Cancer treatment reviews最新文献

{"title":"Chimeric antigen receptor NK cells for breast cancer immunotherapy","authors":"Nisha Wu ,&nbsp;Ning Yang ,&nbsp;Shiqi Zhang ,&nbsp;Haoran Wu ,&nbsp;Xuechun Fang ,&nbsp;Wanying Lin ,&nbsp;Yi Zhang ,&nbsp;Xiaowei Qi ,&nbsp;Ying Gong","doi":"10.1016/j.ctrv.2025.102943","DOIUrl":"10.1016/j.ctrv.2025.102943","url":null,"abstract":"<div><div>Breast cancer, a predominant malignancy afflicting women globally, demands innovative therapeutic strategies beyond traditional treatments such as surgery, chemotherapy, radiotherapy, and endocrine therapy. Among the emerging therapies, immunotherapy has demonstrated substantial promise, particularly employing chimeric antigen receptor (CAR) technology. This review elucidates the prospect of CAR-modified natural killer (NK) cells in treating breast cancer. NK cells, vital components of the immune system, possess the capability to non-specifically target and extinguish neoplastic cells. Through genetic engineering, CAR constructs targeting specific breast cancer antigens, including HER2, EGFR, PD-L1, MSLN, and Trop2, are integrated into NK cells, thereby enhancing their tumor recognition and cytotoxicity. The review delves into the structural optimization of CAR-NK cells, discussing design elements such as scFv, hinge regions, and activation signals, and emphasizes strategies to augment CAR-NK cell functionality and persistence within the tumor microenvironment. Combining CAR-NK cells with other therapeutic modalities (such as chemotherapy and checkpoint inhibitors) is explored to enhance therapeutic efficacy. Preclinical researches emphasized the efficacy of CAR-NK cells in targeting breast cancer cells, paving the way for future clinical applications and offering hope for improved outcomes in breast cancer patients.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"137 ","pages":"Article 102943"},"PeriodicalIF":9.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant CDK4/6 inhibitors in breast cancer: Interpreting trial design, evidence, and uncertainty","authors":"Saroj Niraula","doi":"10.1016/j.ctrv.2025.102944","DOIUrl":"10.1016/j.ctrv.2025.102944","url":null,"abstract":"<div><div>Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have transformed the treatment landscape for metastatic hormone receptor–positive, HER2-negative breast cancer by improving progression-free and Overall Survival (OS). In the adjuvant context, however, results have been discordant and remain immature. The PALLAS and PENELOPE-B trials of palbociclib reported no benefit, while monarchE and NATALEE demonstrated improvements in invasive disease-free survival (iDFS) with abemaciclib and ribociclib, respectively, leading to regulatory approvals despite no demonstrated OS benefit yet.</div><div>It remains possible that adjuvant CDK4/6 inhibition provides meaningful long-term benefit, but that has not been demonstrated. Concerns related to trial design: risk-enrichment, open-label conduct, high treatment-discontinuation rates, and potential informative censoring complicate interpretation. Although iDFS is a recognized intermediate endpoint with potential psychological validity, it is subject to bias in collection and communication, and has not been validated as a surrogate for OS in this setting. Moreover, early inhibition of CDK4/6 may induce resistance and compromise subsequent efficacy. Reported quality-of-life outcomes were preserved, not improved, which holds limited value considering added toxicity, inconvenience, and cost in a largely curable population.</div><div>If even half of eligible patients are treated, estimated annual costs in the United States would exceed $7 billion. As these agents are incorporated into clinical guidelines, it is critical to clarify whether they improve long-term outcomes, delay recurrence without affecting survival, or cause unintended harm. Impulse to intervene early is understandable, but emerging data must be carefully assessed to ensure adjuvant CDK4/6 inhibition offers meaningful benefit to patients and health systems.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"136 ","pages":"Article 102944"},"PeriodicalIF":9.6,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing radiotherapy techniques for Triple-Negative breast cancer treatment","authors":"Saharnaz Sarlak,&nbsp;Gilles Pagès,&nbsp;Frédéric Luciano","doi":"10.1016/j.ctrv.2025.102939","DOIUrl":"10.1016/j.ctrv.2025.102939","url":null,"abstract":"<div><div>Breast cancer is the most prevalent cancer among women worldwide, with various subtypes that require distinct treatment approaches. Among these, Triple-Negative Breast Bancer (TNBC) is recognized as the most aggressive form, often associated with poor prognosis due to its lack of targeted therapeutic options. This review specifically focuses on Radiotherapy (RT) as a treatment modality for TNBC, evaluating recent advancements and ongoing challenges, particularly the issue of radioresistance.</div><div>RT remains an essential part in the management of breast cancer, including TNBC. Over the years, multiple improvements have been made to enhance RT effectiveness and minimize resistance. The introduction of advanced techniques such as Stereotactic Body Radiation Therapy (SBRT) and Stereotactic Radiosurgery (SRS) has significantly improved precision and reduced toxicity. More recently, proton radiation therapy, a novel RT modality, has been introduced, offering enhanced dose distribution and reducing damage to surrounding healthy tissues. Despite these technological advancements, a subset of TNBC patients continues to exhibit resistance to RT, leading to recurrence and poor treatment outcomes.</div><div>To overcome radioresistance, there is an increasing interest in combining RT with targeted therapeutic agents that sensitize cancer cells to radiation. Radiosensitizing drugs have been explored to enhance the efficacy of RT by making cancer cells more susceptible to radiation-induced damage. Potential candidates include DNA damage repair inhibitors, immune checkpoint inhibitors, and small-molecule targeted therapies that interfere with key survival pathways in TNBC cells.</div><div>In conclusion, while RT remains a crucial modality for TNBC treatment, radioresistance remains a significant challenge. Future research should focus on optimizing RT techniques while integrating radiosensitizing agents to improve treatment efficacy. By combining RT with targeted drug therapy, a more effective and personalized treatment approach can be developed, ultimately improving patient outcomes and reducing recurrence rates in TNBC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"136 ","pages":"Article 102939"},"PeriodicalIF":9.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting pediatric adrenocortical carcinoma: Molecular insights and emerging therapeutic strategies","authors":"Michaela Kuhlen ,&nbsp;Maximilian Schmutz ,&nbsp;Marina Kunstreich ,&nbsp;Antje Redlich ,&nbsp;Rainer Claus","doi":"10.1016/j.ctrv.2025.102942","DOIUrl":"10.1016/j.ctrv.2025.102942","url":null,"abstract":"<div><div>Pediatric adrenocortical carcinoma (pACC) is an exceptionally rare and aggressive malignancy, accounting for only 0.2–0.3% of childhood cancers. Characterized by significant endocrine activity and often associated with genetic syndromes such as Li-Fraumeni syndrome, pACC exhibits distinct clinical and molecular profiles compared to adult adrenocortical carcinoma (ACC). Current treatment approaches, largely adapted from adult protocols, center on surgery and chemotherapy, including mitotane. However, the lack of pediatric-specific data and major clinical trials underscores a pressing need for tailored therapeutic strategies.</div><div>Advances in molecular profiling have unveiled actionable targets, such as alterations in the Wnt/β-catenin and MAP/ERK pathways, overexpression of IGF2, and epigenetic dysregulation. Emerging therapies, including immune checkpoint inhibitors, CAR T-cell therapy, and radiopharmaceuticals, hold promise but remain largely untested in pediatric populations. Targeting metabolic vulnerabilities, such as steroidogenesis and lipid metabolism, offers additional avenues for therapeutic innovation. Furthermore, improved diagnostic tools like liquid biopsy and steroid profiling may enhance disease monitoring and early detection.</div><div>Despite progress in understanding pACC biology, significant challenges remain in translating these insights into effective treatments. Collaborative efforts, such as the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT), and the development of pediatric-specific clinical trials are vital for advancing the field. Multidisciplinary care and international research initiatives will be pivotal in addressing the unmet needs of pACC patients.</div><div>By leveraging molecular insights and fostering global collaboration, the field can move toward personalized medicine, improving outcomes and quality of life for children with this challenging disease. Expanding clinical trials, refining diagnostic tools, and integrating novel therapies into treatment regimens will be critical in bridging the gap between pediatric and adult ACC treatment success.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"136 ","pages":"Article 102942"},"PeriodicalIF":9.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management approaches for recurrent or metastatic head and neck squamous cell carcinoma after anti-PD-1/PD-L1 immunotherapy","authors":"Makoto Tahara ,&nbsp;Darren Wan-Teck Lim ,&nbsp;Bhumsuk Keam ,&nbsp;Brigette Ma ,&nbsp;Li Zhang ,&nbsp;Chaojun Wang ,&nbsp;Ye Guo","doi":"10.1016/j.ctrv.2025.102938","DOIUrl":"10.1016/j.ctrv.2025.102938","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally. For patients with recurrent or metastatic (R/M) HNSCC, immunotherapy represents an important advance in clinical practice as an effective and widely used first-line treatment. However, drug resistance following immunotherapy is an emerging problem and, despite the success of immunotherapy in R/M HNSCC, a proportion of patients will become immunotherapy resistant. The mechanisms of immunotherapy resistance are not yet fully understood and subsequent treatment options are limited. Therefore, there is an unmet need for effective and well tolerated treatments for patients who develop immunotherapy-resistant HNSCC.</div><div>In this review, we address these challenges by summarizing the current definitions of immunotherapy resistance (primary and acquired resistance) as well as knowledge of the mechanisms of resistance to immunotherapy in R/M HNSCC. We then review available clinical data on treatment strategies, including rechallenge with immunotherapy, chemotherapy ± cetuximab, other targeted treatments, antibody-drug conjugates, and bispecific antibodies. We also investigate future research directions by reviewing ongoing clinical trials.</div><div>Our review shows that the optimal therapeutic strategy for patients with R/M HNSCC remains unclear. While many therapies have reported promising preliminary results, prospective clinical trials are required to support their adoption in clinical practice. In particular, it appears that immunotherapy and antibody-drug conjugates have high potential in this setting. Our review also highlights the importance of further investigation of the mechanisms underlying immunotherapy-resistant R/M HNSCC, to inform selection of optimal therapeutic strategies on an individual patient basis and improve patient outcomes.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"136 ","pages":"Article 102938"},"PeriodicalIF":9.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From ICI to ICU: A systematic review of patients with solid tumors who are treated with immune checkpoint inhibitors (ICI) and admitted to the intensive care unit (ICU)","authors":"Brigit van Dijk ,&nbsp;Joséphine C. Janssen ,&nbsp;Paul L.A. van Daele ,&nbsp;Maja J.A. de Jonge ,&nbsp;Arjen Joosse ,&nbsp;Henk M.W. Verheul ,&nbsp;Jelle L. Epker ,&nbsp;Astrid A.M. van der Veldt","doi":"10.1016/j.ctrv.2025.102936","DOIUrl":"10.1016/j.ctrv.2025.102936","url":null,"abstract":"<div><h3>Purpose</h3><div>Immune checkpoint inhibitors (ICIs) have improved the survival of patients with different solid tumors and even resulted in cure of metastatic disease. Since the introduction of ICIs, an increasing number of patients is admitted to the ICU for severe and potentially life-threatening immune related adverse events (irAEs). The outcome of patients who are admitted to the ICU because of severe irAEs is still unknown. The aim of this systematic review is to collect evidence on the outcomes of patients with solid tumors who are admitted to the ICU because of irAEs.</div></div><div><h3>Methods</h3><div>Medline, Embase, Cochrane central register of controlled trials and Google Scholar were searched systematically from 1975 to 24 September 2024. Articles were only included when describing patients with solid tumors who were admitted to the ICU because of irAEs after treatment with ICIs. Two independent reviewers extracted the data and assessed the risk of bias.</div></div><div><h3>Results</h3><div>A total of 183 articles were included: two prospective ICU population-based studies, four retrospective ICU population-based studies, 25 retrospective studies describing irAEs with incidental ICU admissions, one review of case reports, and 153 articles with a total of 177 case reports. The six ICU population-based studies contained a total of 169 patients who were admitted to the ICU due to irAEs. In these six studies, the most frequently reported irAEs were pneumonitis and neurological irAEs. Of these 169 patients, 26% of the patients died on the ICU and an additional 8% of patients in the three to six months thereafter due to irAEs or disease progression. In all 183 included articles, various irAEs were described and the reported mortality rate varied from 0 to 53%.</div></div><div><h3>Conclusion</h3><div>The potential favorable outcomes of both the solid tumors and irAEs will probably result in more need for ICU admissions. Prospective clinical trials are needed to optimize the treatment strategy of severe irAEs at the ICU. Based on the favourable outcomes after life-threatening irAEs, ICU admission should definitely be considered for patients with solid tumors who have life-threatening irAEs.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"136 ","pages":"Article 102936"},"PeriodicalIF":9.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary testicular lymphoma","authors":"Brian T. Grainger ,&nbsp;Chan Y. Cheah","doi":"10.1016/j.ctrv.2025.102927","DOIUrl":"10.1016/j.ctrv.2025.102927","url":null,"abstract":"<div><div>Primary testicular lymphoma (PTL) is a rare extranodal lymphoma. The majority of cases are of diffuse large B cell lymphoma (DLBCL) histology (PT-DLBCL) with an activated B-cell-like (ABC) gene expression profile. These are characterised clinically by a high risk of contralateral testis and central nervous system (CNS) relapse, representing an ongoing area of unmet clinical need. Here, we review the epidemiology, clinical presentation and diagnostic evaluation of PT-DLBCL along with the advances in molecular biology that have occurred in the last decade, concerning the now-recognised molecular subtypes of DLBCL and their role of immune escape and sustained signalling in disease pathophysiology. We also appraise the retrospective and prospective clinical trials underpinning modern treatment recommendations, including the updated guidance on the role of radiotherapy and the latest evidence regarding strategies for preventing CNS relapse.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"136 ","pages":"Article 102927"},"PeriodicalIF":9.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing cytokine immunocomplexes and cytokine fusion proteins for cancer Therapy: Mechanisms and clinical potential","authors":"Wei Yang Kong ,&nbsp;Amelia Soderholm ,&nbsp;Andrew J. Brooks ,&nbsp;Jazmina L. Gonzalez Cruz ,&nbsp;James W. Wells","doi":"10.1016/j.ctrv.2025.102937","DOIUrl":"10.1016/j.ctrv.2025.102937","url":null,"abstract":"<div><div>Cytokines are pivotal regulators of cellular functions and immune responses, making them highly promising targets for cancer immunotherapy. Despite their widespread clinical application, the effectiveness of cytokine immunotherapy is often hampered by their pleiotropic effects, short half-lives, uneven biodistribution, and severe side effects at high dosages. Recent advancements in cytokine biology have led to the development of cytokine-antibody immunocomplexes and cytokine fusion proteins, offering a new paradigm in cancer treatments. These innovations foster the ability of cytokines to selectively activate specific cancer-targeting immune cell populations, such as CD8 T cells and NK cells, effectively inhibiting tumour progression. Furthermore, both therapeutic approaches can mitigate systemic toxicities and prolong the biological activity of cytokines in the body. This review delves into the recent advancements of cytokine immunocomplexes and cytokine fusion proteins, with a particular focus on interleukin-2 (IL-2), IL-7 and IL-15, which are in clinical/preclinical development. Moreover, we discuss the therapeutic benefits of these approaches observed in recent preclinical and clinical studies, along with the challenges that must be addressed to fully unlock their potential in cancer immunotherapy.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"136 ","pages":"Article 102937"},"PeriodicalIF":9.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current and future directions in theranostics for neuroendocrine prostate cancer","authors":"Gokce Belge Bilgin ,&nbsp;Fabrice Lucien-Matteoni ,&nbsp;Aadel A. Chaudhuri ,&nbsp;Jacob J. Orme ,&nbsp;Daniel S. Childs ,&nbsp;Miguel Muniz ,&nbsp;Gary G. Li ,&nbsp;Pradeep S. Chauhan ,&nbsp;SeungBaek Lee ,&nbsp;Sounak Gupta ,&nbsp;Matthew P. Thorpe ,&nbsp;Derek R. Johnson ,&nbsp;Geoffrey B. Johnson ,&nbsp;Ayse Tuba Kendi ,&nbsp;Oliver Sartor","doi":"10.1016/j.ctrv.2025.102941","DOIUrl":"10.1016/j.ctrv.2025.102941","url":null,"abstract":"<div><div>Neuroendocrine prostate cancer (NEPC) is rare at the time of initial diagnosis but much more common in patients treated with the combination of androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPI) such as abiraterone and enzalutamide. NEPC is typically characterized by the loss of prostate-specific membrane antigen (PSMA) expression while exhibiting variable neuroendocrine markers. Recent advancements in nuclear medicine have provided a promising avenue for the development of molecular imaging techniques and targeted therapies tailored to NEPC. This review examines the current and future role of theranostics in the diagnosis and management of NEPC and explores potential future directions in this rapidly evolving field.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"136 ","pages":"Article 102941"},"PeriodicalIF":9.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Operationalizing intermediate clinical endpoints: A pragmatic framework for prostate cancer management trials","authors":"Xingyu Xiong ,&nbsp;Shiyu Zhang ,&nbsp;Jiajia Du ,&nbsp;Xinyang Liao ,&nbsp;Jie Yang ,&nbsp;Weitao Zheng ,&nbsp;Hang Xu ,&nbsp;Lu Yang ,&nbsp;Qiang Wei","doi":"10.1016/j.ctrv.2025.102935","DOIUrl":"10.1016/j.ctrv.2025.102935","url":null,"abstract":"<div><div>Despite therapeutic advances, prostate cancer remains lethal for most patients. Accelerated development of novel therapies requires validated surrogate endpoints to circumvent prolonged survival follow-up in phase III trials. This review systematically evaluates intermediate clinical endpoints (ICEs) in prostate cancer to establish methodologically robust alternatives to overall survival (OS). We first synthesized methodological standards for ICE validation. Subsequent analysis encompassed phase III trials (PubMed/Web of Science, Jan. 2025) in metastatic castration-sensitive (mCSPC) and –resistant prostate cancer (mCRPC), requiring: randomization, therapeutic intervention, OS as primary/co-primary endpoint, ≥1 ICE (radiographic progression-free survival (rPFS), milestone survival), and ≥70 participants. Surrogacy was quantified via two-stage meta-analysis, with R² ≥ 0.7 defining validity. Metastasis-free survival (MFS) is validated for localized disease, enabling trial endpoint substitution. In advanced stages, evidence for ICEs remains critically deficient. Our analysis identifies milestone survival as a promising ICE candidate in mCSPC and mCRPC, demonstrating strong trial-level correlation with OS. Current ICE validation in prostate cancer is disproportionately focused on localized disease, leaving advanced-stage therapeutic development constrained. While milestone survival shows surrogacy potential, endpoint validation remains methodologically challenging even in rigorously designed trials. This work underscores the imperative to accelerate ICE standardization through unified methodological frameworks and collaborative cross-trial analyses.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"136 ","pages":"Article 102935"},"PeriodicalIF":9.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}