The Institute of Cancer Research in the UK found that the implementation of gemcitabine-platinum combination chemotherapy within 90 days following nephroureterectomy resulted in longer periods of disease-free survival in patients with locally advanced upper tract urothelial cancer (UTUC) [1]. The phase 3 POUT trial (NCT01993979) randomized 261 post-nephroureterectomy patients to surveillance only, or to receive four 21-day cycles of adjuvant chemotherapy. For participants in the chemotherapy arm, treatment was initiated within 90 days post-surgery and consisted of either a combination of gemcitabine-cisplatin or, in patients with impaired renal function, gemcitabine-carboplatin. Follow-up visits to monitor for signs of recurrence occurred at the same frequency in both treatment arms; namely, at 4, 7, 10, and 13 weeks, corresponding to the end of each chemotherapy treatment cycle. Patients underwent imaging and cystoscopy at each follow-up visit. Disease-free survival within a 3-year time frame comprised the primary endpoint; overall survival (OS) and patient-reported quality of life comprised key secondary endpoints. At a median follow-up of 48.1 months, 52 of the 129 patients in the surveillance group (40.3%), and 41 of the 131 patients in the chemotherapy group (31.3%) had died. Researchers reported a 3-year disease-free survival rate of 71% in the chemotherapy group and 46% in the surveillance group; the 3-year OS rate was 79% in the chemotherapy group and 67% in the surveillance group. In the chemotherapy group, 44% of participants experienced grade ≥3 treatment-emergent adverse events, as compared with only 4% of participants in the surveillance group. These adverse events were consistent with those previously reported for this chemotherapy protocol. Chemotherapy did not have any long-term toxicity associated with it. There were no differences in quality of life outcomes between the groups. The improved DFS outcomes achieved by patients treated with platinum-based chemotherapy within 90 days post-nephroureterectomy have prompted researchers to recommend this protocol be considered a new standard of care for these UTUC patients [2].

  1. Birtle AJ. Updated outcomes of POUT: A phase III randomized trial of peri-operative chemotherapy versus surveillance in upper tract urothelial cancer (UTUC). ASCO Genitourinary Cancers Symposium, 11–13 February 2021.
  2. Birtle A, et al. Lancet. 2020 Apr 18;395(10232):1268-1277.