Optimizing the diagnosis and treatment of bladder cancer using fluorescence cystoscopy and Raman spectroscopy

Abstract

The gold standard for the diagnosis and treatment of bladder cancer is transurethral resection of bladder tumors (TURBT). A relative high recurrence rate and the need for repeated treatments make bladder cancer one the most expensive cancers from diagnosis till death of the patient. The TURBT accounts for a large amount of the treatment costs. Optimizing the quality of the TURBT, i.e., improving the detection and removal of bladder tumors, will directly have an effect on the patient’s outcome and the cost of bladder cancer treatment. Fluorescence cystoscopy or photodynamic diagnosis has been developed to improve the visualization of bladder tumors during transurethral resection and to reduce the number of recurrences. It significantly enhances the sensitivity of bladder cancer detection, but it is hampered by a substantial number of false-positive results or a lower specificity. Our research demonstrated that predisposing factors for false-positive results are female gender, previous TURBTs and previous intravesical instillation with bacillus Calmette-Guérin immunotherapy (BCG). In addition, we found that bladder cancer confined to the bladder mucosa (pTa) is associated with more false fluorescence compared to invasive bladder cancer. The urologist’s skill and experience also have an effect on the quality of the TURBT and fluorescence cystoscopy, and may have an influence on the number of false-positive results. Raman spectroscopy is an optical technique that utilizes the interaction of laser light with molecular bonds to identify anorganic and organic substances. It does this with high specificity. We demonstrated the feasibility in vivo Raman spectroscopy for the diagnosis of bladder cancer. Multivariate analysis algorithm distinguished bladder cancer from normal bladder locations with a sensitivity of 85% and a specificity of 79%. The technique has shown to be a promising diagnostic tool for bladder cancer diagnosis and might be used in combination with fluorescence cystoscopy to improve diagnostic accuracy. Raman spectroscopy could also be applied without the use of fluorescence cystoscopy. The technique may contribute to fast and accurate diagnosis by way of an ‘optical biopsy’ and may reduce treatment delays improving the outcome in bladder cancer. The ultimate goal is to develop a Raman spectroscopy-based system which allows the diagnosis of tumor stage and grade with high specificity whilst leaving out the need for histopathologic diagnosis and allowing for ‘see-and-treat’ strategy protocols in bladder cancer patients. Finally, we demonstrated the feasibility of navigation-assisted mapping of the bladder. Further development of the technology is needed to improve navigation efficiency and to implement augmented reality techniques to facilitate the retrieval of bladder tumors during transurethral resection.