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Article of the week: A four‐group urine risk classifier for predicting outcomes in patients with prostate cancer

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Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

A four‐group urine risk classifier for predicting outcomes in patients with prostate cancer

Shea P. Connell*, Marcelino Yazbek-Hanna*, Frank McCarthy†, Rachel Hurst*, MartynWebb*, Helen Curley*, Helen Walker‡, Rob Mills‡, Richard Y. Ball‡, Martin G. Sanda§, Kathryn L. Pellegrini§, Dattatraya Patil§, Antoinette S. Perry, Jack Schalken**, Hardev Pandha††, Hayley Whitaker‡‡, Nening Dennis†, Christine Stuttle†, Ian G. Mills§§¶¶***, Ingrid Guldvik¶¶, Movember GAP1 Urine Biomarker Consortium1, Chris Parker†††, Daniel S. Brewer*‡‡‡, Colin S. Cooper* and Jeremy Clark*

*Norwich Medical School, University of East Anglia, Norwich, †Institute of Cancer Research, Sutton, ‡Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK, §Department of Urology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA , School of Biology and Environmental Science, Science West, University College Dublin, Dublin 4, Ireland, **Nijmegen Medical Centre, Radboud University Medical Centre, Nijmegen, The Netherlands, ††Faculty of Health and Medical Sciences, The University of Surrey, Guildford, ‡‡Molecular Diagnostics and Therapeutics Group, University College London, London, §§School of Medicine, Dentistry and Biomedical Sciences, Institute for Health Sciences, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK, ¶¶Centre for Molecular Medicine, University of Oslo, Oslo, Norway, ***Nuffield Department of Surgical Sciences, University of Oxford, Oxford, †††Royal Marsden Hospital, Sutton and ‡‡‡Earlham Institute, Norwich, UK

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Abstract

Objectives

To develop a risk classifier using urine‐derived extracellular vesicle (EV)‐RNA capable of providing diagnostic information on disease status prior to biopsy, and prognostic information for men on active surveillance (AS).

Patients and Methods

Post‐digital rectal examination urine‐derived EV‐RNA expression profiles (n = 535, multiple centres) were interrogated with a curated NanoString panel. A LASSO‐based continuation ratio model was built to generate four prostate urine risk (PUR) signatures for predicting the probability of normal tissue (PUR‐1), D’Amico low‐risk (PUR‐2), intermediate‐risk (PUR‐3), and high‐risk (PUR‐4) prostate cancer. This model was applied to a test cohort (n = 177) for diagnostic evaluation, and to an AS sub‐cohort (n = 87) for prognostic evaluation.

Table 2. NanoString gene probes incorporated by LASSO regularization in the final optimal model used to produce the prostate urine risk signatures

Results

Each PUR signature was significantly associated with its corresponding clinical category (P < 0.001). PUR‐4 status predicted the presence of clinically significant intermediate‐ or high‐risk disease (area under the curve = 0.77, 95% confidence interval [CI] 0.70–0.84). Application of PUR provided a net benefit over current clinical practice. In an AS sub‐cohort (n = 87), groups defined by PUR status and proportion of PUR‐4 had a significant association with time to progression (interquartile range hazard ratio [HR] 2.86, 95% CI 1.83–4.47; P < 0.001). PUR‐4, when used continuously, dichotomized patient groups with differential progression rates of 10% and 60% 5 years after urine collection (HR 8.23, 95% CI 3.26–20.81; P < 0.001).

Conclusion

Urine‐derived EV‐RNA can provide diagnostic information on aggressive prostate cancer prior to biopsy, and prognostic information for men on AS. PUR represents a new and versatile biomarker that could result in substantial alterations to current treatment of patients with prostate cancer.

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A taster week in urology and renal transplant in the UK

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A taster week is a training opportunity offered to UK doctors in their first two years of clinical practice to try a new specialty. They are an important learning experience for doctors at this stage, who will have experienced working in six different specialties at most. While taster weeks are only five days long, they offer a unique insight into a new specialty, as well as the chance to network with registrars and consultants.

During medical school I was interested in transplantation, as I found the combination between surgery and immunology interesting. This led me to complete a Master of Research in Transplantation while at medical school. During this degree, I looked at urinary tract infection in transplant patients and this started my interest in urology.

In the UK, the majority of trainees enter the field of transplantation following training in General Surgery. In clinical practice, it is good to have urologists with an active interest in Renal Transplantation for the betterment of these patients but there are few centres where this can be learnt. However, the Freeman Hospital in Newcastle, UK offers a one to two-year fellowship in renal transplantation which can be completed at the end of urology training. I contacted one of the urology and renal transplant surgeons and organised a week’s visit to the Freeman Hospital.

 

During my taster week I had the opportunity to shadow a urology and renal transplant surgeon. I joined urology and transplant ward rounds, including a renal transplant grand round, and I also attended a transplant nephrology clinic where I saw the long-term management of patients who had received kidney transplants.  I observed theatre lists in both urology and transplant and saw the wide variety of operations that urology and transplant surgeons are involved in, such as renal access surgery for dialysis and robotic partial nephrectomy for renal cancer.

I also had a chance to attend multi-disciplinary team meetings about new transplant recipients as well as an x-ray imaging meeting concerning live kidney donors.

Speaking to urology and renal transplant surgeons was an invaluable experience and helped me plan the next steps in my career as well as solidify it as a preferred career choice.

The highlight of my taster week was attending regional surgical teaching. I spent a day in one of the few world-class cadaveric training laboratories in the UK and learnt how to perform an orchidopexy for testicular torsion and vascular anastomosis; two operations that are no doubt necessary for a urology and renal transplant surgeon.

I am very glad I completed a taster week in urology and renal transplantation. It allowed me to experience the variety of work involved in this niche specialty. It was an experience that would have only been available much later in my career otherwise, which would be at a point too late for a career change.

by Matthew Byrne

 

Matthew Byrne recently completed two years as an Academic Foundation Doctor in Cambridge, UK. He graduated MBBS from Newcastle where he also completed a Master of Research in Transplantation. He is now a Urology Clinical Fellow in Cambridge, UK.

 

 

Visual abstract: Current status of artificial intelligence applications in urology and their potential to influence clinical practice

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Video: Resident burnout in USA and European urology residents

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Resident burnout in USA and European urology residents: an international concern

Abstract

Objective

To describe the prevalence and predictors of burnout in USA and European urology residents, as although the rate of burnout in urologists is high and associated with severe negative sequelae, the extent and predictors of burnout in urology trainees remains poorly understood.

Subjects and methods

An anonymous 32‐question survey of urology trainees across the USA and four European countries, analysing personal, programme, and institutional factors, was conducted. Burnout was assessed using the validated abridged Maslach Burnout Inventory. Univariate analysis and multivariable logistic regression models assessed drivers of burnout in the two cohorts.

Results

Overall, 40% of participants met the criteria for burnout as follows: Portugal (68%), Italy (49%), USA (38%), Belgium (36%), and France (26%). Response rates were: USA, 20.9%; Italy, 45.2%; Portugal, 30.5%; France, 12.5%; and Belgium, 9.4%. Burnout was not associated with gender or level of training. In both cohorts, work–life balance (WLB) dissatisfaction was associated with increased burnout (odds ratio [OR] 4.5, P < 0.001), whilst non‐medical reading (OR 0.6, P = 0.001) and structured mentorship (OR 0.4, P = 0.002) were associated with decreased burnout risk. Lack of access to mental health services was associated with burnout in the USA only (OR 3.5, P = 0.006), whilst more weekends on‐call was associated with burnout in Europe only (OR 8.3, P = 0.033). In both cohorts, burned out residents were more likely to not choose a career in urology again (USA 54% vs 19%, P < 0.001; Europe 43% vs 25%, P = 0.047).

Conclusion

In this study of USA and European urology residents, we found high rates of burnout on both continents. Despite regional differences in the predictors of burnout, awareness of the unique institutional drivers may help inform directions of future interventions.

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July 2019 – About the cover

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The Article of the Month for July is the latest NICE guideline on prostate cancer – diagnosis and management. The National Institute for Health and Care Excellence (NICE) based in London, UK was established in 1999 to provide national guidance and advice to improve health and social care. It has published over 50 documents covering urology, including guidance, advice and pathways. Since 2012 NICE has also been responsible for social care guidance. Although its main focus is England, NICE has gained an international reputation as a role model for developing clinical guidelines and providing assessments of new technologies.

The cover image shows the UK from space with the northern lights over the horizon. The best place in the UK to see the northern lights is in the northern part of Scotland, however, if the conditions are right they can be seen as far south as Cornwall.

 

© istock.com/Elen11

Why attend Advanced Prostate Cancer Consensus Conference APCCC 2019?

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From the 29th to the 31st of August 2019 the next Advanced Prostate Cancer Consensus Conference #APCCC19 will take place in Basel, Switzerland. The consensus conference was inspired by the very successful and pioneering early breast cancer consensus conference that was started in 1978 in St Gallen.

APCCC was initiated in 2015 because of the rapid developments in the field of advanced prostate cancer with the aim to discuss the clinical management of men with advanced prostate cancer, with a special focus on situations with a lack of or only weak evidence from the literature or conflicting evidence. Prostate cancer is such a common disease that the majority of men across the globe are not treated in expert centers but rather in smaller hospitals or community-based practices. APCCC wants to help the process of knowledge translation by assembling a large group of international prostate cancer experts that hold highly educational lectures summarizing the available literature and evidence, and discussing controversial questions.

The recommendations from the previous two conferences in 2015 and 2017 have been published open access in renowned scientific journals and have been widely read:

APCCC 2015 report

APCCC 2017 report

The expert panel in action at APCCC 2017

The following topics have been chosen for discussion at the 2019 conference:

  1. Locally advanced prostate cancer
  2. Biochemical recurrence of prostate cancer after local therapy
  3. Management of primary tumour in the metastatic situation
  4. Newly diagnosed metastatic prostate cancer, including oligometastatic prostate cancer
  5. Management of nmCRPC
  6. Management of mCRPC
  7. Bone and bone metastases
  8. Molecular characterization: tissue and blood
  9. Heterogeneity of men with prostate cancer (ethnicity, elderly)
  10. Side effects of hormonal treatments and their management

Difficult questions at APCCC17

Importantly all participants of APCCC can attend the consensus discussion and voting on Saturday morning. The questions and voting results will again form the basis for a report that will be published soon after the conference.

Why attend APCCC 2019?

The management of men with advanced prostate cancer keeps changing rapidly. Practice changing results have been recently presented and controversially discussed at ESMO (e.g. radiation therapy of the primary in the metastatic situation) and important new data will be presented at ASCO 2019 (e.g. results of standard-of-care therapy with or without enzalutamide or apalutamide for metastatic hormone-sensitive prostate cancer), making the choice of treatment in this situation even more challenging.

There are many reasons to attend APCCC 2019:

  • A unique opportunity to focus on the important topic of advanced prostate cancer management for two and a half days and be updated on current standards and state of the art of the care of men with advanced prostate cancer
  • Be involved in a global discussion on questions relevant to daily clinical practice but not investigated well

Expert interactions at APCCC17

  • Help to translate the outcomes from clinical trials into the management of men with prostate cancer in daily practice especially for men treated outside of large prostate cancer centers.
  • Be inspired and organize an APCCC satellite meeting for your country or region as has been done after the previous consensus conferences, with manuscripts published here in the BJUI.
    • Chiong et al. The Asia-Pacific Satellite of the APCCC BJUI 2019
    • Ma WK et al. Consensus statements on the management of clinically localized prostate cancer from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology BJU Int. 2019
    • Omlin A, Gillessen S. The Advanced Prostate Cancer Consensus on a regional level – what can we learn? BJU Int. 2019
  • And of course, enjoy a few wonderful summer days in the beautiful city of Basel!!!

Further information and links

APCCC 2019

Preview of APCCC 2019: Silke Gillessen, in conversation with Alicia Morgans, discusses many of the changes we have experienced in clinical practice since the last APCCC in 2017


APCCC on the THE “NEW” PROSTATE CANCER INFOLINK

 

by Dr Aurelius Omlin

Twitter: @apccc19
 

Video: Prostatic capsular incision during RP has important oncological implications. A systematic review and meta‐analysis

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Prostatic capsular incision during radical prostatectomy has important oncological implications. A systematic review and meta‐analysis

Abstract

Introduction

Capsular Incision (CapI) is an iatrogenic breach of the prostatic capsule during radical prostatectomy that can cause positive surgical margins (PSM) in organ‐confined (pT2) prostate cancer (PCa), or the retention of benign prostatic tissue. We systematically interrogated the literature in order to clarify the definition of CapI, and the implications of this event for rates of PSM and biochemical recurrence (BCR).

Methods

A literature search was conducted according to PRISMA criteria using the search terms ‘CapI’ AND ‘prostatectomy’ and variations of each. 18 studies were eligible for inclusion.

Results

A total of 51,057 radical prostatectomy specimens were included. The incidence of CapI ranged from 1.3‐54.3%. CapI definitions varied, and included a breach of the prostatic capsule “exposing both benign or malignant PCa cells”, “malignant tissue only”, or “benign tissue only”. The incidence of PSM due to CapI ranged from 2.8 – 71.7%. Our meta‐analysis results found that when CapI was defined as “exposing malignant tissue only in organ‐confined prostate cancer” there was an increased risk of BCR compared to patients with pT2 disease and no CapI (RR 3.53, 95%CI 2.82‐4.41; p < 0.00001).

Conclusions

The absolute impact of CapI on oncological outcomes is currently unclear due to inconsistent definitions. However, the data implies an association between CapI and PSM and BCR. Reporting of possible areas of CapI on the operation note, or marking areas of concern on the specimen, are critical to assist CapI recognition by the pathologist.

 

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