefit of survival largely preserves overall HRQoL. However, optimizing the modern survivorship experience requires the widespread adoption of melanoma-specific HRQoL tools and proactive, multidisciplinary care models to manage chronic toxicities, psychosocial distress, and financial burdens.

Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality in Central and Eastern Europe (CEE), where late-stage diagnosis, structural healthcare limitations, and regional epidemiological confounders complicate early detection. This review aimed to synthesize the evidence from Romania, Poland, Hungary, and Bulgaria and to outline a context-adapted multimodal screening strategy for CEE settings. Methods: A structured review of PubMed-, Scopus-, and Web of Science-indexed literature published from 2010 through 27 December 2025 was performed, focusing on lung cancer epidemiology, screening, implementation barriers, risk stratification, and adjunctive diagnostic approaches in the four selected CEE countries. A total of 297 articles were included. Results: The evidence confirms a persistently high burden of late-stage lung cancer across CEE, driven by tobacco exposure, air pollution, radon, comorbidities, diagnostic delays, fragmented registries, workforce shortages, and marked socioeconomic and geographic inequalities. In addition, tuberculosis-related granulomatous lesions and chronic inflammatory lung disease complicate nodule interpretation and reduce screening specificity in parts of the region. Screening experience from Poland and Hungary supports the feasibility of low-dose computed tomography (LDCT) when paired with volumetric assessment and structured follow-up. Risk-prediction models may improve participant selection, while biological triage may help reduce unnecessary invasive procedures, although prospective validation remains limited. Conclusions: In CEE, lung cancer screening should be implemented as a multimodal, context-adapted program combining risk-based enrollment, volumetric LDCT, selective biological triage, smoking-cessation support, and centralized multidisciplinary delivery.

Background/Objectives: Lung cancer in Romania is characterized by high mortality and a lack of organized screening programs, resulting in frequent late-stage diagnoses. This study evaluates diagnostic patterns, stage distribution, and screening eligibility in a Romanian tertiary cohort to highlight the limitations of standard screening criteria and provide evidence for scalable, regionally adapted early detection strategies. Methods: We conducted a retrospective observational study of consecutive lung cancer patients treated at the Oncological Institute of Bucharest. To balance external validity with analytical robustness, the population was divided into a full cohort (Set A, n = 3764) for population-level descriptive analyses and a complete-case subset (Set B, n = 1768). Set B was utilized to simulate theoretical screening eligibility using established guidelines (USPSTF, NCCN, ERS) and to calculate a Missed Opportunity Index (MOI) for early-stage case capture. Results: Advanced-stage disease (Stages III–IV) overwhelmingly dominated the cohort, accounting for approximately 82% of diagnoses among patients with available staging information. Essential screening variables like smoking history were missing in 71.4% of the full cohort. In the complete-case subset, established guideline-based screening models demonstrated high MOI values, failing to capture approximately 69–73% of early-stage (Stage I–II) cases. Conversely, age-only minimal models appeared highly performant, structurally capturing approximately 95% of the cohort due to broad inclusiveness. Conclusions: In retrospective eligibility simulations, smoking-based screening models were associated with high missed opportunity rates for Stage I–II cases, highlighting a mismatch between simplified Western risk models and the multidimensional reality of lung cancer epidemiology in this cohort. These findings strongly support the need to move toward multivariable risk prediction models and population-adapted screening strategies that integrate non-traditional risk factors to better align screening eligibility with the true distribution of disease in real-world settings.

Background/Objectives: The advent of immune checkpoint inhibitors (ICIs) and targeted therapies has revolutionized advanced melanoma treatment but introduced unique immune-related adverse events (irAEs). Hematological irAEs (Hem-irAEs) are rare but carry disproportionately high morbidity and mortality. This review systematically synthesizes current literature to comprehensively understand the incidence, pathophysiology, clinical presentation, and management of Hem-irAEs in modern melanoma therapy. Methods: A comprehensive Web of Science literature search (January 2015 to January 2026) identified studies reporting hematological adverse events associated with melanoma immunotherapy and targeted therapies. After screening 2274 records, 130 relevant studies were included for quantitative data extraction, focusing on incidence rates and toxicity grading. Results: Hem-irAEs occur infrequently (under 4% overall incidence for ICIs) but possess staggering mortality rates between 12% and 15.5%. The most common manifestations are immune thrombocytopenia (ITP), autoimmune hemolytic anemia, and neutropenia. Combination regimens significantly amplify toxicity frequency and severity. Diagnosis requires meticulous baseline monitoring and bone marrow biopsies to differentiate peripheral destruction from central marrow failure. First-line management mandates ICI discontinuation and high-dose corticosteroids, utilizing targeted second-line immunosuppressants for refractory syndromes. Conclusions: Hem-irAEs embody a profound clinical paradox: while mild toxicities often herald a robust anti-tumor response, severe hematological events drastically increase non-cancer mortality, negating these oncological benefits. Navigating this “double-edged sword” demands a paradigm shift toward proactive risk stratification. Integrating predictive biomarkers including baseline autoantibodies, Human Leukocyte Antigens (HLA) profiling, and systemic inflammatory indices is crucial to identify vulnerable populations before treatment. Optimizing outcomes requires highly personalized vigilance to balance the life-saving efficacy of immunotherapy against the catastrophic threat of hematopoietic failure.