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Background <p>Despite the theoretical advantages of neoadjuvant therapy (NAT) in intrahepatic cholangiocarcinoma (iCCA), its impact on post-recurrence overall survival (PROS) remains poorly defined. This study investigated the association between NAT and post-recurrence outcomes.</p> Methods <p>This single-center retrospective study included consecutive patients with histologically confirmed iCCA who underwent curative-intent liver resection at Mayo Clinic Rochester (2000–2024). Neoadjuvant therapy was administered to selected patients with high-risk features. The association between NAT and PROS was evaluated using Kaplan-Meier analysis and multivariable Cox regression adjusted for relevant covariates.</p> Results <p>Among 343 patients with iCCA, NAT recipients were younger, more often treated in the contemporary era, and included a higher proportion of major resections. Targetable molecular alterations (<i>IDH1, FGFR2</i>) were markedly enriched in the NAT group (48.2% vs 13.9%). Neoadjuvant therapy was associated with significantly improved PROS (median, 31.9 vs 16.4 months; <i>p</i> = 0.006) and remained an independent predictor of survival on multivariable Cox regression (hazard ratio, 0.506; <i>p</i> = 0.008), even after the study accounted for era-dependent molecular-profiling. In contrast, older age and early recurrence were independently associated with worse PROS. Recurrence patterns, including location, timing, and median time to recurrence, remained comparable over time. After recurrence, NAT recipients more frequently underwent curative-intent local therapies and advanced systemic treatments.</p> Conclusions <p>Neoadjuvant therapy was associated with improved PROS for resected iCCA patients, consistent with a potential role in biologic selection. Recipients of NAT showed enriched targetable molecular alterations and better PROS despite stable recurrence patterns. These findings position PROS as a relevant endpoint in NAT-treated iCCA, complementing conventional survival metrics.</p>

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The Effect of Neoadjuvant Therapy on Post-Recurrence Overall Survival After Curative Resection for Intrahepatic Cholangiocarcinoma

  • 期刊论文

  • 发表日期：

    2026年6月27日

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  • Yawen Dong,
  • David Pereyra,
  • Vanja Podrascanin,
  • Zhihao Li,
  • Jonas Santol,
  • Markus Ammann,
  • Lionel A. Kankeu Fonkoua,
  • Rondell P. Graham,
  • Caitlin B. Conboy,
  • Nguyen H. Tran,
  • Susanne G. Warner,
  • Rory L. Smoot,
  • Patrick Starlinger

摘要

Background

Despite the theoretical advantages of neoadjuvant therapy (NAT) in intrahepatic cholangiocarcinoma (iCCA), its impact on post-recurrence overall survival (PROS) remains poorly defined. This study investigated the association between NAT and post-recurrence outcomes.

Methods

This single-center retrospective study included consecutive patients with histologically confirmed iCCA who underwent curative-intent liver resection at Mayo Clinic Rochester (2000–2024). Neoadjuvant therapy was administered to selected patients with high-risk features. The association between NAT and PROS was evaluated using Kaplan-Meier analysis and multivariable Cox regression adjusted for relevant covariates.

Results

Among 343 patients with iCCA, NAT recipients were younger, more often treated in the contemporary era, and included a higher proportion of major resections. Targetable molecular alterations (IDH1, FGFR2) were markedly enriched in the NAT group (48.2% vs 13.9%). Neoadjuvant therapy was associated with significantly improved PROS (median, 31.9 vs 16.4 months; p = 0.006) and remained an independent predictor of survival on multivariable Cox regression (hazard ratio, 0.506; p = 0.008), even after the study accounted for era-dependent molecular-profiling. In contrast, older age and early recurrence were independently associated with worse PROS. Recurrence patterns, including location, timing, and median time to recurrence, remained comparable over time. After recurrence, NAT recipients more frequently underwent curative-intent local therapies and advanced systemic treatments.

Conclusions

Neoadjuvant therapy was associated with improved PROS for resected iCCA patients, consistent with a potential role in biologic selection. Recipients of NAT showed enriched targetable molecular alterations and better PROS despite stable recurrence patterns. These findings position PROS as a relevant endpoint in NAT-treated iCCA, complementing conventional survival metrics.