Favourable pathologic response rate with neoadjuvant chemotherapy in high-risk upper tract urothelial carcinoma

In a phase 2 trial, neoadjuvant chemotherapy with gemcitabine plus cisplatin had a favourable pathologic response rate in patients with high-risk upper tract urothelial carcinoma.

Upper tract urothelial carcinoma is a rare but deadly disease; 5-year cancer-specific mortality rates for T2–T4 disease ranges from 21% to 59%. Irrespective of stage, patients with high-grade disease have a significantly worse prognosis [1]. Previously, the POUT trial (NCT01993979) demonstrated that adjuvant gemcitabine-platinum chemotherapy improves disease-free survival in patients with advanced upper tract urothelial carcinoma [2]. In addition, neoadjuvant chemotherapy has proven survival benefits for invasive urothelial carcinoma of the bladder, yet its role in upper tract urothelial carcinoma remains undefined.

The current multicentre, prospective, single-arm, phase 2 study (NCT01261728) evaluated neoadjuvant chemotherapy with gemcitabine and cisplatin in patients with high-risk upper tract urothelial carcinoma. A total of 57 patients received up to 4 cycles of gemcitabine/cisplatin prior to surgical resection and lymph node dissection; 40 participants (70%) tolerated all 4 cycles of gemcitabine/cisplatin, and all participants proceeded to surgery. The primary study endpoint was pathologic response rate (defined as <pT2N0). Dr Wesley Yip (Memorial Sloan Kettering Cancer Center, NY, USA) presented the results [3].

Among 57 patients evaluated, 36 (63%) demonstrated pathologic response, meeting the primary endpoint of the study. A complete response was noted in 11 patients (19%), defined as pT0N0. With a median follow-up of 3.1 years among survivors, 2- and 5-year progression-free survival (PFS) was 78% and 65%; 2- and 5-year overall survival (OS) was 93% and 79%. Participants demonstrating pathologic response had improved PFS and OS compared with those who did not (2-year PFS 91% vs 52%, P<0.001; 2-year OS 100% vs 80%, P<0.001). Overall, the chemotherapy was well tolerated.

“The results show a favourable pathologic response rate with neoadjuvant chemotherapy in patients with high-risk upper tract urothelial carcinoma and this might be considered a new standard of care option for these patients,” concluded Dr Yip.

1. Olgac S, et al. Am J Surg Pathol. 2004;28:1545–1552.
2. Britle A, et al. Lancet. 2020;395:1268–1277.
3. Yip W, et al. Final results of a multicenter prospective phase II clinical trial of gemcitabine and cisplatin as neoadjuvant chemotherapy in patients with high-grade upper tract urothelial carcinoma. Abstract 440, ASCO GU 2022, 17–19 February.

 

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Posted on 8 April 202217 May 2024