Long-term outcome of cytoreductive hepatectomy in metastatic neuroendocrine neoplasia G3: a single center retrospective analysis

Background Cytoreductive hepatectomy for liver metastases from G3 neuroendocrine tumors (NETLM) and neuroendocrine carcinomas (NECLM) remains an issue of controversy, with guidelines recommending surgery for limited metastatic burden from NET G3 and systemic therapy for NEC. We assessed surgical and oncologic outcomes after hepatectomy, and factors associated with overall survival (OS). Methods Patients undergoing liver resections for G3 NETLM (n=27) and NECLM (n=15) between January 2000 to December 2020 were compared, stratified for median OS and opposed to G1 (n=75) and G2 NETLM (n=120). Results Median OS after hepatectomy was 12.5 in NETLM G1 patients, 11.2 in G2, 6.3 in G3 and 2.4 years in NECLM (p<0.001), with progression-free survival of 2.1, 1.3, 0.8 and 0.7 years, respectively (p<0.001). Bilobar lesions (92% vs. 29%; p<0.001) and numbers (p<0.001) were higher in NETLM G3 than in NECLM. Major resections (22% vs. 20%; p=1.000), severe complications (33% vs. 20%; p=0.485), and 90-day mortality (7% vs. 7%; p=1.000) were similarly frequent. NETLM G3 long- survivors did not reach median OS after 7 years and 4 years in NECLM. Lesion diameter and count >10 were associated with survival in NETLM G3, while no patient or tumor characteristics were linked to OS in NECLM. Conclusion Although G3 NETLM and NECLM display significantly worse prognosis after cytoreductive hepatectomy compared to G1 and G2 NETLM, some patients might benefit from surgery. While tumor size and lesion count were linked to OS, identification of factors besides standard clinical characteristics are needed to stratify patients as surgical candidates.