Editing Upper Urinary Tract Urothelial Cancer (section)

====== <span style="color:#ff0000">Primary treatment for low-grade UTUC</span> ======
*Effectiveness of intraluminal therapy has been limited by inadequate exposure to urothelium from fluid preparations due to rapid drainage from (2)
**No storage capacity of UTUC (unlike bladder)
**Ureteral and pelvic peristalsis
*Potential solution is to use reverse thermosensitive polymers, which are liquid at room temperature and convert to a gel at body temperature, resulting in increased dwell time
*'''<span style="color:#ff0000">UGN-101</span>'''
**'''UGN-101 = MMC + reverse thermosensitive polymer'''
***Also known as Mitogel, Jelmyto
**'''<span style="color:#ff00ff">OLYMPUS (Lancet Oncology 2020</span>''')
*** Objective: evaluate the safety and activity of UGN-101 to treat primary and recurrent low-grade UTUC.
*** '''Design: open-label, single-arm, phase 3 trial'''
*** '''Population: 71 patients with primary or recurrent biopsy-proven, low-grade UTUC (involving the renal pelvis or calyces) and ≥1 low-grade lesion above the ureteropelvic junction, measuring 5–15 mm.'''
**** Lesions >15 mm were eligible for endoscopic downsizing before the initiation of treatment.
*** Treatment: 6 once-weekly treatments of UGN-101
*** '''Primary outcome: complete response,''' defined as
**** Negative endoscopic examination AND
**** Negative cytology at the primary disease evaluation AND
**** Negative for-cause biopsy when done
*** '''Results:'''
**** '''Primary outcome:'''
***** '''≈60% complete response at 3 months'''
****** Among those with complete response, ≈60% maintained complete response at 12 months[https://pubmed.ncbi.nlm.nih.gov/34915741/]
**** '''Adverse events'''
***** Common; 94% had any adverse event
***** 37% had ≥1 serious adverse event
****** '''44% ureteric stenosis[https://pubmed.ncbi.nlm.nih.gov/34915741/]'''
****** 20% renal dysfunction
*** [https://pubmed.ncbi.nlm.nih.gov/32631491/ Kleinmann, Nir, et al.] "Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial." ''The lancet oncology'' 21.6 (2020): 776-785.
*'''Technique'''
**'''Approaches:'''
***'''Antegrade via percutaneous nephrostomy'''
*** '''Retrograde through a single J open-ended ureteric stent'''
**** '''Suboptimal because the drug often does not reach the renal pelvis'''
*** Both the antegrade and retrograde approach can be dangerous due to possible ureteric obstruction and consecutive pyelovenous influx during instillation/perfusion.