Table 2 Real-world examples, applying the CanTest Framework

Cancer Antigen (CA)125 is a serum biomarker for epithelial ovarian cancer. It is utilized in strategies to distinguish benign from malignant pelvic masses pre-surgery and in the triage of women in primary care. It has been evaluated as part of screening strategies but is not currently used in that setting.

A non-endoscopic ‘sponge on a string’ test, used for the diagnosis of oesophageal squamous carcinomas in high-risk areas, was adapted for Barratt’s Oesophagus (BO) by combining it with immunocytology

A blood test to detect 8 common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA

Highly selected

single

Reference standard

Performance

Multiple studies e.g. Bast et al. 1983^a: assay developed and threshold set (> 35 U/ml); 1% of healthy patients and 82% of patients with ovarian carcinomas have levels > 35 U/ml.

Mongia et al. 2006^b: Comparison of 6 CA125 assays; acceptable performance and comparability.

Lao-Sirieix et al. 2009^j: Trefoil factor 3 (TFF3) expressed to high levels in BO compared to normal oesophagus or gastric mucosa; sensitivity 78%, specificity 94%

Cohen et al. 2018ⁿ:

For non-metastatic cancers: sensitivity 69–98% for 5 cancer types; specificity > 99%

Multiple studies e.g. Jacobs et al. 1989^c: Pooled sensitivity for ovarian cancer 85%.

N/A

N/A

Highly selecte

Single

Reference

performance

d

Multiple studies e.g. Maggino et al. 1994^d: Sensitivity 78.3%, specificity 82% for ovarian cancer in patients with a pelvic mass.

Ross-Innes et al, 2015^k: Sensitivity 79.9%, specificity 92.4% for BO in patients referred with dyspepsia and reflux symptoms.

N/A

Multiple studies e.g. Medeiros et al. 2009^e: systematic review, Area Under the Curve of 0.9 for distinguishing malignant/borderline and benign tumours.

N/A

N/A

Selected/Real-world

Single/combinations

Reference/ usual care

Medical decision making

N/A

Kadri et al, 2010^l. Accuracy for BO in primary care: sensitivity 90% & specificity 93.5% for clinically relevant segments of 2 cm or more compared with gastroscopy.

N/A

N/A

Kadri et al, 2010^l. Acceptable for patients, and no adverse events.

N/A

Moss et al. 2013^f: Explored GP views on CA125 use in Primary care.

N/A

Gilbert et al. 2012^g: Pilot study of symptom triggered ‘screening’ strategy incorporating CA125 and ultrasound. Study arm patients had more frequently resectable tumours than the control arm (usual care). Definitive results awaited.

N/A

N/A

Real-world

Single/combinations

Usual care

MDM/harms

NICE 2011^h: cost effectiveness comparison of different triaging strategies incorporating CA125.

Offman et al, 2018^m: BEST3 randomised trial underway comparing the Cytosponge-TFF3 test with usual care to facilitate diagnosis of oesophageal pre-cancer in primary care patients with chronic acid reflux.

N/A

Goff et al. 2012ⁱ: Small study; symptom based testing in primary care resulted in minimal additional unnecessary procedures.

N/A

N/A

N/A

N/A

N/A

Real-world

Pop health & costs

N/A

N/A

N/A

N/A

N/A

N/A