Impact of Next-Generation Sequencing on Surgical Decision-Making in Branch-Duct IPMN

Managing branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains challenging, as guideline criteria (worrisome features/high-risk stigmata) and nomograms often leave uncertainty. Next-generation sequencing (NGS) may provide actionable molecular information that influences clinical decision-making.

We conducted a national, vignette-based decision-impact study involving 132 clinicians (gastroenterologists and surgeons). Four complex BD-IPMN vignettes (each with two to four worrisome features) were evaluated twice: pre-NGS and post-NGS after disclosure of either a high-risk mutation (positive) or its absence (negative). The primary endpoint was the within-physician change in management in the NGS-concordant direction (NGS+ surveillance to surgery; NGS- surgery to surveillance) assessed using McNemar's test and mixed-effects logistic regression. Secondary endpoints included change in decision confidence, inter-physician agreement (Fleiss' κappa), and practitioner factors.

NGS significantly changed management in all vignettes (all p < 0.001): with NGS-, surgical plans shifted to surveillance (43% in distal pancreatectomy; 61% in pancreatoduodenectomy scenarios); with NGS+, surveillance shifted to surgery (90% and 72%, respectively; both p < 0.001). In mixed-model, post-NGS reduced surgery in NGS- cases (odd ratio [OR] 0.30, 95%confidence interval [CI] 0.16-0.57) and the post-NGS effect was strongly amplified in NGS+ cases (interaction OR 76.51, 95%CI 26.47-221.13). Population-averaged probabilities of choosing surgery shifted from 20% to 7% (NGS-) and 42% to 94% (NGS+). Decision confidence increased (proportional-odds OR 4.66, 95%CI 3.62-6.02, p < 0.0001). Inter-physician agreement rose from κ = 0.044 (95%CI 0.033-0.055) pre-NGS to κ = 0.590 (95%CI 0.580-0.601) post-NGS (p < 2×10^-16). After NGS, practitioner characteristics no longer explained decision patterns.

In complex BD-IPMN scenarios, NGS significantly influences clinician decision-making and reduces inter-physician variability. These findings support its role as a decision-support tool.