Dr. Venkata Pradeep Babu Koyyala

Director, Shankara Cancer and Research Institute, tezpur, Assam
MBBS (AMC,Gold Medalist),MD (Gen. Med), Doctorate in Medical Oncology,
Former Head, Medical Oncology, ACCF (TATA Trusts), Assam
European Certification in Medical Oncology
Fellow, European Society (PMC, Canada), FUICC, Italy
Former Assistant Professor, TATA Memorial Center, Visakhapatnam.
Ex-Consultant, Rajiv Gandhi Cancer Institute and Research Center,
Associate Editor, Indian Journal of Medical and Pediatric Oncology

GBC-01 is the study by Ostwal and colleagues evaluates the role of gemcitabine–cisplatin (GC) as adjuvant chemotherapy in patients with resected stage II and stage III gallbladder cancer (GBC) in a high-volume Indian center. This is a retrospective analysis of patients treated between 2010 and 2016, drawn from a prospectively maintained database. Out of 242 resected cases, 125 patients with stage II–III disease received adjuvant GC and form the core of this analysis.

The regimen consisted of gemcitabine 1000 mg/m² and cisplatin 25 mg/m² on days 1 and 8 every 21 days, for up to six cycles. A small subset also received “sandwich” chemoradiation. The study is not randomized and lacks a formal comparator arm, but it reflects institutional practice in a region with a high prevalence of gallbladder cancer. We are heavily reliant on western data, for our practice, which usually combines all biliary cancers together and not gall bladder site specific. In the absence of robust GBC-specific adjuvant trials from high-burden regions, such real-world data are clinically relevant.

The median age of patients in this trial was 50 years, and nearly 78% of patients were women. This demographic profile mirrors what many of us see in clinical practice, particularly in North and Northeast India, where gallbladder cancer often affects relatively younger women.

Stage distribution included 28% stage II and 72% stage III disease (with 44% stage IIIB). Most patients (90.4%) underwent R0 resection, reflecting a strong surgical program. About 30% had elevated CA 19-9 at baseline.

In our setting in Northeast India, gallbladder cancer remains one of the most frequent gastrointestinal malignancies. However, many patients present late or undergo suboptimal initial surgery elsewhere. Therefore, a cohort with high R0 rates represents a somewhat selected group, and this should be kept in mind while interpreting survival outcomes. Also a great majority of patients in periphery are operated for non-oncological indications and undergoes a second surgery for completion after initial HPE report.

With a median follow-up of approximately 37 months, the 3-year overall survival (OS) for the entire cohort was 69.5%, and 3-year recurrence-free survival (RFS) was 60.3%. Stage-wise 3-year OS was 91.9% for stage II, 67% for stage IIIA, and 58.1% for stage IIIB disease. These results represents a clear gradient of outcomes by stage at diagnosis.

Toxicity was manageable. Among evaluable patients, grade 3–4 neutropenia occurred in 9.9%, febrile neutropenia in 3.6%, and fatigue in 7.3%. Dose reductions were required in less than 10%, and 84% completed all six planned cycles. These completion rates are noteworthy for a doublet regimen.

Recurrence patterns showed that 75% of relapses were distant rather than locoregional. This reinforces the systemic nature of failure in GBC and the rationale for effective systemic adjuvant therapy.

It is important to note that patients with stage III disease who did not receive adjuvant chemotherapy had a 3-year OS of 43.8%, though this comparison is limited by potential selection bias.

While the results are encouraging, one must interpret these findings cautiously. The absence of a control group makes it difficult to determine the true incremental benefit over observation or over single-agent capecitabine, which has become a commonly accepted adjuvant standard in biliary tract cancers following the BILCAP study.

The authors conclude that adjuvant gemcitabine–cisplatin following predominantly R0 resection in stage II–III gallbladder cancer is feasible, well tolerated, and associated with encouraging survival outcomes in a high-prevalence setting.

Within the constraints of a retrospective design, this conclusion is reasonable. The data support the practical deliverability of GC in the adjuvant setting and add to the limited GBC-specific evidence base from India.

Inisghts from this study:

Gallbladder cancer remains a significant clinical burden in Northeast India. In daily practice, we often face difficult postoperative discussions with patients who have stage III disease and substantial risk of recurrence. In this context, the question of optimal adjuvant therapy is highly relevant.

The strength of this study lies in its focus exclusively on gallbladder cancer and in its relatively mature follow-up. The high R0 resection rate and multidisciplinary approach likely contributed to outcomes. The tolerability profile is reassuring and suggests that GC can be delivered safely in appropriately selected patients.

However, the retrospective design introduces inherent limitations. Patients who received GC were likely fitter and may have had more favorable surgical outcomes. Toxicity reporting was incomplete in a subset, and lower-grade toxicities and quality-of-life parameters were not systematically captured. Therefore, the regimen’s full tolerability profile in routine practice may be broader than reported.

From a practical standpoint, the applicability in Indian practice warrants consideration. Gemcitabine and cisplatin are widely available and relatively affordable compared to newer agents. Most importantly, this is a regimen that is completely covered under Aayushman scheme and most of the state government insurances. Most tertiary centres are experienced with this combination in the metastatic setting. However, the need for intravenous administration and repeated hospital visits may be challenging for patients traveling from remote areas, particularly in Northeast India where geographic access remains a concern.

When comparing to current standards, capecitabine remains a commonly used adjuvant option based on randomized data across biliary tract cancers. Whether GC provides superior benefit in gallbladder cancer specifically remains uncertain. In our setting, treatment decisions often depend on stage, nodal status, margin status, and patient fitness. While we may use Capecitabine in patients with comorbidities, borderline Performance status and frail patients, GC may be considered in selected high-risk patients, particularly those with node-positive or stage III disease, provided performance status and logistics permit.

In summary, this study contributes meaningful Indian data on adjuvant GC in resected stage II–III gallbladder cancer. While not definitive, it supports the feasibility and potential benefit of systemic doublet chemotherapy in a disease that disproportionately affects our region. For clinicians working in gallbladder cancer hotspots, such data help inform balanced, individualized decision-making rather than reliance solely on extrapolated international evidence.