Nikhil Vasdev

Immunotherapy for bladder cancer.

It is nearly 40 years since Bacillus Calmette–Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear.

The Role of Positron Emission Tomography With 68Gallium (Ga)-Labeled Prostate-specific Membrane Antigen (PSMA) in the Management of Patients With Organ-confined and Locally Advanced Prostate Cancer Prior to Radical Treatment and After Radical Prostatectomy

The role of positron emission tomography (PET) with (68)Gallium (Ga)-labeled prostate-specific membrane antigen (PSMA) imaging for prostate cancer is gaining prominence. Current imaging strategies, despite having progressed significantly, have limitations, in particular their ability to diagnose metastatic lymph node involvement. Preliminary results of PET with (68)Ga-labeled PSMA have shown encouraging results, particularly in the recurrent prostate cancer setting. Furthermore, the ability of PET with (68)Ga-labeled PSMA of playing a dual diagnostic and therapeutic setting (theranostics) is currently being investigated as well. PET with (68)Ga-labeled PSMA certainly has a role to play in bridging some of the voids in contemporary prostate cancer imaging tools.

Management of Node-Positive Bladder Cancer After Neoadjuvant Chemotherapy and Radical Cystectomy: A Survey of Current UK Practice

INTRODUCTION Because of the lack of published evidence, this study was done to explore the decisions and rationale of uro-oncology consultants regarding the treatment of patients with muscle-invasive bladder cancer who have positive lymph nodes after radical cystectomy (RC) and neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS An electronic survey was sent to UK pelvic cancer centers regarding: (1) choice of NAC regimen; (2) indications for reimaging; (3) choice and indication of adjuvant chemotherapy (AC) for patients with nodal disease after NAC and RC; (4) choice and indication of chemotherapy regimen if disease continues to progress in patients with advanced bladder cancer; and (5) guidelines used by those surveyed. RESULTS Consultant uro-oncologists from 77% of UK pelvic cancer centers responded, who treated a median of 13 patients per year with NAC before RC. Three cycles of gemcitabine and cisplatin was the most common NAC regimen, with 93% and 67% respondents giving it for downstaging of cN1- and cN2- and 3-positive patients, respectively. Forty-five percent would not give AC after NAC and RC in patients with positive lymph nodes. The patients performance status, followed by response to NAC were key factors in dictating the use of AC. In the presence of disease progression, 46% of participants would use a taxane. Fifty-two percent of responders do not follow any guidelines. CONCLUSION In the United Kingdom, the treatment of patients with nodal disease after NAC and RC is variable. There is little evidence on which to base the management of such patients. The creation of national and international guidelines might help clinicians to optimize care for these patients.

The neurovascular structure‐adjacent frozen‐section examination (NeuroSAFE) approach to nerve sparing in robot‐assisted laparoscopic radical prostatectomy in a British setting – a prospective observational comparative study

To evaluate the neurovascular structure‐adjacent frozen‐section examination (NeuroSAFE) technique in a British setting in men undergoing robot‐assisted laparoscopic radical prostatectomy (RALP) .

Cardiopulmonary exercise testing in patients undergoing radical cystectomy (open, laparoscopic and robotic)

The use of cardiopulmonary exercise testing (CPET) is gaining popularity as a preoperative functional assessment tool and is a useful adjunct to risk stratification before radical cystectomy. It is important for urologists to understand the indications, contraindications, methodology and different parameters evaluated during CPET assessment and use this information acquired to tailor pre-, intra- and postoperative care in patients undergoing a radical cystectomy. We present a review on the increasing role of CPET in patients undergoing a radical cystectomy.

Testicular Germ Cell Tumours - A European and UK Perspective

Testicular Germ Cell tumours (TGCTs) account for between 1% and 1.5% of male neoplasms and 5% of urological tumours in general, with 3-10 new cases occurring per 100,000 males/per year in Western society (1-3). Testicular germ cell tumours (TGCTs) are the most frequent solid tumour of Caucasian adolescents and young adult males and are a diverse group of neoplasms that can also present in extragonadal sites. Within Europe, there has been a general increase in the incidence of TGCTs noted initially in the 1970s and 1980s (4). Over recent years the incidence of TGCTs has risen markedly, making it imperative to understand how and why these tumours arise.

Current Strategies to Enhance Recovery following Radical Cystectomy: Single Centre Initial Experience.

A radical cystectomy (RC) with pelvic lymph node dissection is the gold standard treatment for muscle-invasive bladder carcinoma. The morbidity associated with RC is clearly lower than that in the previous decades; it still continues to remain higher than 30% in the early postoperative period associated with and remains the most effective method for local control. We present current strategies being developed to further enhance recovery in patients undergoing RC and stratifying these into pre, intra, and post operative. We present our current strategies to enhance revcovery in patients undergoing RC which includes a combination of a through preoperative assessment with cardiopulmonary exercise (CPX), preoperative carbohydrate loading drinks, and intraoperative fluid monitoring with the trans-oesophageal Doppler probe (TODP) that may enhance recovery following radical cystectomy. We conclude that using these strategies may not only help in reducing peri/post operative morbidity and the duration of inpatient stay but may also help in enhancing the patients long-term recovery.

Is it still clinically and economically viable in the UK to prescribe vacuum erection devices for patients with erectile dysfunction after radical prostatectomy

The current incidence of erectile dysfunction (ED) after radical prostatectomy (RP) can range between 14 and 89% [2]. The British Society for Sexual Medicine guidelines on erectile dysfunction management recommend phosphodiesterase-5 (PDE-5) inhibitors as well as a VED as first-line management for erectile dysfunction after RP. In the current literature, PDE-5 inhibitors are recommended because of their proven efficacy and cost effectiveness [3]. By contrast, the limited evidence for VED effectiveness in large-scale trials has raised doubts over their use [4]. Despite this ~8000–10 000 VEDs are prescribed in the UK per year.

Robotic Assisted Intracorporeal Neobladder Reconstruction: Surgical Technique

The use of Minimally Invasive Surgery (MIS) and in particular robotic assisted approaches for urologic oncology has gained popularity over the last decade. Recent data has indicated that the vast majority of radical prostatectomy cases are performed robotically. Over the last few years, there has been an increase in robotic assisted radical cystectomy (RARC).

How to write a systematic review: Tips and tricks for surgeons in training

Systematic reviews provide high-quality critical appraisal and evidence-based summaries on a topic. They represent a key resource for time-pressured clinicians as they strive to deliver better patient care. Robust methodology and adhering to rigorous standards forms the foundation of this type of article. As such, writing a systematic review can prove a great challenge. This article aims to provide an overview of the methodology as well as certain tips and tricks which will help the surgeon when taking on such a project.