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

Yin, Ming; Joshi, Monika; Meijer, Richard P.; Glantz, Michael; Holder, Sheldon L.; Harvey, Harold A.; Kaag, Matthew; Putte, Elisabeth E. Fransen van de; Horenblas, Simon; Drabick, Joseph J.

doi:10.1634/theoncologist.2015-0440

Cited by 373 publications

(268 citation statements)

References 43 publications

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“…In retrospective analyses, pCR rates ranged from 19 to 31% with MVAC [8,13,14,22] . The pCR rate of 22.5% seen in our cohort using GC is at the lower end of this spectrum, which is in range with previous studies using GC ( Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…A subsequent meta-analysis included 13 retrospective studies with 1,067 patients treated with GC and 667 patients treated with MVAC. The results showed a pCR rate of 25.7% with GC compared to 24.3% with MVAC ( p = 0.37) [8] . In addition, a prospective evaluation of GC in the neoadjuvant setting has been reported from 3 small prospective trials including between 20 and 35 patients with a maximum median age of 65 years (online suppl.…”

Section: Introductionmentioning

confidence: 92%

“…A meta-analysis of over 3,000 patients confirmed that platinum-based neoadjuvant treatment leads to a 14% decrease in diseasespecific mortality ( p = 0.003) [7] . A recent 2-step metaanalysis confirmed the advantage of neoadjuvant chemotherapy in this setting with a significant benefit in overall survival (OS) (HR 0.87; 95% CI 0.79-0.96) [8] .…”

Section: Introductionmentioning

confidence: 99%

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Neoadjuvant Chemotherapy with Gemcitabine plus Cisplatin in Patients with Locally Advanced Bladder Cancer

Niedersüß-Beke

Puntus²,

Kunit

et al. 2017

Oncology

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Background: Neoadjuvant chemotherapy with methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) is the standard of care for muscle-invasive urothelial bladder cancer. Gemcitabine plus cisplatin (GC) shows similar efficacy with less toxicity in the metastatic setting and has therefore often been used interchangeably with MVAC. We report on the efficacy and safety of neoadjuvant GC in patients with locally advanced urothelial cancer. Materials and Methods: We prospectively evaluated 87 patients in 2 centers. Their median age was 68 years. Treatment consisted of 3× GC prior to radical cystectomy. The primary endpoint was pathologic response. The secondary endpoints were safety, progression-free survival (PFS), and overall survival (OS). Results: In all, 83 patients finished chemotherapy; 80 patients were evaluable for the primary endpoint. Pathologic complete response (pCR) was achieved in 22.5% and near pCR was seen in 33.7% of the patients. The 1-year PFS rate was 79.5% among those patients achieving ≤pT2 versus 100% among those patients achieving pCR or near pCR (p = 0.041). Five-year OS was 61.8% (95% CI 67.6 to NA). GC was well tolerated. Grade 3/4 toxicities occurred in 38% of the patients. There was no grade 3/4 renal toxicity, febrile neutropenia, or death. Conclusion: Neoadjuvant GC is a well-tolerated regimen. Although the pathologic response is lower than that reported with MVAC, our data support GC as a feasible option in the absence of a prospective randomized comparison, particularly for older patients, since its toxicity is lower than that of MVAC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Neoadjuvant Chemotherapy with Gemcitabine plus Cisplatin in Patients with Locally Advanced Bladder Cancer

Niedersüß-Beke

Puntus²,

Kunit

et al. 2017

Oncology

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“…A series of pathogenic factors affect the occurrence of bladder cancer, including aging, smoking and environmental pollution (1). The mortality rate of bladder cancer is increasing, even in childhood (1,2). The pathogenesis of bladder cancer is complex, and involves the activation of oncogenes and the inactivation of tumor suppressor genes.…”

Section: Introductionmentioning

confidence: 99%

Anticancer effect of miR-96 inhibitor in bladder cancer cell lines

et al. 2018

Oncol Lett

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Abstract. The present study aimed to investigate the role of microRNA-96 (miR-96) in the proliferation, invasion and apoptosis of bladder cancer cell lines, and the associated mechanisms. The expression of miR-96 and human ether-à-go-go-related (HERG1) potassium channel in the normal uroepithelium SV-HUC-1 cell line, and bladder cancer T24 and 5637 cell lines were examined using reverse transcription-polymerase chain reaction or/and western blotting. Transfection with miR-96 inhibitor or scrambled control (SC) was used to study the biological activities of miR-96 in bladder cancer cell lines. MTT, flow cytometric and Transwell assays were applied to detect cell viability, apoptosis and invasion, respectively. A dual-luciferase reporter assay was applied to determine the association between miR-96 and HERG1 expression. As demonstrated, miR-96 was highly expressed in the two bladder cancer cell lines, particularly in T24 cells. Following transfection with miR-96 inhibitor, miR-96 expression was significantly reduced in the T24 cell line, compared with SC. The miR-96 inhibitor suppressed cell proliferation and invasion, promoted apoptosis and arrested the cell cycle at the G 1 phase. Consistently, HERG1 was also highly expressed in the two bladder cancer cell lines at the mRNA and protein level, but not in the normal uroepithelium cell line. The miR-96 inhibitor also significantly decreased HERG1 expression compared with SC. The results of the dual-luciferase reporter assay indicated that miR-96 directly targeted wild-type HERG1. In conclusion, miR-96 inhibitor exhibited anticancer effects on bladder cancer cells by inhibiting proliferation and invasion of cells, and promoting their apoptosis. HERG1 was an important target of miR-96. These results provided experimental evidence supporting miR-96 as a therapeutic target for patients with bladder cancer.

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“…Gemcitabine has been considered to be included in NAC regimens because gemcitabine plus cisplatin has a better safety profile than MVAC [36]. A phase III trial comparing GC and MVAC in patients with transitional cell carcinoma of the urothelium demonstrated that both groups had similar efficacy with respect to response, time-to-progression and OS, whereas GC was associated with less toxicity than MVAC [37].…”

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confidence: 99%

Effect of cisplatin-based neoadjuvant chemotherapy on survival in patients with bladder cancer: a meta-analysis

Niu

et al. 2017

CIM

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Effect of cisplatin-based neoadjuvant chemotherapy on survival in patients with bladder cancer: a meta-analysis Abstract Purpose: Cisplatin-based neoadjuvant chemotherapy (NAC) has been shown to improve survival in patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy as compared with patients who underwent surgery alone. It has also been suggested as current standard of care in surgically-fit patients with MIBC. This meta-analysis assessed the effect of cisplatin-based NAC on survival in patients with bladder cancer.Source: PubMed, CENTRAL, and Embase were searched until November 22, 2016. Two-arm randomized controlled trials that compared cisplatin-based neoadjuvant chemotherapy plus local treatment versus the same local treatment without neoadjuvant chemotherapy were selected. Patients with histologically-confirmed bladder cancer (adenocarcinoma, transitional, or squamous-cell carcinoma) were included. The primary outcome was overall survival (OS).Principal findings: Of the 292 articles initially identified, 14 were included in the final analysis. Patients in the NAC group had similar OS as the local treatment (i.e., radiation therapy or cystectomy) group (pooled hazard ratio [HR] = 0.92, 95% confidence interval [CI]: 0.84 to 1.00, P=0.056). No difference in progress-free survival between two groups was observed (P=0.725). Subgroup analysis showed that OS was similar in patients treated with NAC plus radiotherapy or cystectomy compared with patients who received local treatment alone.Conclusions: Platinum-based NAC was associated with similar survival benefit as patients undergoing cystectomy and/or radiotherapy. No conclusion can be drawn about the optimal platinum-based combination to be used in the neoadjuvant setting.

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

Cited by 373 publications

References 43 publications

Neoadjuvant Chemotherapy with Gemcitabine plus Cisplatin in Patients with Locally Advanced Bladder Cancer

Neoadjuvant Chemotherapy with Gemcitabine plus Cisplatin in Patients with Locally Advanced Bladder Cancer

Anticancer effect of miR-96 inhibitor in bladder cancer cell lines

Effect of cisplatin-based neoadjuvant chemotherapy on survival in patients with bladder cancer: a meta-analysis

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