Consensus and Divergence in International Guidelines for Upper Tract Urothelial Carcinoma Management

Comparisons were made among the guidelines provided by the European Association of Urology (EAU), American Urological Association (AUA)/Society of Urologic Oncology (SUO), and National Comprehensive Cancer Network (NCCN) regarding the management of upper tract urothelial carcinoma (UTUC), and the results were published in Cancers.

“In this study, we sought to systematically compare current international guidelines and recommendations and to identify both discrepancies and similarities regarding the management of UTUC,” wrote Savio Domenico Pandolfo, Department of Urology, University of L’Aquila Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples “Federico II,” in Naples, Italy.

The EAU guidelines focus on evidence-based recommendations, categorizing evidence as 'weak' or 'strong.' The AUA/SUO guidelines classify evidence into Grades A, B, and C, with expert opinions filling gaps where evidence is lacking. The NCCN guidelines offer practical guidance for healthcare providers, grading recommendations from 1 (high-level evidence) to 3 (major disagreement), with a focus on treatment options. All guidelines were updated in 2023.

The AGREE II assessment showed high reliability (0.96) among authors, with mean domain scores ranging from 68.7 (editorial independence) to 98.5 (applicability). Epidemiologically, UTUC constitutes 5-10% of urothelial carcinomas, predominantly affecting men aged 70-90. Shared risk factors with bladder cancer include smoking and aristolochic acid exposure, with environmental and hereditary factors also contributing.

Diagnostic guidelines emphasize CT scans (92% sensitivity, 95% specificity), with Magnetic Resonance urography and renal ultrasound as alternatives. EAU guidelines highlight symptoms like hematuria and flank pain and recommend avoiding biopsies during endoscopy due to risks. Staging and classification follow the 2022 WHO and 8th edition TNM systems.

Risk stratification is crucial, with EAU focusing on kidney-sparing versus radical treatments based on risk and AUA/SUO differentiating prognosis. High-risk factors include tumor size, hydronephrosis, and multifocality. Ethnicity, age, tobacco use, and comorbidities are considered.

Disease management varies: EAU and AUA support nephron-sparing approaches for low-risk tumors, while NCCN suggests endoscopic management only for select patients. For high-risk non-metastatic UTUC, radical nephroureterectomy with bladder cuff excision and lymphadenectomy is standard. Neoadjuvant chemotherapy is recommended for preserving renal function, with platinum-based protocols preferred. Adjuvant chemotherapy is considered if neoadjuvant therapy is not administered.

Follow-up strategies differ by guideline. NCCN suggests serial cystoscopies and imaging for low-risk tumors, while EAU advises stringent follow-up post-kidney-sparing treatment. AUA recommends early second-look procedures and periodic imaging for up to 5 years, with follow-up tailored to patient-physician decisions. For high-grade tumors, additional chest imaging and continued follow-up beyond five years are advised.

“Between these three, our research depicted high variability in the addressed sections and approaches in reporting recommendations and opinions,” concluded the study authors.

The authors “encourage urologists to always consider UTUC as an entity per se with its own diagnosis, management, and follow-up strategies.”

Reference
Pandolfo SD, Cilio S, Aveta A, et al. Upper tract urothelial cancer: Guideline of guidelines. Cancers (Basel). 2024;16(6):1115. doi:10.3390/cancers16061115