Table 3.
Important Diagnostic Considerations in MIBC and Upper-Tract UC Clinical Trial Design
| Diagnostic Modality | Workshop Discussion Points | Comments |
|---|---|---|
| Urine test use | • Clinical trials should specify whether urine tests are used for postoperative surveillance and, if so, the specific test and testing interval required. • The 2017 AUA/ASCO/ASTRO/SUO guideline recommends regular voided urine cytologic examination for chemoradiotherapy (grade C), urethral wash cytologic examination for high-risk patients with a retained urethra (expert opinion), and to consider using urine cytologic examination after radial cystectomy for upper-tract cancer detection (expert opinion).30 |
• The level of evidence supporting urine-based screening after radical cystectomy is low.31 Similarly, after chemoradiotherapy, urine test-based tests can be unreliable owing to changes in the cytologic characteristics of radiation-treated urothelium. • The implications of a false positive urine test result can be high, as it usually results in more imaging and often more surgery (eg, ureteroscopy, urethrectomy).32 |
| Augmented endoscopy | • Standard-of-care guidelines for endoscopic surveillance should be followed and defined at the start of the trial. | • Two augmented endoscopy methods appear to have the best evidence of efficacy: (1) hexaminolevulinate (blue-light endoscopy),33,34 and (2) narrow-band imaging.35,36 • Clinical trials should standardize or account for how endoscopy is performed since differences in bladder recurrence and progression rates could be potentially attributable to imbalances in the method of surveillance rather than the intervention being tested. |
| Random bladder biopsies | • Clinical trials should specify whether random bladder biopsies should be obtained or not obtained to rule out occult carcinoma in situ. • It is unclear whether random bladder biopsies should be done for all patients with intact bladders. |
• Most low-grade bladder tumors will have normal urine cytologic characteristics but will be visible as a papillary tumor at cystoscopy. • Most high-grade bladder tumors, however, will have positive cytologic characteristics defined as high-grade malignant cells and will be visible as a flat red patch, a papillary tumor, or a nodular/sessile tumor at endoscopy. • Carcinoma in situ may not be visible with standard white light cystoscopy in up to 50% of patients, providing a rationale for mapping biopsies of normal-appearing bladder mucosa. This is especially important for patients with unexplained positive cytologic test results. • It is not clear that the biopsy of normal-appearing bladder urothelium is of any benefit if results of urine cytologic and cystoscopic examination are normal.37–41 |
Abbreviations: ASCO, American Society of Clinical Oncology; ASTRO, American MIBC, muscle-invasive bladder cancer; SUO, Society of Urologic Oncology; Society for Radiation Oncology; AUA, American Urological Association; UC, urothelial carcinoma.