Adjuvant chemotherapy for gallbladder cancer: Current evidence, controversies, and future directions

Abstract

Gallbladder cancer is an aggressive malignancy notorious for its poor prognosis and treatment challenges, even at early stages. In their recent work, Kim et al utilized data from the National Cancer Database to explore whether adding chemotherapy to surgical intervention could improve survival outcomes for patients diagnosed with stage II gallbladder cancer. The use of adjuvant chemotherapy following curative surgery in this patient population has been a long-standing source of debate. Historically, the lack of clear guidelines for managing stage II gallbladder cancer has resulted in inconsistent, sometimes contradictory findings from various studies regarding the effectiveness of postoperative chemotherapy. Consequently, many clinicians have relied on studies involving other biliary tract cancers to justify the routine use of prophylactic chemotherapy after surgery, aiming to minimize recurrence risk. Given the rarity, high mortality rate, and the small sample sizes typical in gallbladder cancer studies, Kim et al’s contribution represents a significant and commendable effort to address these challenges. Kim et al designed a retrospective cohort study with well-defined inclusion criteria and clear treatment classifications. Notably, their findings suggested that in stage II gallbladder cancer, adjuvant chemotherapy did not yield a meaningful survival benefit over surgery alone. These results therefore casted doubt on the routine practice of administering chemotherapy to all patients postoperatively, prompted clinicians to reconsider their approach. Furthermore, this controversy directly influences clinical decisionmaking and guideline recommendations, as uncertainty regarding the benefit of adjuvant chemotherapy may lead to heterogeneous practices across different institutions and regions. This article critically assessed the research design, methodology, and clinical implications of the study by Kim et al. It also provided an in-depth exploration of the broader question regarding the appropriateness of adjuvant chemotherapy following surgery for stage II gallbladder cancer, highlighting the necessity of rigorous study designs to produce reliable evidence.

Keywords: Gallbladder cancer; Adjuvant chemotherapy; National Cancer Database; Retrospective analysis; Cancer staging

Core Tip: Whether patients with stage II gallbladder cancer should routinely receive adjuvant chemotherapy after surgery remains uncertain. The analysis by Kim et al, based on National Cancer Database data, found no statistically significant survival benefit associated with chemotherapy in these patients. However, the results should not be hastily interpreted as evidence against chemotherapy altogether. Instead, clinicians must consider individualized treatment decisions based on pathological features and the patient’s overall health condition. This article further evaluated the strengths and weaknesses of Kim et al’s research design. It recommended conducting future studies, ideally prospective clinical trials or refined retrospective analyses, to better clarify chemotherapy’s role in this context.