Very Early Recurrence After Liver Resection for Intrahepatic Cholangiocarcinoma

Abstract

IMPORTANCE Although surgery offers the best chance of a potential cure for patients with localized, resectable intrahepatic cholangiocarcinoma (ICC), prognosis of patients remains dismal largely because of a high incidence of recurrence.OBJECTIVE To predict very early recurrence (VER) (ie, recurrence within 6 months after surgery) following resection for ICC in the pre-and postoperative setting. DESIGN, SETTING, AND PARTICIPANTSPatients who underwent curative-intent resection for ICC between May 1990 and July 2016 were identified from an international multi-institutional database. The study was conducted at The Ohio State University in collaboration with all other participating institutions. The data were analyzed in December 2019. MAIN OUTCOMES AND MEASURESTwo logistic regression models were constructed to predict VER based on pre-and postoperative variables. The final models were used to develop an online calculator to predict VER and the tool was internally and externally validated. RESULTS Among 880 patients (median age, 59 years [interquartile range, 51-68 years]; 388 women [44.1%]; 428 [50.2%] white; 377 [44.3%] Asian; 27 [3.2%] black]), 196 (22.3%) developed VER.The 5-year overall survival among patients with and without VER was 8.9% vs 49.8%, respectively (P < .001). A preoperative model was able to stratify patients relative to the risk for VER: low risk (6-month recurrence-free survival [RFS], 87.7%), intermediate risk (6-month RFS, 72.3%), and high risk (6-month RFS, 49.5%) (log-rank P < .001). The postoperative model similarly identified discrete cohorts of patients based on probability for VER: low risk (6-month RFS, 90.0%), intermediate risk (6-month RFS, 73.1%), and high risk (6-month RFS, 48.5%) (log-rank, P < .001). The calibration and predictive accuracy of the pre-and postoperative models were good in the training (C index: preoperative, 0.710; postoperative, 0.722) as well as the internal (C index: preoperative, 0.715; postoperative, 0.728; bootstrapping resamples, n = 5000) and external (C index: postoperative, 0.672) validation data sets. CONCLUSION AND RELEVANCEAn easy-to-use online calculator was developed to help clinicians predict the chance of VER after curative-intent resection for ICC. The tool performed well on internal and external validation. This tool may help clinicians in the preoperative selection of patients for neoadjuvant therapy as well as during the postoperative period to inform surveillance strategies.

Surgical Treatment of Intrahepatic Cholangiocarcinoma: Current and Emerging Principles

“…Important considerations include the presence of extrahepatic disease; radiologic features such as vascular invasion, multifocality, obvious lymph node involvement, or subtle signs of peritoneal involvement; histopathologic features; degree of Ca 19-9 elevation; response to prior therapies; and genetic and molecular features of the tumor. A large international study of patients who underwent resection of ICC noted that large tumor size, higher number of tumors, microvascular invasion, N1 or NX disease, suspicious/metastatic lymph nodes on preoperative imaging and R1 resection were associated with a higher likelihood of very early recurrence (≤6 months), suggesting some patients may have benefited from neoadjuvant chemotherapy [ 34 ].…”

Current and Future Systemic Therapies in Biliary Tract Cancer

“…The high 3-year rate of recurrence that can be up to 80% [4, 5] after curatively intended resection has led to an intensive discussion about the importance of adjuvant therapy concepts. Until 2017, the use of adjuvant treatment was based on meta-analyses from mostly small retrospective phase II studies, which suggested that specifically two high-risk populations benefit from postoperative chemotherapy in terms of mOS: patients with nodal-positive disease and following R1 resection [6, 7].…”

“…Adjuvant and/or neoadjuvant therapy concepts may be especially beneficial in patients with a high risk of very early relapse. A recent study showed that very early recurrence within 6 months after surgery occurs in almost 25% of iCCA patients and is associated with a dismal mOS of 13.8 months and a 5-year OS of 8.9%, compared to 59.7 months and 49.8% ( p < 0.001) in patients without very early recurrence [5]. Not surprisingly, tumor size (OR 1.11), number of tumors (OR 1.36), microvascular invasion (OR 1.55), N1 or Nx status (OR 1.94), and R1 resection (OR 2.14) were associated with a higher probability of early recurrence.…”

Surgical Approach to Recurrent Cholangiocarcinoma

“…About one fourth of patients develop recurrence within 6 months. In these patients resectability is lower and the results are worse [26]. Tsilimigras et al [26] reported a median survival of 9.3 months and a 5-year-survival of 8.9%.…”

“…In these patients resectability is lower and the results are worse [26]. Tsilimigras et al [26] reported a median survival of 9.3 months and a 5-year-survival of 8.9%. This poor outcome is a marker for an unfavorable biology of iCCA; thus particular caution should be exercised when indicating surgery.…”