Disease Management of Clinical Complete Responders to Neoadjuvant Chemotherapy of Muscle-Invasive Bladder Cancer: A Review of Literature

Wu, Jie; Xie, Ruiyang; Cao, Chuanzhen; Shang, Bingqing; Shi, Hongzhe; Shou, Jianzhong

doi:10.3389/fonc.2022.816444

Cited by 7 publications

(4 citation statements)

References 75 publications

(94 reference statements)

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“…As a result, cCR is then proposed as an additional measure endpoint for pCR to evaluate disease status before RC. This has paved the way for a new treatment approach, focusing on bladder-preservation strategies for patients who achieve cCR after neoadjuvant therapy [ 16 ]. Numerous studies suggest that MIBC patients who achieved cCR to NAC had exhibited high survival rates with bladder preservation.…”

Section: Discussionmentioning

confidence: 99%

Effect of Clinical Complete Remission Following Neoadjuvant Pembrolizumab or Chemotherapy in Bladder-Preservation Strategy in Patients with Muscle-Invasive Bladder Cancer Declining Definitive Local Therapy

Chang,

Chen,

Chang

et al. 2024

Cancers

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This study aimed to evaluate the outcomes and identify the predictive factors of a bladder-preservation approach incorporating maximal transurethral resection of bladder tumor (TURBT) coupled with either pembrolizumab or chemotherapy for patients diagnosed with muscle-invasive bladder cancer (MIBC) who opted against definitive local therapy. We conducted a retrospective analysis on 53 MIBC (cT2-T3N0M0) patients who initially planned for neoadjuvant pembrolizumab or chemotherapy after maximal TURBT but later declined radical cystectomy and radiotherapy. Post-therapy clinical restaging and conservative bladder-preservation measures were employed. Clinical complete remission was defined as negative findings on cystoscopy with biopsy confirming the absence of malignancy if performed, negative urine cytology, and unremarkable cross-sectional imaging (either CT scan or MRI) following neoadjuvant therapy. Twenty-three patients received pembrolizumab, while thirty received chemotherapy. Our findings revealed that twenty-three (43.4%) patients achieved clinical complete response after neoadjuvant therapy. The complete remission rate was marginally higher in pembrolizumab group in comparison to chemotherapy group (52.1% vs. 36.7%, p = 0.26). After a median follow-up of 37.6 months, patients in the pembrolizumab group demonstrated a longer PFS (median, not reached vs. 20.2 months, p = 0.078) and OS (median, not reached vs. 26.8 months, p = 0.027) relative to those in chemotherapy group. Those achieving clinical complete remission post-neoadjuvant therapy also exhibited prolonged PFS (median, not reached vs. 10.2 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.004). In the multivariate analysis, clinical complete remission subsequent to neoadjuvant therapy was independently associated with superior PFS and OS. In conclusion, bladder preservation emerges as a viable therapeutic strategy for a carefully selected cohort of MIBC patients without definitive local therapy, especially those achieving clinical complete remission following neoadjuvant treatment. For patients unfit for chemotherapy, pembrolizumab offers a promising alternative treatment option.

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Section: Discussionmentioning

confidence: 99%

Effect of Clinical Complete Remission Following Neoadjuvant Pembrolizumab or Chemotherapy in Bladder-Preservation Strategy in Patients with Muscle-Invasive Bladder Cancer Declining Definitive Local Therapy

Chang,

Chen,

Chang

et al. 2024

Cancers

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“…Immunotherapy, such as immune checkpoint blockade, now offers a novel avenue of treatment for BLCA, improving the survival of patients with advanced bladder Gene sets with a nominal P-value <0.05 and a false discovery rate q-value <0.05 were considered significant. cancer; however, the results remain unsatisfactory (18,19). Therefore, there is an urgent need for new biomarkers both for early screening and for the assessment of treatment effectiveness in bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological and prognostic significance of Ephrin A3 in bladder urothelial carcinoma

Wang,

Hu,

Shen

et al. 2023

Oncol Lett

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Ephrin A3 (EFNA3) is a member of the Eph/ephrin tyrosine kinase family, which is associated with multiple signaling pathways involved in cell growth and tumor cell metastasis. Aberrant regulation of EFNA3 is associated with the occurrence and development of various types of cancer. However, despite the high incidence of EFNA3 upregulation in cancer, studies concerning EFNA3 in urothelial carcinoma have not, to the best of our knowledge, been conducted. In the present study, bioinformatics analyses using data from multiple online databases were performed to confirm the upregulation of EFNA3 in bladder cancer. The co-expression gene set of EFNA3 and enriched signaling pathways were also analyzed. In addition, immunohistochemistry was conducted to detect EFNA3 expression in 491 clinically confirmed bladder urothelial carcinoma samples and 80 non-cancerous bladder tissues. Kaplan-Meier survival analysis, binary logistic regression analysis, and Cox regression analysis were conducted to confirm the validity of EFNA3 in predicting patient prognosis and its significance in clinical pathology. Statistical analysis demonstrated a significant association between EFNA3 expression levels with tumor size, lymph node metastasis, distant metastasis, and pathological grade. In conclusion, high EFNA3 expression may be a potential biomarker that indicates bladder tumor occurrence and patient prognosis.

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“…At present, CDDP-based neoadjuvant chemotherapy (NAC) accompanied by radical cystectomy is regarded as a frontline treatment for patients with aggressive UC (50).…”

Section: Characteristics Of Cebpd Responsive To Cisplatin Treatment I...mentioning

confidence: 99%

The biological impacts of CEBPD on urothelial carcinoma development and progression

Chan

Shiue

2023

Front. Oncol.

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Urothelial carcinoma (UC), which includes urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC), is one of the most common malignancies worldwide. Accordingly, a comprehensive understanding of the underlying mechanism governing UC development is compulsory. Aberrant CCAAT/enhancer-binding protein delta (CEBPD), a transcription factor, displays an oncogene or tumor suppressor depending on tumor type and microenvironments. However, CEBPD has been reported to possess a clear oncogenic function in UC through multiple regulation pathways. Genomic amplification of CEBPD triggered by MYC-driven genome instability is frequently examined in UC that drives CEBPD overexpression. Upregulated CEBPD transcriptionally suppresses FBXW7 to stabilize MYC protein and further induces hexokinase II (HK2)-related aerobic glycolysis that fuels cell growth. Apart from the MYC-dependent pathway, CEBPD also downregulates the level of hsa-miR-429 to enhance HK2-associated glycolysis and induce angiogenesis driven by vascular endothelial growth factor A (VEGFA). Additionally, aggressive UC is attributed to the tumor metastasis regulated by CEBPD-induced matrix metalloproteinase-2 (MMP2) overexpression. Furthermore, elevated CEBPD induced by cisplatin (CDDP) is identified to have dual functions, namely, CDDP-induced chemotherapy resistance or drive CDDP-induced antitumorigenesis. Given that the role of CEBPD in UC is getting clear but pending a more systemic reappraisal, this review aimed to comprehensively discuss the underlying mechanism of CEBPD in UC tumorigenesis.

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Disease Management of Clinical Complete Responders to Neoadjuvant Chemotherapy of Muscle-Invasive Bladder Cancer: A Review of Literature

Cited by 7 publications

References 75 publications

Effect of Clinical Complete Remission Following Neoadjuvant Pembrolizumab or Chemotherapy in Bladder-Preservation Strategy in Patients with Muscle-Invasive Bladder Cancer Declining Definitive Local Therapy

Effect of Clinical Complete Remission Following Neoadjuvant Pembrolizumab or Chemotherapy in Bladder-Preservation Strategy in Patients with Muscle-Invasive Bladder Cancer Declining Definitive Local Therapy

Clinicopathological and prognostic significance of Ephrin A3 in bladder urothelial carcinoma

The biological impacts of CEBPD on urothelial carcinoma development and progression

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