Bladder Cancer最新文献

Abstract

BACKGROUND:

Bladder cancer is the second most common urological cancer worldwide, with low early diagnosis and high mortality. The limited progress in diagnostics and treatment greatly impedes the survival of bladder cancer patients.

OBJECTIVE:

Potential therapeutic biomarkers are urgently needed for future clinical treatment.

METHODS:

We analyzed the sequencing data and corresponding clinicopathological features and survival information of bladder cancer patients in the TCGA database and identified a new zinc finger protein 485 gene, termed ZNF485, which is highly expressed in the tissues of bladder cancer patients and was verified in cells, animal models and tissue microarrays.

RESULTS:

We found that inhibition of ZNF485 in the bladder cancer cell lines T24 and 5637 obviously inhibited proliferation and promoted the apoptosis of cancer cells. Furthermore, wound healing and invasion assays showed that downregulation of ZNF485 significantly decreased the mobility and invasion of T24 and 5637 cells. In addition, ZNF485-shRNA transfection obviously inhibited tumor growth in nude mice. Immunohistochemical results of clinical samples showed that the expression level of ZNF485 protein in cancer tissues was higher than that in adjacent tissues. Mechanistic analysis identified possible downstream target genes.

CONCLUSIONS:

Taken together, the results provide evidence that ZNF485 is involved in bladder cancer proliferation and might be a potential therapeutic biomarker for the treatment of this disease

Abstract

BACKGROUND:

Effective maintenance therapy for urothelial carcinoma (UC) is needed to delay progression after first-line chemotherapy.

OBJECTIVE:

To evaluate S-588410, a cancer peptide vaccine containing five human leukocyte antigen (HLA)-A ^*24:02-restricted epitope peptides derived from five cancer-testis antigens (DEPDC1, MPHOSPH1, URLC10, CDCA1, and KOC1) in chemotherapy-treated, clinically stable patients with advanced or metastatic UC

MATERIALS AND METHODS:

This open-label, international, phase 2 trial enrolled patients with UC who had completed≥4 cycles of first-line platinum-containing chemotherapy without disease progression. Forty-five HLA-A ^*24:02-positive patients received subcutaneous injections of S-588410 (Montanide ISA 51 VG with 1 mg/mL of each peptide) weekly for 12 weeks then once every 2 weeks thereafter for up to 24 months. Thirty-six HLA-A ^*24:02-negative patients did not receive S-588410 (observation group). The primary endpoint was the rate of cytotoxic T-lymphocyte (CTL) induction against≥1 of the peptides at 12 weeks.

RESULTS:

The CTL induction rate in the S-588410 group was 93.3% (p < 0.0001, one-sided binomial test with a rate of≤50% as the null hypothesis). The antitumor response rate was 8.9% in the S-588410 group and 0% in the observation group; median progression-free survival was 18.1 versus 12.5 weeks and median overall survival was 71.0 versus 99.0 weeks, respectively. The most frequent treatment-emergent adverse event was injection-site reactions (47 events, grades 1–3) reported in 93.3% (n = 42/45) of participants.

CONCLUSIONS:

S-588410 demonstrated a high CTL induction rate, acceptable safety profile, and modest clinical response, as maintenance therapy in participants with advanced or metastatic UC who had received first-line platinum-based chemotherapy (EudraCT 2013-005274-22).

Marker research, and in particular urine bladder cancer marker research throughout the past three decades, devours enormous scientific resources in terms of manpower (not to mention time spent on reviewing and editorial efforts) and financial resources, finally generating large numbers of manuscripts without affecting clinical decision making. This is mirrored by the fact that current guidelines do not recommend marker use due to missing level 1 evidence. Although we recognize the problems and obstacles, the authors of this commentary feel that the time has come to abandon the current procedures and move on to prospective trial designs implementing marker results into clinical decision making. Our thoughts and concerns are summarized in this comment.

Abstract

BACKGROUND:

The benefit of surgery of the primary tumor in metastatic bladder cancer is unknown.

OBJECTIVE:

Perform a comprehensive contemporary literature review on the benefit of surgery of the primary tumor in metastatic bladder cancer.

METHODS:

Ovid MEDLINE, Ovid EMBASE, and Cochrane Library from January 1, 1990 to April 20, 2020 were queried for relevant articles published in English. Each article was evaluated by at least two content experts prior to inclusion which were blinded to the other’s evaluation. A third content expert was used when there was not a unanimous decision. Additional articles were added at the discretion of the authors.

RESULTS:

Long-term survival is possible in patients with initially unresectable and/or limited metastatic disease. Multi-modal therapy with chemotherapy and surgery have the most favorable outcomes when compared to single treatment modalities in selected populations. Patients who demonstrate a robust response to pre-surgical therapy are likely to benefit the most from consolidative surgery. Patients with distant metastatic disease may benefit from consolidative surgery; however, this benefit may only be seen in those with metastatic disease limited to one site.

CONCLUSIONS:

Surgery of the primary tumor in metastatic bladder cancer either in the setting of surgery alone, consolidative therapy or coupled with adjuvant therapy may be beneficial in well selected patients and should generally be limited to those who have a response to primary chemotherapy. Randomized clinical control trials are needed to further our understanding of the role of surgery in metastatic bladder cancer.

Systematic Review Registration number: CRD42020182861

Abstract

BACKGROUND:

MRI has been proposed as a new staging tool for bladder cancer (BC), but use is limited by its high costs and low availability. 29-MHz high-resolution micro-ultrasound (mUS) technology has been suggested as an alternative to detect BC and distinguish between muscle-invasive and non-muscle invasive BC.

OBJECTIVE:

The aim was to compare the diagnostic accuracy of mUS vs. magnetic resonance imaging (MRI) in differentiating NMIBC and MIBC at definitive pathological examination.

METHODS:

This is a prospective study of patients with a primary diagnosis of BC with either positive urine cytology (UC) or negative UC and a tumor size > 25 mm from a tertiary care high volume center. mUS, with the ExactVu system with an EV29L 29 MHz side-fire transducer, and a 3-Tesla MRI were performed before transurethral resection of bladder tumor (TURBT) in every patient before undergoing TURBT. We compared the imaging results with pathological reports.

RESULTS:

The analyzed population consisted of 58 individuals. The reported mUS and MRI sensitivity, specificity, positive, and negative predictive values were 85.0%, 76.3%, 65.4%, and 90.6%, versus 85.0%, 50.0%, 47.2%, and 86.4%, respectively. In accuracy analysis, the AUC for mUS and MRI were respectively 0.807 and 0.675.

CONCLUSIONS:

In our population mUS seems to have a better performance in distinguishing NMIBC from MIBC. The main limitation of mUS is the probe shape that makes its use problematic in cases with a large prostate and inadequate rectal preparation. Further studies with a larger population are ongoing to compare and validate these techniques in this setting.

Background: Bladder cancer (BC) is one of the most common malignancies (4.5%of all newly diagnosed cases worldwide). Most of the new BC cases are diagnosed as non-muscle invasive BC (NMIBC), needing continuous follow up after primary endoscopic therapy. Adjuvant bladder therapy with chemo- or immuno- agents, apart from the initial diagnosis, the strict surveillance program and the risk of recurrence, may have a major impact on the patients' physical and mental health.

Objective: We evaluated anxiety and quality of life (QoL) in patients who underwent surgery for NMIBC and followed a bladder instillation programme.

Methods: This is a prospective analysis of patients with histopathologically confirmed NMIBCs. Eligible were all adult patients with a single or multiple NMIBCs who underwent a transurethral tumor resection and followed a therapy with either BCG or Epirubicin instillations. The SF-36 questionnaire Physical and Mental health aspects were used for QoL assessment. Similarly, the STAI-Y was introduced for the state (STAI-Y1) and trait anxiety (STAI-Y2) evaluation.

Results: 117 eligible patients were screened, with 108 entering finally the study; 9 patients were excluded due to disease recurrence. 17 patients (15.7%) received Epirubicin (Ta-T1, Low Grade tumors), whereas 91 patients (84.3%) received BCG (T1, High Grade). Regarding SF-36 Physical a 6 months decrease was followed by an improvement at 12 months (p = 0.008). Similarly, an increase of the SF-36 Mental health score was identified (p = 0.03). In contrast to STAI-Y2 scores (p = 0.945), a long-term reduction of the state anxiety was identified (p = 0.001). Preoperative SF-36 Physical was inversely correlated with age (p = 0.029), while absence of alcohol was associated with lower mental health (p = 0.003). Overall, patient characteristics, habits and the administered treatment did not affect the postoperative QoL and anxiety.

Conclusion: Patient QoL and anxiety improved during follow up. Still, further larger scale studies are required to support our findings.

Background: Sedentarism is an important modifiable risk factor in the struggle against cancer. In the last decades, the relationship between physical activity and different types of cancer has been investigated in depth.

Objective: To provide an overview of the literature on the effectiveness of physical activity in reducing the risk to develop bladder cancer and improving health-related quality of life in patients.

Methods: A systematic review was conducted through a search of the Embase, Cochrane, PubMed, Scopus, and Web of Science (WOS) databases to seek information and PRISMA system to delimitate the research. Outcomes included in searches were physical activity, tobacco consumption, obesity, body mass index, and metabolic syndrome, associated with bladder cancer and quality of life.

Results: Database searches identified 394 records, of which 75 were duplicated. A total of 280 articles were excluded based on abstract screening. An additional 16 full-text articles were excluded because they did not meet the eligibility criteria. Overall, 21 of the 23 studies included in the review reported beneficial effects of physical activity in bladder cancer. The majority of papers found that physical activity is a significant factor in reducing the risk of bladder cancer. Moreover, physical activity improves health-related quality of life in bladder cancer survivors, and diminishes both recurrence and mortality in those who engage in regular activity. Lastly, physical inactivity is associated with increased body mass index, obesity, metabolic syndrome, type 2 diabetes and unfavourable energy balance, which led to a greater probability of suffering from bladder cancer.

Conclusions: These data reinforce the importance of promoting a healthy lifestyle to reduce the risk of bladder cancer and to improve survivorship and health-related quality of life of patients.