Background: Despite recent advances in the management of metastatic renal cell carcinoma (mRCC), real-world outcomes remain heterogeneous, and early treatment failure is common. Predictive biomarkers for time to treatment failure (TTF) outside clinical trials are poorly characterized. Objective: To identify clinical and laboratory predictors associated with early treatment failure in a real-world cohort of mRCC patients treated with immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs), or combination regimens. Methods: We conducted a retrospective, single-center analysis of patients with metastatic non-urothelial RCC treated between 2018 and 2023. Cox proportional hazards regression was used to evaluate the association between baseline biological parameters and TTF for each treatment regimen. Results: Among 137 patients receiving first-line therapy, 50 received Ipilimumab + Nivolumab, 49 Sunitinib, and 17 Avelumab + Axitinib. For Ipilimumab + Nivolumab, elevated AST was significantly associated with shorter TTF. For Avelumab + Axitinib, shorter TTF was associated with lymph node metastases, low lymphocyte count, low creatinine, low BMI, and low hemoglobin. For Cabozantinib in subsequent lines, a higher platelet count, ALT, and presence of liver metastases were associated with shorter TTF. No statistically significant predictors were found for Nivolumab used in the second-line setting. Conclusions: Routine, accessible biomarkers such as AST, hemoglobin, lymphocyte count, and creatinine may serve as predictors of treatment failure in specific therapeutic contexts. These findings support risk-adapted strategies and individualized monitoring in real-world clinical practice, though further validation in larger cohorts is warranted.

Background: Non-small-cell lung cancer (NSCLC) is often diagnosed at stage IV, when prognosis depends on metastatic spread. The impact of histopathology on the first metastatic site remains underexplored. Methods: We retrospectively analyzed 364 patients with stage IV NSCLC diagnosed at OncoHelp Medical Center, Timișoara, Romania (2020–2024). All underwent baseline CT chest–abdomen–pelvis, whole-body FDG PET-CT, and brain MRI within seven days of histological confirmation. Patients were stratified into adenocarcinoma (n = 164), squamous cell carcinoma (n = 112), and large-cell carcinoma (n = 88). The first metastatic site was defined as the earliest confirmed location. Associations were evaluated using Fisher’s exact test and multinomial logistic regression. Results: Histology was associated with the first metastatic site (global p = 0.013). Adenocarcinoma was more likely than squamous carcinoma to present with brain metastases (RRR 3.74, 95% CI 1.48–9.45; p = 0.005; p_FDR = 0.053) and showed directional signals toward bone and adrenal involvement. Squamous carcinoma more frequently spread to the pleura as the first site (adjusted p = 0.008). Large-cell carcinoma showed no consistent differences compared to squamous carcinoma. In adenocarcinoma subgroups, EGFR-mutant tumors most often metastasized to the brain (55.6%), KRAS-mutant tumors to the liver (44.4%), and ALK-rearranged tumors to bone (100%). Conclusions: The first metastatic site in NSCLC follows histology-specific patterns, with adenocarcinoma favoring hematogenous spread and squamous carcinoma showing locoregional involvement. Molecular status further refines these patterns in adenocarcinoma. Incorporating histology into baseline staging may improve diagnostic efficiency and prognostic accuracy.

Background and Objectives: Spiritual well-being is consistently associated with better quality of life in oncology, but the pathways involved are disputed. Two competing accounts exist: spiritual well-being may buffer patients against the impact of physical symptoms, or it may act mainly through emotional distress. We examined whether cross-sectional data from a Romanian cancer cohort are compatible with either account. Materials and Methods: In this single-centre cross-sectional study, 175 adults with cancer completed the FACIT-Sp-12, the Religious Commitment Inventory-10, the EORTC QLQ-C30 and the Hospital Anxiety and Depression Scale; the FACIT-Sp-12, QLQ-C30 and HADS were administered in locally adapted formats that deviate from the validated instruments, so all findings pertain to these adapted versions. Patients were grouped by tertile of FACIT-Sp-12 score. The primary outcome was global health status/quality of life. Multivariable linear regression with heteroscedasticity-consistent standard errors, prespecified bootstrapped mediation analyses (interpreted as cross-sectional statistical decompositions), a multiplicative moderation test, restricted cubic splines and nine prespecified sensitivity analyses were performed. Results: Patients were 62.2 ± 13.1 years old, 65.1% had advanced disease and 51.4% screened positive for clinically significant distress (HADS-Anxiety or HADS-Depression ≥ 8). Global quality of life rose monotonically across spiritual well-being tertiles (53.8 ± 28.0, 65.9 ± 22.3 and 74.5 ± 23.1 points; p < 0.001), with an adjusted high-versus-low difference of 14.9 (4.3 to 25.5) points. In the prespecified primary model, each standard deviation of spiritual well-being was associated with 7.15 (3.45 to 10.86) points of global quality of life. In separate prespecified single-mediator models, the indirect associations through HADS-anxiety (4.21 points, 95% CI 1.89 to 6.86) and HADS-depression (3.03 points, 95% CI 1.17 to 5.43) were both statistically significant (bootstrapped p < 0.001); these cross-sectional decompositions are equally compatible with reverse, bidirectional or common-cause structures. No statistically detectable spiritual well-being × symptom burden interaction was found (β = −1.198, 95% CI −6.355 to 3.959; p = 0.649), but the confidence interval included clinically relevant effect modification in either direction, and there was no evidence of departure from linearity in the dose–response relationship (p for non-linearity = 0.510). Coefficients for the peace subscale were consistently larger than those for faith, although the subscales were modelled separately. Conclusions: Higher scores on the adapted FACIT-Sp-12 were cross-sectionally associated with better global quality of life and lower emotional distress. Anxiety and depression statistically accounted for part of this association, but temporal ordering and causality cannot be determined from these data, and the interaction analysis was too imprecise to support or exclude buffering. Routine assessment of spiritual and emotional concerns alongside symptom control is supported; whether interventions that increase spiritual well-being improve quality of life requires longitudinal and interventional study using the validated instrument formats.

Background/Objectives: Religious engagement may coexist with low existential well-being. We identified spiritual-religious profiles in Romanian patients with cancer, assessed their associations with distress and quality of life, and evaluated spirituality's incremental predictive value. Methods: This single-centre cross-sectional study included 175 adults with cancer. Latent profile analysis used FACIT-Sp Meaning, Peace, and Faith, Religious Commitment Inventory-10, and service attendance. Clinically significant distress was defined as Hospital Anxiety and Depression Scale anxiety or depression scores ≥8. Adjusted regression and a six-predictor logistic model with bootstrap internal validation were used. Results: Three profiles emerged: low spiritual-religious resource (n = 61), religiously engaged but existentially unsettled (n = 52), and integrated spiritual-religious resource (n = 62). Distress prevalence was 68.9%, 61.5%, and 25.8%, respectively (p < 0.001). Compared with the low-resource profile, the integrated profile had lower adjusted odds of distress (OR 0.19, 95% CI 0.08–0.44), higher global quality of life (adjusted difference 14.1 points, 95% CI 4.4–23.8), and lower symptom burden (−11.8 points, 95% CI −18.6 to −5.0). The full model had an apparent AUC of 0.816 (95% CI 0.748–0.875) and an optimism-corrected AUC of 0.789. Its AUC exceeded that of the clinical-only model by 0.064 (95% CI 0.008–0.12; p = 0.023). Conclusions: Religious involvement alone did not indicate resolved spiritual needs. Inner peace may improve distress risk assessment, although prospective external validation is required.

Background: Spiritual wellbeing is increasingly recognised as a key area of complex oncology and palliative care, but evidence from Eastern Europe is still limited. Understanding how spiritual well-being and religiosity are related to psychological distress and quality of life can inform holistic support interventions in cancer patients. Objective: To describe spiritual well-being, religiosity, anxiety, depression, and quality of life in a Romanian cancer cohort, and to examine associations between spiritual well-being and psychological distress. Methods: A cross-sectional study was carried out in 124 cancer-stricken adults at a regional cancer centre in Romania. Participants completed FACIT-Sp-12 (spiritual well-being), RCI-10 (religious belief), HADS (depression), and EQT QLQ-C30 (QoL). Multivariable linear regression was used to determine independent predictors of outcomes in patients. Results: Participants had a median age of 65 years (53–71) and 70 (56%) patients had metastatic disease. Religious involvement was high and spirituality related to disease was commonly reinforced, with 66 (53%). There were twice as many cases of clinical depression symptoms (28%) as anxiety symptoms (14%). A median QoL score of 51 (IQR: 37–64 points) was revealed by descriptive analysis of the EORTC QLQ-C30. In adjusted multivariable models, spiritual well-being was significantly and independently associated with lower anxiety (β = −0.25, p = 0.030) and depression (β = −0.29, p = 0.013), with models accounting for 11.5% and 10.8% of variance, respectively. Global quality of life was best explained by the model (R² = 26.4%), with independent contributions from impaired ECOG performance status (β = −0.27, p = 0.006) and depressive symptoms (β = −0.22, p = 0.014), whereas religious commitment showed no independent association with any primary outcome. Conclusions: In this Romanian cohort, spiritual well-being, not religious adherence, remained independently associated with lower anxiety and depression, suggesting that spiritual well-being is associated with better psychological health among cancer patients. Religious affiliation has not been shown to be independent of any outcome, a difference with direct implications for the screening of spiritual care. Global quality of life, on the other hand, was independently associated with both physical functional status (ECOG) and depressive symptom burden, rather than with spiritual or religious factors, underlining that both functional decline and psychological distress remain central to cancer-related quality of life.