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Outcomes of neoadjuvant and/or adjuvant treatment vs surgical resection alone for patients with cholangiocarcinoma: An inverse probability of treatment weighting with predictive nomogram
Background
Cholangiocarcinoma (CCA) is a rare and heterogeneous cancer, whose incidence and related mortality is increasing globally. Adjuvant chemotherapy (AT) is commonly used in these patients. Neoadjuvant chemotherapy (NAT) may improve resectability. However, the appropriate sequence and patient selection for perioperative treatment in resectable CCA are unclear. This study aimed to determine the impact of perioperative oncological treatment in resected CCA patients and identify subgroups that benefit from NAT/ AT.
Methods
In this retrospective study patients with CCA who underwent surgical resection at a tertiary medical center from 2000 through 2019 were evaluated. Demographics, Eastern Cooperative Oncology Group (ECOG) performance status, radiological findings, surgical pathology, and neoadjuvant and adjuvant treatments were collected. The primary outcomes were disease-free survival (DFS) and overall survival (OS) in patients who received NAT/AT compared to surgery alone.
Results
We identified 182 patients with resected CCA; 80 (44%) received perioperative treatment, and 102 (56%) received surgery only. The perioperative treatment group was more likely to be administered in patients with stage III/IV (51.3% vs 23.5%, p = 0.002) or N1 disease (41.3% vs 19.6 %, p = 0.003), positive margins (17.5% vs 5.9%), p = 0.013), and tumor size > 5 cm (57.6% vs 32.4%, p = 0.02). The median DFS of patients who received NAT/AT compared to those who received surgery only was 26.4 (20.2 – 40.9) vs 31.2 months (18 – 44.5), respectively, p= 0.9196. In the multivariate analysis, receipt of NAT/AT (HR (95% CI) = 0.63(0.41 – 0.98)), p= 0.042, and positive margins (HR (95% CI) = (1.89(1.005 –3.55)), p= 0.048 were significant independent predictors of DFS. Receipt of NAT/AT was significantly associated with longer DFS compared with surgery alone in the following subgroups: stage III/IV CCA (HR (95% CI) = 0.41(0.24, 0.73)), p= 0.006, positive regional lymph nodes (HR (95% CI) =0.36 (0.19 – 0.68), p= 0.003), or positive margins (HR (95% CI) = 0.18 (0.06 – 0.52)), p= 0.004. The median OS of patients who received perioperative treatment compared to surgery only was 68.1 vs 51 months, respectively, p= 0.160. In the multivariate analysis, NAT/AT (HR (95% CI) = 0.46 (0.28 – 0.78)), p= 0.004, N1 disease (HR (95% CI) = 2.79 (1.29 – 6.022)), p= 0.009 and positive margins (HR (95% CI) = 3.696 (1.83 – 7.45)), p= 0.0003 were significant independent predictors of OS. On subgroup analysis, tumor size > 5 cm (HR (95% CI) = 0.31 (0.16, 0.61)), p= 0.002 and positive margins (HR (95% CI) =0.14 (0.43 – 0.45)), p= 0.013 were significantly associated with improved OS with NAT/AT compared to surgery alone. A nomogram, composed of any perioperative treatment, lymph node involvement, tumor stage and size, and resection margin status, could be used to predict the 3-year DFS after surgical resection.
Conclusions
NAT/AT is associated with improved DFS and OS compared to surgery alone in patients with CCA. Perioperative treatment was associated with improved survival in patients with: positive regional lymph nodes, positive margins, and large tumor size. The nomogram provided a prognostic indicator of 3-year DFS after surgical resection.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
All authors have declared no conflicts of interest.
