A recently published study in the Journal of Gastrointestinal Surgery has revealed that neoadjuvant chemotherapy (NAC) followed by a combination of intrahepatic cholangiocarcinoma (hCCA), perihilar cholangiocarcinoma (iCCA), and distal cholangiocarcinoma (dCCA) surgeries compared to surgery alone (SA), can significantly improve overall survival regardless of the nodal or margin status.

The study found no significant additional advantage of NAC over adjuvant chemotherapy on sensitivity analysis, suggesting a thorough and interdisciplinary evaluation to incorporate NAC in the cholangiocarcinoma (CCA) treatment.

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Although NAC has been associated with better oncological results in various gastrointestinal cancers, such as esophageal, gastric, and pancreatic cancer, its effectiveness in localized CCA treatment is not well-defined, the investigators noted. Most of the current research on NAC’s role in treating CCA has been retrospective and has mainly focused on its use before orthotopic liver transplantation, the researchers added.

However, NAC has been reported to be an appealing approach in oncology as it helps control disease progression, reduce tumor size, increase the likelihood of achieving a complete resection, and potentially avoid noncurative surgeries in patients who do not respond to systemic therapy, they said.

The study analyzed 9411 patients who had undergone surgery for CCA between 2010 and 2016, receiving either NAC, adjuvant chemotherapy, or none. The researchers performed cox regression to account for the selection bias and evaluate the impact of surgery alone compared to either NAC or adjuvant chemotherapy on the overall survival.

Among the iCCA patients, 399 (10.6%) patients received NAC, 2140 (56.7%) underwent surgery alone, while 1233 (32.7%) received surgery followed by adjuvant chemotherapy. For the hCCA cohort, only 123 (6.5%) received NAC, in contrast to 940 (50.0%) patients who underwent surgery alone and 816 (43.4%) who received surgery followed by adjuvant chemotherapy. Among the dCCA group, 271 (7.2%) received NAC followed by resection, 1953 (51.9%) underwent surgery alone, and 1536 (40.9%) received surgery followed by adjuvant chemotherapy.

Study results indicated that NAC followed by surgery was associated with a significant improvement in overall survival compared to surgery alone for iCCA, hCCA, and dCCA. However, sensitivity analyses revealed no differences in overall survival between NAC followed by surgery or adjuvant chemotherapy after surgery in iCCA, hCCA, and dCCA.

The authors pointed out several limitations in the study. Despite attempting to account for confounders through multivariable and sensitivity analyses, treatment selection bias may have yet to be entirely addressed. Additionally, granular details such as type, duration, dosage, and the chemotherapy treatment response were missing, which could have played a significant role in interpreting outcomes.

“In summary, notwithstanding several limitations, in this retrospective study which used a contemporary national dataset, we found that NAC, followed by surgery for iCCA, hCCA, and dCCA, was associated with increased survival, compared to surgery alone, regardless of nodal or margin status,” the authors concluded.


Parente A, Kamarajah SK, Baia M et al. Neoadjuvant chemotherapy for intrahepatic, perihilar, and distal cholangiocarcinoma: a national population-based comparative cohort study. J Gastrointest Surg. Published online February 7, 2023. doi: 10.1007/s11605-023-05606-y