Critical reviews in oncology/hematology最新文献

{"title":"TROP-2–directed antibody–drug conjugates in advanced NSCLC: A systematic review and meta-analysis of efficacy, safety, and reconstructed survival outcomes","authors":"Muhammad Ansab ,&nbsp;Shree Rath ,&nbsp;Umama Alam ,&nbsp;Muhammad Burhan ,&nbsp;Hafiza Tooba Siddiqui ,&nbsp;Aakash Desai","doi":"10.1016/j.critrevonc.2025.105093","DOIUrl":"10.1016/j.critrevonc.2025.105093","url":null,"abstract":"<div><h3>Introduction</h3><div>Non-small cell lung cancer (NSCLC) represents the majority of lung cancer cases worldwide, with most patients diagnosed at advanced stages and limited by resistance to existing therapies. TROP-2, an epithelial cell surface glycoprotein overexpressed in many NSCLCs, has emerged as a promising therapeutic target for antibody–drug conjugates (ADCs). This study aims to systematically evaluate the efficacy and safety of TROP-2–directed ADCs in patients with advanced or metastatic NSCLC.</div></div><div><h3>Methods</h3><div>Electronic databases (PubMed, Embase, Clinical Trials and Cochrane Central) were searched up to November 2025 for studies reporting outcomes in advanced NSCLC patients treated with TROP-2–directed ADCs. Eligible studies included adult populations with advanced NSCLC that were treated with datopotamab deruxtecan, sacituzumab govitecan, or sacituzumab tirumotecan, and reported efficacy or safety outcomes. Pseudo–individual patient-level data for survival analyses were reconstructed from published Kaplan–Meier curves. Pooled effect sizes were estimated using random-effects meta-analytic models.</div></div><div><h3>Results</h3><div>Seven studies encompassing 1365 patients with advanced or metastatic NSCLC were included. The pooled median overall survival (OS) was 16.38 months (95 % CI: 11.17–22.96), and the median progression-free survival (PFS) was 6.08 months (95 % CI: 4.93–8.55). The objective response rate (ORR) across studies was 29 % (95 % CI: 19 %–39 %), with a disease control rate (DCR) of 79 % (95 % CI: 74 %–84 %). Subgroup analysis revealed patients with EGFR-mutated tumors had a significantly higher likelihood of response (risk ratio 1.70, 95 % CI: 1.11–2.61). Safety analysis showed treatment-emergent adverse events (TEAEs) in 98 % (95 % CI: 94 %–100 %), grade ≥ 3 TEAEs in 52 % (95 % CI: 38 %–67 %), and interstitial lung disease (ILD) in 9 % (95 % CI: 3 %–16 %).</div></div><div><h3>Conclusion</h3><div>TROP-2–directed ADCs demonstrate meaningful efficacy in previously treated advanced NSCLC, especially among EGFR-mutant and non-squamous histology patients, with survival and response outcomes superior to traditional chemotherapy. However, high rates of adverse events, particularly ILD, necessitate close monitoring. Further randomized and biomarker-driven studies are warranted to refine patient selection and optimize the therapeutic potential of these agents.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105093"},"PeriodicalIF":5.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of adding immune checkpoint inhibitors to standard therapies in non-small cell lung cancer: A systematic review of efficacy outcomes","authors":"Ana Pinto Correia ,&nbsp;Adriana Marques ,&nbsp;Bruno Sepodes ,&nbsp;Carla Torre ,&nbsp;João Rocha","doi":"10.1016/j.critrevonc.2025.105098","DOIUrl":"10.1016/j.critrevonc.2025.105098","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for 85 % of all cases. Although immune checkpoint inhibitors (ICIs) have revolutionized NSCLC treatment, the extent to which they improve survival when combined with standard therapies, rather than used alone, remains unclear. Here, we systematically review published clinical trials evaluating ICIs combined with other standard systemic therapies versus each strategy alone. Methods: A systematic review was conducted using MEDLINE (via PubMed) and EMBASE, following PRISMA guidelines. Randomized controlled trials published until December 2024 that studied the efficacy of immunotherapy regimens combining approved ICIs and other systemic therapies in NSCLC were included. Results We included 36 RCTs with a combined 24,495 participants. Most were open-label (n = 21, 58.3 %), while the remaining studies were double-blinded (n = 15, 41.7 %). Most studies were phase 3 trials (n = 33, 91.7 %) and only three trials were phase 2 (8.3 %). Included trials utilized platinum-doublet chemotherapy as the backbone, with some also incorporating bevacizumab and/or additional immunotherapy. In the included studies, combining immunotherapy with other standard therapies significantly improved survival outcomes compared to either strategy alone. These benefits were consistent across histological subtypes, PD-L1 expression levels, and disease stage. However, the efficacy of this combined approach was limited in EGFR-mutated NSCLC after progression on tyrosine kinase inhibitors. Conclusions: By synthesizing existing evidence from RCTs, this systematic review demonstrates the benefits and limitations of combining immune checkpoint inhibitors with other systemic treatments, clarifying which clinical situations may benefit the most from a combined approach.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105098"},"PeriodicalIF":5.6,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A daily clinical practice decision-making overview for the present metastatic renal cell carcinoma (mRCC) management landscape","authors":"Sergio Bracarda ,&nbsp;Fabio Calabrò ,&nbsp;Ugo De Giorgi ,&nbsp;Giuseppe Procopio ,&nbsp;Roberto Sabbatini ,&nbsp;Camillo Porta","doi":"10.1016/j.critrevonc.2025.105097","DOIUrl":"10.1016/j.critrevonc.2025.105097","url":null,"abstract":"<div><h3>Background</h3><div>Renal cell carcinoma (RCC), originating from renal tubular epithelial cells, represents approximately 80 % of all primary kidney tumors. Roughly 30 % of cases are diagnosed at an advanced stage, and a similar proportion experience recurrence after surgery for localized disease. This recurrence rate may improve with the recent introduction of an effective adjuvant immunotherapy.</div></div><div><h3>Objective</h3><div>This work aims to assess the current therapeutic landscape of metastatic RCC (mRCC), with a focus on immunotherapy-based combinations, and to offer expert, real-world insights into clinical decision-making and adverse event (AE) management.</div></div><div><h3>Methods</h3><div>Six oncologists specialized in mRCC completed a structured survey covering four key areas: (1) overall survival, (2) safety of IO–IO and IO–TKI combinations, (3) treatment selection, and (4) sequential strategies. Responses were reviewed in a virtual meeting, with agreement defined as concurrence by at least five of the six participants. Any areas without unanimous agreement were addressed through subsequent discussion rounds until a final agreement was reached.</div></div><div><h3>Results</h3><div>Nivolumab plus ipilimumab provides durable responses and long-term survival, especially in intermediate- and poor-risk patients. TKI-based combinations, including cabozantinib and lenvatinib, achieve strong disease control, while axitinib offers a greater dosing flexibility due to its short half-life. Toxicity profiles differ by regimen, requiring careful management of immune-related and TKI-associated adverse events. Relapse risk after adjuvant pembrolizumab should guide first-line therapy choice for advanced disease, while metastasis-directed treatments should be considered by multidisciplinary teams.</div></div><div><h3>Conclusions</h3><div>Optimal first-line treatment for mRCC requires consideration of patient characteristics, clinical and molecular prognostic factors, treatment tolerability, all of these parameters should be evaluated during a multidisciplinary team discussion.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105097"},"PeriodicalIF":5.6,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"To ablate or not to ablate? Outcomes of local ablative treatments (LAT) for oncogene addicted (OA) oligo-metastatic (OM) non-small cell lung cancer (NSCLC): A systematic review","authors":"Fabrizio Citarella ,&nbsp;Cristina Fragale ,&nbsp;Matteo Fiorenti ,&nbsp;Maria Luisa Di Guglielmo ,&nbsp;Noemi Mindicini ,&nbsp;Alessio Cortellini ,&nbsp;Alessandro Russo ,&nbsp;Giuseppe Bronte","doi":"10.1016/j.critrevonc.2025.105096","DOIUrl":"10.1016/j.critrevonc.2025.105096","url":null,"abstract":"<div><div>Oncogene-addicted non-small cell lung cancer (NSCLC) encompasses distinct molecular phenotypes, each associated with specific clinical behavior and variable sensitivity to targeted therapies. Therapeutic advancements in the field enhanced clinical outcomes and overall prognostic improvement. Beyond the molecular profile, disease burden serves as a predictive marker for treatment response and overall prognostic outcomes. The current disease staging categorizes patients based on the number and sites of metastatic involvement. In this context, the addition of local ablative therapies (LAT) is candidate to enhance or prolong the effectiveness of standard systemic therapies. Our systematic review aims to summarize current evidence dealing with the outcomes of LAT in the context of oncogene addicted NSCLC. Over response results, we also reported side effects whenever available.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105096"},"PeriodicalIF":5.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional role of neutrophils in lung cancer: Mechanisms and therapeutic implications","authors":"Jing Wang ,&nbsp;Meng Zhang ,&nbsp;Zhiyue Cui ,&nbsp;Jingjing Qu ,&nbsp;Ruimin Chang","doi":"10.1016/j.critrevonc.2025.105087","DOIUrl":"10.1016/j.critrevonc.2025.105087","url":null,"abstract":"<div><div>Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) being the predominant subtype. Despite the availability of traditional treatments such as radiation therapy, chemotherapy, and surgery, as well as emerging immunotherapies, the five-year survival rate and prognosis remain suboptimal. Tumor-associated neutrophils (TANs) are the most abundant immune cells in the tumor microenvironment (TME) of lung cancer, and understanding their role in cancer therapy is highly important. This review comprehensively discusses the dual role of TANs in lung cancer progression. First, we examined the recruitment, classification, and single-cell heterogeneity of TANs, highlighting the distinct molecular expression and functions across subpopulations. Mechanistically, TANs influence tumor behavior through direct cell<img>cell interactions and cytokine production. Additionally, neutrophils engage with other cells in the TME via metabolic reprogramming, programmed cell death, epigenetic modifications, and vesicle secretion. To date, no studies have systematically summarized and connected these mechanisms. Finally, we summarize the clinical applications and prospects of TANs in lung cancer, including their potential role in assisting in diagnosis, predicting prognosis, and targeting neutrophils to increase the efficacy of radiation, chemotherapy, and immunotherapy. We hope that this review provides insights for future research aimed at improving lung cancer prognosis through the targeting of TANs.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105087"},"PeriodicalIF":5.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of ORR and PFS with OS outcomes in phase III trials of immunotherapy in advanced NSCLC: Systematic review and meta-analysis","authors":"Fabio Salomone ,&nbsp;Massimo Di Maio ,&nbsp;Angela Viggiano ,&nbsp;Luigi Liguori ,&nbsp;Carminia Maria Della Corte ,&nbsp;Giuseppe Viscardi ,&nbsp;Fabiana Vitiello ,&nbsp;Fabiana Napolitano ,&nbsp;Antonio Santaniello ,&nbsp;Antonio Nuccio ,&nbsp;Simeone D’Ambrosio ,&nbsp;Filippo Vitale ,&nbsp;Annarita Avanzo ,&nbsp;Alessandra Bulotta ,&nbsp;Luigi Formisano ,&nbsp;Roberto Ferrara ,&nbsp;Roberto Bianco ,&nbsp;Valter Torri ,&nbsp;Alberto Servetto","doi":"10.1016/j.critrevonc.2025.105092","DOIUrl":"10.1016/j.critrevonc.2025.105092","url":null,"abstract":"<div><h3>Background</h3><div>The ability of progression-free survival (PFS) and overall response rate (ORR) to predict overall survival (OS) outcomes in cancer trials is matter of debate. Herein, we investigated whether PFS and ORR predicted OS results in randomized clinical trials (RCTs) testing immune checkpoint inhibitors (ICIs) in advanced NSCLC.</div></div><div><h3>Methods</h3><div>ORR (OR_ORR,%ORR), OS (HR_OS,mOS) and PFS (HR_PFS,mPFS) data were collected from phase III RCTs investigating ICIs in advanced NSCLC. Linear regression, weighted by sample size, between surrogate endpoints and OS were calculated. The power of correlation was defined by the value of coefficient of determination R² (≥0.7 strong, 0.69–0.50 moderate, &lt;0.5 weak).</div></div><div><h3>Results</h3><div>Forty investigational arms of ICIs ± chemotherapy (ChT) were identified for further investigation. Arm-level analysis revealed that mPFS had a strong correlation with mOS in all comparisons (R²=0.71), in ICIs+ChT trials (R²=0.81) and in first-line setting (R²=0.71). A weak correlation was found between mPFS-mOS (R²=0.48) in trials of ICIs without chemotherapy. Next, trial-level analysis revealed a weak correlation between HR_OS and HR_PFS in all different groups, except in ICIs+ChT trial (R²=0.60). In addition, based on arm-level analysis, mOS and %ORR had moderate correlation in all comparisons (R²=0.58), in ICIs+ChT (R²=0.58) or ICIs (R²=0.53). In trial-level analysis, OR_ORR and HR_OS had moderate correlation (R²=0.55) in first-line setting and a strong correlation in ICIs+ChT trials (R²=0.79).</div></div><div><h3>Conclusions</h3><div>Across trials investigating ICIs in advanced NSCLC, PFS and ORR demonstrated various degrees of relationship with OS. Caution should be taken when efficacy of novel ICIs regimens is evaluated only using surrogate outcomes.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105092"},"PeriodicalIF":5.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-coding RNAs and liquid biopsies: Emerging biomarkers for cervical cancer","authors":"Mariana Teixeira Costa ,&nbsp;Valéria Tavares ,&nbsp;Filomena Adega ,&nbsp;Rui Medeiros","doi":"10.1016/j.critrevonc.2025.105091","DOIUrl":"10.1016/j.critrevonc.2025.105091","url":null,"abstract":"<div><div>Cervical cancer (CC) is the fourth most common malignancy among women worldwide, highlighting the urgent need for improved predictive, diagnostic and prognostic biomarkers to enhance disease management and patient outcomes. Non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs), perform various functions in transcriptional, translational and post-translational regulation. Aberrant expression of ncRNAs in CC has been closely associated with disease initiation and progression, underscoring their potential as key regulators of cervical tumorigenesis. Several lncRNAs, such as HOTAIR and PVT1, contribute to cervical tumorigenesis by promoting cell proliferation, migration and invasion. Likewise, circRNAs, such as circ_0018289, act as miRNA sponges, leading to the dysregulation of key target genes. Moreover, specific miRNAs, such as miR-20a and miR-21, promote CC progression (oncogenic miRNAs), whereas others, including miR-214 and miR-218, exhibit a tumor suppressor role. Importantly, many ncRNAs are detectable in body fluids, representing stable and minimally invasive biomarkers suitable for liquid biopsy. Thus, in this comprehensive narrative review, we map the range of candidate ncRNAs reported in the literature and discuss their predictive, diagnostic, prognostic and therapeutic value, including their potential as circulating biomarkers in CC. We also highlight, as a future perspective, how integrated profiling approaches could guide research and support the development of non-invasive strategies for diagnosis, prognostic assessment, and therapy monitoring in CC.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105091"},"PeriodicalIF":5.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential strategies to improve the therapeutic efficacy of oncolytic viruses for cancer through T and NK cells targeting","authors":"Chuanjian Wu ,&nbsp;Hanzhang Liu ,&nbsp;Yujie Shi ,&nbsp;Jie Tang ,&nbsp;Rong Sun ,&nbsp;Xudong Han ,&nbsp;Yihui Fan","doi":"10.1016/j.critrevonc.2025.105086","DOIUrl":"10.1016/j.critrevonc.2025.105086","url":null,"abstract":"<div><div>Oncolytic viruses (OVs) elicit potent tumor lysis and remodel the tumor microenvironment (TME) to activate adaptive and innate immunity, yet their efficacy depends critically on T and NK cell responses. Here, we review recent advances in the characterization and engineering of OVs to enhance lymphocyte-mediated tumor control. CD8⁺ cytotoxic T cells and CD4⁺ helper T cells drive durable antitumor immunity through OV-enhanced antigen presentation, memory formation, and modulation of Tregs, whereas T cell exhaustion and checkpoint interactions remain key barriers. Arming OVs with cytokines, chemokines, bispecific engagers, or metabolic modulators enhances effector T-cell expansion, infiltration, and cytotoxicity in solid tumors. In parallel, NK cells—whose efficacy is often limited by poor intratumoral activity and antiviral competition—are increasingly harnessed by OV platforms expressing immune stimulators or checkpoint modulators. Combination strategies with targeted therapies, checkpoint blockade, or adoptive NK/T cell transfer further potentiate therapeutic efficacy. Importantly, although OVs may inadvertently amplify dominant antiviral responses at the expense of antitumor activity, strategies incorporating tumor antigen encoding and TME reprogramming can overcome this limitation. Collectively, these findings underscore the central role of T and NK cells in OV-based immunotherapy and highlight rational arming and combination approaches to improve tumor control and long-term protection.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105086"},"PeriodicalIF":5.6,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic approaches to prostate cancer: Present landscape and future prospects","authors":"Konstantinos Mesiakaris,&nbsp;Efthalia Kontogianni,&nbsp;Souzana Logotheti,&nbsp;Vasiliki Tzelepi","doi":"10.1016/j.critrevonc.2025.105083","DOIUrl":"10.1016/j.critrevonc.2025.105083","url":null,"abstract":"<div><div>Genetic profiles alone do not fully describe the development and evolution of prostate cancer (PCa), whereas epigenetic alterations are emerging as promising therapeutic targets. This review explores FDA-approved and experimental epigenetic strategies, including DNA methyltransferase inhibitors (DNMTis), histone deacetylase inhibitors (HDACis), histone methyltransferase inhibitors, bromodomain and extra-terminal domain inhibitors (BETi), non-coding RNA therapies, antisense oligonucleotides, and future prospects such as chromatin remodeling, DNA hydroxymethylation, and RNA methylation. Although DNMTis and HDACis have historically dominated clinical trials, mainly in hematologic cancers, the 2020 approval of an epigenetic therapy for a solid tumor marked an important breakthrough. Despite this, epigenetic drugs remain underexplored in PCa: among 2254 clinical studies of such agents, only 58 (2.57 %) included PCa patients. This disparity highlights an urgent need for novel therapeutic approaches beyond chemotherapy and androgen deprivation. By assessing current progress and outlining opportunities in drug repositioning and novel targets, this review underscores epigenetics as a critical frontier for advancing PCa treatment.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105083"},"PeriodicalIF":5.6,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathological ultrastaging of mesocolic lymph nodes after colon cancer resection: A systematic review and meta-analysis","authors":"Bart C.T. van de Laar ,&nbsp;Daan J. Sikkenk ,&nbsp;Gursah Kats-Ugurlu ,&nbsp;Derk Jan A. de Groot ,&nbsp;Wouter B. Nagengast ,&nbsp;Esther C.J. Consten","doi":"10.1016/j.critrevonc.2025.105089","DOIUrl":"10.1016/j.critrevonc.2025.105089","url":null,"abstract":"<div><h3>Background</h3><div>In colon cancer (CC), lymph node (LN) (micro)metastases determine the need for adjuvant chemotherapy. Routine single-section hematoxylin and eosin (H&amp;E) may miss (micro)metastases, resulting in understaging. Histopathological ultrastaging using serial sectioning (SS) and immunohistochemistry (IHC) can improve metastasis detection, for example in the context of organ-preserving surgery using a sentinel lymph node (SLN) procedure. This review evaluates SS and IHC for detecting LN (micro)metastases and aims to identify the ultrastaging method with the highest detection rate. Isolated tumor cells were analyzed separately and were not considered indicative of nodal upstaging.</div></div><div><h3>Methods</h3><div>PubMed, Embase, and the Cochrane Library were searched. Studies were included if they evaluated histopathological ultrastaging alongside routine H&amp;E in patients with CC and reported results separately. Risk of bias was assessed using QUADAS-2. Pooled proportions were calculated using random-effects models.</div></div><div><h3>Results</h3><div>Thirty studies (n = 1822 patients) using SS and IHC were included. In SLN studies (n = 23), 21 % (95 % CI: 12–31 %) of 1070 patients had LN (micro)metastases. Among node-positive patients, 25 % (95 % CI: 6.0–50 %) were identified only by SLN ultrastaging. The absolute benefit of ultrastaging in the total cohort was small, 3.0 % (95 % CI: 1.0–5.0 %), with moderate heterogeneity. In non-SLN studies (n = 7), ultrastaging of all LNs upstaged 6.0 % (95 % CI: 2.0–13 %) of 752 patients, with high heterogeneity. IHC identified only one additional micrometastasis beyond SS. Protocol heterogeneity was considerable.</div></div><div><h3>Conclusion</h3><div>Histopathological ultrastaging detects (micro)metastases, but its clinical impact on adjuvant chemotherapy benefit remains uncertain. Protocol standardization is needed, and the added value of IHC beyond SS appears minimal.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105089"},"PeriodicalIF":5.6,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}