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.

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Journal
BMC Medicine
Published
2026-06-25
DOI
https://doi.org/10.1186/s12916-026-05000-w
Primary Topic
Neuroendocrine Tumor Research Advances
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article
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article

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)

Hongyun Zhao, Yinying Wu, Ce Wang, Dan Cao et al.
BMC Medicine
Neuroendocrine Tumor Research Advances
article

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)

Hongyun Zhao, Yinying Wu, Ce Wang, Dan Cao, Y T, Yanwei Su, Jiaqi Xu, J Hao, Yi-Xiang Wang, 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
article en

Abstract

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.

BMC Medicine
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)
Good health and well-being
Openalex Percentile: Top 8%
Neuroendocrine Tumor Research Advances
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