In the United States, approximately 55% of patients with resected gallbladder cancer undergo oncologic surgery without additional systemic treatment. However, as gallbladder cancer progresses to T3 (locally or regionally advanced) or T4 (distant metastasis) disease, the tumor frequently infiltrates adjacent organs, leading to the consideration of different therapeutic strategies. They can include major liver resection alone or combined with adjacent organs (duodenum, stomach, and/or colon) or vascular structures (removal of the tumor extending beyond the primary site), with chemotherapy and radiotherapy either before or after surgery.
Despite these recommendations, the optimal extent of surgical resection for advanced gallbladder cancer remains a matter of ongoing debate. Although it is well recognized that outcomes for advanced gallbladder cancer remain poor, controversy persists over the appropriate aggressiveness of surgery, particularly because of the limited efficacy of chemotherapy.
In a recent multicenter study led by Boston University (BU) Chobanian & Avedisian School of Medicine, researchers have found that aggressive surgery in patients with advanced gallbladder cancer (T3 or T4) may lead to high complication and mortality rates, especially in patients who have T4 disease with invasion of adjacent organs. These findings were published by Chirban et al in the Journal of Gastrointestinal Surgery.
“Our study supports more careful selection after systemic treatment of patients [with gallbladder cancer] for major surgery and highlights when it might be better to avoid aggressive procedures that may not help and could even cause harm,” explained corresponding author Eduardo Vega, MD, Assistant Professor of Surgery at BU.
Study Details and Results
The researchers reviewed the medical records of more than 1,000 patients with gallbladder cancer from 17 hospitals across 7 countries treated between 1997 and 2022. They were grouped based on how advanced their cancer was (T3 or T4), and the study authors analyzed how different oncologic factors were linked to surgical outcomes, complications, and survival. The researchers found advanced-stage gallbladder cancer outcomes varied with resection status, and removal of the tumor beyond the primary site was associated with increased morbidity, especially in patients with T4 disease, where survival benefits were limited.
Morbidity was nearly 65% in patients with T4 tumors vs about 8% in patients with T3 disease; severe morbidity was 46.3% and 17.1%, respectively. The rate of 90-day mortality was 4.1% for patients with T3 gallbladder cancer and 12% for patients with T4 gallbladder cancer; the 3-year overall survival rate was 33% vs 4%. Predictors of resection status included jaundice before surgery, perineural and/or lymphovascular invasion, adjacent organ resection, overall morbidity, and lymph node metastasis, reported the authors.
According to the researchers, this study introduces the idea that more personalized treatment—guided by individual risk factors such as jaundice or lymph node involvement—may lead to better, more customized outcomes and should play a central role in surgical decision-making. “Careful patient selection for aggressive surgical treatment is crucial to avoid unnecessary morbidity while carefully weighing the potential survival benefits,” they stated.
“By tailoring treatment to the individual, we hope to reduce morbidity and improve quality of life for those facing this aggressive disease. It also highlights the power of international collaboration to advance cancer care, especially for understudied diseases like gallbladder cancer,” added Dr. Vega, who is also a hepatobiliopancreatic surgeon at Boston Medical Center.
Disclosure: For full disclosures of the study authors, visit sciencedirect.com.
