EAU 2021: Upper Urothelial Cancer: Established Treatment and Guidelines

(UroToday.com) The Urology Beyond Europe thematic sessions included the Joint Session of the European Association of Urology (EAU) and the Arab Association of Urology, as well as a presentation by Dr. Arnulf Stenzl discussing established treatment and guidelines for upper tract urothelial carcinoma.

Dr. Stenzl notes that the histopathological assessment of upper tract urothelial carcinoma is challenging given the (i) anatomic considerations of the upper urinary tract, including thin ureteral layers and the dichotomous renal pelvis; (ii) technical implementation of sampling; and (iii) high risk of “understaging” of the tumor. Diagnosis of upper tract urothelial carcinoma is typically made by CT urography, which has the highest diagnostic accuracy, with a pooled sensitivity of 92% and a pooled specificity of 95%. Urine cytology is also used, but it is less sensitive for upper tract urothelial carcinoma than for bladder tumors. FDG-PET/CT has been used for the detection of lymph nodes with promising sensitivity of 82% and specificity of 84%, but these results need to be further validated. Several prognostic biomarkers have been proposed for predicting cancer-specific mortality (ie. high pre-treatment derived neutrophil-lymphocyte ratio, low albumin, high CRP, high AST/ALT ratio, poor kidney function, and high fibrinogen), but none of these to date have been used routinely in the clinical setting.

Risk stratification for patients with upper tract urothelial carcinoma is important, with the aim of identifying patients that are suitable for kidney sparing surgery.1 This is highlighted in the following algorithm from the 2021 EAU upper tract urothelial carcinoma guidelines:

EAU upper tract.jpg 

 

Imperative factors for kidney-sparing surgery include an anatomical or functional solitary kidney, significant renal insufficiency, or bilateral tumors. Elective factors may include low-risk tumors, and selected cases of high-risk tumors (in the distal ureter), whereas additional factors may include tumor location, size, and likelihood of resectability. Generally, the therapeutic options for kidney sparing surgery include endoscopic or percutaneous resection of the tumor and segmental resection of the ureter. Dr. Stenzl advocates for complete tumor resection/destruction and in most cases taking an early second look to ensure the lesion has not been undertreated. His preferred instruments are either a ureteral resectoscope or a surgical laser (10-20 watt, 272-365 um fiber). A percutaneous approach is an option for low-risk upper tract urothelial carcinoma of the pelvicalyceal system (ie. lower calyx inaccessible for flexible ureterorenoscopy), utilizing a resectoscope through a nephrostomy tube or a surgical laser. Potential perioperative complications include bleeding, obstruction of the renal pelvis, injury of other organs, or tumor spillage. However, one advantage of the percutaneous approach is the potential for adjuvant antegrade chemoinstillation via a nephrostomy tube.

Upper urinary tract instillation of BCG or mitomycin is a potential adjuvant treatment option for patients with CIS or Ta-T1 disease and may be injected retrograde via a single-J stent or antegrade via a nephrostomy tube. The single-arm OLYMPUS trial2 included 71 patients that received six once-weekly instillations of UGN-101 as an induction course. Among the 71 patients who received at least one dose, 42 patients (59%, 95% CI 47-71%) had a complete response at the time of primary disease evaluation. Of the remainder, 8 (11%) had a partial response, 12 (17%) had no response, 6 (8%) had newly diagnosed high-grade disease, and 3 (4%) had an indeterminate response. However, there was also a significant burden of urinary tract morbidity: among 71 patients who received at least one dose of study medication, 48 patients (68%) had an adverse event related to the urinary system including 11 (23%) who did not require surgical intervention, 24 (50%) who required transient stent placement, 11 (23%) who required long-term stent placement, and 2 (4%) who required nephroureterectomy due the need for permanent drainage as a result of ureteral stenosis.

With regards to radical nephroureterectomy, it is important to minimal tumor spillage by avoiding entry into the urinary tract, using an endo bag for tumor extraction during minimally invasive surgery, removing the kidney, ureter and bladder cuff en bloc, and using an open approach for T3/T4 N+ tumors. Additionally, a complete bladder cuff excision should be performed to reduce recurrence risk, as well as a template-based lymph node dissection given the pre-operative challenges of risk stratification.

Finally, to conclude his presentation, Dr. Stenzl discussed chemotherapy, noting that neoadjuvant chemotherapy is promising for pathological downstaging and decreasing disease recurrence/mortality, however, there is no randomized controlled trial to date. The phase III POUT trial3 established a new standard of care for adjuvant chemotherapy for pT2-4, N(any) or pTany N1-N3 patients, however, one limitation of the adjuvant approach is that it is difficult for delivery of full dose cisplatin-based regimens after radical nephroureterectomy.

Presented by: Arnulf Stenzl, MD, University Hospital, Tubingen, Germany

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.

References:

  1. Roupret M, Babjuk M, Capoun O, et al. European Association of Urology Guidelines on Upper Tract Urothelial Carcinoma: 2020 Update. Eur Urol 2020 Jun 24:S0302-2838(20)30427-9.
  2. 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.
  3. Birtle A, Johnson M, Chester J, et al. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): A phase 3, open-label, randomized controlled trial. Lancet 2020 Apr 18;395(10232):1268-1277.
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