Microscopic haematuria and other microscopic abnormalities of urine are common findings on routine urinalysis performed in the community for various clinical indications. Most current guidelines suggest relatively resource intensive secondary investigations. Our study suggests that in majority of the patients a more truncated approach may be safe and efficacious.
Our retrospective review has revealed a low rate of malignancy in patients with microscopic haematuria (2%) in line with recent publications (Jung et al. 2010; Samson et al. 2018). In their retrospective review of patients undergoing standard diagnostic workup for asymptomatic microscopic haematuria, Gonzalez et al. identified 25 patients with bladder cancer (1.2%) (Gonzalez et al. 2019). The final pathology for all patients was non-muscle invasive bladder cancer. Samson et al. in 2017 conducted a retrospective analysis on 1049 patients with asymptomatic haematuria and this revealed 6 patients all with non-muscle invasive bladder cancer (0.57%) (Samson et al. 2018). Similarly the final pathology report for all the patients diagnosed with malignancy in our cohort was non-muscle invasive bladder cancer. A recent prospective study of 3556 patients by Tan et al. has revealed similar rates of diagnosis of genitourinary malignancy in patients with microscopic haematuria (3.1%) (Tan et al. 2018a). Interestingly this particular cohort has a significant number of patients diagnosed with muscle invasive bladder cancer (31.3%) amongst patients with microscopic haematuria, and of these patients, one was below the age of 60. The stated studies above have not reported whether cystoscopy led to additional findings beyond what pre-cystoscopy imaging had identified. This is the main point of difference in our study.
One unique feature of our study is that secondary to our outpatient triage protocols, all patients will undergo radiological imaging prior to clinic assessment and cystoscopy. Our retrospective analysis has revealed that coupled with renal tract imaging, cystoscopy provided little additional diagnostic utility with only 1 malignancy (0.2%) detected by flexible cystoscopy alone. Although easy to perform, cystoscopy is invasive, uncomfortable, expensive and consumes significant amount of clinical resources. Issues such as lethargy, dysuria, haematuria and suprapubic pain were common post-cystoscopy (Erkal 2007). Complications such as UTIs can also be significant. The previous literature has published rates of UTI between 2 and 7.5% (Herr 2015; Clark and Higgs 1990). This is further highlighted in the AUA best practice guidelines, in which patients with risk factors for a UTI are recommended to have prophylaxis antibiotics (Wolf et al. 2008). Another important consideration regarding cystoscopy is that it is costly. Halpern et al. in 2017 illustrated this in their decision analytic model to determine the most cost-effective method in investigation asymptomatic haematuria (Halpern et al. 2017). Based on the Medicare Physician Fee Schedule, the cost of cystoscopy alone from the payer’s perspective ranged from $166-$285. The incremental cost of cancer detected for cystoscopy alone was $10 287 (Halpern et al. 2017).
Apart from deciding who needs to be investigated, another issue that faces many urologist is how best to image the renal tract. The recent AUA guidelines suggested the use of CT Urogram as a first line imaging of choice for microscopic haematuria (Davis et al. 2012). Patients who have absolute or relative contraindication to a CT Urogram can be imaged with either a magnetic resonance Urogram or an Ultrasound, in descending order of preference (Davis et al. 2012). In our cohort, 10 out of the 12 patients with malignancy had bladder mass picked up on pre-cystoscopy ultrasound. Only one patient with a normal ultrasound was subsequently diagnosed with pTa bladder malignancy. CT only detected one additional case of malignancy in our cohort. In 2011, Cauberg et al. conducted a prospective review on types of renal tract imaging and found that ultrasound is sufficient to exclude significant upper tract disease in patients with microscopic haematuria (Cauberg et al. 2011). Lisanti et al. has also previously shown that CT Urogram provided no additional benefit over non-enhanced CT in evaluating the upper renal tract in patients with microscopic haematuria (Lisanti et al. 2014). Additionally, previous studies have highlighted the implications of non-urologic CT findings such as added cost and morbidity from invasive tests and treatments (Morgan et al. 2015; Lai et al. 2016).
More recently, the usage of novel urinary biomarkers has been reported to have a high sensitivity and negative predictive value (Tan et al. 2018b). However, to date, these markers are not considered to be a first line investigation tool and are not to be used without cystoscopy (Tan et al. 2018b). Apart from that, the emerging use of CxBladder may offer an alternative in investigating microscopic haematuria. A recent study has revealed a high negative predictive value of 97.4% and 35% of patients avoided cystoscopy (Konety et al. 2019).
Whilst there is ongoing debate regarding the gold standard workup, our results suggests that not all patients with persistent microscopic abnormalities of urinalysis necessarily need to undergo cystoscopy. In our cohort of 552 patients who completed workup, 3.4% of those with microscopic haematuria and 1% of those with other urinalysis abnormalities were diagnosed with malignancy. This is similar to the DETECT I reports with a rate of malignancy of 3.1% amongst patients with microscopic haematuria (Tan et al. 2018a). Although the variables that we analysed (age, smoking status, gender) did not reach any statistically significant results, this may be explained due to our small patient number. This is supported by the fact that multiple reviews has previously shown that older age, male gender and positive smoking status are significantly associated with the risk of underlying malignancy (Davis et al. 2012; Samson et al. 2018; Gonzalez et al. 2019). Based on the literature, a cystoscopy should strongly be considered in elderly male with a history of smoking. Younger patients may not need to undergo a cystoscopy; however, decision should be made after reviewing the presence of other symptoms as well as risk factors. For instance, there might be a benefit in performing a cystoscopy in low risk populations to assist the diagnosis of non-malignant pathology such as benign prostatic enlargement or urethral stricture (Gonzalez et al. 2019). Ultimately, the decision of who should undergo a cystoscopy should be individualised and this needs to be discussed between the treating physician and patient. Our study does not mean that we do not advocate for investigation of urinalysis abnormalities; however, we suggest that with improved contemporary imaging there may be less need to for routine cystoscopy as a diagnostic tool. Furthermore, by only utilising cystoscopy on selected patients and cases, this will render it to be more cost-effective.
Our analysis has several limitations that should be mentioned. Our data collection was limited to a single tertiary referral centre; hence, our results may not be generalisable to the wider population. Additionally, our review was a cross-sectional study; no long-term follow-up was performed. This is crucial as patients with microscopic haematuria with initial negative evaluation still have a 1–3% of developing cancer over time (Wieder 2010).
