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EAU14 – Planning and executing a meeting session: perspective of the chairs

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An interview with Prof. Noel Clarke on the EORTC-GU session

For an academic and/or key opinion leader in urology, the opportunity to plan and execute a meeting session is a tremendous honor, but one that comes with numerous challenges. The trivial but not-so trivial aspects involve the logistics: who will attend, who will speak, what do I do if a speaker cancels, what if the speakers do not stick to time, etc. Of course the easiest way to begin is to chair a session comprised of abstracts on a particular theme. This requires mainly the effort of preparing good questions for discussion and how to keep speakers on time (should we be nice?). The next level up is to plan a session with a broader theme that requires inviting specific speakers, framing debates, and then orchestrating it all into very usable take home messages for the audience. These are tremendous opportunities to come up with a vision for our field to consider.

At the EAU 2014, Prof Noel Clarke (GB) from our consulting editorial board was charged to organize the EORTC-GUCG session along with his co-chair Cora Sternberg (IT). I had a few questions for Prof Clarke, but really ended up just handing him my iPhone with the voice memo running and asking him how he went about planning the session:

“What we were trying to do was give a broad-based and sufficiently detailed overview of where we are in relation to different cancers and understanding of different cancer processes. And we tried to do that with specific reference to areas that have been strong in the EORTC-GU group in the past, particularly linking some of the trials that we’ve done with some of the basic science that is currently ongoing. And trying to project that forward as to how we might design future trials. And the emphasis really is on participation of clinicians with scientists and with data centers to try to overcome some of the problems associated with the prosecution of trials in the modern era. Hence our final talk with was Bertrand Tombal’s talk which is really how we would envisage planning and structuring trials as we go forward because it is certainly very different now than it was in the ‘70s when the EORTC was able to do really large scale trials, following on the ‘80s and 90’s to 2000’s [British pronunciation: “naughties”] where increasingly international trial groups, academic groups, found it difficult to get around the problems of finance, beaurocracy, new agents, interactions with Pharma, and so on. So that really was the essence of how we planned our session.”

Wow – what a gem. Didn’t really need a 2nd question.

Figure 1: SPECTApros trial design

  • Prof. George Thalmann spoke on BCG therapy – an area in need of more standardized protocols and biomarkers for sensitivity/resistance. Ultimately we need successful treatment of CIS and prevention of NMIBC recurrence and progression.  The first step towards success is with a high quality TUR that provides correct staging and therapy. On this note, he cited an EORTC study (Brausi et al. Eur Urol 2002) that showed 7.4-45.8% recurrence rates after TUR and adjuvant chemo when taken for first follow-up cysto. Next, the focus is on ideal BCG therapy in terms of timing, schedules and which strain of BCG. He cited RCT’s planed by SWOG and SAKK/EORTC looking at intradermal BCG 3 weeks before intravesical therapy to improve pre-existing immunity. Not all BCG strains perform equally, and there may need to be a prospective comparison. See Figure 2.

Figure 3: Prof. Necchi’s summary slide on the challenges of translational trials

  • Finally, Prof. Bertrand Tombal, Brussels (BE) presented “Next generation trials for urologists and uro-oncologists, where are we headed?” The introductory observation was that we are increasing the gap between what we know through evidence versus what we do in practice – including both things we do without quality evidence and things we do contrary to quality evidence. Specifically, less than 4% of articles in surgical journals are randomized trials, and most of those are evaluating medical therapies rather than surgery itself. Yet research is increasingly complex with regulatory demands, dependence on pharma, and related strategies to focus on large indications. The key recommendations were to raise important questions when it comes to benefit for patients, assess affordability, and bring trials to the patient rather than the other way around. The SPECTApros design was highlighted again with reference to its integration of nomograms predicting a specific outcome, imaging, and biomarker identification/validation.

So that’s the snapshot of the modern EORTC and I look forward to following the progression of these novel trial designs and strategies.

John W. Davis, MD  FACS
Houston, TX, USA
Associate Editor, BJU International

 

EAU14 – ESOU citations

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Have You Read This?…A bibliography of cited papers on prostate cancer at the Joint Meeting of The European Section of Oncological Surgery (ESOU) and EORTC—Genito-Urinary Cancer Group.

At the BJUI, as with any journal, the published articles are peer reviewed and editorial board reviewed.  The process starts with a triage editor who screens for basic methodology, importance of the topic, and potential for citation factor impact.  The top 50% are sent for full peerreview, which includes 3 reviewers (ad hoc or from the board).  Full review is organized by an associated editor who assigns (and then begs) the 3 reviewers to complete their task, and then makes a final recommendation to the editor in chief.  I could go on about this interesting process, but the point is that a published paper is often really just the opinion of 4-5 experts in the field, including the editor.  Once published, however, papers are then kept alive by repeated citation and meeting discussions, or disappear intoPubMed and forgotten. Future papers that cite a previously published paper will help the impact factor of that journal.  But what about congress events and their cited works?  At the EAU 2014, as with any congress, key opinion leaders are asked to give talks, make arguments, and prove their points.  They may do so with personal experiences, videosor modern abstract quotes, but often they cite recent peer review publications.  At the joint session meeting of the ESOU and EORTC-GUCG, I noted the following cited publications from the prostate cancer talks.  How many have you read so far?

On the topic of circulating tumor cells (CTCs) in prostate cancer, Professor S. Osanto of Leiden (NL) cited (partial citations):

1. Hanahan D et al. The hallmarks of cancer. Cell 2000
2. Klein CA.  Cancer.  The metastasis cascade.  Science 2008.
3. Gerlinger M et al.  Intratumor heterogeneity and branched evolution revealed by multiregionsequencing.  NEJM 2012
4. Allard WJ et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. ClinCancer Research 2004
5. de Bono JS et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Research 2008
6. Attard G et al. Characterization of ERG, AR, and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer.  Cancer Res 2009.
7. Cristofanilli M. Circulating tumor cells, disease progression, and survival in metastatic breast cancer.  NEJM  2004.
8. Goldkorn A et al. Circulating tumor cell counts are prognostic of overall survival in Southwest Oncology Group trial S0421: A phase III trial of docetaxel with or without atrasentan for metastatic castration-resistantprostate cancer.  J Clin Oncol 2014.

From these papers, the conclusions were many and included: 1) CTS can detect early relapse, genomic signatures, target identification, and treatment decisions, 2) surrogate marker for response, and 3) emergence of resistance.

Next, the focus shifted to the popular technical points and outcomes of open versus minimally invasive radical prostatectomy.  Bernardo Rocco (IT) cited the following papers in support of robot-assisted radical prostatectomy for high risk PCa

9. Yuh et al.  The role of robot-assisted radical prostatectomy and pelvic lymph node dissection in themanagement of high-risk prostate cancer: A systematic Review. Eur Urol 2014
10. Montorsi et al. Best practices in robot-assisted radical prostatectomy: recommendations of the Pasadena Consensus Panel. Eur Urol 2012.
11. Silberstein JL et al. A case-mix adjusted comparison of early oncological o utcomes of open and robotic prostatectomy performed by experienced high volume surgeons.  BJU Int 2013.
12. Hu JC. Comparative effectiveness of robot-assisted versus open radical prostate cancer control.  Eur Urol2014
13. Ploussard G et al. Pelvic lymph node dissection during robot-assisted radical prostatectomy efficacy, limitations, and complications—a systematic review of the literature. Eur Urol 2013.
14. Prasad SM et al.  Variations in surgeon volume and use of pelvic lymph node dissection with open and minimally invasive radical prostatectomy. Urology 2008
15. Cooperberg MR et al. Adequacy of lymphadenectomy among men undergoing robot-assisted laparoscopic radical prostatectomy.   BJU Int 2010
16. Feifer AH et al. Temporal trends and predictors of pelvic lymph node dissection in open or minimally invasive radical prostatectomy. Cancer 2011
17. Ficarra et al. The European Association of Urology Robotic Urology Section (ERUS) survey of robot-assisted radical prostatectomy (RARP).  BJU Int 2013.
18. Gandaglia G et al. Is robot-assisted radical prostatectomy safe in men with high-risk prostate cancer? Assessment of perioperative outcomes, positive surgical margins, and use of additional cancer treatments.  J Endourol 2014.
19. Ou Y.C. et al. The trifecta outcome in 300 consecutive cases of robotic-assisted laparoscopic radical prostatectomy according to D’Amico risk criteria.  EJSO 2013.
20. Lavery HJ et al. Nerve-sparing robotic prostatectomy in preoperatively high-risk patients is safe and efficacious.  Urol Oncol 2012.
21. Montorsi F. Robotic prostatectomy for high-risk prostate cancer: translating the evidence into lessons for clinical practice.  Eur Urol 2014

From these citations, the conclusions were that: 1) RP is an adequate treatment for high risk prostate cancer, 2) robotic approach is not inferior to open as far as oncological outcome, 3) lymph node template and yield are adequate in experienced hands in RARP setting, 4) functional outcome after RARP in high risk is preserved, nerve sparing is feasible in selected patients, and 5) Costs of RARP are related to surgical volume and experience.  So there you see a typical meeting presentation—13 papers in 15 minutes plus additional commentary and abstract data.

Next, Prof. Declan Murphy presented the Australian experience with robot-assisted RP for cT3a prostate cancer.  With overlapping topics, it was no surprised some papers were recited from above including #9, #12,He cited:

22. Evans et al. Patterns of care for men diagnosed with prostate cancer in Victoria from 2008-2011.  Med JAust 2013
23. Wilt T et al. Radical prostatectomy versus observation for localized prostate cancer. NEJM 2012
24. Connoly SS et al. Radical prostatectomy as the initial step in multimodal therapy for men with high-risk localized prostate cancer: initial experience of 160 men.  BJU Int 2012.

From these citations, Prof. Murphy concluded that: 1) radical prostatectomy has minimal benefit for low risk men, especially older, 2) The biggest benefit is in high risk disease, 3) active surveillance is being embraced in Australia, 4) RARP is safe and effective with similar outcomes to ORP, 5) RARP has less positive margins and less additional therapy compared to ORP 6) extended PLND not limited by robotic approach.

Prof. Axel Heidenreich then took the opposite point of view in support of open radical prostatectomy.  Despite the references above, he pointed out that there is still no long-term data for robotic prostatectomy, although not proving that with pathologic staging we would expect anything different.  Cost of course can be quite better for open.  He also cited for papers showing positive margins of < 12% in pT3 disease, compared to many other open and minimally invasive series where it is usually 25% and higher. Repeat citations: #9. He also cited:

25. Robertson C et al. Relative effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of localized prostate cancer: a systematic review and mixed treatment comparison meta-analysis.  BJUI 2013.
26. Vora AA et al.  Robot-assisted prostatectomy and open radical retropubic prostatectomy for locally-advanced prostate cancer: multi-institution comparison of oncologic outcomes.  Prostate Int 2013
27. Punnen S et al. How does robot-assisted radical prostatectomy (RARP) compare with open surgery in men with high-risk prostate cancer? BJU Int 2013
28. Sooriakumaran P et al. A multinational, multi-institutional study comparing positive surgical margin rates among 22393 open, laparoscopic, and robot-assiste radical prostatectomy patients. Eur Urol2014
29. Alemozzafar M et al. Benchmarks for operative outcomes of robotic and open radical prostatectomy: results from the health professionals follow-up study.Eur Urol 2014
30. Davison BJ et al Prospective comparison of the impact of robotic-assisted laparoscopic radical prostatectomy versus open radical prostatectomy on health-related quality of life and decision regret. Can J Urol 2014
31. Bolenz C et al.    Costs of radical prostatectomy for prostate cancer: a systematic review.  Eur Urol 2014

From these citations, he concluded that 1) open radical prostatectomy is still viable, 2) not needed for low risk, 3) lack of long-term data for RARP, 4) no inferiority in terms of functional and oncological outcome, or quality of life, 5) better cost effectiveness, especially with median case load of < 300 RP’s per year.

I hope you find this reading list useful.  Could you transfer such a bibliography to an effective review article?  Probably not, and we can ask associate editor Quoc Trinh to comment or write a separate blog on the emerging field of systematic reviews, such as the multiple cited reference 9 by Yuh et al.  A systematic review needs to conform to standards such as the PRISMA guidelines—see www.prisma-statement.org –which is “an evidence-based minimum set of items for reporting in systematic reviews and meta-analyses.  Therefore we have an interesting difference in standards between a meeting presentation and a formal peer-reviewed systematic review—the former can hand-pick articles to make a point, while the latter must be thorough, transparent, and reproducible.

John W. Davis, MD  FACS

Houston, Texas (USA)

Associate Editor, BJUI

 

 

EAU14 – The Multifaceted Goals Of Andrology: Maintaining Quality Of Life

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A famous version of a saying attributed to Benjamin Franklin states “…but in this world nothing can be said to be certain, except death and taxes.” As a urologic oncologist, I cannot help with the taxes, but strive to delay the latter when threatened by urologic cancers.  Our colleagues in andrology, however, are charged with the task of being sure the life lived is of high quality, and I am impressed at the large number of problems they face including infertility, erectile dysfunction, andhypogonadism.  The latter problem is quite comprehensive when you consider the associated risks of cardiovascular disease, type 2 diabetes, sexual dysfunction, reduced energy, reduced muscle mass, weight gain, and many more.  With this challenge, the first plenary session at the 2014 EAU gave an update on andrology with significant cross-over appeal to the uro-oncologist.

Prof W.H-G. Weidner started the session with an overview of male factor infertility, which comprises 50% of the contribution to childless couples.  The causes can be idiopathic but then include primary testicular failure,varicocele, genetic disorder, obstruction, male accessory gland infection, hypogonadism, germ cell malignancy, and ejaculatory dysfunction.  The diagnosis requires a comprehensive andrological exam if two separate semenalyses are abnormal.

 

Figure 1 Prof. W.H-G. Weidner from Giessen (DE) gave the first plenary presentation at the 2014 EAU, Stockholm, Sweden

Varicocele repair is known to improve ejaculate quality, however the effect on pregnancy rates does not always follow—counseling for the couple is also effective.   The other major surgical intervention involves various techniques of microscopic sperm retrieval with essentially 100% retrieval rates.  All factors considered, this leads to an approximate 20% “baby take-home” rate when used with ICSI.  An interesting new trend is pediatric oncologist requesting sperm retrieval and cryopreservation for pre-pubertal patients who need chemotherapy.

Prof. S. Arver from Stockholm (SE) then reviewed the topic of testosterone supplementation in the ageing male.  As a uro-oncologst in the 4th largest city in the USA, this is an every day topic.  On the way to work I heard radio advertisements for local “Low-T Centers” that aim to attract potential patients who may be tired, or having problems with their sex life.  Once I get to work, I see the new patients with an elevated PSA discovered as a downstream event once they’ve started testosterone replacement and had subsequent screenings.  What do we know about the diagnosis of testosterone insufficiency and risks/benefits of replacements?

First, the diagnosis of testosterone (T) insufficiency is a combination of symptoms and laboratory assessment.  Total serum T should be measured as a morning sample between 7-10am and fasting.  If an afternoon measurement is low, it should be repeated in the proper circumstance.  If the level is > 12 nmol/L it is likely normal, while 8-12nmol/L is a “grey zone” and < 8 nmol/L is probably associated with symptoms that would respond to therapy.  The grey zone implies that some men can be symptomatic in the lower end of a normal range.  In addition, a serum LH > 9 supports deficiency as the internal thermostat is trying to compensate, whereas LH 2-9 is uncompensated and may be a transient state.

The symptoms of low T are quite a list and organized under the categories is Physical/metabolic (decreased bone mineral density, muscle strength, etc.), sexual symptoms (libido, ED), and psychological (energy, fatigue, mood, etc.).  To make matters worse, hypogonadism has a high prevalence with chronic renal failure, rheumatic disease, HIV, COPD, cancer therapy, opioid use, steroids, and male infertility.  Of course, the most significant long-term concerns would be cardiovascular risk and type II diabetes. You can infact try using SARMs rather than steroids which is lot more better than steroids as per research studies. You can visit ceasar-boston.org to know more about SARMs.

T replacement is associated with significant responses in properly diagnosed patients, but dosing may be different—older patients may not clear it as fast and need dose titrations.

Prof. G.R. Dohle, Rotterdam (NL) continued the presentation with an emphasis on guidelines.  Overall, the incidence of hypogonadism is 6% of middle age men and increasing in older men.  Testosterone replacement may help with symptoms, increase weight reduction, and improve diabetes and bone mineralization.  The side effects to note include increasing hematocrit, fluid retention, BPH, prostate cancer, gynacomastia, and recently sleep apnea, Arizona sleep apnea care offers treatment for this last one.

Is TRT a “fuel” for prostate cancer?  Based on level 2 evidence, TRT should not be used for locally advanced or metastatic PCa.  For PCa risk itself, there is a lack of evidence of association.  For patients with localized disease treated with radical prostatectomy, there are only observational studies, but no risk of tumor recurrence with limited follow-up.  A saturation model has demonstrated that the androgen receptor is saturated just over the castration level and therefore additional T should not increase further growth.  The guidelines recommend careful monitoring with hematology levels, cardiovascular assessment, and PSA monitoring (for age > 40).  Specifically, hematocrit and hemoglobin and PSA should be checked at 3, 6, and 12 months and then annually. They recommend at least 1 year of biochemical NED follow-up.

 

Figure 2 Prof. G.R. Dohle from Rotterdam (NL) presents he EAU guidelines on testosterone replacement andprostate cancer.  #EAU2014.

The session then switched into another gear with the presentation by Prof John P. Mulhall from New York (USA) with the focused question as to whether or not TRT causes an increased risk of cardiovascular events.  This topic has been covered by the New York Times and the Wall Street Journal based upon a hand full of studies concluding that the risk exists.  These reports, of course, have led to many patients wanting to stop therapy, and the U.S. legal system creating a new industry of tort claims.  This was a “getting into the weeds” talk by an expert with impressively high words per minute speaking pace.  The theme was all about methodology, and I could never re-create the whole talk in summary.  The bottom line was that 3 high profile papers including Basaria et al NEJM 2010,Finkle WD PLOS ONE 2014, and Vigen R JAMA 2013 all had significant limitations in the methods, which ProfMulhall concluded led to erroneous conclusions.  To quote: “Bad science can hurt people,” and “ The good thing about good science is that it is true whether or not you believe it (reference Neil deGrasse Tyson).”

Professor A.L. Burnett from Baltimore (USA) delivered the AUA lecture on sexual function after urologic surgery. This was more of a review talk and a very complete one given the short time.  Of course I am biased in his favor as he highlighted one of my publications on sural nerve grafting (Davis et al Eur Urol 2009) which effectively diminished the previous trend in this procedure with the randomized cohorts showing no difference from unilateral nerve sparing alone.  There are certainly numerous teachings and publications on nerve sparing surgery technique, but even high volume surgeons have demonstrated and published that technique alone does not seem to eliminate the risk of post-operative erectile dysfunction.  Therefore much focus has shifted to post-operative management and novel techniques.

In the post-operative management area, the commonly used term is “penile rehabilitation.”  The concept is straightforward: to stimulate blood, maintain tissue oxygenation, protect endothelial function, and reduce tissue damage/atrophy.  While the data certainly suggests that PDE5 inhibitors, vacuum erection devices, and injections can improve erections after surgery, the data are still not conclusive that a scheduled, rehabilitation is superior to on demand use.  There are papers suggesting a benefit, but reasonable to conclude that this is not “holy grail” in solving the problem.  He then outlined the various other research and alternative pathways under evaluation from neurotropic factors, androgen replacement in select patients, treatment of ejaculatory dysfunction, and counseling—the latter of which seems to augment the standard treatments).

 

 

Figure 3: Professor A.L. Burnett, Baltimore (USA) at #EAU2014

Prof. M. Albersen of Leuven (BE) continued this theme with a review of bench research in erectile dysfunction and the progress of stem cell research.  Early work shows potential benefits at the smooth muscle, fibrosis, and innervation endpoints.  At least 6 trials are now registered at clinicaltrials.gov in this area, but many are still looking at the safety aspects first.  Prof M.J.H. Van Griethuysen ofRotterdam (NL) concluded the session with a review of future research funding.

Congratulations to the organizers and speakers for a strong start to #EAU2014.  Where you in the audience?  What were your take home messages?

John W. Davis, MD, FACS 

Houston, Texas

Associate Editor, Urologic Ongology, BJU International

Another good week for radical prostatectomy

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The SPCG-4 (Bill-Axelson) study updated again in NEJM

In this week’s edition of the NEJM, Anna Bill-Axelson and the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) investigators have written an impressive update to their famous study comparing radical prostatectomy (RP) to watchful waiting (WW) in a setting of mostly clinically detected prostate cancer. In 2002, the group reported in NEJM at a median 8 years of follow-up that RP reduces disease specific mortality, overall mortality, and risk of metastasis and local progression. The declines in prostate cancer specific mortality were 8.6% for RP versus 14.4% for WW. In 2011, they published again with a median 12.8 years of follow-up and the differences were 14.6% versus 20.7%, but the benefit was impressively driven by men under age 65. Now in 2014, the median follow-up time is 13.4 years with up to 23.2 years at the high end, and overall 64% of the cohort has died by end of 2012 — specific to prostate cancer in 17.7% vs. 28.7%. The number needed to treat is 8. 

What stands out in the latest edition of this famous trial? Although previous reports describe differences in metastatic and progressive disease in WW, this report nicely shows that RP reduces metastatic disease burden, androgen deprivation therapy, and palliative treatments across all age groups — even if mortality comparisons are still more notable in younger cohorts. So the paper has evolved into a key lesson in the natural history of prostate cancer and localized curative intervention (side debate — this paper is not really about radical prostatectomy itself, but rather intervention, and I would assume many similar benefits possible with radiation approaches). Prostate cancer outcomes are more complex than simple cure fractions. Patients can suffer from relapsed disease, multiple treatments, long-term androgen deprivation, and, yes, actual prostate cancer mortality that apparently takes a committee of experts to decipher from competing sources. I think the impact of the study will be that healthy men between the ages of 65-75 may benefit from treatment of lethal potential prostate cancer — but perhaps as measured by endpoints other than mortality. This is especially relevant with the evolving library of treatment options for castrate resistant prostate cancer — it may take a lot longer to actually die of prostate cancer, but who really wants to spend their last 5-10 years of life heavily medicated compared to a more effective localized intervention at an earlier time? Between earlier versions of this study and the PIVOT trial, I think we already believe in the benefits of curative therapy for men <65 years with intermediate to high-risk disease. On the other end of the spectrum, the paper still supports the concept of active surveillance for low risk cancer, although more is to be learned from other accruing cohorts of patients who will undergo selective delayed intervention. 

Overall, I found this to be a highly citable paper with a new set of figures destined for use in many PowerPoint talks to come. The overall message is that RP at the right time and right patient can prevent mortality and disease progression. A comprehensive prostate cancer program should start with such biology-based discussions with patients and then carefully integrate active surveillance in the lower risk end and clinical trials of combination therapy at the higher end. Finally, I wonder if the findings of reduced metastatic events in older patients might re-challenge the screening guidelines that are encouraging less screening after age 70?

John W. Davis, MD
Associate Editor, BJUI

Read the NEJM article

What can a Society do to make you a better surgeon?

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World Congress of Endourology 2013 — The Society of Urological Robotic Surgeons meeting report.  

Jean Joseph and Erik Castle

Continuing this theme, Dr. James Borin (Baltimore, USA) reviewed the Fundamentals of Robotic Surgery curriculum in development from a collaborative effort. This would be a device independent curriculum that covers didactics, psychomotor skills, and team building. This is a huge effort with two grant mechanisms moving it along. It has been interesting to see this develop over the past decade, considering when robotics started, Intuitive would just fly in a proctor and pretty much managed training for the first few years. Now we will soon have a very specific set of requirements for new surgeons and their surgical teams.

Personally, I hope simulation improves in what it can offer a trainee. From my practice, with large numbers of fellow and resident trainees, I am stuck with the conflict between the high functioning trainees who say they just want live surgery training, and struggling trainees who say the simulation does not magically fix everything.

Next, Dr. Raju Thomas (New Orleans, LA), our meeting organizer/host, led a panel discussion on surgical complications. There is no way to blog about such an event as it is mostly video of an error — mostly impressive vascular injuries — followed by solutions and comments. These events are not to be missed, as you just cannot learn beyond your training and experiences without them — journals and book chapters can quote stats, but not the experience of having and fixing a complication. Most of the injuries related to vascular as noted, and patient positioning. I think the ideal steep Trendelenburg position technique needs more work. As audience members commented, there is something magic about 4 hours — longer than this and you risk complications including compartment syndrome if the patient slides down from the original position.

During the session, I was struck by the issue of surgical video quality. First, there is the problem with time — always needing to make a major point with a video in 1-2 minutes. How many seconds per edit? 5 seconds, 10, etc.  Some segments are so choppy you have trouble following the flow of the video, but long segments take up so much time that you go over. I’ve had some success with using iMovie to speed up segments to 2X speed — looks as smooth and more content. Another issue is zoom level. With pictures we crop and zoom all the time to get the frame and highlight just right. But in video we cannot. So there were many fine segments of video where the camera was pulled back and the instruments are occupying over half of the screen, when what you needed to see should have been zoomed in. Moving forward, it would be an advance to be able to re-crop video like we do still images.

Koon Ho Rha

What about evidence based medicine?

Dipen Parek (Miami, USA) presented his randomized trial on open versus robotic radical cystectomy. The trial has 14 institutions and is accrued at 295 of 320 patients, so clearly is going to “make it”. It is a non-inferiority trial for oncologic outcomes. This will be a milestone in robotic surgery research and kudos to his team of investigators. Another randomized trial was presented at the 2013 AUA from Memorial Sloan Kettering. In this single site study the endpoint was lower complications for robotic. At the interim analysis there was no difference and the trial halted. These trials and the CORAL study in the UK will be rich for future discussions as to their design choices, findings, and impact on future clinical care. As Dr. Parek pointed out, in the future of medicine, it will be less about what a surgeon wants to do and more about what he/she is “allowed” to do.

At the SURS business meeting it was announced that Dr. Jim Porter (Seattle, USA) was named the President-Elect. Dr. Sundaram has 1 more year to go. It was discussed that the leadership of SURS would like more international involvement, including the possibility of SURS meetings occurring at other international meetings. Finally, Dr. Steven Nakada (Madison, USA) the secretary of the Endourology Society discussed that the Society will have a new vendor to run the meetings and website, so this may open new doors to social media, website content, etc.

John W. Davis, MD
Associate Editor, BJUI

Urological oncology in the BJUI

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Urological oncology is increasingly multi-disciplinary, and hence competitive for high impact thought leadership. Innovation leading to paradigm changes may come from a number of different ideas and sources. Effective leadership in our specialty certainly requires technical innovations in surgical treatments, but also pivotal roles in improving the process of diagnosis, staging, patient counselling, multi-modal therapy, and ultimately evidence-based clinical guidelines. The ultimate end-result of innovation is a peer reviewed publication, and at the BJUI we wish to bring you nothing but the highest quality.

Our daily lives are increasingly busy with our varying mixtures of clinical work, teaching, administration, and research. How much time do we have to read a surgical journal? It is an important part of our learning, but we must be efficient to squeeze it into a busy day. Keeping this in mind, the Editorial Board is more selective than ever in the papers that make it into the BJUI. Each paper we accept needs to represent something valuable to the reader and to our science, such as a technical innovation, large study of a new method to fix an unmet need, multi-institutional validation trial, or updated guideline. For this to work, we need fair and efficient peer reviewers, and high quality submissions.

In this month’s BJUI, we see encouraging work from multiple talented authorship groups who address a plethora of unmet needs. These papers show the diversity of impact the Editorial team is looking for in BJUI urological oncology submissions.

Prostate cancer, of course, is a common topic for new submissions and subsequent citations. In the field of localised prostate cancer and PSA screening, the recent U.S. Preventive Services Task Force (USPSTF) report was critical of our diagnostic practice results in terms of biopsy related complications and, of course, negative (a.k.a. unnecessary, a term we should drop) biopsies. I must confess that I am still stuck in the tradition of the PSA/DRE as the key driver of my recommendation for a biopsy, and several informal ‘raise your hand’ polls at meetings have produced little movement when asked if anyone has adopted newer calculators that incorporate TRUS volume. Why not change? The numbers certainly seem reasonable: an area under the curve (AUC) of 0.71 for DRE/PSA and 0.77 for the risk calculator. You can even make a crude DRE-volume estimate and improve your odds – AUC of 0.73 without and 0.77 with DRE-volume. If that sounds of interest, then perhaps the study by Carlsson et al. in this issue may interest you with their biomarker panel of kallikreins that can do the same work as the combined clinical efforts and reach AUCs of 0.76 alone, or 0.792 if you still want to add the DRE and TRUS volume. I agree with the authors, that this is perhaps a simpler model, which may allow the physician and patient some time to have a look at their risk of a positive biopsy and make a decision, rather than the idea of the last minute TRUS volume that is supposed to put the brakes on a biopsy at a certain size. With further refinement, we can all learn new thresholds for biopsy that are better selected, and in the future should always be calculated as overall cancers detected/missed and high-grade cancers detected/missed.

In addition, the USPSTF criticised the toxicity of a biopsy, and drug-resistant sepsis is an increasing problem. Symons et al. present an instructive series of transperineal biopsies and results, and they seem to have solved the sepsis problem (0.2%), but must weigh the added cost of anaesthesia, physician time, and no obvious difference in bleeding/other minor complications. I am increasingly interested in re-utilising this technique, which previously was only for third-line saturation biopsies. If you are also convinced, Kuru et al. present a tour-de-force presentation of transperineal technique, terminology, and data collection for a multi-centre collaboration.

Finally, in a must-read special article, Carter expands upon the recent AUA guidelines on PSA screening that were intensely debated, especially the recommendations against routine screening in men aged <55 years. Guidelines are an interesting area of study, and can vary in outcome based upon who is on them and what methodology/objectives are selected. If the guideline is meant to be best clinical practice, than the personnel can certainly be influential. However, if the guideline is meant to emphasise evidence-based recommendations, then in theory, any panel of experts will arrive at a similar place. This is the essential message from Carter, that the revised guidelines are meant to reflect the evidence, and currently we do not have level 1 evidence that involved screening men aged <55 years.

Closing this month in ‘Urological Oncology’, Cindolo et al. report an accuracy/generalizability study of the Karakiewicz nomograms for cancer-specific survival with RCC. These articles are, of course, largely statistical exercises, but very necessary, as we define populations suitable for surgery only vs those in need of neoadjuvant/adjuvant inclusion. Wong et al. conclude the month with an innovative report on office-based laser ablation of non-muscle-invasive bladder cancer using local anaesthesia, mostly in an elderly population. The study protocol allowed photodynamic diagnosis, and includes a cost analysis. The results certainly support continued use in this population where we commonly wish to avoid the morbidity of repeat general anaesthetics.

John W. Davis, MD, FACS
Associate Editor, BJUI

Original publication of this editorial can be found at: doi: 10.1111/bju.12380. BJUI 2013; 112: 531–532.

John Davis, BJUI Associate Editor: Urological Oncology

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John Davis, BJUI Associate Editor for urological oncology, talks about why authors should submit to the BJUI.

The aim of the Journal is to publish high-quality papers with high-impact statements. Along with rapid reviews and publication, BJUI is supporting the impact of papers through social media, such as Twitter and Facebook. The journal will still be printed monthly, but additionally have an exciting web interface.

Editorial: Oncological outcomes: open vs robotic prostatectomy

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John W. Davis and Prokar Dasgupta*

Departments of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA and *Guy’s Hospital, Kings College London, London, UK
e-mail: [email protected]

For men at significant risk of dying from untreated prostate cancer within reasonably estimated remaining life spans, which technique offers the best disease-free survival: open radical prostatectomy (RP) or robot-assisted RP (RARP)? The practice patterns in many countries suggest RARP, but many concerns have been raised about the RARP technique for high-risk disease, including positive surgical margin rates, adequate lymph node dissections (LNDs), and the learning curve. In this issue of the BJUI, Silberstein et al provide a convincing study, short of a randomised trial, that suggests that in experienced hands both techniques can be effective, and that surgeon experience had a stronger effect than technique. In contrast to large population-based studies, this study sought to take the learning curve and low-volume surgeon variables out of the equation by restricting the inclusion criteria to four high-volume surgeons from a single centre. The follow-up is short (one year), and may underestimate the true biochemical relapse rates, and needs follow-up study, but for now offers no difference in relapse rates nor pathological staging outcomes.

Beyond the comparative effectiveness research (CER), Silberstein et al also provide a valuable vision for prostate cancer surgeons using any standard technique. Several recent landmark studies on PSA screening, the Prostate cancer Intervention Versus Observation Trial (PIVOT), and comparisons of metastatic progression between RP and radiation, all indicate the need to shift our practice pattern towards active surveillance for lower risk patients (with or without adjunctive focal therapy, but the former still experimental in our view), and curative therapy for intermediate- to high-risk disease. Such a practice pattern is evident when you compare this study (2007–2010) with a similar effort from this institution (2003–2005) comparing RP with laparoscopic RP (LRP). In the former study, >55% had low-risk disease compared with <35% from the current study. As expected, the present study shows higher N1 stage (9%) and positive surgical margin rates (15%) than the former (7% and 11%, respectively). While erectile function recovery was not presented, the authors noted the familiar reality that patients demand nerve sparing whenever feasible, only 2% in this study had bilateral non-nervesparing and 91% had a combination of bilateral or partial nerve sparing. The number of LNs retrieved has increased from 12–13/case to 15–16, and the authors state that even with nomogram-based exclusion of mandatory pelvic LNDs with <2% risk of N1 staging, this modern cohort had a pelvic LND in 94% of cases, including external iliac, obturator, and hypogastric templates.

We fully concur with this practice pattern, and have recently provided a video-based illustration of how to learn the technique, and early experience showing an increase in median LN counts from eight to 16, and an increase in positive LNs from 7% to 18%. By risk group, our positive-LN rate was 3% for low risk, 9% for intermediate risk, and 39% for high risk. We certainly hope that future multi-institutional studies will no longer reflect what these authors found, in that RARP surgeons are five times more likely to omit pelvic LNDs than open, even for high-risk cancers.

Finally, Silberstein et al and related CER publications leave us the question, does each publication on CER in RP have to be comprehensive (i.e. oncological, functional, and morbidity) or can it focus on one question. Members of this authorship line have published the ‘trifecta’ (disease control, potency, and continence) and others the ‘pentafecta’ (the trifecta plus negative surgical margins and no complications). Indeed, Eastham and Scardino stated in an editorial that ‘data on cancer control, continence, or potency in isolation are not sufficient for decision making and that patients agreeing to RP should be informed of functional results in the context of cancer control’. We feel that the answer should be no, focused manuscripts have their merit and publication space/word limits create this reality. But we should not discount the sometimes surprising results when one institution using the same surgeons and methodologies publishes on the broader topic: the Touijer et al. paper discussed above found the same oncological equivalence between RP and LRP as this comparison of RP and RARP, but also included functional data showing significantly lower recovery of continence with LRP. Nevertheless, the recent body of work in the BJUI now provides a well-rounded picture of modern CER including oncological outcomes, complications, recovery of erectile dysfunction, continence and costs. We feel it is reasonable to conclude that patients should be counselled that RARP has potential benefits in terms of blood loss, hospital stay, and complications (at increased costs), but oncological and functional results are probably based upon surgeon experience.

Abbreviations

CER, comparative effectiveness research; LN(D), lymph node dissection; (RA)(L)RP, (robot-assisted) (laparoscopic) radical prostatectomy

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Editorial: What have we learned from the Partin table update?

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The controversies surrounding a physician’s best treatment strategy advice to an individual patient with clinically localized prostate cancer create a continuing need for advanced statistics. Historically, the Partin tables [1] were one of the first statistical tools that physicians and patients found readily usable. The tables have been updated and always focused on prediction of pathologic stage from standard clinical variables. The next commonly cited/used tool was the Kattan nomogram [2] that carried the prediction the next step to the endpoint of biochemical relapse. By 2008, Shariat et al catalogued over 100 predictive tools published from 1966 to 2007 on various endpoints of prostate cancer [3].

 

 

 

What have we learned from this update of the Partin tables?

  1. The pre-operative grade distribution has shifted up slightly with no change in prostatectomy grade/stage distribution. The authors discuss possible causes such as changes in interpreting the Gleason scoring system, shifts in selection for surgery away from lower grade patients, and a possible plateau in stage migration.
  2. The tables have split off Gleason 3+4, 4+3, 8, and 9–10, and found the latter significantly more aggressive, while Gleason 4+3 and 4+4 are more similar. Gleason 9–10 must have a pattern 5 component >5% and may therefore have more aggressive biology. On the other hand, two cases of prostate cancer may have identical volumes of 4 pattern, but if one adds additional 3 pattern, that additional tumour foci paradoxically lowers the sum to 7, but perhaps not the risk of non-organ confined stage.
  3. In the past, the tables were commonly used to predict pT3 stage, with possible change in management away from surgery as that risk increased. Clearly the literature on surgery for higher risk disease has matured, and augmented by the adjuvant/salvage radiation literature such that it is less likely to use the tables for this reason any more. On the other hand, prediction of N1 disease for the purpose of omitting a lymph node dissection remains a useful tool. In this update, using a <2% cut-off you would essentially omit all node dissections in Gleason 6 with PSA < 10 and cT1c/cT2a, while continuing with a dissection for any dominant Gleason 4 pattern. It is noteworthy that this experience was largely based upon standard templates, and those advocating extended templates will find these N1 rates too low. Indeed, when our center adopted the extended template using a robotic technique, the N1 rate for high-risk disease was 39% and 9% for intermediate risk [4]. Moving forward, what tools do we need to provide useful statistics to our patients? Updating old tools with more contemporary patient cohorts is certainly a worthy exercise. Multicentre study based tools will be required for endpoints such as positive surgical margins, quality of life, biochemical recurrence, and other endpoints that may be significantly affected by the experience of the treating physician. Beyond this, the next step should be adaptive nomograms that update in real time rather than en masse every 4–5 years [5].

John W. Davis
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

References
1 Eifler JB, Feng Z, Lin BM et al. An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011. BJU Int 2013; 111: 26–33
2 Kattan MW, Eastham JA, Stapleton AM et al. A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst 1998; 90: 766–71
3 Shariat SF, Karakiewicz PI, Roehborn CG, Kattan MW. An updated catalog of prostate cancer predictive tools. Cancer 2008; 113: 3075–99
4 Davis JW, Shah JB, Achim M. Robot-assisted extended pelvic lymph node dissection (PLND) at the time of radical prostatectomy (RP): a video-based illustration of technique, results, and unmet patient selection needs. BJUI 2011; 108: 993–8
5 Vickers AJ, Fearn P, Scardino PT et al. Why can’t nomograms be more like Neflix? Urology 2010; 75: 511–3

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