Adjuvant chemo
There is level 1 RCT evidence (POUT trial) that adjuvant platinum (cisplatin or carboplatin) + gemcitabine chemotherapy:
- Improves disease-free survival at median 30 months vs no adjuvant treatment
- Carboplatin used if eGFR < 50, cisplatin if > 50
- Included patients with pT2+ or pN+
Retrospective data suggests DFS and OS benefit for adjuvant chemo.
- Not replicated in retrospective studies of variant histology, only pure UC.
The main issue is that nephroureterectomy significantly reduces renal function and therefore may preclude use of cisplatin.
Neoadjuvant chemo
Neoadjuvant chemotherapy has not been well studied. Its main advantage would be the delivery of full dose platinum chemo prior to reducing renal function with surgery.
Premise also based on demonstrable benefit for neoadjuvant chemo for muscle invasive urothelial carcinoma of the bladder.
A prospective phase 2 study showed 14 % pT0, and more than 60 % pT1 or less (Margulin 2020).
Retrospective meta-analysis suggests downstaging or partial response in 30 – 40 % and an overall and CSS benefit cf. nephroureterectomy alone.
No prospective comparative data available.
Immunotherapy
Phase 3 trial of adjuvant nivolumab after T2+ urothelial cancer contained 20 % patients with UTUC – good improvement in disease free survival in overall cohort
Need further subgroup analysis for UTUC – both ureter/pelvic tumours CI crossed 1 (Bajorin NEJM 2021)