Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies
Susumu Hijioka, Daiki Yamashige, Minoru Esaki, Goro Honda, Ryota Higuchi, Toshihiko Masui, Yasuhiro Shimizu, Masayuki Ohtsuka, Yusuke Kumamoto, Akio Katanuma, Naoto Gotohda, Hirofumi Akita, Michiaki Unno, Itaru Endo, Yukihiro Yokoyama, Suguru Yamada, Ippei Matsumoto, Takao Ohtsuka, Satoshi Hirano, Hiroaki Yasuda, Manabu Kawai, Taku Aoki, Masafumi Nakamura, Daisuke Hashimoto, Toshiki Rikiyama, Akihiko Horiguchi, Tsutomu Fujii, Shugo Mizuno, Keiji Hanada, Masaji Tani, Takashi Hatori, Tetsuhide Ito, Masataka Okuno, Shingo Kagawa, Hiroshi Tajima, Tatsuya Ishii, Motokazu Sugimoto, Shunsuke Onoe, Hideki Takami, Ryoji Takada, Takayuki Miura, Yusuke Kurita, Keiko Kamei, Yuko Mataki, Kazuichi Okazaki, Yoshifumi Takeyama, Hiroki Yamaue, Sohei Satoi, Takahiro Tsuchikawa, Takashi Taniguchi, Masahiro Iseki, Masahiro Shimura, Toru Watanabe, Kazuyuki Gyoten, Akinori Shimizu, Hiromitsu Maehira, Hidetoshi Eguchi, Hiroyuki Isayama, Izumi Komoto, Ryuichiro Doi, Junji Furuse, Takuji Okusaka, Chigusa Morizane, Hisato Igarashi, Masayuki Kitano, Tamotsu Kuroki, Seiji Tanno, Yoshihisa Tsuji, Atsushi Masamune, Yoshiki Hirooka
Abstract
BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.