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

Rangelova, E. ; Tingstedt, B. LU ; Strandberg Holka, Peter LU and Kimura, Y. (2025) In Annals of Oncology 36(5). p.529-542
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... (More)
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. © 2025 The Author(s) (Less)
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; ; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CA19-9, neoadjuvant therapy, pancreatic adenocarcinoma, pancreatic body/tail, resectable, tumor size
in
Annals of Oncology
volume
36
issue
5
pages
14 pages
publisher
Oxford University Press
external identifiers
  • scopus:85217968624
  • pmid:39814200
ISSN
0923-7534
DOI
10.1016/j.annonc.2024.12.015
language
English
LU publication?
yes
id
51a57e24-5682-4cc2-847b-37f807e72950
date added to LUP
2025-12-17 15:31:27
date last changed
2025-12-18 03:00:11
@article{51a57e24-5682-4cc2-847b-37f807e72950,
  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. © 2025 The Author(s)}},
  author       = {{Rangelova, E. and Tingstedt, B. and Strandberg Holka, Peter and Kimura, Y.}},
  issn         = {{0923-7534}},
  keywords     = {{CA19-9; neoadjuvant therapy; pancreatic adenocarcinoma; pancreatic body/tail; resectable; tumor size}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{529--542}},
  publisher    = {{Oxford University Press}},
  series       = {{Annals of Oncology}},
  title        = {{The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study}},
  url          = {{http://dx.doi.org/10.1016/j.annonc.2024.12.015}},
  doi          = {{10.1016/j.annonc.2024.12.015}},
  volume       = {{36}},
  year         = {{2025}},
}