SUO 2018: Adding Topical Therapy to Endoscopic Treatment for Upper Tract Urothelial Carcinoma

Phoenix, Arizona (UroToday.com) Dr. Chamie gave a talk on the use of topical agents in upper tract urothelial carcinoma. According to the European Association of Urology (EAU) guidelines, low-risk disease can be treated with endoscopic strategies. Low-grade disease is characterized by unifocal disease, tumor size less than 2 cm, low-grade cytology, low-grade biopsy result, and no invasive aspect on CT scans. In the “real world” there is an increasing trend for endoscopic management in low-risk disease (from 6-11% in tumors of the renal pelvis and from 17% to 20% for tumors in the ureter).1  
Dr. Chamie continued and raised the question of why endoscopic treatment has not been adopted in higher percentages. The first reason is the reliability of biopsies and cytology, which is still poor. 45% of tumors classified as Ta, are actually invasive tumors!2 Low-grade tumors on biopsy correspond to a noninvasive tumor in >70% of cases,3 while high-grade tumors on biopsy correspond to an invasive tumor >60% of cases.4 Furthermore, cytology has a sensitivity of 35-65%, with a specificity of >90%. Positive urine cytology predicts a high-grade tumor with a sensitivity of 56% and invasive tumor with a sensitivity of 62%.

Additionally, analyzing many studies dealing with endoscopic treatment of tumors shows a recurrence rate of 58%, with a cancer-specific survival of 96%, over a median follow-up of 32 months.

The next question raised is whether adding topical therapy to endoscopic treatment would help significantly improve the results. A study analyzing the addition of BCG therapy demonstrated a 28% upper tract recurrence after treatment.5 When assessing the role of adding mitomycin C, upper tract recurrence rates were 38% for low-grade disease and 43% for high-grade disease. Additionally, bladder recurrence of 29% and 33% for low - and high - grade disease, respectively were demonstrated.6

The next topic discussed was the usage of chemoprophylaxis during radical nephroureterectomy. Instillation of mitomycin C vs. placebo after upper tract surgery showed a recurrence rate of 16% vs. 27%.7 The best approach for upper tract instillation was shown to be through a 5 Fr ureteral catheter when compared to a double J stent and a nephrostomy tube.8 This approach demonstrated the highest surface area coverage.

The last topic discussed was the efficacy of primary ablative topical therapy (Figure 1). The MitogelTM is a liquid substance that solidifies in body temperature, enabling it to stay in the upper tract. In an ongoing trial, an interim analysis of 34 patients, demonstrated promising results with complete response in 59% and partial response in 15% of patients. It has been shown to be durable at 3, 6 and 9 months following instillation.9

SUO 2018 UGN101 Mitogel

In summary, there is currently a slow adaption of endoscopic therapy due to unreliable staging and a high recurrence rate, even with adjuvant BCG instillation. Perioperative chemotherapy at the time of nephroureterectomy is beneficial, however, less than 50% of Society of Urologic Oncology (SUO) members use it routinely, and this needs to improve. Retrograde ureteral catheter approach results in the greatest surface area coverage of upper tract instillations. Lastly, topical therapy has demonstrated a benefit for low grade disease (with mitogel) and carcinoma in situ without visible tumor (with BCG), and these should be considered viable options.

Presented by: Karim Chamie, MD, MSHS, Ronald Reagan UCLA Medical Center, University of California, Los Angeles, California

References:
1. Upfill-Brown A et al. World J. Urol 2018
2. Cuttress ML et al. BJUI 2012
3. Keely FX et al. J Urol 1997
4. Messer J et al. BJU 2011
5. Rastinhead AR et al. Urology 2009
6. Metcalfe M et al. J Endourol 2017
7. O’brien T et al. Eur Urol 2011
8. Pollard ME et al. Urology 2013
9. Lerner S et al. AUA abstract 2018

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona
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