The Absolute Effect / Oncology Evidence / Evidence Index / Gallbladder Cancer
POLCAGB
In initially unresectable locally advanced gallbladder adenocarcinoma, does adding concurrent chemoradiotherapy to neoadjuvant chemotherapy improve resection and survival outcomes?
Registry: NCT02867865 · CTRI/2016/08/007199 · One underlying study; aliases and follow-up publications consolidated · Evidence reviewed 3 November 2026.
Study design, population and eligibility
Phase III, open-label, 1:1 randomized trial; interim analysis presented at ASCO 2025.
Protocol target: 314 patients (157 per arm). ASCO 2025 interim analysis: 124 randomized (NACT n=64; NACRT n=60), with 93 OS events and median follow-up 62 months (range 6.9–94).
Fit patients with biopsy-proven locally advanced gallbladder adenocarcinoma, generally T3–T4 with predefined features such as limited liver infiltration, N1 disease, type I/II biliary obstruction, duodenal/colonic abutment without mucosal infiltration or <180° vascular involvement. Resectable upfront disease and distant metastases were excluded. The interim abstract describes a selected, initially non-R0-resectable population.
Treatment and comparator
NACT: Gemcitabine plus a platinum agent for four cycles, followed by surgical reassessment.
NACRT: 55–57 Gy with concurrent gemcitabine, followed by two additional cycles of chemotherapy and surgical reassessment.
The 2019 peer-reviewed protocol prespecified a superiority comparison of NACRT versus chemotherapy alone. The 2025 abstract does not specify the exact concurrent gemcitabine schedule or platinum selection in the abstract summary; those details are not inferred here.
Endpoints
Primary endpoint: Overall survival. Secondary endpoints: Event-free survival, R0 resection rate, acute/late toxicity, postoperative complications and quality of life.
Key efficacy and clinical outcomes
In the 124-patient interim intention-to-treat analysis, median OS was 21.8 months with NACRT versus 10.1 months with NACT (HR 0.56; 95% CI 0.37–0.84; p=0.006). Median EFS was 10.6 versus 4.89 months (HR 0.58; 95% CI 0.39–0.85; p=0.006).
R0 resection was achieved in 51.6% versus 29.7% (p=0.01). Surgical exploration occurred in 65.0% versus 45.3% (p=0.03). Five-year OS was reported as 27% (95% CI 17.7–43) versus 18% (95% CI 10–31); five-year EFS was 21% (95% CI 12–35.7) versus 12.7% (95% CI 6–24.6).
Source-reported outcome visualization
Fixed-time five-year survival estimates and R0 resection proportions reported in the ASCO 2025 interim abstract.
Different endpoints are shown as separate source-reported percentages; do not compare bar lengths across different endpoints as if they were the same outcome.
Absolute effect and NNT/NNH
The interim abstract reports a 9-percentage-point difference in five-year OS (27% versus 18%) and a 21.9-point difference in R0 resection (51.6% versus 29.7%). These are descriptive interim estimates. No definitive NNT is assigned because the study is under-accrued relative to its planned sample, the reported survival estimates have wide confidence intervals and the abstract is not a final peer-reviewed analysis. Median OS difference is not used to derive NNT.
Trial-specific toxicity, grade 3–5 harms and treatment burden
The interim abstract reports Clavien–Dindo grade ≥3 postoperative morbidity among resected patients: 28.1% (9/32) with NACRT versus 18.2% (4/22) with NACT (p=0.30). This is a selected postoperative denominator, not the randomized population.
Comparative acute grade 3–5 systemic/radiation toxicity and treatment-related mortality were not reported in the accessible ASCO abstract. The protocol prespecified toxicity and postoperative outcomes; unreported rates are not imputed. NACRT adds a multiweek radiation course and concurrent gemcitabine before surgery.
Quality of life
Quality of life was prespecified as a secondary endpoint in the protocol, but comparative QoL results were not provided in the accessible interim abstract. No QoL benefit or harm is inferred.Subgroups and applicability
The interim report does not provide adequately powered treatment-by-subgroup interaction results. Do not infer differential benefit by T stage, N1 status, biliary obstruction or vascular involvement.Maturity, limitations and critical interpretation
Interim maturity: 124 enrolled versus 314 planned; accrual was slow and the institutional ethics committee requested an interim analysis. The abstract reports 93 OS events and median follow-up 62 months.
Evidence level: The protocol is peer-reviewed (BMJ Open 2019); efficacy results are currently represented by an ASCO 2025 meeting abstract rather than a full final peer-reviewed trial publication. The study was conducted at two Indian centres, limiting generalizability. Conditional power and interim effect estimates can be optimistic. The trial has not reached its planned sample size.
Clinical interpretation: POLCAGB is an important India-led randomized study suggesting that adding chemoradiotherapy may improve resection and survival in selected locally advanced gallbladder cancer. The striking interim signal is hypothesis-strengthening, not yet a definitive practice-changing final result; confirmatory mature publication and toxicity/QoL reporting remain essential.
Primary sources, protocol and follow-up reports
- POLCAGB protocol, BMJ Open 2019 (PMID 31253621)
- POLCAGB interim phase III results, ASCO 2025 abstract 4007
- ClinicalTrials.gov NCT02867865
Numbers not reported in the accessible primary source are not imputed. Median survival differences are never converted into NNT.
The Absolute Effect · Last quality check: 3 November 2026 · Clinical currency and browser-rendered QA are subject to the status stated above.