Combined Impact of Neoadjuvant Therapy and Preoperative Cachexia in Patients Undergoing Pancreatoduodenectomy: Is There a “Double Jeopardy”? A National Cohort Study Investigating the Association with Short- and Long-Term Outcomes

TL;DR

This study finds that pre-surgery weight loss (cachexia) in cancer patients does not worsen long-term survival and does not interact with pre-surgery therapy to create a 'double jeopardy' after a complex abdominal surgery.

Contribution

The novel contribution is identifying that cachexia and neoadjuvant therapy do not synergistically worsen outcomes after pancreatoduodenectomy.

Findings

Cachexia was associated with higher textbook outcomes but not with worse long-term survival.

Neoadjuvant therapy was linked to higher mortality risk, likely due to confounding factors.

No significant interaction was found between cachexia and neoadjuvant therapy for outcomes or survival.

Abstract

Cachexia is associated with worse postoperative outcomes, but the added role of neoadjuvant therapy (NAT) is unclear. This study evaluated whether preoperative cachexia and NAT act as a “double jeopardy” after pancreatoduodenectomy.

A nationwide observational cohort study was conducted using the Norwegian NORGAST registry (2016–2023). Adults undergoing pancreatoduodenectomy for malignancy were included. Cachexia was defined by consensus weight-loss criteria. Modified Poisson and Cox models (with a cachexia and NAT interaction term) estimated adjusted risk ratios (aRR) for textbook outcome (TO), prolonged length-of-stay (LOS), and adjusted hazard ratios (aHR) for overall survival.

Of 1424 patients undergoing pancreatoduodenectomy, cachexia was present in 588 (41.3%). Having cachexia was associated with higher TO (aRR 1.28, 95% CI 1.13–1.46) with effect modification by body mass index (BMI) (interaction P = 0.047). Patients with cachexia had a lower risk of prolonged LOS (aRR 0.64, 95% CI 0.51–0.80). Cachexia was not independently associated with overall survival (aHR 1.15, 95% CI 0.97–1.36). NAT was associated with a higher hazard of death (aHR 1.44, 95% CI 1.09–1.92), likely reflecting confounding by indication. No statistically significant interaction between cachexia and NAT was observed for TO (P = 0.277) or for survival (P = 0.863).

Preoperative cachexia was associated with higher rates of TO. Higher TO was attributed to patients with overweight or obesity, to a shorter index stay, and more frequent transfers to a secondary facility, but not fewer complications. Cachexia was not associated with worse long-term survival, and a “double jeopardy” between cachexia and receiving NAT was not found.

The online version of this article (10.1245/s10434-025-18941-y) contains supplementary material, which is available to authorized users.

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