What are the treatment options for Upper Tract Urothelial Carcinoma (UTUC) stage 0 Ta or Tis (Carcinoma in situ) lesion?

From the Guidelines

The primary treatment for stage 0 Ta or Tis Upper Tract Urothelial Carcinoma (UTUC) is endoscopic management with kidney-sparing approaches, utilizing laser therapy or electrocautery, followed by adjuvant intracavitary therapy with BCG or mitomycin C. This approach prioritizes preserving the kidney while effectively treating the cancer, given that stage 0 Ta or Tis lesions are superficial and have not invaded the muscle layer. The treatment strategy involves:

• Endoscopic ablation using laser therapy (such as Holmium:YAG or Nd:YAG laser) or electrocautery to destroy the cancerous tissue.
• Adjuvant intracavitary therapy with BCG (Bacillus Calmette-Guérin) or mitomycin C, which can be instilled directly into the upper urinary tract via a nephrostomy tube or retrograde ureteral catheter, as seen in the treatment of bladder cancer 1. A typical regimen for intracavitary therapy includes:
• Weekly instillations for 6 weeks (induction phase).
• Maintenance therapy, which may involve instillations at intervals such as 3,6,12,18,24,30, and 36 months, although the exact schedule can vary based on the clinical context and patient response. Close surveillance is crucial and typically involves:
• Ureteroscopy and cytology every 3 months for the first year.
• Every 6 months for the second year.
• Annually thereafter. For patients with extensive disease, recurrence despite conservative therapy, or those who cannot tolerate endoscopic management, radical nephroureterectomy with bladder cuff excision remains a definitive treatment option, although this is generally considered when kidney-sparing approaches are not feasible or have failed. The choice between BCG and mitomycin C for intracavitary therapy can depend on patient tolerance and specific clinical factors, with BCG being a standard therapy for high-grade lesions like Tis, as indicated by its use in bladder cancer treatment 1.

From the FDA Drug Label

TICE® BCG is indicated for: the treatment and prophylaxis of carcinoma in situ (CIS) of the urinary bladder the prophylaxis of primary or recurrent stage Ta and/or T1 papillary tumors following transurethral resection (TUR)

The treatment options for Upper Tract Urothelial Carcinoma (UTUC) stage 0 Ta or Tis (Carcinoma in situ) lesion are not directly addressed in the provided drug labels.

• Key Point: The labels only discuss the treatment of carcinoma in situ of the urinary bladder, not upper tract urothelial carcinoma.
• Important Note: The provided drug labels do not provide information on the treatment of UTUC stage 0 Ta or Tis lesions, therefore no conclusion can be drawn from these labels 2, 2, 2.

From the Research

Treatment Options for Upper Tract Urothelial Carcinoma (UTUC) Stage 0 Ta or Tis

• Endoscopic management is a reasonable alternative for patients with renal insufficiency or a solitary functional kidney, bilateral disease, or a significant comorbidity that precludes radical surgery 3
• Select patients with a functional contralateral kidney who have low-grade, low-stage tumors may also be candidates for endoscopic management 3
• Adjuvant topical therapy with Bacillus Calmette-Guerin or mitomycin C can be used after endoscopic management of UTUC in an attempt to reduce recurrence 3, 4, 5, 6
• Mitomycin C is the most common adjuvant treatment for UTUC, with bacillus Calmette-Guerin (BCG) being utilized to a lesser extent 5
• UGN-101 is a novel topical gel-based therapy that has shown promising results and has recently garnered Food and Drug Administration (FDA) approval for UTUC 5, 6
• Other treatments such as BCG-IFN, gemcitabine, docetaxel, and drug-eluting stents (DES) may play a future role in UTUC treatment given further research 5
• Sequential endoluminal gemcitabine and docetaxel vs. Bacillus Calmette-Guérin for the treatment of upper tract carcinoma in situ has shown similar oncological outcomes and major adverse event rates 7

Adjuvant Topical Therapies

• Induction and maintenance adjuvant topical mitomycin C for endoscopically resected UTUC is feasible, well tolerated, and shows promising intermediate-term data on recurrence, progression, and nephroureterectomy-free survival 4
• Adjuvant endocavitary (endoureteral) instillations have been proposed to reduce the risk of ipsilateral UTUC recurrence caused by the implantation of floating neoplastic cells after endoscopic resection 6
• The role of UGN-101 as a primary chemoablative treatment of primary noninvasive, endoscopically unresectable, low-grade, UTUC has been analyzed, with a complete response rate of 58% after the induction cycle 6

Administration and Outcomes

• Methods of administration, including percutaneous nephrostomy tube or retrograde ureteral catheter, can affect outcomes, with instillation via percutaneous nephrostomy tube associated with an increased risk of recurrence 7
• Oncologic outcomes, including recurrence-free and nephroureterectomy-free survival, have been reported for various adjuvant topical therapies, with varying degrees of effectiveness 4, 5, 6, 7