The three optical techniques discussed above all have their strengths and weaknesses. However, they also have different goals: whereas photodynamic diagnosis and narrow-band imaging both focus on improvement of the visualization of bladder tumors, optical coherence tomography focuses on real-time pathological diagnosis. Narrow-band imaging and photodynamic diagnosis both can aid in reducing the high rate of early recurrences, because more radical resection can be performed due to better visualization of UC. In addition, in case of positive cytology and negative white light cystoscopy, photodynamic diagnosis (and perhaps also narrow-band imaging) can improve detection of CIS. Optical coherence tomography may possibly assist in differentiation between inflammation and CIS, which both can present as red lesions. It may also aid in accomplishing a more complete resection, by measuring the resection margins with optical coherence tomography and extending resection if vital tumor is still present. In addition, optical coherence tomography may provide pathological diagnosis for the patients with recurrent tumors under followup or before laser treatment.
As mentioned above, all three techniques discussed in this review may aid in accomplishing a more complete resection of bladder cancer. In theory, this consequently will result in lower residual tumor rates and also in longer recurrence-free survival, as already has been proven for photodynamic diagnosis. One can hypothesize that the effect of these techniques may render adjuvant intravesical instillations that aim at reducing recurrences redundant. This is now being evaluated in an international prospective trial randomizing patients to white light-TUR with adjuvant intravesical therapy or photodynamic diagnosis assisted TUR without adjuvant intravesical therapy (HELENA protocol, personal communications, 26-04-2010, Th.M. de Reijke).
When comparing the two visualization techniques, detection rates and false-positive rates seem to be comparable, but photodynamic diagnosis is more established with stronger supporting evidence so far. Photodynamic diagnosis has been recommended in the European guidelines for the detection of CIS.[49
] In addition, the contrast provided with this technique seems more apparent than with narrow-band imaging. However, given the practical disadvantages of photodynamic diagnosis (need for intravesical instillation of fluorescent agent and high costs), narrow-band imaging may be a valid alternative for the detection of NMIBC. Because narrow-band imaging does not rely on intravesical instillation of fluorescent agents, the technique is also well suitable for use in the outpatient clinic.
In future, one may consider combining some of these optical techniques so that the strengths of one technique can be used to overcome the limitations of the other. For example, the combination of photodynamic diagnosis and optical coherence tomography in an animal study led to increased specificity of diagnosing UC in rat bladders.[50
] These results were also shown in human studies that combined photodynamic diagnosis with optical coherence tomography: in one study on 26 patients with suspicion of UC, the false-positive rate of photodynamic diagnosis only (84%) could be decreased (78.7%) by adding optical coherence tomography. In other words, the 16% positive predictive value of photodynamic diagnosis increased to 43% if combined with optical coherence tomography.[48
] Recently, Schmidbauer et al
. showed that adding optical coherence tomography to photodynamic diagnosis increased the overall diagnostic accuracy: sensitivity and specificity were respectively 69.3% and 83.7% for white light cystoscopy, 97.5% and 78.6% for photodynamic diagnosis, and 97.5% and 97.9% for photodynamic diagnosis combined with optical coherence tomography.[51
] These results suggest that combining optical coherence tomography with photodynamic diagnosis can reduce the number of unnecessary false-positive biopsies. To our knowledge, no studies on the combination of narrow-band imaging and optical coherence tomography have been published yet.
Optical coherence tomography and narrow-band imaging may also be applied as diagnostics in the upper tract in future. For photodynamic diagnosis, it seems that this is not feasible due to problems with instillation of the fluorescent agent and inevitable tangential illumination in the ureter causing false-positivity. Narrow-band imaging is not hampered by tangential light beams nor requires fluorescent agents and, therefore, may improve the detection of CIS or small papillary lesions, which can be easily missed by conventional imaging studies of the upper tract (retrograde studies, IVP or CT). Optical coherence tomography may overcome the limitations encountered in upper tract biopsies, which tend to have a high rate of nondiagnostics due to insufficient or low-quality specimen. By applying optical coherence tomography measurements of an upper tract lesion before taking a biopsy (or even replacing biopsy), the diagnostic accuracy may be increased. These days, a correct pretreatment stage and grade is becoming quite essential because more and more upper tract tumors are being treated endoscopically and organ-sparing.