Introduction

Colon capsule endoscopy (CCE) or panenteric capsule endoscopy (PCE) offers a promising, non-invasive diagnostic approach for patients with iron deficiency anaemia (IDA). However, high rates of conversion to conventional colonoscopy (CCC) following capsule procedures reduce cost-effectiveness and patient satisfaction. Optimising the faecal immunochemical test (FIT) threshold may improve patient stratification and reduce unnecessary conversions in future applications within the IDA diagnostic pathway.

Aims & Methods

This study aimed to evaluate the accuracy of faecal immunochemical testing (FIT) in predicting colorectal cancer (CRC) and polyp burden in patients with iron deficiency anaemia (IDA), and to extrapolate these findings to assess FIT’s utility in predicting the likelihood of conversion from CCE to conventional colonoscopy (CCC) based on underlying pathology in IDA.
The CLEAR IDA study was a multicentre, retrospective observational study conducted across four UK hospitals. Data were collected over a six-month study period and included patients referred via the two-week-wait (2WW) cancer pathway for iron deficiency, with or without anaemia, over a 12-month timeframe. Colonoscopy findings were analysed and extrapolated using NHS England’s CCE-to-colonoscopy referral criteria to assess the predictive value of FIT for colorectal cancer (CRC), polyp burden, and CCC using ROC curve analysis. The optimal FIT threshold was identified through three complementary approaches: threshold-based analysis, decision curve analysis, and cost-benefit modelling.

Results

A total of 1,531 patients were analysed; only 1.6% underwent small bowel capsule endoscopy. The diagnostic accuracy (AUC) of FIT for predicting CRC, polypoidal lesions, and CCC was 0.78, 0.58, and 0.69, respectively. Threshold-based analysis identified FIT = 15 µg/g as the lowest level at which CCC rates significantly increased (p = 0.02; OR = 1.87; 95% CI: 1.07–3.14). Decision curve analysis showed maximum net benefit at FIT = 17.6 µg/g, while cost-benefit modelling identified 9 µg/g as the most cost-effective. An optimal cost-effective FIT threshold range was identified between 10 and 17.6 µg/g. Threshold selection should be tailored to local service capacity and resource availability.

Conclusion

Significant pathologies in the IDA pathway were uncommon. A FIT threshold range between 10–17 µg/g may enhance cost-effectiveness and guide appropriate PCE use in IDA.

References

1) Snook J, Bhala N, Beales ILP, et al. British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults. Gut. 2021 Nov;70(11):2030-2051.
2) (NICE) NIFHACE. PillCam COLON 2 for investigation of the colon through direct visualisation: NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE; August 2024 [cited 2025 23/03/2025]; Diagnostics Assessment Programme]. Available from: https://www.nice.org.uk/guidance/gid-dg10083/documents/final-scope-2
3) Turvill J, Haritakis M, Pygall S, et al. Multicentre Study of 10,369 Symptomatic Patients Comparing the Diagnostic Accuracy of Colon Capsule Endoscopy, Colonoscopy and CT Colonography. Aliment Pharmacol Ther. 2025 Feb 26;0:1–13.
4) Cilona A, Zullo A, Hassan C, et al. Is faecal-immunochemical test useful in patients with iron deficiency anaemia and without overt bleeding? Dig Liver Dis. 2011 Dec;43(12):1022-4.
5) Turvill JL, Turnock D, Cottingham D, et al. The Fast Track FIT study: diagnostic accuracy of faecal immunochemical test for haemoglobin in patients with suspected colorectal cancer. Br J Gen Pract. 2021 Aug;71(709):e643-e651.

Introduction

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with limited therapeutic options available for unresectable cases. In recent years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape. Among them, the combination of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4), collectively referred to as Dur/Tre, has demonstrated significant survival benefits in patients with advanced HCC. However, robust prognostic biomarkers specific to patients receiving Dur/Tre therapy have yet to be established. The neutrophil-to-lymphocyte ratio (NLR), a systemic marker of inflammation, has been correlated with prognosis in various malignancies, including HCC [1, 2].

Aims & Methods

This study aimed to assess the prognostic significance of baseline NLR in patients with unresectable HCC treated with Dur/Tre. This multicenter retrospective cohort study included 182 patients with unresectable HCC who received Dur/Tre therapy between May 2022 and June 2024. Eligibility criteria included the availability of baseline NLR data and complete clinical records. The treatment regimen comprised a single 300 mg dose of tremelimumab on day 1, followed by 1500 mg of durvalumab administered every four weeks. Primary endpoints were progression-free survival (PFS) and overall survival (OS), assessed using the Kaplan-Meier method and Cox proportional hazards modeling. Baseline NLR values were calculated, and the optimal cutoff for OS prediction was determined using hazard ratio (HR) spline curve analysis.

Results

The median age of patients was 74 years, and 82.9% were male. The median baseline NLR was 3.13. Dur/Tre was administered as first-line therapy in 29.7% of patients and as second-line or later therapy in 70.3%. The median PFS was 3.5 months (95% confidence interval [CI]: 2.7–4.4 months), while the median OS was not reached (95% CI: 12.1 months–not reached). Multivariate analysis identified administration of Dur/Tre after second-line treatment as an independent predictor of shorter PFS (HR: 1.819; p = 0.003). Notably, an NLR ≥2.56 independently predicted poorer OS (HR: 1.919; p = 0.039). Median OS was not reached in the low-NLR group (<2.56), whereas it was 12.1 months in the high- NLR group (≥2.56) (p = 0.016). A Sankey diagram revealed that patients with higher NLR were more likely to receive best supportive care (BSC) rather than subsequent anticancer therapies post-Dur/Tre (p = 0.046). Spline curve analysis identified an optimal NLR threshold range of 2.3–3.0 for OS prediction.

Conclusion

This large, real-world, multicenter study demonstrated that baseline NLR serves as a significant and independent prognostic biomarker for overall survival in patients with unresectable HCC undergoing Dur/Tre therapy. Higher baseline NLR values (≥2.56) were associated with reduced survival and a lower likelihood of receiving subsequent anticancer treatment, whereas patients with lower NLR values were more likely to continue active therapeutic interventions. These findings suggest that NLR may function not only as a prognostic indicator but also as a practical tool for therapeutic decision-making and patient stratification in clinical settings. Further prospective studies with extended follow-up are warranted to validate these findings and refine NLR-based stratification strategies to optimize immunotherapy outcomes in HCC.

References

1. Tada T, Kumada T, Hiraoka A, et al. Neutrophil-to-lymphocyte ratio is associated with survival in patients with unresectable hepatocellular carcinoma treated with Lenvatinib. Liver Int. 2020; 40: 968-976.
2. Tada T, Kumada T, Hiraoka A, et al. Neutrophil-lymphocyte ratio predicts early outcomes in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab: a multicenter analysis. Eur J Gastroenterol Hepatol. 2022; 34: 698-706.

Disclosure

Toshifumi Tada: lecture fees from AbbVie, AstraZeneca, Eisai, and Chugai
Atsushi Hiraoka: lecture fees from Eisai, Bayer, Eli Lilly, and Otsuka
Hidenori Toyoda: lecture fees from AbbVie, Eisai, Gilead, Terumo, and Bayer