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Another good week for radical prostatectomy

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

Radiation within urology: challenges and triumphs

As gatekeepers urologists remain at the frontline of urological oncology in a position of trust that they have held since Charles Huggins, Nobel Laureate in Urology, pioneered the use of hormone manipulation to treat prostate cancer. However, radiation within urology is an important adjunctive, palliative and even primary treatment method for many urological malignancies. However, within many spheres, particularly internationally regarding prostate cancer, tensions appear to have been simmering between urologists and radiation oncologists. Fortunately, this does not appear to be the case in Australia and New Zealand but it is an important time to reflect on such issues as we move ever forward in the multimodality era.

In the USA the use of self-referral by urologists of men for adjuvant radiotherapy (RT) has come under scrutiny. Some urology groups have integrated intensity modulated RT (IMRT), a RT treatment carrying a high reimbursement rate, into their practice. This was highlighted in a recent New England Journal of Medicine article where the rate of IMRT use by urologists working at National Comprehensive Cancer Network centres remained stable at 8% but increased by 33% among matched self-referring urology groups [1]. This study has been criticised for bias but nonetheless captured political and academic attention. Certainly this situation has not arisen in our hemisphere but it remains important we think critically of what treatments we offer our patients and ensure patient’s best interests are maintained.

Clearly more research is required as to who should be receiving adjuvant RT and at what stage. In the latest issue of the BJUI USANZ supplement we highlight the Radiotherapy – Adjuvant vs Early Salvage (RAVES) trial for prostate cancer biochemical failure and high-risk disease [2]. There is no doubt this is an important trial because to date we have been unable to establish exactly which patients should receive adjuvant RT and when. Recruitment has been challenging as patients doing well after surgery often do not want additional treatment and a very small subset who are still recovering want to be enrolled but due to timing missing eligibility. Enthusiastic patients also may demand treatment rather than be randomised. Critics would also argue that the trial can never really answer the question because many men not requiring adjuvant RT will receive it [3]. Ongoing support of all parties should achieve accrual and in time, robust data. Excitingly imaging with MRI and other modalities will ensure further trials to assist in identifying disease in the salvage setting making choices easier based on more objective data [4].

 

Read the USANZ Supplement

Consumerism has driven robotic surgery [5] and is doing the same for RT but descriptions of treatment would be better placed to remain generic. The use of the term ‘radiosurgery’ has highlighted the shift away from the term ‘radical radiotherapy’. Of course the term ‘robot’ has become synonymous with radical prostatectomy but the ‘radical’ contribution remains and interestingly the term ‘robot’ has been trialled by radiotherapists: ‘image-guided robotic radiosurgery’ or its other more commonly used term Cyberknife® (Accuracy Incorporated, Sunnyvale, CA, USA). Certainly this would be more accurately known as stereotactic body RT (SBRT). It is these terminology changes and continual shifts in treatment regimens that rankles many, with the old argument that RT treatment was done with inferior technology so results should be ignored receives disproportionate use at conferences. All groups need to acknowledge treatments have improved rather than disowning data from older treatment regimes. On the counter side one example from brachytherapy [6] concluded that despite the hype of improving dosimetry and reducing complications, the preoperative condition regarding erectile function and LUTS are the most important factors regarding postoperative outcome. This is almost certainly true for surgery as well. Comparison of side-effects appears unfair with grading of radiation toxicities more lenient than Clavien listed complications – an even playing field for comparison of complications is warranted.

Multimodality treatment for high-risk disease is becoming the standard of care. Urologists are beginning to embrace this regime of planned surgery with likely RT and ultimately systemic therapies. However, radiation oncologists often prefer to use radiation and hormonal manipulation and consider this ‘modified monotherapy’. Some men receive different modes of RT with concerns this leads to significantly more complications and in combination with androgen deprivation comes with all of the secondary effects of such therapy. An ideal study for such high-risk patients would randomise men to RT and androgen deprivation vs a graded multimodality treatment starting with surgery and then progressing to RT and systemic therapies when required (as some men will have T2 or T3a disease with clear margins that can be observed for a PSA rise necessitating treatment).

Complications do develop after any therapy and urologists are expertly placed to deal with them. Yet, there is a belief that RT and its long-term effects are real and these are often underplayed. This is contributed by a paucity of follow-up data beyond 5 years with primary RT. Major problems from surgery are generally able to be repatriated. However, the same may not be stated for RT complications: cystitis, stricture disease, permanent catheter drainage and chronic pain syndromes although uncommon, are not rare events and not easily remedied due to the altered tissues. Urologists are able to assist with these conditions but some feel that their efforts are unrecognised and that they share too much of the burden from somewhat surprised patients when situations are not able to be satisfactorily resolved. This reinforces the involvement by enthusiastic urologists with the patient selection and follow-up of brachytherapy and even other RT treatments being the cornerstone for ideal patient management and success.

Other areas worthy of engagement are with patients who develop a recurrence after RT treatment where the available data are sparse, making a decision even more difficult [3]. The perceived reluctance to refer RT failures to urologists in a timely fashion meaning many men are not offered salvage surgery or other options [7]. Occasionally urologists do the same with surgical failures but with multi-disciplinary teams, this is a rare event.

Communication remains a key to a multidisciplinary approach. Against the successes and strains, there are newer developments that will conspire to bring teams closer together, such as newer systemic therapies and the consideration of RT in men with oligometastatic disease. Also, based on Surveillance, Epidemiology and End Results (SEER) data, it appears that patients with limited metastatic disease may benefit from having treatment of the primary disease with a significant decrease in mortality (slightly more pronounced with surgery than radiation) [8]. This will ensure further debate on how far we stretch our primary treatment boundaries for the betterment of patients. Finally, use of fiducial markers and spacers will hopefully minimise morbidity and these are discussed in this supplement [9].

Just like any long-term relationship, the balance will shift at times and there has to be give and take on both sides. Many of the points in this editorial could be switched the other way with urologists at fault, so we must always be careful to be global, and not focal in our approaches. With everyone working together we have improved outcomes and survival of many with many urological malignancies. Overall, there is still harmony but room for even greater communication and collaboration as we strive towards better outcomes in future decades.

Nathan Lawrentschuk
University of Melbourne, Department of Surgery and Ludwig Institute for Cancer Research, Austin Hospital and Peter MacCallum Cancer Centre, Department of Surgical Oncology, Melbourne, VIC, Australia

Read the USANZ Supplement

References

  1. Mitchell JM. Urologists’ use of intensity-modulated radiation therapy for prostate cancerN Engl J Med 2013; 369: 1629–1637
  2. Pearse M, Fraser-Browne C, Davis ID et al. A Phase III trial to investigate the timing of radiotherapy for prostate cancer with high-risk features: background and rationale of the Radiotherapy – adjuvant versus Early Salvage (RAVES) trialBJU Int 2014; 113: 7–12
  3. Chen RC. Making individualized decisions in the midst of uncertainties: the case of prostate cancer and biochemical recurrence. Eur Urol 2013; 64: 916–919
  4. Thompson J, Lawrentschuk N, Frydenberg M, Thompson L, Stricker P. The role of magnetic resonance imaging in the diagnosis and management of prostate cancer. BJU Int 2013; 112 (Suppl. 2): 6–20
  5. Alkhateeb S, Lawrentschuk N. Consumerism and its impact on robotic-assisted radical prostatectomy. BJU Int 2011; 108:1874–1878
  6. Meyer A, Wassermann J, Warszawski-Baumann A et al. Segmental dosimetry, toxicity and long-term outcome in patients with prostate cancer treated with permanent seed implantsBJU Int 2013; 111: 897–904
  7. de Castro Abreu AL, Bahn D, Leslie S et al. Salvage focal and salvage total cryoablation for locally recurrent prostate cancer after primary radiation therapyBJU Int 2013; 112: 298–307
  8. Cheng J. Would you really do a radical prostatectomy on a man with known metastatic prostate cancer? BJU Int BLOG posted 09 December 2013. Available at: https://www.bjuinternational.com/bjui-blog/would-you-really-do-a-radical-prostatectomy-on-a-man-with-known-metastatic-prostate-cancer/. Accessed January 2014
  9. Ng M, Brown E, Williams A, Chao M, Lawrentschuk N, Chee R. Fiducial markers and spacers in prostate radiotherapy: current applicationsBJU Int 2014; 113: 13–20
 

Text and the city

From the spectacular rise of bitcoin to the passing of Mandela and Thatcher, the horrors of Boston and Nairobi to the resignation of the Pope, the breakthroughs in human stem cell cloning [1] to the promise of medical three-dimensional printing [2] – our personal and professional lives are influenced by global and technological events in a way that seemed unimaginable just a few decades ago.

The clinical and scientific research community has never been more international as it is now. Publications of researchers from China and India in prestigious Science Citation Index (SCI – maintained by Thomson Reuters) journals has increased steadily, with Chinese papers accounting for 9.5% of all published in 2011 from a negligible figure a decade ago, second only to America [3].

At the BJUI, we are proud to be able to facilitate and receive the best high-quality research from any part of the world. Recent efforts in developing our print, online and social media channels have allowed us to disseminate this work to a greater worldwide audience than ever before. We are affiliated with the Urological Associations in Britain, Ireland, the Caribbean, India, Hong Kong and Australia and New Zealand. The ‘I’ in BJUI is something we work hard to foster.

In celebration of the global reach of the BJUI, all our 2014 covers will showcase the city or country of origin of our key feature within the issue. We wanted to reflect the sense of community that runs through the competitive, yet closely linked international network of research teams that are published within the BJUI. We hope that you will appreciate the stunning visual impact that complements the topical diversity, superlative quality and intellectual rigour of each new issue of the BJUI in 2014.

The article of the month in this issue features the androgen receptor and prostate cancer – a reflection of a life time of translational research from David Neal’s group at Cambridge [4]. Our Editor-in-Chief was inspired by the Zacchary Cope lecture at The Royal Society of Medicine, London and convinced David to send his paper to the BJUI. Furthermore during the annual meeting of the BAUS section of Academic Urology this January in Cambridge, it became obvious that punting was just as iconic as the awe inspiring university buildings in this beautiful city.

Tet Yap
Royal College of Surgeons of England, London, UK
Director of Glass Magazine

References

  1. Tachibana M, Amato P, Sparman M et al. Human embryonic stem cells derived by somatic cell nuclear transferCell 2013; 153: 1228–1238
  2. Fischer S. The body printed. IEEE Pulse 2013; 4: 27–31
  3. Scientific Research: Looks good on paper. © The Economist Newspaper Ltd, London (28 September 2013)
  4. Lamb AD, Massie CE, Neal DE. The transcriptional programme of the androgen receptor (AR) in prostate cancerBJU Int 2014; 113: 361–369
 

Surgery or Radiation in Prostate Cancer?

I am sure many of you are familiar with the clinical situation I see every week of a man with newly-diagnosed prostate cancer asking me about his options. While we steer many men with low risk prostate cancer towards surveillance nowadays, for those with intermediate or high risk disease intervention is usually their best option, especially if they have a long life expectancy. This gives us the dilemma of whether to recommend surgery or radiotherapy.

In Oxford, we have a long and pioneering history of evidence-based medicine, and I lament the lack of RCTs in this field. The only one, ProtecT, which is being led also by Oxford, will not report before 2016, and will at least in part be subject to volunteer bias. Now, the question of surgery or radiotherapy for prostate cancer is not a new question. Millions of men have undergone these treatments across the globe and over the decades, and many other investigators have evaluated this question.

Most of these previous studies suggest that surgery in indeed superior but the main problem with them is inadequate control for selection bias (what we term in the trade as confounding by indication) – i.e. that men undergoing surgery are fitter and have better prognosis from their cancer point of view than men undergoing radiotherapy, and thus it’s not a fair comparison. Another problem with these previous studies is that the datasets used are not very comprehensive – not all men are included, and we don’t know all their important risk factors. All this makes it difficult to be confident in their results.

What is different about the BMJ study (https://www.bmj.com/content/348/bmj.g1502) is that the dataset and the statistics were top-notch. More than 98% of men diagnosed with prostate cancer in Sweden from 1998 onwards were included, and virtually all important data points were recorded with <2% incomplete data. Men were followed for up to 15 years and 4 different sets of statistical models were done to balance the surgery and radiotherapy groups with each other.

Remarkably, all sets of models came up with the same answer: that surgery led to better survival results than radiotherapy, especially for the men with intermediate and high risk prostate cancer and even more so if they had a long life expectancy. If I were a barrister, I would say this study provides strong evidence to build the case that surgery is a better option in survival terms for the majority of men who need treatment for localized prostate cancer.  Medicine, like law, is never about absolutes, it’s about risk and probability. Can I prove that surgery is better than radiotherapy from this study – no; but there certainly seems a strong case to argue.

The current BJUI Article of the Week is another excellent article on the same subject (https://www.bjuinternational.com/article-of-the-week/prostate-cancer-sun-shines-light-on-surgical-survival/)

You can download Drs Sooriakumaran & Wiklund’s slideshow on their article by clicking here (1.5mb)

Prasanna Sooriakumaran is a robotic prostate & bladder cancer surgeon and academic at Oxford and Karolinska. @PSooriakumaranu

 

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Image from Razmaria et alBJU Int 2014; 113: 468–475. doi: 10.1111/bju.12284

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Stunned

If you needed inspiration to pursue cognitive ergonomics as a career or hobby, you could do worse than starting with the book “Set Phasers On Stun” by Steven Casey. Presented as a series of bite-sized real-life vignettes, the book illustrates the inherent fallibility in humans who design and use systems in a very engaging manner.

The most relevant story for doctors is the titular tale about a man receiving radiation therapy for a tumour on his shoulder. Ray lay on the treatment table. The tech in the next room attempted to set the machine to an appropriate radiation dose, but accidentally turned it on to full power. She noticed her error, and reset the machine before firing. Unfortunately the software was not sufficiently powerful to acknowledge her rapid typing, and the setting stayed on full. Furthermore, after firing, the screen told the tech there was an error and that no dose had been delivered. She tried twice more, inadvertently dosing Ray each time, unable to hear Ray’s screams from the lead lined treatment room. He only avoided further doses by running away. As Ray died from the treatment over the ensuing weeks, he jokingly told people that “Captain Kirk forgot to put the machine on stun”.

As clinical doctors, we should acknowledge the fact that individually, we do not make that many people better. Disappointing though this is, as it is the Raison d’être for many of us, I think we understand on some level that it is the “Big Picture” people, the Epidemiologists and Public Health physicians that really make the difference. However many cancers I cut out in my career, I’m still likely to make less of a difference than one well in Sub-Saharan Africa. Many of us are prevented from entering the “Big Picture” career paths due to the fact that they are interminably boring. It is much more interesting to counsel and educate patients, and certainly more exciting to perform complex (and at times terrifying) operations than to sit in a small office in the medical school’s worst-funded department crunching numbers. And who is more likely to be invited to appear on Dr. Oz? The Robotic Surgeon? Or the Epidemiologist with meticulously gathered records of malaria rates in South East Asia? The sad truth of the world is that glamour and excitement are usually more revered than self-sacrifice for enduring positive change.

It took a tragedy, and software engineers to solve the problem that killed Ray on the radiation table, but fortunately, there are simpler avenues for clinicians to make a difference beyond the patients they personally treat. This does not necessarily mean being involved in research on expensive new drugs that often have an incremental (or even arguable) benefit over the existing standard. And you don’t have to be Atul Gawande, creating the WHO surgical checklist, but it helps to use his approach. Devoting some time and mental resources to identify problems that affect a large number of people, even if only in a small way adds up to a significant total benefit. This week I was sent a review article on inadvertent diathermy injuries. These are uncommon, but can be debilitating, as in the index case where a patient essentially lost the use of his right hand due to thermal injury-induced tendon contractures. A consistent problem was a loss of contact between skin and earthing plate. Sweat and traction can loosen the plate and result in occult burns, particularly during prolonged cases, or emergency cases where the plate was applied in a rush. Maybe another surgical check should be done at four, or six hours into an operation to assess the need for a second antibiotic dose, and check diathermy plate. If the case is taking significantly longer than expected, should we take the opportunity to ask; “Why is this taking so long? Do I need help, or a second opinion here?”

The electronic age has given us unprecedented opportunity to reach patients with quality information on the nature of their disease, what to expect from their surgery, and advice on when to seek urgent help. In many cases it just takes a person to assume responsibility for writing content for a web page. The more quality health content we write, the more we drown out the snake-oil merchants and charlatans that prey on credulous patients.

My challenge to you in the coming week is to devote some time to thinking of a “Big Picture” issue that could benefit more patients than those you see yourself, or alternatively dig a well in Africa.

James Duthie is a Urological Surgeon/Robotic Surgeon. Interested in Human Factors Engineering, training & error, and making people better through electronic means. Melbourne, Australia @Jamesduthie1

 

Editorial – Prostate cancer surgery vs radiation: has the fat lady sung?

The current article by Sun et al. [1] representing a number of institutions involved in prostate cancer treatment provision is thought-provoking and hypothesis-generating. The authors contention when mining Surveillance, Epidemiology and End Results data for 67 000 men who had localized prostate cancer between 1988 and 2005 is that those with a life expectancy >10 years had less likelihood of prostate cancer death when treated with surgery rather than by radiotherapy or being left to observation. The Scandinavians have already shown, in the randomized study by Hugosson et al. [2], that if you have your prostate cancer removed you have less likelihood of symptomatic local recurrence, lower likelihood of metastasis and progression, and a 29% reduced likelihood of prostate cancer death. The current study asks the question ‘Is radiation therapy less likely to provide a long-term cure for prostate cancer than surgery?’ and gives an answer in the affirmative.

The current paper, in its way, neatly encapsulates the contemporary angst generated in the community when prostate cancer screening, diagnosis and therapy are discussed. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) trial [3] allegedly shows no benefit from treatment over observation and contends perhaps that we surgeons and radiation oncologists are harm-workers, not life-savers. The PLCO has a 52% PSA contamination in its control arm [3]. That flawed trial compared screening with de facto screening and produced, in my view, a null hypothesis. How do we explain the paradox of a 44% reduction in prostate cancer-specific mortality between 1993 and 2009? How do we explain the disconnect between these trials and the facts? What do we do with the data not yet considered by the expert panels showing that early PSA testing at age <50 years is highly predictive of subsequent lethal prostate cancer? [4]

Clinicians are rapidly moving to an era of judicious risk assessment. This can only be done after biopsy is performed. We now frequently enrol patients with apparently indolent prostate cancer into surveillance protocols [5]. So the question should be ‘If the disease found on biopsy is moderate to high risk, and potentially lethal for that man, should we remove his prostate surgically or radiate it with intensity-modulated radiation therapy, brachytherapy, proton therapy, +/- hormone therapy?’.

As a surgeon I have an inherent dislike of combining hormone therapy in primary treatment. At least 50% of men in high-risk prostate cancer cohorts who receive radiation therapy also receive hormone therapy as adjuvant or neoadjuvant treatment [6]. Hormone therapy has a myriad of side effects. Even if the playing field was level between surgery and radiation therapy, the avoidance of hormone therapy as a first-line treatment gives surgery a seductive advantage.

The authors of the current report show a significant survival advantage in the cohort for surgery over radiation therapy and observation. There will never be a randomized trial between the two potentially curative treatment methods surgery and radiation. The scourge of commercial interest with spurious claims of superiority of one form of therapy over another, proton beam vs intensity-modulated radiation therapy, robotics vs high-intensity focused ultrasonography, means that we risk having our decisions regarding appropriate therapy formed by multibillion dollar technology companies with powerful marketing capacity. The current paper confirms what is self-evident: untreated localized prostate cancer can be lethal. Surgery and radiation therapy lower the morbidity and mortality from prostate cancer. Which is the better method of curative therapy is moot, but we do know that cure is very much predicated on the expertise and location of the practitioner.

We know mostly when and who to treat and what treatments work well. In my view, the prostate cancer testing debate resonates with the contemporary discussion about childhood immunization for infectious diseases. Some parents now, who clearly cannot remember the devastating epidemics of polio and other childhood illnesses, refuse to immunize their children. Prostate cancer practitioners who did not live in the quite recent era where the initial presentation of prostate cancer was bone metastasis +/− crush fracture to the vertebra and sometimes paraplegia, may be unknowingly steering us backwards.

At the recent 2013 AUA meeting, Adams et al. [7] reported on the fate of men not screened for prostate cancer, i.e. those men who presented with a PSA >100 ng/mL. There was a 3-year survival rate of 9.7%, a 19.7% cord compression rate and a 64% hospitalization rate. Those who do not learn the lessons of history are condemned to repeat them.

Anthony J. Costello
Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia

Read the full article

References

  1. Sun M, Sammon JD, Becker A et al. Radical prostatectomy vs radiotherapy vs observation among older patients with clinically localized prostate cancer: a comparative effectiveness evaluationBJU Int 2014; 113: 200–208
  2. Hugosson J, Carlsson S, Aus G et al. Mortality results from the Goteborg randomised population-based prostate-cancer screening trialLancet Oncol 2010; 11: 725–732
  3. Andriole GL, Crawford ED, Grubb RL 3rd et al. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-upJ Natl Cancer Inst 2012; 104: 125–132
  4. Vickers AJ, Ulmert D, Sjoberg DD et al. Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40–55 and long term risk of metastasis: case-control studyBMJ 2013; 346: f2023
  5. Evans SM, Millar JL, Davis ID et al. Patterns of care for men diagnosed with prostate cancer in Victoria from 2008 to 2011Med J Aust 2013; 198: 540–545
  6. Cooperberg MR, Vickers AJ, Broering JM, Carroll PR. Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancerCancer 2010; 116: 5226–5234
  7. Adams W, Elliott CS, Reese JH. The fate of men presenting with PSA over 100 ng/mL: what happens when we do not screen for prostate cancer? AUA 2013. Abstract 2696

 

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Ketamine: only for fools and horses

There are many terrifying anecdotes relating to the use of ketamine and the damage that sustained daily use may cause to the urinary tract. These include those reported in the medical literature and through the wider media. Reports of ketamine-related deaths, memory loss, hepatobiliary damage, ureteric obstruction with renal failure and profound bladder pain. Use is recorded in teenagers with the ability for a child to demonstrate symptoms to their peers becoming a badge of honour. At UCLH we are working closely with colleagues to provide improving care for this new disease. We have links with the Club Drug clinic in London and Lifeline, another drug support agency. We aim to help patients come off ketamine and re-assess their symptoms once that is true – a few patients have needed major surgery but many have recovered well without.

The drug is now the most widely used drug of abuse in China – its use appears to be growing elsewhere. In the UK figures from the Home Office in 2013 suggested that 120,000 16–59 year olds had used ketamine over the preceding 12 months. Experts have suggested that between 20 and 30% of daily users will develop urinary symptoms. This was confirmed in a recent survey of ketamine users where 27% reported urinary symptoms and only half improved with cessation.

Many myths exist about how ketamine can be safe if taken with lots of water or that it is not addictive – neither of which are true.  With appropriate questioning we can and do recognize the link between ketamine and damage to the urinary tract. As urologists we are less well informed about the other risks such as the psychological or hepatobiliary damage that are also seen. Support for rehabilitation and cessation of ketamine lies in the hands of a few interested groups and is certainly not widespread. However, there is universal agreement that cessation is a vital component of treatment – patients will often see a substantial improvement in symptoms. Many users seeking help for urological symptoms struggle to find informed support to help come off the drug. It has been suggested that there is little money to support agencies in helping people to stop ketamine use – this may be due to a lack of criminal activity linked to ketamine. Whilst the damage to an individual may be significant – the impact on society is perceived as small and this appears to reflect the money available to tackle it. 

Last week in the UK, as the media reported the death of an 18 year old girl from ketamine, the government announced it had accepted the recommendation of the Advisory Council on Misuse of Drugs and that it was upgrading ketamine from class C to a class B drug.

Reclassification from Class C to B will put ketamine alongside codeine, cannabis, amphetamine and mephedrone. This increases the prison term for possession from two to five years. It remains to be seen whether this will have any direct effect. If it sends a clear message that taking recreational ketamine does you harm or it facilitates an improved environment and support for ketamine cessation then that may benefit some. To the uninitiated the potential risks may be that reclassification could push up cost and that adulterants may be further introduced. This could add to the unpredictability of an effect that even now requires further clarification.

The fact that the issues surrounding ketamine are being discussed is important – it will help users, potential users and healthcare professionals to recognize the symptoms and the risks. Much wider and more detailed education is needed to try and prevent damage to more users.

Mr Dan Wood
Consultant in Adolescent and Reconstructive Urology
University College London Hospitals
Honorary Consultant Urologist, Great Ormond Street Hospital
Honorary Senior Lecturer University College London

Twitter @drdanwood

 

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