Downstaging of Muscle-Invasive Bladder Cancer Using Neoadjuvant Gemcitabine and Cisplatin or Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin as Single Regimens or as Switch Therapy Modalities

Platinum-based neoadjuvant chemotherapy (NAC) is widely used for treating muscle-invasive bladder cancer (MIBC). A systematic review was performed following PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched up to December 2020. We conducted a meta-analysis to compare the oncologic outcomes of ddMVAC (dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin) and GC (gemcitabine and cisplatin), which are the most widely used NAC regimens. Endpoints included pathologic complete response (pCR), pathologic downstaging (pDS), overall survival (OS), and cancer-specific survival (CSS). Five studies, with a total of 1206 patients, were included for meta-analysis. pCR was observed in 35.2% of the ddMVAC arm and in 25.1% of the GC arm, and pCR was significantly higher in ddMVAC than in GC (odds ratio (OR), 1.45; 95% confidence interval (CI), 1.11–1.89; p = 0.006). There was no significant difference in pDS (OR, 1.37; CI, 0.84–2.21; p = 0.20). OS was significantly higher in ddMVAC than in GC (hazard ratio, 2.16; CI, 1.42–3.29; p = 0.0004). Only one study reported CSS outcomes. The results of this analysis indicate that ddMVAC is superior to GC in terms of pCR and OS, suggesting that ddMVAC is more effective than GC in NAC for MIBC. However, this should be interpreted with caution because of the inherent limitations of retrospective studies.

Download Full-text

Perioperative Treatment in Muscle-invasive Bladder Cancer: Analysis of Secondary Endpoints in a Randomized Trial Comparing Gemcitabine and Cisplatin Versus Dose-dense Methotrexate, Vinblastine, Adriamycin, and Cisplatin

European Urology ◽

10.1016/j.eururo.2020.09.018 ◽

2020 ◽

Author(s):

Irbaz Bin Riaz ◽

Syed A. Hussain

Keyword(s):

Bladder Cancer ◽

Randomized Trial ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Perioperative Treatment ◽

Secondary Endpoints ◽

Muscle Invasive ◽

Dose Dense ◽

Gemcitabine And Cisplatin

Download Full-text

Multicenter Prospective Phase II Trial of Neoadjuvant Dose-Dense Gemcitabine Plus Cisplatin in Patients With Muscle-Invasive Bladder Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2017.75.0158 ◽

2018 ◽

Vol 36 (19) ◽

pp. 1949-1956 ◽

Cited By ~ 45

Author(s):

Gopa Iyer ◽

Arjun V. Balar ◽

Matthew I. Milowsky ◽

Bernard H. Bochner ◽

Guido Dalbagni ◽

...

Keyword(s):

Bladder Cancer ◽

Phase Ii ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Durable Response ◽

Term Survival ◽

Gene Alteration ◽

End Point ◽

Muscle Invasive ◽

Dose Dense

Purpose Neoadjuvant chemotherapy followed by radical cystectomy (RC) is a standard of care for the management of muscle-invasive bladder cancer (MIBC). Dose-dense cisplatin-based regimens have yielded favorable outcomes compared with standard-dose chemotherapy, yet the optimal neoadjuvant regimen remains undefined. We assessed the efficacy and tolerability of six cycles of neoadjuvant dose-dense gemcitabine and cisplatin (ddGC) in patients with MIBC. Patients and Methods In this prospective, multicenter phase II study, patients received ddGC (gemcitabine 2,500 mg/m2 on day 1 and cisplatin 35 mg/m2 on days 1 and 2) every 2 weeks for 6 cycles followed by RC. The primary end point was pathologic downstaging to non–muscle-invasive disease (< pT2N0). Patients who did not undergo RC were deemed nonresponders. Pretreatment tumors underwent next-generation sequencing to identify predictors of chemosensitivity. Results Forty-nine patients were enrolled from three institutions. The primary end point was met, with 57% of 46 evaluable patients downstaged to < pT2N0. Pathologic response correlated with improved recurrence-free survival and overall survival. Nineteen patients (39%) required toxicity-related dose modifications. Sixty-seven percent of patients completed all six planned cycles. No patient failed to undergo RC as a result of chemotherapy-associated toxicities. The most frequent treatment-related toxicity was anemia (12%; grade 3). The presence of a presumed deleterious DNA damage response (DDR) gene alteration was associated with chemosensitivity (positive predictive value for < pT2N0 [89%]). No patient with a deleterious DDR gene alteration has experienced recurrence at a median follow-up of 2 years. Conclusion Six cycles of ddGC is an active, well-tolerated neoadjuvant regimen for the treatment of patients with MIBC. The presence of a putative deleterious DDR gene alteration in pretreatment tumor tissue strongly predicted for chemosensitivity, durable response, and superior long-term survival.

Download Full-text