Bladder Cancer最新文献

Abstract

Intravesical therapy is a critical component in the management of non-muscle-invasive bladder cancer (NMIBC), as it reduces rates of disease recurrence and progression. However, the presence of physiologic barriers in the urothelium reduces the penetration and distribution of intravesical chemotherapy, thereby limiting the therapeutic potential. Much progress to overcome this challenge has been made in the realm of intravesical device-assisted therapy. Novel device-assisted treatments include hyperthermia, the radiofrequency-induced thermochemotherapy effect, electromotive drug administration, and implantable drug delivery systems. Notably, chemotherapy enhanced by these device-assisted systems has shown improved oncologic efficacy relative to standard intravesical chemotherapy and comparable outcomes relative to Bacillus Calmette-Guérin (BCG) therapy in patients with intermediate- or high-risk NMIBC. Recent studies also support the utility of device-assisted therapy as a salvage treatment option in patients with BCG-unresponsive disease. Ongoing randomized controlled trials and prospective investigations will further help clarify indications and long-term safety outcomes of these treatment modalities in NMIBC. Herein, we present a comprehensive review of device-assisted therapies and discuss their clinical utilities for the management of NMIBC in the modern era.

Abstract

BACKGROUND:

Standard 24-hour antibiotic prophylaxis is widely employed to minimize the risk of infection complications within 30 days following radical cystectomy. However, a considerable variety of protocols and drug combinations don’t prevent a high complication rate, ranging from 37 to 67%. This paper presents the interim analysis of the MACS clinical trial, comparing antibiotic prophylaxis regimens by duration.

OBJECTIVE:

To evaluate the rate of infection complications within 30 days following radical cystectomy by comparing standard 24-hour antibiotic prophylaxis (Group A) with a prolonged 120-hour regimen (Group B).

METHODS:

Patients were randomized in a 1 : 1 ratio. The primary endpoint was the evaluation of the frequency of infection complications. The secondary endpoints were the rate of re-administrating antibiotics and the dynamics of the inflammation biomarker.

RESULTS:

A total of 78 patients (85.0% of the sample size) were enrolled (Group A: 40 and Group B: 38). The baseline and perioperative features were balanced between groups. The overall complication rate was higher in Group A (65.0% vs. 41.1%, p = 0.043). The infection complication rate was 2.7 times higher in the standard antibiotic prophylaxis group: 37.5% compared to 18.4% cases in Group B (p = 0.041), and upper urinary tract infection was more frequent in Group A (22.5% vs. 2.6%). The prolonged antibiotic prophylaxis reduced the overall frequency of infection complications compared with standard 24-hour prophylaxis (RR = 0.12; 95% CI 0.02–0.88; p = 0.037).

CONCLUSIONS:

In this interim analysis, the administration of prolonged antibiotic prophylaxis over 120 hours appears to be safe and feasible, demonstrating a reduction in the total number of complications, particularly infection complications.

Abstract

BACKGROUND:

In 2023, an estimated 82,290 individuals were diagnosed with bladder cancer in the United States. For muscle-invasive bladder cancer (MIBC), the American Urological Association recommends offering radical cystectomy with cisplatin-based neoadjuvant chemotherapy. However, patients are increasingly requesting alternative treatments.

OBJECTIVE:

To describe factors influencing selection of radical cystectomy with cisplatin-based neoadjuvant chemotherapy (NAC + RC), radical cystectomy monotherapy (RC), or tri-modality therapy (TMT) among patients with MIBC.

METHODS:

Individual, semi-structured phone interviews were conducted with 18 adults who underwent MIBC treatment at the University of North Carolina, recruiting six patients each from three treatment groups: 1) NAC + RC, 2) RC, and 3) TMT. Interview transcriptions were qualitatively analyzed using QSR NVivo, with major themes and sub-themes extracted. Patients also completed the Shared Decision-Making Questionnaire (SDM-Q-9; range 0–100).

RESULTS:

Concern for survival and risks, quality of life, and varied patient preferences for involvement influenced the decision-making process. Concern surrounding sexual function, bladder preservation, and urostomy bags drove patients towards TMT. High levels of shared decision-making were observed overall, with a median SDM-Q-9 score of 95 (IQR 89–100). Patients undergoing TMT reported the highest median SDM-Q-9 score (97, IQR 94–100), while those receiving radical cystectomy alone had the lowest (66, IQR 37–96).

CONCLUSIONS:

Patients with MIBC described a multifaceted treatment decision-making process, highlighting key influences, concerns, and unmet needs. Understanding this process can help address misconceptions and align treatment choices with patient goals. Physicians can use these insights to engage in shared decision-making, ultimately improving patient experiences and outcomes.

Abstract

BACKGROUND:

The intravesical gene therapy nadofaragene firadenovec (rAd-IFNα/Syn3) was FDA approved in 2022 for non-muscle invasive bladder cancer (NMIBC) unresponsive to frontline treatment with BCG, and the first gene therapy developed for bladder cancer. This non-replicating recombinant adenovirus vector delivers a copy of the human interferon alpha-2b gene into urothelial and tumor cells, causing them to express this pleotropic cytokine with potent antitumor effects.

OBJECTIVE:

To provide a historical overview describing how several decades of preclinical and clinical studies investigating the role of interferon in the treatment of bladder cancer ultimately led to the development of gene therapy with nadofaragene for NMIBC.

METHODS:

We conducted a review of the literature using PubMed, Google Scholar, and ClinicalTrials.gov to summarize our knowledge of the evolution of interferon-based therapy in NMIBC.

RESULTS:

The FDA approval of this therapy represents an important landmark in urologic oncology and several decades of research dedicated to the study of interferon’s direct and indirect antitumor properties in NMIBC. The data gathered from the phase 1, 2, and 3 clinical trials continue to provide additional insights into the precise mechanisms underlying both the efficacy of and resistance to nadofaragene.

CONCLUSIONS:

Nadofaragene leverages the cytotoxic, anti-angiogenic, and immune-modulatory roles of interferon to effectively treat NMIBC that is resistant to BCG. Ongoing studies of resistance mechanisms and prognostic biomarkers have been promising; these will ultimately improve patient selection and allow for the modulation of factors in the tumor or immune microenvironment to further increase therapeutic response.

Abstract

BACKGROUND:

Prognostic tools in pathological-node (pN) patients after radical cystectomy (RC) are needed.

OBJECTIVES:

To evaluate the prognostic impact of lymph node (LN)-density on disease-specific survival (DSS) in patients with bladder cancer (BC) undergoing RC with pelvic lymph node dissection.

METHODS:

We analyzed a multi-institutional cohort of 1169 patients treated with upfront RC for cT1-4aN0M0 urothelial BCat nine centers. LN-densitywas calculated as the ratio of the number of positive LNs×100% to the number of LNs removed. The optimal LN-density cut-off value was defined by creating a time-dependent receiver operating characteristic (ROC) curve in pN patients. Univariable and multivariable Cox’ regression analyses were used to assess the effect of conventional Tumor Nodes Metastasis (TNM) nodal staging system, LN-density and other LN-related variables on DSS in the pN-positive cohort.

RESULTS:

Of the 1169 patients, 463 (39.6%) patients had LN-involvement. The area under the ROC curve was 0.60 and the cut-off for LN-density was set at 20%, 223 of the pN-positive patients (48.2%) had a LN-density.20%. In multivariable models, the number of LN-metastases (HR 1.03, p = 0.005) and LN-density, either as continuous (HR 1.01, p = 0.013) or as categorical variable (HR 1.37, p = 0.014), were independently associated with worse DSS, whereas pN-stage was not.

CONCLUSIONS:

LN-density.20% was an independent predictor of worse DSS in BC patients with LN-involvement at RC. The integration of LN-density and other LN-parameters rather than only conventional pN-stage may contribute to a more refined risk-stratification in BC patients with nodal involvement.

Abstract

BACKGROUND:

Bladder cancer is a malignancy greatly affected by behavioral habits. The aim of this study was to examine the effect of opium on changes in the expression of OCT4 and SOX2 in the bladder tissue of rats.

METHOD:

Thirty six rats were divided into six groups: 24 rats in the addicted group received morphine and opium for 4 months with 12 rats in the control group. Blood testing was done for the evaluation of CBC, MDA, and TAC. The bladder tissue was removed and checked by histopathological examination. All total RNA was extracted, then cDNAs were synthesized and the OCT4 and SOX2 gene expressions were evaluated by Real-time PCR.

RESULTS:

The OCT4 mRNA expression level in the opium group of rats was significantly increased compared to the control group (13.5 and 6.8 fold in males and females respectively). Also, in the morphine group, similar augmentation was detected (3.8 and 6.7 fold in males and females respectively). The SOX2 mRNA over-expression level was seen in the morphine group of both genders as compared to the control group (3.7 and 4.2 fold in male and female respectively) but in the opium group, enhancement of mRNA level was seen only in males (6.6 fold). Opium increases both OCT4 and SOX2 expression more than morphine in male rats, but in female rats, SOX2 is increased more by morphine.

CONCLUSION:

Over expression of OCT4 and SOX2 was observed in rats treated with opium and morphine. Increased OCT4 and SOX2 expression was seen in opium-treated male rats, but in female rats, SOX2 was increased more by morphine.