The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study

Background: Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients...

Full description

Authors: Rangelova, E; Stoop, TF; van Ramshorst, TME; Ali, M; van Bodegraven, EA; Javed, AA; Hashimoto, D; Steyerberg, E; Banerjee, A; Jain, A; Sauvanet, A; Serrablo, A; Giani, A; Giardino, A; Zerbi, A; Arshad, A; Wijma, AG; Coratti, A; Zironda, A; Socratous, A; Rojas, A; Halimi, A; Ejaz, A; Oba, A; Patel, BY; Björnsson, B; Reames, BN; Tingstedt, B; Goh, BKP; Payá-Llorente, C; Del Pozo, CD; González-Abós, C; Medin, C; van Eijck, CHJ; de Ponthaud, C; Takishita, C; Schwabl, C; Månsson, C; Ricci, C; Thiels, CA; Douchi, D; Hughes, DL; Kilburn, D; Flanking, D; Kleive, D; Silva, DS; Edil, BH; Pando, E; Moltzer, E; Kauffman, EF; Warren, E; Bozkurt, E; Sparrelid, E; Thoma, E; Verkolf, E; Ausania, F; Giannone, F; Hüttner, FJ; Burdio, F; Souche, FR; Berrevoet, F; Daams, F; Motoi, F; Saliba, G; Kazemier, G; Roeyen, G; Nappo, G; Butturini, G; Ferrari, G; Fusai, GK; Honda, G; Sergeant, G; Karteszi, H; Takami, H; Suto, H; Matsumoto, I; Mora-Oliver, I; Frigerio, I; Fabre, JM; Chen, J; Sham, JG; Davide, J; Urdzik, J; de Martino, J; Nielsen, K; Okano, K; Kamei, K; Okada, K; Tanaka, K; Labori, KJ; Goodsell, KE; Alberici, L; Webber, L; Kirkov, L; de Franco, L; Miyashita, M; Maglione, M; Gramellini, M; Ramera, M; Amaral, MJ; Ramaekers, M; Truty, MJ; van Dam, MA; Stommel, MWJ; Petrikowski, M; Imamura, M; Hayashi, M; D'Hondt, M; Brunner, M; Hogg, ME; Zhang, C; Suárez-Muñoz, MA; Luyer, MD; Unno, M; Mizuma, M; Janot, M; Sahakyan, MA; Jamieson, NB; Busch, OR; Bilge, O; Belyaev, O; Franklin, O; Sánchez-Velázquez, P; Pessaux, P; Holka, PS; Ghorbani, P; Casadei, R; Sartoris, R; Schulick, RD; Grützmann, R; Sutcliffe, R; Mata, R; Patel, RB; Takahashi, R; Franco, SR; Cabús, SS; Hirano, S; Gaujoux, S; Festen, S; Kozono, S; Maithel, SK; Chai, SM; Yamaki, S; van Laarhoven, S; Mieog, JSD; Murakami, T; Codjia, T; Sumiyoshi, T; Karsten, TM; Nakamura, T; Sugawara, T; Boggi, U; Hartman, V; de Meijer, VE; Bartholomä, W; Kwon, W; Koh, YX; Cho, Y; Takeyama, Y; Inoue, Y; Nagakawa, Y; Kawamoto, Y; Ome, Y; Soonawalla, Z; Uemura, K; Wolfgang, CL; Jang, JY; Padbury, R; Satoi, S; Messersmith, W; Wilmink, JW; Abu Hilal, M; Besselink, MG; Del Chiaro, M
Format: Article
Status:Published version
Publication date:2025
Country:España
Institution:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repository:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p19960
Online Access:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19960
Access Level:Open access
Keyword:pancreatic adenocarcinoma
pancreatic body/tail
resectable
neoadjuvant therapy
CA19-9
tumor size
Summary:Background: Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery. Patients and methods: This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated. Results: Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (P-interaction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; P-interaction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (P-interaction = 0.43), splenic vein (P-interaction = 0.30), retroperitoneal (P-interaction = 0.84), and multivisceral (P-interaction = 0.96) involvement. Conclusions: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

Similar Items