Editing Upper Urinary Tract Urothelial Cancer (section)

=====Intraluminal Therapy=====

====== Indications (3): ======
# '''Adjuvant therapy after endoscopic or organ-sparing therapy'''
#'''Primary treatment for CIS (see Special Scenarios)'''
# '''Primary treatment of low-grade UTUC (UGN-101)'''

====== Adjuvant therapy ======
*'''Pelvicalyceal or intravesical chemotherapy following ablation of UTUC tumors[https://pubmed.ncbi.nlm.nih.gov/37096584/]'''
**Principle of an immediate instillation of intravesical or pyelocaliceal (upper tract) chemotherapy at the time of endoscopic tumor ablation for UTUC is undertaken by extrapolation of the data supporting immediate instillation of intravesical chemotherapy at the time of transurethral resection of a bladder tumor
**Options: thiotepa, mitomycin
**'''Indications'''
*** '''Considered optional'''
** Technique
***Prior to administration, must confirm that there is no perforation of the bladder or upper tract
***Approaches (3)
***#Antegrade perfusion by nephrostomy tube
***#Retrograde perfusion via ureteral catheter
***#Bladder instillation by transurethral catheter with reflux via a double J ureteral stent.
***#*In the third scenario, a cystogram and demonstration of adequate reflux of contrast into the pyelocaliceal system is recommended.
*'''Immunotherapy'''
**'''Pelvicalyceal BCG[https://pubmed.ncbi.nlm.nih.gov/37096584/]'''
***'''Indications'''
****'''May be offered to patients with HR favorable UTUC after complete tumor ablation or patients with upper tract carcinoma in situ (CIS).'''
****'''Imperative indications'''
****#'''Solitary kidney status'''
****# '''Bilateral UTUC'''
****#'''Risk of progression to end-stage renal disease'''
***Consists of a 6-week induction course of BCG
* '''Outcomes'''
**'''<span style="color:#ff00ff">Systematic review and meta-analysis (2019)</span>'''
*** Inclusion criteria: studies evaluating patients with upper tract urothelial carcinoma receiving instillation treatment as adjuvant/curative therapy for pTa/pT1 and CIS, respectively.
*** Studies with ≥10 participants included in quantitative analyses
*** Results
**** Included 212 patients from 12 studies of patients that underwent endoscopic laser ablation and instillation therapy for Ta/T1 UTUC
**** Recurrence-free survival: 40%
***** Similar to recurrence-free survival with observation after nephron-sparing surgery
**** Cancer-specific survival: 94%
**** Overall survival: 71%
**** No difference in survival based on approach (antegrade, retrograde, or combined) or drug (MMC vs. BCG)
*** [https://pubmed.ncbi.nlm.nih.gov/30846387/ Foerster, Beat, et al. "Endocavitary treatment for upper tract urothelial carcinoma: a meta-analysis of the current literature." ''Urologic Oncology: Seminars and Original Investigations''. Vol. 37. No. 7. Elsevier, 2019.]
* '''Adverse events'''
**'''Most common complication of intraluminal/instillation therapy is bacterial sepsis'''

====== <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.