Neoadjuvant therapy in frail patients with pancreatic cancer: Impact on surgical safety and outcomes.

BACKGROUND

Frailty predicts poor outcomes after pancreatic resection, but its influence on the use, tolerability, and perioperative safety of neoadjuvant therapy among resected patients remains unclear.

METHODS

Using the American College of Surgeons National Surgical Quality Improvement Program pancreatectomy-targeted database (2014-2023), we identified patients undergoing pancreatoduodenectomy or distal pancreatectomy for pancreatic ductal adenocarcinoma. Frailty was defined as a modified 5-factor frailty index score ≥2. Multivariable logistic regression evaluated the association between frailty and neoadjuvant therapy receipt and the effect of neoadjuvant therapy on 30-day outcomes in frail patients. Effect modification by frailty status was assessed by including an interaction term between frailty and neoadjuvant therapy.

RESULTS

Among 29,528 patients, 7,261 (24.59%) were frail, and 11,235 (38.05%) received neoadjuvant therapy. Frailty was associated with decreased neoadjuvant therapy receipt (odds ratio, 0.881; P < .001). In multivariable analyses of frail patients, neoadjuvant therapy was independently associated with lower odds of delayed gastric emptying (odds ratio, 0.855; P = .034), percutaneous drain placement (odds ratio, 0.744; P < .001), operative drain present at postoperative day 30 (odds ratio, 0.662; P < .001), respiratory events (P < .05), infectious complications (P < .05), cardiac arrest (odds ratio, 0.531; P = .010), and prolonged hospitalization (odds ratio, 0.707; P = .036) when compared with upfront resection. Interaction analyses showed that frailty did not significantly modify neoadjuvant therapy effects; however, frail patients who underwent resection appeared to derive greater benefit regarding cardiac arrest.

CONCLUSION

Frailty alone should not necessarily be considered a contraindication to neoadjuvant therapy. Among frail patients who ultimately proceed to resection, the perioperative risks of neoadjuvant therapy appear manageable.