Optimizing the pathway for upper tract urothelial carcinoma

Upper tract urothelial carcinoma (UTUC) is a rare malignancy, accounting for approximately 5–10% of all urothelial cancers. It occurs more frequently in men than in women and predominantly affects elderly patients, with peak incidence between 70 and 90 years of age. Established risk factors include tobacco exposure, aristolochic acid exposure, and germline mutations in DNA mismatch repair genes associated with Lynch syndrome. In addition, kidney transplant recipients are considered to be at increased risk of developing UTUC.
Most patients are diagnosed after the onset of symptoms, most commonly visible haematuria. When UTUC is suspected, a comprehensive diagnostic work-up is required. According to the European Association of Urology (EAU) guidelines, the recommended diagnostic pathway includes computed tomography urography, urinary cytology, cystoscopy, and, in selected cases, diagnostic ureteroscopy. After confirmation of non-metastatic UTUC, patients are stratified into low-risk or high-risk disease based on tumour characteristics identified during the diagnostic process. This risk stratification is crucial, as it directly guides treatment decisions: low-risk patients are candidates for kidney-sparing surgery (KSS), whereas high-risk patients are generally treated with radical nephroureterectomy (RNU).
While KSS offers the important advantage of preserving renal function, it is associated with a higher risk of ipsilateral upper tract recurrence and intravesical recurrence. Consequently, intensive and long-term follow-up is recommended after KSS. However, current follow-up strategies in the EAU guidelines are largely based on low-level evidence derived from small and heterogeneous studies.
This PhD thesis aimed to improve the entire care pathway for patients with UTUC, addressing challenges across diagnostics, treatment selection, and follow-up strategies, with the ultimate goal of optimizing oncological outcomes while preserving renal function and quality of life.