Tag: #BJUI

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Urologists in the Yellow Submarine – a Periscope to the World

April 20, 2015/5 Comments/by Henry Woo

Over the last few weeks, there has been a lot of chatter about a new Social Media platform. Just when you thought that we had exhausted all possible ways that people could interact online, live video streaming is the talk of the town.

Last month, two competing live video streaming apps were launched. Meerkat initially gained popularity quite rapidly, particularly through Twitter, given the ease and immediacy of being able to share your live video streaming with twitter followers. Twitter acquired its competitor, Periscope, and Meerkat’s access to the twitter followers was cut off no sooner than it had began. Already there are arguments as to which of the two platforms are better but I can already sense from user reactions and expert opinion, that Periscope will be the one that will prevail. The might of Twitter will be very difficult to compete with.

Why on earth would urologists be interested in live broadcasts? The obvious application is live streaming of events such as conferences. The default option is perform a public broadcast and this will have particular value when there is an advocacy focus. There is also an option to broadcast privately only to followers of the Periscope account performing the broadcast. The latter may well be the best option for more sensitive material but there are still issues that need to be sorted out. In particular, there is no simple mechanism to determine which followers should be permitted to follow the broadcasting account in order to see a private live stream. It is inevitable that this will be simplified in the future, as it would be logical for this platform to find a mechanism to attract business users.

As things are at present, one needs to have a twitter account in order to sign on to broadcast using Periscope. This platform is designed for the mobile user – this is both for broadcasting and for watching the live stream. Attempting to do this on a desktop or laptop website is cumbersome and clumsy from my initial attempts to do so whereas the iOS App was straightforward and intuitive, particularly for those already familiar with the Twitter app.

Note the similarity of the iOS Periscope App with the Twitter App interface.

It is my belief that the first ever Periscope live stream broadcast from a medical conference was performed on Sunday 12 April 2015 at the Urological Society of Australia and New Zealand’s (USANZ) Annual Scientific Meeting. Declan Murphy used Periscope to broadcast a message from Prokar Dasgupta, Editor-in-Chief of the BJUI Journal. The video from the Periscope live stream is below. This first, at least for a urological conference, was tweeted by Declan Murphy.

A couple of hours later, I performed a live video stream from the Social Media session when Imogen Patterson gave an excellent presentation on managing our online reputations. During the feed, observers are able to make comments as well as to demonstrate their approval by tapping their screens to trigger a flow of hearts from the bottom right hand corner of the screen.

This is a screenshot from an unrelated live video feed. From the bottom left, the user is notified of those joining the observation of the feed as well as comments. From the bottom right, hearts float upwards in response to positive taps of the screen by watchers.

There are a few issues with Periscope as it is right now. The feed is only available for 24 hours before disappearing from the Periscope platform, however, a video recording minus the comments and hearts, can be stored in the photo stream on your mobile device. As mentioned before, you must have a twitter account to broadcast although you do not need one to view a broadcast. Thirdly, directed broadcasting should be simplified.

Social media platforms come and go but the ability to live stream is an exciting new development. For Periscope, it is my belief that the potential application for a use in medical education seems boundless. Live broadcasting is no longer the exclusive domain of television and cable networks.

Henry Woo (@drhwoo) is Associate Professor of Surgery at the Sydney Adventist Hospital Clinical School of the University of Sydney. He is the Editor-in-Chief of BJUI Knowledge, an innovative on-line CME portal that launches this year.

Editorial: A urologists’ guide to the multi-parametric magnetic resonance imaging (mpMRI)-galaxy

April 15, 2015/by Christof Kastner

The rise of multi-parametric MRI (mpMRI) for the assessment of patients with suspicion of prostate cancer has led to an enormous shift in the practice of every urologist dealing with frontline diagnostics [1].

At the same time, researchers and industry have identified acres of fruitful soil to place the seeds of their respective interests, sometimes in collaboration with each other producing valuable contributions to this shift in practice, sometimes taking benefits by merely assimilating themselves or their product to this development.

Both, the speed of change and the extent of proliferation, make it almost impossible for by-standing clinicians to keep up and filter the evidence-based essence for their local practice.

There are three important issues that need to be considered:

1 The Quality of mpMRI

The development of mpMRI for prostate assessment occurred over the last decade with well-known leaders pushing the frontiers. Their research benefitted from their individual experience of interpreting and reporting MRIs. This is then reflected in their outcomes in form of cancer detection rates and accuracy. More recently we have identified that achieving these results must involve standardisation of MRI protocols and reading [2-4], systematic training in validated courses and a significant learning curve [5]. The latter is only possible to achieve if the practice is embedded in a collaborative team of radiologists, pathologists and urologists. But even then it may be impossible for local teams to deliver the published accuracy, and the urologists and radiologists need to be mindful of that when counselling patients using mpMRI in their local environment.

2 The Technical and Clinical Validity of MRI-Based Biopsies

Transperineal vs transrectal, targeted alone vs targeted with systematic, cognitive vs fusion biopsies – these are the key debates surrounding the application of mpMRI into the urologists’ armamentarium. For none of them there is or will be a unified answer.

Transrectal approaches suit office-based provision of primary diagnostics in many European and USA health economies; although purists can say that the increasing risk of sepsis from antibiotic-resistant bacteria is not acceptable. But, favouring the less infection-prone transperineal approaches will have impact on theatre capacities even in a hospital-based health system like the UK.

Considering the current real-time quality of mpMRI, systematic biopsies in addition to targeted ones are still necessary. Urologists as a group have to come to an agreement about what is acceptable as a remaining risk when reducing or omitting systematic cores.

Cognitive targeting has been shown to be highly accurate; yet, fusion may offer standardisation and reduce user dependency. Not all fusion software on the market has undergone a thorough validated technical development and clinical accuracy evaluation. Peer-reviewed publications can be found involving the systems Urostation-Koelis, Uronav-Philips, Artemis and BiopSee-Medcom.

3 Translation into Clinical Practice

The positioning of the mpMRI within the assessment algorithm is key to optimise the benefit. Use as a pre-biopsy assessment tool may allow omission of further biopsies in some patients or facilitate targeting [6]. However, an established skill in the use of mpMRI and mpMRI-based biopsy is essential. Many UK centres have started the use of mpMRI in their practice further downstream in patients with persistent suspicion after negative first biopsies with good results for patients. It is already part of guidance that active surveillance should involve the use of MRI [1]. Some leading centres advocate that the diagnosis should be confirmed by MRI-based targeted and systematic biopsies.

Knowing that mpMRI will improve the accuracy of our assessment, we need to re-consider follow-up protocols. Increased certainty should be reflected in an improved cancer-related outcome, better patient experience and reduction in costs for the health system.

Prostate mpMRI as part of the urologists’ armamentarium is here to stay. A standardised team- and evidence-based approach will allow us to remain in control of the destination it leads us to.

Read the full article

Christof Kastner

Cambridge University Hospitals, Cambridge, UK

References

1 National Institute for Health and Care Excellence (NICE). NICE clinical guideline 175. Prostate cancer: diagnosis and Treatment. Issued January 2014. Available at: https://www.nice.org.uk/guidance/cg175. Accessed December 2014

2 Barentsz JO, Richenberg J, Clements R et al. ESUR prostate MR guidelines 2012. Eur Radiol 2012; 22: 746–57

3 Moore CM, Kasivisvanathan V, Eggener S et al. Standards of reporting for MRI-targeted biopsy studies (START) of the prostate: recommendations from an International Working Group. Eur Urol 2013; 64: 544–52

4 Kuru TH, Wadhwa K, Chang RT et al. Deﬁnitions of terms, processes and a minimum dataset for transperineal prostate biopsies: a standardization approach of the Ginsburg Study Group for Enhanced Prostate Diagnostics. BJU Int 2013; 112: 568–77

5 Gaziev G, Wadhwa K, Barrett T et al. Deﬁning the learning curve for multi-parametric MRI of the prostate using MRI-TRUS fusion guided transperineal prostate biopsies as a validation tool. BJU Int 2015. [Epub ahead of print]. doi: 10.1111/bju.12892

6 Willis SR, Ahmed HU, Moore CM et al. Multiparametric MRI followed by targeted prostate biopsy for men with suspected prostate cancer: a clinical decision analysis. BMJ Open 2014; 4: e004895

Editorial: The need for standardised reporting of complications

April 8, 2015/by Quoc-Dien Trinh

In the context of diversifying practice models, implementation of new technologies such as the Da Vinci surgical robot and rising healthcare costs, there is growing interest in evaluating the quality of surgical work. This extends into health policy, as reimbursement penalties are introduced for ‘inappropriate’ outcomes (e.g. excessive readmissions). Consequently, there is a significant need to provide an accurate assessment of complications and mortality when reporting on surgical outcomes.

Despite the constant use of outcomes data to measure effectiveness in surgery, no current urology guidelines demand the standardised reporting of surgical complications [1]. As randomised controlled trials are uncommon within the surgical setting, and are associated with significant biases [2], there is a distinct need for a uniform reporting system after urological surgeries. Indeed, the lack of such makes it challenging to compare surgical outcomes between techniques, surgeons and institutions, thus hampering the interpretation of study results [3]. The ongoing (and never-ending) debate on the comparative effectiveness of open vs robot-assisted radical prostatectomy (RP) highlights the need for standardised methods to assess superiority (or inferiority) of surgical results [4].

In this issue of the BJUI, Soares et al. [5] present a single-surgeon study of 1138 laparoscopic RPs (LRPs) with a standardised approach between the years 2000 and 2008, and their 5-year follow-up. Whereas the functional and/or oncological equivalency of LRP compared with open RP has been reported before [6], perhaps the outstanding contribution of this study is the use of the Martin-Donat criteria to report and analyse surgical results [3, 7]. In 2002, Martin et al. [7] introduced a list of 10 standard criteria for accurate and comprehensive reporting of surgical complications (e.g. methods of data acquisition, duration of follow-up, definition of complications, hospital length of stay).

In Table 6 of their manuscript, Soares et al. [5] display surgical and/or oncological outcomes of a total of 17 studies on LRP (including their own data). This table suggests the obvious: there is no consistency of reporting on outcomes. In the 2007 Donat [3] analysis of surgical complications reporting in the urological literature, only 2% of a total of 109 studies met nine to 10 of the critical Martin criteria. Interestingly, these shortcomings have been addressed in more contemporary years as the number of studies complying with most of the Martin criteria has increased between 1999/2000 and 2009/2010 [1]. Yet, despite the increasing use of classification systems for outcomes of surgery and standardised reporting of complications (e.g. Clavien-Dindo classification), they are not routinely applied [1, 8].

In an era where the adoption of a certain surgical approach or technique needs to be carefully weighted against a demand for greater value and decreased costs, a simple case series on positive outcomes is simply not sufficient [9]; at the very least, guideline-compliant assessment of outcomes should be the standard of care.

Read the full article

Marianne Schmid*†, Christian P. Meyer*† and Quoc-Dien Trinh*

*Division of Urologic Surgery and Center for Surgery and Public Health, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA and† Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

References

1 Mitropoulos D, Artibani W, Graefen M, Remzi M, Roupret M, Truss M. Reporting and grading of complications after urologic surgical procedures: an ad hoc EAU guidelines panel assessment and recommendations. Eur Urol 2012; 61: 341–9

2 Omar MI, Lam TB, Alexander CE et al. Systematic review and meta- analysis of the clinical effectiveness of bipolar compared with monopolar transurethral resection of the prostate (TURP). BJU Int 2014; 113: 24–35

3 Donat SM. Standards for surgical complication reporting in urologic oncology: time for a change. Urology 2007; 69: 221–5

4 Schmid M, Gandaglia G, Trinh QD. The controversy that will not go away. Eur Urol 2014; [Epub ahead of print]. doi: 10.1016/ j.eururo.2014.02.052

5 Soares R, Di Benedetto A, Dovey Z, Bott S, McGregor R, Eden C. Minimum 5-year follow-up of 1138 consecutive laparoscopic radical prostatectomies. BJU Int 2014; [Epub ahead of print]. doi: 10.1111/ bju.12887

6 Hruza M, Bermejo JL, Flinspach B et al. Long-term oncological outcomes after laparoscopic radical prostatectomy. BJU Int 2013; 111: 271–80

7 Martin RC 2nd, Brennan MF, Jaques DP. Quality of complication reporting in the surgical literature. Ann Surg 2002; 235: 803–13

8 Yoon PD, Chalasani V, Woo HH. Use of Clavien-Dindo classiﬁcation in reporting and grading complications after urological surgical procedures: analysis of 2010 to 2012. J Urol 2013; 190: 1271–4

9 Novara G, Ficarra V, D’Elia C, Secco S, Cavalleri S, Artibani W. Trifecta outcomes after robot-assisted laparoscopic radical prostatectomy. BJU Int 2011; 107: 100–4

Editorial: Time to replace PSA with the PHI?

April 1, 2015/by Stacy Loeb

Yet more evidence that the PHI consistently outperforms PSA across diverse populations

The Prostate Health Index (PHI) has regulatory approval in >50 countries worldwide and is now being incorporated into prostate cancer guidelines; for example, the 2014 National Comprehensive Cancer Network Guidelines for early prostate cancer detection discuss the PHI as a means to improve specificity, using a threshold score of 35 [1]. The PHI is also discussed in the Melbourne Consensus Statement [2], and it has been incorporated into the multivariable Rotterdam risk calculator smartphone app for use in point-of-care decisions [3].

As the use of this test continues to expand, more data on its performance in specific at-risk populations are of great interest. The investigators from the PROMEtheus multicentre European trial have previously validated the use of the PHI in men with a positive family history of prostate cancer [4]. The new study by Abrate et al. in this issue of BJUI instead addresses another high-risk population – obese men – who have previously been shown to have a greater risk of aggressive prostate cancer [5].

Among the 965 participants in the PROMEtheus study, 14.7% were considered obese based on a body mass index ≥30 kg/m². In this group, 45.8% were diagnosed with prostate cancer from a ≥12-core biopsy, and 67.7% had a Gleason score ≥7. Overall, the PHI significantly outperformed PSA for prostate cancer detection in men with a body mass index ≥30 kg/m² (area under the curve 0.839 vs 0.694; P < 0.001). At 90% sensitivity, the threshold for PHI in obese men was 35.7, with a specificity of 52.3%. The PHI also had the best performance for the detection of Gleason ≥7 disease, with an area under the curve of 0.89.

These findings add to the highly consistent body of evidence supporting the use of the PHI in early prostate cancer detection and risk stratification. In fact, all published studies to date have shown that the PHI outperforms PSA for detection of overall and high-grade prostate cancer detection on biopsy [6]. Numerous studies have also shown a role for the PHI in patient selection and monitoring during active surveillance [7, 8]. Expanded use of this test is warranted to reduce unnecessary biopsies and better identify cancers with life-threatening potential.

Read the full article

Stacy Loeb

Department of Urology and Population Health, New York University, New York, NY, USA

References

1 National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Prostate Cancer Early Detection Version 2014. https://www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf.Accessed May 26, 2014

2 Murphy DG, Ahlering T, Catalona WJ et al. The melbourne consensus statement on the early detection of prostate cancer. BJU Int 2014; 113:186–8

3 Roobol M, Salman J, Azevedo N. Abstract 857: The Rotterdam Prostate Cancer Risk Calculator: Improved Prediction with More Relevant Pre-Biopsy Information, Now in the Palm of Your Hand. Stockholm: European Association of Urology, 2014

4 Lazzeri M, Haese A, Abrate A et al. Clinical performance of serum prostate-speciﬁc antigen isoform [-2]pr oPSA (p2PS A) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project. BJU Int 2013; 112:313–21

5 Freedland SJ, Banez LL, Sun LL, Fitzsimons NJ, Moul JW. Obese men have higher-grade and larger tumors: an analysis of the duke prostate center database. Prostate Cancer Prostatic Dis 2009; 12: 259–63

6 Filella X, Gimenez N. Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis. Clin Chem Lab Med 2013; 51: 729–39

7 Tosoian JJ, Loeb S, Feng Z et al. Association of [-2]proPSA with Biopsy Reclassiﬁcation During Active Surveillance for Prostate Cancer. J Urol2012; 188: 1131–6

8 Hirama H, Sugimoto M, Ito K, Shiraishi T, Kakehi Y. The impact of baseline [-2]proPSA-related indices on the prediction of pathological reclassiﬁcation at 1 year during active surveillance for low-risk prostate cancer: the Japanese multicenter study cohort. J Cancer Res Clin Oncol2014; 140: 257–63

Future Directions in Urological Oncology

March 31, 2015/by R. Houston Thompson

The field of urological oncology is rapidly changing. For example, robotic surgery, targeted therapy, and ablation techniques are oncological options that were in their infancy 10 years ago and are now mainstream in many areas of the world. Additionally, immunotherapy has recently become a promising avenue in multiple urological cancers. As we move forward, expect to see a larger presence of urological oncology literature obtained via social media, which BJUI has initiated and subsequently set the standard for the field. Related to this, this month’s edition of BJUI includes four online ‘Articles of the Week’, with each focusing on urological oncology.

Using data from the pro-PSA Multicentric European Study (PROMEtheuS) project, Abrate et al. [1] evaluated the utility of the Prostate Health Index (PHI) in 142 obese (body mass index BMI >30 kg/m²) men who underwent a prostate biopsy for an abnormal DRE or elevated PSA level. Among the 142 patients, 65 (45.8%) were found to harbour prostate cancer. Using the PHI threshold of 35.7, the authors determined that 46 (32.4%) negative biopsies could have been avoided while six (9.2%) cancers would have been missed. Related to this, Salami et al. [2] compared the cancer detection rates of MRI fusion biopsy vs standard 12-core TRUS-guided biopsy in 140 men with a previous negative prostate biopsy and a lesion appreciated on a multiparametric MRI. While the cancer detection rates were similar overall, the MRI fusion biopsy was more likely to detect clinically significant prostate cancer (48% vs 31%), defined as Gleason ≥7 or Gleason 6 with a lesion volume of >0.2 mL on MRI. In an era where over-diagnosis of prostate cancer is commonplace, data to better stratify patients who need (or do not need) a prostate biopsy and enhanced ways to identify clinically significant prostate cancers are of paramount importance.

Soares et al. [3] report their results among 1 138 contemporary laparoscopic radical prostatectomy patients who had at least 5 years of follow-up. Only one case required an open conversion and the transfusion rate was merely 0.5%. At last follow-up, 85% of patients had an undetectable PSA level, 94% of patients were continent, and 77% of non-diabetic men aged <70 years retained potency. These impressive single-surgeon results further suggest that the morbidity of prostate cancer surgery has diminished with increasing time and experience.

Additionally, Tolchard et al. [4] prospectively evaluated 105 patients with bladder cancer with preoperative cardiopulmonary exercise testing prior to radical cystectomy. Patients who received neoadjuvant chemotherapy were excluded and there was a 6% perioperative death rate with 90 days of follow-up. The results suggest that patients with poor cardiopulmonary reserve along with hypertension are at higher risk of perioperative complications and prolonged hospital stay; median length of stay was 22 and 9 days for patients with and without a complication. Furthermore, while only 2% of patients had a preoperative diagnosis of heart failure, there were a significant proportion of patients (50% in this study) found to have moderate-to-severe heart failure based on preoperative cardiopulmonary exercise testing. These provocative results suggest that the urological community should further investigate the utility of routine cardiopulmonary exercise testing in patients undergoing radical cystectomy along with the optimal incorporation of such testing in patients receiving neoadjuvant chemotherapy.

References

1 Abrate A, Lazzeri M, Lughezzani Gi et al. Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study. BJU Int 2015;115:537–45.

2 Salami SS, Ben-Levi E, Yaskiv O et al. In patients with a previous negative prostate biopsy and a suspicious lesion on magnetic resonance imaging, is a 12-core biopsy still necessary in addition to a targeted biopsy? BJU Int 2015;115:562–70.

3 Soares R, Di BenedettoA, Dovey Z, Bott S, McGregor RG, Eden CG. Minimum 5-year follow-up of 1138 consecutive laparoscopic radical prostatectomies. BJU Int 2015;115:546–53.

4 Tolchard S, Angell J, Pyke M et al. Cardiopulmonary reserve as determined by cardiopulmonary exercise testing correlates with length of stay and predicts complications after radical cystectomy. BJU Int2015;115:554–61.

R. Houston Thompson – BJUI Consulting Editor (Oncology)

Mayo Clinic, Rochester, MN, USA

EAU 2015 Review Days 3 and 4

March 26, 2015/by Declan Murphy

Persistent rain throughout this year’s 30th EAU Annual Congress failed to dampen the spirits of over 12,000 delegates who have enjoyed another fantastic congress here in Madrid. The EAU Scientific Committee, led by Arnulf Stenzl, deserve tremendous credit for the work they have done to construct an extremely comprehensive and stimulating programme once again this year. I do recall my last EAU Congress in Madrid 12 years ago and there is no doubt but that the standard of this meeting has risen exponentially during this time. It is not just be Annual Congress of course which has developed in this time; the EAU has seen enormous growth in its global influence through the meteoric rise of European Urology, the activities of the European School of Urology (even beyond Europe), the pre-eminence of the EAU Guidelines, and the introduction of new initiatives such as UroSource. The Annual Congress is the nidus for much of this activity and it has become an unmissable event for many of us (even when based in Australia as I am!).

Rebecca Tregunna and Matthew Bultitude have already covered some of the highlights of the opening days of this year’s Congress in their BJUI blog . I will give you some further highlights and point you towards the excellent congress website which has archived a huge amount of material to allow you to catch up on sessions you may have missed.

Big highlights for me on day 3 and 4 include the following (please forgive my oncology focus):

PSMA PET scanning – there was considerable interest in the early data on PSMA PET scanning for recurrent prostate cancer at last year’s EAU Congress, and this year has seen some very positive data being presented from Munich and Heidelberg and further enthusiasm for this imaging modality. Tobias Maurer (Munich) presented a number of papers showing the high sensitivity in particular for PSMA PET in detecting recurrent prostate cancer at low levels of biochemical recurrence using either PET CT or PET MRI (poster 928).

Many other plenary speakers also highlighted the positive data surrounding PSMA PET and also the possible theragnostic potential of this in the future (poster 675 and Dr Haberkorn plenary lecture). However in the scientific souvenir session which closed the meeting, Dr Peter Albers burst the bubble somewhat by warning that we need much better data (tissue validation in particular), before we all rush towards PSMA. He has a point of course, although I have been extremely impressed with our initial experience using PSMA PET in Melbourne over the past six months and I do expect it to live up to the hype.

CHAARTED data looking good – Nine months after he made world-wide headlines when he presented the overall survival data of the CHAARTED study at ASCO, Dr Chris Sweeney crossed the Atlantic to again present this data to a packed eUro auditorium. This randomised study of 790 men with metastatic prostate cancer, has demonstrated that men who receive six cycles of docetaxel chemotherapy upfront at the time of starting androgen deprivation therapy, have a considerable survival benefit compared to those who receive ADT on its own (the current standard of care). This was especially so for men with high volume metastases who had a 17 month survival benefit (HR 0.61).

Although the French GETUG study has not shown the same benefit, Sweeney and others have proposed rational explanations for why this might be so. While the final paper has not yet been published (will be submitted this week), very many of us have already embraced the CHAARTED as the new standard of care for men presenting with high-volume metastatic prostate cancer. A proper landmark study.

Metastatic castrate-resistant prostate cancer (mCRPC) – still more questions than answers. What an amazing few years for this disease area! Five years ago, urology trainees only had a handful of “essential reading” papers in the world’s top journal, the NEJM, that we could cite to support evidence-based practice. It is now difficult to keep up with all the landmark trials in NEJM and other top journals reporting overall survival advantage for a variety of agents targeting mCRPC. Enzalutamide has already joined the ranks of these blockbuster drugs and this year’s EAU saw more data illustrating the powerful activity of enzalutamide in the pre-chemo mCRPC space. In the Breaking News session on the final day, Dr Bertrand Tombal presented the final analysis of the PREVAIL study which confirmed the overall survival advantage of patients receiving enza pre-chemo when compared with placebo. The HR of 0.77 was strongly significant (p=0.0002) and the therapy was well tolerated.

However as pointed out by discussant Dr Maria de Santis, we have still a way to go to figure out which patient will benefit from which therapy and when. The sequence and combination of therapies is still being worked out, and while the potential of predictive biomarkers such as AR7 is certainly exciting, we are still bereft of data and tools (and funding), to figure out the best pathways.

Robot vs open surgery – cystectomy is the new battleground. As Alberto Brignati pointed out in his outstanding souvenir session on localised prostate cancer, it appears that the old debate of robotic vs open prostatectomy is no longer of interest. Despite the lack of prospective randomised data, there appears to be little doubt that robotic prostatectomy is the standard of care in many regions. A large number of posters and plenaries demonstrated convincing data of excellent outcomes in robotic prostatectomy series, including data from a multicenter randomised study (REACTT, poster 622) led by Dr Stolzenberg which demonstrated improved potency outcomes for robotic prostatectomy (not the primary endpoint).

The same cannot yet be said of robotic cystectomy. Despite my own enthusiasm for and publications on robotic cystectomy, it is hard to get away from some of the cautionary language being expressed about the role of robotic cystectomy at the moment. An excellent plenary featuring giants in the field of bladder cancer (Dr’s Bochner, Wiklund, Studer, Palou), debated the issue in the main eUro auditorium and the following day’s newsletter summed it up nicely:

This provoked much discussion on Twitter with some prominent names chiming in from the US. Dr Khurshid Guru got involved to reassure us that the International Robotic Radical Cystectomy Consortium which he leads will provide the answer.

Well said @khurshidguru!

On a non-cancer note, it is clear that some of the most popular session and courses at EAU15 were focused on uro-lithiaisis. Stone surgeons are also very active on Twitter and although I did not attend any stone sessions, I was pleased to see that standardization of terminology is also important to the “pebble-ologists”:

Finally, #EAU15 was truly a social experience, not just in the wonderful bars and restaurants of Madrid, but also through Twitter and other social media channels, strongly supported by the excellent communications team at EAU. We recently published a paper in the BJUI documenting the growth of social media at major urology conferences and at EAU in particular. Between 2012 and 2014, the number of Twitter participants increased almost ten-fold, leading to an increase in the number of tweets from 347 to almost 6,000 At #EAU14, digital impressions reached 7.35 million with 5,903 tweets sent by 797 participants.

(From Wilkinson et al BJUI 2015)

As might be expected, #EAU15 has continued this trajectory with almost 8000 tweets sent by 1220 participants.

One of the only criticisms I have of EAU15 is that the scientific program is now so large that it is impossible to get to all the sessions I am interested in. There did seem to be a lot of prostate cancer running simultaneously but I am not sure how much the Scientific Committee can do to avoid such clashes. Thankfully, the EAU meeting website www.eaumadrid2015.org contains a huge amount of material including webcasts, interviews, posters etc which allows delegates and EAU members to catch up on some of the outstanding content.

Another big attraction of the EAU Annual Congress is of course that it takes place in Europe’s most wonderful cities. EAU16 heads to Munich – put the date in your diary 11-15 March 2016.

Declan Murphy, Urologist, Melbourne
Associate Editor – Social Media, BJUI
@declangmurphy

Click here for Declan Murphy’s disclosures

Final Analysis of RT+ADT versus ADT alone in locally advanced CaP

March 23, 2015/by Chris Hillary

The March 2015 international urology journal club #urojc twitter discussion focused on a paper by Mason et al [1]. This article, published in the Journal of Clinical Oncology (Feb 2015), reports on the preplanned final analysis of the randomized trial of radiotherapy (RT) and androgen deprivation therapy (ADT) versus ADT alone in patients with locally advanced prostate cancer between 1995 and 2005.

The authors have previously reported on the survival benefits of RT added to ADT in this cohort of patients and the final analysis demonstrates a sustained longer-term survival outcomes of RT+ADT over a median follow-up of 8 years as compared to ADT alone.

As ever the discussion was lively with some polarized views. The feed commenced at 12:00pm PST on Sunday 1^st March 2015 for a 48-hour period. Initially debate focused on staging and the under-reporting of DRE findings:

Which was perhaps addressed by issues during the screening process…

Despite this, other aspects of staging were discussed, particularly the methods for node staging:

For N staging, the authors included either a clinical assessment (70.5% of patients), Imaging (8.5%) or surgical dissection (2.4%). Meanwhile, the accuracy of ‘clinical’ nodal staging was questioned.

Consideration of the patient inclusion criteria was followed by a discussion over the use of ADT in this patient cohort

In this context, ADT consisted of either BSO or lifelong LHRH agonists

However, the question was asked of ADT in addition to RT ‘is lifelong ADT appropriate?’

While for high-risk disease, evidence suggests that long-term (2-3 years) ADT should be used following RT [2, 3], for intermediate risk cancers, 8 weeks of adjuvant ADT remains the standard of care as highlighted in the recent RTOG 9910 data [4].

The rationale behind RT and ADT was noted:

While the results of the study came as no shock to some:

The addition of RT to ADT significantly improved OS and DSS. The study reports that ‘there was no evidence of any differences in deaths from other causes’, however, the issue of secondary malignancies with RT was ‘highlighted’:

Ultimately, the role of surgery for these patients was questioned. A point highlighted in the paper was not shared by some:

To conclude the March #urojc, some final comments were provided by @_TheUrologist:

Thanks to all those who participated in this months discussion. We look forward to the April #urojc.

References

[1] Mason, M.D., W.R. Parulekar, M.R. Sydes, et al., Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer. J Clin Oncol 2015;.

[2] Horwitz, E.M., K. Bae, G.E. Hanks, et al., Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol 2008;26:2497-504.

[3] Bolla, M., G. Van Tienhoven, P. Warde, et al., External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol 2010;11:1066-73.

[4] Pisansky, T.M., D. Hunt, L.G. Gomella, et al., Duration of androgen suppression before radiotherapy for localized prostate cancer: radiation therapy oncology group randomized clinical trial 9910. J Clin Oncol 2015;33:332-9.

Chris Hillary @chrisjhillary

Clinical Fellow in Urology, Sheffield, UK

EAU 2015 Review Days 1 and 2

March 23, 2015/1 Comment/by Rebecca Tregunna

The 30^th anniversary EAU congress is currently taking place in the beautiful but rainy city of Madrid with over 12,000 delegates attending. The opening Friday proved a monumental day with the start of the congress as well as personally as I gave into the pressure of social media, and joined Twitter. This is being heavily promoted by the EAU this year and with multiple engaging sessions going on at the same time this seemed to be the best way to have my cake and eat it and enjoy highlights from different parts of the meeting.

The second ESO prostate cancer observatory was well attended and led to interesting debates about PSA screening and informed consent due to risks of over-detection and subsequent overtreatment of indolent disease. Indeed Andrew Vickers also highlighted that the results of the much anticipated ProtecT trial should be interpreted with caution given the high number of Gleason 6 patients that have been randomised.

In the evening the opening ceremony took place with an emotional final introduction to the congress by Per Anders Abrahamsson as he steps down and hands over to Chris Chapple as EAU Secretary General (photo courtesy @uroweb).

The EAU also gave out a number of awards including the Crystal Matula award for promising young urologist which was given to Morgan Roupret.

The scientific programme on Saturday started with the main plenary session on controversies in bladder and kidney cancer. It is difficult to draw conclusions regarding lymphadenectomy in upper tract tumours due to a lack of randomised data but certainly based on retrospective data a benefit is seen both in terms of staging and cancer specific survival. A hot topic lecture on molecular profiling in bladder cancer gave a thrilling insight into how agents will be able to target pathways based on specific mutations and Professor Studer, in his last ever plenary session, led to an interesting debate on robotic vs. open radical cystectomy. This has caused much controversy recently with the Bochner randomised controlled trial and this debate will surely run and run. Maybe most importantly, as Studer concluded “The surgeon makes the difference not the instrument”. This was highlighted on the front cover of the congress news with a more downbeat headline on robotic cystectomy.

Next came an intriguingly titled talk “What would Charles Darwin make of renal cell carcinoma?” with discussion about the heterogeneity of renal tumours making it difficult to identify specific targeted treatments based on renal biopsy alone.
Multiple section meetings then ensued. From the EAU section of urolithiasis (EULIS) meeting it seems that PCNLs are increasingly being miniaturised with development to mini, ultra-mini and micro procedures. The issues behind “diabesity” and stones were discussed with Professor Reis Santos predicting an epidemic of stones either due to uric acid stone formation from obesity or calcium oxalate formation from malabsorbative bariatric procedures. There was also a recurring theme with poster and podium sessions on “ESWL – is there still a role?” While the argument is made for ESWL there is no doubt that worldwide treatment rates for ESWL are falling.
As the EAU Section of Female and Functional Urology there was an excellent series of talks on mesh and mesh complications. There was a fantastic review of dealing with these complications through a variety of approaches and techniques and whether all these should all be dealt with in high volume centres. Unfortunately, no one knows what high volume means for this. Interestingly the terminology is changing, moving away from ‘erosion’ to ‘exposure’ and ‘perforation’. Removing the mesh only relieves associated pain in 50% of cases and these dedicated centres need to offer multimodality treatments to deal with pain and ongoing continence issues.
In the parallel EAU section meeting of Genito-urinary Reconstructive Surgeons, Professor Mundy gave a personal 30 year series of 169 patients treated with both clam cystoplasty and artificial sphincter. The majority of complications were related to the sphincter. The largest subgroup was patients with Spina Bifida but were the patients with the best outcomes.
David Ralph in the EAU Section of Andrology stated that shunts were ineffective after 48 hours after priapism and that a prosthesis instead should be inserted to prevent corporal fibrosis.
The EAU section of Oncological Urology also heard that 68Ga-S+PSMA-PET improves detection of metastatic lymph nodes in prostate cancer and can be used intra-operatively in radioguided surgery for targeted lymph node dissection.
Overall the organisers have done a fantastic job with a well organised meeting and a great venue despite the disappointing weather. There were sessions that people could not get in to as the rooms were full.

However, with live TV screens outside those rooms and transmission to an adjacent overflow room this didn’t seem to matter too much. Much to look forward to for the rest of the conference #EAU15.

Rebecca Tregunna, Speciality Trainee, Burton Hospitals NHS Foundation Trust, West Midlands Deanery. @RebeccaTregunna

Matthew Bultitude, Consultant Urologist, Guy’s and St. Thomas’ Foundation Trust; Web Editor BJU International. @MattBultitude

Editorial: The robot to the rescue!

March 18, 2015/by Ben Challacombe

Fortunately injuries to the urinary tract remain rare in obstetric and gynaecological surgery. Their potential for causing serious morbidity, not to mention the substantial medico-legal implications ensure that it remains a highly researched and evocative area [1].

Iatrogenic urinary tract injuries can be broadly divided into two groups; acute complications, such as bladder and ureteric lacerations or ligation and more chronic complications, such as vesicovaginal or ureterovaginal fistulae and ureteric strictures. Historically, iatrogenic trauma to the urinary tract most commonly followed open, abdominal hysterectomy with the most frequent complication being direct bladder injury. Gross bladder injuries are generally both detected and treated intraoperatively. In contrast, the management of more complex ureteric injuries and their long-term sequelae, such as fistula, pose greater surgical challenges. The complexity of these injuries is often further compounded by delay in diagnosis. It is generally accepted that, if possible, immediate repair provides the optimal treatment. However, when diagnosis is delayed, there is little consensus on the best management approach, although the current tendency is towards early repair [2].

The multicentre, retrospective study of robotic repair of 49 iatrogenic genitourinary injuries by Gellhaus et al. [3] should therefore serve to reassure gynaecologists with respect to the incidence of this feared complication. This paper, mainly looking at ureteric re-implants and fistula repairs, constitutes the largest cohort of robotic reconstructions to date. A zero conversion rate to open surgery suggests excellent case selection by the robotic surgeons. Four cases had undergone previous failed open or endoscopic management and this is clearly a challenging cohort. Yet, with the absence of total numbers of urology referrals received for such injuries, it is important to remember that it may not be a panacea for all.

There has been a considerable shift in the management of urological trauma from open to laparoscopic techniques. While the repair of basic injuries has been proven to be effective, less data is available to support the management of more complex injuries, such as ureteric transections or fistulae [4]. Numerous techniques for repairing ureteric injuries and fistulae have been described; nonetheless, the surgery remains technically challenging even for experienced laparoscopic surgeons and is generally limited to high-volume centres [5].

In comparison, this article [3] provides strong evidence for the effectiveness of robot-assisted (RA) repairs, even for complex injuries. The enviable 95.9% success rate from 47 operations is complemented by short recovery times and low complication rates. These results are especially impressive in view of the mean 23.5-month delay time to repair. But the authors do not report the reasons for these delays. Immediate robotic repair of RA injuries is clearly feasible especially in larger units. Whether immediate RA repair should be performed for other iatrogenic injuries needs further discussion. Is it realistic to convert to the robot in the case of laparoscopic trauma or should RA repairs remain a planned return to theatre?

The demand for RA reconstructive surgery and experienced robotic pelvic surgeons is likely to rise in the near future. As the authors note, the continued expansion of minimally invasive procedures is likely to lead to a shift in the patterns of complications from more straightforward bladder injuries to complex ureteric injuries. As mentioned previously these types of injury are more likely to be initially undetected.

Whilst rates of surgical complications involving the urinary tract remain low, obstetrical and gynaecological procedures account for 75% of these injuries. This article provides robust evidence for the key role that RA surgery can play in the management of these complex and feared injuries. When faced with such situations, Gellhaus et al. [3] have shown that it is increasingly likely that the robot saves the day.

Read the full article

Nicholas Raison and Ben Challacombe

Department of Urology, Guy’s and St Thomas’ Hospital,London, UK

References

1 Preston JM. Iatrogenic ureteric injury: common medicolegal pitfalls. BJUInt 2000; 86: 313–7

2 El-Tabey NA, Ali-el-Dein B, Shaaban AA et al. Urological trauma aftergynecological and obstetric surgeries. Scand J Urol Nephrol 2006; 40:225–31

3 Gellhaus PT, Bhandari A, Monn MF et al. Robotic management ofgenito-urinary injuries from obstetrical and gynecological operations: amulti-institutional report of outcomes. BJU Int 2015; 115: 430–6

4 De Cicco C, Ussia A, Koninckx PR. Laparoscopic ureteral repairin gynaecological surgery. Curr Opin Obstet Gynecol 2011; 23:296–300

5 Rassweiler J, Pini G, Gözen AS, Klein J, Teber D. Role of laparoscopy inreconstructive surgery. Curr Opin Urol 2010; 20: 471–82

Editorial: On the Mark? Is AP a surrogate for BMD in hypogonadal men?

March 11, 2015/by Ronald Wiehle

The current issue of the BJUI contains a paper by Dubaja et al. [1] that may be of interest to physicians who have patients with hypogonadism. The authors speak to an unappreciated aspect of low testosterone; namely, the loss of bone in men and the possible recovery with treatment. Their retrospective study looked at 140 men with hypogonadism treated with exogenous testosterone replacement or clomiphene citrate testosterone enhancement. These men were also assessed for bone mineral density (BMD) markers at 6, 12 and 24 months after initial treatment. Importantly, dual-energy X-ray absorptiometry (DEXA) was performed a second time after 2 treatment years for a subset of these men. DEXA showed that there was a gain in BMD and a loss of serum alkaline phosphatase (AP) for all the men over time. The loss of AP was rapid but stabilized at 6 months. Testosterone and free testosterone increased as expected but there were no changes in vitamin D, calcium, parathyroid hormone or sex hormone-binding globulin. There was a correlation between AP and testosterone. The authors recognized poor bone density at baseline in those men with testosterone levels

Bone mineral density is the best way to predict osteoporosis and fragility fractures [2]. Women loose BMD after menopause and that is accompanied by many changes, including gains in AP [3]. The decline in serum oestrogens is a factor for women, and oestrogen replacement therapy historically has been used to prevent that loss. Not all men undergo a similar loss, i.e. andropause is not recognized in the same way as menopause. Even though osteoporosis is less common in men, the associated comorbidity may be more significant.

There is an age-related decline in testosterone and an acute loss for some men such that they approach their physicians with symptoms. The underlying cause of bone loss in men and women may be the same: serum oestrogen loss. Men who lose testosterone are also losing oestrogen because testosterone is the precursor via aromatase. Repros Therapeutics is developing a way to treat men with secondary hypogonadism. An ongoing 1-year DEXA study recruited eligible men. Key inclusion factors were age < 60 years and body mass index > 25 kg/m2. Remarkably 24% of men failed the screening test because of osteopenia, despite the fact that few of them were old or underweight.

The present paper by Dubaja et al. suggests that a readily available serum test may be able to monitor men on testosterone therapies for gain in BMD. Given the relatively low incidence of osteoporosis, screening every man by DEXA is not cost-efficient. The 1 year or more needed to find BMD loss by DEXA also wastes time and resources. Quantitative CT is more costly and is accompanied by high radiation exposure. The use of AP, as suggested in the present study, may represent a reasonable alternative.

The paper is not without its weaknesses. There was no indication of whether these men had primary or secondary hypogonadism. Transdermal testosterone should raise testosterone and oestrogen in both groups of men whereas clomiphene citrate works through changes in LH and FSH and requires an intact hypothalamic-pituitary-gonadal axis (useful in men with secondary hypogonadism only). Indeed, the two kinds of treatment will have the opposite effect on LH and FSH [4]. The authors recognized the importance of Leydig cells in producing testosterone, yet the effects of a transdermal testosterone would be to shut down testosterone production. We commend their suggestion that other factors that contribute to both bone and Leydig cell function, insulin-like 3 [5] and osteocalcin [6] should be studied in relation to AP. The loss of subjects throughout the 2 years was troubling, but it is known that men on transdermal treatments discontinue with disturbing frequency despite satisfaction [7]. If those who stayed in the present study were those with the best outcomes in terms of testosterone and BMD, potential bias may exist. If men can be encouraged to continue therapy through positive effects on BMD being detected as early as 6 months, AP monitoring may improve patient compliance. Only DEXA can give that assurance now. The authors noted the need for a larger prospective trial. Nevertheless, their paper provides a rationale for monitoring men on testosterone therapies that can be implemented with minimal cost or the need for new diagnostics.

Read the full article

Martin C. Michel

Department of Pharmacology, Johannes Gutenberg University, Mainz, German

References

1 Dabaja A, Bryson C, Schlegel P, Paduch D. The eﬀect of hypogonadism and testosterone-enhancing therapy on alkalinephosphatase and bone mineral density. BJU Int 2015; 115: 3

2 NIH Consensus Development Panel. Osteoporosis prevention, diagnosis and therapy. JAMA 2001; 285: 785–95

3 Biver E.Use of bone turnover markers in clinical practice. Curr O pin Endocrinol Dia betes Obes 2012; 19: 468–73

4 Kaminetsky J, Werner M, Fontenot G, Wiehle RD. Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel. JSexMed2013; 10: 1628–35

5 Ivell R, Anand-Ivell R. Biology of insulin-like factor-3 in human reproduction. Hum Reprod Update 2009; 15: 463–76

6 Karsenty G. Bone endocrine regulation of energy metabolism and male reproduction. CRBiol2011; 334: 720–4

7 Kovac J, Rajanahally S, Smith R, Coward R, Lamb D, Lipshultz L. Patient satisfaction with testosterone replacement therapies: the reasons behind the choices. JSexMed2014; 11: 553–62