Adjuvant, Neoadjuvant Chemotherapy Use Low in Surgically Resected Gallbladder Cancers

Gallbladder cancer, computer illustration.
Researchers examined factors linked to using neoadjuvant and adjuvant chemotherapy in individuals with resectable gallbladder cancer.

Although overall use is low in patients with resectable gallbladder cancer, adjuvant chemotherapy is associated with statistically significant improvement in survival, and neoadjuvant chemotherapy is associated with greater benefit in those with node-positive disease, according to study results published in JAMA Network Open.

Researchers reported their findings regarding use of chemotherapy in the neoadjuvant and adjuvant settings compared with surgery alone in patients with localized or locoregionally advanced but resectable gallbladder cancers.

For the retrospective cohort study, researchers sourced data from the National Cancer Database (NCDB). Eligible participants were aged 18 years and older and had localized or locoregionally advanced gallbladder cancers. Study participants had definitive surgery from January 1, 2004, to January 1, 2016 and had stage II to III and IV disease, with no distant metastasis. Researchers used the adjusted Kaplan-Meier method to calculate overall survival with inverse probability of treatment weighted to reduce confounding effects.

A total of 6391 patients (median age, 68 years; IQR, 59-77; 71.3% women) were included. Surgery alone was performed in 3145 patients (49.2%), and 3145 (49.2%) received adjuvant chemotherapy; 101 (1.6%) received neoadjuvant chemotherapy.

Neoadjuvant therapy was used more frequently in younger patients (median age, 59 years [IQR, 52-66]) compared with surgery alone (median age, 72 years [IQR, 63-81]) or adjuvant chemotherapy (median age, 65 years [IQR, 57-72]) (P <.001).

Neoadjuvant chemotherapy was more common in patients with private insurance compared with other types of insurance (65 patients [65%] vs 11 patients [11%] with Medicaid insurance; P < .001). Adjuvant chemotherapy (1438 patients [43%]) and surgery alone (1925 patients [57%]) were common in patients with Medicare insurance. Neoadjuvant chemotherapy was more likely to be administered in academic centers (61 patients [60%]) vs nonacademic settings (38 patients [38%]) (P <.001).

Most differences between the groups were nonsignificant after propensity score matching, except for patients who received treatment in academic vs nonacademic facilities. Multivariable analysis showed that adjuvant chemotherapy was associated with a statistically significant improvement in overall survival compared with surgery alone (22 vs 18 months: hazard ratio [HR], 0.78; 95% CI, 0.63-0.96). Although a higher absolute median survival was observed in the neoadjuvant chemotherapy group, this difference was not statistically significant (27 vs 18 months: HR, 0.78; 95% CI, 0.58-1.04).

Among patients with node-positive gallbladder cancer, longer median overall survival was associated with neoadjuvant chemotherapy (median survival time, 30 months [95% CI, 24-36 months]) vs adjuvant chemotherapy (median survival time, 22 months [95% CI, 19-26 months]) and surgery alone (median survival time, 14 months [95% CI, 11-17]) (P =.002).

The investigators noted that excluding patients with unknown survival status may have introduced selection bias into the analysis, and the study could have unmeasured confounding. Also, the number of patients in the neoadjuvant group was small, and the NCDB lacks details on chemotherapy regimens, number of cycles, and doses.

“These findings suggest that use of adjuvant chemotherapy and neoadjuvant chemotherapy should be considered in the treatment of gallbladder cancer,” the researchers concluded.

Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Ozer M, Goksu SY, Sanford NN, et al. A propensity score analysis of chemotherapy use in patients with resectable gallbladder cancer. JAMA Netw Open. Published online February 16, 2022. doi:10.1001/jamanetworkopen.2021.46912