Annals of Oncology最新文献

{"title":"Shaping the future of ¹⁷⁷Lu-PSMA-617 radiopharmaceutical therapy in prostate cancer: is earlier better, or is patient selection key?","authors":"A A Azad, M S Hofman","doi":"10.1016/j.annonc.2025.09.002","DOIUrl":"10.1016/j.annonc.2025.09.002","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058255","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":"Phase Ib and dose-expansion study of GSK3326595, a PRMT5 inhibitor as monotherapy and in combination with pembrolizumab in patients with advanced cancers.","authors":"M M Gounder, P Martin-Romano, A Italiano, L L Siu, P A Cassier, G S Falchook, I S Lossos, D W Rasco, J F Hilton, M A McKean, F L Opdam, J Strauss, M De Jonge, J S P Vermaat, T Crossman, M Zajac, A Tarkar, F Gonzalez Carreras, B E Kremer, O Barbash, S Segal, R Parasrampuria, S Postel-Vinay","doi":"10.1016/j.annonc.2025.08.3757","DOIUrl":"10.1016/j.annonc.2025.08.3757","url":null,"abstract":"<p><strong>Background: </strong>Protein arginine methyltransferase 5 inhibition often leads to a decrease in cell growth and survival in cancer cell lines. GSK3326595 is a first-generation protein arginine methyltransferase 5 inhibitor.</p><p><strong>Patients and methods: </strong>METEOR-1 was a first-in-human, open-label, multicenter, three-part phase I study (NCT02783300) in patients with solid tumors and non-Hodgkin lymphoma (NHL). The objectives of part 1 were to determine the recommended phase II dose (RP2D), assess safety, evaluate preliminary clinical activity, and study the pharmacokinetics of oral GSK3326595 monotherapy. Part 2 enrolled patients at the RP2D to further evaluate clinical activity and safety. Part 3 explored the RP2D of GSK3326595 with pembrolizumab.</p><p><strong>Results: </strong>A total of 288 patients were treated. In part 1, 69 patients received once daily (od) or twice a day (b.i.d.) GSK3326595 in doses ranging from 12.5 to 600 mg/day. In part 2, 218 patients received either 400 mg or 300 mg od, with the RP2D amended from 400 mg to 300 mg od due to toxicities. In part 3, 10 patients received GSK3326595 at 100 mg/day with pembrolizumab 200 mg intravenously every 3 weeks. Pharmacokinetics revealed that GSK3326595 was rapidly absorbed (T_max: 2-3 hours), with a mean terminal half-life of 4-6 hours. Dose-dependent increases in plasma exposure (C_max and AUC) were observed with both od and b.i.d. dosing. The most common adverse events at the RP2D included fatigue (57%), nausea (48%), and anemia (48%). Four partial responses (PRs) were observed in part 1 at doses of 200 mg (n = 2), 300 mg (n = 1), and 400 mg (n = 1). Two complete responses and one PR were seen in NHL [i.e. follicular (n = 2) lymphoma, diffuse large B-cell lymphoma (n = 1)], one PR in adenoid cystic carcinoma, and one PR in HR-positive breast cancer in part 2. No responses were observed in part 3.</p><p><strong>Conclusions: </strong>GSK3326595 monotherapy demonstrated modest antitumor activity. Further research in adenoid cystic carcinoma and NHL is warranted.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038850","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":"Randomized, Double-Blind, Phase III LEAP-003 Study of First-Line Lenvatinib Plus Pembrolizumab Versus Placebo Plus Pembrolizumab for Unresectable or Metastatic Melanoma.","authors":"A Arance, M-A Berciano-Guerrero, J Guo, M S Carlino, P A Ascierto, M Burotto, L Mortier, P Queirolo, V Chiarion-Sileni, J Schachter, X Zhang, J Martin-Liberal, M Del Vecchio, C E Okpara, C Dutcus, J Zhang, S J Diede, T Neff, G V Long","doi":"10.1016/j.annonc.2025.08.008","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.08.008","url":null,"abstract":"<p><strong>Background: </strong>Lenvatinib plus pembrolizumab demonstrated antitumor activity in advanced melanoma after prior anti-PD-(L)1 therapy in LEAP-004. Here, we report results from LEAP-003 (NCT03820986) which evaluated first-line lenvatinib plus pembrolizumab versus placebo plus pembrolizumab in unresectable advanced melanoma.</p><p><strong>Participants and methods: </strong>Participants with unresectable stage III or IV melanoma, previously untreated with PD-1 or PD-L1 checkpoint inhibitors, were randomly assigned 1:1 to pembrolizumab 200 mg intravenously every 3 weeks plus either lenvatinib 20 mg or placebo orally once daily. Dual primary end points were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review and overall survival (OS). PFS was formally tested at the first interim analysis; OS at the final analysis. An external data monitoring committee regularly reviewed safety and efficacy. Three interim analyses and a final analysis were planned.</p><p><strong>Results: </strong>Overall, 674 participants were assigned to lenvatinib plus pembrolizumab (n = 334) or placebo plus pembrolizumab (n = 340). Median PFS at first interim analysis was 8.4 months for lenvatinib plus pembrolizumab versus 4.0 months for placebo plus pembrolizumab (HR, 0.72; 95% CI, 0.59-0.88; P = 0.0008). This benefit was not maintained at final analysis (HR, 0.83; 95% CI, 0.69-1.00). Median OS at final analysis was 25.8 months for lenvatinib plus pembrolizumab versus 39.5 months for placebo plus pembrolizumab (HR, 1.20; 95% CI, 0.97-1.48; P = 0.9521). Grade 3-5 treatment-related adverse events occurred in 58.7% of participants receiving lenvatinib plus pembrolizumab versus 29.0% receiving placebo plus pembrolizumab.</p><p><strong>Conclusion: </strong>Lenvatinib plus pembrolizumab did not provide additional benefit versus placebo plus pembrolizumab in participants with unresectable advanced melanoma. Thus, the trial was terminated early, and the third interim analysis became the final analysis. Immunotherapy remains the standard of care for advanced melanoma.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939731","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":"Circulating kidney injury molecule-1 (KIM-1) and association with outcome to adjuvant immunotherapy in renal cell carcinoma.","authors":"B I Rini, L Albiges, X Tang, H Koeppen, A Bex, C Suárez, R Uzzo, H Hamidi, Z J Assaf, S Dubey, E T Goluboff, C Carter, S K Pal, R Banchereau, W Xu, M A Huseni","doi":"10.1016/j.annonc.2025.08.007","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.08.007","url":null,"abstract":"<p><strong>Background: </strong>Adjuvant immunotherapy is currently the standard of care for patients with resected renal cell carcinoma (RCC) at increased risk of recurrence, but there are no biomarkers available to guide treatment. Kidney injury molecule-1 (KIM-1) has previously been described as a potential circulating biomarker in renal cell carcinoma.</p><p><strong>Patients and methods: </strong>Biomarkers and outcomes among patients who participated in a randomized phase III trial of adjuvant atezolizumab versus placebo in resected RCC (IMmotion010) were evaluated. This trial did not meet its primary DFS endpoint in the intention-to-treat population. An affinity-based proximity extension proteomics assay was used to compare levels of circulating proteins among baseline (post-nephrectomy) serum samples and samples taken at time of recurrence.</p><p><strong>Results: </strong>Serum KIM-1 was the most significantly enriched protein at recurrence versus baseline. Patients with serum KIM-1^high at baseline had worse disease-free survival (DFS) (hazard ratio 1.68, 95% CI 1.35-2.09), but also had improved DFS when treated with adjuvant atezolizumab versus placebo (hazard ratio 0.72, 95% CI 0.52-0.99). An increase in KIM-1 during follow-up was associated with worse DFS compared to patients with no increase in KIM-1. Within the KIM-1 high subgroup, longer DFS following atezolizumab treatment was associated with increased baseline expression of T effector and Th1 signatures, while shorter DFS was associated with increased baseline expression of matrix remodeling genes and protumor cytokines.</p><p><strong>Conclusion: </strong>These analyses suggest that elevated post-nephrectomy plasma KIM-1 level and kinetics are prognostic, supporting the hypothesis that KIM-1 is a biomarker for minimal residual disease in RCC. As KIM-1^high patients are also enriched for benefit from adjuvant immunotherapy, biomarker driven adjuvant therapy should be evaluated as a potential new paradigm in RCC.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939700","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":"Early and locally advanced non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.","authors":"A Zer, M-J Ahn, F Barlesi, L Bubendorf, D De Ruysscher, P Garrido, O Gautschi, L E Hendriks, P A Jänne, K M Kerr, C Mascaux, T Mitsudomi, S Peters, C Rolfo, A Sacher, S Senan, P Ugalde, N B Leighl","doi":"10.1016/j.annonc.2025.08.003","DOIUrl":"10.1016/j.annonc.2025.08.003","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939687","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":"A-BRAVE trial: a phase III randomized trial with anti-PD-L1 avelumab in high-risk triple-negative early breast cancer patients.","authors":"P F Conte, M V Dieci, G Bisagni, P Schmid, A Zambelli, F Piacentini, M De Laurentiis, A G Favaretto, S Tamberi, G V Bianchi, C Zamagni, S Cinieri, D C Corsi, L Del Mastro, A Ferro, A Gennari, M Mion, A Musolino, L Nicolé, P Del Bianco, G L De Salvo, V Guarneri","doi":"10.1016/j.annonc.2025.08.005","DOIUrl":"10.1016/j.annonc.2025.08.005","url":null,"abstract":"<p><strong>Background: </strong>The A-BRAVE trial evaluated the efficacy of avelumab, an anti-programmed death-ligand 1 (PD-L1) antibody, as adjuvant treatment of patients with early triple-negative breast cancer (TNBC) at high risk.</p><p><strong>Patients and methods: </strong>A-BRAVE is a phase III study that randomly assigned patients with high-risk early TNBC to 1 year of avelumab versus observation, after completion of standard surgery and (neo)adjuvant chemotherapy. High-risk was defined as either: (i) ≥pN2/any pT, pN1/pT2, or pN0/pT3 after primary surgery (stratum A); or (ii) invasive residual disease (breast and/or nodes) after neoadjuvant chemotherapy (stratum B). Coprimary endpoints were disease-free survival (DFS) in the intention-to-treat (ITT) and stratum B populations. Secondary endpoints were overall survival (OS) and DFS in PD-L1-positive patients. PD-L1 was evaluated in treatment-naïve tumor samples by immunohistochemistry (73-10 RUO assay, Agilent Technologies) and digital pathology.</p><p><strong>Results: </strong>From June 2016 to October 2020, 466 patients were randomly assigned: 383 entered stratum B (82%) and 83 entered stratum A (18%). At a median follow-up of 52.1 months, avelumab did not significantly improve DFS in the ITT population [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.61-1.09, P = 0.172; 3-year DFS estimates were 68.3% for avelumab versus 63.2%], or in stratum B (HR 0.80, 95% CI 0.58-1.10, P = 0.170; 3-year DFS estimates were 66.9% for avelumab versus 60.7%). In a descriptive analysis, avelumab reduced the hazard of OS events: HR 0.66, 95% CI 0.45-0.97. The 3-year OS estimates for avelumab and control arm were 84.8% (95% CI 79.5% to 88.8%) and 76.3% (95% CI 70.1% to 81.3%), respectively. PD-L1 status was prognostic but not predictive for avelumab benefit in terms of DFS (test for interaction P = 0.155).</p><p><strong>Conclusions: </strong>For patients with TNBC at high risk of relapse who complete standard treatment with surgery and (neo)adjuvant chemotherapy, 1 year of adjuvant avelumab versus observation did not improve DFS. However, a descriptive analysis suggests a potential favorable impact on OS.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939715","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":"Mechanism-enhanced population science: strengthening population studies through functional insights.","authors":"T Pandya, Y Cao, K Smith-Byrne, C Swanton","doi":"10.1016/j.annonc.2025.08.006","DOIUrl":"10.1016/j.annonc.2025.08.006","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939745","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":"Ten-year survival rates by PSA nadir in patients with metastatic hormone-sensitive prostate cancer: long-term survival analysis from the ECOG-ACRIN 3805 (CHAARTED) trial.","authors":"A Tripathi, Y Chen, D F Jarrard, J A Garcia, R Dreicer, G Liu, M H Hussain, D H Shevrin, M Cooney, M A Eisenberger, M Kohli, E R Plimack, N J Vogelzang, J Picus, M A Carducci, R S DiPaola, C J Sweeney","doi":"10.1016/j.annonc.2025.08.004","DOIUrl":"10.1016/j.annonc.2025.08.004","url":null,"abstract":"<p><strong>Background: </strong>The CHAARTED trial investigated the long-term survival of patients with metastatic hormone-sensitive prostate cancer (HSPC) treated with androgen deprivation therapy (ADT) with or without docetaxel (Taxotere). This analysis focuses on 10-year overall survival (OS) stratified by disease volume and on-therapy prostate-specific antigen (PSA) levels at 6 months.</p><p><strong>Patients and methods: </strong>OS was calculated using the Kaplan-Meier method from randomization to death or last known alive date. Patients were grouped based on baseline disease characteristics [high-volume (HV) or low-volume (LV)] and PSA levels at 6 months (<0.2 ng/ml versus ≥0.2 ng/ml). Multivariable Cox regression analysis was used to evaluate correlation of PSA nadir with OS adjusted for treatment arm, disease volume, Gleason score, and prior local therapy.</p><p><strong>Results: </strong>Of 790 patients, 225 were without recorded death after a median follow-up of 10 years. The 10-year OS was 25.9% (ADT + docetaxel) versus 22.5% [ADT; hazard ratio (HR) 0.78, P = 0.004]. HV patients treated with docetaxel had significantly higher OS (20.9% versus 11.4%, P < 0.0001). PSA <0.2 ng/ml at 6 months was associated with improved median OS in both ADT + docetaxel (100.3 versus 45.4 months, P < 0.0001) and ADT (116.8 versus 31.8 months, P < 0.0001) arms. PSA nadir <0.2 ng/l at 6 months was an independent predictor of improved OS (HR 0.41, P < 0.0001) adjusting for disease volume, prior local therapy, Gleason score and treatment arm.</p><p><strong>Conclusions: </strong>Long-term follow-up confirms that ADT + docetaxel significantly improves OS in metastatic HSPC patients with HV disease. PSA nadir <0.2 ng/ml at 6 months is a strong prognostic marker for OS, supporting its use in response-adapted de-escalation strategies.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939711","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":"Risk of disease progression in first-line metastatic colorectal cancer therapy to guide disease reassessments-analysis of 11 trials by AIO and GONO.","authors":"M M Germani, V Heinemann, D Rossini, L Fischer von Weikersthal, F Pietrantonio, K Heinrich, A Stahler, S Lonardi, F Kaiser, T Decker, L Salvatore, L Weiss, F Morano, M Fuchs, F Bergamo, C Antoniotti, G Masi, S Stintzing, P Frumento, C Cremolini, D P Modest","doi":"10.1016/j.annonc.2025.08.001","DOIUrl":"10.1016/j.annonc.2025.08.001","url":null,"abstract":"<p><strong>Background: </strong>We evaluated the distribution and risk of disease progression (PD) in first-line therapy of unresected metastatic colorectal cancer (mCRC) patients receiving chemotherapy + biologics. The aim of the analysis is to provide guidance for the timing of disease reassessments during first-line therapy.</p><p><strong>Patients and methods: </strong>Individual data of 2939 unresected patients from TRIBE, MOMA, TRIBE2, VALENTINO, ATEZOTRIBE, TRIPLETE, FIRE-3, XELAVIRI, PANAMA, FIRE-4 and FIRE-4.5 were analyzed. The frequency and risk of PD events were calculated for individual timepoints during therapy. RAS/BRAF profiling, tumor sidedness, type of therapy and early tumor shrinkage (ETS) were used to identify subgroups for risk assessment. A Cox regression model to predict first-line progression-free survival (PFS) was built.</p><p><strong>Results: </strong>In the overall population, the maximum frequency of PD events was observed at 7.6 months, with an absolute PD risk of 19%. Then, the PD risk flattened, achieving a maximum of 23% at 14 months in RAS/BRAF-wild-type patients (n = 1786), 25% at 10 months in RAS-mutant patients (n = 973) and 35% at 8 months in BRAF-mutant patients (n = 180). Eastern Cooperative Oncology Group performance status >0, right-sidedness, initially unresected primary tumor, higher number of organs involved by metastases and BRAF mutation were independently associated with a higher risk of PD in first line. The impact of baseline characteristics on PFS was mitigated after incorporation of ETS in the model.</p><p><strong>Conclusions: </strong>The distribution of PD events does not follow a Gaussian pattern, with the highest density observed between the third and fourth reassessment of a bimonthly surveillance schedule. In clearly unresectable patients, restaging should focus on the interval between 6 and 10 months and not on the initiation of systemic therapy. Our model might be helpful to schedule radiological reassessments according to baseline characteristics, early response and the expected duration of each treatment efficacy.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939708","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":"Incidence trends and long-term survival in early-onset colorectal cancer: a nationwide Swedish study.","authors":"S Barot, A Liljegren, C Nordenvall, J Blom, C Radkiewicz","doi":"10.1016/j.annonc.2025.07.019","DOIUrl":"10.1016/j.annonc.2025.07.019","url":null,"abstract":"<p><strong>Background: </strong>Early-onset colorectal cancer (EOCRC, diagnosis before age 50) is increasing globally. Survival comparisons with late-onset colorectal cancer (CRC) are inconsistent, however, and long-term excess mortality remains poorly understood. This Swedish population-based study aimed to evaluate trends in incidence, survival, and long-term excess mortality in early- versus late-onset CRC.</p><p><strong>Materials and methods: </strong>We identified all incident colorectal adenocarcinomas recorded in the Swedish National Cancer Register from 1993 to 2019. Incidence trends were quantified using annual percentage changes and relative survival differences were assessed using excess mortality rate ratios, both from Poisson regression models with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>A total of 47 864 right-sided colon, 40 664 left-sided colon, and 47 082 rectal cancer cases were included. EOCRC patients were more frequently diagnosed with metastatic disease, compared with late-onset CRC. EOCRC incidence increased across all subsites, with annual percentage changes ranging from 2.04 (95% CI 1.51-2.56) for rectal to 2.64 (95% CI 2.02-2.37) for right-sided colon cancer, while an increase among late-onset cases was observed only for right-sided colon cancer. Crude 5-year relative survival was similar across age groups, but after full adjustment (including metastatic stage), EOCRC was associated with better survival, with excess mortality rate ratios ranging from 0.76 (95% CI 0.68-0.84) for rectal cancer to 0.83 (95% CI 0.74-0.92) for right-sided colon cancer. Notably, excess mortality remained elevated 5-10 years after diagnosis in both age groups.</p><p><strong>Conclusions: </strong>EOCRC incidence is increasing in Sweden, aligning with global trends. Although younger patients were more often diagnosed at an advanced stage of disease, they had similar crude survival and better stage-adjusted survival, compared with older patients. The persistent long-term excess mortality in both groups, even during periods when CRC patients are typically considered statistically cured, highlights the need for extended follow-up and tailored survivorship care.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858818","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}