On the up and up.

Top Line: There’s no level I evidence to guide the optimal adjuvant treatment of locally advanced upper tract urothelial carcinoma (UTUC).

The Study: Systemic therapy is often extrapolated from bladder cancer. However, outcomes for UTUC are worse than those for bladder cancer, and guidelines provide fairly weak support for routine use of adjuvant chemo. In the POUT trial, an impressive 260 patients with either muscle-invasive or lymph node positive UTUC were enrolled following nephroureterectomy. Most had muscle-invasive disease, as only one-third even had lymph node dissections and fewer than 10% had pathologically-involved nodes. They were then randomized to receive no further therapy versus 4 cycles of gemcitabine + carboplatin or cisplatin. Three-quarters in the chemo arm completed all 4 cycles. As expected, toxicity was higher in the chemo arm, which resulted in a transient decrease in quality of life. But here’s the kicker. At 3 years, adjuvant chemo significantly(!) improved disease-free survival from 46 → 71%. That’s a 25% absolute improvement. Distant metastasis-free survival was also improved, but overall survival results aren’t yet mature. 

TBL: Adjuvant platinum + gemcitabine for muscle invasive UTUC dramatically improves disease-free survival. | Birtle, Lancet 2020