Association of adjuvant somatostatin analogue therapy with disease-free survival in patients with gastroenteropancreatic neuroendocrine tumours: a Chinese multi-institutional propensity score matched and weighted analysis (CASSANET-GEP)
BACKGROUND: Recurrence remains a major concern after curative-intent resection of gastroenteropancreatic neuroendocrine tumours (GEP-NETs), and evidence to guide postoperative adjuvant therapy is limited. METHODS: We performed a multicentre retrospective cohort study across nine university-affiliated hospitals in China, including patients with grade 1-3 GEP-NETs who underwent curative-intent resection between January 2007 and December 2024; follow-up ended on 1 October 2025. Exposure was postoperative adjuvant SSAs. The primary endpoint was disease-free survival (DFS) and the secondary endpoint was overall survival (OS). DFS and OS were estimated using Kaplan-Meier methods, and associations were evaluated using Cox regression after propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Time-related bias was addressed using time-dependent Cox and landmark analyses at 3 and 6 months after surgery. RESULTS: Among 1602 patients, 358 received adjuvant SSAs. After 1:1 PSM, 560 patients were retained with improved baseline balance. Adjuvant SSAs were associated with a lower recurrence risk in the overall cohort in unadjusted (HR 0.466, 95% CI 0.323-0.673; p < 0.001) and IPTW-adjusted analyses (HR 0.419, 95% CI 0.278-0.631; p < 0.001), with similar directionality in G-NETs and P-NETs, whereas estimates in E-NETs were imprecise. In time-dependent Cox analyses treating SSAs as an ever-started time-varying exposure, adjuvant SSAs remained associated with longer DFS in the whole cohort (adjusted HR 0.519, 95% CI 0.353-0.764; p < 0.001), and findings were consistent in landmark analyses at 3 months (adjusted HR 0.523, 95% CI 0.339-0.806; p = 0.003) and 6 months (adjusted HR 0.537, 95% CI 0.356-0.811; p = 0.003). In the overall cohort, 24- and 36-month DFS rates were 92.4% and 89.3% in the SSAs cohort versus 86.9% and 84.2% in controls, respectively; corresponding 24- and 36-month OS rates were 99.1% and 98.7% versus 97.2% and 96.9%, respectively. CONCLUSIONS: In this large multicentre real-world cohort, adjuvant SSAs were associated with longer DFS after curative-intent resection of GEP-NETs. The overall direction of association remained consistent in propensity-adjusted, time-dependent, and landmark analyses, supporting the robustness of the primary findings. Prospective studies are needed to confirm effectiveness and refine patient selection.
Authors
- Hongyun Zhao (ORCID: https://orcid.org/0000-0002-1251-3888)
- Yinying Wu (ORCID: https://orcid.org/0000-0003-3075-800X)
- Ce Wang (ORCID: https://orcid.org/0000-0002-9729-9592)
- Dan Cao (ORCID: https://orcid.org/0000-0002-3331-823X)
- Y T
- Yanwei Su (ORCID: https://orcid.org/0000-0002-9339-092X)
- Jiaqi Xu (ORCID: https://orcid.org/0000-0002-6735-9267)
- J Hao
- Yi-Xiang Wang (ORCID: https://orcid.org/0000-0002-4021-4228)
- Jie Yu
- M S Wang
- Guiqi Wang
- Qiyun Tang
- Lijie Song
- Dongbing Zhao
- Qilong Chen
- Enxiao Li
- Haibo Lu
- Xiangling Wang
- Xiaofen Li
- Yuanjie Sun
- Huike Wang
Institutions
- Xinjiang Medical University (CN)
- Harbin Medical University (CN)
- Shanxi Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Sichuan University (CN)
- First Affiliated Hospital of Xinjiang Medical University (CN)
- National Cancer Center (US)
- Third Affiliated Hospital of Harbin Medical University (CN)
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- First Hospital of Shanxi Medical University (CN)
- Jiangsu Cancer Hospital (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
- Qilu Hospital of Shandong University (CN)
- Jiangsu Provincial Hospital of Traditional Chinese Medicine (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- BMC Medicine
- Published
- 2026-06-25
- DOI
- https://doi.org/10.1186/s12916-026-05000-w
- Primary Topic
- Neuroendocrine Tumor Research Advances
- Type
- article
- Field-Weighted Citation Impact
- 0.00