Anthony Koupparis

Enhanced recovery after surgery (ERAS) protocols: Time to change practice?

Radical cystectomy with pelvic lymph node dissection remains the standard treatment for patients with muscle invasive bladder cancer. Despite improvements in surgical technique, anesthesia and perioperative care, radical cystectomy is still associated with greater morbidity and prolonged in-patient stay after surgery than other urological procedures. Enhanced recovery after surgery (ERAS) protocols are multimodal perioperative care pathways designed to achieve early recovery after surgical procedures by maintaining preoperative organ function and reducing the profound stress response following surgery. The key elements of ERAS protocols include preoperative counselling, optimization of nutrition, standardized analgesic and anesthetic regimens and early mobilization. Despite the significant body of evidence indicating that ERAS protocols lead to improved outcomes, they challenge traditional surgical doctrine, and as a result their implementation has been slow.The present article discusses particular aspects of ERAS protocols which represent fundamental shifts in surgical practice, including perioperative nutrition, management of postoperative ileus and the use of mechanical bowel preparation.

Enhanced Recovery After Robot-assisted Radical Cystectomy: EAU Robotic Urology Section Scientific Working Group Consensus View

CONTEXTnRadical cystectomy (RC) is associated with frequent morbidity and prolonged length of stay (LOS) irrespective of surgical approach. Increasing evidence from colorectal surgery indicates that minimally invasive surgery and enhanced recovery programmes (ERPs) can reduce surgical morbidity and LOS. ERPs are now recognised as an important component of surgical management for RC. However, there is comparatively little evidence for ERPs after robot-assisted radical cystectomy (RARC). Due to the multimodal nature of ERPs, they are not easily validated through randomised controlled trials.nnnOBJECTIVEnTo provide a European Association of Urology (EAU) Robotic Urology Section (ERUS) policy on ERPs to guide standardised perioperative management of RARC patients.nnnEVIDENCE ACQUISITIONnThe guidance was formulated in four phases: (1) systematic literature review of evidence for ERPs in robotic, laparoscopic, and open RC; (2) an online questionnaire survey formulated and sent to ERUS Scientific Working Group members; (3) achievement of consensus from an expert panel using the Delphi process; and (4) a standardised reporting template to audit compliance and outcome designed and approved by the committee.nnnEVIDENCE SYNTHESISnConsensus was reached in multiple areas of an ERP for RARC. The key principles include patient education, optimisation of nutrition, RARC approach, standardised anaesthetic, analgesic, and antiemetic regimens, and early mobilisation.nnnCONCLUSIONSnThis consensus represents the views of an expert panel established to advise ERUS on ERPs for RARC. The ERUS Scientific Working Group recognises the role of ERPs and endorses them as standardised perioperative care for patients undergoing RARC. ERPs in robotic surgery will continue to evolve with technological and pharmaceutical advances and increasing understanding of the role of surgery-specific ERPs.nnnPATIENT SUMMARYnThere is currently a lack of high-level evidence exploring the benefits of enhanced recovery programmes (ERPs) in patients undergoing robot-assisted radical cystectomy (RARC). We reported a consensus view on a standardised ERP specific to patients undergoing RARC. It was formulated by experts from high-volume RARC hospitals in Europe, combining current evidence for ERPs with experts knowledge of perioperative care for robotic surgery.

Differing levels of testosterone and the prostate: a physiological interplay

Abstract | The controversies surrounding testosterone replacement therapy (TRT) have been addressed in the past few years. Although the androgenic effects of TRT on normal and malignant prostate cells have been studied for over 70 years, little clinical prospective research exists on the physiological responses of prostate tissues to a wide range of serum testosterone levels. The prostate is both an androgen-dependent and an androgen-sensitive organ; active processes are triggered at a threshold or saturation level of testosterone. Despite decades of research, no compelling evidence exists that increasing testosterone beyond this threshold level has a causative role in prostate cancer, or indeed changes the biology of the prostate. Testosterone deficiency has marked physiological and clinical effects on men in middle age and beyond. With subnormal testosterone levels, the potential positive benefits of TRT on factors such as muscle mass, libido or erectile function are likely a dose–response phenomenon, and should be considered differently than the threshold influence on the prostate. This Review will re-examine classic androgen research and reflect on whether testosterone actually stimulates prostatic cellular growth and progression in a threshold or a dose–response (or both) manner, as well as discuss the influence of testosterone on prostate cells in the hypogonadal and eugonadal states.

Early Recurrence Patterns Following Totally Intracorporeal Robot-assisted Radical Cystectomy: Results from the EAU Robotic Urology Section (ERUS) Scientific Working Group

Recurrence following radical cystectomy often occurs early, with >80% of recurrences occurring within the first 2 yr. Debate remains as to whether robot-assisted radical cystectomy (RARC) negatively impacts early recurrence patterns because of inadequate resection or pneumoperitoneum. We report early recurrence patterns among 717 patients who underwent RARC with intracorporeal urinary diversion at nine different institutions with a minimum follow-up of 12 mo. Clinical, pathologic, radiologic, and survival data at the latest follow-up were collected. Recurrence-free survival (RFS) estimates were generated using the Kaplan-Meier method, and Cox regression models were built to assess variables associated with recurrence. RFS at 3, 12, and 24 mo was 95.9%, 80.2%, and 74.6% respectively. Distant recurrences most frequently occurred in the bones, lungs, and liver, and pelvic lymph nodes were the commonest site of local recurrence. We identified five patients (0.7%) with peritoneal carcinomatosis and two patients (0.3%) with metastasis at the port site (wound site). We conclude that unusual recurrence patterns were not identified in this multi-institutional series and that recurrence patterns appear similar to those in open radical cystectomy series.nnnPATIENT SUMMARYnIn this multi-institutional study, bladder cancer recurrences following robotic surgery are described. Early recurrence rates and locations appear to be similar to those for open radical cystectomy series.

Radical prostatectomy for high-risk clinically localized prostate cancer: a prospective single institution series

OBJECTIVEnThe objective of this paper is to report on the pathologic and biochemical progression-free outcomes of patients who underwent radical prostatectomy for high-risk localized prostate cancer.nnnMETHODSnData was collected prospectively from 299 patients who underwent radical prostatectomy for high-risk clinically localized prostate cancer by 2 surgeons at a single institution. High risk was defined as 1 or more of 3 adverse factors: prostate-specific antigen (PSA) >20, biopsy Gleason score 8 to 10 and clinical stage T3. PSA recurrence was defined as PSA >0.4 ng/mL or any salvage therapy.nnnRESULTSnMedian age was 63.3 years (46.1-75.9). Median follow-up was 4.7 years (range 0.5-17.3 years). PSA at diagnosis was >20 ng/mL in 31.4%. Biopsy Gleason score was 8 to 10 in 66.9%. Clinical stage was T3 in 24.4%. 81.6% of patients had a single baseline risk factor, 15.7% had 2 risk factors and 2.7% had all 3 risk factors. Neoadjuvant therapy was administered to 184 patients (61.5%). Pathologic stage was organ-confined in 39.6%, specimen-confined in 26%, non-specimen-confined in 26.4%, and 8% had lymph node positive disease. Overall survival, cancer-specific survival and biochemical progression-free survival was 99%, 99.67% and 70.2%, respectively. Univariate analysis showed that PSA at diagnosis, percentage of cores positive and number of risk factors were predictors of PSA recurrence (p < 0.05). Multivariate analysis showed that PSA at diagnosis was an independent predictor of PSA recurrence (p < 0.05).nnnCONCLUSIONnRadical prostatectomy is associated with favourable biochemical progression-free, clinical and overall survival in selected men with high-risk localized prostate cancer, and should therefore be considered an option in these patients. Baseline PSA >20 ng/mL is a significant independent predictor of PSA recurrence.

Novel targeted agents on the horizon for castration-resistant prostate cancer.

Androgen deprivation treatment in prostate cancer patients is well established; however, resistance to such treatment manifests itself by progression to castration-resistant prostate cancer (CRPC). Despite significant advances in treatment options for patients with CRPC, their prognosis remains poor. Resistance results from multiple processes that facilitate cancer cell growth and survival. Mechanisms underlying the shift to castrate resistance have been attributed to a complex interplay of clonal selection, reactivation of the androgen receptor axis despite castrate levels of serum testosterone, stress-induced prosurvival genes and cytoprotective chaperone networks and alternative mitogenic growth factor pathways. This article discusses several pathways involved in the development of CRPC, with a particular focus on those mechanisms that have led to the development of new targeted therapies.

Cost analysis of open radical cystectomy versus robot-assisted radical cystectomy

To perform a cost analysis comparing the cost of robot‐assisted radical cystectomy (RARC) with open RC (ORC) in a UK tertiary referral centre and to identify the key cost drivers.

Pure malignant rhabdoid tumour of the bladder

We present the case of a 17-year-old girl with pure malignant rhabdoid tumour of the bladder treated with a multimodal approach. She is recurrence-free at her 1-year follow-up.

Robot-assisted radical cystectomy with intracorporeal urinary diversion versus open radical cystectomy (iROC): protocol for a randomised controlled trial with internal feasibility study

Introduction Bladder cancer (BC) is a common malignancy and one of the most expensive to manage. Radical cystectomy (RC) with pelvic lymphadenectomy is a gold standard treatment for high-risk BC. Reductions in morbidity and mortality from RC may be achieved through robot-assisted RC (RARC). Prospective comparisons between open RC (ORC) and RARC have been limited by sample size, use of extracorporeal reconstruction and use of outcomes important for ORC. Conversely, while RARC is gaining in popularity, there is little evidence to suggest it is superior to ORC. We are undertaking a prospective randomised controlled trial (RCT) to compare RARC with intracorporeal reconstruction (iRARC) and ORC using multimodal outcomes to explore qualitative and quantitative recovery after surgery. Methods and analysis iROC is a multicentre prospective RCT in English National Health Service (NHS) cancer centres. We will randomise 320 patients undergoing RC to either iRARC or ORC. Treatment allocation will occur after trial entry and consent. The primary outcome is days alive and out of hospital within the first 90 days from surgery. Secondary outcomes will measure functional recovery (activity trackers, chair-to-stand tests and health related quality of life (HRQOL) questionnaires), morbidity (complications and readmissions), cost-effectiveness (using EuroQol-5 Domain-5 levels (EQ-5D-5L) and unit costs) and surgeon fatigue. Patients will be analysed according to intention to treat. The primary outcome will be transformed and analysed using regression. All statistical assumptions will be investigated. Secondary outcomes will be analysed using appropriate regression methods. An internal feasibility study of the first 30 patients will evaluate recruitment rates, acceptance of randomised treatment choice, compliance outcome collection and to revise our sample size. Ethics and dissemination The study has ethical approval (REC reference 16/NE/0418). Findings will be made available to patients, clinicians, funders and the NHS through peer-reviewed publications, social media and patient support groups. Trial registration numbers ISRCTN13680280 and NCT03049410.

The feasibility of the Prostate cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) dietary and physical activity modifications: a qualitative study

BackgroundThere is increasing evidence that low levels of physical activity and diets low in fruit and vegetables and high in meat and dairy products are risk factors for prostate cancer disease progression. The Prostate cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) aimed to assess a diet and physical activity intervention in men undergoing radical prostatectomy for localized prostate cancer. The trial included a qualitative component to explore the experiences of men participating in the trial in order to understand the acceptability of the intervention and data collection methods. We report the qualitative findings of the trial and consider how these can be used to inform future research.MethodsPrEvENT involved randomizing men to either a dietary and/or physical activity intervention. Semi-structured interviews were conducted with a purposive sample of 17 men on completion of the 6xa0month trial. Interviews took place in clinic or as telephone interviews, if requested by the participant, and were audio recorded, transcribed, and analyzed using the thematic-based framework approach. Analysis was conducted throughout the data collection process to allow emergent themes to be further explored in subsequent interviews.ResultsThree overarching themes were identified: acceptability of the intervention, acceptability of the data collection methods and trial logistics. Participants were predominantly positive about both the dietary and physical activity interventions and most men found the methods of data collection appropriate. Recommendations for future trials include consideration of alternative physical activity options, such as cycling or gym sessions, increased information on portion sizes, the potential importance of including wives or partners in the dietary change process and the possibility of using the pedometer or other wearable technology as part of the physical activity intervention.ConclusionsWe provide insight into the opinions and experiences of the acceptability of the PrEvENT diet and physical activity intervention from the participants themselves. The interventions delivered were acceptable to this sample of participants, as were the data collection methods utilized. We also highlight some considerations for further behavioural change interventions in prostate cancer and other similar populations.Trial registrationISRCTN, ISRCTN99048944. Registered on 17 November 2014.