EAU Guidelines

Editorial: How long is long enough for pharmacological thromboprophylaxis in urology?

December 18, 2019/by Kari Tikkinen

Each year, millions of patients who undergo urological surgery incur the risk of deep vein thrombosis and pulmonary embolism, together referred to as venous thromboembolism (VTE), and major bleeding. Because pharmacological prophylaxis decreases the risk of VTE, but increases the risk of bleeding, and because knowledge of the magnitude of these risks remains uncertain, both clinical practice and guideline recommendations vary widely [1]. One of the uncertainties is the recommended duration of pharmacological thromboprophylaxis.

In this issue of the BJUI, Naik et al. [2] provide an up‐to‐date review that summarises the articles that examined extended thromboprophylaxis in patients with cancer who underwent radical prostatectomy (RP), radical cystectomy (RC) or nephrectomy. The outcomes on which they focussed include risks of VTE, bleeding, renal failure and mortality – all potentially influenced by whether or not patients receive extended prophylaxis.

After screening >3500 articles, the authors included 18 studies, none of them randomised controlled trials (RCTs) [2]. They found that VTE risk is highest in open and robot‐assisted RC, and that, based on observational studies, extended thromboprophylaxis significantly reduces the risk of VTE relative to shorter duration prophylaxis. Evidence suggested that robot‐assisted RP, as well as both open and robot‐assisted partial and radical nephrectomies, incur lower VTE risk than RCs or open RP. They did not find studies comparing extended prophylaxis to standard prophylaxis for RPs or nephrectomies [2].

Overall, these findings are consistent with systematic reviews that estimated the procedure‐ and patient risk factor‐specific risks for 20 urological cancer procedures [3]. As these reviews suggested substantial procedure‐specific differences in the VTE risk estimates, the European Association of Urology (EAU) Guidelines provided separate recommendations for each procedure [4]. For urological (as well as gastrointestinal and gynaecological) patients, the National Institute for Health and Care Excellence (NICE) Guidelines suggest to ‘consider extending pharmacological VTE prophylaxis to 28 days postoperatively for people who have had major cancer surgery in the abdomen’ [5]. Because of variation in both bleeding and thrombosis risks across procedures, this advice is appropriate for some procedures and misguided for others. For instance, the procedure‐specific EAU Guidelines recommend extended VTE prophylaxis for open RC but not for robot‐assisted RP without lymphadenectomy [4].

The review by Naik et al. [2] identified the lack of urology‐specific studies comparing the in‐hospital‐only prophylaxis to extended prophylaxis. The few included studies were observational with considerable limitations (e.g. limited adjustment for possible confounders).

A recent update of a Cochrane review compared the impact of extended thromboprophylaxis with low‐molecular‐weight heparin (LMWH) for at least 14 days to in‐hospital‐only prophylaxis in abdominal or pelvic surgery procedures [6]. The authors identified seven RCTs (1728 participants) evaluating extended thromboprophylaxis with LMWH and generated pooled estimates for the incidence of any VTE (symptomatic or asymptomatic) after major abdominal or pelvic surgery of 13.2% in the control group compared with 5.3% in the patients receiving extended out‐of‐hospital LMWH (odds ratio [OR] 0.38, 95% CI 0.26–0.54).

Most events were asymptomatic, although the incidence of symptomatic VTE was also reduced from 1.0% in the in‐hospital‐only group to 0.1% in patients receiving extended thromboprophylaxis (OR 0.30, 95% CI 0.08–1.11). The authors reported no persuasive difference in the incidence of bleeding complications within 3 months of surgery (defined as major or minor bleeding according to the definition provided in the individual studies) between the in‐hospital‐only group (2.8%) and extended LMWH (3.4%) group (OR 1.10, 95% CI 0.67–1.81).

These findings are consistent with our own modelling study that demonstrated an approximately constant hazard of VTE up to 4 weeks after surgery [7]. That study also found that bleeding risk, by contrast, is concentrated in the first 4 days after surgery [7] (Fig.1). Using these findings, the EAU Guidelines suggest for patients in whom pharmacological prophylaxis is appropriate, extended pharmacological prophylaxis for 4 weeks [4]. Consistent with these recommendations, Naik et al. [2] found that 15 studies of 18 included in their review recommended extended prophylaxis.

**Fig.1** Proportion of cumulative risk (%) of venous thromboembolism (VTE) and major bleeding by week since surgery during the first 4 postoperative weeks. Reproduced from: **Tikkinen et al.** [7].

_{(This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.)}

Overall, as shown also by this review [2], the evidence base for urological thromboprophylaxis is limited. Although current evidence supports extended prophylaxis, definitively establishing the optimal duration of thromboprophylaxis will require large‐scale RCTs. Other unanswered key questions include: baseline risks of various procedures, timing of prophylaxis, patient risk stratification, as well as effectiveness of direct oral anticoagulants. In the meanwhile, suggesting extended duration to patients whose risk of VTE is sufficiently high constitutes a reasonable evidence‐based approach to VTE prophylaxis.

by Kari A.O. Tikkinen and Gordon H. Guyatt

References

Violette PD, Cartwright R, Briel M, Tikkinen KA, Guyatt GH Guidelines of guidelines: thromboprophylaxis for urological surgery. BJU Int 2016; 118: 351– 8
Naik R, Mandal I, Hampson A et al. The role of extended venous thromboembolism prophylaxis for major urological cancer operations. BJU Int 2019; 124: 935-44
Tikkinen KA, Craigie S, Agarwal A et al. Procedure‐specific risks of thrombosis and bleeding in urological cancer surgery: systematic reviews and meta‐analyses. Eur Urol 2018; 73: 242– 51
Tikkinen KA, Cartwright R, Gould MK et al. EAU Guidelines on Thromboprophylaxis in Urological Surgery, 2017. European Association of Urology, 2018. Accessed November 2019
National Institute for Health and Care Excellence (NICE). Venous Thromboembolism in over 16s: reducing the risk of hospital‐acquired deep vein thrombosis or pulmonary embolism. NICE guideline [NG89]. London: NICE, 2018. Accessed November 2019
Felder S, Rasmussen MS, King R et al. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database Syst Rev 2019; 3: CD004318
Tikkinen KA, Agarwal A, Craigie S et al. Systematic reviews of observational studies of risk of thrombosis and bleeding in urological surgery (ROTBUS): introduction and methodology. Syst Rev 2014; 23: 150. DOI: 10.1186/2046‐4053‐3‐150.

The 5th BJUI Social Media Awards

May 17, 2017/1 Comment/by Declan Murphy

It’s hard to believe that we have been doing the BJUI Social Media Awards for five years now! I recall vividly our inaugural BJUI Social Media Awards in 2013, as the burgeoning social media community in urology gathered in the back of an Irish Bar in San Diego to celebrate all things social. At that time, many of us had only got to know each other through Twitter, and it was certainly fun going around the room putting faces with twitter handles for the first time. That spirit continues today as the “uro-twitterati” continues to grow, and the BJUI Awards, (or the “Cult” Awards as our Editor-in-Chief likes to call them), remains a fun annual focus for the social-active urology community to meet up in person.

As you may know, we alternate the Awards between the annual congresses of the American Urological Association (AUA) and of the European Association of Urology (EAU). Last year, we descended on Munich, Germany to join the 13,000 or so other delegates attending the EAU Annual Meeting and to enjoy all the wonderful Bavarian hospitality on offer. This year, we set sail for the #AUA17 Annual Congress in Boston, MA, along with over 16,000 delegates from 100 different countries. What a great few days in beautiful Boston and a most welcome return for the AUA to this historic city. Hopefully it will have a regular spot on the calendar, especially with the welcome dumping of Anaheim and Orlando as venues for the Annual Meeting.

Awards

On therefore to the Awards. These took place on Saturday 13^th May 2017 in the City Bar of the Westin Waterfront Boston. Over 80 of the most prominent uro-twitterati from all over the world turned up to enjoy the hospitality of the BJUI and to hear who would be recognised in the 2017 BJUI Social Media Awards. We actually had to shut the doors when we reached capacity so apologies to those who couldn’t get in! Individuals and organisations were recognised across 12 categories including the top gong, The BJUI Social Media Award 2017, awarded to an individual, organization, innovation or initiative who has made an outstanding contribution to social media in urology in the preceding year. The 2013 Award was won by the outstanding Urology Match portal, followed in 2014 by Dr Stacy Loeb for her outstanding individual contributions, and in 2015 by the #UroJC twitter-based journal club. Last year’s award went to the #ilooklikeaurologist social media campaign which we continue to promote.

This year our Awards Committee consisted of members of the BJUI Editorial Board – Declan Murphy, Prokar Dasgupta, Matt Bultitude, Stacy Loeb, John Davis, as well as BJUI Managing Editor Scott Millar whose team in London (Max and Clare) drive the content across our social platforms. The Committee reviewed a huge range of materials and activity before reaching their final conclusions.

The full list of winners is as follows:

Most Read Blog@BJUI – “The optimal treatment of patients with localized prostate cancer: the debate rages on”. Dr Chris Wallis, Toronto, Canada

Most Commented Blog@BJUI – “It’s not about the machine, stupid”. Dr Declan Murphy, Melbourne, Australia

Most Social Paper – “Novel use of Twitter to disseminate and evaluate adherence to clinical guidelines by the European Association of Urology”. Accepted by Stacy Loeb on behalf of herself and her colleagues.

Best BJUI Tube Video – “Combined mpMRI Fusion and Systematic Biopsies Predict the Final Tumour Grading after Radical Prostatectomy”. Dr Angela Borkowetz, Dresden, Germany

Best Urology Conference for Social Media – #USANZ17 – The Annual Scientific Meeting of the Urological Association of Australia & New Zealand (USANZ) 2017. Accepted by Dr Peter Heathcote, Brisbane, Australia. President of USANZ.

Best Urology App – The EAU Guidelines App. Accepted by Dr Maria Ribal, Barcelona, Spain, on behalf of the EAU.

Innovation Award – BJUI Urology Ontology Hashtags keywords. Accepted by Dr Matthew Bultitude, London, UK, on behalf of the BJUI.

#UroJC Award – Dr Brian Stork, Michigan, USA. Accepted by Dr Henry Woo of Brian’s behalf.

Most Social Trainee – Dr Chris Wallis, Toronto, Canada

Best Urology Journal for Social Media –Journal of Urology/Urology Practice. Accepted by Dr Angie Smith, Chapel Hill, USA, on behalf of the AUA Publications Committee.

Best Urology Organisation – Canadian Urological Association. Accepted by Dr Mike Leveridge, Vice-President of Communications for CUA.

The BJUI Social Media Award 2017 – The Urology Green List, accepted by Dr Henry Woo, Sydney, Australia.

All the Award winners (except Dr Brian Stork who had to get home to work), were present to collect their awards themselves. A wonderful spread of socially-active urology folk from all over the world, pictured here with BJUI Editor-in-Chief, Prokar Dasgupta.

A special thanks to our outstanding BJUI team at BJUI in London, Scott Millar, Max Cobb and Clare Dunne, who manage our social media and website activity as well as the day-to-day running of our busy journal.

See you all in Copenhagen for #EUA18 where we will present the 6th BJUI Social Media Awards ceremony!

Declan Murphy

Peter MacCallum Cancer Centre, Melbourne, Australia

Associate Editor, BJUI

@declangmurphy

Article of the Week: TRUS-Guided RB PCa Detection – Reasons for Targeted Biopsy Failure

July 20, 2016/2 Comments/by admin Z.9

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

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

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Hannes Cash and Patrick Asbach, discussing their paper.

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

Prostate cancer detection on transrectal ultrasonography-guided random biopsy despite negative real-time magnetic resonance imaging/ultrasonography fusion-guided targeted biopsy: reasons for targeted biopsy failure

Hannes Cash*, Karsten Gunzel*, Andreas Maxeiner*, Carsten Stephan*, Thomas Fischer†, Tahir Durmus†, Kurt Miller*, Patrick Asbach†, Matthias Haas† and Carsten Kempkensteffen*

*Department of Urology, and †Department of Radiology, Charite–University of Medicine Berlin, Berlin, Germany M. H. and C.K. contributed equally to the study.

Read the full article

Objective

To examine the value of additional transrectal ultrasonography (TRUS)-guided random biopsy (RB) in patients with negative magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided targeted biopsy (TB) and to identify possible reasons for TB failure.

Patients and Methods

We conducted a subgroup analysis of 61 men with prostate cancer (PCa) detected by 10-core RB but with a negative TB, from a cohort of 408 men with suspicious multiparametric magnetic resonance imaging (mpMRI) between January 2012 and January 2015. A consensus re-reading of mpMRI results (using Prostate Imaging Reporting and Data System [PI-RADS] versions 1 and 2) for each suspicious lesion was performed, with the image reader blinded to the biopsy results, followed by an unblinded anatomical correlation of the lesion on mpMRI to the biopsy result. The potential reasons for TB failure were estimated for each lesion. We defined clinically significant PCa according to the Epstein criteria and stratified patients into risk groups according to the European Association of Urology guidelines.

Results

Our analysis showed that RB detected significant PCa in 64% of patients (39/61) and intermediate-/high-risk PCa in 57% of patients (35/61). The initial mpMRI reading identified 90 suspicious lesions in the cohort. Blinded consensus re-reading of the mpMRI led to PI-RADS score downgrading of 45 lesions (50%) and upgrading of 13 lesions (14%); thus, negative TB could be explained by falsely high initial PI-RADS scores for 32 lesions (34%) and sampling of the target lesion by RB in the corresponding anatomical site for 36 out of 90 lesions (40%) in 35 of 61 patients (57%). Sampling of the target lesion by RB was most likely for lesions with PI-RADS scores of 4/5 and Gleason scores (GS) of ≥7. A total of 70 PCa lesions (67% with GS 6) in 44 patients (72%) were sampled from prostatic sites with no abnormalities on mpMRI.

Conclusion

In cases of TB failure, RB still detected a high rate of significant PCa. The main reason for a negative TB was a TB error, compensated for by positive sampling of the target lesion by the additional RB, and the second reason for TB failure was a falsely high initial PI-RADS score. The challenges that arise for both MRI diagnostics and prostate lesion sampling are evident in our data and support the integration of RB into the TB workflow.

Editorial: MRI-Fusion Biopsy – Behind the Scenes

July 20, 2016/by Lars Budaus

MRI information of the prostate is increasingly used for improving the diagnostic yield of prostate biopsies [1]. However, increasing complexity of a procedure makes it prone to errors at multiple technical and human levels. Incorporating MRI information and ultrasonography (US) images for MRI-fusion biopsies is a technically challenging task. It involves various steps such as the acquisition and fusion of MRI and US images, the needle guidance during biopsy, and the diligence of the pathological evaluation of biopsy specimens. These different steps and interfaces between different medical professions influence the diagnostic performance of MRI-fusion biopsies.

For example, in daily clinical practice, MRIs from different institutions still harbour a great variance of sequences and reporting, despite the European Society of Urogenital Urology (ESUR) recently introducing acquisition and imaging protocols and a new and advanced version of the Prostate Imaging Reporting and Data System (PIRADS) version 2.0 [2]. The usefulness of such reporting schemes is evidenced by a moderate-to-good interobserver agreement between uro-radiologists for tumour lesion interpretation and corresponding κ values ranging from 0.55 to 0.80 [3]. Important pitfalls of image interpretation are benign lesions such as prostatitis, BPH and fibrosis, which might score similarly to prostate cancer lesions. This problem is further aggravated by a high proportion of patients that receive their first multiparametric MRI (mpMRI) of the prostate in the repeat-biopsy setting with a high burden of post-biopsy artefacts (haemorrhage, capsular irregularity) and lower overall cancer detection rate. Also, during MRI-fusion biopsy patient movement, prostate deformation by the US probe, and mismatch of image planes can lead to a biopsy error exceeding 4 mm. Moreover, targeting error might be aggravated by MRI underestimation of the tumour volume compared with final pathology [4]. After various authors reported the advantages and accuracy of MRI/US-fusion biopsy approaches, Cash et al. [5] address potential reasons for targeted biopsy failure to detect prostate cancer compared with random biopsy. Within their analyses the authors address potential limitations and technical considerations. Based on different technical biopsy strategies (with the patient placed within the MRI scanner (‘in-bore’) vs outside) and different technical approaches, these considerations are very important.

In contrast to cognitive fusion, most MRI/US platforms allow needle tracking by archiving the needle orientation, either by an electromagnetic, image-based or stepper-based mechanism [1]. However, lesion targeting by needle guidance is highly dependent on the dimensions of the primary lesion, numbers of relevant lesions, localisation, and overall prostate volume, making MRI-US fusion and cognitive fusion more error prone (i.e. aiming off the mark with the needle) than in-bore biopsies. Moreover, different technical fusion approaches provide different degrees of manual/automated adjustment tools, with for example either rigid or elastic image transformation to facilitate MRI/US image alignment.

Finally, due to the recent introduction of these techniques the influence of learning curve and experience of the uro-radiologist must be considered [6].

In their analyses, Cash et al. [5] found that 34% of negative targeted biopsies could be explained by initially too high estimated PIRADS scores that were downgraded at re-reading. Interestingly, the remaining lesions were without an mpMRI correlate but within this group 92.9% showed a primary Gleason 3 pattern in biopsy pathology, suggesting a high degree of invisibility on mpMRI. Subanalyses did not show an association of targeted biopsy failures in the ventral location. Therefore, the study by Cash et al. [5] is an important precursor for further analyses to address other underlying reasons for targeted biopsy failure. Moreover, it reveals the need for a tight collaboration of radiologists, urologists, and pathologists as interdisciplinary partners involved in MRI-fusion biopsy. Consequently, the optimal diagnostic performance of MRI-fusion biopsies can only be achieved through standardised MRI performance, reading and reporting of MRI findings, as well as final correlation of MRI findings with histopathological work up.

Read the full article

Lars Budaus and Sami-Ramzi Leyh-Bannurah

Martini-Clinic University Hospital Hamburg-Eppendorf, Hamburg, Germany

References

1 Logan JK, Rais-Bahrami S, Turkbey B et al. Current status of magnetic resonance imaging (MRI) and ultrasonography fusion software platforms for guidance of prostate biopsies. BJU Int 2014;114:641–52

2 American College of Radiology. Prostate Imaging Reporting and Data System (PI-RADS), version 2.0. 2015. Available at: https://www.acr.org/ Quality-Safety/Resources/PIRADS/. Accessed November 2015

3 Schimmoller L, Quentin M, Arsov C et al. Inter-reader agreement of the ESUR score for prostate MRI using in-bore MRI-guided biopsies as the reference standard. Eur Radiol 2013;23:3185–90

4 Rud E, Klotz D, Rennesund K et al. Detection of the index tumour and tumour volume in prostate cancer using T2-weighted and diffusion-weighted magnetic resonance imaging (MRI) alone. BJU Int 2014;114: E32–42

5 Cash H, Gunzel K, Maxeiner A et al. Prostate cancer detection on transrectal ultrasonography-guided random biopsy despite negative real- time magnetic resonance imaging/ultrasonography fusion-guided targeted biopsy: reasons for targeted biopsy failure. BJU Int 2016; 118: 35–43

6 Gaziev G, Wadhwa K, Barrett T et al. Deﬁning the learning curve for multiparametric magnetic resonance imaging (MRI) of the prostate using MRI-transrectal ultrasonography (TRUS) fusion-guided transperineal prostate biopsies as a validation tool. BJU Int 2016; 117: 80–6

Video: TRUS-Guided RB Prostate Cancer Detection – Reasons for Targeted Biopsy Failure

July 20, 2016/1 Comment/by admin Z.9

Prostate cancer detection on transrectal ultrasonography-guided random biopsy despite negative real-time magnetic resonance imaging/ultrasonography fusion-guided targeted biopsy: reasons for targeted biopsy failure

Hannes Cash*, Karsten Gunzel*, Andreas Maxeiner*, Carsten Stephan*, Thomas Fischer†, Tahir Durmus†, Kurt Miller*, Patrick Asbach†, Matthias Haas† and Carsten Kempkensteffen*

*Department of Urology, and †Department of Radiology, Charite–University of Medicine Berlin, Berlin, Germany M. H. and C.K. contributed equally to the study.

Read the full article