Pub Date : 2026-03-09DOI: 10.1016/s1470-2045(26)00016-1
Madeleine J Karpinski, Caner Civan, Isabel Rauscher, Osman Güven, Matthias Eiber, Sebastian Hoberück, Matthias Miederer, Ralph A Bundschuh, Tobias Hölscher, Jeremie Calais, Lela Theus, Andrew T Nguyen, Helen Scholtissek, Constantin Lapa, Andrea Di Giorgio, Andrea Farolfi, Dominic Ufton, Alexander Drzezga, Jolanta Kunikowska, Kacper Pełka, Shahrokh F. Shariat
Background
Prostate-specific membrane antigen (PSMA)-PET usage in patients with prostate cancer is growing rapidly. Thus, novel risk-group definitions based on PSMA-PET are urgently needed for guidelines, clinical use, and trial study design. We report improved risk classification based on PSMA-PET Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE; PPP) nomograms (PPP3) to prognosticate 3-year, 5-year, and 7-year overall survival.
Methods
In this international, retrospective, registry-based cohort study, we collected data from the PROMISE PET registry with ongoing overall survival follow-up. Male patients (aged ≥18 years) with histological proven prostate cancer at any disease stage and any performance status, who underwent any PSMA-PET between Dec 6, 2012, and June 26, 2024, were included in the registry. Patients with neuroendocrine pattern or metastasised or disseminated malignancy other than prostate cancer were excluded. 35 investigator sites in Europe, Asia, Australia, North America, and South America were split pairwise (2:1) into development and validation cohorts. Entire investigator sites were split pairwise according to their site characteristics (ie, number of patients per disease group, country, follow-up). The primary study objective was overall survival. PPP3 nomograms were created based on Cox regression models with least absolute shrinkage and selection operator penalty to prognosticate 3-year, 5-year, and 7-year overall survival. Calibration curves and Harrell's c indices were applied and head-to-head comparison with clinical risk scores separated for each disease subgroup was conducted. Based on the visual PPP3 nomogram, a simplified risk-stratification table was created.
Findings
We analysed 11 154 patients and 7253 were included in the development cohort and 3901 in the validation cohort. Median follow-up to censoring or death was 4·9 years (IQR 3·5–6·6). Clinical disease group and PROMISE metrics were combined into visual and quantitative PPP3 nomograms, respectively. C indices were 0·83 (95% CI 0·82–0·84) for the visual nomogram and 0·84 (0·82–0·85) for the quantitative nomogram. Both nomograms and the simplified risk stratification table were accurate and equal or superior compared with established clinical risk scores (International Staging Collaboration for Cancer of the Prostate, European Association of Urology, a nomogram defined by Gafita and colleagues, and National Comprehensive Cancer Network).
Interpretation
We present new risk nomograms by PROMISE along with a simple table to prognosticate 3-year, 5-year, and 7-year overall survival in prostate cancer. PROMISE and PPP3 assessments are freely available online for global implementation.
Funding
German Research Foundation, Prostate Cancer Foundation, Innovative Health Initiative Joint Undertaking, Novartis, AstraZeneca, and Amgen.
前列腺特异性膜抗原(PSMA)-PET在前列腺癌患者中的应用正在迅速增长。因此，迫切需要基于PSMA-PET的新的风险组定义，用于指导、临床应用和试验研究设计。我们报告了基于PSMA-PET前列腺癌分子成像标准化评估（PROMISE； PPP）图（PPP3）的改进风险分类，以预测3年、5年和7年总生存期。方法在这项国际、回顾性、基于注册的队列研究中，我们收集了来自PROMISE PET注册的数据，并进行了持续的总生存随访。在2012年12月6日至2024年6月26日期间接受任何PSMA-PET检查的组织学证实的任何疾病阶段和任何表现状态的前列腺癌男性患者（年龄≥18岁）被纳入登记册。排除除前列腺癌以外的神经内分泌型或转移或播散性恶性肿瘤患者。欧洲、亚洲、澳大利亚、北美和南美的35个研究地点被两两（2:1）分为开发组和验证组。整个研究地点根据其地点特征（即每个疾病组的患者数量、国家、随访）两两分开。主要研究目标是总生存期。PPP3形态图是基于Cox回归模型，以最小的绝对收缩和选择算子惩罚来预测3年、5年和7年的总生存期。采用校正曲线和Harrell’sc指数，与各疾病亚组分离的临床风险评分进行正面比较。基于可视化的PPP3 nomogram，建立了简化的风险分层表。结果：我们分析了1154例患者，其中7253例被纳入发展队列，3901例被纳入验证队列。至死亡的中位随访时间为4.9年（IQR为3.5 - 6年）。临床疾病组和PROMISE指标分别合并为视觉和定量PPP3图。视觉图C指数为0.83 (95% CI 0.82 ~ 0.84)，定量图C指数为0.84 （95% CI 0.82 ~ 0.85）。与已建立的临床风险评分（国际前列腺癌分期合作，欧洲泌尿外科协会，Gafita及其同事定义的nomogram，以及国家综合癌症网络）相比，nomogram和简化的风险分层表都是准确的，并等于或优于前者。我们通过PROMISE提出了新的风险图以及一个简单的表来预测前列腺癌的3年、5年和7年总生存期。承诺评估和公私伙伴关系评估可在网上免费提供，供全球实施。资助德国研究基金会、前列腺癌基金会、创新健康倡议联合事业、诺华、阿斯利康和安进。
{"title":"New prostate cancer risk groups by PSMA-PET (PPP3): an international, retrospective, registry-based cohort study","authors":"Madeleine J Karpinski, Caner Civan, Isabel Rauscher, Osman Güven, Matthias Eiber, Sebastian Hoberück, Matthias Miederer, Ralph A Bundschuh, Tobias Hölscher, Jeremie Calais, Lela Theus, Andrew T Nguyen, Helen Scholtissek, Constantin Lapa, Andrea Di Giorgio, Andrea Farolfi, Dominic Ufton, Alexander Drzezga, Jolanta Kunikowska, Kacper Pełka, Shahrokh F. Shariat","doi":"10.1016/s1470-2045(26)00016-1","DOIUrl":"https://doi.org/10.1016/s1470-2045(26)00016-1","url":null,"abstract":"<h3>Background</h3>Prostate-specific membrane antigen (PSMA)-PET usage in patients with prostate cancer is growing rapidly. Thus, novel risk-group definitions based on PSMA-PET are urgently needed for guidelines, clinical use, and trial study design. We report improved risk classification based on PSMA-PET Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE; PPP) nomograms (PPP3) to prognosticate 3-year, 5-year, and 7-year overall survival.<h3>Methods</h3>In this international, retrospective, registry-based cohort study, we collected data from the PROMISE PET registry with ongoing overall survival follow-up. Male patients (aged ≥18 years) with histological proven prostate cancer at any disease stage and any performance status, who underwent any PSMA-PET between Dec 6, 2012, and June 26, 2024, were included in the registry. Patients with neuroendocrine pattern or metastasised or disseminated malignancy other than prostate cancer were excluded. 35 investigator sites in Europe, Asia, Australia, North America, and South America were split pairwise (2:1) into development and validation cohorts. Entire investigator sites were split pairwise according to their site characteristics (ie, number of patients per disease group, country, follow-up). The primary study objective was overall survival. PPP3 nomograms were created based on Cox regression models with least absolute shrinkage and selection operator penalty to prognosticate 3-year, 5-year, and 7-year overall survival. Calibration curves and Harrell's <em>c</em> indices were applied and head-to-head comparison with clinical risk scores separated for each disease subgroup was conducted. Based on the visual PPP3 nomogram, a simplified risk-stratification table was created.<h3>Findings</h3>We analysed 11 154 patients and 7253 were included in the development cohort and 3901 in the validation cohort. Median follow-up to censoring or death was 4·9 years (IQR 3·5–6·6). Clinical disease group and PROMISE metrics were combined into visual and quantitative PPP3 nomograms, respectively. <em>C</em> indices were 0·83 (95% CI 0·82–0·84) for the visual nomogram and 0·84 (0·82–0·85) for the quantitative nomogram. Both nomograms and the simplified risk stratification table were accurate and equal or superior compared with established clinical risk scores (International Staging Collaboration for Cancer of the Prostate, European Association of Urology, a nomogram defined by Gafita and colleagues, and National Comprehensive Cancer Network).<h3>Interpretation</h3>We present new risk nomograms by PROMISE along with a simple table to prognosticate 3-year, 5-year, and 7-year overall survival in prostate cancer. PROMISE and PPP3 assessments are freely available online for global implementation.<h3>Funding</h3>German Research Foundation, Prostate Cancer Foundation, Innovative Health Initiative Joint Undertaking, Novartis, AstraZeneca, and Amgen.","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383896","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}
Pub Date : 2026-03-05DOI: 10.1016/s1470-2045(26)00063-x
Simone Ribero, Pietro Quaglino
No Abstract
没有抽象的
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Pub Date : 2026-03-02DOI: 10.1016/s1470-2045(26)00015-x
Yeon Hee Park
{"title":"Beyond regional boundaries: crucial gaps in global breast cancer burden estimates","authors":"Yeon Hee Park","doi":"10.1016/s1470-2045(26)00015-x","DOIUrl":"https://doi.org/10.1016/s1470-2045(26)00015-x","url":null,"abstract":"","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"44 1","pages":"270-271"},"PeriodicalIF":0.0,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147360229","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}
Pub Date : 2026-03-02DOI: 10.1016/s1470-2045(25)00720-x
Linde van den Hoek, Mark Burgmans, Thaïs Tong, Jelle Goeman, Frank Speetjens, Stephanie Zunder, Arian van Erkel, Rutger van der Meer, Carla van Rijswijk, Jacob Lutjeboer, Dominique Koolhaas, Mare Jonker-Bos, Inge Roozen, Sabine Kropff, Els van Persijn van Meerten, Remco Zoethout, Elske Sitsen, Hendrik Helmerhorst, Fred Tijl, Christian Blank, Ellen Kapiteijn
<h3>Background</h3>Percutaneous hepatic perfusion can lead to meaningful hepatic tumour control in metastatic uveal melanoma, but its benefit is confined to liver metastases and does not address extrahepatic disease. Immune checkpoint inhibitors ipilimumab and nivolumab show limited activity in uveal melanoma, although retrospective studies suggest improved outcomes when combined with liver-directed therapies. This study aimed to evaluate the efficacy and safety of combining percutaneous hepatic perfusion with ipilimumab and nivolumab.<h3>Methods</h3>In this investigator-initiated, single-centre, open-label, randomised, phase 2 trial, adults aged 18–80 years with unresectable liver-only or liver-dominant metastatic uveal melanoma, WHO performance status 0–1, and with no previous systemic therapy were randomly assigned (1:1) to receive percutaneous hepatic perfusion alone (perfusion group) or percutaneous hepatic perfusion combined with ipilimumab plus nivolumab (combination group). Two perfusions with melphalan (3 mg/kg; maximum 220 mg) were scheduled in weeks 1 and 7. The combination group also received intravenous ipilimumab (1 mg/kg) and nivolumab (3 mg/kg) once every 3 weeks in weeks 0, 3, 6, and 9 without maintenance therapy. The primary endpoint, 1-year progression-free survival, was analysed in the intention-to-treat population; the safety analysis included all treated patients and was prospectively collected and graded using Common Terminology Criteria for Adverse Events version 5.0. The trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> (<span><span>NCT04283890</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>) and EudraCT (2018-004248-49) and is ongoing but no longer enrolling.<h3>Findings</h3>Between Dec 10, 2020, and Nov 15, 2024, 80 patients were screened, of whom 76 were eligible and assigned to the combination group (n=38) or perfusion group (n=38), including 49 (64%) men and 27 (36%) women. Median follow-up was 24·9 months (IQR 15·4–36·0). 1-year progression-free survival was 54·7% (95% CI 36·8–69·5) with combination therapy versus 15·8% (5·8–30·1) with perfusion alone (adjusted hazard ratio 0·34 [95% CI 0·19–0·60]; p=0·0002). Grade 3–4 treatment-related adverse events occurred in 31 (82%) of 38 patients with combination therapy compared to 15 (41%) of 37 patients with perfusion alone, due to both a higher incidence of severe perfusion-related events and immunotherapy-related adverse events. The most common grade 3–4 adverse events were thrombocytopenia (13 [34%] in the combination group <em>vs</em> five [14%] in the perfusion group), leukopenia (ten [26%] <e
{"title":"Percutaneous hepatic perfusion combined with ipilimumab and nivolumab for metastatic uveal melanoma (CHOPIN): a single-centre, open-label, randomised, phase 2 trial","authors":"Linde van den Hoek, Mark Burgmans, Thaïs Tong, Jelle Goeman, Frank Speetjens, Stephanie Zunder, Arian van Erkel, Rutger van der Meer, Carla van Rijswijk, Jacob Lutjeboer, Dominique Koolhaas, Mare Jonker-Bos, Inge Roozen, Sabine Kropff, Els van Persijn van Meerten, Remco Zoethout, Elske Sitsen, Hendrik Helmerhorst, Fred Tijl, Christian Blank, Ellen Kapiteijn","doi":"10.1016/s1470-2045(25)00720-x","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00720-x","url":null,"abstract":"<h3>Background</h3>Percutaneous hepatic perfusion can lead to meaningful hepatic tumour control in metastatic uveal melanoma, but its benefit is confined to liver metastases and does not address extrahepatic disease. Immune checkpoint inhibitors ipilimumab and nivolumab show limited activity in uveal melanoma, although retrospective studies suggest improved outcomes when combined with liver-directed therapies. This study aimed to evaluate the efficacy and safety of combining percutaneous hepatic perfusion with ipilimumab and nivolumab.<h3>Methods</h3>In this investigator-initiated, single-centre, open-label, randomised, phase 2 trial, adults aged 18–80 years with unresectable liver-only or liver-dominant metastatic uveal melanoma, WHO performance status 0–1, and with no previous systemic therapy were randomly assigned (1:1) to receive percutaneous hepatic perfusion alone (perfusion group) or percutaneous hepatic perfusion combined with ipilimumab plus nivolumab (combination group). Two perfusions with melphalan (3 mg/kg; maximum 220 mg) were scheduled in weeks 1 and 7. The combination group also received intravenous ipilimumab (1 mg/kg) and nivolumab (3 mg/kg) once every 3 weeks in weeks 0, 3, 6, and 9 without maintenance therapy. The primary endpoint, 1-year progression-free survival, was analysed in the intention-to-treat population; the safety analysis included all treated patients and was prospectively collected and graded using Common Terminology Criteria for Adverse Events version 5.0. The trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT04283890</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>) and EudraCT (2018-004248-49) and is ongoing but no longer enrolling.<h3>Findings</h3>Between Dec 10, 2020, and Nov 15, 2024, 80 patients were screened, of whom 76 were eligible and assigned to the combination group (n=38) or perfusion group (n=38), including 49 (64%) men and 27 (36%) women. Median follow-up was 24·9 months (IQR 15·4–36·0). 1-year progression-free survival was 54·7% (95% CI 36·8–69·5) with combination therapy versus 15·8% (5·8–30·1) with perfusion alone (adjusted hazard ratio 0·34 [95% CI 0·19–0·60]; p=0·0002). Grade 3–4 treatment-related adverse events occurred in 31 (82%) of 38 patients with combination therapy compared to 15 (41%) of 37 patients with perfusion alone, due to both a higher incidence of severe perfusion-related events and immunotherapy-related adverse events. The most common grade 3–4 adverse events were thrombocytopenia (13 [34%] in the combination group <em>vs</em> five [14%] in the perfusion group), leukopenia (ten [26%] <e","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"16 1","pages":"372-382"},"PeriodicalIF":0.0,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147360230","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}
Pub Date : 2026-03-02DOI: 10.1016/s1470-2045(26)00077-x
{"title":"England's National Cancer Plan: hollow promises?","authors":"","doi":"10.1016/s1470-2045(26)00077-x","DOIUrl":"https://doi.org/10.1016/s1470-2045(26)00077-x","url":null,"abstract":"","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"8 1","pages":"269"},"PeriodicalIF":0.0,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359532","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}
Pub Date : 2026-02-27DOI: 10.1016/s1470-2045(26)00050-1
Andrea Necchi, Brigida A Maiorano, Joep J de Jong, James A Proudfoot, Giuseppe Basile, Antonio Cigliola, Chiara Mercinelli, Valentina Tateo, Michela Piacentini, Giovanni Pastorino, Gaia Latini, Enrico Tomasi, Elai Davicioni, Marco Moschini, Giorgio Brembilla, Maurizio Colecchia, Francesco de Cobelli, Alberto Briganti, Jeffrey S Ross, Dean C Pavlick, Francesco Montorsi
<h3>Background</h3>Standard-of-care treatment for muscle-invasive bladder cancer is radical cystectomy with neoadjuvant chemotherapy; however, approximately 50% of patients are ineligible for or refuse neoadjuvant chemotherapy. Neoadjuvant pembrolizumab and sacituzumab govitecan have shown activity as monotherapy in muscle-invasive bladder cancer. We aimed to evaluate the clinical activity of neoadjuvant sacituzumab govitecan plus pembrolizumab and adjuvant pembrolizumab, within a bladder-sparing approach.<h3>Methods</h3>SURE-02 is a single-arm, phase 2 study, conducted at IRCCS San Raffaele Hospital in Milan, Italy. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status 0–1, were newly diagnosed with histologically confirmed muscle-invasive bladder cancer (stage cT2–T3bN0M0), were deemed ineligible for or declined cisplatin-based neoadjuvant chemotherapy, and were scheduled for radical cystectomy. Patients received four cycles of intravenous pembrolizumab 200 mg on day 1 and intravenous sacituzumab govitecan 7·5 mg/kg on day 1 and day 8, every 3 weeks, followed by radical cystectomy or redo-transurethral resection of the bladder tumour (re-TURBT; after multidisciplinary tumour board discussion in patients who refused to undergo radical cystectomy) and 13 cycles of postsurgical pembrolizumab 200 mg, every 3 weeks. The primary endpoint was the clinical complete response rate, defined as negative imaging and no viable tumour at re-TURBT in patients not undergoing radical cystectomy. Efficacy was assessed in all patients who received at least one dose of study treatment and had a baseline evaluation (intention-to-treat population). This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, <span><span>NCT05535218</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, and is active but not recruiting.<h3>Findings</h3>Between Oct 2, 2023, and Feb 26, 2025, 63 patients were screened, 49 patients (median age 66 years [IQR 61–71]; eight [16%] female and 41 [84%] male; 48 [98%] White and one [2%] Black) were enrolled, treated, and evaluated for safety and efficacy. 33 (67%) had a cT2 stage, 21 (43%) had a centrally confirmed variant histology. After a median follow-up of 14 months (IQR 8–18), 19 (39% [95% CI 25–54]) patients had a clinical complete response; all of whom underwent a re-TURBT. All patients with clinical complete response were metastasis-free; two patients developed an intravesical relapse. Grade 3 treatment-related adverse-events occurred in eight patients (16%), the most common being diarrhoea (in four [8%]). There were n
{"title":"Neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by adjuvant pembrolizumab, in patients with muscle-invasive bladder cancer (SURE-02): a single-arm, phase 2 study","authors":"Andrea Necchi, Brigida A Maiorano, Joep J de Jong, James A Proudfoot, Giuseppe Basile, Antonio Cigliola, Chiara Mercinelli, Valentina Tateo, Michela Piacentini, Giovanni Pastorino, Gaia Latini, Enrico Tomasi, Elai Davicioni, Marco Moschini, Giorgio Brembilla, Maurizio Colecchia, Francesco de Cobelli, Alberto Briganti, Jeffrey S Ross, Dean C Pavlick, Francesco Montorsi","doi":"10.1016/s1470-2045(26)00050-1","DOIUrl":"https://doi.org/10.1016/s1470-2045(26)00050-1","url":null,"abstract":"<h3>Background</h3>Standard-of-care treatment for muscle-invasive bladder cancer is radical cystectomy with neoadjuvant chemotherapy; however, approximately 50% of patients are ineligible for or refuse neoadjuvant chemotherapy. Neoadjuvant pembrolizumab and sacituzumab govitecan have shown activity as monotherapy in muscle-invasive bladder cancer. We aimed to evaluate the clinical activity of neoadjuvant sacituzumab govitecan plus pembrolizumab and adjuvant pembrolizumab, within a bladder-sparing approach.<h3>Methods</h3>SURE-02 is a single-arm, phase 2 study, conducted at IRCCS San Raffaele Hospital in Milan, Italy. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status 0–1, were newly diagnosed with histologically confirmed muscle-invasive bladder cancer (stage cT2–T3bN0M0), were deemed ineligible for or declined cisplatin-based neoadjuvant chemotherapy, and were scheduled for radical cystectomy. Patients received four cycles of intravenous pembrolizumab 200 mg on day 1 and intravenous sacituzumab govitecan 7·5 mg/kg on day 1 and day 8, every 3 weeks, followed by radical cystectomy or redo-transurethral resection of the bladder tumour (re-TURBT; after multidisciplinary tumour board discussion in patients who refused to undergo radical cystectomy) and 13 cycles of postsurgical pembrolizumab 200 mg, every 3 weeks. The primary endpoint was the clinical complete response rate, defined as negative imaging and no viable tumour at re-TURBT in patients not undergoing radical cystectomy. Efficacy was assessed in all patients who received at least one dose of study treatment and had a baseline evaluation (intention-to-treat population). This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT05535218</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and is active but not recruiting.<h3>Findings</h3>Between Oct 2, 2023, and Feb 26, 2025, 63 patients were screened, 49 patients (median age 66 years [IQR 61–71]; eight [16%] female and 41 [84%] male; 48 [98%] White and one [2%] Black) were enrolled, treated, and evaluated for safety and efficacy. 33 (67%) had a cT2 stage, 21 (43%) had a centrally confirmed variant histology. After a median follow-up of 14 months (IQR 8–18), 19 (39% [95% CI 25–54]) patients had a clinical complete response; all of whom underwent a re-TURBT. All patients with clinical complete response were metastasis-free; two patients developed an intravesical relapse. Grade 3 treatment-related adverse-events occurred in eight patients (16%), the most common being diarrhoea (in four [8%]). There were n","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147319980","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}
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