This study demonstrates the high bladder cancer detection rate of CEUS, which had a very high sensitivity for the presence of bladder cancer per patient (90.9%). Tumoural neovascularisation can be evaluated using imaging modalities after the administration of contrast agents and bladder cancer is a hypervascular tumour that shows strong enhancement in the arterial phase, followed by a plateau of enhancement and a slow washout when evaluated with imaging modalities after the administration of contrast agents [14,17
]. Despite conventional ultrasound currently being the preferred non-invasive imaging technique for the screening of bladder cancers, its accuracy depends on several factors, including distension of the bladder, tumour size, morphology and location of the lesions [2
]. The main limitation of ultrasound, which was found to be a factor in the present study, is its low sensitivity in detecting lesions smaller than 1 cm [3
]. CEUS sensitivity for the number of detected bladder cancers was 65.5%, which may be explained by the high number of tumours ≤5 mm detected by cystoscopy (n
= 25). These very small tumours are usually flat and do not produce focal bladder wall thickening or abnormal enhancement owing to the absence of considerable neovascularisation, as has been hypothesised in studies using other imaging techniques [20
]. Our results are slightly worse than those obtained using CT or MRI with contrast agents [18,21
], or using multidetector CT (MDCT) urography [24
]. In the study by Kim et al [18
], using MDCT, the detection rate was 97% for all bladder cancers and 85% for bladder cancers smaller than 1 cm. However, all cancers detected in that study were invasive and only 13 out of 77 were smaller than 1 cm. In a more recent study using dynamic contrast-enhanced MDCT with multiplanar reconstructions, Jinzaki et al [22
] obtained an overall sensitivity of 90% and a sensitivity of 25% for bladder lesions 5 mm or smaller when using 5-mm axial sections as the reconstruction protocol or a sensitivity of 58% using 2.5-mm axial sections with a 1.25-mm overlap. With the use of MDCT urography, Turney et al [25
] and Sadow et al [26
] found a sensitivity of 93% and 79%, respectively in detecting bladder cancer but with a high number of equivocal (20% in the study by Turney) or misinterpreted (9% in the study by Sadow) studies.
With respect to location, we missed lesions from all segments but especially on the bladder floor and fundus. In the literature, there is no agreement regarding the most difficult places to detect bladder cancers using ultrasound. Those suggested include the anterior and posterior bladder wall [3
], the bladder neck or dome areas [20
] and the anterior wall [27
]. Detection of small tumours in the bladder floor can be a challenge in male patients with benign prostatic hyperplasia (BPH) [28
]. A large prostatic central gland protruding into the bladder lumen can be difficult to differentiate from bladder cancer. In our experience, bladder tumours enhance faster than the normal prostate gland owing to its arterial neovascularisation, but intense enhancement in areas of benign prostatic hyperplasia can be found using CEUS, mimicking tumoural enhancement [31
]. Another difficulty when evaluating patients with BPH is the possibility of bladder wall thickening with trabeculations, which in some cases may mimic urothelial cancers.
When compared with baseline ultrasound, in our study CEUS did not significantly improve the sensitivity in detecting more bladder cancers, detecting only three lesions more. However, CEUS significantly increased the accuracy of baseline ultrasound according to the presence or absence of bladder tumour, especially in uncertain baseline ultrasound cases. In clinical practice, several reasons such as the presence of bladder clots, surgical wall changes, bladder wall trabeculation or the impossibility to retain urine to totally distend the bladder may hamper good visualisation of the bladder using baseline ultrasound. In our experience, CEUS is helpful in differentiating these entities from bladder cancer, detecting bladder cancer neovascularisation enhancement [14
One limitation of this study is the recruitment of patients with high suspicion of bladder cancer obtained by flexible cystoscopy who were to undergo rigid cystoscopy and the absence of inclusion of healthy patients. However, radiologists who carried out the ultrasound and CEUS studies and who reviewed the ultrasound and CEUS images did not know the cystoscopic and histological results. With the introduction of this recruitment bias, the real value of CEUS as a screening for bladder cancer in patients with haematuria cannot be provided.
In conclusion, CEUS improves the bladder cancer detection rate of ultrasound, especially in ultrasound studies that are non-conclusive.