Upper urinary tract urothelial carcinoma (UTUC) is a rare but increasingly prevalent form of urothelial cancer, accounting for 5–10% of cases, with an annual incidence of two to three cases per 100,000 individuals in Western Europe. Radical nephroureterectomy (RNU) with bladder cuff excision is the standard treatment for non-metastatic UTUC, often accompanied by adjuvant platinum-based chemotherapy for locally advanced disease. Kidney-sparing surgery is an option for low-risk patients. A major challenge in UTUC management is the high risk of intravesical recurrence (IVR), occurring in 22–47% of patients within two years post-RNU. Diagnostic ureteroscopy (d-URS), commonly used in UTUC workup, is associated with an increased IVR risk, likely due to tumour cell seeding. To address IVR, guidelines recommend postoperative intravesical chemotherapy, but its adoption is limited by concerns over extravesical leakage, which can cause severe complications. The REBACARE trial explored an alternative approach: a single preoperative intravesical instillation of Mitomycin C (MMC) before RNU. This study aimed to reduce IVR risk without the risks associated with postoperative instillation. Although the trial did not achieve its prespecified >40% reduction in IVR, it demonstrated a significant reduction in patients without prior d-URS, with an excellent safety profile and near-perfect compliance. The two-year IVR rate in the REBACARE cohort was 24%, lower than the 33.2% rate observed in populations without perioperative instillation. The trial highlighted the strong association between d-URS and IVR, with 88% of IVR cases occurring in patients who underwent d-URS. This suggests that d-URS may facilitate tumour cell implantation, reducing the efficacy of perioperative instillations. While d-URS offers diagnostic benefits, its risks, including understaging, ureteral injury, and delayed treatment, warrant careful patient selection. The REBACARE findings support restricting d-URS to cases where imaging and cytology are inconclusive, as recommended by the EAU guidelines. The study’s single-arm design and protocol deviations were limitations, but the per-protocol analysis aligned with the intention-to-treat results, suggesting minimal impact on outcomes. Future research should explore strategies like peri-URS chemotherapy instillations to optimise IVR prevention. In conclusion, preoperative MMC instillation is a safe and feasible strategy for reducing IVR in UTUC patients without prior d-URS, offering a viable alternative to postoperative instillation. The trial underscores the need for judicious use of d-URS and further investigation into perioperative interventions to improve UTUC outcomes.
Intravesical instillation of chemotherapy before radical surgery for upper UTUC
Reviewed by Asif H Ansari
Intravesical instillation of chemotherapy before radical surgery for upper urinary tract urothelial carcinoma: the REBACARE trial.
