Three vs. Four Cycles of Neoadjuvant Chemotherapy for Localized Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy: A Retrospective Multi-Institutional Analysis

Matteo Ferro, Ottavio de Cobelli, Gennaro Musi, Giuseppe Lucarelli, Daniela Terracciano, Daniela Pacella, Tommaso Muto, Angelo Porreca, Gian Maria Busetto, Francesco Del Giudice, Francesco Soria, Paolo Gontero, Francesco Cantiello, Rocco Damiano, Fabio Crocerossa, Abdal Rahman Abu Farhan, Riccardo Autorino, Mihai Dorin Vartolomei, Matteo Muto, Michele MarchioniAndrea Mari, Luca Scafuri, Andrea Minervini, Nicola Longo, Francesco Chiancone, Sisto Perdona, Pietro De Placido, Antonio Verde, Michele Catellani, Stefano Luzzago, Francesco Alessandro Mistretta, Pasquale Ditonno, Vincenzo Francesco Caputo, Michele Battaglia, Stefania Zamboni, Alessandro Antonelli, Francesco Greco, Giorgio Ivan Russo, Rodolfo Hurle, Nicolae Crisan, Matteo Manfredi, Francesco Porpiglia, Giuseppe Di Lorenzo, Felice Crocetto, Carlo Buonerba

Research output: Contribution to journalArticlepeer-review


Background: Three or four cycles of cisplatin-based chemotherapy is the standard neoadjuvant treatment prior to cystectomy in patients with muscle-invasive bladder cancer. Although NCCN guidelines recommend 4 cycles of cisplatin-gemcitabine, three cycles are also commonly administered in clinical practice. In this multicenter retrospective study, we assessed a large and homogenous cohort of patients with urothelial bladder cancer (UBC) treated with three or four cycles of neoadjuvant cisplatin-gemcitabine followed by radical cystectomy, in order to explore whether three vs. four cycles were associated with different outcomes.

Methods: Patients with histologically confirmed muscle-invasive UBC included in this retrospective study had to be treated with either 3 (cohort A) or 4 (cohort B) cycles of cisplatin-gemcitabine as neoadjuvant therapy before undergoing radical cystectomy with lymphadenectomy. Outcomes including pathologic downstaging to non-muscle invasive disease, pathologic complete response (defined as absence of disease -ypT0), overall- and cancer-specific- survival as well as time to recurrence were compared between cohorts A vs. B.

Results: A total of 219 patients treated at 14 different high-volume Institutions were included in this retrospective study. Patients who received 3 (cohort A) vs. 4 (cohort B) cycles of neoadjuvant cisplatin-gemcitabine were 160 (73,1%) vs. 59 (26,9%).At univariate analysis, the number of neoadjuvant cycles was not associated with either pathologic complete response, pathologic downstaging, time to recurrence, cancer specific, and overall survival. Of note, patients in cohort B vs. A showed a worse non-cancer specific overall survival at univariate analysis (HR= 2.53; 95 CI= 1.05 - 6.10; p=0.046), although this finding was not confirmed at multivariate analysis.

Conclusions: Our findings suggest that 3 cycles of cisplatin-gemcitabine may be equally effective, with less long-term toxicity, compared to 4 cycles in the neoadjuvant setting.

Original languageEnglish
Pages (from-to)651745
JournalFront. Oncol.
Publication statusPublished - 2021


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