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This image is taken from Ramos et al. assessing the validity of dry laboratory exercises for robotic training.
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Whilst extended pelvic lymphadenectomy has become part of standard care in select patients undergoing radical prostatectomy at some centres, it is not universally accepted or performed and remains controversial, so why is this? The most common reasons cited for not performing a node dissection, or at least an extended node dissection, include lack of proven therapeutic benefit and the increased operative time and risk of complications. But do we really need to show a survival benefit to accept the role of extended pelvic lymphadenectomy for patients undergoing radical prostatectomy? It would take a randomised trial run over at least a decade, thousands of patients and untold cost to prove or disprove. Although randomised trials can be invaluable in assessing some aspects of medical or surgical care, they are not always appropriate or even desirable for surgical outcomes as O’Brien et al eloquently illustrated. What’s more, results from RCTs in surgery can be misleading – consider the Prostate Cancer Intervention Versus Observation Trial, in which overall survival at a median follow-up of 10 years was approximately 50% in both arms. This is equivalent to the overall survival in the observation arm of Messing’s trial, in which virtually no patients died of non-prostate cancer causes and contrasts starkly with the current life expectancy of 65 year old males in Australia of 20 years. Patients in PIVOT weren’t living long enough to die from prostate cancer!
There is no doubt that for accurate nodal staging, an extended lymphadenectomy is currently the gold standard, as reflected in the EAU guidelines on prostate cancer. Two very elegant trials in recent years assessed the performance of similar templates in terms of staging accuracy and concluded that a modified extended template struck the right balance between accuracy and risk of complications. Joniau et al, showed in a prospective cohort of 74 patients, around half of whom were lymph node positive, a modified extended template including the pre-sacral nodes had a staging accuracy of 97% and removed 88% of positive nodes. Omitting the pre-sacral nodes accurately staged 94% of patients and removed 76% of positive nodes. Mattei et al concluded that their modified ePLND removed approximately 75% of “sentinel” nodes in a prospective series of 34 node negative patients. Whether a “modified” ePLND or “plain” ePLND is performed, the staging accuracy is significantly better than a “standard” PLND, which omits the nodes around the internal iliac vessels and according to Joniau et al would accurately stage 76% of patients and remove only 29% of positive nodes. A “limited” node dissection, removing only the tissue within the obturator fossa performed even worse, staging 47% and removing just 15% of positive nodes.
From Mattei et al European Urology 2008, 53:118-125
But what is the real value in accurate nodal staging? Does it change patient management? The Messing trial showed that node positive patients who received adjuvant hormone therapy had improved CSS and OS compared to node positive patients observed until clinical progression. The study, however, has limited application to current real life patient management. Whilst patients with high volume nodal disease are likely to benefit from adjuvant hormone therapy, some patients with node positive disease, particularly those with micro-metastatic disease, will not suffer biochemical progression let alone clinical progression and therefore may not warrant ADT. Furthermore, most patients will be commenced on hormone therapy according to specific PSA criteria long before clinical progression. Despite these apparent weaknesses, the CSS and OS are remarkably similar to many retrospective series of node positive patients outside trials and managed in “real life”. Bader and Schumacher presented series of 92 and 122 node positive patients respectively, none of who received adjuvant hormone therapy. Ten year CSS for both of these series was approximately 60% and 10-yr OS in the Schumacher cohort was 53%, almost identical to the 10-yr OS in the Messing trial. Conversely, a number of retrospective series of node positive patients in which all, or almost all patients received AHT, 10-yr CSS ranged between 74-86% and 10-yr OS was 60 – 67%. These outcomes are similar to the AHT arm in Messing’s trial, in which 10-yr CSS was 85% and 10-yr OS was 75%. This is far from compelling evidence in favour of AHT in node positive patients, but it is certainly food for thought.
Rather than treat all node positive patients equally, however, we should be more sophisticated in our approach. Briganti and Schumacher have shown that patients with 1 or 2 positive lymph nodes have better 10-yr CSS than patients with 3 or more positive nodes whether they receive adjuvant hormone therapy or not. In Schumacher’s series, 10-yr CSS was 72-79% for patients with 1 and 2 positive nodes, versus 33% for patients with 3 or more positive nodes, without AHT. In Briganti’s series, 10-yr CSS for patients with 3 or more positive nodes was 73% and they were almost twice as likely to die from prostate cancer than those with fewer than 3 nodes positive. All patients received AHT. Perhaps then, we should consider patients with higher volume nodal disease on extended pelvic lymphadenectomy for immediate adjuvant hormone therapy, whilst those with micro-metastatic disease may be suitable for observation until predetermined PSA criteria are reached.
Beyond the staging benefit, Jindong et al recently published a prospective, randomised trial showing a BCR free survival benefit for patients undergoing extended versus standard pelvic lymphadenectomy. With a median follow-up of just over 6 years, intermediate risk patients undergoing ePLND had a 12% absolute reduction in biochemical recurrence (73.1% v 85.7%) and high risk patients more than 20% (51.1% v 71.4%) compared to those undergoing a standard node dissection. This may eventually translate into a survival benefit, or at least a clinical progression benefit, but in this cohort of patients, a reduction in biochemical recurrence means a reduction in the numbers requiring salvage radiation therapy and salvage androgen deprivation and the consequent side-effects and complications of these treatments.
It is clear the complication rate following ePLND is higher than with sPLND or no node dissection, but a recent review revealed the difference is accounted for by an increase in the incidence of symptomatic lymphoceles, most of which resolve with conservative management. Ureteric, nerve and major vascular injuries are rare. This would appear to be a much more acceptable complication profile than that following salvage radiotherapy, or androgen deprivation. Although uncommon, membranous urethral stricture following salvage radiation often confers debilitating and enduring morbidity. Continence and potency rates also suffer, not to mention bowel toxicity. A 20% absolute reduction in biochemical recurrence may also swing the pendulum away from adjuvant radiation in high risk disease, benefiting even more patients.
Proving a survival benefit with level 1 evidence is the holy grail of medical and surgical trials, but it is not the only outcome to consider. Biochemical recurrence following radical prostatectomy carries significant psychological burden and salvage therapies can carry significant morbidity. Disease recurrence is most common in the high risk population and there is now level 1 evidence of a real benefit to these patients when ePLND is included as part of their surgical care.
Dr Philip E Dundee
Epworth Prostate Centre and The Royal Melbourne Hospital
T: @phildundee
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This image from Carthon et al. shows a patient with penile cancer.
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Two different prostate pathologies are shown. Images from Korkes et al. BJUI 2014; 113: 822–829. doi: 10.1111/bju.12339
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I was surprised at the referral in the first place, but baffled after seeing the patient in the flesh. It was someone else’s clinic, and the note read that this 94 year-old man on androgen deprivation for asymptomatic low volume metastatic prostate cancer for many years had a climbing PSA. About 8. Please discuss combined androgen blockade with him. I began the talk about how combined blockade has a pretty weak benefit at the best of times, and that in a 94 year-old it almost certainly would not make him live any longer. He was asymptomatic, so he would not feel any better, and he may have a worsening of his side effects. I wrapped it up by telling him he was old enough to make his own decisions about his treatment, and if he didn’t want another pill to take, he could certainly say no. He said yes. I clarified the points about limited or no benefit, and possible exacerbation of side effects. He said if it would give him a few more years, he’d take it. I told him it wouldn’t. He wanted it anyway. I could not promise the treatment would not make him live any longer, and that was good enough for him. At the end of the consultation he was well counseled, and had made his decision. You might think of an 80 year-old you have seen who seemed more like a 60-year old, and think I was being unfair to the man, but I can confirm he was a 94 year-old who seemed very much to be 94.
I tend to assume that when people get to a certain age, they have come to terms with a few things, including death. This is not always the case, and I think running from death is becoming more popular. While research confirms that doctors have few illusions about treatment leading up to their own demise, and plan to refuse much of it, laypeople are hungry for all the invasive treatment they can get. As doctors, we don’t always help with this. We have pills and procedures that make statistically significant improvements in cancer specific survival, and what cancer sufferer would say no to that? We spend a lot more time studying how to hold failing anatomy together than we do learning to let entropy take its course. We have treatments that hint at immortality, nobody needs to die of Condition X anymore, now that we have Drug Y. What if this patient in front of us is the one in a hundred that has a durable remission? What if we kill them through inaction? What about the guilt-ridden estranged son who wants “Everything Done”?
Popular media have kept up a sustained and determined campaign for cardiovascular resuscitation in particular. Having an intelligent, sensitive, pragmatic talk to a family about not resuscitating the palliative patient due to the invasive, undignified nature of resuscitation for a virtually negligible chance of durable success is not as convincing as James Bond being defibrillated in his Aston Martin.
What is the definition of “good survivor” if not continuing to drink, gamble, and assassinate day zero post-resuscitation? Sadly, days or weeks of vegetative decline is much more common.
So what of the 94 year-old, who has already outlasted his cohort’s life expectancy by over 20 years? Who lived through two world wars, the rise and fall of the Soviet Communist state, the invention of Rock ‘n’ Roll, space flight, and electric foot spas? Objectively, he made an informed decision about his health care, prioritizing his values and concluding that the chance of increased quantity, however tiny, trumped quality. I can’t help think that in reality he kidded himself that he was beating death once again. He had evaded those cruel icy fingers, and secretly maybe thought he could live to a hundred and fifty. If he was my Grandpa, maybe I could have talked to him about embracing the end as a part of the natural cycle; not fearing, but accepting. But then, I was just his doctor.
Jim Duthie is a Urological Surgeon/Robotic Surgeon. Interested in Human Factors Engineering, training & error, and making people better through electronic means. Tauranga, New Zealand. @Jamesduthie1
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How many of you have already had a patient get in touch about this latest scare? As one expects nowadays, I first heard about this paper on Twitter within a few minutes of it being published, but it wasn’t long after that a recent patient of mine rang my rooms to challenge me about the reassurance I had given him only last week about the lack of increased risk of prostate cancer, which he had specifically asked me about. And of course since then, we have had headlines in the mass media all over the world alerting us to the results of this 24-year study that suggests that vasectomy confers an increased risk of not just prostate cancer, but high-grade prostate cancer in men undergoing vasectomy. Here are just some of the headlines:
So what are we to make of all this? The private vasectomy counselling has always been a challenging area due to the well documented possibilities of early and late failure, and also of the ever present issue of chronic scrotal pain. And while the area of prostate cancer risk has been raised previously, I must say I have always felt comfortable saying that on balance, the increased risk of developing significant prostate cancer following vasectomy proved to be minimal. “Don’t worry about it” was my typical blithe reassurance. Do I have cause to change my advice now?
Let’s look at this paper from Siddiqui et al. The data is taken from the well-known Health Professionals Follow-up Study (HPFUS), which originally enrolled almost 50,000 men aged between 40 and 75 back in 1986. Of these, about 12,000 (25%) underwent vasectomy and 6000 of these (12.2% of population) were subsequently diagnosed with prostate cancer over the 24-year follow-up period. Of these, 811 (1.6%) died of prostate cancer. The authors calculate that vasectomy was associated with a small overall increase in the risk of prostate cancer (RR = 1.10). However the headlines are coming from the higher relative risk of 1.22 among men subsequently diagnosed with high-grade prostate cancer (Gleason 8 to 10). Also, vasectomy appeared to confer a higher relative risk (1.19) of actually dying of prostate cancer or developing distant metastases compared to men who did not undergo vasectomy. It is these findings that vasectomy appears to confer not just an increased risk of prostate cancer, but an increased risk of developing aggressive or a lethal prostate cancer, which has provoked some concern.
This topic is not new and other studies have shown that this risk does not exist or at best, the risk is minimal and the quality of evidence not good enough to change practice. Does this current paper change all that? It will certainly change the nature of counselling for men considering vasectomy as there may well be a case to consider. As the population of men presenting for vasectomy are not a typical population who would be counselled about the early detection of prostate cancer, perhaps this other difficult counselling area also needs to be broached.
HELP!!!!
Declan Murphy is a urologist at Peter MacCallum Cancer Centre in Melbourne, Australia, and Associate Editor at BJUI. Twitter @declangmurphy
This month’s International Urology Journal Club (@iurojc) truly engaged a global audience with participants from ten countries including author Thomas Herrman (@trwhermann) from Hannover, Germany. A landmark 2000 followers was reached during July, nearly two years since @iurojc’s conception in late 2012. In fact, since this time nearly 1100 people have participated in the journal club from around the world.
Bladder cancer was up for debate for the first time this year and @iurojc trialled the discussion of two complementary articles recently published online ahead of print in the World Journal of Urology. The first article provided an update of the current evidence for transurethral Ho:YAG and Tm:YAG in the endoscopic treatment of bladder cancer, and the second was a randomised controlled trial (RCT) comparing laser to the gold standard transurethral resection of bladder tumour (TURBT). Authorship groups were from Germany and China respectively; our Chinese authors unfortunately unable to join the dialogue due to restriction on all twitter activity in the country.
Initial conversation focussed on the methodology, results and limitations of the RCT, however this soon extended to a more general discussion around the current difficulties with the diagnosis and management of bladder cancer and the pros and cons of using laser for this purpose. Key themes debated over the 48-hour period included the importance of accurate staging, current standards of TURBT, advantages of en bloc resection and the learning curve, cost and usefulness of laser technology.
Both studies reiterated one of the major goals outlined in the EAU guidelines for non-muscle invasive bladder cancer (NMIBC), to achieve correct staging with inclusion of detrusor muscle and complete resection of tumours. This is important in limiting second resection and consequently has a resulting cost offset. In the review article, only 3 studies commented on staging quality and another two commented that laser was suitable for staging but did not specify if detrusor muscle was identified.
@ChrisFilson and @CBayneMD expressed their concern over the RCT by Chen and Colleagues
@linton_kate astutely pointed out another limitation
and author of the review article @trwherrmann summed this up nicely
In the RCT by Chen et al. there was a significantly greater number of pT1 tumours detected with laser than TURBT, the authors suggested this might be due to better sampling. It remains unclear if this would impact on management and this did not enter the arena for discussion during this @iurojc.
Many argued that TURBT techniques and practices should be optimised before newer techniques are introduced.
‘En bloc’ was touted as the new trendy word in endourology. EAU guidelines recommend en bloc resection for smaller tumours. The articles suggested that en bloc resection of bladder tumours should provide more accurate staging however conclusive data is missing to substantiate this in the current literature.
@DrHWoo discussed potential advantages of the laser technique
@linton_kate pointed out that en bloc resection is not limited to the laser technique
Further to this, the lack of obturator nerve reflection with laser was emphasised in the RCT. Obturator kick was noted during TURBT in 18 patients and none during laser resection, however none of these patients suffered bladder perforation. The significance of this was debated and usefulness of obturator block in this context discussed.
The pendulum seemed to the swing out of favour of laser during the discussion, with several limitations outlined including reduced ability for re-resection, cost and the presence of a learning curve.
Regarding additional cost, the host rebutted
The flow of academic dialogue was interrupted midstream (pardon the pun) by a light-hearted discussion around the ergonomics of TURBT.
Below are some of the key take home messages that arose from the usual culprits in this month’s @iruojc discussion
Kindly author @trwherrmann invited us to his upcoming en bloc resection workshop. Keep an eye out for this.
@iurojc would like to thank Prostate Cancer Prostatic Diseases who have kindly provided the prize for this month which is a 12 month on line subscription to the journal. @nickbrookMD’s made efforts to sway the vote his way.
Whilst usually the Best Tweet Prize is reserved for some incisive comment, the repeated complaints from @nickbrookMD for his failure to ever win the Best Tweet prize has seen for the first and final time that the @iurojc has bowed to pressure. Congratulations to @nickbrookMD for finally having made it with the above tweet.
If you haven’t tuned into @iurojc, follow future journal club discussions via the hashtag #urojc, on the first Sunday/Monday of each month.
Dr Marnique Basto (@DrMarniqueB) is a USANZ trainee from Victoria who recently completed a Masters of Surgery in the health economics of robotic surgery and has an interest in SoMe in Urology.
Image from Park et al. BJUI 2014; 113: 864–870. doi: 10.1111/bju.12423
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June 27 to July 1, 2014 saw close to 900 Canadian urologists & associates come together in the country’s most easterly city – St John’s, Newfoundland – for the 69th annual Canadian Urological Association meeting (https://www.cua.org/). As ‘Newfies’ have a well-established reputation in our country for their extreme friendliness, unique traditions and ability to throw one hell of a party, it was a highly anticipated four days!
The meeting kicked off on Friday with various pre-CUA affiliated meetings, such as the Executive Committee Meeting, CAGMO and CUOG meetings. An optional Advanced Laparoscopic and Robotic Urology Skills Course was held over two days on Thursday & Friday. Also on Friday, the incoming final-year residents from across Canada began the annual senior resident retreat (CSUR), which included excellent sessions with Dr Gerald Brock on resident involvement with the CUA and Dr Robert Siemens on critically reviewing the literature. We residents were also lucky enough to be invited to enjoy a lobster dinner and beer tasting at YellowBelly Brewery & Public House – one of the oldest structures in North America dating back to 1725. Sitting at the intersection of Water St & George St, this impressive stone gastropub is the location where the ‘Great Fire of 1892’ was finally extinguished. The evening, for most, carried on to George St – the street with the most bars & pubs per square foot of any street in North America!
The CSUR course finished on Saturday after a great half-day review of urodynamics with Drs Greg Bailly and Jerzy Gajewski. Further affiliated meetings were held including the 2nd CUA Multidisciplinary Meeting for members of CAGMO, CUOG, GUROC and CNUP. An instructional course entitled Better Botox – from patient prep to injection protocols, was also offered to attendees. The major part of the CUA meeting (https://cuameeting.org/index.php/en/) began officially on Saturday afternoon with the first two Educational Forums – both on the topic of Castrate Resistant Prostate Cancer with tips and tools for the Canadian urologist to improve care of patients with CRPC. This included presentations from Drs Neil Fleshner, Ricardo Rendon, Alan So, Lorne Aaron, and Geoff Gotto. Here it was stressed that urologists should be comfortable as the primary physician giving medical treatment for CRPC. Saturday evening held the conference welcome reception – always a fantastic reunion – and unmoderated poster session.
Sunday morning started with a Welcome Address from CUA President Dr Peter Anderson, followed by the first State-of-the-Art Lecture on the role of medical management of nephrolithiasis in the age of lithotripsy with a focus on AUA Guidelines – an excellent overview presented by Dr Glenn Preminger of Durham, NC. A similarly themed Educational Forum covering medical management of stones in a case-based approach followed this; faculty included Dr Preminger as well as Drs Sero Andonian, John Dushinski and Jason Lee. The second State-of-the-Art Lecture saw Dr Surena Matin from Houston, TX present on neoadjuvant chemotherapy for UTUC, where he discussed benefits such as taking advantage of pre-op renal function and results showing both down-staging and a survival advantage. An Educational Forum followed on strategies for upper tract surveillance in urothelial carcinoma, management of post-op urinary diversion complications and contemporary use of biomarkers by Drs Matin, Adrian Fairey and Alan So. In the afternoon, Dr Eric Rovner from Charleston, SC gave a State-of-the-Art Lecture on SUI and slings. He presented an algorithm using the best available evidence on appropriate selection of sling type and reiterated that urodynamic studies are not necessary pre-operatively in the ideal index SUI patient. A forum entitled ‘Innovations in Functional Urology’ had Dr Catherine Dubeau from Worcester, MA joining Drs Sender Herschorn and Eric Rovner to discuss female SUI, post-prostatectomy incontinence and management of elderly patients with OAB. Dr William Gee from Lexington, KY then gave the address of the AUA President-elect, which was followed by the CUASF lecture by Dr Ron Kodama who discussed education & evaluation of residents. The late afternoon took a pediatric turn including a lecture by Dr Anthony Caldamone from Providence, RI on ‘Putting the Undescended Testicle in its Place!’ A point/counterpoint followed between Dr Caldamone and Dr Martin Koyle on the ideal surgical management for congenital duplication anomalies. The day wrapped up with podium sessions on pediatric urology, endourology and surgical education.
The annual CUA ‘fun night’ took place Sunday evening and was entitled Rally in the Alley. This was a very well-organized pub crawl that saw roughly 500 people split into 5 groups, each with a signature scarf colour and a different instrument to follow. For example, if you were in the blue bagpipe group, you put on your blue scarf and followed the bagpiper who would lead from pub to pub on George St (https://www.georgestreetlive.ca/). With one minute left before switching locations, you’d hear the bagpiper start up again – the signal to down your drink and move on! The five groups each did the pubs in a different order so that there was no overlap until everyone convened at the same final destination. In addition, each pub had a very ‘Newfie’ activity for everyone to try – including Irish Dancing, singing Newfie songs (‘we’ll rant and we’ll roar like true Newfoundlanders!’), and of course getting ‘Screeched in’ – a Newfoundland tradition involving reciting a poem, downing a shot of the cheap high alcohol spirit and kissing a freshly caught cod! It was an awesome night that truly gave all the ‘come from away’ folks a glimpse of life in Newfoundland (and perhaps a hangover to boot).
Monday was another full day, starting with moderated poster sessions on prostate cancer, pediatrics and sexual health and infertility. Next, Drs Paul Johnston and Stephen Steele gave a brief overview of clinical pearls that could change your practice. A State-of-the-Art Lecture by Dr Daniel Lin from Seattle, WA followed; he discussed selection of patients and outcomes in active surveillance. An Educational Forum came after this with Drs Laurence Klotz, Daniel Lin, and Chris Morash covering prostate biopsy and active surveillance.
The afternoon kicked off with the EAU Address from Dr Andrzej Borkowski of Warsaw, Polland, followed by a State-of-the-Art Lecture from Dr Mark Speakman of Somerset, UK on LUTS/BPH. Dr Speakman’s lecture was both highly entertaining and informative, and he stressed the importance of exercise and a healthy lifestyle in preventing LUTS progression. Drs Speakman, Gerald Brock, Sender Herschorn, and David Staskin of Boston, MA then gave an educational forum on prevention and management of LUTS/BPH. Dr Laurence Levine then discussed treatment of Peyronie’s Disease in the seventh State-of-the-Art Lecture, giving a useful summary on which type of surgery to choose depending on patient factors such as penile length and erectile function. An Educational Forum finished off the afternoon and covered the often-dreaded topic of Management of Scrotal Pain. Drs Keith Jarvi, Jay Lee, and Laurence Levine emphasized the importance of a multi-disciplinary approach in dealing with this type of chronic pain, and created a systematic approach that most urologists could utilize to avoid feeling helpless in dealing with this disorder. Dr Levine also showed promising results of micro-denervation of the spermatic cord for patients with refractory scrotal pain and good response to a cord block.
Monday evening held the annual President’s Reception. At the back of the room was a bar made entirely from carved ice – proving that Newfies really do love their icebergs. You can even drink beer made using 25,000-year-old iceberg water harvested from a Newfoundland ‘berg! These huge ice formations can be seen, along with whales, from the very picturesque, well-worth-the-climb, Signal Hill in St John’s. The reception also saw Dr Peter Anderson present Dr Jerzy Gajewski with the CUA Lifetime Achievement Award; clearly a surprise to Dr Gajewski but a well-deserved honour. Dr Anderson then handed over the reigns as CUA president to Dr Stuart Oake, who gave a sneak preview of what to expect in Ottawa for the annual meeting in June of 2015.
The final day of the conference started with a smorgasbord of topics in six different moderated poster sessions. Drs Bobby Shayegan and Keith Rourke covered ‘clinical pearls that could change your practice’ – a collection of useful tidbits collected during the various lectures and forums throughout the 4-day conference. Dr Derek Puddester gave a State-of-the-Art Lecture on physician health & wellness, reminding us all to practice mindfulness often. The final State-of-the-Art Lecture was by Dr Axel Heidenreich from Aachen, Germany, who covered the role of radial prostatectomy in the management of locally advance and metastatic prostate cancer. The last educational forum was on optimizing patient outcomes in kidney cancer – a session given by Drs Heidenreich, Rodney Breau, Steven Pauler and Simon Tanguay.
As the conference came to a close, staff and residents from across the country sat in the St John’s airport and reminisced about the week’s events. It was not only a great educational opportunity that many took advantage of; it was also a relaxing reunion for the relatively small group of urologists that are spread out across this vast country. Kudos to Dr Anderson and the Local Organizing Committee lead by Chair Dr Chris French, for putting on a meeting to remember. Newfoundland is certainly a beautiful and unique corner of our great country, and anyone would be wise to pay ‘the Rock’ a visit (https://www.newfoundlandlabrador.com/). Finally, if there is anywhere better to spend Canada Day than the charming easterly city of St John’s Newfoundland, it’s Ottawa, Ontario. So mark your calendars, as everyone is invited to the CUA meeting in Ottawa, June 27-30 2015! See you there!
Ellen Forbes is a Urology Resident at the University of Alberta. Twitter: @DrElForbes