Potential role of photodynamic techniques combined with new generation flexible ureterorenoscopes and molecular markers for the management of urothelial carcinoma of the upper urinary tract

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Sporadic clear cell Renal Cell Carcinoma (ccRCC) is dominated by mutations of the VHL gene located on chromosome 3p in up to 90% of cases. This gene plays a critical role in hypoxia response, including stimulation of neoangiogenesis. Since 2006, anti‐angiogenic therapies targeting this pathway are used in metastatic patients with objective response rate as high as 45%. However, these treatments don't target directly the tumour cell, allowing the potential for disease progression despite treatment. Large scale analysis recently showed that substantial genetic heterogeneity exists in ccRCC. Associated alterations include genes implicated in methylation regulation in 15% of cases, underlying the importance of epigenetic modifications, and truncating mutations in chromatin remodeling complex PRMB1 in 41% of cases. Systematic screening of these tumours is a way to fully determine the somatic genetic architecture of RCC in order to improve tumour classification, to develop prognostic and predictive markers and to target new molecular pathways involved in carcinogenesis. OBJECTIVES To discuss how the development of new generation flexible ureterorenoscopes in combination with photodynamic diagnosis (PDD) improves the assessment of urothelial cell carcinoma of the upper urinary tract (UUT‐UCC). Ultimately, this may allow accurate tumour classification and the ability to select which patients would benefit from conservative treatment as opposed to radical surgery. MATERIALS AND METHODS We conducted an exhaustive Pubmed literature search using a combination of keywords including: ureterorenoscopy, UUT‐UCC diagnosis, PDD, narrow band imaging, conservative treatment UUT‐UCC and molecular urinalysis. We then selected salient high calibre articles relevant to our objective. RESULTS We give specific consideration to anatomical aspects of UUT‐UCC investigation, PDD in UCC, aminolevulinic acid and its derivatives, autofluorescence, narrow band imaging, molecular marker analysis and the recent advances in ureterorenoscopic technology. The traditional pitfalls of UUT‐UCC diagnosis, namely poor visualisation and difficulty in obtaining representative histological samples, are being circumvented by the introduction of modern digital flexible ureteroscopes that can be combined with PDD and molecular analysis to improve tumour classification, deferring to conservative treatment accordingly. CONCLUSION The accuracy of the diagnostic work‐up of UUT‐UCC is improving due to advances in technology, pharmaceutical agents and incorporation of molecular markers, all factors allowing us to characterise tumours of the UUT more definitively.