Clipless Robotic-assisted Radical Prostatectomy and Impact on Outcomes.

BACKGROUND: The use of surgical clips for athermal dissection of the lateral prostatic pedicles and ligation during pelvic lymph node dissection (PLND) while performing robotic-assisted radical prostatectomy (RARP) has been the gold standard. Clips are used to prevent thermal injury of the unmyelinated nerve fibers and lymphceles, respectively. OBJECTIVE: To compare oncological and functional outcomes of a new technique of clipless, lateral pedicle control and PLND with RARP with bipolar energy (RARP-bi) versus the standard RARP technique with clips (RARP-c). DESIGN, SETTING, AND PARTICIPANTS: A retrospective study was conducted among 338 men who underwent RARP between July 2018 and March 2020. SURGICAL PROCEDURE: RARP-c versus RARP-bi. MEASUREMENTS: We prospectively collected data and retrospectively compared demographic, clinicopathological, and functional outcome data. Urinary as well as sexual function was assessed using the Expanded Prostate Cancer Index for Clinical Practice, and complications were assessed using Clavien-Dindo grading. Multivariable regression modeling was used to examine whether the technical approach of RARP-bi versus RARP-c was associated with positive surgical margins (PSMs) or sexual and urinary function scores. RESULTS AND LIMITATIONS: A total of 144 (43%) and 194 (57%) men underwent RARP-bi and RARP-c, respectively. Overall, there were no differences in functional and oncological outcomes between the two approaches. On multivariable regression analysis, the RARP-bi technique was not associated with significant differences in PSMs (odds ratio [OR] = 1.04, 95% confidence interval [CI] 0.6-1.8; p = 0.9), sexual function (OR = 0.4, 95% CI 0.1-1.5; p = 0.8), or urinary function (OR = 0.5, 95% CI 0.2-1.4; p = 0.2). The overall 30-d complication rates (12% vs 16%, p = 0.5) and bladder neck contracture rates (2.1% vs 3.6%, p = 0.5) were similar between the two groups. There was no difference in lymphocele complications (1.4% vs 0.52%, p = 0.58). All complications were of Clavien-Dindo grade I-II. CONCLUSIONS: Despite the concerns for an increased risk of nerve injury secondary to the use of bipolar energy for prostatic pedicle dissection, we demonstrate that this technique is oncologically and functionally similar to the standard approach with surgical clips. There was no difference in complications or lymphocele formation for techniques with versus without clips. PATIENT SUMMARY: We describe a modified technique for prostatic pedicle dissection during robotic-assisted radical prostatectomy, which utilizes bipolar energy and is associated with shorter operative time, without compromising functional or oncological outcomes.

Paraneoplastic limbic encephalitis as initial presentation of testicular neoplasm: A case report.

Paraneoplastic limbic encephalitis (PLE) is an immunopathologic syndrome associated with malignancy and represents a rare remote outcome of tumor on the nervous system. We report a case of PLE caused by a regressed testicular germ cell tumor in an otherwise healthy young man, who presented with acute-onset confusion, memory impairment and anterograde amnesia. Prompt recognition of PLE is critical as it allows early treatment of both the primary tumor and PLE-related neurologic impairments, which can be severe and irreversible if treatment is delayed. Complete tumor treatment response offers the best chance for neurologic recovery in patients with PLE. To our knowledge, this is the second reported case of PLE with radiologic-pathologic correlation in the setting of a regressed testicular germ cell tumor.

Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF Mutations.

African-American men have the highest incidence of and mortality from prostate cancer. Whether a biological basis exists for this disparity remains unclear. Exome sequencing (n = 102) and targeted validation (n = 90) of localized primary hormone-naïve prostate cancer in African-American men identified several gene mutations not previously observed in this context, including recurrent loss-of-function mutations in ERF, an ETS transcriptional repressor, in 5% of cases. Analysis of existing prostate cancer cohorts revealed ERF deletions in 3% of primary prostate cancers and mutations or deletions in ERF in 3% to 5% of lethal castration-resistant prostate cancers. Knockdown of ERF confers increased anchorage-independent growth and generates a gene expression signature associated with oncogenic ETS activation and androgen signaling. Together, these results suggest that ERF is a prostate cancer tumor-suppressor gene. More generally, our findings support the application of systematic cancer genomic characterization in settings of broader ancestral diversity to enhance discovery and, eventually, therapeutic applications.Significance: Systematic genomic sequencing of prostate cancer in African-American men revealed new insights into prostate cancer, including the identification of ERF as a prostate cancer gene; somatic copy-number alteration differences; and uncommon PIK3CA and PTEN alterations. This study highlights the importance of inclusion of underrepresented minorities in cancer sequencing studies. Cancer Discov; 7(9); 973-83. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 920.

Antibody therapeutics for treating prostate cancer: where are we now and what comes next?

INTRODUCTION: Progress in the understanding of molecular events of carcinogenesis and cancer evolution as well as the identification of tumor antigens has led to the development of different targeted therapeutic approaches, including the use of monoclonal antibodies (mAbs). Prostate cancer (PC) is highly amenable to mAb targeting given the existence of prostate-specific targets and the natural history and localization of metastatic disease. Areas covered: Several aspects of the PC phenotype, including growth factors, angiogenesis mediators, bone microenvironment signals, and immune evasion pathways, have become areas of ongoing investigation in terms of mAb targeting. These are reviewed. The greatest success so far has been the development of mAbs against prostate-specific tumor antigen (PSMA), which opened an opportunity to improve diagnostic accuracy and simultaneously target metastatic disease. Expert opinion: As mAb use in PC continues to evolve, more accurate imaging of the extent of disease and more effective mAb therapies (naked or conjugated with drugs, toxins or radioactive molecules) are emerging. In addition, the combination of mAbs with other treatment modalities is expected to further improve responses and overall survival. Identification of validated biomarkers is necessary for better recognition of patient subgroups who will derive the greatest benefit from mAb therapy.

Blocking immune checkpoints in prostate, kidney, and urothelial cancer: An overview.

Despite a long history of immunotherapeutic approaches to treatment, most genitourinary malignancies are not cured by existing immunotherapy regimens. More recently, cell surface molecules known as immune checkpoints have become the focus of efforts to develop more effective immunotherapies. Interactions between these molecules and their ligands inhibit the proliferation and function of tumor-specific lymphocytes. A monoclonal antibody blocking 1 of these checkpoints was approved for the treatment of metastatic melanoma and is now being tested in other malignancies. The objective responses seen in these early trials of checkpoint blockade are driving renewed enthusiasm for cancer immunotherapy. There are several ongoing and planned trials in genitourinary malignancies of single-agent inhibitors, as well as combinations targeting multiple checkpoints or adding other types of therapies to checkpoint blockade.

The evolving role of cytotoxic chemotherapy in the management of patients with metastatic prostate cancer.

Prostate cancer (PC) is the most common cancer in men in the United States. Although outcomes are excellent for early-stage disease, survival for men with metastatic PC is limited. While older studies did not supported the use of chemotherapy in PC, the efficacy of taxane chemotherapy plus prednisone is now well established in men with metastatic castration resistant PC (CRPC). The results of CHAARTED trial have further expanded the use of chemotherapy to patients with metastatic hormone-sensitive disease. The clinical efficacy of taxanes over other chemotherapeutics may be a result of its ability to inhibit microtubule-dependent trafficking of proteins such as the androgen-receptor (AR). Ongoing research uses chemotherapy earlier in the disease course as well as explores the utility of combining cytotoxic chemotherapy with biologic agents.

Novel molecular targets for urothelial carcinoma.

INTRODUCTION: Urothelial cancer (UC) remains a significant public health problem, with no new second-line agents FDA-approved in the US. Next-generation sequencing technologies are starting to generate a molecular landscape of UC thus revealing novel molecular targets. AREAS COVERED: In this review, the authors provide a detailed review of novel molecular targets in UC based on published genomic analyses of urothelial tumors. We provide an overview of each molecular target with a brief discussion of therapeutic strategies and clinical trials targeting each pathway. EXPERT OPINION: UC continues to be a lethal disease with no FDA-approved effective second-line therapies. Platinum resistance continues to be a daunting clinical problem. Next-generation sequencing methods have led to the elucidation of numerous molecular targets in UC, including PI3K, to the elucidation of numerous molecular targets in UC, including PI3K, ERBB2 and FGFR3, among many others. These molecular perturbations can be exploited therapeutically with targeted therapies in patient populations enriched for these molecular alterations, thus paving the way for precision medicine in UC management.