ADXBLADDER (Arquer Diagnostics) is a urine test for detecting bladder cancer in people with symptoms associated with malignancy, including blood in the urine or lower urinary tract symptoms. It is also indicated for detecting bladder cancer recurrence in the urogenital tract during follow-up after surgical treatment of non-muscle-invasive bladder cancer (such as transurethral resection of a bladder tumour [TURBT]). It is unsuitable for use after radical cystectomy. It is intended to be used with cystoscopy. ADXBLADDER is a urine-based lab test, which uses enzyme-linked immunosorbent assay (ELISA) technology to detect minichromosome maintenance complex component 5 (MCM5) protein in full-void urine. MCM5 is expressed by proliferating cells and can act as a biomarker for cancer. Because MCM5-positive cells are shed from tumours on the inner surface of the bladder, the presence of MCM5 in the urine can suggest that cancer is present. The volume of a urine sample can range from 10 ml to 200 ml, and the patient is advised to give a sample at least 2 hours after their last urination.
ADXBLADDER is an in vitro diagnostic test based on a novel biomarker for bladder cancer, MCM5. Compared with urinary cytology, which is a subjective test because it relies on microscopic evaluation, ADXBLADDER acts as an objective method of detecting the presence of bladder cancer. The company claims that the test will be able to detect more cases of bladder cancer compared with cytology. It may also help indicate the presence of upper urinary tract transitional cell carcinoma, which is often difficult to diagnose. Also, because MCM5 is not expressed by red blood cells, inflammatory cells or bacteria, the test result is unlikely to be affected by their presence. This means the test can be done in people with urinary tract infections and haematuria.
Diagnosing bladder cancer is mainly based on cystoscopic investigation of the bladder, biopsy and cytology. NICE's guideline on the bladder cancer does not recommend substituting cystoscopy for urinary biomarkers to investigate suspected bladder cancer or for follow‑up after treatment for bladder cancer, except in the context of a clinical research study. White-light-guided TURBT is recommended for people with suspected bladder cancer if abnormalities are found during cystoscopy. CT or MRI staging should be considered before TURBT if muscle‑invasive bladder cancer is suspected at cystoscopy. According to the guideline, TURBT should be done or supervised by a urologist experienced in the procedure. It should be done with either:
narrow band imaging
a urinary biomarker test (such as UroVysion using fluorescence in-situ hybridisation, ImmunoCyt or a nuclear matrix protein 22 test).
The guideline also states that random biopsies of normal-looking urothelium during TURBT should not be taken unless there is a specific clinical indication (for example, investigation of positive cytology not otherwise explained). Also, the size and number of tumours found during TURBT should be recorded.
Recommendations for the diagnosis and management of non-muscle-invasive bladder cancer are also made by the European Association of Urology (EAU) and are largely in agreement with those made by NICE.
NICE's guideline on bladder cancer describes patient follow-up after treatment for bladder cancer. Periodic cystoscopy should be offered to patients after treatment for non-muscle-invasive bladder cancer. It should also be offered to patients after radical radiotherapy for the treatment of muscle-invasive bladder cancer. The recommended frequency of cystoscopic follow-up varies and should be adjusted according to the severity and risk of bladder cancer (see the guideline for further details).
Urinary biomarkers and cytology can be offered with cystoscopy, except for the follow-up of patients with low-risk bladder cancer, when their use is not recommended. Patients who have had treatment for muscle-invasive bladder cancer (radical cystectomy or radical radiotherapy) should also be offered annual upper-tract imaging and CT of the abdomen, pelvis and chest 6, 12 and 24 months after treatment to monitor for local and distant recurrence. The guideline recommends urgently referring any patient to urological services if they have haematuria or other urinary symptoms and a history of non‑muscle‑invasive bladder cancer.
The intended use for ADXBLADDER would be as a diagnostic test in people presenting with haematuria or lower urinary tract symptoms with a suspicion of malignancy. It is also intended to be used to monitor for recurrence within the urogenital tract during the follow-up of patients after surgical treatment of non-muscle-invasive bladder cancer (for example, TURBT). It is unsuitable for use after radical cystectomy. The test is intended to be used in secondary care with cystoscopy, but instead of urine cytology or other urine biomarker tests that are currently used with cystoscopy for the detection of bladder cancer and recurrence within the urogenital tract. Urine samples would be collected by nurses in a hospital clinic and processed and analysed in a laboratory. The test results would then be sent to the patients' urologist.
The cost of ADXBLADDER is £52 per test (excluding VAT). This does not include the costs of consumables or healthcare professionals' time. The company estimates the cost of consumables (consisting of 1 urine collection pot, 1 centrifuge tube, 1 Eppendorf tube and pipette tips) to be £0.37 per person.
Per test costs (excluding VAT), including the cost of consumables and the healthcare professionals' time, are based on 2018/19 hospital resource group (HRG) tariffs and 2017/18 national schedule of reference costs, and are as follows:
Cystoscopy: £244 (HRG code LB72A, Diagnostic Flexible Cystoscopy, 19 years and over).
Cytology: £12 (currency code DAPS01, cytology).
The technology is being introduced into the NHS but is not yet widely used. If adopted, ADXBLADDER has the potential to be resource releasing if its use results in earlier diagnoses and subsequent treatment by more accurately detecting cases of bladder cancer. However, false-positive results could have cost and resource consequences because they could lead to further testing. Using the test to monitor patients during follow-up may lead to an initial increase in resource use in this setting. There is minimal to no training, and no changes to facilities or infrastructure are needed to adopt the technology because urinalysis and ELISA technology are already used routinely.