The Prognostic Role of True Radical Resection in Perihilar Cholangiocarcinoma after Improved Evaluation of Radial Margin Status

Simple Summary A proper pathological examination of resected perihilar cholangiocarcinoma specimen should take into consideration both the ductal and the radial margin status. Unfortunately, current evidence shows that pathological reports offer a poor assessment of residual disease status, especially in Western centers. The ambiguity in reporting on surgical margins impedes correct staging, prognosis, and the consistent design of survival studies. The present study reviews the Verona (Italy) experience in surgical treatment of PHCC after improved evaluation of surgical margins status and consequently investigates the impact of true R0 (negative ductal and radial margin) on survival. Radial Margin positivity was the most frequent cause of R1, and multivariable analysis identifies residual disease status as the main independent factor affecting both RFS and OS. The improved evaluation of RM status could lead to a more accurate selection of patients for adjuvant therapy. Background: The evaluation of surgical margins in resected perihilar cholangiocarcinoma (PHCC) remains a challenging issue. Both ductal (DM) and radial margin (RM) should be considered to define true radical resections (R0). Although DM status is routinely described in pathological reports, RM status is often overlooked. Therefore, the frequency of true R0 and its impact on survival might be biased. Objective: To improve the evaluation of RM status and investigate the impact of true R0 on survival. Methods: From 2014 to 2020, 90 patients underwent curative surgery for PHCC at Verona University Hospital, Verona, Italy. Both DM (proximal and distal biliary margin) and RM (hepatic, periductal, and vascular margin) status were evaluated by expert hepatobiliary pathologists. Patients with lymph-node metastases or positive surgical margins (R1) were candidates for adjuvant treatment. Clinicopathological and survival data were retrieved from an institutional database. Results: True R0 were 46% (41) and overall R1 were 54% (49). RM positivity resulted in being higher than DM positivity (48% versus 27%). Overall survival was better in patients with true R0 than in patients with R1 (median survival time: 53 vs. 28 months; p = 0.016). Likewise, the best recurrence-free survival was observed in R0 compared with R1 (median survival time: 32 vs. 15 months; p = 0.006). Multivariable analysis identified residual disease status as an independent prognostic factor of both OS (p = 0.009, HR = 2.68, 95% CI = 1.27-5.63) and RFS (p = 0.009, HR = 2.14, 95% CI = 1.20-3.83). Conclusion: Excellent survival was observed in true R0 patients. The improved evaluation of RM status is mandatory to properly stratify prognosis and select patients for adjuvant treatment.