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 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.