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TUF Cycling Challenge in Southern Africa

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(in memory of John Anderson MS FRCS)

As most of you know, sadly John Anderson, President Elect of the British Association of Urological Surgeons, died this summer from advanced prostate cancer, which had spread to his liver (you can read John’s obituary in the BJUI and watch a video of his 2012 address to BAUS).

In his memory during the first week of November a team consisting of 30 urologists and patients are travelling to the tip of Africa for a cycling Challenge to raise funds for The Urology Foundation (TUF) (you can read more about the TUF in this BJUI Comment article). We will be cycling nearly 500 kilometres in 6 days along the Cape route, which encompasses towering mountains looming over passes hewn by hand from the rocks many years ago. We will traverse the semi-desert of the Klein Karroo on mainly dirt roads and encounter steep climbs as well as potholes and slippery patches on the ancient roads. Motorbike Sport site had provided us some awesome tips to ride at any kind of road or terrain as well. Near the coast the wind will start to play a role. The cycling gear we got online will prove to be useful. We carefully read reviews of the best gears to get from ScooterAdviser. This was and still is the Cape of Storms, and we are very likely to have to battle through a howling South Easter to reach our day’s target. Finally, we will cycle across the flats to the Southern most tip of Africa and the lighthouse at Agulhas. This, like our previous cycle challenge across the Andes, is a challenge for the fit, the tough and the stout of heart!

The funds we raise will be used to support the important work of TUF to find better treatments for kidney, bladder, prostate and testicular cancer. And, in addition, to raise awareness of bladder cancer and to train urologists in the arts of robotic, laser and laparoscopic surgery, thereby enhancing patient care. So far we have raised over £130,000. You can support us by posting a comment on this blog, or by sending a donation to TUF. We will be updating this blog with regular accounts of how our cycle challenge is progressing, so do watch this space!

Roger Kirby

 

Movember: The power of the Mo!

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The word Mo is Australasian slang for a moustache and whilst not a northern hemisphere phrase this hasn't prevented rapid dissemination across the globe. Although originally an innovation solely in Australia and New Zealand for its first 6-7 years, Movember is now taking the world by storm with the UK and Canada leading the way. Staggeringly last year in the UK more than 363,000 men grew a hairy upper lip and in doing so raised over £27 million.

The Movember foundation donates the proceeds to men's health charities which is primarily (around 70%) prostate cancer but also donates to charities supporting mental illness and this year will contribute to the orchid trust for testicular cancer. Money raised from the UK campaign goes to Prostate Cancer UK, which received £14.6m for the year to April 2013, and the Institute of Cancer Research, which received £299,891 for the same period.

When working in urology clinics where one meets up to 20 new patients a day that's many conversations about this issue helping to raise awareness and hopefully directing people to the website to donate to the UK Movember site.

Prokar Dasgupta outside the BJUI offices in Movember 2012

 

So Mo brothers and sistas let’s keep up the good work and prepare for another bumper crop of upper lip hair! 

Ben Challacombe
Associate Editor, BJUI 

Movember and the Importance of Patient Advocacy

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In October 2009 the resident on my service was Dr Dean Elterman. I have had many residents and fellows over the years and have always felt that as much as they hopefully learn something from me I probably learn more from my time with them. The concept of ‘drilling down’ to make lasting connections with leaders of the next generation is not something that is always intuitively grasped in the hierarchy of surgical life. As it was, in late October of that year Dean mentioned Movember to me and asked whether I would like to participate. At that point, not knowing what he was talking about I proceeded to tell him to consult his spell-check. Having once before sported facial hair in my early 20s to very little acclaim I had not entertained the thought since. My immediate reaction was dismissive. Nevertheless after some further discussion it became obvious to me that the whole concept of Movember is not simply to raise money for men’s health and prostate cancer research but to generally shine a brighter light on the nature of the disease, the work we do as urologists and to start a dialogue. This grassroots movement, started in 2003 in Australia by Adam Garrone has quickly grown into a worldwide phenomenon. That fall I anchored Dean’s team of residents and we broke into the top 20 of small teams worldwide.

Last year I set up a local team at Toronto East General Hospital with tremendous success. On an individual level I raised $46,000 in support of men’s health, the seventh highest individual total worldwide. While that certainly was nice, as the month wore on what became increasingly clear to me was the larger role that my involvement in Movember had created in engaging patients, other healthcare providers and society at large. The quirky nature of the campaign lends itself to a fun, easy discussion about an important topic. Having a dialogue around prostate cancer including how to screen as well as when and when not to treat is very important. The significant emotional and physical consequences of treatment deserve attention. A particularly great example by the terrific @docmikeevans illustrates the space that Movember now inhabits. The role that urologists in particular have as advocates of men’s’ health is very clear. 

It is with this last thought in mind that I call upon my colleagues in Canada and around the world to take up the charge. In recent years, much of the progress that we have made in treating prostate cancer is at risk of being undermined. The confusing and rather opaque nature of screening guidelines have increasingly promoted prostate cancer as an indolent disease not worth having a discussion about. I certainly have previously written about this and recently a group of experts met in Melbourne and attempted to better make sense of screening and stratify risk. Prostate Cancer Canada, an important advocacy group in Canada has also done a great job this fall with their #knowyournumber campaign. I was proud to be a part of it. Their CEO Rocco Rossi has embarked upon a terrific campaign of support by walking the Camino to Santiago de Compostella this month. All leaders must actively embrace the role of advocacy for our patients. Movember to me is a great vehicle for this. Will you look silly and unprofessional in the clinic during Movember? Absolutely not. In reality, every patient in the clinic is immediately reassured that their urologist walks along beside them, although perhaps not as far as Rocco. 

It is in this context that I would call on all of my urological colleagues to stop shaving in Movember, start a team, create a network and share this experience with our brave patients and their partners for a month. The amount raised is really secondary. Having that visible presence is crucial. With epidemiologists, policy makers and many others expressing expert opinions about a disease that we treat every day don’t you think we should also embrace that role? Movember is the forum where the most important group, our patients, will be having that conversation for a month. Join them. Simply caring for them after diagnosis or waiting for a research grant to materialize is not good enough. My female colleagues can join as ‘mo-sistas’. You can certainly follow my ‘progress’ and support my venture as well. I look forward to seeing my colleagues from around the world and the self-described #urotwitterati that contributes regularly on #urojc in particular to join in the fun. I expect to be pushed on the leaderboard.

Dr Rajiv Singal is a Urologist at Toronto East General Hospital and an Assistant Professor in the Department of Surgery at the University of Toronto

Follow him on Twitter at @DrRKSingal

A Rather Nasty Surprise

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Recently, I encountered, and indeed I actually caused, a complication of robot-assisted radical prostatectomy (RARP) which was new to me, and one which I felt that I should share with other surgeons.

PM, a 60-year old teacher, underwent a completely routine RARP, which took less than 2 hours to perform on a Saturday morning. During Sunday night he developed severe abdominal pain and distension. By Monday morning he was in distress with rebound tenderness and marked tachycardia. A CT scan was requested, which revealed a caecal volvulus. A laparotomy by a general surgeon confirmed the diagnosis and an urgent right hemicolectomy was undertaken. The patient made an uneventful recovery and, I am pleased to say, is still speaking to me. Histology confirmed an ischaemic caecum twisted on its rather thickened mesentery, with no perforation present. The prostate itself contained a Gleason 3+4=7 adenocarcinoma, without evidence of extra-prostatic extension.

Although robotic assistance provides the benefits of very precise, virtually bloodless surgery, with 10 times magnification and 3D vision, it also carries the risk of a specific set of complications. These need to be dealt with promptly and efficiently and can usually be completely resolved. Failure to recognise post-operative problems, such as bowel injury, intra-abdominal bleeding or port-site hernia, however, can place the patient in severe and increasing jeopardy. We recently published an article in the BJUI entitled “Lessons Learned from 1000 robot-assisted radical prostatectomy” in which we discussed how many of the problems could be avoided, and, if they occur how they can be best dealt with. One key message is the importance of an early CT scan to diagnose the nature of a post-operative problem, rather than crossing fingers and hoping things will settle.

I am hoping that this blog, and the BJUI article mentioned above, will stimulate other surgeons to discuss openly and frankly the problems that they themselves have encountered, either with regular laparoscopy or with the da Vinci robot, and how they dealt with them. Learning the lessons, not only from one’s own errors and omissions, but also from those of others, seems the best way to become, and continue to be, a safe and successful surgeon.  

 

Roger Kirby, The Prostate Centre, London

Technological Innovation in the BJUI

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Time waits for no man St. Marher, 1225

Urology is arguably the leading technology driven surgical specialty. This is no accident. As surgeons we have always looked towards minimal invasion to reduce the trauma of access to our patients. One would have thought that the advent of drugs for BPH and OAB would perhaps reduce our hunger for technology.You can visit One Click Power if you are always hungry for knowing trends in technology. On the contrary, many urologists have moved on to effective alternatives to TURP such as HoLEP and having learnt the lessons from previous unproven over enthusiasm, relied on the results of high quality randomised trials before accepting the results.

The BJUI has a long history of publishing innovative manuscripts in the fields of basic science, imaging and therapeutics. We aim to bring the readership entire new paradigms in surgical diagnostics and treatment. Indeed while we enjoy #ERUS13 in sunny Stockholm, the autumn sunshine reminds us of the role played by robotics in the steady rise of technological innovation. This “sub specialty” has become so prominent that the EAU are soon accepting ERUS and its committee as an integral part of the European Association of Urology. The randomised trials, meta analysis and health technology assessments are gradually appearing in contemporary literature such that it is no longer true to say that robotics is just a fad backed up by little or poor evidence. Robotics remains one of the most highly cited parts of the BJUI and therefore together with laparoscopy has its own dedicated section. We were pleased to publish the novel method of suprapubic catheterisation as an alternative to the urethral route after robotic prostatectomy [1] which led to much conversation on the BJUI twitter page. Our readers ultimately decide whether to adopt a particular technique or technology and are now able to vote via the BJUI Poll.

Last month, Mahesh Desai demonstrated microPCNL in London. The technology is truly breathtaking. It is hard to believe that light and image transmission as well as stone disintegration can be effectively achieved via a needle so thin! We almost stopped doing robotics and were thinking of re-training to become stone surgeons. Mahesh and his team went on to back up the technology with a randomised comparison against flexible ureterorenoscopy [2]. It should come as no surprise that such an article should come from the sub-continent where stone disease is endemic.

And the technological innovations in the BJUI continue. This month we present three rather different articles for your reading pleasure. The first is an international collaboration demonstrating the ideal dose and safety of photodynamic TOOKAD therapy (a light-activated vascular occluding agent) in localised prostate cancer. Nearly 80% of patients had negative biopsies at 6 months [3]. Next we evaluate the role of PET CT in bladder cancer patients undergoing cystectomy. With almost a 20% greater pickup than standard imaging, we may be able to save a number of patients a morbid operation in the presence of metastasis. Advanced imaging may also allow better stratification of patients for neo-adjuvant chemotherapy [4]. Finally, we have an exciting paper from Iran on the use of endometrial derived stem cells for creating bladder replacements and alternatives to meshes in prolapse surgery. The immuno and scanning electron micrographic images in this paper are just stunning [5].

The BJUI intends to continue leading technological innovation in urology. We will bring our readers early phase safety data on new technologies in addition to long-term results to truly judge their efficacy and durability. We hope you enjoy reading, citing and interacting with these articles online at bjui.org and ultimately translate them to your own clinical practice.

Prokar Dasgupta, Editor in Chief, BJUI
Ben Challacombe, Associate Editor, BJUI
King’s Health Partners

References

  1. Ghani KR, Trinh Q-D, Sammon JD et al. Percutaneous suprapubic tube bladder drainage after robot-assisted radical prostatectomy: a step-by-step guide. BJU Int 2013; 112: 703–705
  2. Sabnis RB, Ganesamoni R, Doshi A, Ganpule AP, Jagtap J, Desai MR. Micropercutaneous nephrolithotomy (microperc) vs retrograde intrarenal surgery for the management of small renal calculi: a randomized controlled trial. BJU Int 2013; 112: 355–361
  3. Azzouzi A-R, Barret E, Moore CM. TOOKAD® Soluble vascular-targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer. BJU Int 2013; 112: 766–774
  4. Mertens LS, Fioole-Bruining A, Vegt E, Vogel WV, van Rhijn BW, Horenblas S. Impact of 18F-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT) on management of patients with carcinoma invading bladder muscle. BJU Int 2013; 112: 729–734
  5. Shoae-Hassani A, Sharif S, Seifalian AM, Mortazavi-Tabatabaei SA, Rezaie S, Verdi J. Endometrial stem cell differentiation into smooth muscle cell: a novel approach for bladder tissue engineering in women. BJU Int 2013; 112: 854–863
Original publication of this editorial can be found at: doi 10.1111/bju.12431. BJUI 2013; 112: 707.

 

Editorial: Contemplate the template: a new prostate biopsy approach

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Transperineal magnetic resonance imaging – ultrasound fusion targeted biopsies (MRI-US FTB) of the prostate: the future of prostate diagnostics

The prostate cancer diagnostic pathway has remained unchanged for 25 years. At best, laterally directed, peripheral zone (PZ) 12-core transrectal biopsies identify cancer in 44% of cases [1] but transrectal biopsies have an inherent sampling error with a risk of misdiagnosis or mischaracterisation of disease. Of those with negative biopsies who undergo transperineal (TP) biopsies, 30% have cancer, most in the anterior PZ. Active surveillance and the promise of less invasive treatment options are becoming popular because of concerns about ‘over treatment’ for low-risk disease.

Saturation transrectal biopsies have been advocated to improve diagnostic yield but do not address the issue of under sampling of the anterior PZ, particularly in the larger gland [2]. TP biopsies can be used to address the issue of under sampling but prostate template-mapping biopsies are labour intensive and require large numbers of biopsies, often between 60 to 90 cores; however, they have been an essential component of focal therapy trials and the evaluation of novel treatment methods [3].

Primary TP biopsy is the subject of the paper published in this edition of the BJUI titled ‘Outcomes of transperineal template-guided prostate biopsy in 409 patients’ [4]. The authors report a single centre experience of primary TP biopsies. The 14-region protocol described is simpler than prostate template-mapping requiring fewer cores (median of 15 and mean of 19 cores) with a comparable primary diagnostic detection rate of 60% and an encouraging side-effect profile. Unfortunately, the approach still has limitations and the authors admit that their limited biopsy protocol may still mischaracterise disease in the larger gland. In a recent paper from the same group, there was a disappointing correlation between their TP biopsy pathology, MRI abnormalities and radical prostatectomy specimens [5]. Uncertainty prevails, the problem is how best to sample the larger gland. The authors [4] and others, often conclude that more biopsies are necessary for larger glands and resort to mapping protocols and many more biopsies. The solution may not be more biopsies but rather better systematic targeting of the PZ. The impact of hyperplasia within the transition zone (TZ) has a profound effect on PZ anatomy. In the smaller prostate, up to 30 mL, there is little TZ and the PZ is much thicker posteriorly than anteriorly, this difference is even more apparent in glands of 30–50 mL. Above 50 mL TZ expansion causes marked attenuation of the PZ, which becomes much thinner, but the overall volume of the PZ does not change. Less than 4% of cancers originate in the TZ [6], consequently biopsies should be concentrated primarily on the PZ.

The future of prostate cancer diagnosis is likely to be a combination of pre-biopsy multiparametric MRI, followed by targeted biopsies of MRI-identified lesions combined with fewer but better systematic targeted biopsies of the PZ. MRI-ultrasound (MRI-US) fusion techniques have been developed in which axial T2 images of the prostate, diffusion-weighted images and/or dynamic contrast-enhanced MRI images are ‘fused’ with the live US images to allow precise targeting of both regions of interest and the PZ. Commercially available biopsy programs, developed from brachytherapy software systems programs allow individual biopsy sites to be recorded and if combined with inking of the specimen can provide precise pathological localisation of disease within the prostate [7].

There are many potential benefits to this approach. Patients who opt for active surveillance will have an archived record of their disease at a given time to facilitate precise replication of further interval biopsies and assess progression. Improved disease management for an individual should be the aim. The suitability or not for focal or targeted therapies, the planning or boosting of identifed lesions with radiotherapy and/or brachytherapy, and the planning of nerve-sparing surgery or wide excisions should be possible. Feedback to the radiologists of both benign and malignant pathology and grade of disease will improve reporting accuracy and provide imaging sciences with the histopathological characteristics of both MRI ‘visible’ and ‘invisible’ cancer to improve MRI interpretation.

MRI–US fusion targeted biopsies are a significant advance in prostate diagnostics and may resolve some uncertainty within the prostate cancer diagnostic pathway. Benefit vs cost is a recurring issue across health care and questions will continue to be asked about the use of increasingly expensive technology in such an indolent disease. The challenge for investigators will be how to prove the benefit of this approach over standard biopsy protocols and integrate this work in to clinical practice.

Richard Popert
Department of Urology, Guy’s Hospital, London, UK

Read the full article
References
  1. Presti JC, O’Dowd GL, Miller MC et al. Extended peripheral zone biopsy schemes increase cancer detection rates and minimize variance in prostate specific antigen and age related cancer rates: results of a community multi-practice study. J Urol 2003; 169:125–129
  2. Stewart CS, Leibovich BC, Weaver AL, Lieber MM. Prostate cancer diagnosis using a saturation needle biopsy technique after previous negative sextant biopsies. J Urol 2001; 166: 86–92
  3. Onik G, Barzell W. Transperineal 3D mapping biopsy of the prostate: an essential tool in selecting patients for focal prostate cancer therapy. Urol Oncol 2008; 26: 506–510
  4. Symons JL, Huo A, Yuen CL et al. Outcomes of transperineal template-guided prostate biopsy in 409 patients. BJU Int 2013; 112: 585–593
  5. Huo AS, Hossack T, Symons JL et al. Accuracy of primary systematic template guided transperineal biopsy of the prostate for locating prostate cancer: a comparison with radical prostatectomy specimens. J Urol 2012; 187: 2044–2050
  6. Patel V, Merrick GS, Allen ZA et al. The incidence of transition zone prostate cancer diagnosed by transperineal template guided mapping biopsy: implications for treatment planning. Urology 2011; 77: 1148–1152
  7. Hadaschik BA, Kuru TH, Tulea C et al. A novel stereotactic prostate biopsy system integrating pre-interventional magnetic resonance imaging and live ultrasound fusion. J Urol 2011; 186: 2214–2220

Chemoprevention of Prostate Cancer – Is it justified?

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The September #urojc International Urology Journal Club discussion on twitter was based on the paper “Long-Term Survival of Participants in the Prostate Cancer Prevention Trial” published in the New England Journal of Medicine a few weeks earlier.

In 2003, the Prostate Cancer Prevention Trial (PCPT) proved what it set out to do. It significantly reduced the risk of PCa. Unfortunately, the champagne was never even taken off ice, as finasteride was also associated with an increased risk of high-grade prostate cancer. In June 2011, US FDA ordered the drug’s warning label to be updated to state that finasteride may increase the risk of high grade prostate cancer. As a primary prevention drug for PCa, despite many published, favorable subgroup analyses, finasteride was quite flaccid in the eyes of many urologists.

 

Now, ten years after the PCPT was published and with up to 18 years of follow-up, would these long-term results be the catalyst to force an FDA backflip? Or would the specter of erectile dysfunction rise? Amongst the first tweets that were fired (no prizes to guess who it was)

Tweeted link by @LoebStacy

 

To summarise, this post hoc analysis – that wasn’t pre-specified in the original protocol – analysed rates of survival among all original PCPT study participants including those with prostate cancer. Prostate cancer incidence amongst PCPT candidates was collected for an additional year after the original report and the Social Security Death Index was searched to assess survival status until 31st October 2011.

In all 18,880 men, PCa was diagnosed in 10.5% of the finasteride group and 14.9% of the placebo group (RR in finasteride group, 0.70; 95% CI, 0.65 to 0.76; P<0.001). Furthermore, 333 (3.5%) in the finasteride group and 286 (3.0%) in the placebo group had high-grade cancer (GS, 7 – 10, RR, 1.17; 95% CI, 1.00 to 1.37; P=0.05). Fifteen-year survival rates of 78.0% (finasteride) and 78.2%, (control) were reported in the men who died. Unadjusted hazard ratio for death in the finasteride group was not significant. Ten-year survival rates were 83.0% (finasteride) 80.9% (placebo) with low-grade PCa and 73.0% and 73.6%, respectively, with high-grade prostate cancer.

The authors as well as the #urojc community were quick to identify limitations.

 

 

Indeed, since information regarding the mode of death for patients who passed away was unavailable, PCa specific mortality could not be reported by this study. In amongst the discussion regarding limitations, it was important to see twitter etiquette observed.

There was some discussion on whether high grade “finasteride” prostate cancer was morphologically identical to “placebo” prostate cancer or different?

 But at the end of the day, it doesn’t matter how it is discussed, packaged or assembled…

 

In an underpowered study, not designed to look at PCa-specific mortality, there was always going to be conjecture as to the benefit of reducing low grade PCa by 30% (in an era of increased active surveillance) whilst giving 1 in every 200 men offered finasteride high grade PCa.

Erectile dysfunction was an ever present factor during our discussion, although was generally thought of as #firstworldproblems

At times, when drawing conclusions, our intellectual, verbatim-driven minds give way to pictorial clarity; in other words a picture tells a thousand words. I still wonder how many a tweet is worth… In my very humble opinion, my conclusions are

1) 5 ARIs decrease low grade PCa, but low grade PCa doesn’t necessarily equal death, so…

2) Primary prevention for PCa would need to be robust, 5ARIs are too far from the mark

 

3) I thought appropriately chosen patient with bothersome LUTS, a large prostate with elevated PSA (proved to be cancer free or low volume GS 6) should go green (I can already feel the holmium lasers, microwave emitters and diode beams aimed behind my head, but that is a conversation for another time…)

 

The king summed it up well I think,

This month’s prize has been generously donated by Urological Society of Australia and New Zealand, one full registration to USANZ ASM 2014 in Brisbane! There was a clear winner who was novel in tweeting an image that said it all.

Congratulations to Dr Todd Morgan!

 

A warm thank you is extended to all who participated in this month’s #urojc discussion. All of you are encouraged to participate in next month’s discussion starting on 4th-5th October depending on your time zone.

Analytics for for this month’s discussion:

 

 

Dr George Koufogiannis is an Australian Urology Trainee, currently based at Port Macquarie Hospital. @DrVasano78 Vasano = torment, 78 = 1978, the year I began to torment my mother, who gave me the nickname.

Editorial: Salvaging failed radiation therapy: does the tumour location permit a less toxic approach?

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In the introduction to their manuscript in this issue of the BJUI, Meeks et al. outline a significant challenge for physicians managing prostate cancer: from the estimated 240 000 diagnosed annually (USA) to the 120 000 choosing radiation, to the 40 000 estimated biochemical failures in the first 5 years who may benefit from additional local therapy to avoid local and/or systemic progression. The basis of these calculations was from conventional beam radiation, and although we expect dose-escalation strategies to perform better, the ideal management strategy remains to be identified. Indeed, Zelefsky et al. showed that there was a higher risk of metastatic disease with external beam radiation therapy than with surgery for high-risk prostate cancer, although there was some confounding of the results due to the differences in salvage treatment. This confounding may be the key point: more acceptable salvage options may promote optimal local control and fewer progressions.

Certainly, the concern with salvage therapy after failed radiation is the toxicity, and the concept of achieving less urinary incontinence with cryotherapy or even focal cyrotherapy is attractive, as outlined by de Castro Abreu et al. in this issue. In their parallel cohorts of total and focal salvage cryotherapy, urinary incontinence occurred in three (13%) of the 25 salvage total and zero of the 25 salvage focal therapies, and there was only one fistula in either series. However, the cancer control outcomes are different among these non-randomised and non-comparable cohorts: 87% disease-free survival for patients with bilateral disease treated with total cryotherapy and 54% disease-free survival for patients with unilateral disease treated with focal cryotherapy. These comparisons are limited, but one could hypothesise that salvage total therapy has improved disease control over salvage focal therapy.

Returning to the Meeks et al. study, a cohort of 198 patients with biopsy confirmed radiation recurrence underwent a salvage prostatectomy at a single institution. Pre-treatment biopsies showed 48% and 13% Gleason sums 7 and 8–10, respectively, and multifocal location in 61% (92/151 patients). Salvage prostatectomies showed 56% advanced pathological stage and 35% Gleason 8–10, and multifocal location in 57%. In comparing specific biopsy locations to radical prostatectomy mapping, undetected cancers from biopsy ranged from 12% to 26%, and 58% upgrading. In patients with unilaterally localised biopsies, final pathology was unilateral in only half – a statistic that matches the PSA failure rate from focal therapy in the de Castro Abreu et al.’s study. The authors point to a non-radiated biopsy-to-prostatectomy study and by comparison conclude that the accuracy of biopsy in radiated prostates is actually greater, perhaps due to the smaller radiated gland. But let’s be clear – both groups had significant rates of multifocal disease and inaccuracies between biopsy and radical prostatectomy.

These two BJUI studies provide a developing agenda of what we know and do not know about salvage therapy for failed radiation:

  • Local failure after radiation selects patients who probably have significant disease in terms of volume, stage, and grade, and should not be confused with the over-detection of low-volume, low-grade disease seen in primary treatments for PSA-screened disease.
  • Salvage focal therapy for unilateral disease by biopsy may be less morbid but may be only 50% effective.
  • The link between metastatic progression and PSA failure after failed salvage focal therapy is unknown, and completion treatment of the other side could be studied.
  • The additive accuracy of post-radiation biopsy plus imaging is not established.
  • We are basing most of our treatment recommendations on tumour morphology (histopathology, location, size) and surrogates (PSA failure definitions) rather than biology and survival.
  • The current management of post-radiation local failure should consider total gland treatments as the standard and focal therapies as experimental.

John W. Davis and Seungtaek Choi*
Departments of Urology and *Radiation Oncology, UT MD Anderson Cancer Center, Houston, TX, USA

Article by Meeks et al.
Article by de Castro Abreu et al.

Conference Report: Prostate Cancer World Congress 2013, Melbourne, Australia

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Melbourne played host to the Prostate Cancer World Congress last week. With over 1,000 delegates and a stellar International faculty comprising of 21 global leaders, it was no surprise that tweeters worldwide battled off sleep to keep up with the action.

 

 

 

 

Amidst a buzzing crowd, overlooking the iconic @MCG #pcwc13 President Tony Costello reminisced about the very first conference; 2 speakers, 27 delegates made up largely of residents only fourteen years ago. Undoubtedly the highlight of the conference was the release of ‘The Melbourne Consensus Statement on Prostate Cancer Testing’. This gathering of worldwide experts allowed for the ideal opportunity to generate a set of consensus statements with the goal of finally ending the confusion that exists with current guidelines and allow for early detection of prostate cancer. 

https://www.bjuinternational.com/bjui-blog/the-melbourne-consensus-statement-on-prostate-cancer-testing/

As well as major media coverage following the statements release #PCWC13 caused a stir virally around the globe. With tweeters from New Zealand, United Kingdom, Ireland, United States, Canada and all states and territories of Australia the success of #SoMe was a hot topic of discussion around the Convention Centre. Novel and newbie #SoMe users could not resist joining the frenzy of twitter traffic which grew in strength over the five days.

 

 

Dr Stacy Loeb kickstarts #PCWC live on @abc

The conference featured three main streams; Clinical Urology #CU, Translational Science #TS and Nurses & Allied Health #NAH, a programme which ensured the multidisciplinary team and all practitioners involved in prostate cancer care could learn and share expertise. Day 1 the tone was set at the moderated poster presentations by @DrHWoo who outlined some conference housekeeping rules ‘All phones on silent and everyone must be adequately tweeting!!’.

 

An exceptionally high standard of candidates left decision making difficult for poster judges; @DrDanielMoon and @DrHWoo. A clever addition to the #PCWC13 welcome package was the BJUI supplement containing all #CU abstracts, allowing delegates and faculty to gain further knowledge of each individual presentation.

 

That evening @AustProstate The Australian Prostate Cancer Research function and drinks allowed faculty to relax and mingle while receiving a warm welcome from Professor Rosemary Knight from the Dept. of Health, Canberra, Hon David Davis MP, Victorian Minister for Health and Hon Dr Andrew Southcott, Federal Shadow Spokesman for Health.

 

On Wednesday morning at the opening multidisciplinary plenary @SwannyQLD the Honourable Wayne Swan MP gave an emotional account of his personal battle with prostate cancer. His heartfelt story touched all those present, emphasising that underlying the scientific and clinical excellence of a conference of this magnitude remains the care of our patients.

 

@LoebStacy Assistant Professor of Urology and Population Health from NYU followed with a superb summation of ‘Practice-changing publications in prostate cancer this year’. Dr Loeb condensed a typically three hour session by herself and Dr. William J. Catalona into twenty minutes addressing the most prominent issues in prostate cancer, including ‘Nature V Nurture’, the fish oil debate, the FDA approval of Radium-223 and the PSA recommendations by USPSTF.

Prof Noel Clarke from the Christie Hospital in Manchester presented the inaugural BJUI Lecture “Breaking the Mould in Prostate Cancer Trials”, to a packed audience including clinicians and scientists.

On his fourth trip to Australia and attending the conference, Dr. Patrick C Walsh delivered the inaugural speech so named after the orator himself, a lecture which will continue to be an annual highlight of the APCC.  An insightful look at the progress in prostate cancer genetics, over the last two decades, from one of the fathers of Urology kickstarted #PCWC13.

 

#PCWC13 co- convenor A/Prof Declan Murphy released ‘The Melbourne Consensus statement ‘at 1pm sparking major national and global media attention.

 

https://www.heraldsun.com.au/lifestyle/health-fitness/prostate-cancer-test-should-be-taken-by-men-in-their-40s/story-fni0diac-1226692750214

https://www.theaustralian.com.au/news/breaking-news/prostate-experts-end-psa-test-confusion/story-fn3dxiwe-1226692802245

https://www.businessweek.com/news/2013-08-06/prostate-test-warrants-rational-use-as-cancer-gauge-doctors-say

The signatories outlined five major points with a view to clarifying the use of PSA testing and media representatives were given the chance to address pressing questions with @LoebStacy, @proftcostello, Dr. Walsh, Dr Catalona and Mr Murphy (@declangmurphy) at the press conference.

 

https://www.couriermail.com.au/lifestyle/health-fitness/prostate-cancer-test-should-be-taken-by-men-in-their-40s/story-fnihoylo-1226692750214
https://www.news.com.au/lifestyle/health-fitness/prostate-cancer-test-should-be-taken-by-men-in-their-40s/story-fneuzlbd-1226692750214
https://www.theaustralian.com.au/news/breaking-news/prostate-experts-end-psa-test-confusion/story-fn3dxiwe-1226692802245
https://au.news.yahoo.com/thewest/a/-/newshome/18405046/debate-reignites-on-prostate-screening/
https://www.medicalobserver.com.au/news/international-experts-support-psa-testing
https://www.bloomberg.com/news/2013-08-07/prostate-test-warrants-rational-use-doctors-say.html
https://localtoday.com.au/get-local/news/88156-prostate-experts-end-psa-test-confusion.html 
 
 

 

Late morning and afternoon on Wednesday was filled with an extensive range of sessions in all three streams, including discussion and developments on tumour imaging, therapies & biomarkers and management of sexual rehabilitation. A round table discussion on PSA testing and the ‘Melbourne Consensus Statement’ caused some heated debate with controversial questions from the audience. Cocktails in the exhibition centre followed, where delegates were given the opportunity to mingle with faculty and further discuss the monumental statement which has undoubtedly put Melbourne and Victoria on the map as a centre of Urological academia. Pharmaceutical and surgical sponsors showcased their latest innovations and enthusiasts were given the chance to practise skills robotic on the Da Vinci console. An eventful day drew to a close @MCEC with the announcement of the poster winners, generously sponsored by Ipsen Pharmaceuticals.

#CU- Survival disparities between Maoiri and non-Maoiri men with non-localised prostate cancer in New Zealand. Zuzana Obertova

#NAH-New prostate cancer diagnoses-improving timeliness of communication with patients General Practitioners. Sue Stanbridge

#TS-Engineering a High-Throughout Prostate Cancer Stem Cell Niche Mimic. Micael Doran

 

The BJUI were major supporters of this year’s PCWC and published all of the accepted abstracts in a special supplement (https://onlinelibrary.wiley.com/doi/10.1111/bju.2013.112.issue-s1/issuetoc)

 

 

 

 

Thursday flew into action bright and early with breakfast talks from Dr. Joseph Smith, Professor Paul Waring and an expert #NAH panel. A combined multidisciplinary plenary addressed risk stratification and imaging, with notable speakers including Dr Matt Cooperberg on the issues in treating localised prostate cancer and Dr Tom Aherling ‘The critical role of hypogonadism or low testosterone in prostate cancer’. Key topics addressed in sessions on Thursday included active surveillance, changes in treatment of options of metastatic prostate cancer and screening. Highlights included an excellent lecture on Radium 223 by Dr. Oliver Sartor, an anecdotal insight into the recent work of Dr. Niall Clarke and Dr. Monique Roobol addressed ‘The PRIAS project’. For those delegates that had thus far escaped the #SoMe excitement, a workshop to twitter with the times was provided and the evening closed with an extensive global perspective on prostate cancer.

An academic programme and faculty line-up that would surely struggle to be matched, was further enhanced by the splendour and uniqueness of Thursday evenings congress dinner. Guests enjoyed pre-dinner drinks and canapés while exploring the National Sports Museum before being treated with the rare honour of stepping out onto the ‘hallowed turf’ of the mighty MCG. As if we had not been spoiled enough, the Aussie experience continued upon entering the Members dining room where we got the chance to cuddle a Koala, pose with crocs and if one dared; to dangle a python around your neck! It had both young and more mature delegates jumping around like children. The magnificence of the location was conveyed further to guests by a fun fact quiz on @MCG. Main course was an Australian culinary delight, with accompanying national wines and a surreal view of Australia’s most spectacular sporting venue. Mark Holden had guests laughing while Catarina Torres ensured faculty and delegates of all ages put on their #dancingshoes.

Masterclasses on Friday in robotic-assisted surgery remains one of the most favoured aspects of the program with surgeons of all levels looking forward to hearing tips and techniques from #robotics worldwide leaders. The da Vinci Prostatectomy Masterclass was conveend by Dr Daniel Moon and Dr Geoff Coughlin. Key speakers included Dr Tom Aherling and Dr David Gillatt, between whom have experience of over 15,000 radical prostatectomies. Dr Aherling talked through a full length RARP case sharing advanced tricks, followed by Dr. James Borin’s discussion on the intricacies of UV anastomosis. Trainees enjoyed a more intimate opportunity to engage with experts such as @LoebStacy, @dr_coops, @JGrummet, @DrDanielMoon, @lawrentschuck in a master class engineered for budding future urologists. Knock off drinks took place that evening on the glistening Southbank as the success of #PCWC13 could hardly be disputed. A sunny Melbourne Saturday saw GPs provide a workshop for GPs to improve both their knowledge and management of men with prostate cancer both in terms of testing and treatment.

By the end of the week, data from symplur.com using the #pcwc13 hashtag showed just how imapct this year’s Congress had on social media.

The BJUI Social Media team were very pleased to be a part of this success.

It was my first Urology conference and as a medical student I was excited to have an opportunity to be in the same centre as such a stellar line-up of experts. In all honesty I was star-struck. As a member of the BJUI social media team I was tweeting until my thumbs ached but not only did this allow me to engage with @urotwitteraiti household names virally, in many cases it gave me a window to engage with them in person. #Surreal. A fact that surely emphasises the power of #SoMe and would quash any reservations of #tweeterdoubters.

#pcwc13 #RoaringSuccess

Follow the link to Australian Prostate Cancer Research to see highlights of all the action. https://www.facebook.com/media/set/?set=a.503695969711643.1073741827.232024796878763&type=1

Authors:
The BJUI Social Media Team at PCWC – Áine Goggins, Medical Student, Queens University Belfast and University of Melbourne; Dr Marni Basto, Peter MAccAllum Cancer Centre, Melbourne; Dr Sarah Wilkinson, Monash University, Melbourne.
@gogsains @DrMarniqueB @wilko3040

 

 

Is Gleason 6 really cancer?

/7 Comments/by

The recently published Viewpoint of the National Cancer Institute working group on “Overdiagnosis and Overtreatment in Cancer” by Esserman and colleagues [1] raises continued discussion as to whether some lesions currently classified as carcinomas should have the designation of “cancer” removed, based on low rates of progression, death, and other adverse outcomes. Pertinent to those interested in urology, a central example in the article is prostatic adenocarcinoma.

One simple answer to this question is that to a small extent, a subgroup of prostatic lesions has already been reclassified as not cancer: In current practice, needle biopsy or radical prostatectomy specimens with an overall Gleason score (GS) of 5 or less are now quite rare in current practice. This shift is due in part to modern updates to the Gleason grading system [2], under which many tumors now reach thresholds for GS6 or above. However, at least some lesions previously considered adenocarcinoma with a low overall GS would now be categorized as atypical adenomatous hyperplasia or adenosis in the era of immunohistochemistry for markers of prostatic basal cells. Nonetheless, the current and more controversial debate surrounds whether some (or all?) tumors currently classified as GS6 could be recategorized as not “cancer”.

Arguments against removing the cancer designation from some prostatic adenocarcinomas:

A major difficulty from the pathologic standpoint in adopting a non-cancer nomenclature for some tumors (such as GS6 adenocarcinomas) is that the Gleason pattern 3 component of a GS 3+3=6 tumor (small, round prostatic glands that lack a basal cell layer and infiltrate between benign glands) is for all intents and purposes identical to the Gleason pattern 3 component of a GS 3+4=7 or higher prostate cancer. These similarities are not limited exclusively to the microscopic appearance but also include a number of immunohistochemical and molecular features, as summarized in a recent article addressing this question [3]. Therefore, no pathologic features are as yet defined that ideally predict whether Gleason pattern 3 glands in a biopsy specimen represent a pure GS6 tumor or a component of higher-grade tumor in which the high-grade component is not represented. Not surprisingly, it is not unusual for tumors with GS6 on needle biopsy to be upgraded to GS7 at radical prostatectomy [3], particularly when a high tumor volume is present in the needle biopsy.

Gleason pattern 3 glands from a GS7 tumor, identical to those of a GS6 tumor.

To compare to other cancers with low risk of aggressive behavior, basal cell carcinoma and squamous cell carcinoma of the skin similarly show locally infiltrative properties, supporting their classification as carcinomas by a classical pathologic definition. Despite that the word “carcinoma” continues to be used for these tumors, most patients are not concerned that they have a life-threatening disease and these lesions are even excluded from the American Cancer Society statistics regarding cancers [4]. In the same way, Gleason pattern 3 glands exhibit infiltrative growth by extending between benign glands, invading nerves, and sometimes extending outside of the prostate. This difference in mindset regarding some types of “cancers” could be considered supportive evidence for the assertion in the recent Melbourne Consensus Statement that uncoupling prostate cancer diagnosis from intervention may be more appropriate than removing its “cancer” nomenclature.


This small GS6 adenocarcinoma was an incidental finding in a radical cystoprostatectomy specimen for bladder cancer but surprisingly extended into periprostatic fat via this focus of perineural invasion.

Supporting removal of the cancer designation from some prostatic adenocarcinomas:

A valid argument of the NCI Viewpoint is that a neoplasm should have a substantive rate of progression and patient death if it is to be considered a cancer. Likewise, others have questioned whether low-volume GS6 tumors fulfill other molecular and pathogenetic hallmarks of cancer, such as unlimited replicative potential and other features [5].

In general, benign and malignant neoplasms can be regarded as having some prototypical gross and microscopic pathologic characteristics, such as a circumscribed vs infiltrative growth and homogeneous vs pleomorphic cell population. However, differentiating benign from malignant lesions also relies heavily on parameters specific to the organ involved. Clear cell renal cell carcinoma, another genitourinary tract tumor, often does not possess these prototypical features of malignancy. Tumors often form a well-circumscribed mass without an “invasive” growth pattern and they often are composed of a uniform population of cells. However, based on known behavior of these tumors, their status as a malignancy is not in doubt. Conversely, renal oncocytoma is a benign neoplasm that shares some of these general features (a round mass composed of a homogeneous population of renal tubular cells). Occasionally oncocytomas appear infiltrative by extending into the perinephric fat or renal vein, yet their status as benign is also not the subject of debate. If some prostate cancers do not have a substantial likelihood of resulting in progression and death, they may not meet an important criterion for a diagnosis of cancer, despite that other features, such as infiltration of tissues, invasion of nerves, and loss of the basal cell layer are characteristic of a malignant neoplasm.

Since a diagnosis of GS6 by needle biopsy is not always predictive of a radical prostatectomy overall GS6, a major challenge to such an approach would be to determine where such a cutoff could be drawn between “cancer” and “not cancer” [5]. If based on tumor volume, it would be difficult to conceptualize that a small amount of GS6 glands would be regarded as a benign lesion, whereas a large amount of identical glands would represent a malignant lesion. Alternatively, the presence of Gleason pattern 4 could used as the point of differentiation (GS7 or above). In the endometrium, a disorganized proliferation of crowded glands with some cytologic features of cancer is regarded as complex atypical hyperplasia. Diagnosis of adenocarcinoma is then reserved for proliferations with a confluent growth of these glands, similar to the threshold for recognizing a component of cribriform glands as Gleason pattern 4. A limitation to such an approach, however, is that a substantial fraction of patients with a needle biopsy GS6 are upgraded to GS7 at radical prostatectomy, as discussed above. Likewise, the ability to treat and monitor GS6 adenocarcinoma nonsurgically is not quite analogous to that of endometrial hyperplasia.

Higher magnification of image 2 shows Gleason pattern 3 glands invading a nerve with ganglion cells.

Other points of discussion

The NCI Viewpoint also suggests that high-grade prostatic intraepithelial neoplasia (HGPIN) no longer be considered cancer or even neoplasia.  A comparison to ductal carcinoma in situ (DCIS) of the breast for this argument is somewhat flawed, as HGPIN neither contains the word “carcinoma” nor is justification for treatment in and of itself. Its status as a risk factor for a future cancer even remains debated. The proposal to remove “neoplasia” from HGPIN is also a confusing one, particularly as cervical cancer is noted as an example of the successful application of screening, in which “cervical intraepithelial neoplasia” is the preferred term for precancerous lesions. The authors suggest the designation “indolent lesions of epithelial origin” (IDLE) for cancers in this category to convey their low likelihood of aggressive behavior. However, would recognizing the status of these lesions as at least premalignant neoplasms be more appropriate?

Likely a typographical error in the Viewpoint is that the authors also cite reclassification of urothelial papilloma as papillary urothelial neoplasm of low malignant potential [1]. Since urothelial papilloma has never been considered a malignant neoplasm, the authors likely meant reclassifying “grade 1 urothelial carcinoma” to papillary urothelial neoplasm of low malignant potential.

References
[1]        Esserman LJ, Thompson IM, Reid B. Overdiagnosis and Overtreatment in Cancer: An Opportunity for Improvement. JAMA. 2013 Jul 29:

[2]        Epstein JI, Allsbrook WC, Jr., Amin MB, Egevad LL. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2005 Sep: 29:1228-42

[3]        Carter HB, Partin AW, Walsh PC, et al. Gleason score 6 adenocarcinoma: should it be labeled as cancer? J Clin Oncol. 2012 Dec 10: 30:4294-6

[4]        Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan: 63:11-30

[5]        Ahmed HU, Arya M, Freeman A, Emberton M. Do low-grade and low-volume prostate cancers bear the hallmarks of malignancy? Lancet Oncol. 2012 Nov: 13:e509-17

 

Sean Williamson is Senior Staff Pathologist in the Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit MI, USA. @Williamson_SR

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