Neoadjuvant chemotherapy with gemcitabine and cisplatin for muscle-invasive bladder cancer: multicenter retrospective study

Okabe, Ko; Shindo, Tetsuya; Maehana, Takeshi; Nishiyama, Naotaka; Hashimoto, Kimio; Itoh, Naoki; Takahashi, Atsushi; Taguchi, Keisuke; Tachiki, Hitoshi; Tanaka, Toshiaki; Masumori, Naoya

doi:10.1093/jjco/hyy122

Cited by 8 publications

(3 citation statements)

References 29 publications

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“…In another retrospective study, including 58 patients treated with neoadjuvant GC therapy and 74 treated with neoadjuvant MVAC, similar pathologic complete response rates were obtained (20.7% vs. 18.9%, P = 0.83, respectively). Of note, while neoadjuvant GC yielded improved 2-year OS rate than neoadjuvant MVAC for clinical T2 disease (95.2% vs. 70.8%, P = 0.036), in patients with T3 or more advanced disease, neoadjuvant MVAC provided more pT0 (20.0% vs. 5.6%, P = 0.07) and better 2-year OS than neoadjuvant GC (71.1% vs. 55.0%, P = 0.142), although the difference was not statistically significant ( 17 ).…”

Section: Discussionmentioning

confidence: 95%

Three vs. Four Cycles of Neoadjuvant Chemotherapy for Localized Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy: A Retrospective Multi-Institutional Analysis

et al. 2021

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BackgroundThree 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.MethodsPatients 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.ResultsA 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.ConclusionsOur 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.

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Section: Discussionmentioning

confidence: 95%

Three vs. Four Cycles of Neoadjuvant Chemotherapy for Localized Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy: A Retrospective Multi-Institutional Analysis

et al. 2021

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“…It has also been reported that GC therapy showed similar efficacy but less toxicity compared to MVAC ( Sonpavde et al, 2012 ). A recent retrospective study stated that GC therapy is comparable to MVAC and MVAC therapy is not superior to GC ( Okabe et al, 2018 ). The standard treatment protocol approach for metastatic bladder cancer shows shift towards GC therapy.…”

Section: Discussionmentioning

confidence: 99%

Targeting the anaphase-promoting complex/cyclosome (APC/C) enhanced antiproliferative and apoptotic response in bladder cancer

Nalkiran

Yildiz

Saydam

et al. 2023

Saudi Journal of Biological Sciences

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“…Patients with advanced or metastatic BC have a poor prognosis despite treatment with standard chemotherapies including combination therapy with gemcitabine and cisplatin (GC therapy) (2). Furthermore, in patients with muscle-invasive BC, the 2-year recurrence-free survival rate was reported to be 60.9% if pT0 was not obtained by neo-adjuvant GC chemotherapy (3). Accordingly, information regarding the pathological characteristics of BC cells is important to improve outcomes for patients with BC.…”

Section: Introductionmentioning

confidence: 99%

Pathological roles of c‑Met in bladder cancer: Association with cyclooxygenase‑2, heme oxygenase‑1, vascular endothelial growth factor‑A and programmed death ligand�1

et al. 2020

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c-Met is a receptor tyrosine kinase that binds a specific ligand, namely hepatocyte growth factor (HGF). The HGF/c-Met system is important for malignant aggressiveness in various types of cancer, including bladder cancer (BC). However, although phosphorylation is the essential step required for biological activation of c-Met, pathological roles of phosphorylated c-Met at the clinical and molecular levels in patients with BC are not fully understood. In the present study, the expression levels of c-Met and the phosphorylation of two of its tyrosine residues (pY1234/pY1235 and pY1349) were immunohistochemically examined in 185 BC tissues. The associations between these expression levels and cancer cell invasion, metastasis, and cyclooxygenase-2 (COX-2), heme oxygenase-1 (HO-1), VEGF-A and programmed death ligand 1 (PD-L1) levels were investigated. c-Met was associated with muscle invasion (P= 0.021), as well as the expression levels of HO-1 (P= 0.028) and PD-L1 (P<0.001), whereas pY1349 c-Met was associated with muscle invasion (P=0.003), metastasis (P=0.025), and COX-2 (P=0.017), HO-1 (P=0.031) and PD-L1 (P= 0.001) expression. By contrast, pY1234/1235 c-Met was associated with muscle invasion and metastasis (P= 0.006 and P= 0.012, respectively), but not with the panel of cancer-associated molecules. Furthermore, COX-2 and PD-L1 expression were associated with muscle invasion and metastasis, respectively (P= 0.045 and P= 0.036, respectively). Hence, c-Met serves important roles in muscle invasion by regulating HO-1 and PD-L1, whereas its phosphorylation at Y1349 is associated with muscle invasion and metastasis via the regulation of COX-2, HO-1 and PD-L1 in patients with BC. Furthermore, phosphorylation at Y1234/1235 may lead to muscle invasion and metastasis via alternate mechanisms associated with c-Met and pY1349 c-Met.

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Neoadjuvant chemotherapy with gemcitabine and cisplatin for muscle-invasive bladder cancer: multicenter retrospective study

Abstract: Neoadjuvant GC had no inferiority in oncological outcomes to MVAC for MIBC.

Cited by 8 publications

References 29 publications

Three vs. Four Cycles of Neoadjuvant Chemotherapy for Localized Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy: A Retrospective Multi-Institutional Analysis

Three vs. Four Cycles of Neoadjuvant Chemotherapy for Localized Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy: A Retrospective Multi-Institutional Analysis

Targeting the anaphase-promoting complex/cyclosome (APC/C) enhanced antiproliferative and apoptotic response in bladder cancer

Pathological roles of c‑Met in bladder cancer: Association with cyclooxygenase‑2, heme oxygenase‑1, vascular endothelial growth factor‑A and programmed death ligand�1

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