SUO 2021: Intraluminal Therapy for Upper Tract Urothelial Carcinoma

(UroToday.com) The Society of Urologic Oncology (SUO) 2021 annual meeting in Orlando, FL was host to an excellent presentation by Dr. Katie S. Murray, DO, MS, FACS regarding intraluminal therapy for upper tract urothelial carcinoma (UTUC).


Dr. Murray started her presentation by emphasizing the importance of risk stratification in UTUC. Low-risk UTUC has the following features:

  • Unifocal disease
  • Tumor size <2cm
  • Low-grade cytology
  • Low-grade ureteroscopic biopsy
  • No invasive aspect on axial imaging

This is in contrast to high-risk UTUC:

  • Hydronephrosis
  • Tumor size >2 cm
  • High-grade cytology
  • High-grade ureteroscopic biopsy
  • Multifocal disease
  • Previous radical cystectomy for bladder cancer
  • Variant histology

Treatment for UTUC should be risk-adapted, avoiding aggressive interventions and sparing nephrons in low-risk disease. This is critical because of the metachronous disease potential, the importance of preserving renal function for potential subsequent chemotherapy treatment, and other medical comorbidities that may affect renal function.  It should always be performed when possible and safe via endoscopic or chemo ablative techniques.  

The current National Comprehensive Cancer Network (NCCN) guidelines recommend endoscopic resection with or without postsurgical intrapelvic chemotherapy or BCG as an option for low-risk UTUC. They do note however that “complete or near complete endoscopic resection or ablation is recommended prior to mitomycin ureteral gel application, which is most suitably indicated for a residual, low-grade, low-volume (5-15 mm), solitary tumor in the upper urinary tract for a patient, not a candidate for or not seeking nephroureterectomy as a definitive treatment.”

There is currently no level one evidence for endoscopic ablation with all current data based on retrospective studies. Dr. Murray highlighted a study by Petros et al. with a median follow up of 24-58 that demonstrated UTUC recurrence rate of 65%, bladder recurrence rate of 44%, progression to surgical resection rate of 0-33%, overall survival rate of 35-100% and cancer-specific survival rate of 70-100%.1 BCG has been given for upper tract disease with curative intent for carcinoma in situ disease or in the adjuvant setting for Ta/T1 disease. A study of 55 patients with a median follow-up of 42 months demonstrated a 47% recurrence rate with an adverse event rate of 20% (one death due to sepsis). Aqueous chemotherapy has also been used in 27 patients adjuvantly. Data with 19 months median follow up demonstrated 36-month outcomes as follows:

  • Recurrence-free survival of 60%
  • Progression-free survival of 80%
  • Radical nephroureterectomy free survival of 76%
  • Cancer-specific mortality of 0%
  • Overall survival of 93%
  • Nine treatment-related adverse events (no systemic toxicity)

Next, Dr. Murray went on to discuss the OLYMPUS Trial- Mitomycin for Pyelocaliceal Solution (UGN-101) which led to Gelmyto’s ® approval by the Food and Drug Association in April 2020. This was a single-arm, phase 3, open-label trial with low-risk UTUC patients treated with reverse thermal hydrogel technology Mitomycin (Jelmyto ®). Seventy-one patients were enrolled and the primary endpoint was complete response four to six weeks after completion of the six-week induction course. The primary endpoint of complete response was met in 59% of patients (95% CI: 47-71%) and the secondary endpoint of durability at 12 months was met in 82%. The main adverse event was ureteral obstruction in 58% of patients (17% Grade 3). Importantly, if the tumor was >1.5 cm, then ablation/debulking was permitted prior to treatment application. Patients had to have had one measurable papillary lesion above the ureteropelvic junction. Notably, 48% of patients had papillary disease that could not be reached endoscopically with a laser, and the response rate was 59% in this population.3

Although this trial clearly provides a unique, novel option for UTUC patients, Dr. Murray felt that many questions regarding this treatment modality remained:

  • Prognosis consequences of understaging/undergrading in UTUC
  • What should the follow-up regimen be?
  • What is the rate of recurrence and progression?
  • What should the maintenance schedule be?
  • Should this be primary therapy, adjuvant therapy or both?
  • What about partial responders?
  • Is this the new standard of care?

Currently, the Endoluminal Light Activated Treatment of Upper Tract Urothelial Cancer (ENLIGHTED) trial is actively recruiting patients. This is a single-arm, open-label multicenter international trial that evaluates the treatment efficacy of Tookad (Padeliporfin di-potassium) VTP therapy in biopsy-proven low-grade tumors in the renal pelvis and ureter. The objectives of this trial are to evaluate complete response (endoscopically and cytology), evaluate its safety profile and 12-month durability. The target sample size is 100 patients across 30 centers.

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Dr. Murray ended her presentation by re-emphasizing the following key points:

  • Nephron sparing is necessary
  • Intraluminal therapy is now here and approved to assist in that sparing            

Presented by: Katie S. Murray, DO, MS, FACS, Assistant Professor, Urologic Oncology, Missouri University, MO

Written by: Rashid Sayyid, MD, MSc – Urology Chief Resident, Augusta University/Medical College of Georgia, @rksayyid on Twitter during the 2021 Society of Urologic Oncology (SUO) Winter Annual Meeting, Orlando, FL, Wed, Dec 1 – Fri, Dec 3, 2021. 

References:

  1. Petros FG, Li R, Matin S. Endoscopic Approaches to Upper Tract Urothelial Carcinoma. Urol Clin North Am. 2018 May;45(2):267-286.
  2. Giannarini G, Kessler TM, Birkhäuser FD, Thalmann GN, Studer UE. Antegrade perfusion with bacillus Calmette-Guérin in patients with non-muscle-invasive urothelial carcinoma of the upper urinary tract: who may benefit? Eur Urol. 2011 Nov;60(5):955-60.
  3. Kleinmann N, Matin SF, Pierorazio PM, 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. Lancet Oncol 2020 Jun;21(6):776-785.
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