Department of Urology and Urological Oncology, Pomeranian Medical University, Szczecin, Poland.
Department of Oncology and Chemotherapy, Pomeranian Medical University, Szczecin, Poland.
PLoS One. 2021 Nov 3;16(11):e0259526. doi: 10.1371/journal.pone.0259526. eCollection 2021.
Neoadjuvant chemotherapy has become standard of care for cisplatin-eligible patients with muscle-invasive bladder cancer qualified to radical cystectomy, providing a modest increase in 5-year overall survival rate. Several regimens are being employed for neoadjuvant treatment, largely because of their efficacy in metastatic setting. There is however a scarcity of evidence on the optimal cytotoxic regimen for neoadjuvant chemotherapy.
We evaluated the efficacy of different protocols of neoadjuvant chemotherapy amongst patients who underwent radical cystectomy at our institution.
This is a single-center, retrospective, observational study including a cohort of 220 patients who underwent radical cystectomy between 2014 and 2020. The neoadjuvant chemotherapy cohort included 79 patients and was compared to the cohort of historical controls including 141 patients operated prior to routine administration of neoadjuvant chemotherapy and those who opted for upfront surgery.
Administration of neoadjuvant chemotherapy decreased the risk of overall and cancer-specific mortality HR = 0.625 (95% CI 0.414-0.944), p = 0.025 and HR = 0.579 (95% CI 0.348-0.964), p = 0.036. Rates of downstaging, complete responses, lymph node metastasis, extravesical extension and positive surgical margins significantly favored neoadjuvant chemotherapy. Out of cytotoxic regimens, dose-dense MVAC and gemcitabine-cisplatin were similarly efficacious providing 46.9% and 50% of downstaging to <ypT2N0 respectively, including 30.6% and 25% of complete remissions. However, only dose-dense MVAC was associated with reduction of all-cause and cancer specific mortality risk HR = 0.385 (95% CI 0.214-0.691) p = 0.001 and HR = 0.336 (95% CI 0.160-0.703), p = 0.004 respectively.
Our study implies that neoadjuvant chemotherapy with subsequent radical cystectomy provides significant improvement over upfront surgery in locoregional control and long-term prognosis of muscle-invasive bladder cancer. The urologic community should strive to maximize utilization of neoadjuvant chemotherapy, yet further research, including randomized control trials, is needed to validate superiority of dose-dense MVAC as the preferred regimen for cisplatin-eligible patients.
新辅助化疗已成为适合接受顺铂治疗且有根治性膀胱切除术适应证的肌层浸润性膀胱癌患者的标准治疗方法，可适度提高 5 年总生存率。目前有多种方案用于新辅助治疗，主要是因为它们在转移性疾病中的疗效。然而，对于新辅助化疗的最佳细胞毒性方案，证据仍然有限。
我们评估了我院接受根治性膀胱切除术的患者中不同新辅助化疗方案的疗效。
这是一项单中心、回顾性、观察性研究，纳入了 2014 年至 2020 年间接受根治性膀胱切除术的 220 例患者。新辅助化疗组包括 79 例患者，并与历史对照组（包括 141 例在常规应用新辅助化疗前接受手术的患者和选择直接手术的患者）进行比较。
新辅助化疗可降低总死亡率和癌症特异性死亡率的风险，HR=0.625（95%CI 0.414-0.944），p=0.025 和 HR=0.579（95%CI 0.348-0.964），p=0.036。降期、完全缓解、淋巴结转移、膀胱外延伸和阳性手术切缘的发生率均明显有利于新辅助化疗。在细胞毒性方案中，密集剂量 MVAC 和吉西他滨-顺铂同样有效，分别使<ypT2N0 的降期率达到 46.9%和 50%，包括 30.6%和 25%的完全缓解率。然而，只有密集剂量 MVAC 与降低全因死亡率和癌症特异性死亡率的风险相关，HR=0.385（95%CI 0.214-0.691），p=0.001 和 HR=0.336（95%CI 0.160-0.703），p=0.004。
我们的研究表明，新辅助化疗联合根治性膀胱切除术在局部区域控制和肌层浸润性膀胱癌的长期预后方面优于直接手术。泌尿外科医生应该努力最大限度地利用新辅助化疗，但还需要进一步的研究，包括随机对照试验，以验证密集剂量 MVAC 作为适合顺铂治疗的患者的首选方案的优越性。
