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Highlights from BAUS 2016

July 5, 2016/3 Comments/by Nishant Bedi

In the week following Britain’s exit from Europe after the BREXIT referendum, BAUS 2016 got underway in Liverpool’s BT convention Centre. This was the 72^nd meeting of the British Association of Urological Surgeons and it was well attended with 1120 delegates (50% Consultant Member Urologists, 30% Trainees, 10% Non member Urologists/Other, 10% Nurses, HCP’S, Scientists).

Monday saw a cautionary session on medicolegal aspects in Andrology, focusing on lawsuits over the last year. Mr Mark Speakman presented on the management issue of testicular torsion. This sparked further discussion on emergency cover for paediatrics with particular uncertainty noted at 4 and 5 year olds and great variation in approach dependent on local trust policy. Mr Julian Shah noted the most litigious areas of andrology, with focus on cosmesis following circumcisions. Therefore serving a reminder on the importance of good consent to manage patients’ expectations.

In the Dragons’ Den, like the TV show, junior urologists pitched their ideas for collaborative research projects, to an expert panel. This year’s panel was made up of – Mark Emberton, Ian Pearce, and Graeme MacLennan. The session was chaired by Veeru Kasivisvanathan, Chair of the BURST Research Collaborative.

Eventual winner Ben Lamb, a trainee from London, presented “Just add water”. The pitch was for an RCT to investigate the efficacy of water irrigation following TURBT against MMC in reducing tumour recurrence. Ben proposed that water, with its experimental tumouricidal properties, might provide a low risk, low cost alternative as an adjuvant agent following TURBT. Judges liked the scientific basis for this study and the initial planning for an RCT. The panel discussed the merits of non-inferiority vs. superiority methodology, and whether the team might compare MMC to MMC with the addition of water, or water instead of MMC. They Dragons’ suggested that an initial focus group to investigate patients’ views on chemotherapy might help to focus the investigation and give credence to the final research question, important when making the next pitch- to a funding body, or ethics committee.

Other proposals were from Ryad Chebbout, working with Marcus Cumberbatch, an academic trainee from Sheffield. Proposing to address the current controversy over the optimal surgical technique for orchidopexy following testicular torsion. His idea involved conducting a systematic review, a national survey of current practice followed by a Delphi consensus meeting to produce evidence based statement of best practice. The final presentation was from Sophia Cashman, East of England Trainee for an RCT to assess the optimal timing for a TWOC after urinary retention. The panel liked the idea of finally nailing down an answer to this age-old question.

Waking up on Tuesday with England out of the European football cup as well as Europe the conference got underway with an update from the PROMIS trial (use of MRI to detect prostate cancer). Early data shows that multi-parametric MRI may be accurate enough to help avoid some prostate biopsies.

The SURG meeting provided useful information for trainees, with advice on progressing through training and Consultant interviews. A debate was held over run through training, which may well be returning in the future. The Silver cystoscope was awarded to Professor Rob Pickard voted for by the trainees in his deanery, for his devotion to their training.
Wednesday continued the debate on medical expulsion therapy (MET) for ureteric stones following the SUSPEND trial. Most UK Urologists seem to follow the results of the trial and have stopped prescribing alpha blockers to try and aid stone passage and symptoms. However the AUA are yet to adopt this stance and feel that a sub analysis shows some benefit for stones >5mm, although this is not significant and pragmatic outcomes. Assistant Professor John Hollingsworth (USA) argued for MET, with Professor Sam McClinton (UK) against. A live poll at the end of the session showed 62.9% of the audience persuaded to follow the SUSPEND trial evidence and stop prescribing MET.

In the debate of digital versus fibreoptic scopes for flexible ureteroscopy digital triumphed, but with a narrow margin.

In other updates and breaking news it appears that BCG is back! However during the shortage EMDA has shown itself to be a promising alternative in the treatment of high grade superficial bladder cancer.
The latest BAUS nephrectomy data shows that 90% are performed by consultant, with 16 on average per consultant per year. This raises some issues for registrar training, however with BAUS guidelines likely to suggest 20 as indicative numbers this is looking to be an achievable target for most consultants. Robotic advocates will be encouraged, as robotic partial nephrectomy numbers have overtaken open this year. The data shows 36% of kidney tumours in the under 40 years old are benign. Will we have to consider biopsying more often? However data suggests we should be offering more cytoreductive nephrectomies, with only roughly 1/10 in the UK performed compared to 3/10 in the USA.

The andrology section called for more recruitment to The MASTER trial (Male slings vs artificial urinary sphincters), whereas the OPEN trial has recruited(open urethroplasty vs optical urethotomy). In the treatment of Peyronie’s disease collagenase has been approved by NICE but not yet within the NHS.

Endoluminal endourology presentation showed big increases in operative numbers with ureteroscopy up by 50% and flexible ureteroscopy up by 100%. Stents on strings were advocated to avoid troubling stent symptoms experienced by most patients. New evidence may help provide a consensus on defining “stone free” post operation. Any residual stones post-operatively less than 2mm were shown to pass spontaneously and therefore perhaps may be classed as “stone free”.

Big changes seem likely in the treatment of benign prostatic hyperplasia, with a race to replace the old favorite TURP. Trials have of TURP (mono and bipolar) vs greenlight laser are already showing similar 2 year outcomes with the added benefit of shorter hospital stays and less blood loss. UROLIFT is an ever more popular alternative with data showing superiority to TURP in lifestyle measures, likely because it preserves sexual function, and we are told it can be performed as a 15 minute day case operation. The latest new therapy is apparently “Aquabeam Aquablation”, using high pressured water to remove the prostate. Non surgical treatments are also advancing with ever more accurate super selective embolisation of the prostatic blood supply.

This year all accepted abstracts were presented in moderated EPoster sessions. The format was extremely successful removing the need for paper at future conferences? A total of 538 abstracts were submitted and 168 EPosters displayed. The winner of best EPoster was P5-5 Altaf Mangera: Bladder Cancer in the Neuropathic Bladder.

The best Academic Paper winner was Mark Salji of the CRUK Beatson institute, titled “A Urinary Peptide Biomarker Panel to Identify Significant Prostate Cancer”. Using capillary electrophoresis coupled to mass spectrometry (CE-MS) they analysed 313 urine samples from significant prostate cancer patients (Gleason 8-10 or T3/4 disease) and low grade control disease. They identified 94 peptide urine biomarkers which may provide a useful adjunct in identifying significant prostate cancer from insignificant disease.

The Office of Education offered 20 courses. Popular off-site courses were ultrasound for the Urologist, at Broadgreen Hospital, a slightly painful 30 min drive from the conference centre. However well worth the trip, delivered by Radiology consultants this included the chance to scan patients volunteers under guidance, with separate stations for kidneys, bladder and testicles and learning the “knobology” of the machines.

Organised by Tamsin Greenwell with other consultant experts in female, andrology and retroperitoneal cancer, a human cadaveric anatomy course was held at Liverpool university. The anatomy teaching was delivered by both Urology consultants and anatomists allowing for an excellent combination of theory and functional anatomy.

BAUS social events are renowned and with multiple events planned most evenings were pretty lively. The official drinks reception was held at the beautiful Royal Liver Building. The venue was stunning with great views over the waterfront and the sun finally shining. Several awards were presented including the Gold cystoscope to Mr John McGrath for significant contribution to Urology within 10 years appointment as consultant. The Keith Yeates medal was awarded to Mr Raj Pal, the most outstanding candidate in the first sitting of the intercollegiate specilaity examination, with a score of over 80%.

During the conference other BAUS awards presented include the St Peter’s medal was awarded to Margeret Knowles, Head of section of molecular oncology, Leeds Institute of Cancer and Pathology, St James University hospital Leeds. The St Paul’s medal awarded to Professor Joseph A. Smith, Vanderbilt University, Nashville, USA. The Gold medal went to Mr. Tim Terry, Leicester General Hospital.

An excellent industry exhibition was on display, with 75 Exhibiting Companies present. My personal fun highlight was a flexible cystoscope with integrated stent remover, which sparked Top Gear style competiveness when the manufacturer set up a time-trial leaderboard. Obviously this best demonstrated the speed of stent removal with some interesting results…

Social media review shows good contribution daily.

Thanks BAUS a great conference, very well organised and delivered with a great educational and social content, looking forward to Glasgow 2017! #BAUS2017 #Glasgow #BAUSurology

Nishant Bedi

Specialist Training Registrar North West London

Twitter: @nishbedi

Editorial: One Day Protocol for Early Penile Cancer – The Way to Go

June 15, 2016/by Paul Hegarty

The present article by Dimopoulos et al. [1] has some useful lessons on the development of new services. The authors have kept a detailed database of all patients going through their super-regional network, and have designed the protocol around the patient, whereby the primary and regional lymph nodes are dealt with in one visit. Previously, bilateral inguinal lymph node dissection (ILND) was so fraught with complications that it would not be combined routinely with organ-sparing surgery of the penis [2]; however, the significantly lower complication rate of dynamic sentinel node biopsy (DSNB) has allowed the more streamlined approach. The ‘only handle it once’ (OHIO) philosophy is surely not only preferable for the patient, but also reduces the risk of patients not receiving ideal management. In most cases, a biopsy at the time of presentation, along with physical examination/imaging, can determine those requiring DSNB instead of waiting for final pathology from the primary tumour. The controversy surrounding DSNB compared with ILND has been the false-negative rates. The pioneering group from the Netherlands reported four deaths in six patients with false-negative results [3]. In the present paper, the overall false-negative rate was 5.8%, but the smaller and newer cohort of patients underwent a same-day protocol and had zero false-negatives. This may be attributable to the fact that biopsies were taken from a total sample of 65 or that slightly more nodes were taken in this group. We expect the one-day protocol to become standard, and future independent reports will be welcome. Should there truly be a 0% false-negative rate then the controversy is resolved and prophylactic ILND will become a historical procedure. Finally, the lower morbidity of the present study cohort allowed the authors to move the intermediate-risk group from surveillance to nodal biopsy, which proved justified because some of these cases had micrometastatic disease. We congratulate the group for their scientific approach to improving the quality of care for patients and for bringing their data to publication.

Read the full article

Paul K. Hegarty and Peter E. Lonergan

Urology, National Penile Cancer Centre, Mater Misericordiae University Hospital, Dublin, Ireland

References

1 Dimopoulos P, Christopoulos P, Shilito S et al. Dynamic sentinel lymph node biopsy for penile cancer: a comparison between 1- and 2-day protocols. BJU Int 2016; 117: 890–6

2 Hegarty PK, Eardley I, Heidenreich A et al. Penile cancer: Organ-sparing techniques. BJU Int 2014; 114: 799–805

3 Kroon BK, Horenblas S, Meinhardt W et al. Dynaminc sentinel node biopsy in penile cancer: evaluation of 10 years experience. Eur Urol 2005; 47: 601–6

Controversies in management of high-risk prostate and bladder cancer

October 12, 2015/by Stacy Loeb

Recently, there has been substantial progress in our understanding of many key issues in urological oncology, which is the focus of this month’s BJUI. One of the most substantial paradigm shifts over the past few years has been the increasing use of radical prostatectomy (RP) for high-risk prostate cancer and increasing use of active surveillance for low-risk disease [1,2].

Consistent with these trends, this month’s BJUI features several useful articles on the management of high-risk prostate cancer. The ﬁrst article by Abdollah et al. [3] reports on a large series of 810 men with D’Amico high-risk prostate cancer (PSA level >20 ng/mL, Gleason score 8–10, and/or clinical stage ≥T2c) undergoing robot-assisted RP (RARP). Despite high-risk characteristics preoperatively, 55% had specimen-conﬁned disease at RARP, which was associated with higher 8-year biochemical recurrence-free (72.7% vs 31.7%, P < 0.001) and prostate cancer-speciﬁc survival rates (100% vs 86.9%, P < 0.001). The authors therefore designed a nomogram to predict specimen-conﬁned disease at RARP for D’Amico high-risk prostate cancer. Using PSA level, clinical stage, maximum tumour percentage quartile, primary and secondary biopsy Gleason score, the nomogram had 76% predictive accuracy. Once externally validated, this could provide a useful tool for pre-treatment assessment of men with high-risk prostate cancer.

Another major controversy in prostate cancer management is the optimal timing of postoperative radiation therapy (RT) for patients with high-risk features at RP. In this month’s BJUI, Hsu et al. [4] compare the results of adjuvant (≤6 months after RP with an undetectable PSA level), early salvage (administered while PSA levels at ≤1 ng/mL) and late salvage RT (administered at PSA levels of >1 ng/mL) in 305 men with adverse RP pathology from the USA Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. At 6.2 years median follow-up, late salvage RT was associated with signiﬁcantly higher rates of metastasis and/or prostate cancer-death. By contrast, there was no difference in prostate cancer mortality and/or metastasis between early salvage vs adjuvant RT. A recent study from the USA National Cancer Data Base reported infrequent and declining use of postoperative RT within 6 months for men with adverse RP pathology, from 9.1% in 2005 to 7.3% in 2011 [5]. As we await data from prospective studies comparing adjuvant vs early salvage RT, the results of Hsu et al. [4] are encouraging, suggesting similar disease-speciﬁc outcomes if salvage therapy is administered at PSA levels of <1 ng/mL.

Finally, this issue’s ‘Article of the Month’ by Baltaci et al. [6] examines the timing of second transurethral resection of the bladder (re-TURB) for high-risk non-muscle-invasive bladder cancer (NMIBC). The management ofbladder cancer at this stage is a key point to improve the overall survival of bladder cancer. Re-TURB is already recommended in the European Association of Urology guidelines [7], but it remains controversial as to whether all patients require re-TURB and what timing is optimal. The range of 2–6 weeks after primary TURB was established based on a randomised trial assessing the effect of re-TURB on recurrence in patients treated with intravesical chemotherapy [8], but it has not been subsequently tested in a randomised trial. Baltaci et al. [6], in a multi-institutional retrospective review of 242 patients, report that patients with high-risk NMIBC undergoing early re-TURB (14–42 days) have better recurrence-free survival vs later re-TURB (73.6% vs 46.2%, P < 0.01). Although prospective studies are warranted to conﬁrm their results, these novel data suggest that early re-TURB is signiﬁcantly associated with lower rates of recurrence and progression.

References

1 Cooperberg MR, Carroll PR. Trends in management for patients with localized prostate cancer, 1990–2013. JAMA 2015; 314: 80–2

2 Loeb S, Berglund A, Stattin P. Population based study of use and determinants of active surveillance and watchful waiting for low and intermediate risk prostate cancer. J Urol 2013; 190: 1742–9

3 Abdollah F, Klett DE, Sood A et al. Predicting pathological outcomes in patients undergoing robot-assisted radical prostatectomy for high- risk prostate cancer: a preoperative nomogram. BJU Int 2015; 116: 703–12

4 Hsu CC , Paciorek AT, Cooperberg MR, Roach M 3rd, Hsu IC, Carroll PR. Postoperative radiation therapy for patients at high-risk of recurrence after radical prostat ectomy: does timing matter? BJU Int 2015; 116: 713–20

5 Sineshaw HM, Gray PJ, Efstathiou JA, Jemal A. Declining use of radiotherapy for adverse features after radical prostatectomy: results from the National Cancer Data Base. Eur Urol 2015; [Epub ahead of print]. DOI: 10.1016/ j.eururo.2015.04.003

6 Baltacı S, Bozlu M, Yıldırım A et al. Signiﬁcance of the interval between ﬁrst and second transurethral resection on recurrence and progression rates in patients with high-ris k non-muscle-invasive bladder cancer treated with maintenance intravesical Bacillus Calmette-Guerin. BJU Int 2015; 116: 721–6

7 Babjuk M, Bohle A, Burger M et al. European Association of Urology Guidelines on Non-Muscle-Invasive Bladder Cancer (Ta, T1, and CIS). Available at: https://uroweb.org/wp-content/uploads/EAU-Guidelines- Non-muscle-invasive-Bladder-Cancer-2015-v1.pdf. Accessed September 2015

8 Divrik RT, Yildirim U, Zorlu F, Ozen H. The effect of repeat transurethral resection on recurrence and progression rates in patients with T1 tumors of the bladder who received intravesical mitomycin: a prospective, randomized clinical trial. J Urol 2006; 175: 1641–4

Stacy Loeb – Department of Urology, Population Health, and the Laura and Isaac Perlmutter Cancer Center, New York University, New York City, NY, USA

Maria J. Ribal – Department of Urology, Hospital Clinic, University of Barcelona, Barcelona, Spain

Article of the Week: HAL fluorescence cystoscopy in the diagnosis of NMIBC

July 15, 2015/by admin Z.9

Every Week the Editor-in-Chief selects the 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.

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

Effectiveness of hexaminolevulinate fluorescence cystoscopy for the diagnosis of non-muscle-invasive bladder cancer in daily clinical practice: a Spanish multicentre observational study

Juan Palou, Carlos Hernandez*, Eduardo Solsona†, Ramon Abascal‡, Juan P. Burgues§, Carlos Rioja¶, Jose A. Cabrera**, Carlos Gutierrez††, Oscar Rodrıguez, Inmaculada Iborra†, Felipe Herranz**, Jose M. Abascal‡, Guillermo Conde†† and Jose Oliva¶

Fundacio Puigvert, Universitat Autonoma de Barcelona, Barcelona,*Hospital Gregorio Maranon, Madrid, †Instituto Valenciano de Oncologıa, Valencia, ‡Hospital Central de Asturias, Oviedo, §Hospital Universitari Son Dureta, Palma de Mallorca , ¶Hospital Royo Vilanova, Zaragoza , **Hospital Central de Defensa Gomez Ulla, Madrid, and ††Hospital Son Llatzer, Palma de Mallorca, Spain

Read the full article

OBJECTIVE

To assess the sensitivity and specificity of blue-light cystoscopy (BLC) with hexaminolevulinate as an adjunct to white-light cystoscopy (WLC) vs WLC alone for the detection of non-muscle-invasive bladder cancer (NMIBC), in routine clinical practice in Spain.

PATIENTS AND METHODS

An intra-patient comparative, multicentre, prospective, observational study. Adults with suspected or documented primary or recurrent NMIBC at eight Spanish centres were included in the study. All patients were examined with WLC followed by BLC with hexaminolevulinate. We evaluated the detection rate of bladder cancer lesions by WLC and BLC with hexaminolevulinate, overall and by tumour stage and compared with histological examination of the biopsied lesions. Sensitivity and specificity was calculated.

RESULTS

In all, 1 569 lesions were identified from 283 patients: 621 were tumour lesions according to histology and 948 were false-positives. Of the 621 tumour lesions, 475 were detected by WLC (sensitivity 76.5%, 95% confidence interval [CI] 73.2–79.8) and 579 were detected by BLC (sensitivity 93.2%, 95% CI 91.0–95.1; P < 0.001). There was a significant improvement in the sensitivity in the detection of all types of NMIBC lesions with BLC compared with WLC. Of 219 patients with tumours, 188 had NMIBC [highest grade: carcinoma in situ (CIS), n = 36; Ta, n = 87; T1, n = 65). CIS lesions were identified more with BLC (n = 27) than with WLC [n = 19; sensitivity: BLC 75.0% (95% CI 57.8–87.9) vs WLC 52.8% (95% CI 35.5–69.6); P = 0.021]. Results varied across centres.

CONCLUSIONS

This study shows that improvement in diagnosis of NMIBC, mainly CIS and Ta tumours, obtained with BLC with hexaminolevulinate as an adjunct to WLC vs WLC alone can be shown in routine clinical practice.

Editorial: Fluorescence cystoscopy – the end of biopsies for CIS detection?

July 15, 2015/by admin Z.9

The present prospective study by Palou et al. [1], conducted in eight Spanish centres, documents the use of hexaminolevulinate fluorescence cystoscopy (FC)-guided bladder tumour resection and biopsies in 283 patients with non-muscle-invasive bladder cancer (NMIBC). It is an inpatient comparison between white-light cystoscopy and FC. The study presents data from routine practice in Spain and the results show an improvement in diagnosis of NMIBC, especially Ta tumours and carcinoma in situ (CIS) with FC-guided resections. These results are confirmation of reports in the literature, including a number of randomized controlled trials and a recent large meta analysis [2]. Although the magnitude of the difference between FC and white-light cystoscopy was somewhat lower in the present study, apparently even in normal daily practice the difference was significant. Moreover, as the rate of CIS in Spain is very high, up to 19% in a large Spanish series [3], I can imagine that the use of FC is of specific interest in this country.

Apart from the confirmation of the better detection rate (75.5 and 93.2% for white-light cystoscopy and FC, respectively, figures similar to those in the recent literature) and confirmation of safety of hexaminolevulinate FC, there are two particular points regarding the present study that I would like to highlight.

The first item that deserves some discussion is mucosal biopsies. In this study the number of false-positive results (948/1569; 60.4%) was very high. This was predominantly explained by the inclusion or mucosal biopsies from ‘normal appearing urothelium’ in these calculations. Only 36 lesions were detected with biopsies, which suggests a very low detection rate. Assuming that >800 random biopsies were taken (apparently six biopsies were taken per patient, and biopsies were taken in 49.1% of the 283 patients), the detection rate was <4%, and one might ask whether it was still worthwhile to take these biopsies. Even though 26.7% of patients with CIS were only diagnosed by biopsies in this study, the number was small. The authors also indicate that it was surprising that CIS was not found more often with FC, but they blame it on the learning curve for FC. The value of mucosal biopsies was also questioned by some reviewers, and in fact by the present authors too. In their introduction they explain the biopsy policy by the high rate of CIS in Spain; however, they also indicate that this incidence seems to be decreasing. Taking together the disappointing detection rate of mucosal biopsies and the high detection rate of CIS with FC, the message should be clear: stop taking mucosal biopsies from normal-looking urothelium. As a matter of fact, this had already been suggested before the era of FC by the authors of other large studies, such as an analysis by the European Organisation for the Research and Treatment of Cancer [4] and a large Dutch study [5]. The false-positive rate for FC was not very high (15.7%, similar to the more recent studies with hexaminolevulinate FC). And I assume that these figures would even be much lower if biopsies of normal urothelium were to be excluded from these calculations.

The second point that deserves attention is the learning curve for FC and its impact on the results. The authors indeed mention as an important limitation of this study ‘the investigators’ lack of experience’ with FC. They point out that this might be the reason that the advantage of FC for the detection of CIS seemed to be less pronounced than in published series, although still significantly better than with white light. In their cohort, 27 of 36 patients with CIS (75%) were detected with FC. The impact of the learning curve and the limited experience of some of the centres is also illustrated by the wide range between centres in, for example, the false-positive rates. Indeed, some training with this FC technique is mandatory. Unfortunately, however, the authors were not able to provide details of the relationship between experience and detection of CIS or false-positive rates.

In conclusion, even in routine practice, FC significantly improves the detection of NMIBC. The advantage is seen especially in Ta tumours and CIS, similarly to recent publications. The use of FC can, in my view, replace the use of random mucosal biopsies of normal-looking urothelium with white light because the detection rate of these biopsies is only a few percent. Finally, the present study also shows that a learning curve significantly improves the detection rate of NMIBC with FC and decreases the rate of false-positives. This should probably be somewhere between 5 (the number used in some of the registration studies for hexaminolevulinate) and 20 as suggested by a recent Canadian study [6].

Read the full article

J. Alfred Witjes

Department of Urology, Radboud University Nijmegen Medicalm Centre, Nijmegen, The Netherlands

References

1 Palou J, Hernandez C, Solsona E et al. Effectiveness of hexaminolevulinate ﬂuorescence cystoscopy for the diagnosis of non-muscle-invasive bladder cancer in daily clinical practice: a Spanish multicentre observational study. BJU Int 2015; 116: 37–43

2 Burger M, Grossman HB, Droller M et al. Photodynamic diagnosis of non-muscle-invasive bladder cancer with hexaminolevulinate cystoscopy: a meta-analysis of detection and recurrence based on raw data. Eur Urol 2013; 64: 846–54

3 Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, Palou J, Algaba F, Vicente-Rodriguez J. Primary superﬁcial bladder cancer risk groups according to progression, mortality and recurrence. J Urol 2000; 164: 680–4

4 van der Meijden A, Oosterlinck W, Brausi M, Kurth KH, Sylvester R , de Balincourt C. Signiﬁcance of bladder biopsies in Ta,T1 bladder tumors: a report from the EORTC Genito-Urinary Tract Cancer Cooperative Group. EORTC-GU Group Superﬁcial Bladder Committee. Eur Urol 1999; 35: 267–71

5 Kiemeney LA, Witjes JA, Heijbroek RP, Koper NP, Verbeek AL, Debruyne FM. Should random urothelial biopsies be taken from patients with primary superﬁcial bladder cancer? A decision analysis Br J Urol 1994; 73: 164–71

6 Gravas S, Efstathiou K, Zachos I, Melekos MD, Tzortzis V.Is there a learning curve for photodynamic diagnosis of bladder cancer with hexaminolevulinate hydrochloride? Can J Urol 2012; 19: 6269– 73

Highlights from #BAUS15

June 24, 2015/by Rebecca Tregunna

#BAUS15 started to gain momentum from as early as the 26^th June 2014 and by the time we entered the Manchester Central Convention Complex well over 100 tweets had been made. Of course it wasn’t just Twitter that started early with a group of keen urologists cycling 210 miles to conference in order to raise money for The Urology Foundation.

Monday 15^th June 2015

By the time the cyclists arrived conference was well under way with the andrology, FNUU and academic section meetings taking place on Monday morning:

The BJU International Prize for the Best Academic Paper was awarded to Richard Bryant from the University of Oxford for his work on epithelial-to-mesenchymal transition changes found within the extraprostatic extension component of locally invasive prostate cancers.
Donna Daly from the University of Sheffield received the BJUI John Blandy prize for her work on Botox, demonstrating reductions in afferent bladder signaling and urothelial ATP release.

Professor Reisman’s talk on ‘Porn, Paint and Piercing’ as expected drew in the crowds and due to a staggering 44% complication rate with genital piercings it is important for us to try to manage these without necessarily removing the offending article as this will only serve to prevent those in need from seeking medical attention.
With the worsening worldwide catastrophe of antibiotic resistance, the cycling of antibiotics for prevention of recurrent UTIs is no longer recommended. Instead, Tharani Nitkunan provided convincing evidence for the use of probiotics and D-Mannose.

The afternoon was dominated by the joint oncology and academic session with Professor Noel Clarke presenting the current data from the STAMPEDE trial. Zolendronic acid conferred no survival benefit over hormones alone and consequently has been removed from the trial (stampede 1). However, Docetaxal plus hormones has shown benefit, demonstrated significantly in M1 patients with disease-free survival of 65 months vs. 43 months on hormones alone (Hazard ratio 0.73) (stampede 2). This means that the control arm of M1 patients who are fit for chemotherapy will now need to be started on this treatment as the trial continues to recruit in enzalutamide, abiraterone and metformin arms.

The evening was rounded off with the annual BAUS football tournament won this year by team Manchester (obviously a rigged competition!), whilst some donned the

lycra and set out for a competition at the National Cycle Centre. For those of us not quite so energetic, it was fantastic to catch up with old friends at the welcome drinks reception.

Tuesday 16^th June 2015

Tuesday kicked off bright and early with Professor John Kelly presenting results from the BOXIT clinical trial, which has shown some benefit over standard treatment of non-muscle invasive bladder cancer, but with significant cardiovascular toxicity.

The new NICE bladder cancer guidelines were presented with concerns voiced by Professor Marek Babjuk over discharging low-risk bladder cancer at 12 months given a quoted 30-50% five-year recurrence risk. Accurate risk stratification, it would seem, is going to be key.

The President’s address followed along with the presentation of the St. Peter’s medal for notable contribution to the advancement of urology, which was presented to Pat Malone from Southampton General Hospital. Other medal winners included Adrian Joyce who received the BAUS Gold Medal, and the St. Paul’s medal went to Mark Soloway.

A plethora of other sessions ensued but with the help of the new ‘native’ BAUS app my programme was already conveniently arranged in advance:

‘Heartsink Conditions’ included pelvic and testicular pain and a fascinating talk by Dr Gareth Greenslade highlighted the importance of early and motivational referral to pain management services once no cause has been established and our treatments have been exhausted. The patient’s recovery will only start once we have said no to further tests: ‘Fix the thinking’

Poster sessions are now presented as ‘e-posters’, abolishing the need to fiddle with those little pieces of Velcro and allowing for an interactive review of the posters.

Pravisha Ravindra from Nottingham demonstrated that compliance with periodic imaging of patients with asymptomatic small renal calculi (n=147) in primary care is poor, and indeed, these patients may be better managed with symptomatic imaging and re-referral as no patients required intervention based on radiograph changes alone.

Archana Fernando from Guy’s presented a prospective study demonstrating the value of CTPET in the diagnosis of malignancy in patients with retroperitoneal fibrosis (n=35), as well as demonstrating that those with positive PET are twice as likely to respond to steroids.

Wednesday 17^th June 2015

Another new addition to the programme this year was the Section of Endourology ‘as live surgery’ sessions. This was extremely well received and allowed delegates to benefit from observing operating sessions from experts in the field whilst removing the stressful environment and potential for risk to patient associated with live surgery. This also meant that the surgeon was present in the room to answer questions and talk through various steps of the operation allowing for a truly interactive session.
Wednesday saw multiple international speakers dominating the Exchange Auditorium:

The BJU International guest lecture was given by Professor Hendrik Van Poppel: a heartfelt presentation describing what he believes to be the superiority of surgery over radiotherapy for high-risk localised prostate cancer.
The Urology Foundation presented the Research Scholar Medal to Ashwin Sachdeva from Freeman Hospital, Newcastle for his work on the ‘Role of mitochondrial DNA mutations in prostate carcinogenesis’. This was followed by an inspiring guest lecture by Inderbir Gill on ‘Robotic Urologic Oncology: the best is yet to come’ with the tag line ‘the only thing that should be open in 2015 is our minds’
Robotic Surgery in UK Urology: Clinical & Commissioning Priorities was a real highlight in the programme with talks from Jim Adshead and Professor Jens-Uwe Stolzenburg focussing on the fact that only 40% of T1a tumours in the UK were treated with partial (as opposed to radical) nephrectomy, and that the robot really is the ‘game-changer’ for this procedure. Inderbir Gill again took to the stage to stress that all current randomised trials into open vs. robotic cystectomy have used extracorporeal reconstruction and so do not reflect the true benefits of the robotic procedure as the dominant driver of complications is in the open reconstruction.

These lectures were heard by James Palmer, Clinical Director of Specialised Commissioning for NHS England who then discussed difficulties in making decisions to provide new technologies, controlling roll out and removing them if they show no benefit. Clinical commissioning policies are currently being drafted for robotic surgery in kidney and bladder cancer. This led to a lively debate with Professor Alan McNeill having the last word as he pointed out that what urologists spend on the robot to potentially cure cancer is a drop in the ocean compared with what the oncologists spend to palliate!

Thursday 18^th June 2015

The BJU International session on evidence-based urology highlighted the need for high-quality evidence, especially in convincing commissioners to spend in a cash-strapped NHS. Professor Philipp Dahm presented a recent review in the Journal of Urology indicated that the quality of systematic reviews in four major urological journals was sub-standard. Assistant Professor Alessandro Volpe then reviewed the current evidence behind partial nephrectomy and different approaches to this procedure.

Another fantastic technology, which BAUS adopted this year, was the BOD-POD which allowed delegates to catch-up on sessions in the two main auditoria that they may have missed due to perhaps being in one of the 21 well designed teaching courses that were available this year. Many of these will soon be live on the BAUS website for members to view.

The IBUS and BAUS joint session included a lecture from Manoj Monga from The Cleveland Clinic, which led to the question being posed on Twitter: ‘Are you a duster or a basketer?’The audience was also advised to always stent a patient after using an access sheath unless the patient was pre-stented.

The updates session is always valuable especially for those studying for the FRCS (Urol) exam with far too many headlines to completely cover:

Endourology: The SUSPEND trial published earlier this year was a large multi-centre RCT that showed no difference in terms of rates of spontaneous passage of ureteric stone, time to stone passage or analgesic use between placebo, tamsulosin and nifedipine. There was a hot debate on this: should we be waiting for the meta-analysis or should a trial of this size and design be enough to change practice?
Oncology-Prostate: The Klotz et al., paper showed active surveillance can avoid over treatment, with 98% prostate cancer survival at 10 years.
Oncology-Kidney: Ellimah Mensah’s team from Imperial College London (presented at BAUS earlier in the week) demonstrated that over a 14-year period there were a higher number of cardiovascular-related admissions to hospital in patients who have had T1 renal tumours resected than the general population, but no difference between those who have had partial or radical nephrectomy.
Oncology-Bladder: Arends’s team presented at EAU in March on the favourable results of hyperthermic mitomycin C vs. BCG in the treatment of intermediate- and high-risk bladder cancer.
Female and BPH: The BESIDE study has demonstrated increased efficacy with combination solifenacin and mirabegron.
Andrology: Currently recruiting in the UK is the MASTER RCT to evaluate synthetic sling vs. artificial sphincter in men with post-prostatectomy urinary incontinence.

Overall BAUS yet again put on a varied and enjoyable meeting. The atmosphere was fantastic and the organisers should be proud of the new additions in terms of allowing delegates to engage with new technologies, making for a memorable week. See you all in Liverpool!

Rebecca Tregunna, Urological Trainee, West Midlands Deanery @rebeccatregunna

Dominic Hodgson, Consultant Urologist, Portsmouth @hodgson_dominic

RSM Bladder Day

May 12, 2015/by Rebecca Tregunna

The urology section of the RSM left Wimpole Street and travelled up to sunny Queen Elizabeth Hospital in Birmingham on the 24th April to be educated in the ‘Management of Non-Muscle invasive and Muscle Invasive Bladder Cancer’. This meeting was organised in collaboration with Nick James and Rik Bryan at the Birmingham Warwick Uro-Oncology unit as the RSM looks to add to its regional programme of teaching days.

The meeting was well attended by both experts as well as trainees and we kicked off with John McGrath and a review of the evidence behind current haematuria investigations as well as the new NICE guidelines. Professor Charles Hutchinson from the University of Warwick then gave a detailed talk on pre-operative imaging in bladder cancer and this led to an interesting debate on the necessity of performing a full TURBT in cases of known muscle invasive disease if the patient will ultimately require a cystectomy. No consensus was reached although if definitely proceeding to cystectomy it is unlikely to be beneficial. If radiotherapy is considered then debulking is important.

Eva Comperat from the Service d’Anatomie and Cytologie Pathologiques du Pr Capron presented a fascinating histopathological perspective of bladder cancer and it was interesting to see that even amongst eminent pathologists there can be challenges in distinguishing pTa from pT1 disease with only 44% in one large study showing full agreement. The importance in reporting histological variants such as micropapillary or plasmocytoid was discussed due to the aggressive nature of these types and the need for more radical treatment. This was also re-iterated by Peter Rimington while discussing early cystectomy which should be offered to all suitable patients at high risk of progression according to EORTC tables, especially in young patients and in tumours which are multifocal, difficult to resect, have deep lamina propria or prostatic involvement and those with associated CIS.

A highlight for me was Professor John Kelly’s talk on the treatment option of hyperthermic Mitomycin C. HYMN Trial.

Data from the HYMN trial which looked at hyperthermic MMC vs. standard treatment in BCG failures was disappointing in that there was no difference in terms of disease free survival at 24 months. Outcomes were found to be worse in patients with CIS, but in patients with papillary disease, hyperthermic MMC had far more favourable results. This has led to the HIVEC I and HIVEC II trials currently recruiting in the UK and Spain looking at standard MMC vs. hyperthermic MMC in intermediate risk disease. It was also interesting to see new immunotherapy drugs currently in phase III trials which will hopefully be available in the near future.

Rik Bryan’s presentation on the evolving role of bio markers explained that the Bladder Cancer Diagnostic Programme had found that contrary to our beliefs, patients trust, and would rather accept certainty over burden and thus would rather continue with cystoscopic surveillance over bio-markers, unless the sensitivity of these bio-markers was over 99%. No such bio-marker has yet been found to be that accurate but current research into odor-readers, urinary dipsticks and DNA all look promising in terms of potential for both diagnosis and prognosis.

Both Nick James and Hugh Mostafid highlighted current research trials with the CALIBER RCT on chemo resection in recurrent low risk bladder cancer as well as the PHOTO trial looking at both clinical and cost effectiveness of photo-dynamic cystoscopy leading the way in terms of surgical trials currently recruiting. Nick also caused a stir on Twitter as he presented data showing a median survival advantage of more than a year between surgeons performing low or high volume of cystectomies annually. Surely we do not need more convincing evidence to centralise such surgery?

Reviewing bladder cancer from the oncologist’s perspective, Syed Hussein from the University of Liverpool explained that although there is a 6% overall survival benefit with neo-adjuvant chemotherapy there have been no RCT on MVAC vs gemcitabine/cisplatin regimes. Nick James’ talk on bladder preserving treatment added to this that synchronous chemoradiotherapy could be complementary to neo-adjuvant treatment and the addition of synchronous chemotherapy has been shown to provide a significant improvement in terms of loco regional control.

Vijay Ramani presented his series on salvage cystectomy with no significant difference in terms of complications for salvage vs. primary surgery as long as certain techniques were adopted such as division of ureters outside of the pelvis and using bowel at least 15-20cm proximal from the ileocaecal valve.

To complete the diverse and stimulating programme, Professor Peter Wiklund from the Karolinska University Hospital, Stockholm, presented a state of the art lecture on “Reconstruction rules! The robot has taken over?”. With discussion and impressive videos demonstrating intra-corporeal robotic neobladder reconstruction it was difficult not to be in awe of such an impressive series, with a 90% continence rate in males.

Overall it was fantastic to have the RSM in the West Midlands. Roger Plail has done much to reach out to those of us outside of London and I look forward to the Geoffrey Chisholm Prize Meeting and AGM on the 22nd May in Hastings. RSM President’s Day.

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

Is maintenance BCG an unnecessary evil? Summary of the April 2015 #urojc

May 1, 2015/by Sophia Cashman

The current BCG shortage, and the effect this is having on our bladder cancer patients, is an issue that continues to weigh heavily on many urologists. With no immediate solution in sight, and limited availability, a variety of tactics are being advocated to optimally use the current supply.

The April 2015 International Urology Journal Club #urojc debate focused on the timely paper by Martínez-Piñeiro et al¹. This paper reported the results of a randomised trial evaluating the outcomes of BCG induction followed by a modified three year maintenance regimen versus standard BCG induction alone in patients with high-risk non-muscle-invasive bladder cancer. The investigators concluded there was no observed decrease in recurrence and progression rates in those receiving just induction compared to induction and maintenance regimen.

This very topical debate kicked off on Sunday 12^th April.

Coinciding with the USANZ Annual Scientific Meeting, this month’s debate gave both those who were live tweeting at the conference, and those learning about the benefits of social media as a new concept, the opportunity to see the #urojc debate in action.

One of the first points of discussion raised was the difference between the maintenance protocol used in the study, consisting of one BCG installation every three months for three years, and the standard SWOG schedule.

The lack of difference in outcome between the two groups raised the question as to whether this indicated that their modified maintenance protocol is less effective that the current strategies.

The theme of alternative maintenance schedules continued, with some variation in practice noted.

Some of the variability in maintenance may be due to the tolerability and side effects experienced.

Although there may be a degree of acceptance amongst patients if there is thought to be a chance of improvement in risks of disease recurrence or progression.

The reason for the variability of response to BCG therapy between patients remains unclear.

For the patient, the lack of understanding of why this is the case may be a cause of distress, especially when faced with adverse effects and toxicity.

Inevitably it was not long until the key on-going issue of the lack of available BCG was raised.

This issue continues to cause a lot of angst for both patients and their treating urologists, with no immediate solution evident. There may however be light at the end of a somewhat long tunnel with the restarting of production by Sanofi.

In the mean time, the downstream effects of the production delay continues to compromise the treatment options for bladder cancer patients.

As the availability remains largely outside of clinicians’ hands, perhaps our focus at present needs to be on other factors we can control in order to improve the outcomes for our bladder cancer patients.

This debate surrounding this paper has raised a number of key points that, in the face of the BCG shortage, are worth considering. Until the supply is re-established, the BCG we have needs to be optimally used – however perhaps the most effective maintenance schedule needs further investigation. Or perhaps, due to the variation in tolerability and effectiveness between individuals, maintenance therapy needs to remain a more fluid concept.

As always, the #urojc debate involved healthy international discussions. This gives the unique ability to understand the global viewpoints on the study findings, and the current BCG crisis. Analytics of the debate using the #urojc hash tag from the website www.symplur.com again demonstrated the excellent involvement from participants, with over 180,000 unique impressions.

Thanks to all of those who participated this month. We look forward to the #urojc May debate – I am sure it will be as lively as ever.

1. Martínez-Piñeiro L, Portillo JA, Fernández JM, et al. Maintenance Therapy with 3-monthly Bacillus Calmette-Guérin for 3 Years is Not Superior to Standard Induction Therapy in High-risk Non-muscle-invasive Urothelial Bladder Carcinoma: Final Results of Randomised CUETO Study 98013. European Urology March 2015 (Article In Press)

Radical cystectomy for bladder cancer – is there a changing trend?

January 23, 2015/by Greg Nason

The first #urojc instalment of 2015 discussed the recent European Urology paper ‘Trends in operative caseload and mortality rates after radical cystectomy (RC) for bladder cancer in England for 1998-2010’. Hounsome et al., examined a total of 16,033 patients who underwent RC – over the study period 30-day and 90-day mortality rates decreased and 30-day, 90-day, 1-year and 5-year survival rates significantly improved.

Henry Woo (@DrHWoo) suggests this paper is breaking the mould in comparison to other series.

Analysis of the SEER database would suggest otherwise – there has been little or no change in the incidence, survival or mortality rates with respect to bladder cancer over an even longer study period (1973-2009). Likewise, Zehnder noticed no survival improvement in patients undergoing RC over the last three decades (1980-2005).

However, Jim Catto (@JimCatto) and Alexander Kutikov (@uretericbud) were quick to point out the differences between survival rates and mortality rates, although Hounsome et al., reported beneficial outcomes in both parameters.

In the UK, the Improving Outcomes in Urological Cancers guidance (IOG) recommends patients be considered for RC for muscle invasive bladder cancer (MIBC) and high risk recurrent non-muscle invasive bladder cancer (NMIBC). Key aspects of this guidance include – a minimum caseload requirement for performing RC, an MDT approach and specific 30day mortality rates of 50% despite no change in the incidence of bladder cancer. The reasoning for this is multifactorial but in part due to designated cancer centres are offering surgery to more candidates as a result of service improvements that include service reconfiguration, improved surgical training, neoadjuvant chemotherapy, enhanced recovery principles, and continued improvements in peri-operative care.

The on-line debate moved towards discussing the effect of centralisation of cancer services as a causative factor behind these positive results.

Rather intuitively, in a systematic review in 2011, Goossens-Laan et al., postoperative mortality after cystectomy is significantly inversely associated with high-volume providers.

Although the benefits of being treated in a cancer centre of excellence are undoubted- high volume fellowship trained surgeons, a multidisciplinary approach and improved peri-operative conditions; the impact of distance from central services was broached. O’Kelly et al., postulated a higher stage of prostate cancer based on distance from a tertiary care centre, other studies have shown for a variety of cancers (lung, colon)that distance from a central provider can impact outcomes. Outside of the impact on oncological outcomes, the impact on the patient’s lifestyle as well as the economic consequences were not discussed.

While contrary to this, Jim Catto (@JimCatto) highlighted the deskilling associated with centralisation.

A further significant implicating factor in the positive results seen in this study is due to the use of neo-adjuvant chemotherapy, a question often posed by the patient.

Rather contentiously, David Chan (@dytcmd) remarked that optimal surgical results have already been achieved, a statement challenged by Jim Catto (@JimCatto).

This study although examining a vast number of patients over a lengthy time period is not without its limitations. Specifically the lack of tumour stage, smoking status and the use of chemotherapy as well as issues surrounding a retrospective study looking at data collected by individual hospital coding systems.

This month’s #urojc attracted substantial coverage on Twitter – keep it up.

Many thanks to those you participated in the debate. We look forward to next month’s #urojc discussion.

Greg Nason (@nason_greg) is a Specialist Registrar in Urology, Beaumont Hospital, Dublin, Ireland

Article of the Month: Comparing health-related QoL outcomes for robotic cystectomy with those of traditional open radical cystectomy

December 3, 2014/by admin Z.9

Every week the Editor-in-Chief selects the 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.

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 Dr. Dipen Parekh discussing his paper.

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

Health-related quality of life from a prospective randomised clinical trial of robot-assisted laparoscopic vs open radical cystectomy

Jamie C. Messer, Sanoj Punnen*, John Fitzgerald, Robert Svatek and Dipen J. Parekh

Department of Urology, University of Texas Health Sciences Center at San Antonio, San Antonio, TX and *Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA

Read the full article

Objective

To compare health-related quality-of-life (HRQoL) outcomes for robot-assisted laparoscopic radical cystectomy (RARC) with those of traditional open radical cystectomy (ORC) in a prospective randomised fashion.

Patients and Methods

This was a prospective randomised clinical trial evaluating the HRQoL for ORC vs RARC in consecutive patients from July 2009 to June 2011. We administered the Functional Assessment of Cancer Therapy–Vanderbilt Cystectomy Index questionnaire, validated to assess HRQoL, preoperatively and then at 3, 6, 9 and 12 months postoperatively. Scores for each domain and total scores were compared in terms of deviation from preoperative values for both the RARC and the ORC cohorts. Multivariate linear regression was used to assess the association between the type of radical cystectomy and HRQoL.

Results

At the time of the study, 47 patients had met the inclusion criteria, with 40 patients being randomised for analysis. The cohorts consisted of 20 patients undergoing ORC and 20 undergoing RARC, who were balanced with respect to baseline demographic and clinical features. Univariate analysis showed a return to baseline scores at 3 months postoperatively in all measured domains with no statistically significant difference among the various domains between the RARC and the ORC cohorts. Multivariate analysis showed no difference in HRQoL between the two approaches in any of the various domains, with the exception of a slightly higher physical well-being score in the RARC group at 6 months.

Conclusions

There were no significant differences in the HRQoL outcomes between ORC and RARC, with a return of quality of life scores to baseline scores 3 months after radical cystectomy in both cohorts.