Bladder cancer diagnosis during haematuria investigation – implications for practice guidelines

Abstract

Bladder cancer is the eighth most common cancer in Australia, with an estimated 2880 new diagnoses and 1165 deaths from the disease in 2016 [1]. Patients with bladder cancer typically present with haematuria, although only a small proportion of patients with haematuria have an underlying bladder cancer, with most due to benign or unknown causes. However, a systematic review of the literature that we have recently undertaken has identified that patients with haematuria are inconsistently evaluated [2]. This finding was further corroborated in our study showing that many patients presenting to our institution with haematuria experience delays or gaps in their evaluations [3].A paucity of contemporary, evidence-based Australian guidelines, along with a lack of consensus among published guidelines worldwide may be important contributory factors. Thus, the AUA suggests cystoscopic evaluation for all patients with visible haematuria and those aged ≥35 years with nonvisible haematuria [4]. In contrast, the UK National Institute for Health and Care Excellence (NICE) recommendations, promulgated by the BAUS, suggest urgent urological referral for patients aged ≥45 years with unexplained visible haematuria, and those aged ≥60 years with non-visible haematuria and either dysuria or elevated white cell count [5]. This latter recommendation reflects a more conservative approach to investigation of haematuria, particularly in younger patients and those with non-visible haematuria, given that their risk of bladder cancer is relatively low.In the context of varying worldwide guidelines and with a view to informing an appropriate approach to haematuria in Australia, we undertook a retrospective cohort study to identify predictors of bladder cancer diagnosis after evaluation of haematuria. We assessed patients undergoing cystoscopic procedures at our institution for investigation of visible haematuria over a 12-month period in 2015. Those with a known history of bladder, renal or other urinary tract cancer were excluded from our study. Patient data including age at cystoscopy, gender, socioeconomic status (SES) from postcode of residence, and smoking status were collected. Histology results were obtained for those who underwent tumour resection or biopsy. Multivariable logistic regression models with the above co-variates were used to predict the probability of a cancer diagnosis on histology. Age was entered as a continuous variable, then as a restricted cubic spline with interior knots at the tertiles for the prediction model.Overall, our present sample comprised 231 patients, of whom 39 (17%) were found to have histologically confirmed bladder cancer, with the youngest of these aged 54.7 years. Only age at cystoscopy was found to be an independent predictor of bladder cancer diagnosis on multivariable analysis. The predicted probabilities of cancer after adjustment for gender, smoking status and SES were: <1% at age <45 years, 13% (95% CI 4.5-22%) at age 65 years, and 26% (95% CI 16-36%) at age 80 years (Fig. 1).Patients prese...

Urinary TERT promoter mutations as non-invasive biomarkers for the comprehensive detection of urothelial cancer

“…The UroMuTERT (cfDNA or cellDNA) PPV of 87·6% and NPV of 94·4% extrapolated to at high-risk subjects of developing UC (30% estimated risk [12], see materials and methods) reached 88·4% and 97·4% respectively when combined with cytology and assuming 100% specificity for cytology. Because the risk estimate of 30% may be inflated by the study design, we also considered lower hypothetical risks of 20% and 5% for UC in patients with haematuria [20] and micro-haematuria [21], and obtained PPVs of 81·4% and 48·0% and NPVs of 98·4% and 99·7% respectively, which still demonstrates the superior diagnostic value of combined urinary UroMuTERT and cytology. However, the predictive values of the biomarkers must be accurately assessed in large well-defined high-risk group populations before urological societies may reconsider recommendations for UC screening in such groups [23].…”