Diagnostic performance of biomarkers for bladder cancer suitable for primary care: a systematic review

Start Date May 2021

Code C16-C

Status Ongoing

Project Lead
Senior Lead
Dr Evie Papavasiliou, Dr Natalia Calanzani, Dr Hannah Harrison, Dr Claudia Snudden, Prof Grant D Stewart (all Cambridge), Dr Erica di Martino (Leeds), Prof Matthew Thompson (Washington), Ms Jennifer Bovaird (PPI)    


Bladder cancer is the 11th most common cancer in the United Kingdom. Early-stage diagnosis is associated with better survival rates. Given that the majority of bladder cancers are diagnosed following a referral (urgent or non-urgent) from a general practitioner in the UK, timely referral of suspected cases is paramount. However, diagnosis also poses challenges, as a significant proportion of bladder cancer patients do not present with visible haematuria, which is the only alarm symptom that is easily recognisable and detectable by patients and clinicians.

Although a screening program (or programs) for individuals with a high risk of developing bladder cancer could increase early-stage detection and potentially reduce mortality, these are still in early development. Furthermore, evidence suggests that there is scope to improve timely diagnosis and reduce missed diagnostic opportunities in symptomatic patients who are subsequently diagnosed with bladder cancer.

Novel urinary biomarkers have been developed in the recent years to aid the diagnosis of urinary tract cancer, in particular, bladder cancer. These have largely been developed and tested in patients who have been referred for further investigation for suspected urological cancer, but evidence on their diagnostic performance for both detecting and ruling out urinary tract cancer especially in the general population, is limited.

Against this background, we set out to systematically review the evidence of all biomarkers (individual and in panels/combinations) in the literature which have been evaluated for the diagnosis of bladder cancer. This review will be an update of previous similar reviews of specific biomarkers as well as those examining a wider range of urinary biomarkers.

Aims & objectives

We aim to update the evidence on the diagnostic performance of existing biomarkers for bladder cancer (urinary and others) across different population groups. To address our review question, we will:


Comprehensive literature searches were conducted in MEDLINE and EMBASE from 1st January 2000 to June 2021 using the OVID interface. The search strategy included free-text terms and database specific subject headings – MESH terms for MEDLINE and Emtree terms for EMBASE – relating to each of the following areas: “bladder cancer”, “biomarker”, “diagnosis/detection”, “accuracy/performance”. Hand-searching of reference lists of included studies will also be performed.

The study selection process will comprise the following stages:

Outputs & impact

Biomarkers that can be used to triage patients in primary care (for either monitoring or referring to specialist examinations) can be transformational. They can be particularly important for bladder cancer as there are no available screening programmes. Furthermore, the key predictive symptom (haematuria) is not always visible and not specific to bladder cancer. There is also evidence indicating missed opportunities for early diagnosis of bladder cancer after symptomatic presentation in primary care. This review can identify much needed evidence on which existing biomarkers have the potential to be used in primary care to facilitate assessment and GP decision-making.


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