Oncology and Therapy最新文献

{"title":"Toward Personalized Treatment of Urogenital Cancers: The Role of Patient-Derived Organoids.","authors":"Serena Sagliocchi, Michele Musone, Stefano Chianese, Annunziata Gaetana Cicatiello, Silvia Del Mastro, Francesco Del Giudice, Monica Dentice, Felice Crocetto","doi":"10.1007/s40487-025-00411-w","DOIUrl":"10.1007/s40487-025-00411-w","url":null,"abstract":"<p><p>Urogenital cancers, including prostate, kidney, and bladder cancer, remain a significant clinical challenge due to their high incidence, molecular heterogeneity, and frequent resistance to standard therapies. Despite progress in genomic profiling and precision oncology, the translation of molecular data into effective therapeutic decisions remains limited by the lack of functional models capable of capturing tumor complexity. Patient-derived organoids (PDOs) have emerged as transformative tools in this context, offering the unique advantage of preserving the genetic, phenotypic, and functional features of individual tumors ex vivo. Beyond their well-established applications in drug screening and resistance studies, PDOs contribute to personalized treatment strategies by enabling functional molecular stratification, modeling tumor-microenvironment interactions, and predicting the efficacy of targeted and immunotherapeutic approaches. When integrated with liquid biopsy analyses, PDOs also allow real-time tracking of clonal evolution and can be repeatedly generated during the disease course, providing dynamic insights that guide longitudinal treatment decisions. As organoid biobanking and multi-omic integration advance, PDOs are poised to evolve into clinically actionable avatars that complement genomic profiling and help tailor therapeutic strategies for patients with urogenital cancers. Nevertheless, the clinical integration of PDOs still faces important barriers, including variability in culture protocols, incomplete representation of the native tumor microenvironment, and the time required for organoid establishment. Moreover, the predictive value of PDO-based drug screening-although promising-needs rigorous prospective validation in large patient cohorts. This review highlights the pivotal role of PDOs in bridging the gap between laboratory research and clinical oncology, emphasizing their application in guiding personalized therapeutic strategies. As organoid biobanking and genomic profiling expand, the integration of PDOs into precision oncology pipelines holds promise for reshaping the clinical management of urogenital malignancies and advancing toward truly individualized cancer treatment.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"155-171"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145935366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burgeoning Non-Muscle Invasive Bladder Cancer Space: AUA 2025 Clinical Trials Presented (Doctor/Patient Podcast).","authors":"Rick Bangs, Roger Li","doi":"10.1007/s40487-025-00409-4","DOIUrl":"10.1007/s40487-025-00409-4","url":null,"abstract":"<p><p>In this plain language podcast, the authors discuss highlights from the American Urological Association (AUA) Annual Meeting 2025. These insights come from the perspective of an expert patient and physician, both of whom have experience and expertise in the field of bladder cancer. This podcast is intended to broaden the reach of complex data and insights from AUA 2025 to a broader audience, including non-specialists, helping enable better informed treatment decisions between patients and healthcare professionals. The authors introduce the current treatment landscape for patients and discuss four clinical trials focusing on patients with bacillus Calmette-Guérin (BCG)-naïve and BCG-unresponsive high-risk non-muscle invasive bladder cancer (HR-NMIBC). Three trials presenting novel treatment approaches and their impact on survival and disease progression are discussed: PD-1 inhibitors in combination with BCG, a first-in-use intravesical drug delivery system that targets treatment directly to the bladder, and a novel oncolytic tumor-directed therapy. Authors highlight the strengths and limitations of these novel mechanisms vs standard of care, including convenient and more accessible treatment, similar or more effective disease response, and safety profiles. Finally, a prospective observational trial comparing patient quality of life outcomes is discussed, highlighting the differences between patients receiving bladder preservation vs radical cystectomy, the current gold standard of treatment. Key data from AUA showcase the growing number of treatment options available to patients with BCG-naïve and BCG-unresponsive HR-NMIBC and present promising new agents and broader possibilities for existing agents. They also raise the continued need for a nuanced approach towards navigating bladder preservation and the importance of shared-decision-making and goals of care discussions between patients and their physicians when discussing care. Podcast (MP4 122704 kb).</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"73-80"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venetoclax Plus Rituximab for Relapse/Refractory Chronic Lymphocytic Leukemia: A Systematic Review and Network Meta-analysis of Treatments Available in Brazil.","authors":"Bruno M Barros, Márcia Gisele S Costa, Marcelo G Correia, Carlos S Magliano, Pedro Vitor P Lima, Natália B Santoni, Andreas Duva, Maria Isabel Duran","doi":"10.1007/s40487-026-00418-x","DOIUrl":"10.1007/s40487-026-00418-x","url":null,"abstract":"<p><strong>Introduction: </strong>Venetoclax represents a significant advancement in target anticancer therapy in the management of relapsed/refractory chronic lymphocytic leukemia (RR-CLL). This study aims to compare the efficacy and safety of the venetoclax + rituximab (VenR) regimen with other therapies approved in Brazil.</p><p><strong>Methods: </strong>A systematic review and network meta-analysis (NMA) was conducted to evaluate the efficacy and safety of treatments approved in Brazil for RR-CLL. Comprehensive literature searches were performed to identify randomized controlled trials. Risk of bias and certainty of evidence for each outcome were assessed across the included studies. The NMA was conducted using a frequentist framework. The primary efficacy outcomes were progression-free survival, overall survival, overall response rate, and time to next therapy. Safety was assessed on the basis of the incidence of serious adverse events.</p><p><strong>Results: </strong>A total of 24 publications related to 12 trials were identified and included. VenR was associated with better survival outcomes when compared with standard regimens such as rituximab (HR 0.16; 95% CI 0.03-0.74) and physician choice (HR 0.17; 95% CI 0.04-0.81). In terms of progression-free survival, VenR achieved HR < 0.20, supported by narrow confidence intervals, when compared to treatments such as bendamustine plus rituximab, ofatumumab and physician choice, in addition to significantly favorable results compared to ibrutinib and acalabrutinib. Approximately half of the studies presented a low risk of bias, and the certainty of evidence assessed using the GRADE-NMA approach resulted in very low certainty of evidence, mainly due to risk of bias, intransitivity, and imprecision.</p><p><strong>Conclusion: </strong>This NMA provides valuable evidence to support rational therapeutic choices for RR-CLL in Brazil, highlighting VenR and Bruton tyrosine kinase inhibitors as leading treatment options across diverse clinical scenarios.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"205-224"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Response to: Letter to the Editor Regarding \"Cost-Effectiveness of Elranatamab Versus Current Therapies for the Management of Patients with Triple-Class Exposed, Relapsed and Refractory Multiple Myeloma, Including Other Bispecific and Physician's Choice of Treatment in Spain\".","authors":"Virginia Lozano, Julia Llinares, Patrick Halavacek, Olivia Ashman, David Carcedo, Cristina Encinas, Joaquín Martínez-López","doi":"10.1007/s40487-026-00421-2","DOIUrl":"10.1007/s40487-026-00421-2","url":null,"abstract":"","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"429-435"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147318670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Podcast Discussion on Medical Treatment in R/M-SCCHN in the Year 2025-Standard and Considerations for an Individualized Treatment.","authors":"Philipp Ivanyi, Tabea Fröhlich, Jonas Paul Wiegmann, Konrad Klinghammer","doi":"10.1007/s40487-025-00396-6","DOIUrl":"10.1007/s40487-025-00396-6","url":null,"abstract":"<p><p>Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) remains a disease with limited treatment options. Once salvage surgery or radiotherapy is no longer feasible, systemic medical therapy becomes the mainstay of treatment. This article discusses the general principles of systemic therapy, with a focus on key phase 3 clinical trials such as KEYNOTE-048 and EXTREME. The strengths and limitations of these studies are evaluated, and in the context of additional phase 2 trials, considerations are made regarding individualized treatment strategies based on patient-specific characteristics when selecting first-line therapy. Although there is limited evidence to define an ideal second-line therapy, switching the mechanism of action from the first-line treatment remains a reasonable approach. In conclusion, as of 2025, for fit patients, the choice of first-line therapy should be guided by PD-L1 combined positive score (CPS) and the clinical need for rapid remission, as well as other patients individual parameters. Second-line treatment decisions should be based on the mode of action used in the first-line setting-pending further clinical trials to establish optimal treatment sequencing. However, upcoming innovation within the landscape of medical treatment, with introduction of PD1 inhibition into the neoadjuvant setting, will need within the near future a reconsideration of hole treatment journey in head and neck. Podcast Audio (MP4 285072 KB).</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"27-40"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden of Treatment, Treatment Sequencing and Healthcare Resource Utilization in Multiple Myeloma in Latin America: A Targeted Literature Review.","authors":"Cristian Maximiliano Seehaus, Guillermina Remaggi, Jayr Schmidt Filho, Paola Ochoa, Ricardo Bigni, Roberto José Pessoa de Magalhães, Ruddy Dalfeor, Bhumika Aggarwal, Claudia Soares, Jacopo Bitetti","doi":"10.1007/s40487-025-00400-z","DOIUrl":"10.1007/s40487-025-00400-z","url":null,"abstract":"<p><p>Approval of key drug classes has improved survival for patients with multiple myeloma (MM). However, most patients experience relapse or become refractory to these treatments, with retreatment having limited efficacy. Access to these key treatments varies widely across countries in Latin America (LATAM), which can lead to suboptimal clinical outcomes. This targeted literature review aimed to understand the epidemiology, burden of treatment, treatment sequencing and availability for MM in Argentina, Brazil, Chile, Colombia and Mexico, exploring recent literature on patient and clinical outcomes, and healthcare resource utilization (HCRU), in these countries. A literature search was conducted using four literature databases: PubMed, Embase, SciELO and LILACS (timeframe: 1 January 2014-1 November 2024). Articles of interest reported on patients with MM in the relevant LATAM countries focusing on epidemiology, any therapy for MM, treatment patterns, patient and clinical outcomes and HCRU. Findings were analyzed by geography, line of therapy and intervention, where data were available. Of 878 articles identified, 40 reported on outcomes of interest, which were mostly retrospective observational studies (n = 33). Epidemiology reported in these studies largely aligned with global data but varied across the countries. Treatments varied by country and healthcare settings, with newer drugs (such as lenalidomide, daratumumab, bortezomib) more likely to be used in private than public healthcare settings. Survival outcomes were variable and greater in private versus public healthcare settings. Adverse events were inconsistently reported across studies; generally, few events were serious or severe. HCRU was seldom reported. Overall, this review revealed a high variability in treatment patterns, limited availability of globally accepted standard of care treatments and disparate outcomes in countries in LATAM. Furthermore, we identified substantial gaps in the literature; filling these knowledge gaps in treatment utilization and outcomes may provide pathways to improving access for newer, more effective therapies, alleviating the substantial burden of MM in LATAM.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"113-154"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145606717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Cost of Genomic Testing for Biomarker-Driven Therapies in Oncology.","authors":"Jamie P Grossman, Elizabeth A Sheppard, Zhuofan Yan, Magdalene Crabbe, Yogesh S Punekar","doi":"10.1007/s40487-026-00416-z","DOIUrl":"10.1007/s40487-026-00416-z","url":null,"abstract":"<p><strong>Introduction: </strong>Genomic profiling is used in the diagnosis, monitoring, and treatment of malignancies. Comprehensive genomic profiling (CGP) is a next-generation sequencing (NGS) approach that can test multiple genes simultaneously, potentially saving time, money, and sample material. Costs associated with genomic profiling could be a prohibitive barrier to the widespread implementation of genomic testing in routine clinical practice.</p><p><strong>Methods: </strong>A cost calculator was developed to demonstrate the cost difference between targeted panel NGS and individual single-gene testing (SGT). The calculator evaluates the cost of testing for more than 30 biomarkers included in the 2024 update of the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets. Sensitivity and specificity data for NGS and SGT, biomarker prevalence, and the number needed to predict (NNP) metric were used to estimate the cost of each test per correctly identified patient (CCIP) in different types of tumors. Calculator results are available in EUR (€) and USD ($), inflated to 2025 values. The calculator generates results for 14 different advanced malignancies.</p><p><strong>Results: </strong>At base case in EUR (€), CCIP was lower with NGS than sequential SGT for metastatic colorectal cancer (mCRC), advanced prostate cancer, advanced pancreatic ductal adenocarcinoma (PDAC), advanced cholangiocarcinoma (CC), advanced soft-tissue sarcoma (STS), advanced thyroid cancer, and cancer of unknown primary origin (CUP). In USD ($) all of the aforementioned tumors except for advanced CC had more favorable CCIPs for NGS, compared with sequential SGT.</p><p><strong>Conclusion: </strong>The insights provided by this calculator demonstrate lower costs using NGS compared with SGT for many malignancies, which suggests that opportunities exist for the expanded use of NGS in routine clinical practice for molecular profiling of patients with cancer.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"389-407"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146214344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding Head and Neck Surgical Services in East Africa through Innovative Training Initiatives.","authors":"K Thomas Robbins, Johannes Fagan, Douglas Senyonjo, Samuel Okerosi, Desderius Chussi, Karthik N Rao, Sreeram M P, Orlando Guntinas-Lichius, A Ferlito","doi":"10.1007/s40487-025-00414-7","DOIUrl":"10.1007/s40487-025-00414-7","url":null,"abstract":"<p><p>Similar to other sub-Saharan regions, east African countries struggle to meet their overwhelming medical challenges, including a lack of well-trained doctors. New strategies for sub-speciality training are underway that may improve the workforce for head and neck surgeons and lessen the burden for patients with morbid and life-threatening diseases of this region. Detailing this approach is intended to encourage further training activity, increase global awareness, and create more intercontinental collaboration toward an improved skilled surgical workforce.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"1-8"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of SV2B Inhibits Matrix-Stiffness-Induced Tumorigenesis and EMT in Glioma via FAK/PI3K/AKT Signaling Pathway.","authors":"Dengzhen Ma, Yunda Wang, Longyu Sang, Taihong Gao","doi":"10.1007/s40487-025-00410-x","DOIUrl":"10.1007/s40487-025-00410-x","url":null,"abstract":"<p><strong>Introduction: </strong>Growing evidence suggests that increased matrix stiffness can significantly enhance the malignant characteristics of glioma cells. However, the mechanisms by which increased matrix stiffness regulates the tumorigenesis of glioma cells remain largely unknown. A growing number of studies show that carcinogenesis in various human cancers is linked to cell membrane glycoproteins and their corresponding receptors. Among these, synaptic vesicle glycoprotein 2 isoforms B (SV2B) has emerged as a transmembrane glycoprotein with significant functional implications. However, whether SV2B is involved in matrix-stiffness-mediated glioma tumorigenesis and its related mechanisms remains to be elucidated.</p><p><strong>Methods: </strong>In this study, we aimed to investigate whether SV2B mediates the effects of matrix stiffness on the focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. To examine the expression of SV2B in patients with glioma, we analyzed data from bioinformatics databases. Furthermore, we assessed SV2B variation in glioma and its impact on overall survival. In vitro experiments included Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analyses to determine protein and messenger RNA (mRNA) expression in glioma cell lines. Cell viability and DNA replication capacity were evaluated using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and colony formation assays. Migration ability was assessed through Transwell and wound healing assays. Flow cytometry was employed to analyze apoptotic rates in glioma cells. Additionally, an orthotopic tumorigenesis model was established to investigate the in vivo effects of SV2B.</p><p><strong>Results: </strong>Our results demonstrated low expression of SV2B in glioma tissues. Overexpression of SV2B was found to inhibit proliferation and migration and induce apoptosis of glioblastoma cells, while knockdown of SV2B promoted these processes. Furthermore, we observed that SV2B overexpression suppressed the epithelial-mesenchymal transition (EMT) process and inhibited the activation of the FAK/PI3K/AKT signaling pathway in glioma cells, with similar effects observed in vivo. Finally, we demonstrated that increased matrix stiffness can promote glioma tumor growth through FAK/PI3K/AKT pathway, while overexpression of SV2B can inhibit this effect.</p><p><strong>Conclusions: </strong>Our study provides insights into the functional role of SV2B in matrix-stiffness-driven glioma progression, elucidating its molecular mechanisms and highlighting its potential as a therapeutic target.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"351-372"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant Therapy in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer: Recent Progress, Challenges, and Future Directions in the Era of TAR-200 and Enfortumab Vedotin Plus Pembrolizumab.","authors":"Giuseppe Di Lorenzo, Massimo Di Maio, Carlo Buonerba","doi":"10.1007/s40487-026-00417-y","DOIUrl":"10.1007/s40487-026-00417-y","url":null,"abstract":"<p><p>Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy remains the standard of care for patients with nonmetastatic muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin. However, many patients cannot receive cisplatin because of renal dysfunction, frailty, neuropathy, ototoxicity, or comorbidities, leaving an unmet need for effective cisplatin-free perioperative options. Single-arm phase 2 studies of neoadjuvant immune checkpoint inhibitors (ICIs) have shown encouraging pathologic complete response (pCR) rates in patients who are ineligible for cisplatin or who decline it, and randomized survival evidence has only recently begun to mature. Two conceptually distinct cisplatin-free paradigms are now shaping the field: (1) systemic intensification with perioperative enfortumab vedotin plus pembrolizumab, an antibody-drug conjugate (ADC) plus programmed death 1 (PD-1) inhibitor regimen supported by phase 3 data; and (2) bladder-centered intensification with TAR-200 (intravesical sustained-release gemcitabine) combined with systemic PD-1 blockade, which has demonstrated promising pathologic activity in early-phase studies but remains investigational in MIBC. This narrative review summarizes the evolving perioperative evidence base across traditional NAC, neoadjuvant ICI monotherapy, ADC-ICI combinations, and locoregional drug delivery approaches; highlights key interpretive challenges including heterogeneous trial populations and endpoints and the limitations of cross-trial comparisons; and discusses future directions such as response-adapted escalation and de-escalation strategies using circulating tumor DNA and urinary tumor DNA. We present a conceptual framework for future prospective trials evaluating how systemic and bladder-centered strategies might be selected and sequenced, rather than definitive guidance for routine clinical practice.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"189-204"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}