Impact of Chemotherapy and External-Beam Radiation Therapy on Outcomes among Patients with Resected Gallbladder Cancer: A Multi-institutional Analysis

Abstract

Background Use of adjuvant chemotherapy (CTx) and chemoradiation therapy (cXRT) for the treatment of gall-bladder cancer (GBC) remains varied. We sought to define the utilization and effect of adjuvant therapy for patients with GBC. Methods Using a multi-institutional national database, 291 patients with GBC who underwent curative-intent resection between 2000 and 2015 were included. Patients with metastasis or an R2 margin were excluded. Results Median patient age was 66.6 years. Most patients had a T2 (46.2 %) or T3 (38.6 %) lesion, and 37.8 % of patients had lymph node (LN) metastasis. A total of 186 (63.9 %) patients underwent surgery alone, 61 (21.0 %) received CTx, and 44 (15.1 %) patients received cXRT. On multivariable analysis, factors associated with worse overall survival (OS) included T3/T4 stage [hazard ratio (HR) 1.82], LN-metastasis (HR 1.84), lymphovascular invasion (HR 2.02), perineural invasion (HR 1.42), and R1 surgical margin status (HR 2.06); all P <0.05). In contrast, receipt of CTx/cXRT was associated with improved OS (CTx, HR 0.38; cXRT, HR 0.26; P < 0.001) compared with surgery alone. Similar results were observed for disease-free survival (DFS) (CTx, HR 0.61; cXRT, HR 0.43; P < 0.05). Of note, only patients with high-risk features, such as AJCC T3/T4 stage (HR 0.41), LN metastasis (HR 0.45), and R1 disease (HR 0.21) (all P <0.05) derived an OS benefit from CTx/cXRT. Conclusions Adjuvant CTx/cXRT was utilized in 36 % of patients undergoing curative-intent resection for GBC. After adjusted analyses, CTx/cXRT were independently associated with improved long-term outcomes, but the benefit was isolated to only patients with high-risk characteristics.

Validation of the 8th Edition of the American Joint Committee on Cancer Staging System for Gallbladder Cancer and Implications for the Follow-up of Patients without Node Dissection

“…6 examined lymph nodes as recommended by the 8th edition staging manual. Our results are concordant with one previous Western study [18]. However, the survival difference between patients with N1 and N2 gallbladder cancers disappeared, when we examined < 6 lymph nodes or all cases with any number of harvested lymph nodes.…”

“…Several previous studies in Japan recommended to evaluate a minimum of six lymph nodes [20][21][22]. In contrast, one study proposed to examine at least four lymph nodes [18]. Therefore, further studies are required to identify the best cut-off number of lymph nodes evaluated in gallbladder cancers.…”

A retrospective analysis of patients with gallbladder cancer: surgical treatment and survival according to tumor stage

“…The phase-III ABC-02 study (cisplatin + gemcitabine vs cisplatin alone) randomized clinical trial has shown a benefit for advanced biliary or metastatic tumors (28). Adjuvant therapy resulted in improved survival, even in patients with stage T3/T4 disease, nodal involvement and R1 resection (29). Radiotherapy is also increasingly used as it significantly reduces local recurrence rates and increases short-term survival (30).…”

Long-Term Outcomes and Prognostic Factors in Advanced Gallbladder Cancer: Focus on the Advanced T Stage

“…The range of chemotherapy includes gemcitabine, fluoropyrimidines or gemcitabine-based combination chemotherapy[33]. In a latest multi-institutional analysis, adjuvant therapies were reported independently associated with improved long-term outcomes in GBC patients with advanced T stage, LN metastasis and R1 margin[52], and a similar conclusion was also declared by Ma et al in a meta-analysis[53]. However, very few patients would like to receive these adjuvant therapies in our district so that we could not analyze the relationship between adjuvant therapies and prognosis in this research.…”