Journal of the National Comprehensive Cancer Network : JNCCN最新文献

{"title":"Breast Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology.","authors":"William J Gradishar, Meena S Moran, Jame Abraham, Vandana Abramson, Rebecca Aft, Doreen Agnese, Kimberly H Allison, Bethany Anderson, Janet Bailey, Harold J Burstein, Nan Chen, Helen Chew, Chau Dang, Anthony D Elias, Sharon H Giordano, Matthew P Goetz, Rachel C Jankowitz, Sara H Javid, A Marilyn Leitch, Janice Lyons, Susie McCloskey, Melissa McShane, Sameer A Patel, Laura H Rosenberger, Hope S Rugo, Cesar A Santa-Maria, Bryan P Schneider, Mary Lou Smith, Hatem Soliman, Corey Speers, Melinda L Telli, Mei Wei, Kari B Wisinski, Amulya Yellala, Kay T Yeung, Jessica S Young, Ryan Schonfeld, Rashmi Kumar","doi":"10.6004/jnccn.2026.0033","DOIUrl":"10.6004/jnccn.2026.0033","url":null,"abstract":"<p><p>The NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Breast Cancer focuses on the recommendations for the management of recurrent or stage IV (M1) metastatic breast cancer. It summarizes the treatment strategies stratified by tumor biology, including hormone receptor status and HER2 expression, as well as clinical factors such as prior therapy and disease-free interval. Throughout all treatment lines, supportive care, quality of life preservation, toxicity minimization, and clinical trial participation are emphasized as integral components of patient care.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":"24 7","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NCCN Guidelines® Insights: Myeloproliferative Neoplasms, Version 2.2026.","authors":"Aaron T Gerds, Jason Gotlib, Peter Abdelmessieh, Haris Ali, Mariana Castells, Brian J Chernak, Manuel R Espinoza-Gutarra, Ruth Fein Revell, Steven Green, Krishna Gundabolu, Elizabeth Hexner, Tania Jain, Catriona H Jamieson, Irum Khan, Andrew T Kuykendall, Yazan F Madanat, Lucia Masarova, Brandon McMahon, Sanjay R Mohan, Kalyan V Nadiminti, Stephen Oh, Jeanne Palmer, Ami B Patel, Anand A Patel, Nikolai Podoltsev, Lindsay Rein, Rachel Salit, Mary Sehl, Moshe Talpaz, Martha Wadleigh, Sarah A Wall, Mary Anne Bergman, Cindy Hochstetler","doi":"10.6004/jnccn.2026.0034","DOIUrl":"10.6004/jnccn.2026.0034","url":null,"abstract":"<p><p>The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of heterogenous hematologic malignancies characterized by the proliferation of blood cells and consist of myelofibrosis, polycythemia vera, and essential thrombocythemia. The NCCN Guidelines for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the aim of providing recommendations for the comprehensive care of adults with these diseases. The panel of experts convenes at least once a year to discuss requested changes to the Guidelines and to evaluate emerging data. These Guideline Insights focus on some of the recent updates for myelofibrosis.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":"24 7","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What is Optimal Neoadjuvant Therapy in HER2-Positive Breast Cancer?","authors":"Daniel S Peiffer, Caitlin Maloney, Nan Chen","doi":"10.6004/jnccn.2026.7047","DOIUrl":"https://doi.org/10.6004/jnccn.2026.7047","url":null,"abstract":"<p><p>HER2-positive breast cancer accounts for approximately 15%-20% of breast cancers and was historically associated with poor outcomes. The introduction of HER2-targeted therapies has significantly improved prognosis, particularly in the treatment of early-stage disease. Neoadjuvant HER2-directed therapy combined with chemotherapy is the standard of care for patients with stage II and III HER2-positive breast cancer, enabling pathologic complete response-guided treatment personalization. This review summarizes current evidence guiding the neoadjuvant management of early-stage HER2-positive breast cancer. We discuss pivotal trials establishing dual HER2 blockade with trastuzumab and pertuzumab, strategies to optimize and de-escalate chemotherapy backbones, and emerging data supporting chemotherapy-sparing approaches in selected patients. Recent studies evaluating taxane-only regimens, carboplatin omission, antibody-drug conjugates, and immunotherapy-based combinations are reviewed with attention to efficacy, toxicity, and clinical applicability. We further examine validated and emerging biomarkers of response, including molecular subtyping, genomic assays, tumor immune features, circulating tumor DNA, and functional imaging, all of which may enable risk-adapted treatment strategies. Finally, we review mechanisms of resistance to HER2-targeted therapies, as well as novel therapeutic approaches under investigation to overcome treatment resistance. This review provides a contemporary, evidence-based framework for individualized neoadjuvant treatment of early-stage HER2-positive breast cancer.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":"24 7","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Quality Care in Small Cell Lung Cancer: Highlighting Therapeutic Advancements and Integration of Early Palliative Care.","authors":"Misty D Shields, Jacob Sands, Nathan Gray, Toby C Campbell","doi":"10.6004/jnccn.2026.7033","DOIUrl":"https://doi.org/10.6004/jnccn.2026.7033","url":null,"abstract":"","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":"24 7","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Getting the Rug Pulled Out From Under You.","authors":"Daniel M Geynisman","doi":"10.6004/jnccn.2026.0035","DOIUrl":"https://doi.org/10.6004/jnccn.2026.0035","url":null,"abstract":"","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":"24 7","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Virtual Reality Psychosocial Intervention for Patients Undergoing Bone Marrow Transplantation (BMT-VR): Pilot Randomized Clinical Trial.","authors":"Hermioni L Amonoo, Richard Newcomb, Riley Psenka, Upeka Samarakoon, Joseph A Greer, Ashley M Nelson, Anna Barata, Lara Traeger, Emelia J Farnam, Julia Pepper, Ella Caruso, Isabella S Larizza, Emma P Keane, Sid Desai, Nik Vassev, Dustin J Rabideau, Nora Horick, Zachariah DeFilipp, Yi-Bin Chen, Jennifer S Temel, Areej El-Jawahri","doi":"10.6004/jnccn.2026.7024","DOIUrl":"10.6004/jnccn.2026.7024","url":null,"abstract":"<p><strong>Background: </strong>Patients undergoing bone marrow transplantation (BMT) experience significant physical and psychological symptoms. Scalable psychosocial interventions to reduce distress and improve quality of life (QoL) are limited. Virtual reality (VR), with its 3-dimensional capabilities, offers a novel, scalable, patient-centered modality to address these needs.</p><p><strong>Methods: </strong>We randomized adult patients with hematologic malignancies undergoing autologous or allogeneic BMT to receive either a VR supportive care intervention (BMT-VR) or usual care during hospitalization. BMT-VR consists of 6 modules focused on: (1) psychoeducation and managing expectations; (2) psychosocial skill-building to promote coping; and (3) strategies to facilitate acceptance while facing uncertainty. The primary endpoint was feasibility (≥60% enrollment and ≥60% completion of ≥4 of 6 modules). Secondary outcomes included QoL (Functional Assessment of Cancer Therapy-Bone Marrow Transplant), depression and anxiety (Hospital Anxiety and Depression Scale), and posttraumatic stress disorder symptoms (Post-Traumatic Stress Disorder Checklist-Civilian Version) at baseline and at weeks 2, 4, 12, and 24 post-BMT. The System Usability Scale (≥80 indicates excellent usability) was administered at 4 weeks post-BMT.</p><p><strong>Results: </strong>Of eligible patients, 62.5% (85/136) consented and 59.6% (81/136) enrolled in the study (mean [SD] age, 57.9 [14.7] years; 51.9% female; 70.4% underwent allogeneic BMT). Among those assigned to BMT-VR, 64.1% completed ≥4 of 6 modules, exceeding feasibility benchmarks, and 69.2% (27/39) rated usability as excellent. After 4 weeks, patients assigned to BMT-VR reported improved QoL (108.2 vs 96.8; P=.014) and anxiety symptoms (3.6 vs 5.3; P=.016) versus usual care. No differences in depression or PTSD symptoms emerged at 4 weeks. Longitudinally, BMT-VR participants showed greater improvements in QoL (β = 3.8; P=.002), depression (β = -0.8; P<.001), and PTSD (β = -1.7; P=.006), but not in anxiety, compared with usual care.</p><p><strong>Conclusions: </strong>A VR-delivered psychosocial intervention is feasible during hospitalization for autologous or allogeneic BMT and shows promising preliminary effects on QoL and psychological outcomes. A future multisite trial is needed to assess efficacy for improving QoL and psychological distress in BMT recipients.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nationwide Trends in Colorectal Cancer Screening by the End of the COVID-19 Pandemic: Racial/Ethnic Differences and Opportunities.","authors":"Saeed Soleymanjahi, Nicolette Juliana Rodriguez, Young-Rock Hong, Sneha Saha, Juhan Lee, Michelle L Hughes, Sapna Syngal, Xavier Llor","doi":"10.6004/jnccn.2026.7023","DOIUrl":"10.6004/jnccn.2026.7023","url":null,"abstract":"<p><strong>Background: </strong>Although studies have reported on the impact of the COVID-19 pandemic on colorectal cancer (CRC) screening, data on long-term changes remain limited, particularly during the later phases of the pandemic (post 2021) and among racial and ethnic subgroups.</p><p><strong>Patients and methods: </strong>We analyzed data from the 2019, 2021, and 2023 National Health Interview Survey to assess clinician recommendations for CRC screening, past 2-year screening rates, and screening modalities used. Trends were compared across racial/ethnic groups and social determinants of health, including insurance status and income.</p><p><strong>Results: </strong>Our sample represented 95 million individuals in 2019, 97 million in 2021, and 98 million in 2023. Compared with 2019, CRC screening recommendations dropped by 20% in 2021 (P<.0001), with larger decreases among Hispanics (28%) and uninsured individuals (41%). Recommendations remained 11% lower in 2023 (P=.03). In 2021, past 2-year colonoscopy use declined by 8% (P=.001), whereas multitarget stool DNA testing (mt-sDNA) increased by 18% (P=.03) and fecal immunochemical test/fecal occult blood test (FIT/FOBT) use increased by 55% (P<.001). Colonoscopy declines were greatest among Asian individuals (32%), whereas increases in FIT/FOBT use were highest among Hispanic (78%) and Black (92%) individuals. By 2023, colonoscopy use had returned to prepandemic levels (28%), and mt-sDNA use increased by an additional 40%, resulting in an overall 8% increase in past 2-year screening compared with 2019 (P<.001).</p><p><strong>Conclusions: </strong>Early in the pandemic, increased stool-based testing offset reduced colonoscopy uptake. Colonoscopy rates have since recovered, whereas stool-based testing continues to increase, with notable differences across ethnic groups. This sustained shift toward stool-based testing offers an opportunity to improve screening, especially where colonoscopy access is limited.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Payers' Views on Insurance Coverage for Confirmatory Diagnostics After a Noncovered Multicancer Early Detection (MCED) Test.","authors":"Julia R Trosman, Christine B Weldon, Allison W Kurian, Emily Mrig, Mark Robson, Kathryn A Phillips","doi":"10.6004/jnccn.2026.7016","DOIUrl":"10.6004/jnccn.2026.7016","url":null,"abstract":"<p><strong>Background: </strong>Multicancer early detection (MCED) tests are not currently covered by most payers but have begun to emerge in clinical practice. Little is known about whether payers would cover confirmatory diagnostics that are necessary after a positive MCED test. Understanding coverage for confirmatory testing is particularly important for oncology professionals who receive referrals for patients with positive MCED results ordered elsewhere, typically in primary care. Our objective was to examine the views of US private payers on coverage for confirmatory diagnostics after a positive, noncovered MCED test.</p><p><strong>Methods: </strong>We conducted semistructured interviews with 16 private payers: 8 large national insurers, 5 regional insurers, and 3 organizations providing coverage decision support to insurers. Thematic analysis was complemented by simple frequencies of themes to further describe findings.</p><p><strong>Results: </strong>Although no payers in our cohort covered MCED, most (63%; 10/16) would cover confirmatory testing after a positive MCED test, although 70% (7/10) would cover it only under specific clinical scenarios (high risk or symptoms). Only a minority (19%; 3/16) would cover repeat confirmatory testing if cancer was not diagnosed. No payer had a formal policy for post-MCED confirmatory testing and only 19% (3/16) planned to establish such a policy. Almost all payers expressed general concerns about patient barriers to confirmatory testing, and most (63%; 10/16) planned to address patient barriers to confirmatory testing if/when MCED is covered, but only 5 payers would consider reducing related patient cost-sharing.</p><p><strong>Conclusions: </strong>Our findings inform oncology professionals caring for patients with positive MCED results, institutions implementing MCED programs, and payers, policymakers, and researchers addressing MCED challenges. Our study highlights the importance of developing explicit coverage policies for confirmatory diagnostics following a noncovered detection test, as this issue will likely extend beyond MCED for similar novel tests. Patient cost-sharing should be addressed as a national policy issue as MCED adoption grows.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Impact of Adjuvant Immunotherapy in Merkel Cell Carcinoma.","authors":"Bryant Morocho, Sasha Lightfoot, Abdul Saied Calvino, Ponnandai Somasundar, Steve Kwon","doi":"10.6004/jnccn.2026.7018","DOIUrl":"10.6004/jnccn.2026.7018","url":null,"abstract":"<p><strong>Background: </strong>The role of adjuvant immunotherapy (IO) in the treatment of Merkel cell carcinoma (MCC) is currently being explored in clinical trials. Here we aim to evaluate the real-world impact of adjuvant IO on survival in patients with MCC.</p><p><strong>Methods: </strong>A retrospective analysis of the National Cancer Database was performed to identify patients with stage I-III MCC. Our main predictor of interest was IO in an adjuvant setting, stratified by receipt of radiotherapy (RT). A multivariable Cox proportional hazards regression model with inverse probability treatment weighting was used to estimate overall survival.</p><p><strong>Results: </strong>A total of 353 patients received adjuvant IO, while 5,340 underwent surgery without adjuvant therapy. Among patients who received adjuvant IO, 10.2% had stage I disease, 7.1% stage II, and 82.7% stage III. Overall, adjuvant IO was not associated with a difference in survival (hazard ratio [HR], 1.04; 95% CI, 0.86-1.26). Stratified analyses by stage demonstrated similar findings (stage I: HR, 1.4; 95% CI, 0.79-2.50; stage II: HR, 1.45; 95% CI, 0.67-3.13; stage III: HR, 0.98; 95% CI, 0.79-1.20). However, when an interaction term with RT was introduced with adjuvant IO, both treatments were associated with improved survival compared with surgery alone (HR, 0.53; 95% CI, 0.28-0.99), whereas adjuvant IO without RT was not associated with a significant survival difference (HR, 1.14; 95% CI, 0.83-1.60).</p><p><strong>Conclusions: </strong>The association between adjuvant IO on survival may be modified by RT, which should be considered when interpreting current adjuvant IO trials in MCC.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148311227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surrogacy of Intermediate Clinical Endpoints for Overall Survival in Patients With Localized Muscle-Invasive Bladder Cancer.","authors":"Pietro Scilipoti, Mario de Angelis, Constance Thibault, Aleksander Ślusarczyk, Francesco Del Giudice, Roberto Contieri, Rodolfo Hurle, José Daniel Subiela, Giuseppe Simone, Flavia Proietti, Keiichiro Mori, Shahrokh Shariat, David D'Andrea, Stefania Zamboni, Nazareno Suardi, Hajime Tanaka, Shunya Matsumoto, Yasuhisa Fujii, Riccardo Bertolo, Alessandro Antonelli, Elliott Diamant, Dimitri Vordos, Pierre-Etienne Gabriel, Théo Harber, Marc Colombel, Paul Hanquiez, Vera Chatain, Igor Duquesne, Mihnea Bogdan Borz, Gregory Verhoest, Anne Mauger De Varennes, Louis Surlemont, Marion Ghenassia, Alexandra Masson-Lecomte, Arthur Peyrottes, Cédric Lebacle, Peter Beniac, Priscilla Léon, Stéphane Larré, Fayek Taha, Gautier Marcq, Aleksandra Szostek, Benjamin Pradere, Giorgio Calleris, François Audenet, Evanguelos Xylinas, Yves Allory, Anne-Sophie Bajeot, Doriane Prost, Elisabeth Grobet-Jeandin, Francesco Montorsi, Andrea Necchi, Alberto Briganti, Marco Moschini, Mathieu Roumiguié, Morgan Rouprêt, Thomas Seisen","doi":"10.6004/jnccn.2026.7014","DOIUrl":"10.6004/jnccn.2026.7014","url":null,"abstract":"<p><strong>Background: </strong>Although intermediate clinical endpoints (ICEs) may expedite completion of randomized controlled trials (RCTs) evaluating perioperative systemic treatments for localized muscle-invasive bladder cancer (MIBC), no validated surrogate for overall survival (OS) has been established. We aimed to assess the surrogacy of pathologic complete response (pCR), pathologic objective response (pOR), and disease-free survival (DFS) for OS.</p><p><strong>Patients and methods: </strong>We analyzed 4,828 patients with MIBC (cT2-T4N0M0) who underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) across 29 European centers (2001-2024). The inverse probability of treatment weighting (IPTW) approach was used to adjust for confounding between NAC and RC-only groups. Surrogacy was evaluated using: (1) adapted Prentice criteria to test whether each ICE remained a significant predictor of OS while the treatment effect disappeared in IPTW-adjusted multivariable Cox models; (2) the proportion of treatment effect explained (PTE); and (3) an emulated 2-stage meta-analytic framework to estimate the pseudo-trial-level R2 between treatment effects on each ICE and OS across 1,000 replicates of 5 random clusters. The surrogate threshold effect (STE) was calculated for ICEs demonstrating strong surrogacy (R2≥0.7).</p><p><strong>Results: </strong>Overall, 1,288 (26.7%) patients received NAC followed by RC and 3,540 (73.3%) underwent RC alone. In IPTW-adjusted Cox regression analyses including NAC and each ICE separately, pCR (hazard ratio [HR], 0.32; 95% CI, 0.24-0.41; P<.001), pOR (HR, 0.26; 95% CI, 0.21-0.31; P<.001), and DFS (HR, 5.17; 95% CI, 4.56-5.86; P<.001) were independent predictors of OS. The PTE was 0.42 (95% CI, 0.22-0.54), 0.48 (95% CI, 0.24-0.58), and 0.84 (95% CI, 0.66-0.96) for pCR, pOR, and DFS, respectively. At the pseudo-trial level, the R2 was 0.22 (95% CI, 0.20-0.25), 0.33 (95% CI, 0.31-0.36), and 0.83 (95% CI, 0.81-0.84) for the correlation between treatment effects on pCR, pOR, and DFS and OS, respectively. The STE was 0.82 (95% CI, 0.81-0.84) for DFS.</p><p><strong>Conclusions: </strong>We observed uncertainty regarding the surrogacy of pCR and pOR in patients undergoing RC with or without NAC for localized MIBC. Only DFS consistently mediated the treatment effect on OS, supporting its use as a surrogate for RCT dimensioning when a recurrence or death risk reduction of ≥18% is expected.</p>","PeriodicalId":520697,"journal":{"name":"Journal of the National Comprehensive Cancer Network : JNCCN","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}