Tag: PROMIS

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PRECISION delivers on the PROMIS of mpMRI in early detection of prostate cancer

March 19, 2018/38 Comments/by Declan Murphy

Today, Dr Veeru Kasi of University College London, presented the results of the PRECISION (PRostate Evaluation for Clinically Important disease: Sampling using Image-guidance Or Not?) study in the “Game Changing” Plenary session at the #EAU18 Annual Meeting in Copenhagen. The accompanying paper was simultaneously published in the New England Journal of Medicine. And it is stunning! Everyone in the packed eURO auditorium knew they were witness to a practice-changing presentation, and the swift reaction on social media around the world confirms this.

Fundamental paradigm shift in prostate cancer diagnostics, from @veerukasi @mrsprostate #EAU18 today, and @NEJM now online. What a day https://t.co/U7MW3oeCvV pic.twitter.com/MfpgpgGkgV

— Declan Murphy (@declangmurphy) March 19, 2018

PRECISION: MRI-targeted biopsy strategy leads to fewer men needing biopsy. Article with video interviews with Veeru Kasivisvanathan and Declan Murphy https://t.co/QXaWZLaBvo

— European Association of Urology (EAU) (@Uroweb) March 19, 2018

Congratulations to Veeru (a second year urology resident in London), senior author Dr Caroline Moore, Prof Mark Emberton, and all the collaborators on this multicenter international trial. I had the great privilege to be the Discussant in the Plenary session so have been digesting this study in detail for the past few weeks.

Let me summarise the PRECISION study in brief. In this multicenter international study, 500 men with a suspicion of prostate cancer (mean age 64, median PSA 6.7), were randomised to receive a standard of care (SOC) diagnostic pathway (12 core TRUS biopsy), or an MRI directed pathway. In the MRI pathway, all patients had an MRI, and if the MRI was abnormal (72% of men), they had a targeted biopsy of the lesion(s) (with no systematic biopsy; ie only the abnormal lesion was biopsied). If the MRI was normal (28% of men), they did not have a biopsy, and continued on routine PSA surveillance. The primary outcome was detection rate of clinically significant cancer; and secondary outcomes included the detection rate of clinically insignificant cancer. In the standard of care arm, the detection rate of clinically significant cancer was 26%, and the detection rate of clinically insignificant cancer was 22%. In the MRI pathway, the detection rate of clinically significant cancer was 38%, and the detection rate of taking insignificant cancer was 9%. This is depicted below in one of my summary slides from the plenary discussion.

Therefore, despite the fact that over one quarter of men in the MRI pathway actually avoided a biopsy, the detection rate of clinically significant cancer was much greater in this arm (ie UNDER-diagnosis was reduced). Furthermore, the detection rate of the clinically insignificant cancer was much less (ie OVER-diagnosis was reduced). And all this with a median number of biopsy cores of only four, compared with 12 in the SOC arm. The reduction in core numbers along that too much less complications for these patients.

This looks like WIN-WIN all round!

And I truly believe that these findings should provoke an immediate change in our diagnostic pathway for early prostate cancer in two ways:

All patients with a clinical suspicion of prostate cancer should be offered an MRI as part of their informed/shared decision making pathway
All patients with an abnormality on their MRI scan should be offered be targeted biopsy alone.

The obvious concern of course, is the fate of those patients with a normal MRI (28% of patients), who despite a clinical suspicion of prostate cancer, did not have a biopsy. How many clinically significant cancers might we miss by not offering biopsy to those patients? Of course, we already have an idea of what we would find, as the PROMIS study also included extensive biopsy (transperienal mapping) for patients with a normal MRI.

In PROMIS, the negative predictive value of MRI for detecting any pattern 4 cancer is 76% ie up to 1 in 4 men will have some pattern 4 cancer on transperineal biopsy. However, no primary pattern 4 cancers were missed on MRI. This is something we have to digest. I think that we can accept missing some pattern 4 cancers in some men, provided the “routine follow up” is adequate. But we must also continue to use the other tools we have in our multivariable approach to early detection, and if there are red flags due to family history, palpable nodules, adverse PSA parameters (including PSA density), BRCA mutations, then there will clearly be a role for systematic biopsy in some of these men with normal MRI scans.

In my opinion, we now have enough evidence to fully embrace mpMRI in our approach to early detection of prostate cancer. Following on from the PROMIS study, published in the Lancet 2017, the PRECISION study provides us with the imprimatur to fully embed MRI in the assessment of men with a suspicion of prostate cancer. The era of blind random prostate biopsy is surely over, except perhaps in those patients in whom MRI is contra-indicated. The next challenge will be to create enough capacity and expertise to make this paradigm available to all.

Resourcing will inevitably be an issue, but the PROMIS and PRECISION papers provide a compelling health economic argument for funders. Less men undergoing biopsy; less biopsy cores; less complications; less insignificant cancer – this surely makes economic sense. In Australia, where MRI has already been enthusiastically embraced, a high-quality mpMRI on a 3T machine costs $USD300, and costs are usually borne by patients. In the USA, we hear that a 1.5T MRI (with an endorectal coil) can cost USD$2-3000!! Why is this?! Australia is an expensive country – an iPhone or a da Vinci robot costs 1.5 times the cost in the USA; why therefore should an MRI cost so much in the USA? A symptom of a much broader issue with the bloated US health economy, and likely a barrier to adoption of the paradigm proposed by PRECISION.

So there you have it. A truly practice-changing study. While there will be much discussion about the nuances, I for one will immediately embrace this paradigm:

MRI for all (I already do this)
Targeted biopsy alone for those with MRI lesions (a new departure for me)
No biopsy for those with normal MRI scans (unless there are other red flags).

My concluding slide from the plenary discussion:

Congrats again Veeru, Caroline, Mark and colleagues for publishing this landmark study.

Declan G Murphy

Urologist & Director of Genitourinary Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia

Twitter: @declangmurphy

EAU 2017 Congress Days 1&2

April 5, 2017/4 Comments/by Rajesh Nair

≠WeAreNotAfraid. Perhaps the standout memory of EAU – London 2017. The 32nd Annual EAU Congress in London was marked with a message of defiance from colleagues and delegates from London, Great Britain, Europe and Worldwide. These were messages of solidarity, which rang through in person and on social media after an attack at Westminster. It was quite simple. London, Europe and the World will continue regardless of these tragic events and our urological fraternity beautifully demonstrated this as days following, a record-breaking attendance of 12000 delegates from over 123 countries descended to the Excel Centre in London, UK.

EAU-2017 had surpassed many a milestone. A record breaking 5000 abstracts were submitted for poster and video presentations from over 81 countries. 1200 presentations were displayed across 300 poster and video sessions. This year showcased an expansion of the number of plenary sessions from 4 to 7 allowing for a greater choice for all delegates. The quality, breadth and expertise behind the EBUS educational courses must be commended. Finally, as always, live surgery, which has year on year, proved to be popular was broadcast from Guy’s Hospital, London. They showcased the crème de la crème of surgical talent from live procedures with over 30 surgeons involved in operating, moderating, acting as patient advocates and in organisation. I, as I am sure all delegates extend our gratitude to the patients involved during the live surgical broadcast.

The camaraderie was clear to see. One could not take more than ten steps without running into a colleague or friend. It was a perfect opportunity to catch up, network and build relationships. Perhaps it was Prof. Sir Bruce Keogh (NHS England’s Medical Director and Commissioner of the Commission for Health Improvement (CHI)) who described it best in his opening address: ‘meetings like this are vitally important since it is at these occasions that knowledge and professional links are developed, and at these events ideas take seed and take hold: the important ideas that will later lead to significant work and progress in medicine.”

In addition, the opening ceremony showcased some the serious talent in urology. Awards for Prof. Paul Abrams, Prof. Per-Anders Abrahamsson, Prof. Christian Gratzke, Dr. Riccardo Autorino and Mr. Richard Turner-Warwick demonstrated their commitment, hard work and dedication to the specialty.

Day 1 began with multiple subspecialty meetings and meetings between affiliated sections. These themed discussions were stimulating and really addressed the trials and tribulations as well as successes in the delivery of urology worldwide. Day 1 also showcased a fantastic session organised by the prostate cancer prevention group. They examined the role of active surveillance in low risk prostate cancer with specific reference to data from ProtecT, ESRPC and the PLCO trials. Prof. Hamdy gave a comprehensive overview of the ProtecT study and reminded the audience that the risk of death from prostate cancer remains low (1% over ten years), and that surgery and radiotherapy although reduce cancer progression can result in bothersome side effects. The increasing role of urine based biomarkers; microRNA, imaging and genetic testing were all discussed when redefining the cohort of patients suitable for active surveillance.

The night ended with drinks at the Healtap, a bar outside Guy’s hospital, London. This was a throwback to the past for many. Old friends and colleagues, past fellows and current urologists all gathered to reminisce about past UK experiences. Following this, a late night serious session of serious recording and video production ensued with Declan Murphy and Alastair Lamb. For those open surgical protagonists who wonder ‘what have the robots ever done for us?’ I encourage you to watch:

The opening plenary session of Day 2: ‘Sleepless nights: Would you do the same again?’ chaired by Mr. Tim O’Brien critically re-evaluates some of the management decisions for kidney cancer from a medico-legal perspective. This session was fascinating and almost akin to a TV drama. A medico-legal lawyer (Mr. Leigh) vociferously cross-examining key members of faculty and an audience watching them sweat over what would have been initially perceived an acceptable clinical decision. A key message: allow your patients to take on decisions and not shoulder the entire burden yourself and the phrase; ‘your skills are for your patient, your notes are for yourselves’ continues to resonate.

Another EAU annual conference goes by with yet more casualties from a verbal punch up. The second session showcased a debate on robotic salvage prostatectomy between Declan Murphy and Axel Heidenreich. Perhaps the blood spilt from this joust reminded the audience that despite the rising bank of evidence favouring salvage prostatectomy, there will always remains debate when a salvage procedure is associated with increased morbidity and risk for the patient.

The ‘twitosphere’ was heavily active. The beauty of this as always is that if you were to miss sessions, lectures or abstracts, the ability to follow them on twitter in real time adds another dimension to conference attendance.

The most re-tweeted slide was presented by Dr. Ashish Kamat, a simple yes incredibly powerful slide demonstrating the equivalence in disease specific survival between high grade T1 urothelial carcinoma of the bladder and advanced prostate cancer reminded us all of the need to be vigilant and aggressive with high grade non muscle invasive disease of the bladder.

Day 2 brought out some of the best in abstracts, EBUS courses and updates in clinical trials. The latest developments in urological research include: the PROstate MRI Imaging Study (PROMIS) trial results reviewed by Hashim Ahmed and futher evidence and discussion from the Prostate Testing for Cancer and Treatment (ProtecT) trial by Freddie Hamdy. Prof. Jim Catto gave an eloquent talk examining the role of the enhanced recovery programme in radical cystectomy.

What a fantastic start to the meeting! As you shall see, the remainder of the meeting did not disappoint. Dr. Hendrick Borgmann will reveal all in the update of day 3 and 4.

Mr. Rajesh Nair

Fellow in Robotics and Uro-Oncology

The Royal Melbourne Hospital & Peter MacCallum Hospital, Melbourne, Australia

Twitter: @nairajesh

The times they are a-changin’

February 15, 2017/2 Comments/by Prokar Dasgupta

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

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

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

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

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

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

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

Prokar Dasgupta @prokarurol

Editor-in-Chief, BJUI

In search of the ROSETTA stone (again)?

October 31, 2016/2 Comments/by Prokar Dasgupta

We are having an amazing year of scientific discovery in our specialty. 2016 has already seen the results of the only randomised trial comparing open versus robotic radical prostatectomy from Australia and the ProtecT trial from UK discussed intensively on Blogs@BJUI. The PROMIS of MRI is expected to change the practice of prostate biopsies in response to a raised PSA. The teams completing these trials deserve our heartiest congratulations as it is well known how difficult randomised trials in surgery are to initiate and complete.

As if this was not enough, this month the randomised controlled trial comparing Botox (Onabotulinum toxin A) to Interstim (sacral neuromodulation) in patients with refractory overactive bladder has been reported in JAMA. It is otherwise known as the ROSETTA study (Refractory Overactive Bladder: Sacral NEuromodulation v. BoTulinum Toxin Assessment).

This is an example of what collaboration between individuals and teams within a pelvic floor group can achieve. Cindy Amundsen, the lead author, presented the trial results at the #AUA16 late breaking abstract session in San Diego.

The CONSORT diagram is shown here

The primary outcome measure showing Botox winning over Interstim (narrowly) in reducing urgency urinary incontinence is demonstrated in this diagram.

The summary results are shown here

So what would you do for your patient with refractory overactive bladder who has failed Anticholinergics and Mirabegron?

I have spent the last week thinking about the trial results carefully and was asked exactly this question at the International Endourology Forum in China. There are a number of important aspects to consider. The dose of Botox used in the trial was 200 units while the licensed dose is 100 units for overactive bladder of non-neurogenic origin. We know that one size does not fit all and indeed some patients failing 100 units need higher doses of Botox. It remains unknown as to what would have happened if 100 units of Botox was compared to Interstim as the authors are quite guarded about their own conclusions about the benefits.

The side effects also need to be carefully discussed with the patient. The UTI rate in the Botox group is about three times that of the Interstim group. Most patients may accept a period of oral antibiotics to counter this. The risk of CISC dropped from 8% at 1 month to 2% at 6 months in the Botox group. This is lower than previously reported in Phase lll studies. The need for revision or removal in the Interstim patients was around 3% – small but not to be ignored.

Punchline
If I was the patient in question, I would have Botox initially, preserving Interstim for later. It is less invasive and can be repeated roughly once a year if needed. Call me “lilly livered” but I do not like the idea of having a little box, however tiny, inside my bum and occasionally having to sit on it! I look forward to the smarter new generation of minimally invasive or even non-invasive nerve stimulators. But then it would need another randomised trial, many years of unanswered questions, perhaps even wastage of a lot of grant money…………..yawn!!

In the meantime, I will take my chances with Botox and counsel my patients accordingly. Unlike the famous ROSETTA stone, the key to understanding the mystery behind hieroglyphs and the controversy as to whether it should at all be in the British museum, I fail to see any such controversy with this nice trial in JAMA.

My thoughts and message are clear. Are yours?

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

The PROMIS of MRI

June 24, 2016/1 Comment/by Hashim Ahmed

The prostate cancer pathway is controversial and views are often polarized. For a researcher, this is the perfect melting pot for innovation and practice-changing studies. It is clear that we need to reduce the harms of treatment, not only by treating very few low-risk cancers but also by innovations in surgery. It is pleasing to see Grasso et al. [1] systematic review of surgical innovation that may potentially lead to improvements in urinary incontinence after radical prostatectomy. This was a diligently conducted systematic review and points to the need for a randomized trial, which the authors tell us is currently being conducted.

The era of multiparametric MRI (mpMRI) for prostate cancer diagnosis is upon us. Few of us will live through such a wholesale change in the entire pathway for diagnosis and treatment of a cancer, and a common one at that. Whilst a few of us have been using mpMRI prior to first biopsy, there can be no doubting that we now have level 1b evidence to support the adoption of mpMRI prior to a first prostate biopsy as the standard care. The NIHR-HTA/MRC-CTU/UCL PROstate MR Imaging Study (or PROMIS) has been long awaited, and its initial results were presented at ASCO last month [2]. mpMRI performed better than expectations in a multicentre setting across 11 NHS trusts and just over a dozen radiologists. Sensitivity was 93% (95% CI 88–96) and the negative predictive value was 89% (95% CI 83–94). Although the focus, quite rightly, has been on mpMRI, equally significant has been the discovery of how bad a test TRUS-guided biopsy really was, with a sensitivity for clinically significant prostate cancer of only 48% (95% CI 42–55).

These findings answer several criticisms of mpMRI. First, that it is not as accurate as retrospective data suggest. It is, provided you do not expect it to find every millimetre of significant disease. Second, it is not reproducible outside of expert centres. It is, provided you quality assure every scanner, optimize the sequences iteratively, quality control scans and have robust training for radiologists. Third, it cannot be carried out on 1.5-Tesla scanners. It can; all the PROMIS scans were 1.5 Tesla without an endorectal coil. Fourth, it misses lots of clinically significant prostate cancers. It does not, but this depends on your definition of clinical significance. In this respect, the study by Cash et al. [3] is pertinent. They evaluated the rates of subsequent cancer found on ‘negative’ mpMRIs and, using the very conservative Epstein definition, found a high rate of missed ‘significant’ cancers. The rate of Gleason 7 disease missed was lower and some missed cancers were attributable to interobserver variability in mpMRI reporting. All centres should evaluate their own data to determine where their own negative predictive value sits and then strive to improve upon this through a constant iterative dialogue between urology and radiology. PROMIS shows that mpMRI has very high performance characteristics that should be possible across the board.

There is considerable work still to be done. Cost-effectiveness analyses are under way; with these data, NICE will need to consider their clinical recommendations, having laboured the point that they wished to await PROMIS. The challenge of dissemination and maintenance of quality standards is not to be underestimated. Work on determining what is out there, who is capable of performing such scans and reporting them, whether there is enough capacity in the NHS and whether all centres are capable of carrying out targeted biopsies are all legitimate health policy issues.

Similar to mammography standards laid down centrally, we will need to insist on: independent (not self-) accreditation; independent scan and report audits, with outliers (too many negatives, too many positives, too many equivocals) reviewed to determine whether further standardization training is required; rates of clinically significant and insignificant cancers detected on subsequent biopsy; rates of repeat biopsies; and rates of unnecessary radical therapy on low risk cases. We should all look within our centres to ensure we can meet these expectations.

Hashim U. Ahmed, BJUI Consulting Editor – Imaging Division of Surgery and Interventional Sciences, UCL, and
Department of Urology, UCL Hospital NHS Foundation Trust, London, UK

References

1. Grasso AAC, Mistretta FA, Sandri M et al. Posterior musculofascial reconstruction after radical prostatectomy: an updated systematic review and a meta-analysis. BJU Int 2016; 118: 20–34 Wiley Online Library

2. Ahmed HU. The PROMIS study: a paired-cohort, blinded confirmatory study evaluating the accuracy of multi-parametric MRI and TRUS biopsy in men with an elevated PSA. J Clin Oncol 2016; 34: (suppl; abstr 5000)

3. Cash H, Günzel 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 Wiley Online Library

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