(UroToday.com) The 2023 American Urological Association (AUA) annual meeting held in Chicago, was host to an upper tract transitional cell carcinoma podium session. Dr. Craig Labbate presented the results of a study analyzing the efficacy and safety of mitomycin gel (UGN-101) as adjuvant therapy following complete endoscopic management of upper tract urothelial carcinoma (UTUC).
Endoscopic-only management of UTUC lesions is associated with high rates of early failure (~50%). Previous attempts at adjuvant treatment of UTUC lesions have included the use of aqueous mitomycin C in the 1990s. However, the routine use of aqueous mitomycin C was complicated by the need for slow infusions and the need to position patients in the Trendelenburg position.
Mitomycin C in the form of JELMYTO (UGN-101) utilizes an RTGel® reverse-thermal hydrogel technology allowing for a dwell time of 4-6 hours. The OLYMPUS trial was a phase 3, open-label, single arm, multicenter prospective study that evaluated a six weekly induction course of JELMYTO in patients with new or recurrent non-invasive LG UTUC. A complete response was observed in 58% of patients, with a further 11% having a partial response. Significantly, 82% of patients with a complete response maintained such a response for 12 months.
The objective of this study was to evaluate the oncologic efficacy and safety profile of UGN-101 instillations after complete endoscopic ablation of UTUC lesions. This was a retrospective, multicenter analysis from 13 US-based sites, commenced post-commercialization.
This cohort included 52 patients who received adjuvant therapy and had at least 1 post-treatment surveillance ureteroscopy to evaluate for disease recurrence. The median follow-up was 6.9 months.
With regards to baseline characteristics, 85% had low grade disease (15% with high grade disease received UGN-101 off-label) and 83% received the full 6-week induction course. Disease was present in the renal pelvis in 73% of patients, with over half having multifocal disease (56%). Ureteral-only disease was present in 6^ of patients.
At the primary endoscopic evaluation (i.e., the first surveillance ureteroscopy performed), 69% of patients had no evidence of recurrent tumor. This proportion was significantly higher for low-grade patients (72% versus 50% for high grade).
Next, the authors evaluated whether ipsilateral disease-free survival varied based on whether UGN-101 was administered for adjuvant or chemoablative purposes (an additional, separate cohort of 73 patients). As demonstrated below, ipsilateral recurrence-free survival was significantly better in the adjuvant group, highlighting the importance of mechanical tumor ablation, where feasible.
As expected, disease-free survival was worse for patients with multifocal disease.
Next, the authors evaluated disease progression, defined as development of high-grade disease, increase in cT stage, or development of metastatic disease. As demonstrated below, none of the patients in the adjuvant UGN-101 group had any progression events, with significantly higher rates of progression in the chemoablative cohort.
Ureteral stenosis was observed in 19% and 28% of patients in the adjuvant and chemoablative groups, respectively, which were both significantly lower than the rates observed in the OLYMPUS trial (44%). Of note, 40-50% of patients in this cohort had UGN-101 instilled via a nephrostomy tube (all via retrograde instrumentation in OLYMPUS).
Dr, Labbate concluded that:
- Among patients receiving adjuvant UGN-101 following endoscopic management of UTUC lesions, the recurrence-free rate at the first examination 3 months post-operatively was 69%.
- High grade lesions are more likely to recur at 3 months (50% versus 28%)
- Progression events are rare following complete endoscopic ablation of UTUC lesions with adjuvant UGN-101
- Low rate (18%) of ureteral stenosis in the adjuvant UGN-101 group
- Longer follow-up is planned with prospective registries
Presented by: Craig Labbate, MD, Society of Urologic Oncology Fellow, MD Anderson Cancer Center, Houston, TX
Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Urological Association (AUA) Annual Meeting, Chicago, IL, April 27 – May 1, 2023