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

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.

doi:10.1016/j.annonc.2024.12.015

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.