AUA: Upper Tract Urothelial Carcinoma (2023)

See Original Guidelines

• Literature search up to January 2023

Background

• UTUC refers to urothelial tumors that originate from the inner lining of the ureter, calyces, or renal pelvis
• Estimated annual incidence in US: 7000
  • Slightly less than annual incidence of testicular cancer: 8000-10000
• Approximately 25% of cases will present as localized disease, over 50% will have regionally advanced cancers, and nearly 20% will have distant disease at the time of diagnosis.
• Peak incidence is seen in adults aged >70 years
• 3x more common in men than women in western countries
• Risk factors
  • occupational exposure
  • Geographic location
  • Balkan endemic nephropathy associated with aristolochia herbal ingestion
  • Chronic upper tract inflammation
  • Hereditary factors such as Lynch and Lynch-like syndromes

Diagnosis and Evaluation

• Recommended investigations in patients with suspected UTUC
  • Cystoscopy
    • Essential component of the evaluation for patients with suspected UTUC due to the risk of concurrent lower tract urothelial cancer in this population
  • Cross-sectional imaging of the upper tract with contrast including delayed images
    • Preferred modality: multiphase computed tomography (CT) scan with excretory phase imaging of the urothelium.
      • Pooled sensitivity of 92%
      • Pooled specificity of 95%
    • In patients with contraindications to contrast-enhanced CT such as chronic kidney disease (CKD) or untreatable allergy to iodinated contrast medium, use magnetic resonance (MR) urography
      • MRI is less sensitive than CT, similar specificity
    • In patients with contraindications to contrast-enhanced CT such as chronic kidney disease (CKD) or untreatable allergy to iodinated contrast medium, use magnetic resonance (MR) urography.
    • In patients with contraindications to multiphasic CT and MR urography, use retrograde pyelography in conjunction with non-contrast axial imaging to assess the upper urinary tracts. Renal ultrasound (US) may also have utility in providing additional diagnostic assessment.
• In patients with UTUC on imaging when diagnostic and prognostic details are needed
  • Diagnostic ureteroscopy and biopsy of any identified lesion
    • Document key descriptive features of UTUC including:
      • Tumor size
      • Number
      • Location
      • Focality
      • Appearance
      • These factors may guide further diagnostic testing and inform therapeutic interventions as well as provide points of comparison for subsequent ureteroscopic surveillance.
      • See checklist in Table 3
    • Methods of biopsy
      • Ureteroscopic biopsy with forceps
      • Fluoroscopically guided retrograde brush biopsy
      • Mucosal abnormalities may be difficult to biopsy effectively and thus attempted tissue confirmation may be facilitated with the use of brush biopsies or percutaneous image-guided biopsy.
    • Rare situations where endoscopic upper tract evaluation may not be necessary, when other diagnostic means clearly confirm the diagnosis of UTUC and thus histologic tissue confirmation is not clinically required.
      • High-grade (HG) selective cytology or other source of tissue diagnosis, and clear and convincing radiographic findings of upper tract urothelial-based tumor(s) such as patients with an obvious enhancing, urothelial based soft-tissue filling defect on contrast-enhanced imaging with urography. Such situations may be particularly relevant in patients with a history of HG urothelial cancer.
      • When findings would not influence decision-making, such as patients with severe co-morbidities who are ineligible for intervention or request expectant management.
  • Cytologic washing from the upper tract system being investigated
    • cytologic barbotage washing with saline obtained from selective ipsilateral collection prior to use of any contrast is preferred to a voided urinary specimen due to improved cellular yield, to avoid potential contamination in case of concomitant bladder and/or prostatic urethral disease as well as theoretical dilution of the specimen from a normal contralateral unit, all of which further reduce sensitivity.
    • urine cytology is reported according to seven categories (Paris System): nondiagnostic, negative for HG urothelial carcinoma (NHGUC), atypical urothelial cells (AUC), suspicious for HG urothelial carcinoma (SHGUC), HGUC, low-grade (LG) urothelial neoplasm (LGUN), and other malignancies
• Optional
  • Urine fluorescence in situ hybridization (FISH)
    • May be considered adjunctively to adjudicate atypical or suspicious cytology results.
• In patients who have concomitant lower tract tumors (bladder/urethra) discovered at the time of ureteroscopy, the lower tract tumors should be managed in the same setting as ureteroscopy.
  • Consensus on prioritization of procedure sequencing (managing bladder before or after same-setting ureteroscopy) is lacking and heavily scenario-dependent. Rationale for managing the bladder first include optimizing visualization within the bladder, avoiding back�pressure or back-washing into the upper tract in the case of post-ureteroscopy stenting, and permitting final confirmation of bladder hemostasis. Addressing the upper tract first may be preferred in cases of bulky bladder tumor involvement where complete resection is not possible or bulky upper tract disease in which risk assessment is the priority. Seeding of tumors from bladder to upper tract or from upper tract to the lower tract have been raised as legitimate concerns which some have addressed by advocating use of ureteral access sheaths in such circumstances, yet the benefits of this approach require further prospective study.
• In cases of existing ureteral strictures or difficult access to the upper tract, clinicians should minimize risk of ureteral injury by using gentle dilation techniques such as temporary stenting (pre-stenting) and limit use of aggressive dilation access techniques such as ureteral access sheaths.

Management

Surgical management

• When performing NU or distal ureterectomy, the entire distal ureter including the intramural ureteral tunnel and ureteral orifice should be excised, and the urinary tract should be closed in a watertight fashion.
• . In patients undergoing RNU or SU (including distal ureterectomy) for UTUC, a single dose of perioperative intravesical chemotherapy should be administered in eligible patients to reduce the risk of bladder recurrence.
• Lymph node dissection
  • If HR UTUC, LND recommended
    • No RCTs to evaluate the effect of LND on oncologic outcomes in patients undergoing NU or SU
    • There is sufficient non-randomized evidence to suggest an oncologic benefit to LND at the time of NU for patients with “HR” stratification by guidelines
    • Recommended minimal templates in non-metastatic disease
      • Tumors in the pyelocaliceal system: lymph nodes of the ipsilateral great vessel extending from the renal hilum to at least the inferior mesenteric artery.
      • Tumors in the proximal 2/3 of the ureter: lymph nodes of the ipsilateral great vessel extending from the renal hilum to the aortic bifurcation.
      • Tumors in the distal 1/3 of the ureter: ipsilateral pelvic LND to include at minimum the obturator and external iliac nodal packets.
      • Internal and common iliac nodal packets may be removed in the appropriate clinical setting.
      • Limited data suggest cranial migration of lymph node metastases to the ipsilateral great vessels such that higher dissection may be considered in the appropriate clinical setting and per clinician judgement
  • If LR UTUC, LND optional
• Neoadjuvant/Adjuvant Chemotherapy and Immunotherapy