AUTHOR=Ferro Matteo , de Cobelli Ottavio , Musi Gennaro , Lucarelli Giuseppe , Terracciano Daniela , Pacella Daniela , Muto Tommaso , Porreca Angelo , Busetto Gian Maria , Del Giudice Francesco , Soria Francesco , Gontero Paolo , Cantiello Francesco , Damiano Rocco , Crocerossa Fabio , Farhan Abdal Rahman Abu , Autorino Riccardo , Vartolomei Mihai Dorin , Muto Matteo , Marchioni Michele , Mari Andrea , Scafuri Luca , Minervini Andrea , Longo Nicola , Chiancone Francesco , Perdona Sisto , De Placido Pietro , Verde Antonio , Catellani Michele , Luzzago Stefano , Mistretta Francesco Alessandro , Ditonno Pasquale , Caputo Vincenzo Francesco , Battaglia Michele , Zamboni Stefania , Antonelli Alessandro , Greco Francesco , Russo Giorgio Ivan , Hurle Rodolfo , Crisan Nicolae , Manfredi Matteo , Porpiglia Francesco , Di Lorenzo Giuseppe , Crocetto Felice , Buonerba Carlo TITLE=Three vs. Four Cycles of Neoadjuvant Chemotherapy for Localized Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy: A Retrospective Multi-Institutional Analysis JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.651745 DOI=10.3389/fonc.2021.651745 ISSN=2234-943X ABSTRACT=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.