The American Urological Association (AUA) and Society of Urologic Oncology (SUO) have released a new guideline on the management of nonmetastatic upper tract urothelial carcinoma (UTUC). The guideline, published in The Journal of Urology, provides evidence-based recommendations on diagnosis, risk stratification, and treatment of UTUC, a rare but often fatal disease. Below is a synopsis of the report’s major recommendations to surgeons.
Diagnosis and Evaluation
For patients with suspected UTUC, perform cystoscopy and cross-sectional imaging of the upper tract with contrast, according to the guideline report. In likely cases, perform diagnostic ureteroscopy, biopsy of lesions, and cytologic washing of the upper tract.
When ureteroscopy is not possible, attempt selective upper tract washing or barbotage for cytology. Use pyeloureterography in the absence of computed tomography or magnetic resonance urography.
In patients with high probability of Lynch-related cancers, perform universal histologic testing of UTUC with additional studies, such as immunohistochemical or microsatellite instability.
To facilitate clinical staging and risk assessment, the report recommends documenting the focality, location, appearance, and size of lesions based on endoscopy and recording features such as invasion, obstruction, and lymphadenopathy observed on imaging.
After standardized assessment, stratify patients as “low” or “high” risk for invasive pT2 or higher disease based on endoscopic, cytologic, pathologic, and radiographic findings. Biopsy alone is not sufficient. Further stratify patients into favorable and unfavorable risk groups.
Tumor ablation, a nephron-sparing option, is recommended for patients with favorable low-risk UTUC. Tumor ablation also may be offered to patients with unfavorable low-risk UTUC and select patients with favorable high-risk UTUC who have low-volume tumors or cannot undergo radical nephroureterectomy (RNU), according to the report. After ablation and ruling out perforation, consider instilling adjuvant pelvicalyceal chemotherapy. When tumor ablation isn’t feasible or progression has occurred, perform RNU or segmental resection of the ureter.
Surgery: Perform RNU or segmental ureterectomy in suitable high-risk UTUC cases. When performing RNU or distal ureterectomy, excise the entire distal ureter including the intramural ureteral tunnel and ureteral orifice, and seal the urinary tract. Also perform lymph node dissection. Follow with a single dose of perioperative intravesical chemotherapy. Clinicians also may consider lymph node dissection in low-risk cases.
Chemotherapy and Immunotherapy
Clinicians should offer cisplatin-based neoadjuvant chemotherapy to surgery patients with high-risk UTUC. They should offer platinum-based adjuvant chemotherapy to patients with advanced pathologic stage UTUC after RNU or ureterectomy if they have not received neoadjuvant platinum-based therapy.
Adjuvant nivolumab therapy may be given to patients who received neoadjuvant platinum-based chemotherapy and have ypT2-T4 or ypN+ disease or patients with pT3, pT4a, or pN+ disease who are ineligible for perioperative cisplatin.
The full guideline also provides recommendations for UTUC surveillance using cystoscopy, cytology, upper tract endoscopy, abdominal/pelvic CT or MRI with contrast, and basic metabolic panel. Recommendations and schedules vary for patients with low-risk vs high-risk UTUC who received kidney-sparing approaches and patients with low-stage (less than pT2) vs high-stage UTUC who underwent nephroureterectomy. Clinicians should refer patients with declining kidney function to nephrology. They should also discuss healthy lifestyle behaviors, such as smoking cessation.
Applying the Guideline
At the American Urological Association’s 2023 Annual Scientific Meeting, guideline chair Jonathan Coleman, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, offered highlights from the new guideline. He noted that UTUC is prone to mismanagement and requires a standardized approach. UTUC is the third most common cancer associated with Lynch syndrome — affecting 9%-12% of patients — so he emphasized that clinicians should be screening their patients for it.
Surena F. Matin, MD, of MD Anderson Cancer Center in Houston, Texas, asked a panel of urologists focused on UTUC treatment for advice on applying the new AUA/SUO guideline in clinical practice. The panel included Jay D. Raman, MD, of Penn State Health Milton S. Hershey Medical Center in Pennsylvania, Sima P. Porten, MD, MPH, of University of California, San Francisco, and Tomonori Habuchi, MD, of Akita University in Japan. The panel debated management of real-world patients with low-grade UTUC, and high-grade, high-risk UTUC who had good kidney function.
Dr Matin summarized the take-home messages from the debate in an AUA presentation:
Managing low-grade UTUC
- Consider mitomycin hydrogel for low-grade recurrent UTUC
- Use intravesical chemotherapy with nephroureterectomy
- Consider intravesical chemotherapy after ureteroscopic biopsy, based on anecdotal evidence
Managing high-risk UTUC
- Risk stratify upper tract tumors
- Estimate post-nephroureterectomy kidney function to help patients decide between initial surgery or neoadjuvant chemotherapy
- Consider lymphadenectomy
The new AUA/SUO guideline follows the release of the European Association of Urology’s 2020 update to its UTUC guideline.
Coleman JA, Clark PE, Bixler BR, et al. Diagnosis and management of non-metastatic upper tract urothelial carcinoma: AUA/SUO guideline. J Urol. 2023;209(6). doi:10.1097/JU.0000000000003480
Coleman JA. Plenary: Friday Afternoon: AUA Guidelines: Upper Tract Urothelial Carcinoma (UTUC). Presented at AUA 2023; April 28, 2023.
Matin S. Friday afternoon: Panel Discussion: Management of Upper Tract Urothelial Carcinoma. Presented at AUA 2023; April 28, 2023.
Managing upper tract urothelial carcinoma in the real world. News release. American Urological Association; April 28, 2023.