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
Division of Urology of European Institute of Oncology (IEO), IRCCS, Milan, Italy.
Department of Oncology and Hematology Oncology, Faculty of Medicine and Surgery, University of Milan, Milan, Italy.
Front Oncol. 2021 May 11;11:651745. doi: 10.3389/fonc.2021.651745. eCollection 2021.
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.
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.
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.
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.
对于肌层浸润性膀胱癌患者，三或四个周期的顺铂为基础的化疗是膀胱切除术之前的标准新辅助治疗。尽管美国国立综合癌症网络（NCCN）指南推荐4个周期的顺铂-吉西他滨方案，但在临床实践中也普遍采用三个周期的方案。在这项多中心回顾性研究中，我们评估了一大组同质的尿路上皮膀胱癌（UBC）患者，这些患者接受了三或四个周期的新辅助顺铂-吉西他滨治疗，随后接受根治性膀胱切除术，以探讨三个周期与四个周期的治疗是否与不同的结果相关。
这项回顾性研究纳入的组织学确诊为肌层浸润性UBC的患者，在接受根治性膀胱切除术加淋巴结清扫术前，必须接受3个周期（A组）或4个周期（B组）的顺铂-吉西他滨作为新辅助治疗。比较A组和B组之间的结果，包括病理降期至非肌层浸润性疾病、病理完全缓解（定义为无疾病-ypT0）、总生存和癌症特异性生存以及复发时间。
这项回顾性研究纳入了在14个不同的大型机构接受治疗的219例患者。接受3个周期（A组）与4个周期（B组）新辅助顺铂-吉西他滨治疗的患者分别为160例（73.1%）和59例（26.9%）。在单因素分析中，新辅助周期数与病理完全缓解、病理降期、复发时间、癌症特异性生存和总生存均无关。值得注意的是，在单因素分析中，B组患者与A组相比显示出更差的非癌症特异性总生存（HR = 2.53；95%CI = 1.05 - 6.10；p = 0.046），尽管这一发现未在多因素分析中得到证实。
我们的研究结果表明，在新辅助治疗中，与4个周期相比，3个周期的顺铂-吉西他滨可能同样有效，且长期毒性更小。
