Neoadjuvant therapy is well established for pure muscle-invasive urothelial carcinoma; however, its role in tumors with histological variants remains controversial, particularly outside European and North American cohorts. This study evaluated the impact of neoadjuvant therapy in Latin American patients with urothelial carcinoma and histological variants undergoing radical cystectomy.
We conducted a retrospective analysis of patients who underwent radical cystectomy between 2005 and 2025 at a tertiary oncology center. Patients with urothelial carcinoma and histological variants identified on transurethral resection or cystectomy specimens were included. Clinical, pathological, and oncologic outcomes were collected. Survival outcomes were compared between patients treated with and without neoadjuvant therapy.
The initial cohort included 733 patients, with a mean age of 67 years; 66.3% were male. The most frequent variants were squamous (56%), glandular (11.2%), and micropapillary (8%). Among patients receiving neoadjuvant therapy, complete pathological response (pT0) occurred in 10% (n = 5) and positive surgical margins in 12% (n = 6), compared with 4.65% (n = 6) and 18.6% (n = 24), respectively, in those treated with upfront surgery. No significant survival differences were observed in the overall cohort. In the squamous variant, pT0 was achieved in 8% (n = 2) of patients receiving neoadjuvant therapy versus 1.32% (n = 1) without it. In the micropapillary variant, pT0 rates were 16.67% (n = 2) with neoadjuvant therapy and 25% (n = 3) without, while nodenegative disease (pN0) occurred in 66.67% (n = 8) and 50% (n = 6), respectively. In the glandular variant, neoadjuvant therapy was associated with numerically higher pT0 rates (20% vs. 8.33%) and improved survival outcomes; however, these findings should be interpreted cautiously given the limited sample size and number of events.
In this largest Latin American cohort to date, neoadjuvant therapy conferred a clear oncologic benefit only in patients with glandular differentiation. For other histological variants, upfront radical cystectomy remains the preferred approach when complete resection is feasible.
Clinical genitourinary cancer. 2026 Mar 11 [Epub ahead of print]
Caio Vinícius Suartz, Richard Dobrucki de Lima, Débora Narumi Demitrol Setoue, Pedro Henrique Souza Brito, Pedro Vasconcelos Henry Sant'Anna, Maria Fernanda Dias Azevedo, Caio Mazzoneto Teófilo de Moraes, Luiz Guilherme Pereira da Silva, Leonam Bringhenti Schumacher, Victor Vion Sant Galvez, Maurício Cordeiro Dener, William Carlos Nahas, Leopoldo Alves Ribeiro-Filho
Department of Urology, Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada. Electronic address: ., Department of Urology, University of São Paulo, Sao Paulo, SP, Brazil.