Second Resections in Gallbladder Cancer Tied to Better OS, but Barely Used

Second definitive surgery in gallbladder cancer was associated with improved overall survival (OS), a retrospective study found, but the practice goes largely underutilized.

In a study of 6,175 patients, those who underwent re-resection — defined as definitive surgery within 180 days after the first operation — had a median OS of 44 months compared with 23 months for those who did not (P<0.0001), reported Marianna Papageorge, MD, of Boston Medical Center, and colleagues.

After propensity score matching, re-resection continued to be associated with superior survival (median OS 44 vs 31 months; P=0.0004), according to the findings in Annals of Surgical Oncology.

“Despite [National Comprehensive Cancer Network] guidelines that recommend re-resection, our study found that only 7.6% of patients underwent a second operation,” the group wrote.

Gallbladder cancer is rare and has a 5-year survival rate ranging from 80% for stage I disease to 4% for stage IV disease. Rates of this disease are growing because of an increase in the incidence of risk factors, such as cholelithiasis, chronic cholecystitis, bacterial infections, porcelain gallbladder, obesity, and poor diet, they said.

Most cases of gallbladder cancer are diagnosed incidentally during or after a simple cholecystectomy performed for gallstone disease, cholecystitis, or gallbladder polyps. While early-stage gallbladder cancer has an overall good prognosis and is usually treated with a simple cholecystectomy without the need for additional procedures, guidelines for advanced disease recommend surgical resection with en bloc liver resection, portal lymphadenectomy, and bile duct resection. These recommendations are supported by studies showing that most patients who undergo re-resection for gallbladder cancer following laparoscopic cholecystectomy end up having residual disease, Papageorge and team noted.

“Despite these findings, the survival benefit of patients undergoing re-resection has been variable,” they wrote. “In addition, controversies persist about the value of lymphadenectomy and adjuvant therapy among patients undergoing re-resection.”

The researchers used the National Cancer Database to identify patients with gallbladder adenocarcinoma (which represents about 90% of all gallbladder cancers) who underwent surgical resection from 2004 to 2015. OS was the primary outcome. Patients who underwent re-resection did so after a median interval of 42 days (interquartile range 28-59).

Patients who underwent re-resection compared with those who did not were younger (65 vs 72 years) and more likely to have private insurance (41.6% vs 27.1%), receive treatment in the Northeast (22.8% vs 20.4%) and at an academic medical center (50.4% vs 29.7%), have negative margins on final pathology (90.1% vs 72.6%), and receive chemotherapy (53.7% vs 35.8%).

The authors also noted some racial disparities. For example, they found that Black patients were less likely to undergo re-resection, and that those who did not had worse survival compared with other races. However, they also found that there were no differences in survival based on race, insurance status, or treatment facility in patients who did undergo re-resection.

“This is encouraging as it demonstrates that those who are undergoing re-resection are achieving equitable outcomes, in contrast to the survival differences present among those who did not undergo re-resection,” observed Papageorge and colleagues.

In an accompanying editorial, Jessica Keilson, MD, and Shishir Maithel, MD, both of the Winship Cancer Institute at Emory University in Atlanta, noted that the results are suggestive of a practice pattern that is “encountered all too frequently in the management of this rare disease, where patients are ultimately managed with only chemotherapy and/or radiation and are never referred to a surgical oncologist for re-resection.”

They noted that there are several reasons why adherence to guidelines for gallbladder cancer is low, including a lack of familiarity with how to manage such a rare disease, as well as patient-centric and system-wide barriers that hinder a patient’s ability to reach and receive specialty care.

More education, particularly in community-level practice, as well as increased referral for surgical oncology consultation and improved access to care, are necessary to achieve better outcomes for gallbladder cancer patients, Papageorge and colleagues concluded.