Adjuvant Chemotherapy Regimens in Resected Biliary Tract Cancers: National, Comparative, Observational Study (
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Erman Akkus, Mehmet Kayaalp, Müzeyyen Aslı Ergözoğlu, Ilgın Koç Kuş, Doğan Bayram, Bilgeşah Kılıçtaş, Emel Ayvaz Güneyin, Ali Kalem, Haydar Temizyürek, Mehmet Mutlu Çatlı, Mehmet Sinan Akarca, Maral Martin Mıldanoğlu, Görkem Turhan, Mahmut Kara, Hacı Arak, Feyza Arslan Tan, Burak Paçacı, Berkay Yeşilyurt, Orhun Akdoğan, Emine Bihter Çetin, Selahattin Çelik, Fatma Keskin Uzundere, Elif Şahin, Zehra Sadak Öcal, Lamia Şeker Can, Bahadır Köylü, Mehmet Cem Fidan, Esmanur Kaplan Tüzün, Teoman Şakalar, Elif Sertesen Çamöz, Haydar Çağatay Yüksel, Onur Yazdan Balçık, Pınar Peker, Mehmet Yılmaz, Şeymanur Ala Enli, Erdem Kölemen, Sibel Oyucu Orhan, Yakup Düzköprü, Mustafa Ersoy, Tuğba Akın Telli, Mesut Yılmaz, Yusuf İlhan, Atila Yıldırım, Ramazan Coşar, Müslih Ürün, Arif Hakan Önder, Murat Araz, Ertuğrul Bayram, Havva Yeşil Çınkır, Ali Alkan, Mustafa Gürbüz, Nilüfer Avcı, Fatma Paksoy Türköz, İsmail Oğuz Kara, Fatih Köse, İlkay Tuğba Ünek, Ahmet Bilici, Öznur Bal, Şuayib Yalçın, Lorenza Rimassa, Hatime Arzu Yaşar ABSTRACT
The recommended adjuvant chemotherapy (adj‐ChT) regimen for resected biliary tract cancers (BTC) is capecitabine (Cape); yet, the recommendation is based on limited evidence. Although varied adj‐ChTs have been employed in practice, robust real‐world data is scarce. We conducted a national, multicenter, hospital‐based registry study to evaluate adj‐ChTs in resected BTCs. Patients who received adj‐ChT (± radiotherapy) between 2010 and 2024 were included. Recurrence‐free (RFS) and overall survival (OS) were analyzed by adjusted Cox‐regression and propensity score‐based inverse‐probability‐of‐treatment‐weighting (IPTW), addressing selection bias. Among 617 patients from 44 centers, 513 were eligible. The most frequent adj‐ChTs were Cape (35.5% [ n = 182]), gemcitabine–cisplatin (Gem‐Cis; 22.4% [ n = 115]), gemcitabine–capecitabine (Gem‐Cape; 20.1% [ n = 103]), and gemcitabine (Gem; 10.7% [ n = 55]). Median RFS and OS with Cape were 19.7 (95% Confidence Interval [95% CI]: 14.2–41.1) and 41.9 months (95% CI: 25.9–69.2). In adjusted/controlled comparisons with Cape, no differences in RFS or OS were observed with Gem‐Cis (RFS: Hazard Ratio [HR] 1.13 [95% CI: 0.77–1.66]; OS: HR: 1.03 [95% CI: 0.66–1.61]), Gem‐Cape (RFS: HR 0.97 [95% CI: 0.68–1.38]; OS: HR: 0.81 [95% CI: 0.52–1.24]), or Gem (RFS: HR 1.00 [95% CI: 0.63–1.59]; OS: HR: 0.93 [95% CI: 0.55–1.57]). Similarly, IPTW analyses showed no difference in RFS and OS. Radiotherapy appeared to be associated with improved survival. Performance status, T‐stage, lymph‐node positivity, and R1‐resection were independently associated with RFS and OS. In conclusion, this real‐world study did not identify a regimen superior to Cape. Given the modest benefit of adj‐ChTs, novel approaches, including neoadjuvant and targeted/immunotherapy strategies, are needed.