Resected Biliary Tract Cancer Research Articles

Different biliary tract cancers, same operation: Importance of cancer origin in patients with hilar-invading tumors.

For patients with biliary tract cancer involving the hepatic hilum, major hepatic resection with extrahepatic bile duct resection may be required. In addition to perihilar cholangiocarcinoma (PHCC), the same extent of surgery is used in advanced gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (IHCC) with hilar involvement. Few studies compare prognostic factors and long-term outcomes across tumor types. This study compared risk characteristics and outcomes after surgery in all subtypes of biliary tract cancer with hilar involvement. Patients with biliary tract cancer with hilar involvement undergoing major liver resection and extrahepatic bile duct resection between 2011 and 2021 at a single center were retrospectively analyzed. The primary postoperative outcome was overall survival. Secondary outcomes were recurrence-free survival and postoperative complications. Survival analysis was performed with Cox regression analysis and Kaplan-Meier method. One-hundred and eight patients were included. Seventy-three (67%) had PHCC, 24 (22%) had GBC, and 11 (10%) had IHCC. Hilar-invading IHCC and GBC had more adverse histopathological factors like lymph node positivity (p = 0.021), higher number of positive nodes (p = 0.043), and larger tumor size (p < 0.001) compared with PHCC. Peritoneal invasion and lymph node positivity were significant independent predictors for survival (p = 0.011 and p = 0.004, respectively). Median overall survival was 29 months for PHCC, 22 months for GBC and 21 months for IHCC (p = 0.53). IHCC tended to recur earlier (p = 0.046) than GBC and PHCC (6, 15, and 18 months, respectively). Patients with biliary tract cancer with hilar involvement undergoing major liver resection and resection of extrahepatic bile ducts had similar overall survival regardless of subtype, while IHCC recurred earlier. Peritoneal cancer invasion was common in all subtypes, including PHCC, and was an independent prognostic factor. This finding may support routine reporting of peritoneal invasion-status in resected biliary tract cancer.

5-Fluorouracil metabolic pathway genes predict recurrence risk following adjuvant S-1 therapy: Results of an ancillary analysis from a phase III trial of resected biliary tract cancer (JCOG1202A1).

S-1, an oral fluoropyrimidine derivative, is standard adjuvant therapy for resected biliary tract cancer (BTC), based on the results of the JCOG1202, a phase III trial evaluating the survival benefit with adjuvant S-1 following curative resection for BTC compared to surgery alone. This multicenter ancillary study of the JCOG1202 aimed to evaluate the prognostic impact of the 5-fluorouracil (5-FU) metabolic pathway genes including thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). The 5-FU metabolic pathway genes were measured in tumor cells from formalin-fixed paraffin-embedded resected specimens from 183 patients (surgery alone: n = 94; adjuvant S-1: n = 89). We randomly divided them into training (n = 96) and validation sets (n = 87) for evaluating the interaction between gene levels and RFS benefits in the treatment arm. RFS benefits of adjuvant S-1 were observed in the low DPD (HR = 0.440 and 0.748, respectively in the training and validation sets) and the low TP groups (HR = 0.709 and 0.602, respectively). Clinicopathological characteristics were well balanced between low and high DPD populations. More advanced stage tumors were observed in high TP populations as compared to those in low TP populations (p = .0332). The results suggest the RFS benefit of adjuvant S-1 in resected BTC patients with low DPD and low TP gene expressions.

Transmembrane serine protease 4 expression in the prognosis of radical resection for biliary tract cancer.

Recent advancements in biliary tract cancer (BTC) treatment have expanded beyond surgery to include adjuvant therapy, yet the prognosis remains poor. Identifying prognostic biomarkers could enhance the assessment of patients who have undergone radical resection for BTC. To determine transmembrane serine protease 4 (TMPRSS4) utility as a prognostic biomarker of radical resection for BTC. Medical records of patients who underwent radical resection for BTC, excluding intrahepatic cholangiocarcinoma, were retrospectively reviewed. The associations between TMPRSS4 expression and clinicopathological factors, overall survival, and recurrence-free survival were analyzed. Among the 85 patients undergoing radical resection for BTC, 46 (54%) were TMPRSS4-positive. The TMPRSS4-positive group exhibited significantly higher preoperative carbohydrate antigen 19-9 (CA19-9) values and greater lymphatic invasion than the TMPRSS4-negative group (P = 0.019 and 0.039, respectively). Postoperative overall survival and recurrence-free survival were significantly worse in the TMPRSS4-positive group (median survival time: 25.3 months vs not reached, P < 0.001; median survival time: 28.7 months vs not reached, P = 0.043, respectively). Multivariate overall survival analysis indicated TMPRSS4 positivity, pT3/T4, and resection status R1 were independently associated with poor prognosis (P = 0.032, 0.035 and 0.030, respectively). TMPRSS4 positivity correlated with preoperative CA19-9 values ≥ 37 U/mL and pathological tumor size ≥ 30 mm (P = 0.016 and 0.038, respectively). TMPRSS4 is a potential prognostic biomarker of radical resection for BTC.

Network meta-analysis of adjuvant chemotherapy in biliary tract cancers: Setting the scene for new randomized evidence.

The best adjuvant chemotherapy for resected biliary tract cancer (BTC) is under debate, with capecitabine supported by weak evidence. Aim of this network meta-analysis is to estimate the efficacy of different phase II/III regimens, comparing monotherapies (gemcitabine or fluoropyrimidines) head-to-head, against observation and combination regimens. A comprehensive literature search was conducted on PubMed and EMBASE for phase II/III randomized clinical trials (RCTs) available as of December 2023, reporting hazard ratios (HRs) of overall survival (OS) and event-free survival (EFS). A frequentist framework employing a random-effects model was applied; treatment rankings were outlined according to P-score, based on direct and indirect evidence. Exploratory subgroup analyses for OS were also performed (primary site, resected margin status and nodal involvement). Six RCTs (1979 total patients) were identified. Fluoropyrimidine monotherapy showed significantly better OS (HR .84 [.72-.97]) and EFS (HR .79 [.69-.91]) than observation, as any monotherapy did (HR .84 [.74-.96]; HR .79 [.70-.89]). In the head-to-head comparison for OS, only S1 confirmed to be superior to observation alone (HR .69 [.49-.98]) while fluoropyrimidines achieved the best P score (.81), similarly to any monotherapy (0.92). Combinations failed to prove superior to monotherapies with respect both to OS and EFS. Subgroup analyses were inconclusive due to results' inconsistency and limited sample size. Our work confirmed that adjuvant chemotherapy grants OS and EFS benefit for resected BTC patients. Fluoropyrimidines appeared the most effective option, confirming capecitabine as the preferred choice for the Western population.

A phase 3, randomized study of adjuvant rilvegostomig plus chemotherapy in resected biliary tract cancer: ARTEMIDE-Biliary01.

TPS4199 Background: Biliary tract cancer (BTC) is a rare but aggressive heterogenous group of gastrointestinal cancers that arise from the intra- or extrahepatic bile ducts (cholangiocarcinoma [CCA]) or the gallbladder (GBC). In early-stage disease following curative resection, adjuvant chemotherapy with a fluoropyrimidine- or gemcitabine-based regimen is usually recommended, however, recurrence rates remain high (e.g. in the BILCAP study, 5-year recurrence-free survival with adjuvant capecitabine was 34%). Immunotherapy is efficacious as adjuvant therapy in other cancer types. Results from the TOPAZ-1 and KEYNOTE-966 studies support combining immunotherapy and chemotherapy in advanced BTC, including in locally advanced non-metastatic disease. Furthermore, dual inhibition of programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) and the novel immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), has shown promising results across multiple tumor types without major increases in high-grade toxicity compared with PD-1 or PD-L1 inhibition alone. Rilvegostomig is an anti-PD-1/-TIGIT bi-specific monoclonal antibody that appears active and well tolerated in non-small-cell lung cancer. ARTEMIDE-Biliary01 will investigate the efficacy of rilvegostomig plus standard of care adjuvant chemotherapy in patients with BTC after curative intent resection. Methods: ARTEMIDE-Biliary01 (NCT06109779) is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, global study to assess the efficacy and tolerability of rilvegostomig IV every three weeks versus placebo in combination with investigator's choice of chemotherapy (capecitabine, S-1 [tegafur/gimeracil/oteracil] or gemcitabine/cisplatin) as adjuvant treatment in patients with BTC after curative intent resection. This study will enroll approximately 750 adults with histologically confirmed adenocarcinoma of the biliary tract (intrahepatic or extrahepatic CCA or muscle-invasive GBC) after macroscopically complete resection (R0 or R1) and an ECOG PS of 0–1. Key exclusion criteria include locally advanced, unresectable, or metastatic disease at initial diagnosis and any anti-cancer therapy for BTC prior to surgery. The primary endpoint is recurrence-free survival, and the key secondary endpoint is overall survival. Additional endpoints include progression-free survival following recurrence, patient-reported tolerability, and safety. Enrollment has begun, and approximately 200 sites will be recruiting globally across Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT06109779 .

Adjuvant S-1 vs. observation for resected biliary tract cancer: 5-year follow-up of the JCOG1202/ASCOT.

4119 Background: S-1, an oral fluoropyrimidine derivative, demonstrated significant improvement in overall survival (OS) over observation in patients with curatively resected biliary tract cancer (BTC) (hazard ratio [HR] 0.694, p=0.008; the 3-year OS, 67.6% vs. 77.1%, Lancet 2023). We present updated efficacy data based on a 5-year follow-up of JCOG1202/ASCOT. Methods: Patients aged 20-80 years who had histologically confirmed extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma, or intrahepatic cholangiocarcinoma in a resected specimen and had undergone R0/R1 resection were randomly assigned (1:1) to undergo observation or to receive S-1 (at the dose of 40 mg/m2 twice daily for 4 weeks, followed by 2 weeks of rest, for 4 cycles). The primary endpoint was OS, and the secondary endpoints were relapse-free survival (RFS), adverse events, and proportion of treatment completion. Results: From September 2013 to June 2018, a total of 440 patients (observation, n=222; adjuvant S-1, n=218) were enrolled. The final data cutoff date was June 23, 2023, and the median follow-up duration was 61.5 months. Of all the randomized patients, 215 (48.4%) had died (118 [53.2%] in the observation group; 97 [44.5%] in the S-1 group). The 5-year OS was 52.2% in the observation group and 64.1% in the S-1 group (stratified HR 0.723, 95% confidence interval [CI], 0.551-0.948; one-sided p=0.019). Of the 440 patients, 239 (54.3%) had RFS event (127 [57.2%] in the observation group; 112 [51.4%] in the S-1 group). The 5-year RFS was 45.9% in the observation group and 53.6% in the S-1 group (unstratified HR 0.797, 95% CI 0.618-1.028, stratified HR 0.761, 95% CI 0.589-0.984 in the sensitivity analysis). Most prespecified subgroup analyses (age, primary site, stage, lymph node metastases, types of resections, and serum CA19-9 levels) revealed favorable OS and RFS for the S-1 group. Conclusions: Adjuvant S-1 therapy maintained its survival benefit in a 5-year long-term follow-up, with clinically meaningful improvement in RFS, suggesting that it could be a standard of care for BTC. Clinical trial information: UMIN000011688.

Durvalumab plus gemcitabine/cisplatin/nab-paclitaxel in resectable biliary tract cancer: A phase II, single-arm, open-label study (DurGAP).

e16260 Background: Biliary tract cancer (BTC) presents a formidable challenge, marked by its aggressive nature and dismal prognosis. While surgical resection remains the lone potentially curative option, 5-year survival rates have plateaued below 50%, largely due to high rates of recurrences and metastases. Given these sobering statistics, the imperative for neoadjuvant therapy to enhance outcomes is evident. Building upon the success of the TOPAZ-1 trial, which established durvalumab in combination with gemcitabine and cisplatin as a standard regimen for advanced BTC, this study seeks to assess the safety and efficacy of incorporating neoadjuvant durvalumab alongside gemcitabine, cisplatin, and Nab-paclitaxel for resectable BTC. Methods: Resectable, treatment-naïve BTC patients (pts) were enrolled and administered 3 cycles of neoadjuvant durvalumab (1000mg, iv, d1, q3w) + GAP (gemcitabine 1000mg/m2, cisplatin 25mg/m2, Nab-paclitaxel 100mg/m2, d1, d8, 21d cycle). Primary endpoints included assessing Adverse Events (AEs) and Objective Response Rate (ORR). Secondary endpoints comprised R0 resection rate, Recurrence-Free Survival (RFS), Overall Survival (OS). Results: Between Feb, 2023 to Jan, 2024, a total of 24 patients were enrolled, 12 (50.0%) were male, all with ECOG 0 and 18 (75.0%) presenting with N1 status. Median age: 65 years. Primary sites: intrahepatic (50.0%), extrahepatic (33.3%), gallbladder (16.7%). Median follow-up: 8.75 months; all pts received ≥2 neoadjuvant cycles. The ORR was 62.5%, with all 15 pts demonstrating partial responses (PR). The DCR was 87.5% with 15 PR and 6 stable disease (SD) responses. The most common treatment-related adverse events (TRAEs) were increased ALT/AST (28.6%), anemia (21.8%), hypoalbuminemia (16.0%). Grade ≥3 TRAEs occurred in 2 (8.3%) pts. 13 pts underwent resection, achieving R0 resection in 12 (92.3%) of cases, comprising 10 PR, 2 SD, and 1 pt deemed eligible for surgery post-assessment despite a PD response. 11 pts did not undergo resection, with reasons including patient refusal (4 PR, 1 SD), not meeting resection criteria (2 PD), lost to follow-up (1 PR, 1 SD), and still under active follow-up (2 SD). Conclusions: Neoadjuvant durvalumab combined with gemcitabine/cisplatin/Nab-paclitaxel demonstrated a promising ORR and DCR, with a tolerable safety profile, warranting further investigations in a larger cohort. Clinical trial information: NCT05640791 .

A phase II/III randomized clinical trial of CisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative chemotherapy versus immediate resection in patIents with resecTable BiliarY Tract Cancers (BTC) at high risk for recurrence: PURITY study

BackgroundBiliary tract cancers (BTCs) are rare and lethal cancers, with a 5-year survival inferior to 20%(1–3). The only potential curative treatment is surgical resection. However, despite complex surgical procedures that have a remarkable risk of postoperative morbidity and mortality, the 5-year survival rate after radical surgery (R0) is 20–40% and recurrence rates are up to ~ 75%(4–6). Up to ~ 40% of patients relapse within 12 months after resection, and half of these patient will recur systemically(4–6). There is no standard of care for neoadjuvant chemotherapy (NAC) in resectable BTC, but retrospective reports suggest its potential benefit (7, 8).MethodsPURITY is a no-profit, multicentre, randomized phase II/III trial aimed at evaluating the efficacy of the combination of gemcitabine, cisplatin and nabpaclitaxel (GAP) as neoadjuvant treatment in patients with resectable BTC at high risk for recurrence. Primary objective of this study is to evaluate the efficacy of neoadjuvant GAP followed by surgery as compared to upfront surgery, in terms of 12-month progression-free survival for the phase II part and of progression free survival (PFS) for the phase III study.Key Secondary objectives are event free survival (EFS), relapse-free survival, (RFS), overall survival (OS), R0/R1/R2 resection rate, quality of life (QoL), overall response rate (ORR), resectability. Safety analyses will include toxicity rate and perioperative morbidity and mortality rate.Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues and longitudinal ctDNA analysis are planned to identify potential biomarkers of primary resistance and prognosis.DiscussionConsidering the poor prognosis of resected BTC experiencing early tumor recurrence and the negative prognostic impact of R1/R2 resections, PURITY study is based on the rationale that NAC may improve R0 resection rates and ultimately patients’ outcomes. Furthermore, NAC should allow early eradication of microscopic distant metastases, undetectable by imaging but already present at the time of diagnosis and avoid mortality and morbidity associated with resection for patients with rapid progression or worsening general condition during neoadjuvant therapy. The randomized PURITY study will evaluate whether patients affected by BTC at high risk from recurrence benefit from a neoadjuvant therapy with GAP regimen as compared to immediate surgery.Trial registrationPURITY is registered at ClinicalTrials.gov (NCT06037980) and EuCT(2023–503295-25–00).

Preoperative Myosteatosis and Prognostic Nutritional Index Predict Survival in Older Patients With Resected Biliary Tract Cancer.

Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with cancer. This study evaluated the prognostic significance of sarcopenia (myopenia and myosteatosis) and systemic inflammatory markers in older patients (aged ≥80 years) with resected biliary tract cancer. Patients who underwent resection for biliary tract cancer between July 2010 and January 2023 at the NHO Fukuyama Medical Center were retrospectively reviewed. Preoperative computed tomography measured myopenia and myosteatosis, using the psoas muscle index and modified intramuscular adipose tissue content. Associations between clinicopathological characteristics, inflammation-based prognostic scores, and overall survival were analyzed using Cox proportional hazards models. Univariate analysis revealed low C-reactive protein-to-albumin ratio (<0.125), low prognostic nutritional index (<42), low modified intramuscular adipose tissue content, higher T-stage (T3-4), lymph node metastasis, and postoperative complications associated with worse overall survival in older patients (aged ≥ 80 years) with resected biliary tract cancer (n=48). Multivariate analysis identified low prognostic nutritional index (<42) (p=0.007), low modified intramuscular adipose tissue content (p=0.015), higher T-stage (T3-4) (p<0.001), lymph node metastasis (p=0.001), and postoperative complications (p=0.017) as independent predictors of overall survival. Preoperative myosteatosis and low prognostic nutritional index are independent prognostic factors for overall survival in older patients (aged ≥80 years) with resected biliary tract cancer. These factors may be useful for risk stratification and clinical decision-making. Early interventions, such as nutritional support and physical exercise, may improve outcomes after resection of biliary tract cancer.

Prognostic Significance of Sarcopenia and Systemic Inflammatory Markers in Biliary Tract Cancer: A Retrospective Cohort Study.

To evaluate the prognostic significance of sarcopenia and systemic inflammatory markers in patients with surgically resected biliary tract cancer (BTC). Between July 2010 and December 2022, 146 patients were recruited. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used to calculate the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine prognostic factors for overall survival (OS) and recurrence-free survival (RFS). P < 0.05 was considered statistically significant. Sixty-four patients had sarcopenia. Sarcopenia was associated with body mass index (< 22 kg/m2), lymph node metastasis, and low PNI (< 42). R1/R2 resection (P = 0.02), sarcopenia (P < 0.001), lymph node metastasis (P = 0.007), intrahepatic cholangiocarcinoma (P < 0.001), and low PNI (P = 0.01) were independent predictors of OS, while male sex (P = 0.04), R1/R2 resection (P < 0.001), lymph node metastasis (P = 0.005), intrahepatic cholangiocarcinoma (P < 0.001), tumor differentiation (other than well; P = 0.003), and low PNI (P = 0.03) were independent predictors of RFS. Patients were stratified into no sarcopenia and high PNI (≥ 42; A), sarcopenia or low PNI (B), and sarcopenia and low PNI (C) groups. Group C had worse OS than the other two groups (P < 0.001 and P = 0.02, respectively). Sarcopenia is associated with the PNI. Sarcopenia and the PNI are independent prognostic factors among patients with resected BTC. Sarcopenia may have better prognostic value when combined with the PNI.

Survival outcome of patient with pT1N0 biliary tract cancer treated with surgery alone

IntroductionAdjuvant chemotherapy (AC) with S-1 or capecitabine monotherapy is now the standard of care for resected biliary tract cancer (BTC) according to the Adjuvant S-1 for Cholangiocarcinoma Trial (ASCOT) and the BILCAP study. Patients selection criteria, especially regarding pT1N0 BTC, differed in both trials. We aimed to clarify the survival outcomes regarding resected pT1N0 BTC without AC. MethodsAmong patients with macroscopically complete resection for BTC treated without AC between September 1992 and December 2020, the survival outcomes of those with pT1N0 BTC, except for intrahepatic cholangiocarcinoma, according to the Union for International Cancer Control 7th and 8th edition (TNM7 and 8), were investigated. ResultsOf 749 patients who underwent curative resection for BTC, 69 were identified as having pT1N0 BTC according to TNM8. Six patients (9 %) developed recurrence during the median follow-up period of 53 months (range: 14–263 months) with only one patient (2 %) being pT1N0 according to TNM7. Based on TNM8, the 5-year recurrence-free survival, disease-specific survival, and overall survival reached 90.7 % (95 % confidence interval [CI]: 80.3–95.7 %), 96.4 % (95 % CI: 86.1–99.1 %), and 85.3 % (95 % CI: 71.2–92.8 %), respectively. Perineural invasion (PNI) was significantly associated with recurrence, and the recurrence rate in patients with PNI reached as high as 40 %. ConclusionsThe survival outcomes regarding resected pT1N0 BTC according to TNM7 were excellent without AC; however, those of TNM8 were not, with PNI being associated with recurrence risk.

Prognostic impact of peritoneal washing cytology in patients with biliary tract cancer

PurposeTo elucidate the clinical significance of peritoneal washing cytology (PWC) in patients with resectable biliary tract cancer (BTC).MethodsClinical data of patients with BTC, who received PWC at curative intent surgery from March 2009 to December 2021, were retrospectively analyzed. Eligible patients were stratified into two groups according to positive or negative PWC. Recurrence-free survival and overall survival were compared between the two groups. Independent factors associated with positive PWC were investigated using multivariate analysis.ResultsAmong the 284 patients analyzed, all 53 patients with ampullary carcinoma showed negative PWC and these patients were excluded. Among the remaining eligible 231 patients, 41 patients had intrahepatic cholangiocarcinoma, 55 had gall bladder carcinoma, 72 had hilar cholangiocarcinoma, and 63 had distal cholangiocarcinoma. Eleven (4.8%) patients had positive PWC, and 220 (95.2%) had negative PWC. The median recurrence-free survival in the positive and negative PWC groups were 12.0 vs. 60.7 months (p = 0.005); the median overall survival times were 17.0 vs. 60.6 months (p = 0.008), respectively. Multivariate analysis revealed that serum carbohydrate antigen 19–9 level over 80 U/mL and multiple lymph node metastasis were independently associated with positive PWC (odds ratio [OR]: 5.84, p = 0.031; OR: 5.28, p = 0.021, respectively).ConclusionPatients with positive PWC exhibited earlier recurrence and shorter survival times compared with those with negative PWC.

Continuation rather than early induction in S-1 adjuvant chemotherapy and prognosis in patients after biliary tract cancer resection.

474 Background: The efficacy of S-1 monotherapy as adjuvant chemotherapy (AC) for pancreatic cancer has been demonstrated, and the long-term results are clearly improving.1 In biliary tract cancer, the JCOG1201 trial in Japan also demonstrated the usefulness of S-1 AC recently.2 We have been also performed S-1 AC for biliary tract cancer in recent years in accordance with the clinical necessity. In this article, we herein retrospectively analyze the S-1 AC for biliary tract cancer especially in the significance of initiation day or therapy continuation. Methods: 134 patients with the resection of biliary tract cancer (intrahepatic cholangiocarcinoma 25/ hilar 17/ gallbladder 27/ distal bile duct 38/ papillary 25 from January 2017 to December 2021 were included in this study. Age 73(30-87) years, 47 hepatic resections/66 pancreatecticoduodenectomies/21 peri-gallbladder resection. The decision to administer AC was made at the discretion of the attending doctor and in consultation with the patient, and the decision to discontinue was based on the patient's physical condition. If there was no particular need to discontinue, the treatment was continued for six months at least. Results: S-1 AC was performed in 57/137 (43%) of eligible patients. Age was similar between with or without AC patients (73 vs. 73 years old). There were no significant differences by the cancer location. Although pathological stage was higher in the patients with AC (stage 0:1:2:3:4 = 0: 20: 39: 31: 9%) than without AC ( = 9: 45: 33: 10: 3%) (p &lt; 0.001), 2 years recurrence free survival (2y- RFS) was similar between with AC or without AC patients (66.6 vs 71.6%, p=0.82). In the subgroup analysis of the patients with AC, although comparisons of induction day of AC within or after postoperative 6 weeks showed no difference in patient’s prognosis, patients with continuation of AC for at least 6 months after initiation clearly had a better prognosis than without it (2y-RFS: 89.6 vs 41.7%, p=0.003). Conclusions: In S-1 AC for the patients after biliary tract cancer resection, early induction does not play much role, but continuation is important to maintain better prognosis. 1. Uesaka et al. Lancet, 2016. 2. Nakachi et al. Lancet, 2023.

Efficacy of S-1 Adjuvant Chemotherapy for Resected Biliary Tract Cancer: A Retrospective Propensity-Matched Analysis.

Surgical resection is considered an effective cure for biliary tract cancer (BTC); however, the prognosis is unsatisfactory despite improved surgical techniques and perioperative management. The recurrence rate remains high even after curative resection. The efficacy of adjuvant chemotherapy in pancreatic and gastric cancers has been previously reported, and the feasibility of adjuvant therapy with S-1 has recently been reported in patients with resected BTC. We aimed to retrospectively investigate the effects of adjuvant chemotherapy with S-1 on resected advanced BTC. We included data from 438 BTC patients who underwent resection between 2001 and 2020. After excluding patients with pTis-pT1 (n = 112) and other exclusion criteria, 266 patients were included in the analysis. After propensity score matching, 48 patients received S-1 adjuvant chemotherapy (S-1 group), and 48 patients received non-S1 adjuvant chemotherapy or underwent surgery alone (Non-S-1 group). The patients in the S-1 group had significantly better overall survival (OS) than those in the non-S-1 group (MST 51 vs 37 months, hazard ratio [HR]:.54, 95% confidence interval [CI]:.30-.98, P = .04). The S-1 group had a significantly better recurrence-free survival (RFS) than the non-S-1 group (94 vs 21 months, HR: .57, 95% CI: .33-.97, P = .03). Subgroup analyses for OS and RFS exhibited the benefits of S-1 in patients aged <75 years and in patients with primary sites of extrahepatic and perineural invasion and curability of R0. S-1 adjuvant therapy is promising for improving the postoperative survival of patients with resected advanced BTC, positive nerve invasion, and R0 resection.

Adjuvant Chemotherapy and Outcomes in Older Adult Patients With Biliary Tract Cancer

The association of adjuvant chemotherapy (AC) with survival in the general population of patients with resected biliary tract cancer (BTC) remains controversial. As such, the role of this treatment in the treatment of older adult patients (aged ≥70 years) needs to be evaluated. To describe the patterns of use of AC and compare survival outcomes of AC and observation in older adult patients following resection of BTC. This retrospective cohort study included 8091 older adult patients with resected BTC with data available in the National Cancer Database from January 1, 2004, to December 31, 2019. Patients were divided into 2 cohorts: AC and observation. The AC cohort was subdivided into single-agent and multiagent AC treatment. Adjuvant chemotherapy vs observation following BTC resection. The primary outcome was overall survival (OS) of patients who received AC compared with observation following resection of BTC as evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Inverse probability of treatment weighting and propensity score matching were performed to address indication bias. Between 2004 and 2019, of 8091 older adult patients with resected BTC identified (median [range] age, 77 [70-90] years; 5136 women [63.5%]; 2955 men [36.5%]), only one-third (2632 [32.5%]) received AC. There was an increase in the use of AC across the study period from 20.7% (n = 495) in 2004 to 2009 to 41.2% (n = 856) in 2016 to 2019. Age 80 years or older (odds ratio, 0.29; 95% CI, 0.25-0.33; P < .001) and gallbladder primary site (odds ratio, 0.71; 95% CI, 0.61-0.83; P < .001) were associated with a lower odds of AC. Following inverse probability of treatment weighting, as a composite, AC was not associated with improved survival (median OS, 20.5 months; 95% CI, 19.2-21.7 months) compared with observation (median OS, 19.0 months; 95% CI, 18.1-20.3 months). A longer median OS was associated with single-agent AC (21.5 months; 95% CI, 19.9-24.0 months) but not multiagent AC (19.1 months; 95% CI, 17.5-21.1 months) compared with observation (median OS, 17.3 months; 95% CI, 16.1-18.4 months). This improvement in OS with single-agent AC was not apparent on multivariable analysis (hazard ratio [HR], 0.97; 95% CI, 0.89-1.05; P = .44). However, age at diagnosis of 80 years or older (HR, 1.35; 95% CI, 1.28-1.42; P < .001) and treatment at nonacademic centers (HR, 1.14; 95% CI, 1.07-1.20, P < .001) were associated with worse OS. In this cohort study of older adult patients, AC was not associated with an improvement in survival compared with observation following BTC resection. These findings suggest the need for further study of AC for older adult patients who may benefit after curative intent surgery for BTC.

Real-world experience supporting the role of oncologic resection and adjuvant chemotherapy in biliary tract cancers.

Complete resection followed by adjuvant chemotherapy is the gold standard for patients with localized cholangiocarcinoma (CC) or gallbladder cancer (GBC). However, this is not always feasible, and recurrence rates remain high. To understand the real-world proportions and reason for treatment failure in resected biliary tract cancers. We performed a retrospective population-based review of patients with GBC or CC [intrahepatic (IHCC) or extrahepatic (EHCC)] resected between 2005 and 2019 using the BC Cancer provincial database. A chart review was conducted to characterize demographics, treatments received and outcomes. In total, 594 patients were identified of whom 416 (70%) had disease recurrence. Most GBCs (96%) were diagnosed incidentally, and repeat oncologic resection was performed in 45%. Adjuvant chemotherapy was received in 51% of patients diagnosed after 2017 (mostly capecitabine). Patient co-morbidities, disease progression and patient preference were the commonest reasons for not proceeding with adjuvant chemotherapy. One-third of patients did not complete all planned cycles. Median overall survival was significantly higher in those with complete (R0) versus incomplete (R1) resection [31.6 versus 18 months, hazard ratio (HR): 0.43, 95% confidence interval (CI): 0.35-0.53] and in those with versus without re-resection for GBC [29.4 versus 19 months, HR: 0.55, 95% CI: 0.41-0.73]. There was a trend towards improved survival with versus without adjuvant therapy (HR: 0.79, 95% CI: 0.61-1.02). Only 25% in the more contemporary cohort (2017-2019) had an R0 resection and completed adjuvant chemotherapy. Complete resection, including reresection for incidentally diagnosed GBCs, and adjuvant chemotherapy were associated with improved outcomes in this retrospective cohort, yet many patients were not able to complete these treatments. Neoadjuvant strategies may improve treatment delivery and ultimately, outcomes.

Completion of adjuvant S-1 chemotherapy after surgical resection for biliary tract cancer: A single center experience

BackgroundsA recent randomized control trial (JCOG1202; ASCOT trial) demonstrated the efficacy of adjuvant S-1 chemotherapy (ASC) for biliary tract cancer (BTC) after surgical resection; however, the significance of the completion of ASC in the real-world setting remains unknown. MethodsData of consecutive patients who underwent surgical resection for biliary tract cancer (BTC) from 2011 to 2021 were retrospectively reviewed. Of these, patients who underwent ASC were enrolled in this study. Patients were divided into two groups according to whether ASC was completed: the completion group and the non-completion group. Clinicopathological features and survival outcomes were assessed. ResultsOf the 223 patients with BTC who underwent surgical resection, 75 patients who underwent ASC were included for analysis. Among them, 48 (64.0 %) completed the intended ASC course, while 27 cases (36.0 %) discontinued the treatment. The most common reason for the discontinuation was adverse event (n = 16, 59.3 %), followed by disease recurrence (n = 9, 33.3 %). Patients in the completion group showed significantly better overall survival (OS) (p < 0.001) and recurrence-free survival (RFS) (p < 0.001) compared to the non-completion group. Further, after excluding the patients in the non-completion group who discontinued ASC due to disease recurrence, the significance of ASC completion was retained for both OS and RFS. ConclusionThe completion of ASC was associated with improved prognosis in patients with BTC after surgical resection. The achievement of ASC should be the goal after surgical resection, while further study may be warranted regarding the resistance of ASC.

Adjuvant chemotherapy for resected biliary tract cancers: A fluorouracil-based scheme beats out a gemcitabine-based scheme for the win.

Adjuvant chemotherapy for resected biliary tract cancers: A fluorouracil-based scheme beats out a gemcitabine-based scheme for the win.

A critical appraisal of the potential benefit of post-operative structured follow-up after resection for biliary tract cancer

BackgroundThere is currently no evidence to support structured use of imaging or biomarkers during follow-up of patients after curative resection of biliary tract cancer (BTC). Besides, the influence of early detection of recurrence and subsequent start of palliative chemotherapy on overall survival remains unknown. The aim of this study is to describe and compare the results of two follow-up strategies. MethodsThis retrospective multicenter cohort study compared patients from the Amsterdam UMC undergoing pragmatic clinical follow-up, to patients from the observational cohort of the BILCAP study undergoing structured follow-up. Primary outcome was overall survival. ResultsA total of 315 patients were included n=91 pragmatic, n=224 structured follow-up). At median follow-up of 56.9 months, 189 (60%) patients were diagnosed with recurrence. After recurrence, more patients received palliative (chemo) therapy in the structured group (43% vs 75%, P<0.001). Median overall survival was lower in the pragmatic group (27.7 vs 39.1 months, P=0.003). Median overall survival of patients who actually received chemotherapy was comparable (27.2 vs 27.7 months, P=0.574). ConclusionThis study describes the results of two follow-up strategies. Although these groups are biased, it is noted that after pragmatic follow-up fewer patients received palliative chemotherapy but that those who actually received chemotherapy had similar overall survival compared to patients undergoing structured follow-up.

129P Prognostic factors associated with survival in resected biliary tract cancers: A multicentre Italian experience

129P Prognostic factors associated with survival in resected biliary tract cancers: A multicentre Italian experience