The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study
Abstract
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 (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 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.
Author
Rangelova, E
Stoop, T F
van Ramshorst, T M E
Ali, M
van Bodegraven, E A
Javed, A A
Hashimoto, D
Steyerberg, E
Banerjee, A
Jain, A
Sauvanet, A
Serrablo, A
Giani, A
Giardino, A
Zerbi, A
Arshad, A
Wijma, A G
Coratti, A
Zironda, A
Socratous, A
Rojas, A
Halimi, A
Ejaz, A
Oba, A
Patel, B Y
Björnsson, B
Reames, B N
Tingstedt, B
Goh, B K P
Payá-Llorente, C
Del Pozo, C D
González-Abós, C
Medin, C
van Eijck, C H J
de Ponthaud, C
Takishita, C
Schwabl, C
Månsson, C
Ricci, C
Thiels, C A
Douchi, D
Hughes, D L
Kilburn, D
Flanking, D
Kleive, D
Silva, D S
Edil, B H
Pando, E
Moltzer, E
Kauffman, E F
Warren, E
Bozkurt, E
Sparrelid, E
Thoma, E
Verkolf, E
Ausania, F
Giannone, F
Hüttner, F J
Burdio, F
Souche, F R
Berrevoet, F
Daams, F
Motoi, F
Saliba, G
Kazemier, G
Roeyen, G
Nappo, G
Butturini, G
Ferrari, G
Kito Fusai, G
Honda, G
Sergeant, G
Karteszi, H
Takami, H
Suto, H
Matsumoto, I
Mora-Oliver, I
Frigerio, I
Fabre, J M
Chen, J
Sham, J G
Davide, J
Urdzik, J
de Martino, J
Nielsen, K
Okano, K
Kamei, K
Okada, K
Tanaka, K
Labori, K J
Goodsell, K E
Alberici, L
Webber, L
Kirkov, L
de Franco, L
Miyashita, M
Maglione, M
Gramellini, M
Ramera, M
Amaral, M J
Ramaekers, M
Truty, M J
van Dam, M A
Stommel, M W J
Petrikowski, M
Imamura, M
Hayashi, M
D'Hondt, M
Brunner, M
Hogg, M E
Zhang, C
Suárez-Muñoz, M Á
Luyer, M D
Unno, M
Mizuma, M
Janot, M
Sahakyan, M A
Jamieson, N B
Busch, O R
Bilge, O
Belyaev, O
Franklin, O
Sánchez-Velázquez, P
Pessaux, P
Holka, P S
Ghorbani, P
Casadei, R
Sartoris, R
Schulick, R D
Grützmann, R
Sutcliffe, R
Mata, R
Patel, R B
Takahashi, R
Rodriguez Franco, S
Cabús, S S
Hirano, S
Gaujoux, S
Festen, S
Kozono, S
Maithel, S K
Chai, S M
Yamaki, S
van Laarhoven, S
Mieog, J S D
Murakami, T
Codjia, T
Sumiyoshi, T
Karsten, T M
Nakamura, T
Sugawara, T
Boggi, U
Hartman, V
de Meijer, V E
Bartholomä, W
Kwon, W
Koh, Y X
Cho, Y
Takeyama, Y
Inoue, Y
Nagakawa, Y
Kawamoto, Y
Ome, Y
Soonawalla, Z
Uemura, K
Wolfgang, C L
Jang, J Y
Padbury, R
Satoi, S
Messersmith, W
Wilmink, J W
Abu Hilal, M
Besselink, M G
Del Chiaro, M
Stoop, T F
van Ramshorst, T M E
Ali, M
van Bodegraven, E A
Javed, A A
Hashimoto, D
Steyerberg, E
Banerjee, A
Jain, A
Sauvanet, A
Serrablo, A
Giani, A
Giardino, A
Zerbi, A
Arshad, A
Wijma, A G
Coratti, A
Zironda, A
Socratous, A
Rojas, A
Halimi, A
Ejaz, A
Oba, A
Patel, B Y
Björnsson, B
Reames, B N
Tingstedt, B
Goh, B K P
Payá-Llorente, C
Del Pozo, C D
González-Abós, C
Medin, C
van Eijck, C H J
de Ponthaud, C
Takishita, C
Schwabl, C
Månsson, C
Ricci, C
Thiels, C A
Douchi, D
Hughes, D L
Kilburn, D
Flanking, D
Kleive, D
Silva, D S
Edil, B H
Pando, E
Moltzer, E
Kauffman, E F
Warren, E
Bozkurt, E
Sparrelid, E
Thoma, E
Verkolf, E
Ausania, F
Giannone, F
Hüttner, F J
Burdio, F
Souche, F R
Berrevoet, F
Daams, F
Motoi, F
Saliba, G
Kazemier, G
Roeyen, G
Nappo, G
Butturini, G
Ferrari, G
Kito Fusai, G
Honda, G
Sergeant, G
Karteszi, H
Takami, H
Suto, H
Matsumoto, I
Mora-Oliver, I
Frigerio, I
Fabre, J M
Chen, J
Sham, J G
Davide, J
Urdzik, J
de Martino, J
Nielsen, K
Okano, K
Kamei, K
Okada, K
Tanaka, K
Labori, K J
Goodsell, K E
Alberici, L
Webber, L
Kirkov, L
de Franco, L
Miyashita, M
Maglione, M
Gramellini, M
Ramera, M
Amaral, M J
Ramaekers, M
Truty, M J
van Dam, M A
Stommel, M W J
Petrikowski, M
Imamura, M
Hayashi, M
D'Hondt, M
Brunner, M
Hogg, M E
Zhang, C
Suárez-Muñoz, M Á
Luyer, M D
Unno, M
Mizuma, M
Janot, M
Sahakyan, M A
Jamieson, N B
Busch, O R
Bilge, O
Belyaev, O
Franklin, O
Sánchez-Velázquez, P
Pessaux, P
Holka, P S
Ghorbani, P
Casadei, R
Sartoris, R
Schulick, R D
Grützmann, R
Sutcliffe, R
Mata, R
Patel, R B
Takahashi, R
Rodriguez Franco, S
Cabús, S S
Hirano, S
Gaujoux, S
Festen, S
Kozono, S
Maithel, S K
Chai, S M
Yamaki, S
van Laarhoven, S
Mieog, J S D
Murakami, T
Codjia, T
Sumiyoshi, T
Karsten, T M
Nakamura, T
Sugawara, T
Boggi, U
Hartman, V
de Meijer, V E
Bartholomä, W
Kwon, W
Koh, Y X
Cho, Y
Takeyama, Y
Inoue, Y
Nagakawa, Y
Kawamoto, Y
Ome, Y
Soonawalla, Z
Uemura, K
Wolfgang, C L
Jang, J Y
Padbury, R
Satoi, S
Messersmith, W
Wilmink, J W
Abu Hilal, M
Besselink, M G
Del Chiaro, M
Date
2025-01-13
Type
Journal Article
Subject
Pancreatic neoplasms, Neoplasms
Collections
Citation
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, Kito Fusai G, 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 MÁ, 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, Rodriguez Franco S, 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; European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS); International Consortium on Advanced Pancreatic Surgery. The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study. Ann Oncol. 2025 May;36(5):529-542. doi: 10.1016/j.annonc.2024.12.015. Epub 2025 Jan 13.
Journal / Source Title
Annals of Oncology
DOI
10.1016/j.annonc.2024.12.015
PMID
39814200
Publisher
Elsevier
Publisher’s URL
https://www.sciencedirect.com/journal/annals-of-oncology