In patients with locally advanced upper tract urothelial carcinoma (UTUC), adjuvant platinum-based chemotherapy increases disease-free survival compared with surveillance, according to the results of a phase 3 trial.
Due to limited symptoms, the majority of patients with UTUC present with muscle-invasive or locally advanced disease, resulting in a mortality rate of over 50%. Few large clinical trials have been conducted in this space due to the rarity of the disease, and nephroureterectomy—a surgical procedure in which the renal pelvis, kidney, ureter, and bladder cuff are removed—is considered the standard treatment approach, followed by surveillance. In the POUT trial, the largest randomized trial conducted exclusively in this patient population, a team of researchers evaluated the efficacy of adjuvant platinum-based chemotherapy administered after nephroureterectomy in patients with locally advanced UTUC.
The trial enrolled 261 patients with muscle-invasive, lymph node-positive, or metastasis-free locally advanced UTUC who were randomized in a 1:1 ratio to receive adjuvant platinum-based chemotherapy or to undergo surveillance after nephroureterectomy. Patients in the chemotherapy group received either cisplatin or carboplatin plus gemcitabine, initiated within 90 days after surgery and administered in four 21-day cycles. The primary end point was disease-free survival, with secondary end points of metastasis-free and overall survival, acute and late toxicity, and patient-reported quality of life.
At a median follow-up of 30.3 months, median disease-free survival was higher in patients receiving chemotherapy compared with surveillance (not reached vs 29.8 months), with a 55% reduced risk of disease recurrence or death in patients in the chemotherapy group. Three-year event-free estimates were significantly higher in the chemotherapy group compared with surveillance (71% vs 46%). Fewer disease-related events were reported in patients receiving chemotherapy compared with surveillance (27% vs 47%). Grade 3 or higher treatment-emergent adverse events occurred in 44% of patients who started chemotherapy, compared with 4% of patients managed by surveillance. There were no treatment-related deaths.
"Adjuvant platinum-based chemotherapy should be adopted as a new standard of care for patients with locally advanced UTUC for whom systemic chemotherapy is not contraindicated," conclude the researchers, led by first author Alison Birtle, MD, an oncologist at Royal Preston Hospital's Rosemere Cancer Centre in Preston, the United Kingdom. "This regimen should be routinely considered for all patients in this population, and future studies should focus on combinations with novel agents in the adjuvant setting, which might further improve the prognosis for locally advanced UTUC."
For More Information
Birtle A, Johnson M, Chester J, et al (2020). Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet. [Epub ahead of print] DOI:10.1016/S0140-6736(20)30415-3
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