Search Results (16,450)

Background: Colorectal cancer (CRC) is the third most diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. Recent therapeutic advancements have significantly improved clinical management, underscoring the importance of routine molecular profiling to guide personalised treatment strategies. This study aims to evaluate the prognostic impact of main molecular alterations—including allele frequency (AF) of RAS mutations—on survival outcomes in a real-world hospital-based cohort of patients with metastatic CRC. Methods: A total of 208 consecutive patients with a histologically confirmed diagnosis of CRC and complete clinical, molecular, and survival data were retrospectively analysed. Somatic mutations in KRAS, NRAS, BRAF, and the occurrence of microsatellite instability (MSI) were assessed using pyrosequencing and real-time PCR assays, respectively, on formalin-fixed, paraffin-embedded tumour samples. Associations between mutational status, clinicopathological parameters, and overall survival (OS) were evaluated. Results: Overall, 138 patients (66.3%) harboured at least one somatic mutation: 115 (55.3%) in KRAS, 8 (3.8%) in NRAS, and 15 (7.2%) in BRAF. MSI was detected in 17/208 (8.2%) patients. A statistically significant improvement in OS was observed in patients lacking mutations in any of the three genes—referred to as wild-type (WT) patients—with BRAF mutated cases showing the worst survival (p = 0.041). Increasing age at the time of first-line therapy for advanced disease stage was associated with a statistically significant increase in the hazard of death (p = 0.031). Conclusions: In the advanced disease stage, RAS/BRAF wild-type colorectal cancers were significantly associated with a survival advantage. Full article

Background: Pancreatic neuroendocrine tumors (pNETs) represent a heterogeneous group of neoplasms characterized by variable biological behavior and clinical outcomes. Multiple therapeutic strategies have been investigated, including surgery, targeted therapies, peptide receptor radionuclide therapy, and systemic treatments. The present study aimed to summarize survival-related outcomes reported across studies investigating the management of pNETs. Methods: A systematic review of the literature was conducted including studies reporting clinical outcomes in patients with pancreatic neuroendocrine tumors. A total of 27 studies were included in the qualitative analysis. Survival-related outcomes, such as progression-free survival (PFS), recurrence-free survival (RFS), and recurrence rates, were extracted. Studies reporting quantitative survival values were included in the meta-analytical component. A random-effects model was applied, and a forest plot was generated to summarize the reported outcomes. Results: Reported survival outcomes varied substantially across studies. Median PFS values ranged from approximately 5.6 to 86.5 months, while several surgical series reported 5-year overall survival rates exceeding 90%. Recurrence rates following surgical resection ranged from approximately 12% to 26% in some cohorts. The pooled estimate derived from the meta-analytical model was 32.22 (95% CI: 15.65–48.80). Conclusions: The analysis summarizes survival-related outcomes reported in studies investigating pancreatic neuroendocrine tumors and provides a quantitative overview of the reported progression-related endpoints across the analyzed literature. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with limited therapeutic options, a high mortality rate, and poor overall survival, necessitating the development of new therapeutic and diagnostic strategies. This study investigated the potential of plasma-derived small extracellular vesicles (sEVs) as a source of molecular biomarkers associated with the treatment response. Methods: Plasma samples were obtained from patients with locally advanced and borderline resectable PDAC at baseline and following neoadjuvant chemotherapy, either FOLFIRINOX (5-FU [fluorouracil], leucovorin, oxaliplatin, and irinotecan) or GEM-ABRAX ( gemcitabine plus nab-paclitaxel), followed by stereotactic body radiation therapy (SBRT). sEVs were isolated from plasma at baseline, after neoadjuvant chemotherapy, and following SBRT, and were characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), nano-flow cytometry, and real-time PCR (RT-PCR). Results: The isolated sEVs exhibited an average size of <200 nm, expressed canonical exosome markers (CD63 and CD9), and exhibited pancreatic cancer (PanC)-associated markers, including cholecystokinin A receptor (CCK-AR) and carbohydrate antigen 19-9 (CA19-9). The sEV cargo included several PanC-associated microRNAs (miRNAs). Notably, the expression profiles of these miRNAs demonstrated interpatient variability, though a subset of miRNAs showed statistically significant changes following treatment. Conclusions: These findings support the feasibility of sEV isolation and molecular profiling from patient plasma and warrant further investigation as a potential source of biomarkers in pancreatic cancer. Full article

Background: Osteosarcoma remains the most common primary malignant bone tumor in children and adolescents, with largely unchanged survival outcomes in recent decades. Non-invasive biomarkers for preoperative risk stratification are urgently needed. Circulating immune checkpoint proteins (ICPs) and bone remodeling factors (BRFs) represent promising candidates; however, their combined prognostic value in osteosarcoma remains unclear. Methods: We prospectively analyzed plasma samples from 47 patients with osteosarcoma, selecting the earliest available sample before disease progression or the last follow-up. A panel of ICPs and BRFs was quantified using multiplex immunoassays. sHVEM and sCD27 were used to construct a two-marker ICP signature (ICP2); subtypes were defined by unsupervised consensus clustering (k = 2) applied to log₂-transformed sHVEM and sCD27 concentrations, and sOPN was included for integrative analysis. Survival associations were assessed using Kaplan–Meier analysis and Firth’s penalized Cox regression. The model performance was evaluated using Harrell’s C-index. Results: Two ICP2 subtypes were identified (type1, n = 26; type2, n = 21). ICP2-type2 was associated with significantly worse progression free survival (PFS) (p = 0.0045) and overall survival (OS) (p = 0.0024) and remained an independent predictor after adjusting clinicopathological factors. The ICP2 model demonstrated high discriminative performance (C-index 0.924 for PFS and 0.903 for OS). Internal validation by leave-one-out cross-validation (LOOCV), in which consensus clustering was re-derived at each fold, yielded corrected C-indices of 0.612 for PFS and 0.806 for OS (versus apparent estimates of 0.687 and 0.689, respectively), confirming acceptable-to-good discrimination after accounting for overfitting. Elevated sOPN was associated with poorer survival in the exploratory analyses, although its prognostic value was less consistent under a pre-specified cutoff. In the combined models, sOPN provided modest additional value for OS stratification, with the grdgfdgICP2-type2/OPN-high subgroup exhibiting the poorest outcome. Conclusions: The circulating sHVEM/sCD27 signature defines prognostically distinct osteosarcoma subtypes with a strong discriminative performance. This minimally invasive model may support preoperative risk stratification. Integration with sOPN suggests a potential biological link between immune regulation and bone remodeling, warranting validation in larger cohorts. Full article

Background: Liver metastases from breast cancer (BCLM) are associated with poor prognosis and represent a significant clinical challenge in the era of modern systemic therapies. Local ablative therapies (LATs), including microwave ablation (MWA) and transarterial chemoembolization (TACE), have emerged as potentially beneficial locoregional approaches in selected patients. However, data on survival outcomes and prognostic determinants of LAT in BCLM remain limited. This study aimed to evaluate the survival outcomes and prognostic factors of LAT in patients with breast cancer liver metastases at a tertiary care center. Methods: Patients with de novo or metachronous breast cancer liver metastases who underwent LAT (MWA and/or TACE) between 2013 and October 2023 at a single tertiary center were retrospectively analyzed. Primary endpoints were overall survival (OS), defined as the time from LAT initiation to death from any cause, and progression-free survival (PFS), defined as the time from LAT initiation to the first radiographically confirmed progression. Treatment response was assessed per RECIST 1.1 criteria. Results: A total of 20 female patients were included. Median age at diagnosis was 42 years (IQR: 37–53). The majority had invasive ductal carcinoma (90%) and grade 3 disease (60%). Hormone receptor-positive, HER2-positive, and triple-negative subtypes comprised 45%, 25%, and 30% of the cohort, respectively. MWA was performed in 16 patients (80%), TACE was performed in 2 patients (10%), and both modalities were performed in 2 patients (10%). Complete response per RECIST 1.1 was achieved in 40% of patients. No grade 3–4 adverse events were recorded. Median OS was 20 months (95% CI: 14.9–25.1), and median PFS was 6 months (95% CI: 0–17.5). In univariate analysis, factors associated with improved OS included LM size < 18 mm (23 vs. 11 months, p < 0.001), unilateral lobar involvement (23 vs. 5 months, p = 0.025), and LAT application during first-line therapy (48 vs. 19 months, p = 0.021). Factors associated with improved PFS included LM size < 18 mm (19 vs. 5 months, p < 0.001) and achievement of complete ablative response per RECIST 1.1 (18 vs. 5 months, p = 0.005). Conclusions: LAT is a safe and feasible treatment modality in selected BCLM patients. In univariate analysis, smaller lesion size, unilateral hepatic involvement, and early-line LAT applications are associated with improved OS, while complete ablative response is associated with improved PFS. These findings warrant validation in prospective studies with larger cohorts. Multidisciplinary patient selection is essential to optimize outcomes. Full article

Background: This study sought to evaluate overall survival (OS) following palliative radiotherapy in glioblastoma and to identify clinically applicable predictors supporting patient-centred treatment decisions, with exploration of early mortality. Methods: This retrospective single-centre study analysed 169 glioblastoma patients treated with palliative radiotherapy between 2010 and 2025. Baseline clinical and treatment variables were assessed. OS calculated from the last day of radiotherapy was estimated using Kaplan–Meier analysis; predictors were analysed using Cox regression. Early mortality (≤30 and ≤60 days) was evaluated using logistic regression. Results: Median age at diagnosis was 75 years, median Karnofsky Performance Status (KPS) was 60%, with 63% of patients < 70%. Impaired mental status, sensorimotor deficits, and steroid use were observed in 47%, 68%, and 86% of patients, respectively. Median OS was 3.5 months. Impaired mental status (HR 2.25), sensorimotor deficits (HR 1.77), steroid use (HR 1.39), multilobar involvement (HR 1.44), and age (HR 1.03) were independently associated with OS, whereas KPS was not. The rate of early mortality at 30 and 60 days was 18% and 31%. Early mortality analysis indicated impaired mental status and steroid use as indicators of very limited survival. Conclusions: Impaired mental status and steroid use identify patients with limited survival, whereas KPS lacks independent prognostic value in this setting. Full article

Background/Objectives: KRAS mutations are among the most common oncogenic driver alterations in non-small cell lung cancer (NSCLC) and define a biologically heterogeneous disease. In the current era of molecular oncology, with targeted therapies increasingly incorporated into clinical practice, the prognostic relevance of individual KRAS mutation subtypes and their relationship with immune biomarkers such as programmed cell death ligand 1 (PD-L1) require further clarification. This study aimed to evaluate the prognostic impact of KRAS mutation subtypes and their association with PD-L1 expression in patients with NSCLC. Methods: In this retrospective analysis, 150 patients with KRAS-mutant NSCLC who underwent next-generation sequencing at Trakya University Faculty of Medicine between January 2015 and December 2023 were included. Clinicopathological features, KRAS mutation subtypes, PD-L1 expression, and survival outcomes were assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: KRAS G12C was the most frequent subtype (40.7%), followed by G12V (20.7%) and G12D (14.7%). OS differed significantly among KRAS mutation subtypes (log-rank p = 0.007), with median OS values of 18 months for G12D, 11 months for G12C, 11 months for other rare variants, 9 months for G12A and G12V, and 5 months for G13. PD-L1 positivity was significantly higher in KRAS G12C tumors compared with non-G12C subtypes and remained independently associated with improved OS in multivariate Cox regression analysis (HR = 0.622; 95% CI, 0.426–0.907; p = 0.014). In multivariate analysis, age, ECOG performance status, disease stage, and PD-L1 positivity were independent prognostic factors, whereas KRAS mutation subtype did not retain independent prognostic significance. Conclusions: These findings suggest that KRAS-mutant NSCLC represents a clinically and molecularly heterogeneous subgroup and that integrating KRAS mutation subtypes with immune biomarkers may support more refined prognostic stratification. Full article

Interpreting and directing treatment based on comprehensive genomic testing for patients with cancer can be challenging. Molecular tumor boards (MTBs) can help by establishing collaborative frameworks to deliver patient care plans with the appropriate incorporation of genomic data. Our retrospective observational study evaluates the impact of MTB on the outcomes of adult patients diagnosed with advanced-stage cancer. Patients between 1 September 2017 and 1 January 2023 were grouped into those who received at least one treatment recommended by the MTB and those who did not. Hazard ratios (HR) for overall survival (OS), progression-free survival (PFS), and time on treatment (ToT) were determined using Kaplan–Meier analysis and multivariate Cox proportional hazards model adjusted for age, stage, line of therapy, and primary site of diagnosis. Of 238 evaluable patients, 138 (58%) received at least one treatment recommended by the MTB. Patient characteristics were well-balanced between the cohorts, except for higher proportions of lung adenocarcinoma, melanoma, and a lower proportion of glioblastoma in the matched cohort. Median OS, PFS, and ToT were all increased in patients on matched treatment compared to those who did not (18.5 months vs. 9.1 months, HR 0.64, 95% confidence interval (CI) 0.43–0.96, p = 0.030); 9.7 months vs. 4.3 months, HR 0.64, 95% CI 0.42–0.97, p = 0.035; and 4.3 months vs. 2.8 months, HR 0.58, 95% CI 0.41–0.83, p = 0.0027, respectively). Our findings show that MTB at a community cancer center is feasible and improves survival among patients with cancer, even after adjusting for confounding variables. Full article

Background: Diffuse Large B-cell Lymphoma (DLBCL) is a biologically heterogeneous subtype of non-Hodgkin’s lymphoma (NHL), accounting for 30–40% of cases worldwide. Despite the incorporation of rituximab into standard chemo-immunotherapy regimen, approximately one-third of patients present with relapsed or refractory disease, implicating the need for improved prognostic markers and therapeutic targets. Gene expression profiling successfully classified DLBCL into Germinal Center B-cell-like (GCB) and non-GCB subtypes, which differ in genetic alterations, response to therapy, and clinical outcome. While intrinsic tumor biology has been extensively studied, the contribution of the tumor microenvironment (TME) to disease progression and therapeutic resistance still remains incompletely understood. Methods: In this study, we investigated the mutational landscape of stromal-related genes in DLBCL and evaluated their impact on gene expression, downstream signaling pathways, and tumor progression. Results: A total of 176 DLBCL patients were screened, of which 113 were enrolled based on availability of complete clinical data. The cohort demonstrated male predominance (male:female ratio: 2.1:1), advanced disease stage in 72.6% of patients, and elevated serum lactate dehydrogenase levels in 57.5%. Based on immunohistochemistry, 43.4% cases were classified as GCB-DLBCL and 56.6% as non-GCB DLBCL. Although the International Prognostic Index (IPI) retained prognostic significance for event-free survival (EFS) and overall survival (OS), considerable heterogeneity was observed within similar risk groups. Whole-exome sequencing (WES) uncovered recurrent somatic mutations in key oncogenic and epigenetic regulators, including TNFAIP3, NFIB, NOTCH1, TSC2, EZH2, EP300, KMT2D, and B2M, with subtype-specific distribution. Pathway enrichment analysis implicated role of Notch, Wnt, mTOR, JAK-STAT, TGF-β, and antigen-presentation pathways. Comprehensive WES analysis identified multiple novel mutations in genes associated with the stromal/extracellular matrix with distinct patterns in GCB and non-GCB DLBCL, accompanied by concordant alterations in gene expression profiles, suggesting functional relevance within the TME. Functional validation through primary cell culture demonstrated significantly elevated Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) cytokines in co-cultures containing both neoplastic cells and stromal components, underscoring the role of TME in DLBCL progression. Conclusions: Taken together, this study provides novel insights into stromal mutational signatures and cytokine-mediated tumor–stroma interactions, offering potential prognostic biomarkers and therapeutic targets for the improved management of DLBCL. Full article

Background: Pathological T0 (pT0) prostate cancer following radical prostatectomy is uncommon, and its prognostic significance remains unclear, particularly after neoadjuvant hormonal therapy (NHT). We investigated the incidence of pT0 disease in a multicenter Japanese cohort and described postoperative biochemical recurrence (BCR) outcomes. Methods: This retrospective study analyzed 3079 patients who underwent robot-assisted radical prostatectomy at nine Japanese centers between 2011 and 2021. Patients were classified as having pT0 or non-pT0 disease. Because only four pT0 cases occurred without NHT, these are summarized descriptively. Exploratory Kaplan–Meier and log-rank analyses of biochemical recurrence-free survival (BRFS) were performed for the NHT subgroup. Results: Twenty-seven pT0 cases (0.9%) were identified, and 85.2% were identified after NHT. Overall, 399 patients (13.0%) developed BCR. Among patients who did not undergo NHT, the 1- and 2-year BRFS rates were 100% and 100%, respectively, in the pT0 group and 92.4% and 88.1%, respectively, in the non-pT0 group. In the NHT subgroup, the corresponding rates were 92.9% and 92.7%, versus 91.8% and 85.5%, respectively (p = 0.651). Conclusions: pT0 disease after robot-assisted radical prostatectomy is rare and occurs predominantly after NHT. Given the possibility that late-onset recurrences may have been overlooked, the results of this trial should be understood as providing evidence from the short- to intermediate-term perspective. Full article

IDH-wildtype glioblastoma remains the most aggressive primary brain tumor, with a median overall survival (OS) of 14–16 months despite maximal treatment. A small subset of patients, however, survive beyond 30 months, suggesting distinct underlying biological features. The aim of this pilot study was to explore whether selected molecular alterations detectable by FISH show differing distribution patterns between patients with prolonged and poor survival in IDH-wildtype glioblastoma. We retrospectively analyzed 20 patients with newly diagnosed primary IDH-wildtype glioblastoma who underwent gross-total resection followed by standard radiotherapy and temozolomide treatment between 2016 and 2022. Patients were categorized into two predefined groups according to survival outcomes: long-term survivors (OS > 30 months) and short-term survivors (OS < 10 months). Fluorescence in situ hybridization (FISH) was used to evaluate alterations in ATRX, BRAF, and PIK3CA. MGMT promoter methylation, EGFR amplification, and TERT promoter mutation status were obtained from routine diagnostic reports. Because survival groups were intentionally pre-selected as extreme phenotypes, time-to-event analysis was not appropriate. Therefore, statistical comparisons were performed using Fisher’s exact test and multivariable logistic regression with long-term versus short-term survival as a binary outcome. Short-term survivors had a significantly higher median age (57.5 vs. 46.5 years, p = 0.043) and a higher rate of EGFR amplification (100% vs. 50%, p = 0.033). Strikingly, combined BRAF and PIK3CA alterations (predominantly polysomy) were detected in 8 out of 10 (80%) long-term survivors, compared to 0 out of 10 (0%) short-term survivors (p = 0.0007). In multivariable logistic regression adjusted for age and MGMT promoter methylation, BRAF/PIK3CA alteration remained strongly associated with long-term survival, though the effect size was mathematically inflated due to perfect separation (0 events in Group B). BRAF and PIK3CA copy number alterations were observed exclusively in long-term survivors in this small exploratory cohort, suggesting a possible association with prolonged survival. However, given the limited sample size, the selection of extreme survival groups, and the predominance of chromosomal polysomy detected by FISH, these findings should be interpreted as hypothesis-generating only. Further validation in larger cohorts using high-resolution genomic methods is warranted. Full article

Background: Soft-tissue sarcomas (STSs) are rare and heterogeneous malignancies with generally poor and unpredictable prognosis. Tertiary lymphoid structures (TLSs) have been identified as favorable prognostic indicators in several cancer types, yet their role in STS remains poorly defined. This study investigates the prognostic relevance of TLS presence, maturity, location and density in resected STSs. Methods: We retrospectively analyzed 219 cases of primary STS surgically resected at the Bergonié Institute (France) between 1990 and 2020. TLSs were assessed for presence, spatial distribution, semi-quantitative density and degree of maturity using CD20 and CD23 immunohistochemistry, categorizing tumors as fully mature TLS-positive (fmTLS⁺) or -negative (fmTLS⁻). RNA sequencing was performed on 126 formalin-fixed paraffin-embedded samples to characterize immune microenvironment profiles. Survival outcomes—including overall survival (OS), time to locoregional progression (TTLRP), and time to distant progression (TTDP)—were analyzed using Kaplan–Meier estimates and Cox proportional hazards models. Results: The presence of fmTLS was significantly associated with improved 5-year OS (p = 0.012) and cause-specific survival (p = 0.006). Unexpectedly, fmTLS⁺ tumors showed a higher rate of local recurrence (22.9% vs. 8.1%, p = 0.002). On multivariate analysis, high-density fmTLS⁺ tumors conferred a 2.68-fold increased risk of locoregional progression (95% CI: 1.28–5.59, p = 0.009). Transcriptomic profiling confirmed a significant correlation between fmTLS⁺ status and a high-immune phenotype (Φ = 0.30, p < 0.001). Conclusions: STSs with fmTLS are associated with improved OS but increased risk of local recurrence. These findings support fmTLS as a dual prognostic biomarker and highlight the need for tailored surveillance and adjuvant strategies in fmTLS⁺ patients. Full article

Background: ABO-incompatible living-donor liver transplantation (ABOi LDLT) can expand the donor pool for patients with hepatocellular carcinoma (HCC), but concerns remain regarding tumor recurrence and long-term survival. Methods: A systematic review and meta-analysis was performed according to PRISMA 2020. PubMed, Embase, and Web of Science were searched. Comparative studies evaluating oncologic outcomes after ABOi versus ABO-compatible (ABOc) LDLT for HCC were included in the quantitative synthesis; non-comparative studies were included in the qualitative synthesis. Hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival (OS) were pooled using a random-effects model. When HRs were not directly reported, they were estimated from Kaplan–Meier curves using established methods. Results: Sixteen reports were screened, 12 full-text articles were assessed, and 8 studies were included in the systematic review. Three comparative single-center cohort studies were eligible for meta-analysis. Pooled analysis showed no significant difference between ABOi and ABOc LDLT for RFS (HR 1.07, 95% confidence interval [CI] 0.77–1.49; I² = 0%) or OS (HR 1.08, 95% CI 0.74–1.57; I² = 0%). Five additional studies were synthesized qualitatively, suggesting that recurrence risk may be influenced more by tumor biology and peri-transplant management, including desensitization intensity and immunosuppression exposure, than by ABO incompatibility itself. Conclusions: Current limited comparative evidence does not demonstrate inferior RFS or OS after ABOi LDLT in carefully selected patients with HCC. Larger multicenter comparative studies with standardized reporting of tumor biology, desensitization protocols, and immunosuppression exposure are warranted to confirm these findings and clarify protocol-related effects on post-transplant recurrence. Full article

Mesothelin (MSLN) is a cell surface glycoprotein with limited expression in normal tissues but frequent overexpression in solid tumors, including gynecological malignancies. This review summarizes the state of the art on the biological role, diagnostic value, prognostic significance, and therapeutic potential of MSLN in ovarian, endometrial, and cervical cancers. Evidence from clinical and experimental studies indicates that MSLN contributes to tumor progression through interactions with CA125, promotion of cell adhesion and peritoneal metastasis, activation of oncogenic signaling pathways, modulation of immune responses, and development of chemoresistance. Elevated MSLN expression has been associated with advanced clinical stage of the disease, platinum resistance, and poorer survival outcomes, particularly in ovarian cancer patients, although prognostic findings remain inconsistent. Circulating soluble MSLN may serve as a minimally invasive biomarker and may improve diagnostic accuracy when combined with established markers. Therapeutic MSLN strategies—antibody-drug conjugates, CAR-T and NK cell therapies, monoclonal antibodies, immunotoxins, vaccines, and checkpoint blockade—provide promising pre-clinical and early clinical results, particularly in resistant or recurrent forms of the disease. Overall, MSLN constitutes a promising target for precision oncology in gynecological cancers, although further clinical studies are required to validate its diagnostic utility and optimize targeted therapeutic approaches. Full article

Background and Objectives: Metastatic renal cell carcinoma (mRCC) remains a lethal disease despite advances with immune checkpoint inhibitors such as nivolumab. However, a substantial proportion of patients exhibit primary resistance or early progression, highlighting the need for reliable and easily accessible prognostic biomarkers. The C-reactive protein–albumin–lymphocyte (CALLY) index is a novel immunonutritional biomarker integrating systemic inflammation, nutritional status, and immune competence. Materials and Methods: In this retrospective single-center study, 91 patients with mRCC treated with nivolumab were analyzed. Patients were stratified into low and high CALLY index groups based on a receiver operating characteristic-derived cut-off (0.322). Survival outcomes were assessed using Kaplan–Meier analysis and Cox regression models. Results: Patients with a low CALLY index demonstrated significantly shorter progression-free survival (4.5 vs. 13.5 months, p < 0.001) and overall survival (9.1 vs. 25.5 months, p = 0.003). Multivariate analysis confirmed the CALLY index as an independent prognostic factor for both progression-free survival (HR: 2.63, p = 0.002) and overall survival (HR: 1.88, p = 0.035). Conclusions: The CALLY index is a simple, cost-effective, and reproducible biomarker that independently predicts survival in nivolumab-treated mRCC. It may serve as a practical tool for risk stratification and personalized treatment planning in the immunotherapy era. Full article