Cancers

19 pages, 2272 KB

Open AccessArticle

Enhancing PRRT Outcome Prediction in Neuroendocrine Tumors: Aggregated Multi-Lesion PET Radiomics Incorporating Inter-Tumor Heterogeneity

by Maziar Sabouri, Ghasem Hajianfar, Omid Gharibi, Alireza Rafiei Sardouei, Yusuf Menda, Ayca Dundar, Camila Gadens Zamboni, Sanchay Jain, Marc Kruzer, Habib Zaidi, Fereshteh Yousefirizi, Arman Rahmim and Ahmad Shariftabrizi

Cancers 2025, 17(23), 3887; https://doi.org/10.3390/cancers17233887 - 4 Dec 2025

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Abstract

Introduction: Peptide Receptor Radionuclide Therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTA-TATE is effective in treating advanced Neuroendocrine Tumors (NETs), yet predicting individual response in this treatment remains a challenge due to inter-lesion heterogeneity. There is a lack of standardized, effective methods for using multi-lesion [...] Read more.

Introduction: Peptide Receptor Radionuclide Therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTA-TATE is effective in treating advanced Neuroendocrine Tumors (NETs), yet predicting individual response in this treatment remains a challenge due to inter-lesion heterogeneity. There is a lack of standardized, effective methods for using multi-lesion radiomics to predict progression and Time to Progression (TTP) in PRRT-treated patients. This study evaluated how aggregating radiomic features from multiple PET-identified lesions can be used to predict disease progression (event [progression and death] vs. event-free) and TTP. Methods: Eighty-one NETs patients with multiple lesions underwent pre-treatment PET/CT imaging. Lesions were segmented and ranked by minimum Standard Uptake Value (SUV_min) (both descending and ascending), SUV_mean, SUV_max, and volume (descending). From each sorting, the top one, three, and five lesions were selected. For the selected lesions, radiomic features were extracted (using the Pyradiomics library) and lesion aggregation was performed using stacked vs. statistical methods. Eight classification models along with three feature selection methods were used to predict progression, and five survival models and three feature selection methods were used to predict TTP under a nested cross-validation framework. Results: The overall appraisal showed that sorting lesions based on SUV_min (descending) yields better classification performance in progression prediction. This is in addition to the fact that aggregating features extracted from all the lesions, as well as the top five lesions sorted by SUV_mean, lead to the highest overall performance in TTP prediction. The individual appraisal in progression prediction models trained on the single top lesion sorted by SUV_min (descending) showed the highest recall and specificity despite data imbalance. The best-performing model was the Logistic Regression (LR) classifier with Recursive Feature Elimination (RFE) (recall: 0.75, specificity: 0.77). In TTP prediction, the highest concordance index was obtained using a Random Survival Forest (RSF) trained on statistically aggregated features from the top five lesions ranked by SUV_mean, selected via Univariate C-Index (UCI) (C-index = 0.68). Across both tasks, features from the Gray Level Size Zone Matrix (GLSZM) family were consistently among the most predictive, highlighting the importance of spatial heterogeneity in treatment response. Conclusions: This study demonstrates that informed lesion selection and tailored aggregation strategies significantly impact the predictive performance of radiomics-based models for progression and TTP prediction in PRRT-treated NET patients. These approaches can potentially enhance model accuracy and better capture tumor heterogeneity, supporting more personalized and practical PRRT implementation. Full article

(This article belongs to the Section Methods and Technologies Development)

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17 pages, 1383 KB

Open AccessArticle

Exploratory Immunohistochemical Profiling of FOXP3, PD-1 and CD32B in Resectable Lung Adenocarcinoma

by Long-Wei Lin, Hong-Jing Chuang, Kuan-Hsun Lian, Yu-Ting Tseng and Chung-Yu Chen

Cancers 2025, 17(23), 3886; https://doi.org/10.3390/cancers17233886 - 4 Dec 2025

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Abstract

Background: Regulatory T cells (FOXP3⁺), checkpoint signaling (PD-1), and inhibitory B-cell signaling (CD32B/FCGR2B) may shape recurrence risk after resection of lung adenocarcinoma, but small, stage-heterogeneous cohorts complicate inference. Methods: We profiled 21 resected lung adenocarcinomas by immunohistochemistry (IHC) for CD3, CD8, [...] Read more.

Background: Regulatory T cells (FOXP3⁺), checkpoint signaling (PD-1), and inhibitory B-cell signaling (CD32B/FCGR2B) may shape recurrence risk after resection of lung adenocarcinoma, but small, stage-heterogeneous cohorts complicate inference. Methods: We profiled 21 resected lung adenocarcinomas by immunohistochemistry (IHC) for CD3, CD8, FOXP3, PD-1, CD19, and CD32B. Five systematically sampled 200× fields per stain were quantified in ImageJ to derive continuous percentages and prespecified ratios: FOXP3/CD8 and CD32B/CD19 (primary), and PD-1/CD8 (exploratory). Analyses emphasized effect sizes with exact non-parametric tests for clinicopathologic associations and Cox time-to-event models for disease-free survival (DFS). Kaplan–Meier plots used median splits for visualization only. Results: Higher immunosuppressive balance associated with adverse features and shorter DFS. Patients with higher FOXP3/CD8 and CD32B/CD19 had markedly shorter DFS on K-M displays (FOXP3/CD8: 18.9 vs. 45.6 months; CD32B/CD19: 25.0 vs. 72.8 months). In Cox models, each ratio was associated with increased hazard of recurrence (FOXP3+PD-1/CD8, HR 2.03, 95% CI 1.26–3.29; CD32B/CD19, HR 1.98, 95% CI 1.16–3.37). Conclusions: In this hypothesis-generating pilot, an immunosuppressive tumor microenvironment, indexed by higher FOXP3 (relative to CD8) and higher CD32B (relative to CD19), portends earlier recurrence after surgery. These results support external validation in larger, stage-balanced cohorts and motivate incorporation of quantitative IHC ratios into postoperative risk stratification. Full article

(This article belongs to the Special Issue Lung Cancer—Advances in Therapy and Prognostic Prediction)

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2 pages, 146 KB

Open AccessEditorial

Tracking CTC Dynamics: Trop2 and EpCAM in Metastatic Breast Cancer Progression

by Álvaro González and Estibaliz Alegre

Cancers 2025, 17(23), 3885; https://doi.org/10.3390/cancers17233885 - 4 Dec 2025

Viewed by 313

Abstract

Breast cancer is the most prevalent malignancy worldwide and a leading cause of cancer-related mortality, primarily due to distant metastasis [...] Full article

(This article belongs to the Special Issue Circulating Tumor Cells (CTCs) and the Implementation of Liquid Biopsy (2nd Edition))

13 pages, 466 KB

Open AccessArticle

Organizational Resources in Rare Cancer Outcomes: Survival Analysis After Surgery for Pheochromocytoma and Paraganglioma

by Kelvin Memeh, Sara Abou Azar, Nicholas R. Suss and Tanaz M. Vaghaiwalla

Cancers 2025, 17(23), 3884; https://doi.org/10.3390/cancers17233884 - 4 Dec 2025

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Abstract

Background: For very-rare cancers such as pheochromocytoma and paraganglioma (PPGL), center-level case volume is uniformly low, rendering the traditional volume–outcome paradigm uninformative. This study examines whether cancer programs’ institutional resources, after adjusting for tumor-specific case volume, impact overall survival (OS) after surgery. [...] Read more.

Background: For very-rare cancers such as pheochromocytoma and paraganglioma (PPGL), center-level case volume is uniformly low, rendering the traditional volume–outcome paradigm uninformative. This study examines whether cancer programs’ institutional resources, after adjusting for tumor-specific case volume, impact overall survival (OS) after surgery. Methods: The 2004–2021 National Cancer Database was queried for patients with a diagnosis of PPGL with malignant potential. Demographics, clinicopathologic characteristics, socioeconomic status, and treatment and survival variables—together with program resource tier (high resource = Academic/Research + Comprehensive Community Cancer Programs; low resource = Community Cancer + Integrated Network Programs), were extracted. IPW-Cox proportional hazard model and survival analysis were performed. Results: 1306 patients were identified, of whom 1066 (81.6%) were treated at high-resource programs. Mean age was 59.0 years and 55.1% were female (n = 719). Median follow-up was 61.7 months (maximum 207 months). Mortality was 28.3% (n = 278). Age, race, median income, tumor size, and surgical approach did not differ by resource tier. Patients treated at high- vs. low-resource programs differed by Charlson– Deyo score (p = 0.008), gender (p = 0.033), insurance status (p = 0.004), and distance traveled to facility (p < 0.001). On adjusted survival analysis, treatment at a high-resource program was associated with improved OS (HR = 0.64, p = 0.043) and a mean survival advantage of 23 months (p = 0.009) vs. a low-resource program. Age (HR = 1.03), tumor size >10 cm (HR = 4.18), and metastasis (HR = 4.17) independently predicted worse OS. Conclusions: Despite uniformly low PPGL case volumes nationally, treatment at high-resource cancer programs was associated with a 23-month longer mean survival and a 36% lower risk of death compared with low-resource cancer programs. Further studies are needed to identify the specific institutional factors that drive this survival advantage in rare cancers. Full article

(This article belongs to the Special Issue New Insights into Pheochromocytoma and Paraganglioma)

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30 pages, 1934 KB

Open AccessReview

Low pH, High Stakes: A Narrative Review Exploring the Acid-Sensing GPR65 Pathway as a Novel Approach in Renal Cell Carcinoma

by Michael Grant, Barbara Cipriani, Alastair Corbin, David Miller, Alan Naylor, Stuart Hughes, Tom McCarthy, Sumeet Ambarkhane, Danish Memon, Michael Millward, Sumanta Pal and Ignacio Melero

Cancers 2025, 17(23), 3883; https://doi.org/10.3390/cancers17233883 - 4 Dec 2025

Viewed by 802

Abstract

Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy accounting for 3% of adult cancers globally. Despite advances in immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor (VEGF)-targeted therapies, durable disease control remains elusive for many patients. Increasing evidence implicates the acidic [...] Read more.

Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy accounting for 3% of adult cancers globally. Despite advances in immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor (VEGF)-targeted therapies, durable disease control remains elusive for many patients. Increasing evidence implicates the acidic tumour microenvironment (TME) as a critical mediator of RCC progression, immune evasion, and therapeutic resistance. Solid tumours, including RCC, exhibit reversed pH gradients, characterised by acidic extracellular (pH 6.2–6.9) and alkaline intracellular conditions. This dysregulation arises from enhanced glycolysis, hypoxia-driven lactate accumulation, and the overexpression of pH-regulating enzymes such as carbonic anhydrase (CA9). Acidic TMEs impair cytotoxic T-cell and NK-cell activity, promote tumour-associated macrophage (TAM) polarisation towards an immunosuppressive phenotype, and upregulate alternative immune checkpoints. These mechanisms collectively undermine ICI efficacy and contribute to primary and secondary treatment resistance. Proton-sensing G-protein-coupled receptors (GPCRs), notably GPR65, have emerged as pivotal mediators linking extracellular acidosis to immune dysfunction. Preclinical studies demonstrate that GPR65 antagonists restore anti-tumour immune activity by reversing acidosis-driven immunosuppression and enhancing antigen processing. In RCC models, selective GPR65 inhibitors have shown the ability to reduce immunosuppressive cytokine IL-10 production, induce immunoproteasome activation, and synergise with anti-PD-1 therapy. The first-in-class GPR65 inhibitor, PTT-4256, is now under evaluation in the Phase I/II RAISIC-1 trial (NCT06634849) in solid tumours, including RCC. Targeting acid-sensing pathways represents a novel and promising therapeutic strategy in RCC, aiming to remodel the TME and overcome ICI resistance. Integrating GPR65 inhibition with existing immunotherapies may define the next era of RCC management, warranting continued translational and clinical investigation. Full article

(This article belongs to the Special Issue Understanding the Molecular Basis and Immunobiology of Renal Cell Carcinoma and Exploring Novel Therapeutic Strategies)

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19 pages, 4965 KB

Open AccessArticle

PLS3 Is a Prognostic Biomarker and Correlates with Immune Infiltrates in Head and Neck Squamous Cell Carcinoma

by Yuhong Wang, Kunyi Chen, Guoli Tian, Chen Hou, Yingzhao Huang, Fan Song, Ming Zhang and Jinsong Hou

Cancers 2025, 17(23), 3882; https://doi.org/10.3390/cancers17233882 - 4 Dec 2025

Viewed by 364

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) features aggressive progression and a complex immunosuppressive microenvironment, contributing to poor patient prognosis and highlighting the need to identify key molecular drivers. The actin‑binding protein PLS3 (Plastin‑3) is involved in tumor metastasis, yet its expression, [...] Read more.

Background: Head and neck squamous cell carcinoma (HNSCC) features aggressive progression and a complex immunosuppressive microenvironment, contributing to poor patient prognosis and highlighting the need to identify key molecular drivers. The actin‑binding protein PLS3 (Plastin‑3) is involved in tumor metastasis, yet its expression, function, and therapeutic potential in HNSCC remain unclear. Methods: PLS3 expression was analyzed via polymerase chain reaction (PCR), Western blot (WB), and immunohistochemistry (IHC). PLS3 was knocked down in vitro to assess its effects on HNSCC cell functions, and in vivo models were established to evaluate tumor progression and immune microenvironment. Bioinformatics analyses explored the relationship between PLS3 and tumor immunity. Results: PLS3 was upregulated in HNSCC tissues and correlated with adverse clinical outcomes. Knockdown of PLS3 inhibited cell proliferation, migration, and invasion in vitro, and suppressed tumor growth in vivo. Mechanistically, PLS3 promoted HNSCC progression by activating the epithelial-mesenchymal transition (EMT) program. Bioinformatics and animal studies further linked PLS3 overexpression to an immunosuppressive microenvironment characterized by reduced CD8+ T-cell infiltration and downregulated chemokine expression. Conclusions: This study elucidates the oncogenic role of PLS3 in HNSCC and supports its potential as a prognostic biomarker and therapeutic target. Full article

(This article belongs to the Section Cancer Biomarkers)

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15 pages, 1501 KB

Open AccessSystematic Review

Association Between Gastroesophageal Reflux Disease and Extraesophageal Malignancies: A Systematic Review and Meta-Analysis

by Yu-Si Xu, Zhe-Ran Chen, Yan Bian, Ye Gao, Lei Xin and Luo-Wei Wang

Cancers 2025, 17(23), 3881; https://doi.org/10.3390/cancers17233881 - 4 Dec 2025

Viewed by 753

Abstract

Background/Objectives: The association between gastroesophageal reflux disease (GERD) and extraesophageal malignancies remains unclear. This study aimed to systematically evaluate the relationship between GERD and these cancers. Methods: PubMed, Embase, Scopus, Cochrane Library, and Web of Science were searched for studies reporting risk estimates—risk [...] Read more.

Background/Objectives: The association between gastroesophageal reflux disease (GERD) and extraesophageal malignancies remains unclear. This study aimed to systematically evaluate the relationship between GERD and these cancers. Methods: PubMed, Embase, Scopus, Cochrane Library, and Web of Science were searched for studies reporting risk estimates—risk ratios (RRs), odds ratios (ORs), hazard ratios (HRs), or standardized incidence ratios (SIRs)—of GERD and extraesophageal malignancies. Mendelian randomization (MR) studies with available risk estimates and 95% confidence intervals (CIs) were also included. Pooled estimates with 95% CIs were calculated using a random-effects model. Results: As of 21 May 2025, a total of 37 studies were included in the analysis. GERD was significantly associated with an increased risk of several extraesophageal malignancies, including pharyngeal cancer (pooled RR = 2.04; 95% CI: 1.38–3.02), with a particularly high risk observed for hypopharyngeal cancer (RR = 2.95; 95% CI: 1.99–4.37; I² = 60.24%). Elevated risks were also identified for laryngeal cancer (RR = 2.23; 95% CI: 1.41–3.52) and lung cancer (RR = 1.20; 95% CI: 1.01–1.42). No significant association was found between GERD and colorectal cancer (RR = 1.19; 95% CI: 0.68–2.09), and findings regarding oral cancer were inconsistent across studies. Six MR studies confirmed a positive causal relationship between GERD and lung cancer, while one MR study suggested a potential causal association with oral cancer and another with pancreatic cancer. Conclusions: Our findings suggest that GERD may be a significant risk factor for pharyngeal, laryngeal and lung cancers. Appropriate evaluation and surveillance in patients with GERD may be warranted. Full article

(This article belongs to the Special Issue Cancer and Chronic Illness)

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19 pages, 1492 KB

Open AccessSystematic Review

Comparing Isocitrate Dehydrogenase Inhibitors with Procarbazine, Lomustine, and Vincristine Chemotherapy for Oligodendrogliomas

by Gerardo Duran, Diego Pichardo-Rojas, Ahmed Hashim Ali, Peter Passias, Angela Downes, Wilson Z. Ray, Gregory J. Zipfel, Hakeem J. Shakir, Andrew Bauer, Andrew Jea, Ian F. Dunn, Jeffrey A. Zuccato, Christopher S. Graffeo and M. Burhan Janjua

Cancers 2025, 17(23), 3880; https://doi.org/10.3390/cancers17233880 - 4 Dec 2025

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Abstract

The abstract has been submitted for presentation to the AANS 2026 meeting being held in San Antonio, TX, USA. Introduction: Oligodendrogliomas are an uncommon subset of gliomas that are molecularly defined by 1p/19q codeletion in the setting of an isocitrate dehydrogenase (IDH) 1/2 [...] Read more.

The abstract has been submitted for presentation to the AANS 2026 meeting being held in San Antonio, TX, USA. Introduction: Oligodendrogliomas are an uncommon subset of gliomas that are molecularly defined by 1p/19q codeletion in the setting of an isocitrate dehydrogenase (IDH) 1/2 mutation. Standard-of-care management involves maximal safe resection followed by adjuvant chemoradiation with procarbazine, lomustine, and vincristine (PCV). Although PCV confers a durable survival advantage, treatment-limiting toxicity is common and often necessitates discontinuation. IDH inhibitors such as vorasidenib have demonstrated promising efficacy and more favorable tolerability profiles, but a paucity of comparative data across therapeutic classes limits optimal treatment decision-making. Methods: A systematic search was conducted through to 7 March 2025 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Eligible studies included adult patients (≥18 years) with IDH-mutant, 1p/19q-codeleted oligodendrogliomas treated with PCV chemotherapy or IDH inhibitors and with a minimum follow-up of 12 months. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and grade ≥ 3 adverse events (AEs) that led to treatment discontinuation. Results: Twenty-eight studies met the inclusion criteria, with a total of 406 patients. All 406 patients carried a confirmed diagnosis of oligodendroglioma. For mixed-histology cohorts, only oligodendroglioma-specific data were extracted and analyzed. Among PCV cohorts, median PFS ranged from 24.3 months to 8.4 years and median OS was reported up to 14.7 years in long-term follow-up from RTOG 9402 and EORTC 26951. Grade ≥ 3 AEs resulted in treatment discontinuation in 65–70% of patients, primarily due to hematologic or neurologic events. In comparison, vorasidenib achieved a median PFS of 27.7 months in the phase III INDIGO trial (HR 0.39; 95% CI 0.27–0.56; p < 0.001), with median OS not yet reached at 14.2 months of follow-up. Grade ≥ 3 AEs occurred in 22.8% of patients and led to treatment discontinuation in only 1–3%, primarily due to asymptomatic transaminitis. Early real-world data from expanded-access programs similarly support these tolerability findings. Conclusions: While PCV chemotherapy remains the standard-of-care systemic therapy for oligodendroglioma supported by mature survival data, IDH inhibitors represent a mechanistically targeted alternative with encouraging early-phase outcomes and a significantly improved safety profile. Direct comparison across these regimens is constrained by differences in study design and limited long-term OS data for IDH inhibitors. Prospective head-to-head trials are essential for defining the optimal therapeutic sequence in this evolving treatment landscape. In the interim, we provide a recommend approach for current use. Full article

(This article belongs to the Special Issue Combination Therapies for Brain Tumors)

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12 pages, 1160 KB

Open AccessArticle

The Prognostic Role of Different Blood Cell Count-to-Lymphocyte Ratios in Patients with Lung Cancer at Diagnosis

by Ourania Papaioannou, Oraianthi Fiste, Eva Theohari, Fotios Sampsonas, Foteinos-Ioannis Dimitrakopoulos, Angelos Koutras, Ioannis Gkiozos, Ioannis Vathiotis, Elias Kotteas and Argyrios Tzouvelekis

Cancers 2025, 17(23), 3879; https://doi.org/10.3390/cancers17233879 - 4 Dec 2025

Viewed by 434

Abstract

Background: Lung cancer (LC) is a complex-to-treat disease and remains the leading cause of cancer-related mortality. Methods: Our aim was to investigate the prognostic role of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio [...] Read more.

Background: Lung cancer (LC) is a complex-to-treat disease and remains the leading cause of cancer-related mortality. Methods: Our aim was to investigate the prognostic role of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) in patients with LC. In this retrospective study, examining the period between 1 June 2020 and 31 May 2024, we recorded consecutive patients who presented to the Department of Respiratory Medicine, University Hospital of Patras, Patras, Greece, and received a first diagnosis of LC. The primary outcome was mortality risk analysis based on NLR, PLR, and MLR at diagnosis. Secondary outcomes included associations of tumor, node, metastasis (TNM) staging, and smoking with NLR, PLR, and MLR at diagnosis. Results: We identified 353 patients with a first diagnosis of LC. The mean age ± SD at the time of diagnosis was 68.1 ± 9.1 years. Most patients were male (77.9%, n = 275) and current or ex-smokers (58.1%, n = 205, and 39.1%, n = 138, respectively). Histological diagnosis was non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), and not otherwise specified (NOS) in 67.1% (n = 237), 29.8% (n = 105), and 3.1% (n = 11) of patients, respectively. Adenocarcinoma NSCLC was more common (40.2%, n = 142) compared to squamous NSCLC (25.5%, n = 90). In 12.9% of patients, we identified EGFR, KRAS, ALK, or BRAF molecular driver mutations, while PD-L1 expression was positive in 20.7% of patients. The majority of enrolled patients presented with advanced stage IV LC at diagnosis (63.2%, n = 223). Kaplan–Meier curves showed that patients with higher than the median NLR and PLR at diagnosis were associated with significantly higher mortality risk compared to those with lower than the median [HR: 0.58, (95% CI: 0.42 to 0.81) p = 0.0009 and HR: 0.71, (95% CI: 0.53 to 0.95) p = 0.02, respectively], while no differences in mortality risk were observed between patients with higher versus lower than the median MLR [HR: 0.84, (95% CI: 0.63 to 1.12) p = 0.22]. With regard to secondary outcomes, no associations between higher versus lower than the median NLR, PLR, or MLR values and TNM staging [4.0 (95% CI: 4.0–4.0) vs. 4.0 (95% CI: 4.0–4.0), p = 0.95, 4.0 (95% CI: 4.0–4.0) vs. 4.0 (95% CI: 4.0–4.0), p = 0.09, 4.0 (95% CI: 4.0–4.0) vs. 4.0 (95% CI: 4.0–4.0), p = 0.4, respectively], as well as smoking status [70 (95% CI: 60–80) vs. 80 (95% CI: 60–80), p = 0.10, 70 (95% CI: 60–80) vs. 80 (95% CI: 60–80), p = 0.46, 80 (95% CI: 60–80) vs. 70 (95% CI: 60–80), p = 0.96, respectively] were reported. Conclusions: NLR and PLR could serve as reliable and clinician-friendly prognosticators of clinical outcomes in patients with LC. Further validation cohorts are sorely needed to prove this notion. Full article

(This article belongs to the Special Issue The Role of Neutrophils in Tumor Progression and Metastasis)

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14 pages, 4302 KB

Open AccessArticle

Performance of an Artificial Intelligence Support System on Screening Mammography Cases Proceeding to Stereotactic Biopsy

by Anandita Mathur, Colleen McNally, Arielle Sasson, Nicholas Thoreson, Sadaf Sahraian, David S. Mendelson and Laurie R. Margolies

Cancers 2025, 17(23), 3878; https://doi.org/10.3390/cancers17233878 - 4 Dec 2025

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Abstract

Background/Objective: The objective was to evaluate the standalone performance of an AI system, Transpara 1.7.1 (ScreenPoint Medical), in screening mammography cases proceeding to stereotactic biopsy using histopathological results as ground truth. Methods: This retrospective study included 202 asymptomatic female patients (mean age: 57.8 [...] Read more.

Background/Objective: The objective was to evaluate the standalone performance of an AI system, Transpara 1.7.1 (ScreenPoint Medical), in screening mammography cases proceeding to stereotactic biopsy using histopathological results as ground truth. Methods: This retrospective study included 202 asymptomatic female patients (mean age: 57.8 years) who underwent stereotactic biopsy at a multicenter academic institution between October 2022 and September 2023 with a preceding screening mammogram within 14 months. Transpara AI risk scores were compared to pathology results (benign versus malignant). Performance metrics for AI including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) were calculated. Results: Transpara AI classified 20 of 39 malignant findings (51%) as elevated risk compared with 50 of 211 total findings (24%). AI score was positively correlated with malignancy (r = 0.29, p < 0.001). Sensitivity for detecting malignancy (classifying as intermediate or elevated risk) was 94.9% (95% CI: 81.4–94.1), specificity was 24.4% (95% CI: 18.3–31.7), PPV was 22.2% (95% CI: 16.3–29.4), and NPV was 95.5% (95% CI: 83.3–99.2). Transpara had fair performance in detecting breast cancer with AUC 0.73 (95% CI: 0.63–0.82). Conclusions: Transpara AI is a useful screening mammography triage tool. Given its high sensitivity and high negative predictive value, AI may be used to guide radiologists in making biopsy or follow up recommendations. However, the high false-positive rate and presence of two false negatives underscore the need for radiologists to use caution and clinical expertise when interpreting AI results. Full article

(This article belongs to the Special Issue Advances in Radiology for the Detection, Diagnosis, and Management of Breast Cancer)

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18 pages, 1169 KB

Open AccessArticle

The Role of Plasmacytoid Dendritic Cells in the Immune Contexture of TP53-Mutated High-Grade Serous Ovarian Cancer

by Katharina Steger, Heidelinde Fiegl, Katja Rungger, Katharina Leitner, Irina Tsibulak, Barin Feroz, Christoph Ebner, Christian Marth, Hubert Hackl and Alain Gustave Zeimet

Cancers 2025, 17(23), 3877; https://doi.org/10.3390/cancers17233877 - 3 Dec 2025

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Abstract

Background/Objectives: This study aimed to characterize dendritic cell (DC) heterogeneity, immune associations, and prognostic relevance across three TP53-mutated tumor entities—high-grade serous ovarian cancer (HGSOC), triple-negative breast cancer, and endometrial cancer—focusing on plasmacytoid DCs (pDCs) in HGSOC. Methods: RNA-sequencing and clinical [...] Read more.

Background/Objectives: This study aimed to characterize dendritic cell (DC) heterogeneity, immune associations, and prognostic relevance across three TP53-mutated tumor entities—high-grade serous ovarian cancer (HGSOC), triple-negative breast cancer, and endometrial cancer—focusing on plasmacytoid DCs (pDCs) in HGSOC. Methods: RNA-sequencing and clinical data of 603 patients from The Cancer Genome Atlas were analyzed. DC subset abundance was assessed for cDC progenitor, conventional DC type 1 (cDC1), conventional DC type 2 (cDC2), plasmacytoid DC (pDC), and mature DC by marker gene signatures. Differences in DC scores across tumors were analyzed using Kruskal–Wallis. Survival analyses were performed using Kaplan–Meier and Cox regression. Spearman’s correlation was used to determine associations between parameters. Results: HGSOC showed the lowest pDC abundance, yet high pDC scores were independently associated with shorter PFS (HR = 1.55, 95% CI: 1.05–2.27; p = 0.027), representing the only DC-subset-related prognostic signal observed across tumor types. pDCs correlated positively with neutrophils and negatively with monocytes, and pDCs, cDC2s, and cDC progenitors correlated inversely with TMB. No consistent link was found between pDC and TP53 mutation classes. However, tumors harboring specific TP53 mutations within established hotspot regions exhibited significantly lower pDC levels (p = 0.015). Conclusions: Our findings reveal distinct DC infiltration patterns and highlight the immunological vulnerability of TP53-mutated HGSOC. pDCs appear to exert a tumor-promoting, immune-evasive role, suggesting that DC function depends on their programming and tumor context. Selective targeting of DC subsets may offer novel therapeutic opportunities in TP53-mutated, low-TMB cancers. Full article

(This article belongs to the Special Issue Cancer Immunotherapy as Part of Precision Clinical Medicine)

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32 pages, 4475 KB

Open AccessArticle

CRISPR-Cas9 Genome and Double-Knockout Screening to Identify Novel Therapeutic Targets for Chemoresistance in Triple-Negative Breast Cancer

by Shuai Shao, Shangjia Li, Yang Huo, Shan Tang, Birkan Gökbağ, Kunjie Fan, Yirui Huang, Lingling Wang, Gregory Nagy, Jeffrey Parvin, Daniel Stover, Lijun Cheng and Lang Li

Cancers 2025, 17(23), 3876; https://doi.org/10.3390/cancers17233876 - 3 Dec 2025

Viewed by 842

Abstract

Background/Objectives: Triple-negative breast cancer (TNBC) accounts for 15 to 20% of breast cancer cases and contributes to a disproportionate 35% of breast cancer deaths. Its resistance to chemotherapy presents a significant challenge. Methods: We firstly compared transcriptomic profiles between TNBC cell [...] Read more.

Background/Objectives: Triple-negative breast cancer (TNBC) accounts for 15 to 20% of breast cancer cases and contributes to a disproportionate 35% of breast cancer deaths. Its resistance to chemotherapy presents a significant challenge. Methods: We firstly compared transcriptomic profiles between TNBC cell lines and patient samples and inferred the MDA-MB-231 cell line as the most representative model for TNBC with poor response to chemotherapy. We then conducted a genome-wide CRISPR-Cas9 screening and RNA-seq analysis in MDA-MB-231. Results: This analysis revealed 96 and 93 genes that could re-sensitize cisplatin and doxorubicin treatment, respectively, with 19 overlapping genes. Among these genes, 28 have been studied and published previously in chemoresistance research. MCM9 was found as a new TNBC chemoresistance target. Its target drug, KPT-185, showed an additive effect with cisplatin in treating TNBC cells. In the follow-up gene combination double-knockout experiment among 65 genes selected from cell death pathways, 242 synthetic lethal gene pairs were discovered to overcome chemoresistance in TNBC. Conclusions: In this study, we identified synthetic lethal targets in treating TNBC with cisplatin and doxorubicin through a genome-wide CRISPR-Cas9 screening and gene combination double-knockout screening. Full article

(This article belongs to the Section Cancer Therapy)

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8 pages, 705 KB

Open AccessViewpoint

Rethinking EPO: A Paradigm Shift in Oncology?

by Jean-Marc Ferrero, Baharia Mograbi, Rym Bouriga, Jocelyn Gal and Gérard Milano

Cancers 2025, 17(23), 3875; https://doi.org/10.3390/cancers17233875 - 3 Dec 2025

Viewed by 608

Abstract

Erythropoietin (EPO) is a hormone mainly produced by the kidney. EPO stimulates red blood cell production in response to hypoxia. EPO represents one of the most compelling paradoxes in medical oncology. For decades, recombinant EPO has been prescribed as an effective therapy for [...] Read more.

Erythropoietin (EPO) is a hormone mainly produced by the kidney. EPO stimulates red blood cell production in response to hypoxia. EPO represents one of the most compelling paradoxes in medical oncology. For decades, recombinant EPO has been prescribed as an effective therapy for cancer-related anemia and fatigue, significantly improving patients’ quality of life while reducing their dependence on blood transfusions. Yet, accumulating scientific evidence knowledge has highlighted the complex interactions between EPO and tumor biology that extend well beyond its hematopoietic functions. The putative expression of EPO receptors on tumor cells has raised concerns about a potential role of EPO in promoting tumor progression, although conclusive clinical evidence remains lacking. Recent studies have revealed that EPO may contribute to immunosuppressive mechanisms within the tumor microenvironment, thereby reshaping our understanding of its risk/benefit profile in oncology. This evolving body of evidence calls for an objective reassessment of EPO’s dual nature as both a therapeutic ally and a potential oncological threat, in order to bring more caution around decision-making in the current era of strongly evolving cancer care. Full article

(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025)

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18 pages, 445 KB

Open AccessArticle

Exploring the Coordination of Cancer Care for Teenagers and Young Adults in England and Wales: BRIGHTLIGHT_2021 Rapid Qualitative Study

by Elysse Bautista-Gonzalez, Rachel M. Taylor, Lorna A. Fern, Julie A. Barber, Jamie Cargill, Rozalia Dobrogowska, Richard G. Feltbower, Laura Haddad, Nicolas Hall, Maria Lawal, Martin G. McCabe, Sophie Moniz, Louise Soanes, Dan P. Stark and Cecilia Vindrola-Padros

Cancers 2025, 17(23), 3874; https://doi.org/10.3390/cancers17233874 - 3 Dec 2025

Viewed by 386

Abstract

Background: Commissioning of ‘joint care’ across teenage and young adult (TYA) principal treatment centres (PTC) and regional designated hospitals was introduced to enable cancer care closer to home, while providing support through the TYA multidisciplinary team. We aimed to explore the processes being [...] Read more.

Background: Commissioning of ‘joint care’ across teenage and young adult (TYA) principal treatment centres (PTC) and regional designated hospitals was introduced to enable cancer care closer to home, while providing support through the TYA multidisciplinary team. We aimed to explore the processes being used to enable inter-organisational collaboration under joint care models through rapid ethnography. Methods: Healthcare professionals in TYA PTCs in England and Wales between June 2022 and December 2023 were identified by the TYA lead in each PTC as delivering TYA cancer care. Semi-structured interviews were conducted virtually or by telephone based on the structuration model of collaboration proposed by D’Amour. Data were analysed against the model through framework analysis. Results: Our study highlighted variation across the different dimensions of inter-organisational collaboration. We found that healthcare professionals delivering TYA cancer care were working toward a shared goal but this was not always achieved. Social interaction between professionals was required to develop relationships and trust, but opportunities for social interaction were not regularly available. Processes for sharing information were not streamlined, so there were instances when information could not be shared between organisations. Interventions to achieve coordinated care, such as an outreach team, supported the delivery of joint care but these were not available in every region. While there were some levels of leadership within aspects of services, there were limited examples nationally or across geographical regions, which hindered the development of coordinated care. Conclusions: Coordination of care is mostly developing; however, the shared vision and goals dimension did achieve full active collaboration. The implementation of a service specification will address regional leadership requirements, but resources are required to extend the delivery of interventions to support coordination and collaboration, allowing the commissioned model of care to be delivered safely. Full article

(This article belongs to the Special Issue New Developments in Adolescent and Young Adult Oncology)

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13 pages, 5164 KB

Open AccessReview

Emerging Role of Transcutaneous Ultrasound in the Diagnostic of Lung Cancer

by Corinna Trenker-Burchert, Marius Dohse, Hajo Findeisen, Andreas Schuler and Christian Görg

Cancers 2025, 17(23), 3873; https://doi.org/10.3390/cancers17233873 - 2 Dec 2025

Viewed by 495

Abstract

Lung cancer is one of the most commonly diagnosed malignancies worldwide and continues to be a leading cause of cancer-related mortality. Precise staging is crucial for predicting outcomes and directing treatment decisions. Current international guidelines mainly recommend imaging techniques like CT and PET-CT, [...] Read more.

Lung cancer is one of the most commonly diagnosed malignancies worldwide and continues to be a leading cause of cancer-related mortality. Precise staging is crucial for predicting outcomes and directing treatment decisions. Current international guidelines mainly recommend imaging techniques like CT and PET-CT, with limited references to transcutaneous ultrasound, which is only suggested in particular clinical cases. Ultrasound provides real-time imaging, high resolution in near-field structures, and the ability to assess thoracic wall infiltration, supraclavicular and cervical lymph nodes, pleural effusions, and metastatic lesions. Furthermore, ultrasound-guided biopsies can enable quick and safe histological confirmation of accessible lesions. Based on these advantages and a review of current literature, we propose that integrating ultrasound into staging algorithms could improve diagnostic efficiency, decrease invasive procedures, and support prompt treatment planning. We also highlight the need for further research in this area. Full article

(This article belongs to the Special Issue Advances in Lung Ultrasound in Cancer Patients)

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11 pages, 1045 KB

Open AccessArticle

Processed Transcript Insertion as a Novel Germline Mutational Mechanism in BRCA1-Associated Hereditary Breast Cancer

by Anikó Bozsik, Henriett Butz, Vince Kornél Grolmusz, Petra Nagy, Tímea Pócza, Erika Tóth, Erzsébet Csernák, Attila Patócs and János Papp

Cancers 2025, 17(23), 3872; https://doi.org/10.3390/cancers17233872 - 2 Dec 2025

Viewed by 356

Abstract

Background/Objectives: Germline BRCA1 mutations account for ~15–20% of hereditary breast and ovarian cancer (HBOC) cases. While most are small sequence variants, structural rearrangements also contribute significantly to the pathogenic landscape. Conventional diagnostic workflows often miss such events, underscoring the need for comprehensive [...] Read more.

Background/Objectives: Germline BRCA1 mutations account for ~15–20% of hereditary breast and ovarian cancer (HBOC) cases. While most are small sequence variants, structural rearrangements also contribute significantly to the pathogenic landscape. Conventional diagnostic workflows often miss such events, underscoring the need for comprehensive approaches. Here, we report a previously undescribed pathogenic mechanism—a transposon-mediated processed transcript insertion—expanding the mutational spectrum underlying hereditary breast cancer susceptibility. Methods: The studied case was discovered during our germline genotyping routine: next-generation sequencing followed by library preparation with a custom hereditary cancer panel. The identified variant was validated by orthogonal sequencing and multiplex ligation-dependent probe amplification (MLPA). RNA-level functional assays, including nonsense-mediated decay inhibition, were conducted to assess transcript stability. Constitutional origin was confirmed by analysis of multiple normal tissues, and tumor material was evaluated for loss of heterozygosity (LOH). Results: NGS detected a 700 bp insertion in exon 16 of BRCA1, corresponding to a complete processed transcript of RPL18A. The insertion caused a frameshift and premature stop codon, triggering degradation of the aberrant transcript. The variant was present in multiple somatic tissues, and its heritable nature was further confirmed by genotyping a first-degree relative, who was also found to carry the insertion. Tumor DNA analysis revealed strong LOH with retention of the variant allele. Conclusions: This study identifies, for the first time, a heritable processed transcript insertion as a pathogenic event in BRCA1. Such variants are undetectable by conventional diagnostic workflows lacking structural variant analysis, highlighting the importance of comprehensive approaches for accurate diagnosis and genetic counselling in hereditary cancer syndromes. Full article

(This article belongs to the Special Issue Sequence Variants in Breast/Ovarian Cancer Susceptibility Genes: From Risk Assessment to Clinical Management in Carrier Individuals and Their Blood Relatives)

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28 pages, 1673 KB

Open AccessReview

Immunological Crossroads: Optimizing Antirejection Regimens to Sustain Antitumor Immunity in Liver Transplant Recipients with Hepatocellular Carcinoma

by Chao Zhang, Xin Yuan and Kunlin Xie

Cancers 2025, 17(23), 3871; https://doi.org/10.3390/cancers17233871 - 2 Dec 2025

Viewed by 634

Abstract

Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC). However, lifelong immunosuppressive therapy required to prevent graft rejection inevitably compromises antitumor immunity, thereby increasing the risk of HCC recurrence and metastasis, particularly common in the lungs. This review delves into the [...] Read more.

Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC). However, lifelong immunosuppressive therapy required to prevent graft rejection inevitably compromises antitumor immunity, thereby increasing the risk of HCC recurrence and metastasis, particularly common in the lungs. This review delves into the complex dynamic equilibrium between immune cell subsets mediating rejection and antitumor immunity, systematically analyzes the impact of current immunosuppressive regimens on this balance, and highlights emerging strategies aimed at minimizing rejection while preserving or enhancing antitumor efficacy. These strategies include immunosuppressive regimen optimization, such as mTOR inhibitor application and calcineurin inhibitor (CNI) minimization, novel immunotherapies, including immune checkpoint inhibitors (ICIs) and adoptive cell therapy (ACT), and immune tolerance induction. This review also summarizes advances in biomarker research guiding immunosuppressant withdrawal, aiming to provide a theoretical basis and clinical insights for personalized immunotherapy strategies and comprehensive tumor management in LT recipients with HCC. Full article

(This article belongs to the Section Cancer Immunology and Immunotherapy)

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25 pages, 372 KB

Open AccessReview

Current Immunotherapy Strategies and Emerging Biomarkers for the Treatment of Hepatocellular Carcinoma

by Audrey Kapelanski-Lamoureux, Anthoula Lazaris, Nicholas Meti and Peter Metrakos

Cancers 2025, 17(23), 3870; https://doi.org/10.3390/cancers17233870 - 2 Dec 2025

Viewed by 1199

Abstract

Background/Objectives: Hepatocellular carcinoma (HCC), the predominant form of liver cancer, ranks as the third leading cause of cancer-related deaths worldwide. With the shift from viral hepatitis to metabolically dysfunction-associated steatosis liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) as primary etiologies, we aimed [...] Read more.

Background/Objectives: Hepatocellular carcinoma (HCC), the predominant form of liver cancer, ranks as the third leading cause of cancer-related deaths worldwide. With the shift from viral hepatitis to metabolically dysfunction-associated steatosis liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) as primary etiologies, we aimed to review ongoing clinical trials in adult HCC patients to highlight emerging treatments, particularly for nonviral HCC cases. Methods: We searched ClinicalTrial.gov (last March 2025) for interventional trials. We included ongoing (recruiting/active/not recruiting), phase I-IV, adults (>18 years old), and HCC-focused only clinical trials. We excluded observational and interventional (biological, genetic, device, or procedure) clinical trials. Results: This review highlights recent advances in HCC treatment, with a focus on the transformative role of immunotherapy. Evidence suggests that nonviral HCC, as well as HCC with MASLD/MASH background livers, may have reduced sensitivity to immunotherapy. Thus, there is a critical need for molecular insights to improve patient stratification. Moreover, we examine how new diagnostic tools, including liquid biopsies, influence treatment decisions and aid in monitoring responses. Limitations limited MASLD/MASH-specific trial data. Conclusions: We review current research and its integration into clinical practice, advancing HCC therapy toward personalized, patient-centered care. Full article

(This article belongs to the Special Issue Tumor Microenvironment Dynamics in Hepatocellular Carcinoma)

20 pages, 5495 KB

Open AccessArticle

Canady Helios Cold Plasma Induces Non-Thermal (24 °C), Non-Contact Irreversible Electroporation and Selective Tumor Cell Death at Surgical Margins

by Saravana R. K. Murthy, Taisen Zhuang, Olivia Z. Jones, Yasmine Dakak, Michael Keidar, Aviram Nissan and Jerome Canady

Cancers 2025, 17(23), 3869; https://doi.org/10.3390/cancers17233869 - 2 Dec 2025

Viewed by 664

Abstract

Background: The Canady Helios Cold Plasma (CHCP) system is a non-thermal, non-contact cold atmospheric plasma technology that generates transient electric fields and reactive species capable of disrupting cancer cell membranes. This study investigated the voltage-dependent membrane irreversible electroporation (IRE) dynamics induced by CHCP [...] Read more.

Background: The Canady Helios Cold Plasma (CHCP) system is a non-thermal, non-contact cold atmospheric plasma technology that generates transient electric fields and reactive species capable of disrupting cancer cell membranes. This study investigated the voltage-dependent membrane irreversible electroporation (IRE) dynamics induced by CHCP across biologically distinct breast cancer subtypes. Methods: Four breast cancer cell lines, triple-negative (MDA-MB-231 and Hs578T), ER⁺/PR⁺/HER2⁻ (MCF-7), and ER⁺/PR⁺/HER2⁺ (BT-474), were exposed to CHCP for 5 min at 25 V (~1675 V/cm PTEF) or 30 V (~2010 V/cm), either directly or with Plasma Activated Media (PAM). Membrane permeability was assessed by propidium iodide (PI) uptake over 120 min. Morphological changes were evaluated microscopically. Functional electroporation was examined via BCL2A1-targeting siRNA delivery and clonogenic survival. Ex vivo analyses of Phase I clinical trial tumor specimens (NCT04267575) were performed to characterize CHCP-induced tissue responses. Results: CHCP produced voltage- and time-dependent membrane permeabilization in all breast cancer cell lines, with 30 V generating robust and sustained PI uptake compared to transient effects at 25 V. Treated cells exhibited morphological features consistent with membrane disruption. CHCP enabled intracellular siRNA delivery and significantly reduced clonogenic potential, confirming functional pore formation. Ex vivo CHCP treatment selectively damaged tumor cells while sparing adjacent non-cancerous tissue. Conclusions: This study demonstrates CHCP as a non-thermal (24 °C), non-contact plasma-based IRE platform which induces controlled membrane permeabilization and selective cancer cell death. CHCP offers a translational strategy to eradicate residual tumor cells at the surgical margins, and prevent local recurrence, positioning it as a versatile adjunct in precision surgical oncology. Full article

(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025)

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18 pages, 526 KB

Open AccessArticle

Does Joint Care Impact Teenage and Young Adult’s Patient-Reported Outcomes After a Cancer Diagnosis? Results from BRIGHTLIGHT_2021

by Lorna A. Fern, Elysse Bautista-Gonzalez, Julie A. Barber, Jamie Cargill, Richard G. Feltbower, Laura Haddad, Maria Lawal, Martin G. McCabe, Safia Samih, Louise Soanes, Dan P. Stark, Cecilia Vindrola-Padros and Rachel M. Taylor

Cancers 2025, 17(23), 3868; https://doi.org/10.3390/cancers17233868 - 2 Dec 2025

Viewed by 547

Abstract

Background: Healthcare policy in the United Kingdom recognizes that teenagers and young adults (TYA:16–24 years at diagnosis) require specialist care. In England, Principal Treatment Centers (PTCs) exist, delivering enhanced care exclusively within the PTC or as ‘joint care’ with designated hospitals (DHs). We [...] Read more.

Background: Healthcare policy in the United Kingdom recognizes that teenagers and young adults (TYA:16–24 years at diagnosis) require specialist care. In England, Principal Treatment Centers (PTCs) exist, delivering enhanced care exclusively within the PTC or as ‘joint care’ with designated hospitals (DHs). We examined whether joint care impacted patient-reported outcomes when compared to care at one site. Methods: A cross-sectional survey was conducted in England, Scotland, and Wales. This included validated measures of quality of life (QoL), anxiety and depression, health status, social support, and illness perception. Comparisons were made based on young people’s exposure to specialist care within 6 months of diagnosis, defined as care in a TYA PTC: all-TYA-care (all care in a TYA unit), no-TYA-care (no care in a TYA unit, care delivered in a children’s/adult unit only), and joint-care (care in a TYA-PTC and in a children’s/adult unit). Results: Overall, 260/1009 (25.8%) participants responded (England n = 241; Scotland/Wales n = 19). Due to different healthcare policies, statistical analysis was applied to England only. Mean QoL scores were <69.7, the threshold indicating impaired QoL (mean 58.65, standard deviation 20.13). After adjustment for confounding factors, no clinically significant differences in mean QoL between categories existed. The adjusted mean difference for all-TYA-care (n = 66) versus no-TYA-care (n = 89) was −2.28 units (95% confidence interval (CI: −8.85 to 4.29) and for joint-care versus no-TYA-care (n = 85), −4.35 units (CI: −10.34 to 1.63). Similarly, no notable differences in social support, anxiety, depression, or illness perception between categories existed. Patients receiving all-TYA-care had a lower average health status compared with no-TYA-care (difference in means −0.09 (CI:−0.18 to −0.01). Conclusions: No evidence that patient-reported outcomes differ by categories of care existed. This may suggest the evolution of TYA cancer services has led to similar outcomes regardless of care category. However, given the small sample size it is not possible to draw firm conclusions. Full article

(This article belongs to the Special Issue New Developments in Adolescent and Young Adult Oncology)

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39 pages, 2332 KB

Open AccessReview

SARS-CoV2 and Anti-COVID-19 mRNA Vaccines: Is There a Plausible Mechanistic Link with Cancer?

by Ciro Isidoro

Cancers 2025, 17(23), 3867; https://doi.org/10.3390/cancers17233867 - 2 Dec 2025

Viewed by 6146

Abstract

To contrast the COVID-19 pandemic brought by the corona virus SARS-CoV-2, two mRNA-based anti-COVID-19 vaccines (by Pfizer-BioNTech and Moderna) were made available relatively quickly and deployed worldwide based on an emergency approval. Being considered vulnerable and at risk of infection, cancer patients have [...] Read more.

To contrast the COVID-19 pandemic brought by the corona virus SARS-CoV-2, two mRNA-based anti-COVID-19 vaccines (by Pfizer-BioNTech and Moderna) were made available relatively quickly and deployed worldwide based on an emergency approval. Being considered vulnerable and at risk of infection, cancer patients have been prioritized for COVID-19 vaccination and vaccinated repeatedly because of the short time protection provided by these vaccines. Recently, a surge in the incidence and rapid progression of cancers has been observed in many countries, which could (at least partially) represent cancers undiagnosed or untreated during the pandemic. It has also been suggested that the SARS-CoV-2 itself or even the anti-COVID-19 mRNA vaccines could have contributed to the recurrence and worse clinical outcome in cancer patients, given the high incidence of COVID-19 in hospitalized patients and that these patients have been vaccinated with priority several times and in a short period. Although it appears extremely unlikely that SARS-CoV-2 and anti-COVID-19 mRNA vaccines elicit genotoxic events and cause neo-cancerogenesis in a short time, they could still cause non-genotoxic pro-carcinogenic effects by triggering an exaggerated inflammatory reaction, compromising immune homeostasis, stimulating cell proliferation, and negatively affecting cellular stress response and damage repair machinery. This could result in the promotion of regrowth of dormant micrometastases or relapses of stable minimal residual disease. Such a harmful outcome may likely result from a synergy between the virus and the vaccine, especially in multi-vaccinated and multi-infected individuals. Here, I bring the cell pathologist’s point of view and discuss the multiple possible mechanisms by which the virus and the anti-COVID-19 mRNA vaccine might favor tumorigenesis. While a causal link cannot be established at this stage, knowledge of potential carcinogenic risks could help doctors and health policymakers take the best actions to protect vulnerable patients and convince the vaccine developer to design a vaccine free from such harm. Full article

(This article belongs to the Special Issue Mastering the Immunosuppressive Tumor Microenvironment with Cancer Vaccines)

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29 pages, 15316 KB

Open AccessReview

Pleural Mesothelioma Diagnosis for the Pulmonologist: Steps Along the Way

by Alberto Fantin, Nadia Castaldo, Ernesto Crisafulli, Giulia Sartori, Filippo Patrucco, Horiana B. Grosu, Paolo Vailati, Giuseppe Morana, Vincenzo Patruno, Stefano Kette, Avinash Aujayeb and Aleš Rozman

Cancers 2025, 17(23), 3866; https://doi.org/10.3390/cancers17233866 - 1 Dec 2025

Viewed by 675

Abstract

Background/Objectives: Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis and complex diagnostic pathways. Pulmonologists often play a central role in its initial recognition and investigation. This narrative review synthesizes the current evidence on the diagnostic approach to [...] Read more.

Background/Objectives: Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis and complex diagnostic pathways. Pulmonologists often play a central role in its initial recognition and investigation. This narrative review synthesizes the current evidence on the diagnostic approach to MPM, with emphasis on imaging, tissue sampling, histopathology, and emerging diagnostic innovations relevant to clinical pulmonology. Methods: English-language studies published between January 2005 and June 2025 were identified from PubMed and Scopus. International guidelines and consensus documents were also reviewed to provide an updated overview of diagnostic strategies. Results: Diagnosis of MPM relies on a stepwise integration of clinical, radiological, and pathological information. Thoracic ultrasound, computed tomography, positron emission computed tomography and magnetic resonance imaging complement each other across different stages of the diagnostic pathway. Image-guided pleural biopsy and medical thoracoscopy remain the gold standard for tissue confirmation, supported by immunohistochemistry and molecular testing. The 2021 World Health Organization classification of pleural tumors and the International Association Study of Lung Cancer 9th Edition Tumour-Node-Mestastatis system have refined histologic and staging criteria, thereby improving reproducibility and prognostic accuracy. Emerging tools, including liquid biopsy, novel serum and molecular biomarkers, artificial-intelligence-based radiomics, and breathomics, offer promise for earlier and less invasive diagnosis but require prospective validation. Conclusions: Current advances are redefining MPM diagnosis toward integrated, multidisciplinary, and precision-based models. Future priorities include standardizing diagnostic algorithms, validating minimally invasive biomarkers, and integrating AI and molecular profiling into clinical workflows to enhance patient stratification. Full article

(This article belongs to the Special Issue Mesothelioma: Diagnosis and Therapy)

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11 pages, 464 KB

Open AccessArticle

Pericardial Mesothelioma: Diagnostic and Therapeutic Management, a Population-Based Study in Italy

by Simona Stella, Dario Consonni, Giovanni Luca Ceresoli, Barbara Dallari, Riccardo Perduri, Cinzia Storchi, Enrica Migliore, Manuela Gangemi, Carlo Genova, Lucia Benfatto, Vera Comiati, Valentina Zabeo, Sara Piro, Lucia Giovannetti, Iolanda Grappasonni, Cristiana Pascucci, Francesca Larese Filon, Flavia D’Agostin, Luigi Vimercati, Ilaria Cozzi, Franco Calista, Giuseppe Cascone, Italo Francesco Angelillo, Alessandra Binazzi, Alessandro Marinaccio and Carolina Mensi Show full author list Hide full author list

Cancers 2025, 17(23), 3865; https://doi.org/10.3390/cancers17233865 - 1 Dec 2025

Viewed by 393

Abstract

Background: Pericardial mesothelioma (PM) is an extremely rare cancer with a poor prognosis and no consensus on diagnostic and therapeutic management. We conducted a registry-based study on PM cases in Italy diagnosed between 1993 and 2021. Methods: Based on data from the Italian [...] Read more.

Background: Pericardial mesothelioma (PM) is an extremely rare cancer with a poor prognosis and no consensus on diagnostic and therapeutic management. We conducted a registry-based study on PM cases in Italy diagnosed between 1993 and 2021. Methods: Based on data from the Italian National Mesothelioma Registry (ReNaM), we performed a descriptive analysis of PM cases including clinical presentation, diagnostic work-up, asbestos exposure, and therapeutic management. Overall survival was calculated. Hazard ratios (HRs) and 95% confidence intervals (CI) for selected variables were estimated with univariate and multivariate Cox models. Results: We identified 72 cases (46 men and 26 women). Median age was 66 years (range 22–89). The most frequent histological subtypes were epithelioid and unspecified mesothelioma. Almost two-thirds of cases had been exposed to asbestos. The most common clinical presentation was pericardial effusion. Overall median survival was 2.8 months (95% CI 1.2–6.6) and older age at diagnosis was a negative prognostic factor. Clinical and treatment data were available for 47 patients (65%). Approximately one out of two patients underwent surgery (palliative, in one-third of cases). Adjuvant therapy was administered to seven patients (15%). In cases with treatment information, sarcomatoid subtype (HR 2.74, 95% CI: 1.06–7.06) was a negative prognostic factor; adjuvant therapy was associated with better survival (HR 0.38, 95% CI 0.14–1.02), but confounding by indication cannot be excluded. Conclusions: We confirmed the very poor prognosis of PM. An international network collecting PM cases with treatment information is needed to improve patient quality of life and survival. Full article

(This article belongs to the Special Issue Mesothelioma Epidemiology, Pathogenesis, Emerging Treatments and Pre-Clinical Models)

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26 pages, 358 KB

Open AccessReview

Rationale and Emerging Evidence on the Potential Role of HoLEP-Mediated Relief of Bladder Outlet Obstruction in NMIBC Outcomes Through Optimal Management of Chronic Urinary Retention

by Angelo Porreca, Filippo Marino, Davide De Marchi, Marco Giampaoli, Daniele D’Agostino, Francesca Simonetti, Mauro Ragonese, Antonio Amodeo, Paolo Corsi, Francesco Claps and Luca Di Gianfrancesco

Cancers 2025, 17(23), 3864; https://doi.org/10.3390/cancers17233864 - 1 Dec 2025

Viewed by 461

Abstract

Background: Non-muscle-invasive bladder cancer (NMIBC) represents approximately 70–75% of newly diagnosed bladder cancers and is characterized by high recurrence rates despite guideline-based management. Chronic urinary retention and bladder outlet obstruction (BOO) have been proposed as under-recognized modifiers of NMIBC outcomes through prolonged exposure [...] Read more.

Background: Non-muscle-invasive bladder cancer (NMIBC) represents approximately 70–75% of newly diagnosed bladder cancers and is characterized by high recurrence rates despite guideline-based management. Chronic urinary retention and bladder outlet obstruction (BOO) have been proposed as under-recognized modifiers of NMIBC outcomes through prolonged exposure to urinary carcinogens, inflammation, and altered intravesical pharmacokinetics. This narrative review qualitatively synthesizes biological and clinical evidence linking BOO-related dysfunction with NMIBC behavior and explores the emerging, but preliminary, role of Holmium Laser Enucleation of the Prostate (HoLEP) as a functional adjunct in selected patients. Methods: A narrative review was conducted according to SANRA guidelines. PubMed/MEDLINE, Embase, and Scopus were searched (January 2000–October 2025) using predefined terms for NMIBC, BOO, urinary retention, and HoLEP. Two reviewers independently screened records, with disagreements resolved by consensus. Sixty-one studies met inclusion criteria. Results: Elevated postvoid residual (PVR) (>80–100 mL) and moderate to severe lower urinary tract symptoms (LUTS) were consistently associated with higher NMIBC recurrence rates, independent of tumor stage and grade, in heterogeneous cohorts. Retention correlated with reduced efficacy of Bacillus Calmette–Guérin (BCG) and mitomycin C, likely via uneven drug distribution and a chronically inflamed urothelium. Mechanistic data support a plausible link between BOO-related inflammation, barrier dysfunction, and tumor biology, although direct biomarker correlations with PVR or pharmacokinetic studies are lacking. HoLEP provides durable relief of BOO, reduces PVR, and improves LUTS. Limited retrospective data suggest an association between HoLEP and lower recurrence, but these observations are confounded and should be viewed as hypothesis-generating. Conclusions: Chronic urinary retention and BOO appear to be modifiable functional factors that may influence NMIBC recurrence and intravesical therapy performance. HoLEP is a promising option to optimize bladder emptying in carefully selected patients, but its oncologic impact remains unproven and should be considered hypothesis-generating pending prospective, risk-adjusted studies. Full article

(This article belongs to the Special Issue Clinical and Translational Research of Urological Cancer)

32 pages, 973 KB

Open AccessReview

Circulating Biomarkers and Targeted Therapy in Pleural Mesothelioma

by Christopher R. Grant, Lyudmila Bazhenova and Karen M. Yun

Cancers 2025, 17(23), 3863; https://doi.org/10.3390/cancers17233863 - 1 Dec 2025

Viewed by 825

Abstract

Pleural mesothelioma (PM) is a rare and aggressive cancer. Standard of care for unresectable disease consists of chemotherapy, vascular endothelial growth factor inhibition, immunotherapy, or combinations thereof. Despite recent therapeutic advances, validated diagnostic and prognostic biomarkers are lacking, and no targeted therapies have [...] Read more.

Pleural mesothelioma (PM) is a rare and aggressive cancer. Standard of care for unresectable disease consists of chemotherapy, vascular endothelial growth factor inhibition, immunotherapy, or combinations thereof. Despite recent therapeutic advances, validated diagnostic and prognostic biomarkers are lacking, and no targeted therapies have been approved by the U.S. Food and Drug Administration (FDA) to date. Given the growing body of research investigating molecular alterations in PM, this review summarizes emerging diagnostic and prognostic biomarkers, discusses potentially targetable molecular alterations, and examines ongoing trials directed at targeting specific molecular mechanisms in this disease. Full article

(This article belongs to the Special Issue Biomarkers and Targeted Therapy in Malignant Pleural Mesothelioma)

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31 pages, 1513 KB

Open AccessReview

Natural Killer (NK) Cell-Based Therapies Have the Potential to Treat Ovarian Cancer Effectively by Targeting Diverse Tumor Populations and Reducing the Risk of Recurrence

by Kawaljit Kaur

Cancers 2025, 17(23), 3862; https://doi.org/10.3390/cancers17233862 - 1 Dec 2025

Viewed by 1637

Abstract

Ovarian cancer is the sixth leading cause of cancer-related deaths among women in the United States. This complex disease arises from tissues such as the ovarian surface epithelium, fallopian tube epithelium, endometrium, or ectopic Müllerian components and is characterized by diverse histological and [...] Read more.

Ovarian cancer is the sixth leading cause of cancer-related deaths among women in the United States. This complex disease arises from tissues such as the ovarian surface epithelium, fallopian tube epithelium, endometrium, or ectopic Müllerian components and is characterized by diverse histological and molecular traits. Standard treatments like surgery, chemotherapy, and radiation have limited effectiveness and high toxicity. Targeted therapies, including poly (ADP-ribose) polymerase PARP inhibitors, anti-angiogenics, and immune checkpoint inhibitors (ICIs), face obstacles such as adaptive resistance and microenvironmental barriers that affect drug delivery and immune responses. Factors in the tumor microenvironment, such as dense stroma, hypoxia, immune suppression, cancer stem cells (CSCs), and angiogenesis, can reduce drug efficacy, worsen prognosis, and increase the risk of recurrence. Research highlights impaired immune function in ovarian cancer patients as a contributor to recurrence, emphasizing the importance of immunotherapies to target tumors and restore immune function. Preclinical studies and early clinical trials found that natural killer (NK) cell-based therapies have great potential to tackle ovarian tumors. This review explores the challenges and opportunities in treating ovarian cancer, focusing on how NK cells could help overcome these obstacles. Recent findings reveal that engineered NK cells, unlike their primary NK cells, can destroy both stem-like and differentiated ovarian tumors, pointing to their ability to target diverse tumor types. Animal studies on NK cell therapies for solid cancers have shown smaller tumor sizes, tumor differentiation in vivo, recruitment of NK and T cells in the tumor environment and peripheral tissues, restored immune function, and fewer tumor-related systemic effects—suggesting a lower chance of recurrence. NK cells clinical trials in ovarian cancer patients have also shown encouraging results, and future directions include combining NK cell therapies with standard treatments to potentially boost effectiveness. Full article

(This article belongs to the Special Issue New Insights into Cancer Immunotherapy: From Immune Cell to Clinical Practice)

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18 pages, 863 KB

Open AccessReview

From Fibrosis to Malignancy: Mechanistic Intersections Driving Lung Cancer Progression

by Bing Chen, Hayam Hamdy, Xu Zhang, Pengxiu Cao, Yi Fu and Junling Shen

Cancers 2025, 17(23), 3861; https://doi.org/10.3390/cancers17233861 - 1 Dec 2025

Viewed by 772

Abstract

Background/Objectives: Pulmonary fibrosis (PF) and lung cancer (LC) are major global health challenges that share several pathogenic mechanisms despite their distinct clinical features. PF leads to progressive fibrotic remodeling and respiratory decline, while LC is characterized by uncontrolled proliferation, invasion, and metastasis. Growing [...] Read more.

Background/Objectives: Pulmonary fibrosis (PF) and lung cancer (LC) are major global health challenges that share several pathogenic mechanisms despite their distinct clinical features. PF leads to progressive fibrotic remodeling and respiratory decline, while LC is characterized by uncontrolled proliferation, invasion, and metastasis. Growing evidence shows that PF markedly increases the risk of LC development. This review aims to clarify the convergent molecular and cellular mechanisms that link fibrogenesis to tumorigenesis. Methods: Published studies exploring shared pathogenic pathways, molecular signaling networks, immune microenvironment alterations, and mitochondrial and genomic disturbances in PF and LC were systematically examined and integrated to identify common mechanisms contributing to fibrosis-associated carcinogenesis. Results: Findings highlight several overlapping processes between PF and LC, including oxidative stress, genomic instability, dysregulated DNA damage repair, immune microenvironment remodeling, mitochondrial dysfunction, and alterations in the ubiquitin–proteasome system. These aberrations drive chronic inflammation, epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and other hallmarks shared by both diseases. Key signaling pathways—such as transforming growth factor-β (TGF-β), programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1), and tumor microenvironment–mediated immune evasion—further contribute to disease progression and increased LC risk in PF patients. Conclusions: Integrating molecular and pathological insights reveals a strong biological continuum between PF and LC. Understanding these convergent mechanisms may facilitate the identification of diagnostic biomarkers and therapeutic targets, ultimately helping to mitigate PF-associated lung carcinogenesis. Full article

(This article belongs to the Section Cancer Pathophysiology)

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15 pages, 2162 KB

Open AccessArticle

The Immune Landscape of Canine Soft Tissue Sarcomas as a Model for Human Soft Tissue Sarcomas

by Regina Hayburn, Dongjun Chung, Arkobato Gupta, Shane Sills, Jennifer Donglan Wu, Andy Ambrus, Weiqing Jing, Juliana Ng, Pablo Penaloza-MacMaster, Aubrie Selmek, Seth M. Pollack and Shay Bracha

Cancers 2025, 17(23), 3860; https://doi.org/10.3390/cancers17233860 - 30 Nov 2025

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Abstract

Background/Objectives: Soft tissue sarcomas (STS) remain a therapeutic challenge due to their limited response to radiation and conventional chemotherapies. While recent advances in immunotherapy have improved outcomes in several cancers, these strategies have been largely disappointing in STS patients. Naturally occurring STS in [...] Read more.

Background/Objectives: Soft tissue sarcomas (STS) remain a therapeutic challenge due to their limited response to radiation and conventional chemotherapies. While recent advances in immunotherapy have improved outcomes in several cancers, these strategies have been largely disappointing in STS patients. Naturally occurring STS in dogs have been suggested as a spontaneous, immunocompetent model of human STS, but further characterization of its tumor immune microenvironment is needed to validate its relevance. This study aimed to identify the shared immune-related components of canine and human STS and to determine how these factors influence the tumor biology, progression, and prognosis. Results: Data from 75 dogs with STS was analyzed. In addition, we characterized the tumor immune microenvironment using immunohistochemistry and compared gene expression between canine and human STS. Progression-free survival and time to metastasis was significantly longer in castrated males in comparison to females. In addition, dogs with appendicular tumors had better progression- and recurrence-free survival, whereas tumor recurrence following surgical excision was associated with a shorter time to metastasis. Immunohistochemistry revealed infiltration of CD204⁺ cells in most of the tumors examined, and disease-free intervals were shorter in dogs with tumors exhibiting FOXP3⁺ cell infiltration. Gene expression profiling demonstrated similarities between canine STS and human undifferentiated pleomorphic sarcomas, with MYC dysregulation emerging as a poor prognostic indicator for dogs. Conclusions: The comparative analysis between the human and canine STS microenvironment offers a valuable insight into the clinical behavior and immune landscape of canine STS, underscoring its potential as a relevant preclinical model for the translation and development of future immunotherapies. Full article

(This article belongs to the Section Tumor Microenvironment)

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11 pages, 785 KB

Open AccessArticle

Nevus-Associated and De Novo Melanoma: A Cross-Sectional Study on Prognostic Differences

by Emi Dika, Federico Venturi, Biagio Scotti, Alberto Gualandi, Carlotta Baraldi, Sabina Vaccari, Sebastiano Posenato, Corrado Zengarini, Aurora Alessandrini, Leonardo Veneziano, Marco Ardigò and Elisabetta Magnaterra

Cancers 2025, 17(23), 3859; https://doi.org/10.3390/cancers17233859 - 30 Nov 2025

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Abstract

Background/Objectives: Melanomas may develop de novo or in association with a pre-existing nevus (nevus-associated melanoma, NAM). Whether these subtypes differ in their clinical and biological behavior remains uncertain. We aimed to compare the clinicopathologic features and outcomes of NAM and de novo [...] Read more.

Background/Objectives: Melanomas may develop de novo or in association with a pre-existing nevus (nevus-associated melanoma, NAM). Whether these subtypes differ in their clinical and biological behavior remains uncertain. We aimed to compare the clinicopathologic features and outcomes of NAM and de novo melanoma (DNM) in a large single-center cohort. Methods: We retrospectively analyzed 378 patients with invasive melanoma diagnosed between 2007 and 2021 at a tertiary referral center. Tumors were classified as NAM when histopathologic continuity with a nevus was present, and as DNM otherwise. Clinical, histologic, and prognostic variables were compared using univariate and multivariate analyses. Results: Of 378 melanomas, 90 (24%) were NAM and 288 (76%) were DNM. Patients with NAM were slightly younger (mean 52 vs. 54 years) and more often presented with tumors on the trunk (65.6% vs. 51.7%). NAMs exhibited lower Breslow thickness (0.55 vs. 0.84 mm), reduced mitotic activity (0.17 vs. 1.21/mm²), and less frequent ulceration (2.2% vs. 9.4%). Distant metastases occurred only in DNM (6.6%). Sentinel lymph node positivity (1.1% vs. 6.3%) and melanoma-specific mortality (0% vs. 0.69%) did not differ significantly. Multivariate analysis identified Breslow thickness and mitotic rate as independent predictors of subtype. Conclusions: NAMs present with more favorable histopathologic features than DNMs, yet long-term outcomes appear similar. These findings support divergent pathways of melanoma development and underscore the need for molecular and imaging studies to refine risk stratification and guide management. Full article

(This article belongs to the Special Issue Oncologic Pathology: Diagnostic Challenges, Molecular Advances, and Clinical Correlations)

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17 pages, 1691 KB

Open AccessSystematic Review

Outcome After Laparoscopic Compared to Open Interval Debulking Surgery for Advanced Stage Ovarian Cancer: A Systematic Review and Meta-Analysis

by Jana von Holzen, Franziska Siegenthaler, Noah Locher, Christine Baumgartner, Sara Imboden, Michael David Mueller and Flurina Annacarina Maria Saner

Cancers 2025, 17(23), 3858; https://doi.org/10.3390/cancers17233858 - 30 Nov 2025

Viewed by 567

Abstract

Background/Objectives: This systematic review and meta-analysis evaluates the oncological safety and outcomes of minimally invasive versus open interval debulking surgery after neoadjuvant chemotherapy in advanced ovarian cancer, addressing whether laparoscopy represents a safe alternative to the standard open procedure. Methods: The [...] Read more.

Background/Objectives: This systematic review and meta-analysis evaluates the oncological safety and outcomes of minimally invasive versus open interval debulking surgery after neoadjuvant chemotherapy in advanced ovarian cancer, addressing whether laparoscopy represents a safe alternative to the standard open procedure. Methods: The Ovid/Medline, Pubmed, and Cochrane databases were systematically screened for studies investigating surgical resection status and/or patient survival after laparotomy compared to minimally invasive interval debulking surgery for FIGO stage III-IV ovarian cancer. A meta-analysis was performed using a random-effects model and risk of bias was assessed. Results: Overall, 14 observational and randomized studies published between 2015 and 2024 with a total of 16,578 patients (4310 laparoscopy and 12,268 laparotomy) were included. A complete cytoreduction to no visible tumour was achieved significantly more often after minimally invasive surgery compared to laparotomy (RR = 1.12; 95% CI [1.01, 1.23]; p = 0.03). Overall survival showed no significant difference between the two groups (HR = 0.81; 95%CI [0.64, 1.04]); progression-free survival was significantly more common after laparoscopy (HR = 0.67; 95% CI [0.48, 0.94]; p = 0.02; I² = 55%; p = 0.07). Patients undergoing minimally invasive surgery experienced significantly fewer postoperative complications (RR = 0.50; 95% CI [0.33, 0.76]; p ≤ 0.001), a lower mean blood loss (165 mL vs. 325 mL; SMD −0.58, 95% CI [−0.82, −0.35]; p ≤ 0.001), a shorter mean hospital stay (3 days vs. 5 days; SMD −0.79, 95% CI [−1.06, −0.52], p ≤ 0.001), and a faster initiation of adjuvant chemotherapy (mean 25 ± 32 days vs. 33 ± 28 days). Conclusions: This study indicates that laparoscopic interval debulking surgery is an oncologically safe alternative in selected patients with advanced-stage ovarian cancer. However, randomized controlled trials should confirm these findings as certainty of evidence is low and residual confounding cannot be excluded. Trial registration: PROSPERO Identifier CRD42024524725. Full article

(This article belongs to the Special Issue Primary and Recurrent Gynecological Cancer: Epidemiology, Management and New Therapies)

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Cancers, Volume 17, Issue 23 (December-1 2025) – 166 articles

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