Intensive follow-up program and oncological outcomes of 278 biliary tract cancer patients after curative intent surgery: A single-center retrospective experience

Background: Biliary tract cancer (BTC) encompasses a group of rare and heterogeneous malignancies with poor prognosis, including gallbladder cancer, ampulla of Vater cancer, intrahepatic cholangiocarcinoma (iCCA), and extrahepatic cholangiocarcinoma (eCCA), with the latter further subdivided into perihilar (pCCA) and distal (dCCA). Unfortunately, potentially curative surgical resection is possible in approximately the 25% of BTC patients at diagnosis, and even following radical surgery, relapse rates remain high. The aim of this research was to evaluate the impact of an intensive follow-up program in BTC patients who had received surgical resection with curative intent at a tertiary referral hospital. Methods: Medical records of all consecutive BTC patients treated with curative intent surgery at S. Orsola Malpighi Hospital, Bologna, Italy, from January 2000 to November 2020, were retrospectively reviewed. The BTC-specific overall survival (OS) and disease-free survival (DFS) status were determined by the Kaplan-Meier method; univariate and multivariate analysis were performed to assess the impact of covariates on survival. Results: A total of 398 BTC patients receiving surgery with curative intent were included in the analysis. Macroscopic residual tumor was observed in 29 patients, while 329 BTCs underwent R0 (n¼222; 67%) or R1 (n¼107; 33%) surgery. Among these, 278 patients started a follow-up program at our institution based on physical examination, serum CEA and CA19-9 and abdominal/chest CT scan every 3-4 months in the first two years and every 6 months from the third to the fifth year; 80% of this group (222/278) started follow-up after adjuvant chemotherapy (in case of R0 surgery) or chemoradiotherapy (in R1 resection). The median age of the follow-up group was 63 years (range 31-85 years) and 164 (49.5%) were females. Overall, 116 (32.5%) and 126 (38.6%) patients had iCCA and eCCA (78 pCCAs and 48 dCCAs), respectively. At a median follow-up of 37.4 months, median OS was 50.8 and 35 months in R0 and R1 patients, respectively (p¼0.04); similarly, median DFS was 16.4 and 12.3 months in the same groups (p¼0.02). No relapse was observed in 129 out of 329 BTCs (39%), while the 61% of R0/R1 patients (200/329) experienced disease relapse, including 39% of iCCA and 38% of eCCA; liver was the most frequent site of relapse (78%) followed by peritoneum and locoregional lymph nodes. In terms of treatment at the relapse, 15% (30/200) of patients underwent second surgery (R0¼14, R1¼6, R2¼3, exploratory laparotomy¼7) while 20% (40/200) received a locoregional approach, the most frequent of which was radiofrequency ablation (n¼22). None of the 14 BTC patients receiving second surgery with R0 experienced disease relapse. Overall, 127 BTCs received first-line chemotherapy following relapse, with gemcitabine-cisplatin as the most commonly used regimen (52%). Conclusions: Based on the results of our 20-year, single-center experience of 278 BTC patients, an intensive follow-up after surgical resection with curative intent could help in the identification of disease relapse, leading to early treatment and prolonged survival in selected cases, as reported in BTCs treated with second surgical resection with negative margins.