SUO 2018: POUT Trial - Adjuvant Therapy for Upper Tract Urothelial Carcinoma
In this discussion, the POUT trial was presented in a summarized form. This was a multicenter study done in the UK, designed to enroll 360 patients but was closed early because it met its efficacy endpoint. This was the first study that prospectively assessed the role of adjuvant chemotherapy administered within 90 days following radical nephroureterectomy.
Between May 2012 and Sept 2017, 260 patients with locally advanced or node-positive UTUC disease (pT2-T4 N0-3 M0) were recruited. The patients were then randomized (1:1 ratio) to 4 cycles of gemcitabine-cisplatin (GFR ≥ 50 ml/min)/gemcitabine-carboplatin (GFR 30-49 ml/min) or surveillance 90 days following radical nephroureterectomy. Patients with a GFR < 30, and those with an incompletely resected tumor were excluded from the trial. Overall, in a total of 57 UK centers, 129 patients were randomized to the surveillance arm; and 131 patients were randomized to the chemotherapy arm. Patients were followed closely with cross-sectional imaging and cystoscopy every 6 months for the first two years, which then changed to annual follow-up for a total of 5 years. The primary end-point for the trial was disease-free survival (DFS), and the secondary endpoints were overall survival (OS), recurrence-free survival (RFS), toxicity and quality of life (QoL).
The results demonstrated that baseline characteristics were comparable between the groups. Importantly, most patients enrolled had pT3 disease (65%) and were node negative following node dissection (91%). After a median follow-up of 17.6 months, a significant difference in DFS (HR 0.49, CI 0.31-0.76, p=0.001) favoring the chemotherapy arm was observed. Following adjustment for nodal involvement, microscopic margin status and planned chemotherapy type, the difference was even more pronounced with an HR 0.47, CI 0.30-0.74, p=0.001).
When analyzing the secondary end-points, adjuvant chemotherapy was also associated with an improved RFS (HR 0.49 0.30-0.78, p=0.02). Unfortunately, the OS is not mature enough, and the although the results demonstrate a separation in the OS curves, no significant difference can be discerned at this time point. Expectedly, patients in the chemotherapy arm had lower global health status during active treatment, secondary to nausea, vomiting, and fatigue. However, at 12 and 24 months of follow-up, no difference was noted in the quality of life between patients in both arms.
Dr. Srinivas concluded by stating that the POUT trial currently represents level 1 evidence that adjuvant chemotherapy should be given to patients with locally advanced or node-positive UTUC. Longer follow-up time is needed to assess if any difference will manifest in the OS.
Presented by: Sandy Srinivas, MD, Stanford Health Care, Stanford University, Standford, California
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona