Editorial Comment

Byline: Chad R. Ritch Author Affiliation: Vanderbilt University Medical Center, Nashville, TennesseeAcademi

Recent trends in the management of advanced prostate cancer [version 1; referees: 3 approved]

Advanced prostate cancer includes a wide spectrum of disease ranging from hormone naïve or hormone sensitive to castration resistant, both containing populations of men who have demonstrable metastatic and non-metastatic states. The mainstay of treatment for metastatic hormone-sensitive prostate cancer is androgen deprivation therapy (ADT). However, recent level 1 evidence demonstrates that the addition of chemotherapy or abiraterone acetate to ADT results in significant survival advantage as compared with ADT alone. Furthermore, in non-metastatic castration-resistant prostate cancer (M0 CRPC), two second-generation anti-androgens, apalutamide and enzalutamide, when used in combination with ADT, have demonstrated a significant benefit in metastasis-free survival. Here, we review the most recent studies leading to these significant changes in the treatment of advanced prostate cancer

Photodynamic therapy for low risk prostate cancer

No substitute for active surveillance ye

Urinary biomarkers in bladder cancer: where do we stand?

To provide a current comprehensive review of the available urinary biomarkers for the detection and surveillance of bladder cancer. The limitations of urine cytology and invasive nature of cystoscopic evaluation have led to a growing search for an ideal, cost-effective biomarker with acceptable sensitivity and specificity. Current FDA approved biomarkers such as UroVysion fluorescent in situ hybridization, Immunocyt, and nuclear matrix protein 22 do not have the specificity, and thus positive predictive value to warrant their cost as a routine adjunct or replacement for cystoscopy. Several promising commercially available assays such as Cxbladder, Assure MDx, and Xpert BC may perform better than cytology in select populations. Novel genomic, epigenetic, inflammatory, and metabolomic-based assays are being analyzed as potential urinary biomarkers. Urinary biomarkers with high sensitivity and specificity are an unmet need in bladder cancer. Several new assays may meet these criteria and future research may justify use in clinical practice

Port Placement in Robotic Urologic Surgery

In 2001, the da Vinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA) was approved for use in urology (www.fda.gov) and the technological improvements have translated to a paradigm shift, especially in the field of urologic oncology. Robotic-assisted laparoscopic prostatectomy (RALP) has quickly become the minimally invasive surgical procedure of choice at most centers of excellence and robotic-assisted laparoscopic radical and partial nephrectomy (RALPN/RALN) and cystectomy (RALC) are also increasing in numbers. The impetus for the robotic approach to surgical management is based on a combined need for minimally invasive treatment with optimal surgical outcomes. Historically, conventional laparoscopy has been at the forefront of minimally invasive surgical technique and the fundamental principles of robotic surgery are founded upon those used in laparoscopic surgery. However, the advanced technology utilized in robotics has required modifications of these techniques to capitalize on the enhanced capabilities of robotic surgery. Whereas laparoscopic surgery is limited by counterintuitive movement, 2D visualization, and a decreased range of motion, robotic surgery offers 3D visualization, seven degrees of freedom, and is a natural reflection of the surgeon’s movement. Robotic surgery therefore offers enhanced capabilities for visualization, surgical dexterity, and exposure to the surgical field but these are ultimately dependent on the proper placement of the ports used for access. This chapter will provide a comprehensive overview of the standard techniques for access and port placement in a number of major robotic urologic procedures focusing on the nuances of prostate, renal, bladder, and female robotic urologic surgery

Prostate cryotherapy: current status

Minimally invasive options to treat low-risk prostate cancer are more desirable than radical therapy. Technological improvements in cryotherapy have increased its use, and long-term data on its efficacy are emerging. In this review, we discuss contemporary data on cryotherapy with specific focus on studies using the newest technology. With respect to biochemical recurrence rates, cryotherapy appears to be as effective for low-risk prostate cancer as other treatment modalities. The definition of recurrence remains problematic, though contemporary studies are more consistently using both the American Society for Therapeutic Radiation Oncology and Phoenix criteria. Erectile dysfunction rates are universally high after whole-gland cryoablation, but incontinence and urethrorectal fistula rates appear to be low with third-generation cryo systems. Focal cryotherapy has encouraging short-term efficacy in terms of biochemical disease-free survival rate for unifocal disease, and rates of erectile dysfunction are dramatically lower than those seen with whole-gland cryoablation. Cryosurgery has a promising role in primary and salvage treatment of select prostate cancer patients. Focal cryotherapy for unilateral disease offers the added benefit of minimal adverse effects. Long-term data are emerging to support cryosurgery, and large multicenter databases have been developed to answer questions regarding optimal treatment outcomes and patterns

Advances in the management of castration resistant prostate cancer

Docetaxel based chemotherapy showed survival benefit and emerged as the mainstay of treatment for castration resistant prostate cancer (CRPC) in 2004. However, therapeutic options have expanded rapidly since 2011. The spectrum of new agents is broad and includes drugs that target the androgen axis (enzalutamide, abiraterone), immunotherapy (sipuleucel-T), bone seeking radionuclides (radium-223), and second line chemotherapy (cabazitaxel). In addition, new agents have been developed to reduce skeletal related events (denosumab). Given that docetaxel was the standard first line treatment for metastatic CRPC, the newer oral agents that affect the androgen axis were initially approved in the post-docetaxel setting. However, subsequent randomized trials have led to their approval in the pre-chemotherapy setting as well. Patients with CRPC are clinically heterogeneous, ranging from patients who are asymptomatic and do not have metastases to those with substantial symptoms and both bony and visceral metastases. CRPC is a clinically challenging disease entity, therefore, with a wide array of treatment options and multiple possible sequencing combinations depending on the individual patient. This review will summarize the findings of the randomized trials that led to the approval of the therapies for CRPC. It will also discuss recent guidelines and provide suggestions for sequencing of drugs based on the best available evidence

Predicting Response to Intravesical Therapy in Non–muscle-invasive Bladder Cancer

The ability to predict response to intravesical therapy (IVT) following transurethral resection in non–muscle-invasive bladder cancer holds important prognostic information. However, few predictive tools are available to guide urologists. We reviewed the most recent studies investigating the predictors of response to IVT. A literature search was conducted using PubMed database from January 1, 2013 to April 1, 2018 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. For our search strategy, we used the combination of the MeSH terms of “Administration, Intravesical” and “Urinary Bladder Neoplasms” with any of the following words: “Biomarkers,” “Predictive Value of Tests,” “response,” “recurrence,” and “progression.” We limited our search to the English language. Risk stratification models utilizing clinicopathological features are the most cost-effective and widely used tools currently available to predict response to IVT. Additionally, urinary fluorescence in situ hybridization testing and urinary cytokine-based nomograms (Cytokine Panel for Response to Intravesical Therapy) may enhance predictive ability. Protein-based biomarkers have been associated with predicting recurrence. Several gene-based biomarkers quantifying mutations in DNA damage repair genes may have predictive ability. However, genomic data are relatively new and lack validation. Clinicopathological criteria remain the most widely utilized tool for predicting IVT response. Further research to validate protein- and genomic-based biomarkers are needed before adoption in clinical practice. We reviewed contemporary studies that investigated how to predict response to medication instilled in the bladder (intravesical therapy) for bladder cancer. We found that most predictive tools use clinical data, such as tumor stage and grade, to determine the outcome. Newer biological (gene, protein, cytokines) marker tests are being studied. We concluded that the combination of clinical data with levels of certain experimental markers (fluorescence in situ hybridization test or urinary cytokines) may improve predictive ability. Genetic testing methods may also yield additional predictive markers in the future, but this needs more validation. Novel nomograms that combine clinicopathological criteria with the fluorescence in situ hybridization test and/or urinary cytokine expression may constitute a useful approach to predicting intravesical therapy response. Further research into genetic sequencing using large cohorts with follow-up validation is essential to identify novel predictors of response

Clinical Scenario: Large Volume, Non-metastatic T2 Bladder Tumor

The optimal treatment of bulky, non-metastatic, and locally advanced muscle-invasive bladder cancer (MIBC) involves a combination of chemotherapy and radical cystectomy. Evidence exists to support the use of neoadjuvant chemotherapy in the treatment of MIBC; however, there are a number of scenarios where this approach is not feasible or may not be practical. The goal of this chapter is to describe our approach to the treatment of MIBC, in particular the timing and use of chemotherapy with radical cystectomy, and to provide a practical guide based on our clinical experience