FOIU 2018: Urothelial Carcinoma of the Upper Tract Following Radical Cystectomy

Tel-Aviv, Israel (UroToday.com) Seth Lerner, MD, gave an overview of urothelial carcinoma of the upper tract (UTUC) occurring following radical cystectomy (RC). He began his talk mentioning a systematic review including 57 studies¹, demonstrating an incidence of UTUC following RC of 4-10%. The variables associated with UTUC after RC include:

Bladder carcinoma in situ (CIS)
History of non-muscle invasive bladder cancer (NMIBC)
CIS in the distal ureter

The majority (84%) of cases present with localized disease and treated with surgery. However, 66% of patients die due to their disease within a median follow-up of 9 months.

According to the AUA guidelines, follow-up of patients after RC should include:

Chest imaging
Cross-sectional imaging of the abdomen and pelvis with CT or MRI at 6-12 months intervals for 2-3 years and then annually

According to the NCCN guidelines, follow-up of patients after RC should include:

CT urography or MRI urography of the abdomen and pelvis every 3-6 months for two years
Chest imaging every 3-6 months for two years
At year 3-5 CT/MR or PET and chest imaging annually
At 6-10 years renal ultrasound annually

There have been studies attempting to assess the utility of urine biomarkers in these patients. In a study published in 2012, 270 patients after RC were assessed.² A total of 10 (3.4%) of the patients developed UTUC with a median follow-up of 31 months (2-202). The study analyzed the role of urine cytology, FISH, and their combination. The false positive rate was 89.3%, 76.9%, and 57.1% for urine cytology, FISH, and their combination, respectively. Due to the low prevalence of UTUC following RC, the utility of urine biomarkers is limited. Second primary tumors of the upper tract are commonly present at an advanced stage and are more likely to be invasive. They harbor a higher probability of occult metastatic disease, warranting integration of cisplatin-based chemotherapy and nephroureterectomy. Also, the reduction in EGFR pre- and post-radical cystectomy may affect treatment decisions for managing high-grade UTUC following RC (Figure 1). Therefore, perioperative chemotherapy should be given in the neoadjuvant setting whenever possible.

Figure 1 – EGFR reduction pre- and post- radical cystectomy:

The known risk factors for UTUC following RC include³:

RC performed for CIS or NMIBC as CIS imposes a higher risk, and NMIBC is associated with a longer life expectancy.
Positive ureteral margins (Odds ratio of 7.163, p<0.001)
Prostatic urethra or membranous urethra involvement in women (Odds ratio 7.19, p<0.001)
History of UTUC (Odds ratio of 7.25, p=0.03)

The diagnostic challenges facing the urologist diagnosing these secondary tumors include:

The feasibility of retrograde ureteroscopy via ileal conduit and neobladder
The anatomy of the afferent limb may restrict access in the neobladder
Continent cutaneous diversion requires antegrade approach, however, percutaneous ureteral stent facilitates retrograde ureteroscopy.

Dr. Lerner concluded his talk emphasizing that UTUC following RC are usually high-grade and invasive tumors. They are usually symptomatic but approximately 1/3 are detected on routine cross-sectional imaging. The surgical treatment of these secondary tumors significantly reduces EGFR, preventing most patients from receiving adjuvant chemotherapy. Therefore, chemotherapy should be given in the setting of neoadjuvant chemotherapy, whenever possible.

Presented by: Seth Lerner, MD, FACS, Baylor College of Medicine, Houston, TX, USA

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2018 FOIU 4th Friends of Israel Urological Symposium, July 3-5. 2018, Tel-Aviv, Israel

References:
1. Gakis et al. Eur Urol. 71:545, 2017
2. Fernandez, et al. Urol Oncol 30:821, 2012
3. Picozzini, et al. J Urol 188:2046, 2012

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