Muscle-invasive bladder cancer organ-preserving therapy: systematic review and meta-analysis

Purpose

To determine the effectiveness and harms of bladder-preserving trimodal therapy (TMT) as a first-line treatment versus radical cystectomy (RC) plus radical pelvic lymphadenectomy in the treatment of muscle-invasive bladder cancer in terms of overall survival.

Methods

We included parallel clinical trials and prospective and retrospective cohort studies that included patients older than 18 years old, diagnosed with muscle-invasive bladder cancer, who underwent TMT compared with RC. The planned comparison was TMT versus RC plus pelvic lymphadenectomy as first-line treatment. The primary outcome was overall survival (OS) and secondary outcomes were salvage cystectomy and cancer-specific survival and progression-free survival. A search strategy was designed for MEDLINE, CENTRAL, Embase, and LILACS. We saturated information with conference abstracts, in progress clinical trials, literature published in non-indexed journals, and other sources of gray literature. Standardized tools assessed the risk of bias independently. We performed the statistical analysis in R v3.4.1 and effect sizes were reported in terms of hazard ratios (HR) and the corresponding 95% confidence intervals (95%CI). Accordingly, we used a random effect model due to the statistical heterogeneity found in included studies.

Results

We found 2682 records with the search strategies and, finally, 11 studies were included in the quantitative analysis. The summary HR for OS was 1.06 95%CI (0.85–1.31) I²?=?77%, showing no statistical difference. Regarding cancer-specific survival, the summary HR was 1.23 95%CI (1.04–1.46) I²?=?14%. On the other side, for the progression-free survival, the summary HR was 1.11 95%CI (0.63–1.95) I²?=?78%. Only one study described HR for adverse events (1.37 95%CI 1.16–1.59).

Conclusion

We found no differences in overall survival and progression-free survival between these two interventions. Nonetheless, we found that cancer-specific survival favored patients who received radical cystectomy.

     

Muscle-invasive transitional cell carcinoma of the bladder: strategies for bladder preservation

For patients with invasive bladder cancer, radical cystectomy remains the gold standard of treatment. However, based upon success with combination chemotherapy, physicians have begun to use this modality in an integrated approach with radiotherapy. This approach is of interest for elderly patients with poor medical conditions and for younger patients who may prefer to retain their bladders. Thorough transurethral resection of the bladder followed by chemotherapy with or without radiotherapy has become the focus of several studies. Bladder-conserving therapy may be offered to selected patients with invasive bladder cancer as a viable alternative to radical cystectomy.     

Muscle-invasive bladder cancer developing after nephroureterectomy for upper urinary tract urothelial carcinoma

ObjectivesTo evaluate the risk factors and prognosis of muscle-invasive bladder cancer (MIBC) developing after nephroureterectomy for upper urinary tract urothelial cell carcinoma (UUT-UC).Materials and methodsWe reviewed the medical records of 422 patients who underwent nephroureterectomy for UUT-UC between 1990 and 2010, and identified 173 (40.9%) with intravesical recurrence and 28 (6.6%) with MIBC. We evaluated the clinicopathologic features, risk factors, and cancer-specific survival (CSS) using the Kaplan-Meier method and the Cox proportional hazards regression models.ResultsThe median intervals from nephroureterectomy to intravesical recurrence and the development of MIBC were 8 and 17 months, respectively. On multivariate analysis, the pathologic stage (≥pT3 vs. Ta/T1, HR 5.03, P = 0.001) and ureteral tumor location (HR 2.79, P = 0.011) were independent risk factors for the development of MIBC, whereas a history of previous or concomitant bladder tumor was the only significant risk factor for intravesical recurrence. The probability of developing MIBC 5 years after nephroureterectomy was 12.6% in patients with 1 risk factor and 20.6% in patients with both risk factors. Patients with MIBC had significantly worse CSS than those without MIBC (P = 0.004), whereas CSS rates were similar in patients with and without intravesical recurrence (P = 0.593). However, stratification analysis for matching pathology revealed that CSS rates were not significantly different in patients with pT2 or higher stage of UUT-UC.ConclusionsApproximately 5% of the patients developed MIBC after nephroureterectomy with a median interval of 17 months. Patients with advanced pathologic stage (≥pT3) and a ureteral tumor location are at increased risk of developing MIBC after nephroureterectomy.     

Muscle-invasive bladder cancer: does it arise de novo or from pre-existing superficial disease?

This study examines the clinical and pathologic features of 20 consecutive patients with muscle-invasive bladder cancer diagnosed between January 1, 1983, and December 31, 1984, at The Mount Sinai Hospital. On retrospective analysis, 18 patients (90%) had muscle-invasive bladder cancer at their initial presentation. The interval between onset of symptoms and histologic documentation of cancer was less than two months in 14 cases (78%), and in the remaining 22 per cent, the intervals of six, six, twelve, and twenty-four months were attributable to delay in seeking medical attention or delay in biopsy. In contrast, in the 2 patients who had presented with superficial tumors, the intervals were thirteen and one hundred eighty months. It therefore appeared that most patients with invasive bladder cancer had no therapeutically significant prior clinical or symptomatic history of superficial disease, and that invasion either was already present when symptoms had begun, or occurred rapidly after symptoms had initially appeared. These findings confirm the broad applicability of this pattern of bladder cancer in the general population, thereby complementing similar findings reported in recent years by secondary referral centers.     

Molecular aspects of bladder cancer IV: gene therapy of bladder cancer

Cancer gene therapy is the applied consequence of the intense research on cell function during the last decades. With the discovery of genes, the genetic code and gene functions many diseases, like bladder cancer, were linked to dysfunction of the cell's genetic material. Soon the wish for a direct treatment of the underlying cause of such genetically based diseases, a "gene therapy", arose and the first successful attempt in 1990 jumpstarted the development of gene therapies [Hum. Gene Ther. 4 (1993) 521], especially for cancer.To date treatment of bladder cancer remains a challenge to physicians. In spite of advances in diagnose and treatment over the last decades recurrence and progression rates remain high, especially in superficial bladder cancer. Gene therapy may provide the yet missing additional treatment to finally achieve a reduction of recurrence and progression. The variety of gene therapy strategies for bladder cancer developed or under investigation reflects the desire for a further treatment option for bladder cancer. This review intends to explain general strategies and state of the art approaches in bladder cancer gene therapy, highlight recent advances and give an outlook on what to expect from gene therapy in future.     

Molecular epidemiology of bladder cancer: Known chemical causes of bladder cancer: Occupation and smoking

This article reviews the evidence concerning well known risk factors for bladder cancer, including several occupational exposures and tobacco smoking, and the underlying mechanistic processes. Emphasis is put on recent developments in the field of molecular epidemiology, including the study of carcinogen-DNA adducts in exfoliated bladder cells, of carcinogen-hemoglobin adducts, and of the modulating role played by genetically-based metabolic polymorphisms such as N-acetyltransferase. A model for bladder carcinogenesis in humans is offered. It is postulated that metabolic polymorphism plays a modulating role over the formation of macromolecule adducts, particularly at low doses of exposure.     

Xpert bladder cancer monitor in surveillance of bladder cancer: Systematic review and meta-analysis

IntroductionThere is a need for sensitive and specific biomarkers for detecting recurrences in patients with non-muscle invasive bladder cancer (NMIBC) on surveillance. Xpert bladder cancer (BC) monitor is the latest rapid in vitro qualitative test that detects expression of 5 mRNAs using a GeneXpert instrument. The primary aim of this review was to systematically review and pool the data regarding the diagnostic performance of Xpert BC in patients with NMIBC.MethodsSystematic literature search using 4 electronic databases (PubMed, EMbase, Scopus and Web of science) was performed. Pooled sensitivity, specificity and diagnostic odds ratio (DOR) were estimated using DerSimonian-Laird random-effects model. Standard Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed and the study protocol was registered with PROSPERO (CRD42021249762).ResultsIn this review, 11 prospective studies with 2,896 patients were included. Pooled sensitivity and specificity for Xpert BC were 73% (95% confidence interval (CI) 65%–80%) and 77% (95% CI 69%–84%) respectively. Area under curve (AUC) for Xpert BC monitor was 0.81 (0.78–0.84) respectively. Subgroup analysis from 7 studies for patients with high-grade recurrence revealed sensitivity, specificity and AUC of 0.86 (0.77–0.92), 0.78 (0.75–0.81) and 0.87 (0.84–0.90) respectively. Similar analysis for patients with low-grade recurrence revealed sensitivity, specificity and AUC of 0.58 (0.47–0.68), 0.79 (0.75–0.82) and 0.79 (0.75–0.82) respectively.ConclusionXpert BC monitor has overall acceptable diagnostic accuracy. Sensitivity is higher for high-grade disease for detecting recurrences in patients with NMIBC on surveillance.     

Follow-up strategies and management of recurrence in urologic oncology bladder cancer: invasive bladder cancer

A surveillance program following cystectomy should consider a patient's individual risk for the development of local and distant recurrences and any specific needs related to the urinary tract reconstruction performed (Table 1). Well-documented recurrence patterns following cystectomy are available from many large surgical series and provide the background information needed for tailoring follow-up based on pathologic criteria. Economic issues also must be considered, given that the health care-related expenses of treating and following patients with bladder cancer is twice as much as that expended for the treatment of prostate cancer. Because of the ever-increasing fiscal constraints placed on clinicians, risk-adjusted follow-up strategies are reasonable, but will require prospective evaluation to validate their appropriateness.     

Micropapillary bladder cancer

A characteristic clinical course of a patient with micropapillary bladder cancer, a rare histological variant with high metastatic potential, is presented. An 80-year-old woman had locally advanced high-grade bladder cancer with a focal micropapillary variant identified which was treated with intra-arterial chemotherapy with radiation therapy. Standard follow-ups involving cystoscopy with cold-cup biopsies and computed tomography could not detail the bladder carcinoma; however, the patient died of carcinomatosis 20 months after treatment. At autopsy, carcinomas proliferated under benign mucosa and infiltrated diffusely in the retro peritoneum. This behavior differs from the normal pattern of invasive transitional cell carcinoma, which usually proliferates forming a mass lesion. Thus, it may be difficult to detect micropapillary bladder cancer by computed tomography which demonstrates only increased tissue density in retroperitoneal fascia; therefore, care should be taken in the follow-up of micropapillary bladder cancer.     

Screening for bladder cancer: a perspective

Bladder cancer is the seventh most common cancer worldwide in men and the 17th in women with an overall number of 356,000 new cases of urinary bladder cancer worldwide in 2002. It is one of the most expensive cancers from diagnosis to death and the fifth most expensive cancer in terms of total medical care expenditures in the US. A screening program that resulted in detection of bladder cancer at an earlier stage, prior to muscle invasion or metastasis, could render a significant improvement in patient morbidity and overall survival. Acceptance of wide-spread screening strategies requires careful consideration of the competing risks, benefits, and costs associated with such policies. In this article, we will review the pros and cons of bladder cancer screening with a focus on cost-effectiveness and who should be screened. Dr Malats is partly supported by Fondo de Investigación Sanitaria/Instituto de Salud Carlos III, Espanya (G03/174 and PI061614), Fundació La Marató de TV3 (#050830), and Division of Cancer Epidemiology and Genetics, National Cancer Institute, USA.