Search Results (31,242)

Background/Objectives: Neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC) is a standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC), yet baseline tools to refine prognostic stratification remain limited. We aimed to develop and internally validate a clinicopathological nomogram integrating the neutrophil-to-lymphocyte ratio (NLR) to estimate event-free survival (EFS) in patients with MIBC treated with NAC. Methods: We retrospectively analyzed 210 patients with cT2–T4aN0–1M0 MIBC treated with cisplatin-based NAC at two Spanish institutions between 2010 and 2021. Candidate predictors included demographic, clinicopathological, and routine laboratory variables. A multivariable Cox model with backward selection based on the Akaike information criterion (AIC) was used to derive the final model, and internal validation was performed using 1000 bootstrap resamples. Results: Sex, age, prior non–muscle-invasive bladder cancer (NMIBC), and NLR were retained in the final nomogram. The model showed moderate discrimination, with a Harrell’s c-index of 0.60 and an optimism-corrected c-index of 0.58. The nomogram stratified patients into low-, intermediate-, and high-risk groups, with median EFS not reached, 47.5 months, and 18.0 months, respectively. High-risk patients also showed lower pathological complete response (pCR) rates. Conclusions: This exploratory nomogram integrates an accessible systemic inflammatory marker with baseline clinical variables to identify patients with poorer outcomes despite NAC. External validation in contemporary cohorts is warranted before clinical implementation. Full article

Patients with BRAF^V600E-mutated metastatic lung cancer benefit from both BRAF plus MEK inhibitors and immune checkpoint inhibitor (ICI)–chemotherapy. This study evaluated the cost-effectiveness of first-line ICI–chemotherapy compared with BRAF plus MEK inhibitors in these patients. This economic analysis, with a 15-year time horizon and an annual 3% discount, was conducted from the perspective of the healthcare sectors in Taiwan and the US. Simulated patients were entered into partitioned survival models upon initiation of first-line therapies. The model inputs were derived from the FRONT-BRAF study (progression-free/overall survival, adverse events, and subsequent therapies), insurance payments or retail prices (costs of drugs, physician visits, monitoring, adverse events, and end-of-life care), and a hospital cohort (health utility). Deterministic and probabilistic analyses were performed. The incremental cost-effectiveness ratios (ICERs) of ICI–chemotherapy compared with BRAF plus MEK inhibitors (Taiwan: $73,561/QALY; US: $290,279/QALY) exceeded the willingness-to-pay (WTP) thresholds (Taiwan: $70,000/QALY; US: $150,000/QALY). The drug costs of subsequent therapies and the utility values of the progressive-disease state were the major determinants of ICERs. In Taiwan, ICI–chemotherapy had a 41.0% probability of being cost-effective at the WTP threshold. ICI–chemotherapy had a higher probability of being cost-effective than BRAF plus MEK inhibitors when the WTP exceeded $300,000/QALY in the US. Our analysis suggests that, despite the longer survival of first-line ICI–chemotherapy compared with BRAF plus MEK inhibitors, ICI–chemotherapy is not a cost-effective strategy for patients with BRAF^V600E-mutated metastatic lung cancer. Full article

Background/Objectives: Acral (AM) and mucosal melanomas (MM) have certain genetic similarities compared to non-acral cutaneous melanomas and share a restricted influence of UV radiation in their etiology. Yet, AM and MM arise in quite different locations from a histological perspective. This study aimed to report differences between AM and MM for the most prominently mutated genes in melanoma: BRAF, NRAS, KIT, and TERT promoter. Methods: We conducted a retrospective, single-center study including 152 patients diagnosed with AM (n = 121) or MM (n = 31) at the Fundación Instituto Valenciano de Oncología between 2000 and 2024. Clinical and histopathological data were collected, and mutational analyses of BRAF, NRAS, KIT, and the TERT promoter were performed using targeted sequencing. Results: MM presented with significantly greater Breslow thickness and higher rates of hematogenous metastasis compared to AM. While BRAF, NRAS, and TERT promoter mutations were similarly distributed between subtypes, KIT mutations were significantly more frequent in MM (33% vs. 12.3%; p = 0.043) and exhibited a broader mutational spectrum. Survival outcomes were poorer in MM, with lower 5- and 10-year survival rates compared to AM. Discussion: Despite shared UV-independent biology, AM and MM differ in clinically and molecularly meaningful ways. The higher prevalence and diversity of KIT mutations in MM suggest subtype-specific oncogenic mechanisms and potential therapeutic implications. These findings support a more refined classification of UV-independent melanomas based on anatomical and molecular distinctions. Full article

Nectin-4 has emerged as a clinically relevant target in muscle-invasive bladder cancer (MIBC), primarily because of its role in antibody–drug conjugate-based therapies. However, the broader biological context of Nectin-4 expression and its association with tumor-promoting signaling pathways in MIBC remain insufficiently characterized. In this single-institution study, Nectin-4 expression (H-score 0–300) was assessed by immunohistochemistry in two independent MIBC cohorts. Associations between Nectin-4 expression and key markers related to growth signaling, metabolic regulation, and inflammation were analyzed alongside clinicopathological characteristics. Nectin-4 expression was significantly higher in malignant tissue than in non-malignant tissue (p = 0.0016 and p = 0.0302, respectively). Nectin-4 expression was not associated with demographic or clinicopathological parameters; however, a trend toward lower expression in more advanced disease stages was observed. Significant positive correlations were identified between Nectin-4 expression and protein kinase B (p = 0.0004), cytoplasmic (p = 0.0115) and membranous somatostatin receptor 2 (p = 0.0125), insulin receptor substrate 1 (p = 0.03), and interleukin-1 receptor antagonist (IL-1RA; p = 0.0045). In contrast, a negative correlation was observed with the IL-1β/IL-1RA ratio (p = 0.0246). Although Nectin-4 expression was not significantly associated with cancer-specific or overall survival, a trend toward shorter relapse-free survival was observed in patients with lower Nectin-4 expression (p = 0.0531). In multivariate analysis, patient age, but not Nectin-4 expression, emerged as an independent prognostic factor. Although Nectin-4 expression does not appear to have independent prognostic value, its biological associations suggest that it reflects an integrated tumor-related signaling context. These findings support further investigation of Nectin-4 as part of rational, biology-driven therapeutic strategies in bladder cancer. Full article

Serratia marcescens has emerged as an important opportunistic pathogen in intensive care units (ICUs), where critically ill patients, invasive devices, antimicrobial exposure, and complex environmental reservoirs create favorable conditions for colonization, infection, and recurrent outbreaks. This narrative review synthesizes evidence from the past decade regarding the clinical and molecular epidemiology, environmental persistence, device-associated transmission, biofilm-mediated resistance, and infection-control strategies of S. marcescens in ICU settings. The literature was reviewed using an integrative approach informed by Ferrari’s narrative review framework, with thematic synthesis across clinical, microbiological, environmental, and genomic domains. Recent evidence indicates that ICU-associated S. marcescens infections frequently involve respiratory tract colonization, ventilator-associated pneumonia, bloodstream infection, urinary tract infection, and device-related transmission. Hospital water systems, sink drains, wet surfaces, ventilator circuits, reusable equipment, and contaminated antiseptic or liquid products may serve as persistent reservoirs, particularly when biofilm formation supports long-term survival and recurrent dissemination. At the molecular level, S. marcescens demonstrates substantial genomic diversity, intrinsic and acquired antimicrobial resistance, inducible AmpC β-lactamase activity, efflux-mediated tolerance, and plasmid-associated resistance gene transfer. This review particularly emphasizes the molecular determinants that enable S. marcescens to persist in ICU ecosystems, including AmpC-mediated β-lactam resistance, efflux-associated tolerance, quorum-sensing-regulated biofilm formation, plasmid-mediated horizontal gene transfer, and WGS-defined clonal transmission. Whole-genome sequencing, rapid molecular diagnostics, active surveillance, environmental sampling, and integrated infection-control bundles have become increasingly important for distinguishing clonal outbreaks from endemic transmission and guiding timely interventions. Emerging perspectives emphasize the need to combine antimicrobial stewardship, environmental engineering, respiratory-care auditing, anti-biofilm strategies, and AI-assisted real-time surveillance into adaptive ICU infection-control frameworks. Overall, S. marcescens should be regarded not merely as an episodic outbreak organism, but as a highly adaptable ICU-associated pathogen requiring multidisciplinary prevention strategies. Full article

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with poor survival rates of late-stage disease. While immune checkpoint blockade (ICB) therapy has transformed treatment for mismatch repair-deficient (MMRd)/microsatellite instability-high (MSI-H) tumors, most CRC cases are mismatch repair-proficient (MMRp)/microsatellite-stable (MSS) and derive little to no benefit from current immunotherapy regimens. Tumor-associated macrophages (TAMs) constitute a significant component of the tumor microenvironment (TME) and exhibit a phenotypic gradient between pro-inflammatory (M1-like) and anti-inflammatory, immunosuppressive (M2-like) states. Although their polarization status is increasingly recognized as a key modulator of immunotherapy efficacy in CRC, a comprehensive synthesis of the literature regarding macrophage polarization and its relevance to improving CRC immunotherapy remains lacking. Methods: A systematic literature search was conducted across PubMed, EMBASE, and ScienceDirect from inception to December 2025 using terms encompassing macrophages, immunotherapy, immune checkpoint expression, colorectal cancer, and microsatellite stability status. Title, abstract, and full-text screening were performed independently by multiple authors. Sixty-five studies were included following PRISMA guidelines. The protocol was prospectively registered on PROSPERO (ID: CRD420251244320). Results: Three key themes were identified: (1) macrophage-mediated mechanisms of resistance to ICB, including M2 polarization driven by the PI3Kγ, STAT3, mTOR, and SIRT-1 axes, immunosuppressive cytokine production (IL-10, TGF-β), and altered immune checkpoint ligand expression; (2) macrophage polarization status and associated biomarkers as prognostic indicators of therapeutic response; (3) emerging macrophage-targeted therapeutic strategies in ongoing clinical trials, including CSF1R inhibitors, CD40 agonists, CD47/SIRPα blockade, and STING agonists. Conclusions: TAM polarization is a critical determinant of immunotherapy resistance and patient prognosis in CRC. Macrophage-targeted strategies, particularly M2-to-M1 repolarization approaches used in combination with existing ICB regimens, represent a promising avenue for expanding immunotherapy efficacy beyond MSI-H disease. Further translational research and randomized controlled trials are needed to validate these targets clinically. Full article

Background: Several factors have been reported to influence the prognosis of medullary thyroid cancer (MTC). This study aimed to identify prognostic variables associated with progression-free survival (PFS) and overall survival (OS) in a cohort of patients treated at our institution. Patients and Methods: We performed a retrospective analysis of 107 consecutive patients with histologically confirmed MTC who were followed for at least 12 months. Demographic, clinical, and pathological data were retrieved from medical records. The association between baseline variables and survival outcomes was evaluated using univariate Cox proportional hazards regression models. The study was approved by the local ethics committee. Results: The median age at diagnosis was 56 years (range, 10–80 years), and 63% of the patients were female. Germline REarranged during Transfection (RET) mutations were identified in 10% of cases. The median follow-up duration was 100 months (range, 12–464 months). At diagnosis, disease stages were distributed as follows: stage I, 52%; stage II, 12%; stage III, 17%; and stage IV, 19%. Female patients showed significantly longer PFS compared with males (Hazard Ratio (HR) = 0.41, 95% Confidence Interval (CI) (0.21–0.82); p = 0.012). Factors associated with PFS by Cox regression models were post-operative serum calcitonin (CT) values after 1 and 3 months of surgery (HR = 0.08, 95% CI (0.03–0.20); p < 0.001; HR = 0.03, 95% CI (0.01–0.11); p < 0.001, respectively), Tumor, Node, and Metastasis (TNM) stage III–IV (HR = 16.86, 95% CI (5.87–48.44); p < 0.001), presence of lymph nodes metastasis at diagnosis (HR = 9.6, 95% CI (3.59–25.63); p < 0.001), multifocal disease (HR = 2.37, 95% CI (1.07–5.28); p = 0.034) and capsular invasion (HR = 10.72, 95% CI (4.45–25.87); p < 0.001). Factors associated with OS by Cox regression models were age at diagnosis (HR = 1.07, 95% CI (1.01–1.12); p = 0.019) and TNM Classification of Malignant Tumours stage III-IV (HR = 6.69, 95% CI (1.42–31.62); p = 0.016). Although lymph node metastasis and capsular invasion were not significantly associated with overall survival (p = 0.178 and p = 0.094, respectively), both variables showed a trend toward an association with OS. Conclusions: The study confirmed that post-operative serum CT values, male sex, lymph nodes metastasis at diagnosis, TNM stage III and IV and capsular invasion were all associated with a lower PFS. Factors associated with OS were age at diagnosis, presence of lymph nodes metastasis, TNM stage III–IV and capsular invasion. Full article

Background: Normothermic machine perfusion (NMP) is increasingly being used to improve organ utilization in liver transplantation (LT). However, its non-physiological perfusion setting may cause focal hepatic hypoperfusion (FHH), which remains insufficiently characterized in terms of its incidence, risk factors, and clinical impact. Methods: Data on liver grafts that underwent NMP prior to LT at the Department of General, Visceral, and Transplant Surgery, University Hospital Münster, between October 2019 and August 2024 were retrospectively analyzed. Recipients who underwent contrast-enhanced computed tomography within 30 days post-LT were included. The primary outcomes were the Comprehensive Complication Index (CCI) and overall graft survival rate. Ninety-one patients met the inclusion criteria and were stratified according to the presence of FHH in the FHH+ (n = 27) and FHH- (n = 64) groups. Results: FHH was detected in 29.7% of the grafts. Higher graft weight was the only independent predictor of FHH. In addition, graft weight correlated with the extent of FHH (τ = 0.40, p < 0.001). FHH did not affect graft or patient survival but was associated with higher CCI scores (p = 0.001) and prolonged intensive care unit length of stay (p = 0.028). Conclusions: FHH is a common radiological finding after NMP. Although it does not affect graft loss, its association with a higher complication burden warrants further attention. Whether avoiding NMP in very heavy grafts could reduce the incidence of FHH remains to be determined. Full article

Background: Awake craniotomy with intraoperative mapping is the standard of care for gliomas located in language-eloquent regions, enabling maximal safe resection while preserving functional integrity. This study aimed to identify clinical and intraoperative predictors of postoperative language worsening and overall survival in patients undergoing awake surgery for malignant glioma. Methods: In this retrospective multicenter cohort study, 37 patients with malignant glioma in the dominant hemisphere underwent awake craniotomy with intraoperative mapping. Clinical, radiological, intraoperative, and postoperative variables were analyzed. Language outcome was classified as unchanged or worsened. Univariable and parsimonious multivariable logistic regression analyses were used to identify predictors of language worsening. Overall survival was assessed using univariable Cox regression. Results: Postoperative language worsening occurred in six patients (16.2%). Increasing age was associated with higher odds of postoperative language worsening in univariable logistic regression (OR 1.12 per year, 95% CI 1.02–1.23, p = 0.019). Due to the limited number of outcome events, multivariable logistic regression was not performed. In survival analysis, increasing age (HR 1.10, 95% CI 1.05–1.16, p < 0.001) and WHO grade 4 (HR 18.15, 95% CI 3.91–84.19, p < 0.001) were associated with shorter overall survival. No statistically significant association between extent of resection and overall survival was detected in this small cohort. Conclusions: Awake glioma surgery with intraoperative mapping was associated with favorable language outcomes in most patients at the 3-month follow-up. Increasing age was associated with postoperative language worsening in univariable analysis. These findings should be interpreted as exploratory because of the limited sample size and low number of outcome events. Larger prospective studies with standardized longitudinal language assessment are needed. Full article

Background/Objectives: Established AECOPD prognostic tools (DECAF, BAP-65, PEARL) predict mortality or readmission rather than length of stay (LOS), and no admission-based instrument specifically targets prolonged hospitalization. We tested whether admission PaCO₂ and the Prognostic Nutritional Index (PNI), reflecting ventilatory failure and nutritional–immune reserve, are independently associated with prolonged LOS and examined their interaction. Methods: In this single-center retrospective cohort, 213 adults hospitalized exclusively for AECOPD were analyzed after excluding concomitant pneumonia, pulmonary embolism, decompensated heart failure, and in-hospital deaths. Prolonged hospitalization was pre-specified as LOS > 7 days. Multivariable logistic regression evaluated admission PaCO₂ (per +10 mmHg) and PNI (per +5 units) with a PaCO₂ × PNI interaction; continuous LOS was modeled by Gamma regression. Discrimination was compared with DECAF using DeLong’s test. Results: Prolonged hospitalization occurred in 83 patients (39.0%). Admission PaCO₂ was independently associated with prolonged LOS (OR 1.52, 95% CI 1.25–1.88; p < 0.001), and PNI showed a borderline association (OR 0.84, 95% CI 0.71–1.00; p = 0.049); their interaction was significant but exploratory (OR 1.16, 95% CI 1.02–1.32; p = 0.025). In Gamma regression, PaCO₂ (RR 1.18 per 10 mmHg) and PNI (RR 0.92 per 5 units) remained associated with LOS. The two-variable model achieved an AUC of 0.682, showing discrimination similar to DECAF in this cohort (AUC 0.695; DeLong p = 0.76), with optimism-corrected AUC 0.672 and calibration slope 0.96. Within moderate hypercapnia (PaCO₂ 45–60 mmHg), the prolonged-LOS rate was 44.4% in low-PNI versus 15.6% in high-PNI patients. Conclusions: In this single-center retrospective cohort of AECOPD patients surviving to discharge, admission PaCO₂ and PNI were jointly associated with prolonged hospitalization, reflecting acute ventilatory burden and nutritional–immune reserve. Using only two admission inputs, the framework showed discrimination similar to DECAF without meaningful reclassification gain (IDI −0.02; NRI 0.02). Given only moderate discrimination (AUC ~ 0.68), external validation is required before clinical use, with the main practical value likely in complementary stratification within moderate hypercapnia. Full article

Background: Colorectal cancer (CRC) prognosis, particularly in liver metastasis (CRLM), is influenced by histopathological and molecular factors. Methods: A narrative analysis of the specialized literature was conducted using databases such as PubMed, MEDLINE, Scopus, and Embase. The review focused on original articles published between 2005 and 2025. Results: Lymph node involvement is a critical prognostic factor, with lymph node-positive CRC correlating with increased risk of liver metastasis and significantly reduced survival rates. Poorly differentiated tumors (G3) exhibit a higher likelihood of metastasis, including liver involvement, and are associated with worse clinical outcomes. Vascular emboli and perineural invasion are indicative of hematogenous spread and higher metastatic potential, leading to poorer survival outcomes. Genetic mutations, such as KRAS, NRAS, and BRAF, are associated with therapy resistance, complicating treatment and highlighting the importance of personalized approaches. MSI-H and HER2 amplification further affect treatment response, with MSI-H tumors showing a favorable response to immunotherapy, while HER2-positive CRCs may benefit from targeted therapies. Tumor budding, high levels of which predict poor survival, is another key histopathological feature associated with aggressive metastatic behavior. Systemic inflammatory markers, such as the Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and C-Reactive Protein-to-Albumin Ratio (CAR), offer prognostic insights into CRLM patient survival. Conclusions: Histopathological features, molecular alterations, and immune microenvironment factors significantly impact the prognosis of CRC with liver metastasis. The integration of molecular profiling, immunotherapy, and targeted therapies offers promise for improving treatment outcomes. Personalized treatment strategies, incorporating these factors, are essential for overcoming therapy resistance and improving survival in CRLM patients. Full article

Background/Objectives: Patients with relapsed/refractory multiple myeloma (RRMM) have poor survival outcomes and limited treatment options. The increasing utilization of multiagent therapies for earlier lines of treatment and novel drug classes including BCMA-targeting agents in subsequent lines of therapy has created a need for innovative treatment platforms in patients who have relapsed after or are refractory to these current standard-of-care approaches. Iopofosine I 131 is a ¹³¹iodide (¹³¹I)–phospholipid conjugate that exploits the selective uptake and retention of phospholipid ethers through lipid rafts to facilitate tumor delivery of ¹³¹I. Methods: The objective of this phase 1 dose-escalation study was to assess the safety and tolerability of single and fractionated dose schedules of iopofosine I 131 + low-dose dexamethasone in heavily pretreated patients with RRMM. Results: The most common AEs overall were cytopenias, notably thrombocytopenia (93.5%), lymphopenia (74.2%), anemia (71%), leukopenia (61.3%), and neutropenia (58.1%). All patients experiencing hematologic adverse events recovered from those events with median time of recovery 21 days post-nadir. Nonhematologic adverse events were mostly limited to Grade 1 and 2. Dose-limiting toxicities included four Grade 4 thrombocytopenia events lasting longer than 7 days, one Grade 4 neutropenia, and one Grade 3 insomnia. The DMC determined 31.25 mCi/m² was the maximum tolerated dose in the single-dose group, and 20 mCi/m² × 2 doses was the maximum tolerated dose in the fractionated-dose group. For patients monitored through 85 days following the first infusion, 22 of 26 (84.6%) achieved stable disease after treatment, and 4 of 26 (15.4%) achieved a partial response. Conclusions: A favorable safety and tolerability profile and preliminary clinical activity support further development of iopofosine I 131 in RRMM. Full article

Background/Objectives: Advanced hormone receptor-positive (HR+), epidermal growth factor 2-negative (HER2−) breast carcinoma (BC) patients receive frontline therapy with cyclin-dependent tyrosine kinase 4/6 inhibitors + endocrine therapy (ET). At progression, the best management includes mutational analysis for ESR-1, allowing second-line therapy with elacestrant. The aim of this study was to evaluate the efficacy and safety of elacestrant in an Italian real-world setting. Methods: A multicenter, observational study with a mixed retrospective and prospective design was conducted in 13 medical oncology units across Italy. The study population included adult patients with HR+/HER2− locally advanced or metastatic breast cancer with an activating ESR1 mutation documented by liquid biopsy and progressing after at least one line of endocrine therapy containing a CDK4/6 inhibitor. Mutational analysis of plasma was performed using next-generation sequencing with a multigene panel that included ESR1, PIK3CA, AKT, and PTEN. The sample size was calculated according to the two-stage Simon design. Toxicity was classified according to CTCAE version 5.0 criteria. Survival analyses were conducted using the Kaplan–Meier method. Results: At the time of analysis, 39 evaluable patients were enrolled, all female and Caucasian, with a median age of 67 years (range 41–89). The efficacy analysis documented an overall ORR of 28% and a disease control rate of 56%. The median duration of response was 6+ months (95% CL: 3.5–10.6 m). Median overall survival was not reached with a median follow-up of 10 months. The toxicity profile was overall favorable: grade ≥2 asthenia was the most frequent adverse event (23%), followed by gastrointestinal toxicity, which was generally mild. No treatment-related toxicity was reported in 64% of patients. Dose reductions were necessary in 15% of cases, while permanent treatment discontinuation due to toxicity occurred in only 4%. Conclusions: The results of this Italian multicenter observational study confirm the efficacy and tolerability of elacestrant in HR+/HER2− metastatic breast cancer with ESR1 mutation, in a real-world context consistent with the data from the pivotal EMERALD study and with real-world data present in the literature. Full article

Cutaneous Melanoma is a biologically heterogeneous malignancy. Although recent therapeutic advances have improved survival, durable remissions remain elusive for many patients. Surgical excision with stage-appropriate margins and selective nodal staging remains the cornerstone of curative-intent management. In contrast, conventional cytotoxic chemotherapy now plays a limited, largely palliative role given its modest efficacy and substantial toxicity. Targeted therapy with BRAF/MEK inhibitors has improved outcomes in patients with BRAF V600-mutant melanoma, resulting in rapid tumor regression and meaningful survival benefits. However, long-term disease control is frequently compromised by adaptive resistance, commonly driven by MAPK pathway reactivation or compensatory PI3K/AKT signaling. In parallel, immune checkpoint inhibitors targeting PD-1, CTLA-4, and emerging pathways have reshaped treatment across disease stages, enabling deep and sometimes durable responses. Despite this progress, primary and acquired resistance, as well as acute and chronic immune-related toxicities, continue to pose significant clinical challenges. Current therapeutic strategies focus on rational combinations of targeted therapy, checkpoint blockade, IL-2-based approaches, oncolytic viruses, and adoptive cell therapies such as tumor-infiltrating lymphocytes to enhance response depth and durability. However, these intensified regimens carry increased toxicity risks, highlighting the need for improved patient selection and monitoring. Overall, emerging evidence supports a paradigm shift toward optimized treatment sequencing, response-adapted surgical strategies, and biomarker-guided personalization to maximize clinical benefit while minimizing toxicity. Full article

Background: Adjuvant therapy decisions for T3N0 stage II colon cancer remain controversial. This study evaluates long-term outcomes, recurrence patterns, and conditional relapse-free survival (RFS) in pathologic T3N0 colon cancer. Methods: This retrospective study included 306 patients undergoing curative resection for T3N0 colonic adenocarcinoma (1995–2020). Early recurrence was defined as recurrence or death within 3 years after surgery. Survival was estimated via Kaplan–Meier. Cox regression, adjusted for treatment eras, evaluated survival factors. Inverse Probability of Treatment Weighting (IPTW) minimized selection bias. Conditional RFS utilized a 5-year landmark analysis. Results: Over a 133-month median follow-up, 72 patients (23.5%) recurred. Most recurrences (81.9%) occurred within 3 years; only 9.7% after 5 years. Five- and 10-year OS rates were 80.9% and 70.4%. Inadequate lymph node dissection (<12 nodes) was performed in 29.7% of the entire cohort and was found to be an independent adverse prognostic factor for OS. Adjuvant chemotherapy lacked overall OS benefit, though IPTW analysis suggested potential benefit in patients with inadequate dissection. Conditional RFS (5–10 years) for patients recurrence-free at 60 months was 95.0%. Exploratory analyses showed descriptive differences in post-relapse survival based on the clinical triggers prompting radiological evaluation (marker-triggered versus symptom-triggered presentations). Conclusions: T3N0 colon cancer recurrences occur predominantly within the first 3–5 years after surgery. Inadequate lymph node dissection is the primary adverse prognostic factor. Although a 5-year follow-up period appears adequate for most patients, individualized extended surveillance may be considered for selected high-risk patients. Adjuvant treatment and follow-up strategies should be tailored according to surgical quality and risk factors. Full article