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From Famine to Feast. Systemic Therapy for Prostate Cancer Comes of Age.

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OR The Hare Becomes the Tortoise??

When I was a medical oncology trainee in 2001 looking for an area to specialise in my mentors told me prostate cancer was going to be the next big thing. I must admit I was dubious but now more than 10 years later this is amongst the best advice I have ever received. On a par with support Manchester United and buy property in London! Systemic treatment for prostate cancer has well and truly arrived and we are in a position where at times we are spoilt for choice.

So how did we get here and why did it take so long. To answer the second part first we need to go back to 1941 and Huggins and Hodges ground-breaking work showing the profound effect of castration on metastatic prostate cancer. Both the original paper and the Nobel lecture are fascinating reading. Castration remains a cornerstone of the treatment of prostate cancer. The androgen receptor is one of, if not the, most dominant biological pathway in solid tumour oncology. Apart from chemotherapy for testicular cancer, another urological success, I cannot think of another systemic treatment that has such profound activity both in terms of clinical response and disease control rates. For instance androgen deprivation far surpasses the activity seen with tamoxifen in ER +ve breast cancer. So prostate cancer got off to a flier and perhaps was the hare to the tortoise when compared to other cancers, which have slowly but surely overtaken.

There was a long lull with very little positive data for metastatic prostate cancer. Why was this? Perhaps the activity of androgen deprivation set too high a bar for subsequent treatments and a sense of nihilism for those that followed. This is shown by the negative reaction to the data on docetaxel first published in 2004. The 50% PSA response rate (a decline in PSA of 50% or greater) is impressive particularly in this highly pre-treated population. More importantly docetaxel improves quality of life and provides a small but significant survival advantage against an active comparator. We now have a second chemotherapy, cabazitaxel, which again shows a significant survival advantage. Whilst chemotherapy in prostate cancer remains controversial, and worthy of a future blog, there is no doubt for a significant number of patients it provides real benefit.

Prostate cancer is leading the way for other areas of systemic therapy. Sipuleucel-T is one of the only immunotherapies to show a survival benefit in solid tumour oncology. Whilst Sipuleucel-T is controversial and has many detractors, it does have level 1 evidence to support it. During my fellowship with Phil Kantoff’s group in Boston, I saw several patients who I am convinced benefited from this treatment. Alpharadin is the first radionucleotide to show a survival advantage and is likely to become an integral part of systemic therapy for CRPC.

The drugs that have provided most excitement and the greatest benefit in day-to-day practise are abiraterone and enzalutamide. These drugs build on the work of Huggins and Hodges and show that 70 years of targeting the androgen receptor is still relevant even with castration. These drugs have changed how we describe the disease moving from ‘hormone-refractory’ to ‘castration-refractory’. Abiraterone is now licensed in the pre- and post-chemotherapy setting and it is likely that enzalutamide will follow in the not too distant future. In my own practise these drugs are game changers. Ones that provide real benefits relieving symptoms, controlling disease and allowing some men with prostate cancer to live much longer.

Who should be responsible for all these new drugs? Medical oncologists? Urologists? Nurse specialists? For me this shouldn’t be territorial. I want men with prostate cancer looked after by those with a real interest in this area. The days of people dabbling should be in the past and testicular cancer has shown us that patients do better when looked after in high volume centres. In reality men with metastatic prostate cancer have complex medical needs and only with the input from the whole multidisciplinary team are we able to give them the best care.

So systemic treatment for prostate cancer is suddenly fashionable and my mentors (Ellis and Harper) were proved right! ‘Told you so Chowdhury!’ This is only going to be the beginning with prostate cancer, which is now at the forefront of cancer research. Our understanding of the biology of prostate cancer is likely to grow exponentially and with it our ability to improve treatment. So watch this blog – to be continued…

 

Simon Chowdhury is Consultant Medical Oncologist at Guy’s, King’s and St Thomas’ Hospitals, London. He is actively involved in clinical trial research into urological cancers.

 

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Prostate Cancer Outcomes Study Meets Twitter Face to Face

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The International Urology Journal Club on Twitter discussion for February 2103 was based upon the recently published Prostate Cancer Outcomes Study in the New England Journal of Medicine on 31 January 2013.

The originally planned discussion paper that was only hours away from being announced when it became apparent through Twitter notification by @NEJM that the PCOS paper was going to be published that day. With this news, ‘urology twitter’ spoke loud and clearly (well, tweeted to be technically correct), and it was clear that this paper required our urgent attention.

The primary and senior authors of the PCOS manuscript in Matthew Resnick and David Penson, respectively, were kind enough to commit to making themselves available for the twitter discussion and proved to be valuable contributors.

 

In short, PCOS examined 1655 men who had been diagnosed with prostate cancer in 1994 or 1995, between the ages of 55 and 74 years, and who had either undergone radical prostatectomy (1164 men) or radiotherapy (491 men). Functional status was assessed at ‘baseline’ and at 2, 5 and 15 years after diagnosis. The study found patients undergoing surgery were more likely to have urinary incontinence and erectile dysfunction at 2 and 5 years, but there was no significant difference at 15 years. Patients undergoing surgery were less likely to have bowel urgency at 2 and 5 years, but again, there was no discernible distinction between the two groups at 15 years.

The functional results as stated in the manuscript are poor and this generated discussion that attempted to place these results into context. It was pointed out by Stacey Loeb that with the Massachusetts Male Aging Study (MMAS), 79% of men had ED as defined by IIEF and that there was a concern that, with the present data, the media could interpret it as that all prostate cancer treatments universally cause ED. A later constructive comment was made that if the study had followed matched controls to 15 years, it would allow for meaningful estimation of risk with treatment superimposed on aging.

Discussion shifted to the changes that have occurred over time since men entered the study. A number contributors, including Matt Coward, Rajiv Singal, Quoc Trinh and others commented to the effect that many of the men treated in that era would probably no longer be treated radically and would be managed conservatively. Ben Davies in agreement declared that he would promise never to operate on a man with a Gleason score 2–4 prostate cancer. However, Sean Williamson, Alanna Jacobs and others pointed out that this was not really relevant to the study, which was an examination of functional outcomes.

Is the data applicable to today? In response to Tony Finelli’s tweet of “Why is it that the urologic community always criticizes longterm well designed studies with ’The data are no longer applicable today?’“, Rajiv Singal made a very sobering comment that “Data is very applicable. Study well designed. It’s just that over Tx in many in this group makes side effects more appalling”

Prokar Dasgupta provided some British input with “are patients happier if they are clear of cancer @15 years or would they rather be potent?” Michael Leveridge from Canada provided constructive input with “As rational CaPr treatment shifts toward higher risk (wide fields, less nerve sparing), functional outcomes may actually get worse”

Criticism made that there were many men who missed out on completing their 2 and 5 year questionnaires was responded to by Dave Penson who explained that they were included in the study by using imputed data with a hot deck technique – whilst imperfect, it was the best that they could do to overcome this issue.

Stacey Loeb pointed out that a key strength of the study was that it showed that many short-term differences functional outcomes between RP & RT dissipate over time. From a functional perspective, Tim Averch may have a point when he commented that at 15 years that it may not make any difference as to whether we had performed surgery or radiotherapy.

The question was raised about correlating nerve-sparing surgery and subsequent results. Author Matt Resnick indicated that this was something that was being analysed right now with results forthcoming. On the general issue of improvements in surgery and radiotherapy leading to improved functional outcomes, Matt Resnick indicated that “While tech. improvements in RP and EBRT may incrementally improve outcomes, likely non-differential.” Towards the end of the discussion, it was generally agreed that robotic surgery was the primary manner by which surgery was being performed (at least in the US) and that it was an ‘operative leveler’ in terms of how well surgeons performed a radical prostatectomy.

Helen Nicholson from Australia asked if the late serious effects of radiotherapy were considered and on a similar theme, Matt Cooperberg raised the issue of where only incontinence was reported with regard to urinary function but irritative urinary symptoms were often of greater bother and worse with radiotherapy. Dave Penson responded in that they had data on bother from urinary symptoms and that it was worse at 2 and 5 years for surgery but the same for both radiotherapy and surgery at 15 years.

To complete the round up of the discussion content, the Best Tweet Prize was awarded to Dr Rajiv Singal for the following tweet:-

The Best Tweet Prize was kindly donated by Urology Match.

The above summary only touches upon the discussion, which had 32 participants who made a total of 171 recorded tweets to the hashtag #urojc. This does not include participants and their tweets where the #urojc had been omitted. We had quite a number of new participants this month who were still learning the necessity to include #urojc in all tweets in order for them to be visible to the discussion.

It is also interesting to look at the impact of the Superbowl. The first dip is related to our North American friends signing off to concentrate on the Superbowl and the last dip correlates when the majority of participants are with their heads buried in a robot console/wound or asleep on the other side of the world.

We look forward to seeing your participation in the March #urojc. For further information about what #urojc is all about, see my earlier blog entry on the subject.

 

Henry Woo is an Associate Professor of Surgery at the Sydney Adventist Hospital Clinical School of the University of Sydney in Australia. He has been appointed as the inaugural BJUI CME Editor. He is currently the coordinator of the International Urology Journal Club on Twitter. Follow him on Twitter @DrHWoo

 

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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

Read the full article

Dr Silberstein’s commentary on open vs robotic prostatectomy

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A case-mix-adjusted comparison of early oncological outcomes of open and robotic prostatectomy performed by experienced high volume surgeons

Jonathan L. Silberstein*, Daniel Su*, Leonard Glickman*, Matthew Kent†, Gal Keren-Paz*, Andrew J. Vickers†, Jonathan A. Coleman*‡, James A. Eastham*‡, Peter T. Scardino*‡ and Vincent P. Laudone*‡

*Department of Surgery, Urology Service, and †Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, and ‡Department of Urology,Weill Cornell Medical Center, New York, NY, USA

Read the full article
OBJECTIVE

• To compare early oncological outcomes of robot assisted laparoscopic prostatectomy (RALP) and open radical prostatectomy (ORP) performed by high volume surgeons in a contemporary cohort.

METHODS

• We reviewed patients who underwent radical prostatectomy for prostate cancer by high volume surgeons performing RALP or ORP.

• Biochemical recurrence (BCR) was defined as PSA  0.1 ng/mL or PSA  0.05 ng/mL with receipt of additional therapy.

• A Cox regression model was used to evaluate the association between surgical approach and BCR using a predictive model (nomogram) based on preoperative stage, grade, volume of disease and PSA.

• To explore the impact of differences between surgeons, multivariable analyses were repeated using surgeon in place of approach.

RESULTS

• Of 1454 patients included, 961 (66%) underwent ORP and 493 (34%) RALP and there were no important differences in cancer characteristics by group.

• Overall, 68% of patients met National Comprehensive Cancer Network (NCCN) criteria for intermediate or high risk disease and 9% had lymph node involvement. Positive margin rates were 15% for both open and robotic groups.

• In a multivariate model adjusting for preoperative risk there was no significant difference in BCR rates for RALP compared with ORP (hazard ratio 0.88; 95% CI 0.56–1.39; P = 0.6). The interaction term between © 2013 The Authors 206 BJU International © 2013 BJU International | 111, 206–212 | doi:10.1111/j.1464-410X.2012.11638.x Urological Oncology nomogram risk and procedure type was not statistically significant.

• Using NCCN risk group as the covariate in a Cox model gave similar results (hazard ratio 0.74; 95% CI 0.47–1.17; P = 0.2). The interaction term between NCCN risk and procedure type was also non-significant.

• Differences in BCR rates between techniques (4.1% vs 3.3% adjusted risk at 2 years) were smaller than those between surgeons (2.5% to 4.8% adjusted risk at 2 years).

CONCLUSIONS

• In this relatively high risk cohort of patients undergoing radical prostatectomy we found no evidence to suggest that ORP resulted in better early oncological outcomes then RALP.

• Oncological outcome after radical prostatectomy may be driven more by surgeon factors than surgical approach.

The Fifth and Final Hike for Hope

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The idea of a joint fund-raising trek in support of Prostate Cancer UK (formerly Prostate Action) and Well-Being of Women (WoW) dates back to 2005, when almost 100 trekkers joined us to walk across the desert to Petra in Jordan to raise more than £600,000 for these two noble causes. Neither Marcus Setchell nor I thought then that subsequently we would go on to trek in Kenya, Sinai, Kerala, and most recently Morocco, to raise an eventual cumulative sum of £1.3 million.

The fifth and final Hike for Hope started inauspiciously with dark clouds and pouring rain, even though we were in Morocco in September, just a couple of hundred miles North of the Sahara desert. They told us it hadn’t rained for the whole year before we got there! Undaunted, but with little in the way of rain-gear, rather, an excess of redundant sunscreen products, we set off across the Ante-Atlas mountains in the direction of Marrakesh.

This time, there were 27 intrepid trekkers, including the redoubtable Andrew Etherington, Felicity Hoare and Rex Willoughby, veterans who had each accompanied us on all the previous four Hikes for Hope, as well as Rosemary Macaire. Unfortunately on day one the rain became steadily heavier, with the result that the beds of the mountain streams, usually dry, became minor torrents, which were more and more difficult to cross. We made the decision to abandon the last hour’s walking to the camp and instead managed to persuade some of the local people to let us shelter in two of their mountain huts for that night.

Days two and three were tough trekking, but in fine dry weather. We got to the very highest point of the mountain before holding a minute’s silence for those relatives and friends who had succumbed to prostate or pelvic cancer, the cures for which we were raising money. Perhaps as the result of our efforts, we are a little closer to that goal.

On day four the rain returned, this time with even greater intensity, and accompanied by a bitterly cold wind. With little in the way of protective clothing, hypothermia became an issue. Again the amazing hospitality of the local Berber goat herders came to our rescue. Cold, wet and shivering, packed in again like sardines, we managed to get some sleep, occasionally interrupted by a goat or two, who seemed justifiably irritated to be displaced from their usual place of nocturnal shelter!  To the credit of the guides, the trek doctor and the trekkers themselves, morale and good humour were maintained.

On the final day the weather improved sufficiently for us to trek down the mountain to join the first road we had encountered for five days. A drive through the Atlas Mountains took us to the wonderful city of Marrakesh, where a well-deserved celebratory dinner and award ceremony took place. The trials and tribulations of our mountain trek had brought us all much closer together, so it was with a tinge of sadness that the Hikers for Hope disbanded and headed for home. The final sum of money raised and the camaraderie and bonding that occurred during the trek made the whole experience so very worthwhile.

The Flaws of the PIVOT Study of Radical Prostatectomy versus Observation; Don’t Give up on PSA Just Yet.

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A recent editorial in the BMJ by Christopher Parker (Treating prostate cancer. BMJ 2012; 345: e5122) uses the “best available evidence” from the PIVOT study (Wilt TJ, et al) to argue the case for watchful waiting for low risk prostate cancer and question the need to diagnose the condition at all. Unfortunately the PIVOT trial was marred by a number of serious flaws that should make us doubt its conclusions.

The original design of the PIVOT trial included a randomisation of 2000 patients to surgery or observation (Prostate cancer, uncertainty and a way forward. NEJM 2012; 367: 270-1). Unfortunately, this goal was not achieved; the design was modified to justify a randomization goal of only 740 patients. Median survival was assumed to be 15 years in the original study design and 10 years in the updated version. If the median survival of 12 years in the study’s observation group is taken and 7 years for enrollment and 8 years of follow-up assumed, the sample requires 1200 patients in order to detect a 25% relative reduction in mortality with 90% power and a two-sided alpha level of 0.05. With an actual enrollment of only 731 patients, the study was consequently underpowered to detect this relatively large clinical effect. The wide 95% confidence interval around the hazard ratio for death in the treatment group illustrates this point. A relative increase of 8% to a relative reduction of 29% in the risk of death in the prostatectomy group, as compared with the observation group, cannot be excluded with 95% confidence. Only 15% of the deaths were attributed to prostate cancer or its treatment.

Although a “life expectancy of at least 10 years” was an entry criterion, by 10 years almost half the participants had died, leaving only 176 men in the surgery group and 187 in the observation cohort, and by 15 years only 30% were alive. The investigators therefore did not recruit healthy men who would be the normal candidates for surgery and randomize them to observation; instead they recruited elderly and co-morbid men with very limited life expectancy and randomised them to surgery (with one fatality!). Furthermore, the finding that one fifth of patients did not adhere to the assigned treatment further reduces the ability of the trial to discern a treatment effect.

Prostate cancer is a slowly progressive condition which eventually, and after many years, results in a painful death from metastases in a significant number of patients, unless mortality from other causes supervenes. Radical prostatectomy, now usually performed minimally invasively with robotic assistance (Goldstraw MA, et al), prevents disease progression in >80% of well-selected cases. We appear to manage localised prostate cancer in a much more holistic way than our American colleagues and MDT decision-making and robust active surveillance programmes have enhanced this. Others were also outraged by the Parker editorial and the intrinsically flawed results of the PIVOT study should definitely not encourage us to turn our backs on a disease that kills more than 10,000 men per annum in the UK and hundreds of thousands more worldwide.

 

Roger Kirby, Ben Challacombe and Prokar Dasgupta
The Prostate Centre, London W1G 8GT and Guy’s Hospital, King’s College London, King’s Health Partners

 

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Anaesthesia for robotic-assisted laparoscopic radical prostatectomy

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Richard MoreyHere’s my technique for anaesthetising patients for robotic-assisted laparoscopic radical prostatectomy and I’d be interested to hear any thoughts, comments and ideas.

Pre-op. I try to fast the patients for as short a time as possible and also include pre-operative carbohydrate loading. This is in line with Enhanced Recovery After Surgery (ERAS) Guidelines for major bowel surgery and has been shown to reduce the negative nitrogen balance that occurs following major surgery. I use 200ml cartons of Polycal, which is clear and non-particulate, prescribed 12 and 3 hours pre-operatively. Clear fluids are encouraged up to 2 hours pre-op as this improves gastric emptying and minimises pre-operative dehydration.

Intra-op. I use a mixed technique of both general and regional anaesthesia. The general consists of a fairly standard technique with a Propofol induction and maintenance with Desflurane and a Remifentanil infusion. To reduce post-operative nausea and vomiting I use ondansetron, cyclizine and dexamethasone. The regional part is a spinal anaesthetic using 0.5% Hyperbaric Bupivacaine with additional intrathecal Diamorphine. Regional anaesthesia has been shown to reduce peri-operative DVT formation, probably by blocking sympathetic activity and improving blood flow through the legs, it also produces profound muscular relaxation enabling better pelvic vision and easier insufflation. In addition there is some evidence that appears to suggest regional anaesthesia may reduce the recurrence rate of prostate cancer. As the patients are positioned in a steep trendelenberg they are all intubated and ventilated with a small amount of additional PEEP to reduce pulmonary atelectasis.

Post-op. Intrathecal diamorphine usually provides 12-14 hours of good quality post operative analgesia. Intrathecal opiates act locally producing segmental analgesia and therefore do not produce the systemic side effects to the same degree as intravenous opiates. The ondansetron given peri-operatively may reduce the incidence of opiate induced pruritus as well as acting as an excellent antiemetic. Additional analgesia will be required but usually paracetamol and ibuprofen are sufficient. It is unusual for patients to require any additional stronger opioid medications and this is helpful in ensuring that gastric stasis and reduced gut motility do not occur. This enables the patients to be rapidly progressed on to a light solid diet that in turn further reduces the occurrence of a post-operative ileus.

Fluid Management. Using this starvation policy, patients should commence their surgery with only a minimum degree of dehydration. Remifentanil produces an extremely cardio-stable anaesthetic and with the patients being head down peri-operative hypotension is unusual.  Should this however occur blood pressure should be maintained with the judicial use of vasopressors and fluid if necessary. Post-operative urine output can be maintained if required with plasma expanders and diuretics.

 

Richard Morey qualified from MHMS in 1987 and has been a Consultant Anaesthetist in SE London since 1997. His particular interests are ERAS/ Laparoscopic Surgery along with ENT and Difficult Airways.

@morphthegasman

 

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What prophylactic steps should we take to prevent DVT/PE after RARP?

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Deep vein thromboses (DVT) and pulmonary embolism (PE) are rare, but potentially devastating, complications of major pelvic surgery. We have performed more than 1000 robot assisted radical prostatectomy (RARP) procedures in Central London (Lessons learned from 1000 RARP operations BJUI 2013;111(1):9-10.) and to date encountered just a couple of DVTs, as well as a single, non-fatal instance of PE. However, in the case of one of us (RK), a close relative passed away as a result of a PE 10 days after a routine hip replacement performed in Oxford, a very sad event which highlighted the very negative impact on the family of this preventable surgical complication.

Guidance from NICE recommends that evidence-based steps be taken to reduce the risk of venous thromboembolism (VTE). Failure to do so therefore renders us open to criticism if a DVT, or worse a PE, does develop. On the other hand, pelvic haematoma and haematuria are troublesome complications of RARP, the risks of which may be exacerbated by anticoagulation.

What therefore should we be doing to reduce the risk of before and after laparoscopic pelvic surgery? Few would disagree that TED stockings should be worn before and after surgery, but how long should they be retained, as many patients do find them rather uncomfortable? Calf compression boots during surgery and for 12 hours or so post-operatively should also be standard practice.

More contentious is the duration of use of low molecular weight heparin (LMWH). Some surgeons use a single dose immediately prior to the operation; we have used 5000 Units of Clexane post-operatively for 2-3 days. Orthopaedic surgeons are increasingly continuing LMWH for 28 days at home after joint replacement surgery, which carries a significant risk of VTE. Should we follow their lead? A simpler alternative from the patients’ viewpoint is daily use of one of the new oral anti-coagulants such as dabigatran.

Perhaps the most sensible approach clinically is to perform a risk assessment of all RALP candidates pre-operatively. A calf compression device and TED stockings should be used for all patients, together with LMWH, while in hospital. Those considered especially at risk with, for example, a BMI >30 (Becattini CA) (See Box 1), should usually go home for a month with either LMWH injections or daily oral dabigatran, or equivalent oral anticoagulant agent.

We would be most interested in the views, experiences and current practice of the readers of this piece. Please do post your own response.

 

Roger Kirby, Ben Challacombe and Prokar Dasgupta
The Prostate Centre, London W1G 8GT and Guy’s Hospital, King’s College London, King’s Health Partners

 

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Ten stories of 2012, part II

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Thanks for all the helpful input regarding my first blog post. Constructive criticism is always helpful, especially if I am to get better at this.

If you haven’t read it, part 1 is here.

So, in no particular order, part 2 of 2:

+ Metastatic prostate cancer – it’s getting complicated…

2012 was a year of hope for metastatic prostate cancer patients.  First, Enzalutamide (also known as MDV3100), in the context of a phase III RCT, was shown to prolong the survival of men with metastatic prostate cancer after chemo. And just when we thought the year was over, Abiraterone, which was previously shown to improve survival in patients with metastatic prostate cancer after chemotherapy, was found to be beneficial even in chemo-naive patients. All this translates into more complicated algorithms for castrate-resistant prostate cancer.  That said, my question is the following: what happens if these drugs are effective at treating localized prostate cancer? It seems that some medical oncologists are trying to figure that out. Prostatectomists, murky waters lie ahead! Oh wait, I’m part of that group.

+ The changing landscape of surgical education

Times They Are a-Changin’. Residents are working less but don’t sleep more. 16-hour work day restrictions. More women are admitted into surgical fields. Protected nap (sleep) time during calls. Residents not covering floor consults during the day (those are actually the rules where I work). Most trainees now value quality of life above anything else, possibly even the quality of their training (do read this beautiful piece by a Urologist in JAMA: ‘Considering Life Before Lifestyle‘. Yet, the amount of knowledge a resident needs to consolidate during residency is at least 10-fold greater than what the old geezers had to learn back in the days (the current Campbell-Walsh is 134 chapters, 4320 pages). Whether or not you agree with any of the above (which is irrelevant anyways, because it’s happening whether you like it or not), attending surgeons and urologists are finding it hard to adapt or understand. “Honey, things were much harder back when I was a resident…” How do we evolve as a sub-specialty without compromising surgical education (or lengthening residency)? Status quo is not an option.

+ Radiotherapy for prostate cancer – what’s up with that?

A nice observational study from Sheets et al in the JAMA thematic issue on Comparative Effectiveness Research showed that “use of IMRT compared with conformal radiation therapy was associated with less gastrointestinal morbidity and fewer hip fractures but more erectile dysfunction“. Yet, Jacobs et al, using the same dataset and almost the same study years, showed that the risks of salvage therapy and complications are comparable between the two modalities, for most patients. And let’s not get started about proton-beam therapy. Whilst this costly approach is gaining precedence in the treatment of localized prostate cancer, severe doubts exist regarding its efficacy. The bombshell: another observational study from Yale, based on Medicare data: “Although proton radiotherapy is substantially more costly than IMRT, there was no difference in toxicity in a comprehensive cohort of Medicare beneficiaries with prostate cancer at 12 months post-treatment“. Ouch.  To be perfectly honest (sometimes I’m told I should shut up), it would be hypocrisy for robotic surgery fanboys to condemn proton beam therapy right now. As we all know, it took years before convincing observational data showed that robotic radical prostatectomy is better than open, at some levels. Maybe someone responsible will actually perform a prospective comparative effectiveness assessment between these modalities. As an avid blogger suggests, maybe the proton beams and the robots should fight for world domination.

+ Urology at the forefront of the social media revolution

As a group, we should be proud of how we embraced social media in 2012. In the field of medicine, where anything novel is usually met with smirk and mockery (see: surgery, robot-assisted), social media has been surprisingly well received, thanks to a tight-knit community of twitter champions (if you’re new to twitter, you should definitely follow urologymatch.com’s list of key opinion leaders (KOLs) in Urology. Moreover, the first International Urology Journal Club was held in November 2012 and has been a global success ever since. I’m sure that 2012 was only the start. It will be exciting to see the role of social media in upcoming international meetings such as the EAU, AUA and BAUS. Virtual high-five everyone!

+ Be inspired.

OK, so this one has nothing to do with Urology, or Medicine for that matter. Here’s a toast to the events that shook 2012, and let’s hope that 2013 will be a great year!

 

 

Quoc-Dien Trinh
@qdtrinh

 

Quoc-Dien Trinh is a minimally-invasive urologist and co-director of the Cancer Prognostics and Health Outcomes Unit. His research focuses on patterns of care, costs and outcomes in prostate cancer treatment.

 

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Twitter: my #eurekamoment #pennydrops #babyvomit

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I remember distinctly when the penny dropped for me. It was about 2am on a warm summer’s night in early January 2012 (apologies to those of you shivering in the Northern Hemisphere). I had my one-week old son in one arm, swinging between sleeping and spewing, and an iPad in my other hand, providing distraction between nappy changes and feeds. The sleep-deprivation had dulled my senses considerably and my brain was capable of no more than light reading.

It was then I read a piece in the New York Times online about the power of Twitter in medical communication. Previously, I thought Twitter was the domain of Lady Gaga, Justin Bieber, Kim Kardashian (Kim who?) and various narcissistic cricket and football players. It seemed like puerile nonsense for a generation that I no longer belonged to. However, reading this opinion piece made me think again. It was clear that there is a whole generation of significant academic clinicians, researchers and publishers who have embraced social media and who use Twitter, in particular, to disseminate their work with a speed and reach that is simply unachievable through any other medium. I was struck by various examples of how key scientific publications are first flagged on Twitter and how within hours, responses are made by key opinion leaders and these responses are again disseminated rapidly around the Twittersphere. And although none of the examples were based around urology, it was clear to me that oncologists and surgeons were getting on board the social media rollercoaster.

So between nappy changes and having wiped some baby vomit off my iPad, I logged onto Twitter and created a username. I searched for prostate cancer and urology and quickly found my way to a few key resources and super-users who seemed to have a very active Twitter presence and who were tweeting content that immediately appeared of interest to me. Within a few minutes I had identified a few highly valuable Twitter users to follow and within their lists of followers and those who they were following, I quickly built up a useful stream of tweets dropping into my timeline. And then of course, a few of these Twitterers started following me back, which was mildly exciting. Within a few days and having posted a few tweaks, I began to feel part of the Twittersphere.

As the weeks went by, I continued to be astounded by just how fast information travels on Twitter. While I get emails with the table of contents for the various journals that I subscribe to, these only drop in my inbox every few weeks. Also, because there are a number of significant journals that I do not subscribe to (non-urological mostly), there are many papers published out there that do not come immediately to my attention. Depending on which Twitter sites you follow, all key papers related to your area of interest find their way into your timeline instantaneously as soon as they are published. Not just that, very interesting comment from others also gets to you very quickly. For example, key findings in prostate cancer tend to be picked up by the major US news sites who then invite comment from key leaders in major cancer centres. A typical example is that of the PSA screening recommendations made by the United States Preventive Services Taskforce in June 2012, which provoked huge controversy. Twitter came to life and key opinion leaders such as Matt Cooperberg (@cooperberg_ucsf) helped drive the conversation through Twitter and blogs (e.g.The Huffington Post blog) at lightning speed. These comments get tweeted out and responses to these comments also get blogged and within hours of a paper being published you have news of the paper, expert comment and wider reaction…… all in 140 characters or less!

And while none of us have much time in the day to add an extra task, I find that waiting for my coffee in the morning or while the resident puts an arterial line in my next patient, there are a few spare moments in the day where the Twitter app on my iPhone comes to life. Twitter is perfectly suited to the smart phone user and that is where the majority of tweets around the world are generated from. It is also perfectly suited for one of the other very exciting areas in which I have seen Twitter play a very useful role – that of conferencing. At the EAU in Paris, a small but energetic group of Twitter users started tweeting content from various sessions at this large meeting and started engaging with other Twitter users around the world. For me, I believe conferencing is about to be transformed by the power of social media but more about that soon.

For now, at the new BJUI, we want to grow the audience and get you all to join the conversation. Through Twitter, blogging, Facebook, YouTube and other social media platforms, we are building for the future of communication in urology. The next generation of trainees will be deeply embedded in all of these platforms and will expect to be engaged through them. We are entering a new generation of medical communication – come join the conversation.

Declan Murphy
@declangmurphy

 

Declan Murphy is Honorary Clinical Associate Professor at the Department of Surgery, University of Melbourne, St Vincent’s Hospital and Director of Robotic Surgery at the Peter MacCallum Cancer Centre. He had previously been consultant urological surgeon at Guys & St Thomas’ NHS Foundation Trust in London.

 

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