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Practice change: No benefit of extended lymphadenectomy at radical cystectomy in patients with muscle invasive bladder cancer

Fahmy O, Kochergin M, Asimakopoulos AD, Gakis G

Semin Oncol, 2023;50(3-5):102-104.
PMID: 37718162 DOI: 10.1053/j.seminoncol.2023.09.001

For many decades, extended pelvic lymph node dissection has been an integral part during radical cystectomy for patients with muscle invasive bladder cancer. This practice was based on large retrospective meta-analyses suggesting an oncologic benefit to an extended dissection. This mini review and meta-analysis includes the two available randomized trials in the current literature. Therefore, it can be considered as the strongest level of evidence regarding the prognostic benefit of an extended pelvic lymphadenectomy. Based on current randomized data, standard pelvic lymph node dissection up to the level of iliac bifurcation is sufficient, and extension of the dissection above this level does not provide any additional oncologic benefit.
Role of inguinal and pelvic lymph node dissection for primary urethral carcinoma: a systematic review

Kochergin M, Fahmy O, Asimakopoulos AD, Gakis G

Curr Opin Urol, 2023 Jul 01;33(4):288-293.
PMID: 37158221 DOI: 10.1097/MOU.0000000000001101

PURPOSE OF REVIEW: Primary urethral carcinoma (PUC) is a rare urologic tumor. There is limited evidence on this entity. This review summarizes the existing evidence on lymph node dissection (LND) in patients with PUC.
RECENT FINDINGS: We performed a systematic search of the PubMed, EMBASE, and Web of Science databases to evaluate the impact of inguinal and pelvic LND on the oncological outcomes of PUC and to identify indications for this procedure.
RESULTS: Three studies met the inclusion criteria. The cancer detection rate in clinically nonpalpable inguinal lymph node (cN0) was 9% in men and 25% in women. In clinically palpable lymph node (cN+), the malignancy rate was 84% and 50% in men and women, respectively. Overall cancer detection rate in pelvic lymph nodes in patients with cN0 was 29%. Based on tumor stage, the detection rate was 11% in cT1-2 N0 and 37% in cT3-4 N0. Nodal disease was associated with higher recurrence and worse survival. Pelvic LND seems to improve overall survival for patients with LND regardless of the location or stage of lymph nodes. Inguinal LND improved overall survival only in patients with palpable lymph nodes. Inguinal LND had no survival benefit in patients with nonpalpable lymph nodes.
SUMMARY: The available, albeit scarce, data suggest that inguinal LND derives the highest benefit in women and in patients with palpable inguinal nodes, whereas the benefit of pelvic LND seems to be more pronounced across all stages of invasive PUC. Prospective studies are urgently needed to further address the prognostic benefit of locoregional LND in PUC.
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.