Analysis of Optimal Treatment Sequencing of Surufatinib and Somatostatin Analogs in Neuroendocrine Tumors: A Retrospective Cohort Study

Inclusion criteria

• Histopathologically confirmed locally advanced unresectable, metastatic, or postoperative recurrent neuroendocrine tumors (NETs), any primary site.
• Grade G1 or G2 based on Ki-67 index and/or mitotic count.
• Somatostatin receptor 2 (SSTR2) positive confirmed by immunohistochemistry (IHC) or somatostatin receptor imaging (e.g., 68Ga-PET/CT).
• Received one of the following two sequential treatment patterns:

Cohort A (Surufatinib → SSA): First-line surufatinib monotherapy followed by second-line long-acting somatostatin analog (SSA; lanreotide or octreotide long-acting release formulation) after disease progression.

Cohort B (SSA → Surufatinib): First-line long-acting SSA monotherapy followed by second-line surufatinib after disease progression.

• Each line of treatment duration at least 1 cycle (surufatinib ≥4 weeks; SSA ≥1 injection).
• Complete baseline clinical data, treatment start/end dates, and serial imaging evaluation reports available to determine progression-free survival for each line.
• Age ≥18 years at first-line treatment initiation.
• Permitted concomitant treatments during study drug administration (not considered as exclusion criteria):

Best supportive care (e.g., antidiarrheals, analgesics, hepatoprotective agents, symptomatic treatment for hormone secretion).

Local palliative interventions for focal lesions (e.g., transarterial embolization/chemoembolization, ablation for liver metastases) or cytoreductive surgery, provided they do not interrupt systemic study treatment or violate protocol.

For functional NETs, short-acting somatostatin analogs as rescue therapy for symptom control (frequency and dose to be recorded).

Exclusion criteria

• Received any combined systemic therapy (e.g., chemotherapy, other targeted therapy, immunotherapy) in addition to surufatinib or SSA during first-line or second-line treatment.
• Missing key baseline data (e.g., pathological grade, primary tumor site) or incomplete treatment/follow-up imaging data precluding accurate assessment of progression-free survival.
• Presence of active, uncontrolled serious infection or another active malignancy at the start of first-line treatment that may interfere with assessment of neuroendocrine tumor progression or patient survival prognosis (except cured skin basal cell carcinoma or carcinoma in situ).