A role for neoadjuvant gemcitabine plus cisplatin in muscle‐invasive urothelial carcinoma of the bladder

Abstract

BACKGROUND. Neoadjuvant cisplatin‐based chemotherapy improves survival in muscle‐invasive urothelial cancer, with MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) considered the standard regimen. Gemcitabine plus cisplatin (GC) has similar efficacy and less toxicity than MVAC in metastatic disease, but is untested as neoadjuvant treatment. METHODS. The authors retrospectively evaluated patients with muscle‐invasive urothelial carcinoma who received neoadjuvant GC before radical cystectomy between November 2000 and December 2006 at Memorial Sloan‐Kettering Cancer Center. Post‐therapy pathological downstaging to either residual disease at cystectomy (pT0) or no residual muscle‐invasion (<pT2, ie, pT0, pTIS, pT1), chemotherapy delivery, and disease‐free survival were the endpoints of interest. For comparison, similar endpoints were assessed in a historical cohort treated with neoadjuvant MVAC. RESULTS. Four cycles of neoadjuvant GC were given over 12 weeks (n = 42). Thirty‐nine (93%) of 42 patients received 4 cycles, with a median 91% drug delivery for cisplatin and 90% for gemcitabine. The pT0 proportion was 26% (95% confidence interval [CI], 14‐42), and no residual muscle‐invasive disease proportion (<pT2) was 36% (95% CI, 21‐52); pT0 was achieved in 28% (95% CI, 16‐42) and <pT2 in 35% (95% CI, 23‐49) of 54 MVAC‐treated patients. All 15 GC patients achieving <pT2 pathologic stage remained disease‐free at a median follow‐up of 30 months. CONCLUSIONS. Neoadjuvant GC is feasible and allows for timely drug delivery. The proportion of GC‐treated patients whose primary tumors were downstaged, with prolonged disease‐free survival and minimal or no residual disease, was similar to MVAC‐treated patients. Cancer 2008. © 2008 American Cancer Society.

Predictors of referral for neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer and changes in practice over time

“…In a previously described case series from Alberta, receipt of NACT plus cystectomy versus cystectomy alone was significantly associated with tumour down staging (56.3% vs. 25.9%, respectively, p = 0.009), 16 similar to results reported by others. 27,28 Average surgeon caseload was not associated with receipt of NACT consultation or OS. However, there was a trend towards NACT consultation and reduced mortality with increasing caseload.…”

Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Systematic Review and Two-Step Meta-Analysis

“…Although the study by Cortesi et al was not published, it was included in previous meta-analyses [6,7] and therefore was included in our analysis. For the second step of the meta-analysis, a total of 13 reports met the inclusion criteria.Notably, partof the patient informationcontained inthe studies by Dash et al [17], Pal et al [18], and Alva et al [19] were later incorporated into a larger investigation by Galsky et al [20], whereas part of the patient information contained in the study by Fairey et al [21] was later incorporated into the investigation by Zargar et al [22]. We included all 13 studies in our analysis because some clinical information, such as tumor downstaging, was available in only small studies, but we also repeated our analysis excluding studies with redundant information.…”

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

“…Regimen and dosing recommendations are mainly based on studies in advanced disease. 17,22,[35][36][37] Carboplatin has not demonstrated a survival benefit and should not be substituted for cisplatin in the perioperative setting. It should be noted that patients with tumors that are ≤pT2 and have no nodal involvement or lymphovascular invasion after cystectomy are considered to have lower risk and are not recommended to receive adjuvant chemotherapy.…”