A Novel Pathology-Based Preoperative Risk Score to Predict Locoregional Residual and Distant Disease and Survival for Incidental Gallbladder Cancer: A 10-Institution Study from the U.S. Extrahepatic Biliary Malignancy Consortium

Abstract

Background This study was designed to develop a more robust predictive model, beyond T-stage alone, for incidental gallbladder cancer (IGBC) for discovering locoregional residual (LRD) and distant disease (DD) at reoperation, and estimating overall survival (OS). T-stage alone is currently used to guide treatment for incidental gallbladder cancer. Residual disease at re-resection is the most important factor in predicting outcomes. Methods All patients with IGBC who underwent reoperation at 10 institutions from 2000 to 2015 were included. Routine pathology data from initial cholecystectomy was utilized to create the gallbladder cancer predictive risk score (GBRS). Results Of 449 patients with gallbladder cancer, 262 (58 %) were incidentally discovered and underwent reoperation. Advanced T-stage, grade, and presence of lymphovascular (LVI) and perineural (PNI) invasion were all associated with increased rates of DD and LRD and decreased OS. Each pathologic characteristic was assigned a value (T1a: 0, T1b: 1, T2: 2, T3/4: 3; well-diff: 1, mod-diff: 2, poor-diff: 3; LVI-neg: 1, LVI-pos: 2; PNI-neg: 1, PNI-pos: 2), which added to a total GBRS score from 3 to 10. The scores were separated into three risk-groups (low: 3–4, intermediate: 5–7, high: 8–10). Each progressive GBRS group was associated with an increased incidence LRD and DD at the time of re-resection and reduced OS. Conclusions By accounting for subtle pathologic variations within each T-stage, this novel predictive risk-score better stratifies patients with incidentally discovered gall-bladder cancer. Compared with T-stage alone, it more accurately identifies patients at risk for locoregional-residual and distant disease and predicts long-term survival as it redistributes T1b, T2, and T3 disease across separate risk-groups based on additional biologic features. This score may help to optimize treatment strategy for patients with incidentally discovered gallbladder cancer.

Gallbladder Cancer Presenting with Jaundice: Uniformly Fatal or Still Potentially Curable?

“…Lymphovascular invasion has been shown to be a surrogate for an aggressive malignant phenotype in GBC. 21, 22 Because lymphovascular invasion can be pathologically examined following cholecystectomy or with a preoperative (laparoscopic, endoscopic, or percutaneous) biopsy, it may be a useful tool in the selection of jaundiced GBC patients for radical surgery.…”

Predicting Residual Disease in Incidental Gallbladder Cancer: Risk Stratification for Modified Treatment Strategies

“…Ethun et al recently published the Gallbladder Risk Score (GBRS) based on univariate significance of LVI, PNI, T-stage and grade (11). This was the first study to propose a prognostic score to predict RD in incidental gallbladder cancer and prompted investigation of a preoperative model within our data.…”

“…Involvement of regional lymph nodes, while also prognostic, is not routinely available with the cholecystectomy specimen and unknown until re-operation and staging (10). Utilizing only factors available from the pathology report from the original cholecystectomy, a recent study found univariate associations between T stage, grade, lymphovascular invasion (LVI), and perineural invasion (PNI) with loco-regional residual disease, distant residual disease and overall survival (11). Preoperative prediction of residual disease has the potential to impact patient management and selection for modified treatment strategies.…”

A Novel T-Stage Classification System for Adrenocortical Carcinoma: Proposal from the US Adrenocortical Carcinoma Study Group

“…11–18,23 In addition, LVI has been associated with other poor prognostic factors, such as poorly differentiated pathology, increased preoperative serum carcinoembryonic antigen levels, and lymph node metastasis. 11,16,24 Several studies have proposed using LVI as an independent risk factor, in lieu of lymph node involvement, to help guide prognosis and adjuvant treatment decisions, especially for diseases where lymph node status often cannot be deter-mined.…”

“…11–18 Our group recently proposed a novel staging system for distal cholangiocarcinoma based on tumor size and LVI status, which better differentiated patient survival compared with the current AJCC T-stage system. Although lymph node involvement is a known poor prognostic factor, its prognostic value is limited in some malignancies due to low lymph node yields during resection.…”