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Fulltext Systematic Review and Meta-Analysis on the Role of Perioperative Blood Transfusion in Patients Undergoing Radical Cystectomy for Urothelial Carcinoma

Kochergin M, Fahmy O, Esken L, Goetze T, Xylinas E, Stief CG, et al.

Bladder Cancer, 2022;8(3):315-327.
PMID: 38993684 DOI: 10.3233/BLC-201534

BACKGROUND: Radical cystectomy (RC) is the standard of care in patients with muscle-invasive bladder cancer. The impact of perioperative red blood cell (RBC) transfusion on oncological outcomes after RC is not clearly established as the existing publications show conflicting results.
OBJECTIVES: The aim of this systematic review and meta-analysis was to investigate the prognostic role of perioperative RBC transfusion on oncological outcomes after RC.
METHODS: Systematic online search on PubMed was conducted, based on PRISMA criteria for publications reporting on RBC transfusion during RC. Publications with the following criteria were included: (I) reported data on perioperative blood transfusion; (II) Reported Hazard ratio (HR) and 95% -confidence interval (CI) for the impact of transfusion on survival outcomes. Primary outcome was the impact of perioperative RBC transfusion on recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Risk of bias assessment was performed using Newcastle-Ottawa Scale. Statistical analysis was performed using Revman 5.4 software.
RESULTS: From 27 primarily identified publications, 19 eligible articles including 22897 patients were selected. Perioperative RBC transfusion showed no impact on RFS (Z = 1.34; p = 0,18) and significant negative impact on CSS (Z = 2.67; p = 0.008) and OS (Z = 3.22; p = 0.001). Intraoperative RBC transfusion showed no impact on RFS (Z = 0.58; p = 0.56) and CSS (Z = 1.06; p = 0.29) and OS (Z = 1.47; p = 0.14).Postoperative RBC transfusion showed non-significant trend towards improved RFS (Z = 1.89; p = 0.06) and no impact on CSS (Z = 1.56; p = 0.12) and OS (Z = 0.53 p = 0.60).
CONCLUSION: In this meta-analysis, we found perioperative blood transfusion to be a significant predictor only for worse CSS and OS but not for RFS. This effect may be determined by differences in tumor stages and patient comorbidities for which this meta-analysis cannot control due to lack of respective raw data.
Fulltext New Intravesical Agents for BCG-Unresponsive High-Risk Non-Muscle Invasive Bladder Cancer

Asimakopoulos AD, Kochergin M, Colalillo G, Fahmy O, Hassan F, Renninger M, et al.

Bladder Cancer, 2023;9(3):237-251.
PMID: 38993180 DOI: 10.3233/BLC-230043

BACKGROUND: With the exception of the FDA-approved valrubicin and pembrolizumab, there are no standard second-line treaments for BCG-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC).
OBJECTIVES: To provide a systematic review of the novel intravesically administered therapeutic agents for the salvage treatment of BCG-unresponsive NMIBC.
METHODS: Online search of the PubMed, EMBASE and Web of Science databases was performed. The endpoints of this review were to evaluate the efficacy of the agents in terms of complete response rates (CR) and durability of CR, overall survival, recurrence-free survival and cancer-specific survival and to report on their toxicity profile. A search on Clinicaltrials.gov was performed to identify ongoing clinical trials.
RESULTS: 14 studies were included in this review. The critical clinical need for the development of an effective, safe and durable intravesical drug for the salvage treatment of high-risk NMIBC seems to be met mainly by intravesical gene therapy; in fact, data support the FDA-approved nadofaragene firadenovec as a potentially important therapeutic advancement in this context. Promising results are also being obtained by the combination of N-803/BCG and by innovative drug delivery systems.
CONCLUSIONS: Considering the plethora of novel intravesical treatments that have completed phase II evaluation, one can reasonably expect that clinicians will soon have at their disposal new agents and treatment options for BCG-unresponsive NMIBC. In the near future, it will be up to the urologist to identify, for each specific patient, the right agent to use, based on safety, results and cost-effectiveness.
Systematic Review and Meta-Analysis on the Impact of Hexaminolevulinate- Versus White-Light Guided Transurethral Bladder Tumor Resection on Progression in Non-Muscle Invasive Bladder Cancer

Gakis G, Fahmy O

Bladder Cancer, 2016 Jul 27;2(3):293-300.
PMID: 27500197

Introduction: Although there is evidence that hexaminolevulinate (HAL)-based transurethral bladder tumor resection (TURBT) improves the detection of Ta-T1 non-muscle-invasive bladder cancer (NMIBC) as well as carcinoma in situ there is uncertainty about its beneficial effects on progression. Material and Methods: A systematic literature search was conducted according to the PRISMA statement to identify studies reporting on HAL- vs. white-light (WL-) based TUR-BT in non-muscle invasive bladder cancer between 2000 and 2016. A two-stage selection process was utilized to determine eligible studies. Of a total of 294 studies, 5 (4 randomized and one retrospective) were considered for final analysis. The primary objective was the rate of progression. Results: The median follow-up for patients treated with HAL- and WL-TURBT was 27.6 (1-55.1) and 28.9 (1-53) months, respectively. Of a total of 1301 patients, 644 underwent HAL- and 657 WL-based TURBT. Progression was reported in 44 of 644 patients (6.8%) with HAL- and 70 of 657 patients (10.7%) with WL-TURBT, respectively (median odds ratio: 1.64, 1.10-2.45 for HAL vs. WL; p = 0.01). Data on progression-free survival was reported in a single study with a trend towards improved survival for patients treated with HAL-TURBT (p = 0.05). Conclusions: In this meta-analysis the rate of progression was significantly lower in patients treated with HAL- vs. WL-based TURBT. These results support the initiation of randomized trials on HAL with progression as primary endpoint.
Fulltext Survival after Metastasectomy for Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis

Patel V, Collazo Lorduy A, Stern A, Fahmy O, Pinotti R, Galsky MD, et al.

Bladder Cancer, 2017 Apr 27;3(2):121-132.
PMID: 28516157 DOI: 10.3233/BLC-170108

Background: Cisplatin-based combination chemotherapy is standard treatment for metastatic urothelial carcinoma; however, the vast majority of patients experience disease progression. As systemic therapy alone is rarely curative for the treatment of metastatic urothelial cancer, not only are new therapies needed but also refinement of general treatment principles. Herein, we conducted a systematic review and meta-analysis to explore the role of metastasectomy in metastatic urothelial carcinoma. Methods: We conducted a systematic review of the literature regarding local treatment for metastatic urothelial carcinoma. An online electronic search of the PubMed/MEDLINE and EMBASE databases was performed to identify peer-reviewed articles. All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Information was then extracted including number of patients, gender, the site of the primary urothelial tumor, site of metastasis, chemotherapy before or after metastasectomy, overall survival (OS), and disease specific survival (DSS) after metastasectomy. A meta-analysis was performed with those studies with sufficient survival data to obtain pooled overall survival. The article quality was assessed using the Cochrane Handbook "risk of bias" tool. Results: Seventeen out of 3963 articles were eligible for review between 1990-2015, including a total of 412 patients. The mean time to recurrence after metastasectomy was 14.25 months. The overall survival from time of metastasectomy ranged from 2 to 60 months. Pooled analyses of studies reported survival data revealed an improved overall survival for patients treated with metastasectomy compared with non-surgical treatment of metastatic lesions (HR 0.63; 95% CI, 0.49-0.81). All, except for three studies, were retrospective and non-randomized, leading to a high risk of bias associated with patient selection, patient attrition, and reporting. Such high potential of selection bias may lead to higher OS than expected. Additionally, treatment and outcome details reported across studies was highly variable. Conclusions: Limited conclusions can be drawn from the available literature exploring the role of metastasectomy in the management of metastatic urothelial cancer due to lack of uniform reporting elements and multiple sources of bias particularly related to a lack of prospective randomized trials. As a subset of patients treated with metastasectomy achieve durable disease control, this approach may be considered for select patients.