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Should we abandon live surgery: reflections after Semi-Live 2017

Prokar_v2Ever since 2002, I have performed live surgery almost every year where it is transmitted to an audience eager to learn. This year I was invited by Markus Hohenfellner to the unique conference, Semi Live 2017 in Heidelberg. To say that it was an eye opener is perhaps stating the obvious. One look at the program will show you that the worlds most respected Urological surgeons had been invited to participate, but with a difference. There was no live surgery. Instead videos of operations – open, laparoscopic and robotic were shared with the attendees “warts and all” as a learning experience. These were not videos designed to show the best parts of an operation. There were plenty of difficult moments, do’s and don’ts and troubleshooting, but all this was achieved without causing harm or potential harm to a single patient.

My highlights were laparoscopic sacrocolpopexy (Gaston), robotic IVC thrombectomy up to the right atrium (Zhang) and reconstructive surgery for the buried penis (Santucci). The event takes place every 2 years and the videos are all available on the meeting app which can be downloaded here and is an outstanding educational resource.

We were treated to a heritage session which included the superstars Walsh, Hautmann, Clayman, Mundy, Schroder and Ghoneim. This was followed by our host Markus Hohenfellner comparing and contrasting the art of Cystectomy and reconstruction by Ghoneim, Stenzl and Studer.

 

Open surgery is certainly not dead yet. The session ended with Seven Pillars of Wisdom from Egypt which turned out to be a big hit on Twitter.

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The editor’s choice session, a new innovation for 2017, allowed me to showcase the Best of BJUI Step by Step, a section that has now replaced Surgery Illustrated with fully indexed and citable HD videos and short papers.

Has live surgery had its day?

Many on Twitter seemed to agree that in 20 years time we might look back and say that it was not the right thing to do.

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Surgeons do not operate “live” every day. Most doctors in a survey, would not subject themselves or their families to be patients during live surgery. Talk about hypocrisy!! Why should it be any different for our patients? Live surgery is NOT a blood sport practised in Roman times….

The counterpoint is that patients often have the services of the best surgeons during live surgery, recorded, edited videos are not quite the same and that the whole affair has become safer thanks to patient advocates and strict guidelines from some organisations like the EAU. Others have banned the practice for good reason. While the debate continues, I for one came away feeling that Semi-Live was as educational, less stressful and much safer for our patients.

 

Prokar Dasgupta @prokarurol
Editor-in-Chief, BJUI 

 

RSM Urology Winter Meeting 2017, Northstar, California

rsm-2017-blogThis year’s Annual RSM Urology Section Winter Meeting, hosted by Roger Kirby and Matt Bultitude, was held in Lake Tahoe, California.

A pre-conference trip to sunny Los Angeles provided a warm-up to the meeting for a group of delegates who flew out early to visit Professor Indy Gill at the Keck School of Medicine.  We were treated to a diverse range of live open, endourological and robotic surgery; highlights included a salvage RARP with extended lymph node dissection and a robotic simple prostatectomy which was presented as an alternative option for units with a robot but no/limited HoLEP expertise.

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On arrival to Northstar, Dr Stacy Loeb (NYU) officially opened the meeting by reviewing the social media urology highlights from 2016. Next up was Professor Joseph Smith (Nashville) who gave us a fascinating insight into the last 100 years of urology as seen through the Journal of Urology. Much like today, prostate cancer and BPH were areas of significant interest although, in contrast, early papers focused heavily on venereal disease, TB and the development of cystoscopy. Perhaps most interesting was a slightly hair-raising description of the management of IVC bleeding from 1927; the operating surgeon was advised to clamp as much tissue as possible, close and then return to theatre a week later in the hopes the bleeding had ceased!

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With the promise of beautifully groomed pistes and stunning views of Lake Tahoe, it was hardly surprising that the meeting was attended by a record number of trainees. One of the highlights of the trainee session was the hilarious balloon debate which saw participants trying to convince the audience of how best to manage BPH in the newly inaugurated President Trump. Although strong arguments were put forward for finasteride, sildenafil, Urolift, PVP and HoLEP, TURP ultimately won the debate. A disclaimer: this was a fictional scenario and, to the best of my knowledge, Donald Trump does not have BPH.

The meeting also provided updates on prostate, renal and bladder cancer. A standout highlight was Professor Nick James’ presentation on STAMPEDE which summarized the trial’s key results and gave us a taste of the upcoming data we can expect to see in the next few years.

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We were fortunate to be joined by prominent American faculty including Dr Trinity Bivalacqua (Johns Hopkins) and Dr Matt Cooperberg (UCSF) who provided state-of-the-art lectures on potential therapeutic targets and biomarkers in bladder and prostate cancer which promise to usher in a new era of personalized therapy.

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A personal highlight was Tuesday’s session on learning from complications. It was great to hear some very senior and experienced surgeons speaking candidly about their worst complications. As a trainee, it served as a reminder that complications are inevitable in surgery and that it is not their absence which distinguishes a good surgeon but rather the ability to manage them well.

There was also plenty for those interested in benign disease, including topical discussions on how to best provide care to an increasingly ageing population with multiple co-morbidities. This was followed by some lively point-counterpoint sessions on robot-assisted versus open renal transplantation (Ravi Barod and Tim O’Brien), Urolift vs TURP (Tom McNicholas and Matt Bultitude) and HOLEP vs prostate artery embolization for BPH (Ben Challacombe and Rick Popert). Professor Culley Carson (University of North Carolina) concluded the session with a state-of-the art lecture on testosterone replacement.

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In addition to the excellent academic programme, delegates enjoyed fantastic skiing with perfect weather and unparalleled views of the Sierra Nevada Mountains. For the more adventurous skiiers, there was also a trip to Squaw Valley, the home of the 1960 Winter Olympics. Another highlight was a Western-themed dinner on the shores of Lake Tahoe which culminated in almost all delegates trying their hand at line dancing to varying degrees of success! I have no doubt that next year’s meeting in Corvara, Italy will be equally successful and would especially encourage trainees to attend what promises to be another excellent week of skiing and urological education.

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Miss Niyati Lobo
ST3 Urology Trainee, Brighton and Sussex University Hospitals NHS Trust

@niyatilobo

 

February Editorial: Raising the bar for systematic reviews with Assessment of Multiple Systematic Reviews (AMSTAR)

The BJUI has a longstanding track record in promoting the dissemination of high-quality unbiased evidence and helping their readership to understand why the principles of evidence-based medicine matter. This devotion is witnessed by the work that goes into every issue of the journal, as well as past initiatives such as providing a level of evidence rating for clinical research articles or publishing educational articles such as the ‘Evidence-Based Urology in Practice’ series [1, 2].

Major foci for clinically oriented specialty journals are systematic reviews and meta-analyses. Systematic reviews have a preeminent role in guiding the practice of evidence medicine by addressing focused clinical questions in a systematic, transparent and reproducible manner. Defining criteria of a high-quality systematic review include: an a priori registered protocol, a comprehensive search of multiple sources including unpublished studies (to avoid publication bias), an assessment of the quality of evidence that goes beyond study design alone, and a thoughtful interpretation of the findings. Systematic reviews inform clinicians and patients at the point of care, form the foundation of evidence-based clinical practice guidelines, and help shape health policy [3]. They also find frequent citation and can raise a journal’s impact factor. There is therefore more than one good reason for journals to care about the quality of systematic reviews.

Meanwhile, a study in this issue of the BJUI [4] shows that the methodological quality of systematic reviews published in the urological literature is modest, varies substantially, and has failed to improve over time. This contrasts to randomised controlled trials’ reporting quality that appears to have improved substantially over time, probably due to increased awareness among clinical researchers, urology readers and journal reviewers [4, 5]. The study [4] used the Assessment of Multiple Systematic Reviews (AMSTAR), a validated 11-item instrument, to measure the methodological quality of systematic reviews with higher scores reflecting better quality.

The authors [4] surveyed four major urological journals and compared the periods 2013–2015 to 2009–2012 and 1998–2008. Despite a dramatic increase in the number of systematic reviews published each year, methodological quality has stagnated with mean AMSTAR scores ± standard deviations of 4.8 ± 2.4 (2013–2015; = 125), 5.4 ± 2.3 (2009–2012; = 113) and 4.8 ± 2.0 (1998–2008; = 57). The average systematic review therefore has deficits in over half the 11 AMSTAR criteria and is of only modest quality thereby undermining our confidence in their results. Although the mean AMSTAR score of 5.6 ± 2.9 for 25 systematic reviews published in the BJUI in 2013–2015 compared favourably to similar studies in other leading urology journals, the difference was not statistically significant.

What are we going to do about it? Inspired by these findings, the BJUI is launching a new initiative to raise awareness for the issue of methodological quality of systematic reviews among its readership and raise the bars for its contributors. Future systematic review authors will be asked to submit an AMSTAR-based checklist to provide enhanced transparency about its methods that will be reviewed as part of the editorial review process. These include documentation of an a priori written protocol and ideally, registration of the systematic review through the Cochrane Collaboration or the Prospective Register of Systematic Reviews (PROSPERO). Such a protocol should outline all important steps of the review process including the definition of outcomes, study inclusion and exclusion criteria, details about the literature search, study selection and data abstraction process, analytical approach including planned sensitivity and subgroup analyses. Authors should also rate the quality of evidence looking beyond study limitation alone by using an approach such as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), which recognises such additional domains such as imprecision, inconsistency, indirectness and publication bias [6]. Critical steps of the systematic review process should be completed in duplicate to guard against random and systematic error and authors should provide readers with the information about who funded the studies included in the review, as well as their own potential conflicts of interests. To guard against publication bias, systematic review authors should also search for ongoing trials and unpublished studies through registries and abstract proceedings.

It is understood that the methodological handiwork that goes into the planning, execution and reporting of a systematic review do not assure clinical relevance or newsworthiness, nor does it address any issues surrounding the limited quality of studies that the review may be summarising. However, it is nevertheless a sine quae no to assure readers that they can be confident of the results. The new BJUI initiative will raise awareness for the issue of systematic review quality by providing a summary AMSTAR score to accompany each article. We hope that with this initiative we will provide a beacon for other specialty journals to follow, with the goal of raising the bar for all published systematic reviews and ultimately leading to improved patient care.

Philipp Dahm

 

Department of Urology, Minneapolis Veterans Administration Health Care System and University of Minnesota , MinneapolisMN, USA


References

 

1 Dahm P, Preminger GM. Introducing levels of evidence to publications in urology. BJU Int 2007; 100: 2467

 

 

 

4 HanJL, Gandhi S, Bockoven CG, Narayan VM, Dahm PThe landscape osystematic reviews in urology (1998 to 2015): an assessment of methodological quality. BJU Int 2016 [Epub ahead of print]. doi: 10.1111/bju.13653.

 

5 Narayan VM, Cone EB, Smith D, Scales CD Jr, Dahm P. Improved reporting of randomized controlled trials in the urologic literature. Eur Urol 2016; 70: 10449

 

6 Guyatt GH, Oxman AD, Vist GE et al. What is quality of evidence and why is it important to clinicians? BMJ 2008; 336: 9958

 

The times they are a-changin’

The other day, as the New York Times was getting excited about Nobel Laureate Bob Dylan new album ‘Triplicate’, I had the opportunity of remembering one of his classic songs. Let me explain. I turned up at the School of Surgery in central London for an academic committee meeting early that morning only to find that it had been cancelled. Due to a IT problem the email with this information never reached me! Rather than brave the London tube again, I decided to walk back to my hospital, which took me past my old hospital which sadly no longer exists.

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The old hospital in question was The Middlesex Hospital in Mortimer Street, London (Fig.1). The original institution was built in 1745 at Windmill Street and moved in 1757 to Mortimer Street. I arrived there over 20 years ago to train at the Institute of Urology/St. Peter’s Hospital, a highly desirable post amongst surgical residents.

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The Middlesex Hospital was closed in 2005 and sold to developers. It now houses swanky apartments and businesses around a beautiful Pearson Square, named after John Loughborough Pearson, who designed the Fitzrovia Chapel (Fig. 2) in 1890 inside the hospital. The Chapel survived the redevelopment as it is a protected building. So did one of the walls of the old hospital along Nassau Street which housed the radiotherapy building (Fig. 3). That facade has been preserved beautifully although there are no patients housed behind it anymore (Fig. 4).

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So why I am telling you all this? Nostalgia you may say. But in fact much more. The 3 mile walk that morning allowed me to reflect on my own contribution to science and that of two friends who although slightly ahead of me in the training program at The Middlesex Hospital are gentlemen that I greatly admire.

One is Mark Emberton, now Professor at UCL, who has, through the PROMIS study, established the use of MRI prior to prostate biopsies rather than random TRUS biopsies for patients with a raised PSA. The other is David Ralph, an acclaimed Andrologist, who has just published our Priapism Guidelines, a must read for everyone managing this emergency. There is no doubt that both have made significant contributions to British Urology and patient care in the last 20 years during which so many things have changed.

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As for me, I headed to Queen Square from The Middlesex Hospital, where many years of basic research in a Medical Research Council (MRC) funded lab led to the description of the so called “Dasgupta technique” of injecting Botox into overactive bladders. I was pleasantly surprised to hear that it had made its way into a number of texts including Smith’s Textbook of Endourology.

There are however certain things that do not change much. Next to the Middlesex Hospital, on Cleveland Street was the legendary Ragam’s (Fig. 5), which many would regard as THE go to South Indian restaurant. The masala dosa (pancake with spicy potatoes and hot lentil soup) used to cost £3.95 in 1994; 20 years later the price has gone up by only £2 to £5.95 (Fig. 6), while the quality remains as outstanding as ever.

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Prokar Dasgupta @prokarurol
Editor-in-Chief, BJUI 

 

5th International Neuro-Urology Meeting (INUM)

The Annual Congress of the International Neuro-Urology Society (INUS), organized by the Swiss Continence Foundation (SCF)

Neurogenic urinary tract, sexual and bowel dysfunction is highly prevalent and affects the lives of millions of people worldwide. It has a major impact on quality of life and, besides the debilitating manifestations for patients, it also imposes a substantial economic burden on every healthcare system.

It was a great honour and pleasure to organize the 5th International Neuro-Urology Meeting (INUM), which took place from 25-28 January 2017, in Zürich, Switzerland. We are proud to announce that the International Neuro-Urology Meeting, organized under the umbrella of the Swiss Continence Foundation (www.swisscontinencefoundation.ch), has become the official annual congress of the International Neuro-Urology Society (INUS, www.neuro-uro.org), a charitable, non-profit organization aiming to promote all areas of Neuro-Urology at a global level and whose inauguration was inspired during the last INUMs.

The world’s leading experts in Neuro-Urology provided an overview on the latest advances in research and clinical practice of this rapidly developing and exciting discipline. This unique meeting combined state-of-the-art lectures, lively panel discussions, and hands-on workshops with emphasis placed on interactive components. There were many opportunities to exchange thoughts, experiences and ideas and also to make new friendship.

The Swiss Continence Foundation Award: To promote the next generation of outstanding young researchers and clinicians who represent the future of Neuro-Urology, the prestigious Swiss Continence Foundation Award of 10’000 Swiss francs was awarded to the best contribution from a young Neuro-Urology talent: Marc Schneider from Zürich, Switzerland, convinced the international jury with the presentation of his PhD project “Anti-Nogo-A antibodies as a potential causal treatment for neurogenic lower urinary tract dysfunction after spinal cord injury”. He demonstrated in an animal model that intrathecally applied antibodies against the central nervous system protein Nogo-A which inhibits nerve fibre growth had beneficial effects on lower urinary tract dysfunction in rats with incomplete spinal cord injury by re-establishing a physiological micturition and preventing detrusor sphincter dyssynergia. This effect presumably occurs due to neuronal re-wiring of descending micturition circuits facilitated by the anti-Nogo-A antibodies. Anti-Nogo-A immunotherapy enters currently clinical trials in humans and could become a unique causal treatment option for lower urinary tract dysfunction in patients with incomplete spinal cord injury.

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One of many other highlights was the joint presentation of the EAU Secretary General Christopher R. Chapple and the BJUI Editor-in-Chief Prokar Dasgupta on the challenging topic “What should the neuro-urologist learn from the onco-urologist and vice-versa?”

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Finally, we are delighted to announce the 6th International Neuro-Urology Meeting to be held in Zürich, 25 to 28 January 2018. Save the date! For details please visit: www.swisscontinencefoundation.ch. We are looking forward to seeing you in Zürich!

Thomas M. Kessler, SCF Chairman and INUS Vice-President

Ulrich Mehnert, SCF Vice-Chairman and INUS Treasurer

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January 2017 Editorial: Infographics

‘A picture is worth a thousand words’ is an English idiom that has been in use for over a 100 years. Never has it been truer than in the age of social media, when fans are perhaps more interested in ‘selfies’ with their celebrity superstars than in their autographs!

With this in mind, we at the BJUI launched infographics last year for some of our very best papers. And what a success it has been based on the positive responses from our avid readers on Twitter. The titles of the articles that were selected for this format were:

  1. Oncological and functional outcomes 1 year after radical prostatectomy for very-low-risk prostate cancer: results from the prospective LAPPRO trial [1].
  2. Nephron-sparing surgery across a nation – outcomes from the British Association of Urological Surgeons 2012 national partial nephrectomy audit [2].
  3. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement [3].

All three featured amongst the list of the top 20 papers with most page views on www.bjui.org and the top 10 most downloaded articles from Wiley online library (WOL), reaching a figure of >2500. This compares well to our most downloaded ‘Guideline of Guidelines’on thromboprophylaxis [4] at 2264. The infographics lay out clear messages on important topics in a concise manner and have undeniable appeal to busy clinicians, who often have just a few valuable minutes to keep abreast with the latest highlights (Fig. 1).

Figure 1. Extract of infographics for the Fernando et al. [2] paper ‘Nephron-sparing surgery across a nation – outcomes from the British Association of Urological Surgeons 2012 national partial nephrectomy audit’. NSS, nephron-sparing surgery.

We also thought we would kick off the New Year with Guidelines on minimally invasive adrenalectomy from the International Consultation on Urological Diseases (ICUD) consultation [5]. And of course the ‘hot topic’ of enhanced recovery to try and reduce the length of stay for our cystectomy patients without increasing complications or readmission rates [6].

We are looking forward to engaging with you with more infographics in 2017.

Prokar Dasgupta, BJUI Editor-in-Chief
Kings Health Partners, London, UK

 

 

References

  1. Carlsson S, Jaderling F, Wallerstedt A et al. Oncological and functional outcomes 1 year after radical prostatectomy for very-low-risk prostate cancer: results from the prospective LAPPRO trial. BJU Int 2016; 118: 205–12
  2. Fernando A, Fowler S, O’Brien T, British Association of Urological Surgeons (BAUS). Nephron-sparing surgery across a nation – outcomes from the British Association of Urological Surgeons 2012 national partial nephrectomy audit. BJU Int 2016; 117: 874–82
  3. Kim ED, McCullough A, Kaminetsky J. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement. BJU Int 2016; 117: 677–85
  4. Violette PD, Cartwright R, Briel M, Tikkinen KA, Guyatt GH. Guideline of guidelines: thromboprophylaxis for urological surgery. BJU Int 2016; 118: 351–8
  5. Ball MW, Hemal AK, Allaf ME. International Consultation on Urological Diseases and European Association of Urology International Consultation on Minimally Invasive Surgery in Urology: laparoscopic and robotic adrenalectomy. BJU Int 2017; 119: 13–21
  6. Baack Kukreja JE, Kiernan M, Schempp B et al. Quality improvement in cystectomy care with enhanced recovery (QUICCER study). BJU Int 2017; 119: 38–49
See more infographics

Public Pronouncements and Individual Responsibility

jonathan-glassThe articles beneath headlines in the media relating to medicine rarely contain anything truly revolutionary or even anything particularly new despite what the headlines might have suggested.  We have all seen headlines promising a new cure for cancer, condemning an individuals practice and suggesting they are a charlatan and articles suggesting doctors are under-treating patients and depriving them of life changing care or over-treating patients and wasting and misusing limited resources.  More often than not the hyperbole of the headlines fail to truly represent the truth.  What is claimed to be new turns out to be old news, cures for cancer never show the results that were promised, and the extremes of over or under treatment are never quite as extreme as suggested.

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A week or two ago we have seen the newspapers filled with headlines about a list of 40 treatments or tests that form part of current practice that are deemed unnecessary.  This list was originated from the ChoosingWisely group, an American group now established in the UK.  This organisation encourages both patients and clinicians to question what they are doing and whether certain processes or interventions are wise, necessary and appropriate resource efficient.

Much of the recommendations on these lists in these sites are undoubtedly true and worth looking at to make sure your practice is mainstream although much of the advice is old and well established.  The AUA has 10 recommendations on the US based Choosingwisely.org website the vast majority of which are simply current practice (don’t do a bone scan in men with low risk prostate cancer), however one or two make me feel uncomfortable and one or two differ on the UK and US websites.

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The recent headlines were predictable –  ‘40 common treatments and tests that doctors say aren’t necessary‘ & ‘Senior doctors condemn 40 treatments and tests as being of little or no use‘. Among the advice that reached the headlines obtained from the UK site (choosingwisely.co.uk) was the statement ‘Unless a patient is at risk of prostate cancer because of race or family history, PSA based screening does not lead to a longer life’.  The UK site has also commented on the use of chemotherapy in ‘advanced’ cancer saying it may not be appropriate – also evidently true.  The US site includes the recommendation that creatinine is not measured in men with benign prostate disease and minor lower urinary tract symptoms. 
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One particular problem with these public health, committee lead recommendations and advice is that treating populations is easy.  Populations don’t sue public organisations, individual patients sue individual practitioners and therein lies the nub.  What may be right as an idea – not measuring creatinine in men with low grade LUTS – is fine until the chap who has significant renal impairment walks in to your clinic and asks you why you didn’t measure his creatinine when he saw you a year ago.   Not measuring a PSA seems fine until the patient with missed prostate cancer reappears and suggests he asked you about testing his PSA, but as he had no family history and wasn’t black you told him it wasn’t necessary;  you showed him a website and explained to him we’d be wasting resources if you tested his PSA.   He may not understand that the delay may not have impacted on his survival.  Patients don’t hear that if they perceive there has been a delay in establishing a diagnosis.

Treating individuals, caring for the person across the table from you is very different from making pronouncements about populations.   It’s easy to recommend that chemotherapy is not used, until you are the one being offered a chance, if only small, of being offered some hope and a chance of survival.

I recognise that resources are not endless and that it is right for clinicians and healthcare workers in all sectors to think about how resources are used. The problem however is that the user of healthcare resource – the patient – wants their care to be lowest risk, independent of cost, and increasingly they are resorting to using legal channels if they perceive that care has been anything other than perfect.

Of the men on those panels not recommending use of PSA, I wonder how many of them would refuse to have it checked, or indeed would refuse chemotherapy if it was their only, if slim, hope?

 

Jonathan Glass

Consultant Urologist

Guy’s & St Thomas Hospital

 

Immunotherapy in urological malignancies: can you take your knowledge to the next level?

bju13648-fig-0001In this month’s issue of the BJUI, we highlight the evolving era of immunotherapy in solid tumour therapy. As urological surgeons, we spend a large portion of our time working with anatomy, instruments, and robots – things we can see, touch, and control. Immunotherapy is a different conversation – cartoon pathways, process blockades, molecular expression levels, combination therapies, and treatment resistance. Curing a patient with a successful operation is a major draw to our field, but we know our limitations when faced with lethal variant prostate cancer, and high-grade/high-stage bladder and kidney cancers in particular. Systemic therapies have been around for decades and are part of our guidelines – so why all the excitement over immunotherapy?

Our highlighted articles are a review from Mataraza and Gotwals [1] and a comment from Elhage et al. [2]. I urge you to start with the review article [1] and give it a full line-by-line read. You may need to pull out pen and paper, and practice spelling and pronouncing a number of new compounds. They may sound as awkward as abiraterone did the first time you heard of it years ago but will eventually become familiar and attached to yet another catchy trade name from pharma. Here is a quick list/homework assignment: ipilimumab, nivolumab, pembrolizumab, pidilizumab, atezolizumab. Another 20 or more are in development. Challenge yourself to write out their pathways, and you may re-learn a thing or two about familiar agents like sipuleucel-T, interferon α, and interleukin 2.

A major theme in both articles is the experience with immunotherapy in advanced melanoma. The enticing message is that a cohort of patients with metastatic melanoma treated with ipilimumab survived 3 years and the Kaplan–Meier curves plateau out to 10 years. This observation sparks different possible futures such as immune ‘memory’, durable response, and ultimately the word we like to use in surgery – cure.

The picture in urological cancers is not entirely as rosy as the melanoma Kaplan–Meier curve. Multiple trials are highlighted by our review with familiar themes of single agent trials, combination immunotherapies, and combined immunotherapy plus anti-angiogenesis agents. Many trials enrol heavily pre-treated populations with limited remaining options. Many endpoints still observe responses followed by resistance patterns. An important theme to follow is the coupling of biomarkers that link expression to treatment response (i.e. predictive vs prognostic), and the USA Food and Drug Administration (FDA) has approved such a biomarker for nivolumab response. However, even this story line is perplexing, as drug response is not always linked to the marker, and immune cell expression may be ‘inducible and dynamic’ [1].

Last step – re-read the review and comment articles and see if you can write down some key agenda items for future immunotherapy. How are checkpoint inhibitors different from vaccines? How do we generate a durable immune response? What is the ‘abscopal effect’? What are three major areas of research and development in immunotherapy?

If you can spend the time on these articles and ponder these challenging questions, you will move up to the next level of understanding and enjoy a greater appreciation of the next abstract you hear at a major meeting. In closing, I am reminded of the oft-repeated words from the hit television show Game of Thrones (based on the novels of George R.R. Martin) from the House Stark: ‘Winter is Coming’. In urological oncology, ‘Immunotherapy is Coming’, so be prepared!

 

John W. Davis

BJUI Associate Editor Urological Oncology

 

References

1 Mataraza JM, Gotwals P. Recent advances in immuno-oncology and its application to urological cancers. BJU Int 2016; 118: 50614

 

2 Elhage O, Galustian C , Dasgupta P. Immune checkpoint blockade treatment for urological cancers? BJU Int 2016; 118: 498505

 

Asia-Pacific Prostate Cancer Conference 2016 Highlights

JSAfter briefly venturing to tropical Cairns in 2015, the Asia-Pacific Prostate Cancer Conference returned to its traditional home in Melbourne for its 17th edition in 2016 (#APCC16). The meeting has previously featured the who’s who of prostate cancer and this year was no different with an all-star multidisciplinary faculty consisting of 18 international members in addition to our local experts. The meeting was well attended by over the 750 delegates from all parts of the globe and remains one of the largest prostate cancer educational events worldwide.

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Conference president Professor Tony Costello opened the conference with the famous Whitmore aphorisms and outlined the impressive progress and discoveries we have made in the field over the last century. The first case of prostate cancer was described in 1853 in the London Hospital and was noted by the surgeon to be a “very rare disease” whereas now it is known to be the most commonly diagnosed malignancy amongst men. Pleasingly, research and emphasis on men’s health has grown with the disease highlighted by the newly completed, world-class Parkville Biomedical precinct in Melbourne, which includes “The Royal Men’s Hospital” (@APCR). Melbourne’s Lord Mayor (@LordMayorMelb) also dropped-by to reiterate his support for the meeting and the advancements made in men’s health.

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In what is becoming an annual tradition, honourary Melbournian and Australian, Dr Stacy Loeb (@LoebStacy) once again got the sessions off to a flying start by delivering the ‘prostate cancer year in review’ which was an excellent overview of the abstracts produced over the last 12 months. The male attendees in particular were excited by the recent paper suggesting that more than 21 ejaculations per month acted as a protective factor for the development of prostate cancer. Although confounding factors may have played a role in the association seen, these were easily over-looked and its results were accepted as gospel and promoted as a public health message. The abstract featured the following day on the home page of The Australian Financial Review (https://www.afr.com/lifestyle/health/mens-health/tell-your-partner-frequency-counts-even-against-cancer-20160831-gr5fs4) – who knew that the answer to the world economic problems was so simple!

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The meeting did however become more scientific as we heard from a range of international and local experts on the challenges of trying to find the balance of precision oncology in a time of tumour heterogeneity. It was clear that the future has arrived with recent advances in the field of genomics and biomarkers. These discoveries appear to be only the tip of the iceberg and further research holds the key in understanding tumour behavior in order to tailor treatment on a patient-to-patient level. Having witnessed a variety of experts from all parts of the globe present their finding there is little doubt that a major breakthrough is just around the corner. A special mention to Dr Niall Corcoran whose research was of such high quality that A/Prof Henry Woo (@DrHWoo) raised the white flag early in the Melbourne vs. Sydney inter-city rivalry.

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The named lectures of #APCC16 were highlights of the conference. Keeping with the theme of the first morning, Dr Martin Gleave delivered the 4th Patrick C Walsh lecture titled ‘Two Tales of Precision Oncology.” Prof Peter Wiklund gave the inaugural ERUS lecture on the role of surgery for high risk and metastatic prostate cancer.

It wouldn’t have been a prostate cancer conference without the age-old debate of surgery vs. radiotherapy being revisited. Over three days Dr Robert Nam presented a series of talks on Canadian long-term outcomes and meta-analysis showing favourable results for team surgery. He also predicted that the highly anticipated ProtecT randomised trial due in the NEJM would show no difference ensuring the debate prolongs into the future and vowed to “eat my shorts” if the trial demonstrated a result favouring either modality. Dr John Violet flew the flag strongly for radiation oncologists in presenting the promising outcomes for 177Lu-PSMA in the mCRPC setting. Similarly, Dr Andrew Kneebone presented a compelling case for stereotactic radiation for oligometastatic disease.

1.5

Imaging of the prostate was a hot topic throughout the conference. The excitement around PSMA-PET was at a climax following The Victorian Comprehensive Cancer Centre’s (@VCCC) experience that was presented by Associate Professors Michael Hofman (@DrMHofman) and Nathan Lawrentschuk (@lawrentschuk). The proceeding panel discussion focused on how to best utilise the technology and the role it currently plays in the prostate cancer landscape.  Despite not being FDA approved, its role in evaluating recurrence appears to be entrenched with data to support its superiority over other modalities but it was also proposed that it might have a place in initial staging of high-risk cancer.  The advancement of PSMA over conventional imaging also raised the question of how we now interpret previous trials such as CHAARTED and STAMPEDE whose results are based on superseded technology.

The hype surrounding PSMA-PET only just eclipsed that of mpMRI in the imaging landscape. Professor Philip Stricker presented a nomogram, which integrated MRI in determining who to biopsy and Dr Rob Reiter reported a terrific novel study of using 3D modeling to compare MRI results to final histopathology to determine correlation but did caution us with performing targeted biopsies alone which risks missing clinically significant cancers. Dr Nam also chimed in with a pilot study of using MRI as a screening test.

Suspense was built until Friday for the highly anticipated session on open vs. robotic surgery featuring the first presentation of the Brisbane RCT. The results of the trial have been already widely debated in the urological community and a discussion similar to the recent BJUI blog (https://www.bjuinternational.com/bjui-blog/its-not-about-the-machine-stupid/) ensued. Regardless of individual opinions on the trial, there is no dispute about the volume of work required to conduct a surgical randomised trial and there was wide praise for the efforts of the Brisbane team. Prof Peter Wiklund and Dr Homi Zargar (@hzargar) also reported the Swedish and Victorian experience respectively. The overall consensus was that robotic surgery offers the benefit of minimally invasive surgery but it is the surgeon rather than the modality, which has the most significant impact on outcomes.

1.6

There was a strong multi-disciplinary theme throughout the conference. The Nursing & Allied Health and Translational Science streams both had strong contingents attending. The quality of research presented and engagement amongst attendee was of the highest standard. This was exemplified by the session ‘MDT 2020’, which was a case-centred discussion by a panel of experts from a variety of professions and highlighted the value of a multidisciplinary approach in patient care.

1.7

1.8

The social program of #APCC16 was not overshadowed by its academic counterpart. The conference dinner was held at The Glasshouse where the food was exquisite and entertainment was provided by three waiters come tenors. Their classical renditions were received by guests with napkin twirling and swinging wine glasses. The frivolities were thoroughly enjoyed by all.

1.9

The final day of the conference was highlighted by the masterclasses. The 6th da Vinci© Prostatectomy Masterclass was convened by Drs Daniel Moon (@DrDanielMoon) and Geoff Coughlin and featured international faculty involvement by Dr John Davis (@jhdavis) and Professors Thalman and Wiklund. Considering the hype surrounding MRI it was no surprise that the 3rd Prostate MRI Imaging and Biopsy masterclass reached capacity many months ago. It should also be mentioned that the sponsored satellite meetings and breakfast sessions in the previous days which starred Dr Stacy Loeb, Dr Tia Higano (@thigano), Dr Jaspreet Sandhu, Prof Bertrand Tombal (@BertrandTOMBAL) and Genevieve Muir-Smith drew large numbers of attendees.

We would like to congratulate all attendees and their teams on the abstracts presented throughout the conference. The BJUI once again proudly supported the meeting with all accepted abstracts published in a special supplements issue and BJUI Associate Editors Declan Murphy (@declanmurphy), John Davis, and Nathan Lawrentschuk being prominent figures throughout the conference. A special mention to the poster prize winners from this year:

  • Clinical Urology: Jonathan Kam – Do multi-parametric MRI guided biopsies add value to the standard systematic prostate needle biopsy? – early experience in an Australian regional centre
  • Nursing & Allied Health: Thea Richardson – An Androgen Deprivation Therapy Clinic: An integrative approach to treatment
  • Translational Science: Natalie Kurganovs – Identifying the origins and drivers of castration resistant prostate cancer

1.10

On behalf of all the delegates, we thank the entire international and local faculty who shared their knowledge over the conference and devote their time to improving men’s health. Furthermore, meetings such as this would not occur without the unheralded behind the scenes work. We extend our thanks to president Prof Costello, the convenors of the streams (A/Prof Declan Murphy, Dr Niall Corcoran, A/Prof Chris Hovens, Ms Helen Crowe (@helenrcrowe) & Mr Dave Gray (@DavidGrayAust)) and the APCC committee. We also graciously thank our sponsors without whom none of this would be possible and are vital to further advancements in men’s health.

Last but not least, given the rich history of social media seen at this conference, it would be remiss not to acknowledge another #SoMe landmark. Melbourne has previously been responsible in welcoming urology SoMe royalty, Dr Stacy Loeb, to the twitter world and this year the twitterati were introduced to Dr Peter Carroll (@pcarroll_). He managed to send out 4 tweets and eclipse 100 followers before the end of the conference.

1.11

#APCC17 will return to Melbourne on 30th of August 2017 – we hope to see you there!

Dr Niranjan Sathianathen (@NiranjanJS) is a researcher at Peter MacCallum Cancer Centre, Melbourne.

 

Randomised Controlled Trials in Robotic Surgery

PDGSep16It has been nearly 15 years since one of the first ever randomised controlled trials (RCT) in robotic surgery was conducted in 2002. The STAR-TRAK compared telerobotic percutaneous nephrolithotomy (PCNL) to standard PCNL and showed that the robot was slower but more accurate than the human hand [1].

In the 24 h since the much anticipated RCT of open vs robot-assisted radical prostatectomy was published in The Lancet [2], our BJUI blog from @declangmurphy was viewed >2500 times, receiving >40 comments, making it one of our most read and interactive blogs ever. It is a negative trial showing no differences in early functional outcomes between the two approaches.

And it is not the only negative trial of its kind as a number of others have matured and reported recently. The RCT of open vs robot-assisted radical cystectomy and extracorporeal urinary diversion showed no differences in the two arms [3], and likewise a comparison of the two approaches to cystectomy as a prelude to the RAZOR (randomised open vs robotic cystectomy) trial showed no differences in quality of life at 3-monthly time points up to a year [4]. The only RCT comparing open, laparoscopic and robotic cystectomy, the CORAL, took a long time to recruit and yet again showed no differences in 90-day complication rates between the three techniques [5].

In all likelihood, despite the level 1 evidence provided in The Lancet paper showing no superiority of the robotic over the open approach, the Brisbane study may not change the current dominance of robotic prostatectomy in those countries who can afford this technology. Why is this? Apart from the inherent limitations that the BJUI blog identifies, there are other factors to consider. In particular, as observed previously in a memorable article ‘Why don’t Mercedes Benz publish randomised trials?’ [6], there may be reasons why surgical technique is not always suited to the RCT format.

A few additional reflections are perhaps appropriate at this time:

  1. Despite the best statistical input many of these and future studies are perhaps underpowered.
  2. Many have argued that the RCTs have shown robotics to be as good, although not better than open surgery, even in the hands of less experienced surgeons.
  3. Patient reported quality of life should perhaps become the primary outcome measure because that in the end that is what truly matters.
  4. Cost-effectiveness ratios should feature prominently, as otherwise there is much speculation by the lay press without any hard data.
  5. Industry has a role to play here in keeping costs manageable, so that these ratios can become more palatable to payers.
  6. Surgery is more of an art than a science. The best surgeons armed with the best technology that they are comfortable with will achieve the best outcomes for their patients.

While this debate will continue and influence national healthcare providers and decision makers, the message looks much clearer when it comes to training the next generation of robotic surgeons. A cognitive- and performance-based RCT using a device to simulate vesico-urethral anastomosis after robot-assisted radical prostatectomy (RARP) showed a clear advantage in favour of such structured training [7]. In this months’ issue of the BJUI, we present the first predictive validity of robotic simulation showing better clinical performance of RARP in patients [8]. This is a major step forward in patient safety and would reassure policy makers that investment in simulation of robotic technology rather than the traditional unstructured training is the way forward.

Most of our patients are knowledgeable, extensively research their options on ‘Dr Google’ and decide what is good for them. It is for this reason that many did not agree to randomisation in other robotic vs open surgery RCTs, like LopeRA (RCT of laparoscopic, open and robot assisted prostatectomy as treatment for organ-confined prostate cancer) and BOLERO (Bladder cancer: Open vs Lapararoscopic or RObotic cystectomy). Many of them continue to choose robotic surgery without necessarily paying heed to the best scientific evidence. Perhaps what patients will now do is select an experienced surgeon whom they can trust to use their best technology to deliver the best clinical outcomes.

Prokar Dasgupta @prokarurol
Editor-in-Chief, BJUI 

@declangmurphy

Associate Editor BJUI

References

2 Yaxley JW, Coughlin GD, Chambe rs SK et al. Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: early outcomes from a randomised controlled phase 3 study. Lancet 2016 [Epub ahead of print]. doi: 10.1016/S0140-6736(16)30592-X
3 Bochner BH, Sjoberg DD, Laudone VP, Memorial Sloan Kettering Cancer Center Bladder Cancer Surgical Trials Group. A randomized trial of robot-assisted laparoscopic radical cystectomy. N Engl J Med 2014; 371:38990

4

Messer JC, Punnen S , Fitzgerald J et al. Health-related quality of life from a

6 OBrien T, Viney R , Doherty A, Thomas K. Why dont Mercedes Benz publish
randomised trials? BJU Int 2010; 105 : 2935
8 Aghazadeh MA, Mercado MA, Pan MM , Miles BJ, Goh AC. Performance of

 

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