When diagnosing bladder cancer, there are several tests available. These include urine cytology, flexible cystoscopy, rigid cystoscopy, ureteroscopy with or without a biopsy, retrograde ureteropyelography, intravenous urography, ultrasound, CT urography, and MR urography. Due to constraints of time, Dr. Cowan discussed only on the role of ultrasound, Ct urography and MR Urography in diagnosis.
The optimal patient “journey” should be short and accurate and ideally, it should include risk stratification, one diagnostic test and then immediate treatment. There are several diagnostic strategies for bladder cancer. One approach includes performing an ultrasound and then a CT scan. Another approach is going straight to a CT scan. Data has shown us that the specificities of ultrasound and CT for diagnosing bladder cancer are similar, but CT has a higher sensitivity. The high specificity of the CTU enables us to directly refer patients for tumor resection in the operating theater, without performing flexible cystoscopy.
Dr. Cowan next discussed the different phases of the CT urography scans. In total, this test has seven distinct phases. These include the immediate nonenhanced phase, the arterial phase occurring 15-25 seconds after intravenous injection of contrast dye, the urothelial phase occurring 50 seconds after injection, portal venous stage – 70 seconds, nephrogenic phase – 100 seconds, excretory phase 300-900 seconds, and finally, the delayed excretory phase, occurring after more than 900 seconds. Without the delayed excretory phase, the entire test should not take more than 5-10 minutes.
In a study assessing the best attainable role of CT urography, two triage options were analyzed.1 In the first option, CT urography was first performed, if it were positive, patients would be referred for rigid cystoscopy in the operating theater. If the CT urography was equivocal or negative for a bladder tumor, the patient was referred for flexible cystoscopy. In the second option, if The CT was positive, the patient underwent a rigid cystoscopy in the operating theater.
If it was equivocal, the patient underwent flexible cystoscopy, and if it was negative, the patient was discharged, without any further tests. The study demonstrated that the first option was deemed to be the most accurate for diagnosis.
The next topic discussed was the role imaging has in the local staging of the bladder cancer. The most important information we want to receive from imaging is to differentiate whether the bladder tumor is worse than T1 high-grade disease or not. Recently, MRI of the bladder for local staging was introduced in an attempt to surpass the limited diagnosing abilities of the CT. The use of MRI in the staging of bladder tumors introduced the Vesical Imaging-Reporting And Data System (VI-RADS).2 The VIRADS staging system is depicted in figure 1. This is a very similar staging classification to the one used in MRI for prostate cancer, which is called the PIRADS system. The VIRADS has just recently been introduced, and more clinical data is needed to validate its usefulness.
Figure 1- VIRADS MRI staging system for bladder cancer:
Next, Dr. Cowan discussed the indications for upper tract imaging. In approximately 52-72% of cases, CT scans do not find any disease in the upper-tracts, and the positive predictive value is between 0.5-0.87, with a negative predictive value of 0.97-1, a sensitivity of 0.67-1, and a specificity of 0.93-0.99. The false positive rate for CT of the upper tract is quite high with various diagnoses causing the high false positive rate. The differential diagnoses include clots, debris, ureteral kink, fibroepithelial polyp, ureter injury, stone passage, stent placement, ureteritis cystica, metastases, flow artifacts, amyloid, cauliflower papilla (a normal variant), lymphoma, vascular impression, and inflammation and fibrosis.
When diagnosing the etiology of hematuria, it is important to differentiate between visible and non-visible hematuria. Age is also a factor that needs to be considered. In patients with visible hematuria, whether they are younger or older than 50, a CT urography should always be performed. Therefore, it is not the grade or stage of bladder cancer that should determine the indications for upper tract imaging, but rather the process of risk stratification of the investigation of hematuria that should drive the decision.
The role of imaging used for diagnosing positive nodes was discussed next. Nodes are the most frequent site of metastases in bladder cancer, followed by the bone, lung, and liver. The size of the lymph nodes is critical in the accuracy of the CT scan in diagnosing a metastatic lymph node. Lymph nodes over the size of 10 mm have a sensitivity of 37% and a specificity of 100%, while lymph nodes larger than 4 mm, have a sensitivity of 93% and a specificity of 58%, as can be seen in table 1. Dr. Cowan strongly believes that CT is not enough to accurately diagnose positive lymph nodes.
Table 1 – The accuracy of the CT scan for diagnosing positive retroperitoneal lymph nodes:
A nice study compared the diagnostic accuracy of CT, MRI and PET/CT.3 These results clearly show the highest sensitivity for MRI and an equal specificity for all three modalities around 0.92. All these imaging modalities are quite limited by the accuracy that they can provide in diagnosing metastatic lymph nodes. Dr. Cowan gave an example of a patient with recurrent prostate cancer, who initially underwent choline PET-CT scan, demonstrating only one positive node. He later underwent A PSMA PET -CT scan, demonstrating five positive nodes. Finally, he underwent a robotic-assisted salvage lymph node dissection removing 44 positive lymph nodes!
The last topic discussed was the diagnosis of bone metastasis using imaging tests. In a meta-analysis on the detection of bone metastasis using either standard bone scan or 18F-FDG PET-CT, the results demonstrated that sensitivity and specificity of 18F-FDG PET CT and bone scan were 0.93 and 0.96 vs. 0.71 and 0.91, respectively. The PET scan had a clear advantage over the bone scan.4 CT and standard bone scans have the lowest sensitivity and specificity in diagnosing bone metastasis, when compared to SPECT, 18F-FDG PET-CT, MRI, and 18 NaF-PET-CT. 5
Dr. Cowan concluded his talk, stating that the diagnostic accuracy of every diagnostic test should be assessed using the following parameters: diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy), cost of the test, time it takes to perform it, and patient acceptability of the test. Finally, he provided summarized answers to the three questions he raised at the beginning of his discussion:
- What are the indications for upper tract imaging? It is important to consider the overall risk stratification for investigating hematuria, not just tumor grade and stage
- Is CT enough or do we need a PET? If PET is used, it should be used as a triage or replacement test, and not as an additional test.
- How good is imaging for lymph node metastasis? At best, it is considered quite average.
Presented by: Nigel Cowan, MD, The Queen Alexandra Hospital, UK
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the Global Conference on Bladder Cancer 2018 - September 20-21, 2018 Madrid, Spain
References:
1. Blick CGT et al. BJU INT 2011
2. Panebianco V. et al. Eur Urol 2018
3. Crozier et al. World J of Urol 2018
4. Wu F et al. Biomedical Research 2017
5. O’Sullivan et al. 2015