Infectious Complications of Kidney Stone Surgery

Infectious Complications of Kidney Stone Surgery

Our latest Guest Blog is by Dr Michael Wong, Director of the Singapore Urology, Fertility and Gynaecology Centre. He is a US Fellowship Trained Urologist, and previous President of the Singapore Urology Association. Michael gives an up to date and comprehensive account of Infective Complications in the Surgical Management of Urinary Stones.

Infective Complications in the Surgical Management of Urinary Stones


Despite the significant advancements in the surgical management of urinary stones, morbidity and even mortality are still being reported. Krambeck reported in the Journal of Urology in 2013 that deaths still occur after surgery, particularly in the elderly population as their immunity is lower and there could be delay in diagnosis due to lack of classical symptoms. The importance of appropriate antibiotic prophylaxis and assessment of risk factors prior to treatment cannot be underestimated.

Infective Issues with Percutaneous Nephrolithotomy (PCNL)

PCNL is most appropriate for large renal stones. One of the feared complications of PCNL is urosepsis. A common composition for staghorn stones is struvite,5 which results from the presence of urea-splitting organisms, and non-struvite stones may also harbor bacteria. There is therefore an increased risk for sepsis during the procedure. Further, PCNL utilizes large volumes of irrigation relative to ureteroscopy, which may increase the risk of sepsis.

The practice of prophylaxis for PCNL is not for debate. David Tolley reported that the rate of UTI reduces 3 fold when using prophylaxis for PCNL. Recently, the CROES group reported a series of 162 patients from multiple institutions who underwent PCNL without pre-operative antibiotics and matched them to patients who did receive antibiotics6 All patients had negative pre-operative urine cultures and matching was based on infectious risk factors such as diabetes, nephrostomy tubes and staghorn stones. They found that antibiotic prophylaxis led to fewer fevers (2.5% vs. 7.4%) and other complications (1.9% vs. 22%) and higher stone free rate (86.3% vs. 74%). The explanation for this finding may be that stones themselves may harbor bacteria that may not manifest in a voided urine culture.


Techniques to culture stones were described over 40 years ago. In a study examining infection rates in patients undergoing PCNL, 35% of patients had positive stone cultures, compared with 21% of upper tract and 11% of bladder urine cultures. Stone manipulation and lithotripsy can result in the release of bacteria and contamination of urine with possible systemic transudation resulting in sepsis or systemic inflammatory response syndrome (SIRS). Stone cultures have been shown to be a better predictor of sepsis and SIRS than voided cultures. Mariappan showed a positive stone culture to have over 80% sensitivity and a positive predictive value of 70% in predicting SIRS.7 Overall, positive stone cultures increased the risk of SIRS 4-fold. Along with bacteria, stones contain endotoxins that can potentially result in a systemic immune response clinically similar to sepsis.

The greatest limitation of stone cultures is that they are only available after a procedure with some days to allow bacteria culture and so cannot influence immediate peri-operative treatment. The utility of obtaining stone cultures in clinical practice is to guide antibiotic choice in the event of sepsis following ureteroscopy or PCNL rather than predicting it. Having said this, it is reassuring to routinely collect stone cultures intraoperatively from patients undergoing PCNL.

Understanding the Risk factors for Urosepsis during PCNL

Many groups have reviewed their experience with PCNL in an attempt to identify risk factors for post-operative fever, sepsis or SIRS. A positive pre-operative urine culture was associated with increased infectious risk (OR 2.2 -16.7), as were positive pelvic urine (OR 10.2 – 24.1) and stone cultures (4.88 – 25.6). Other factors such as female sex, hydroureteronephrosis, pre-operative nephrostomy tube, large or complex stone burden, and diabetes have all been associated with an increased risk of post-operative fever or sepsis.

Korets and colleagues showed that an increased number of access tracts increased the risk of SIRS (HR 4.8) when controlling for patient sex, stone culture and composition, while several other groups have found increased operative time to be a risk factor for fever. Dogan also showed volume of irrigation fluid required was a significant predictor. These three factors are likely all surrogates for stone size and complexity, resulting in a prolonged procedure.

Infective Issues with Ureteroscopy

A 2003 RCT by Knopf et al. that included 113 patients found a single prophylactic oral dose of fluoroquinolone prior to ureteroscopy reduced the incidence of post-operative bacteriuria (1.8% vs. 12.5%, p=0.02). There were, however, no incidences of symptomatic UTI. This study guided the AUA Best Practice Policy in recommending antibiotic prophylaxis prior to ureteroscopy for the management of stone disease.3 The guideline committee states that the potential risk of bacteriuria is 30% and UTI ranges from 4% - 25% without prophylaxis. There is no difference in efficacy between oral fluoroquinolone and intravenous cefazolin.

A Korean group reviewed their experience of infectious complications following ureteroscopy and identified several risk factors.4 They noted an overall UTI rate of 3.8%. Furthermore, they found hydronephrosis, bacteriuria, and an indwelling ureteral stent or nephrostomy tube was associated with an increased risk of post-procedural fever. Administration of antibiotics after the procedure was not as effective as pre-procedural prophylaxis.

flexi scope

Eswara and colleagues retrospectively reviewed their experience with stone cultures in patients undergoing ureteroscopy (n=274) or PCNL (n=54). They found that while pre-operative urine cultures were only positive at some point in 7% of patients, stone cultures were positive in 29%. Their overall sepsis rate was about 3-4% for all patents. In patients with positive stone cultures, the sepsis rate was significantly higher at 8% compared to only 1% in those who had negative stone cultures. Ultimately, urine cultures had a sensitivity of 11% versus 64% in stone cultures and there was a concordance of 64% between the stone culture pathogen and the one causes sepsis compared to only 9% of pre-operative urine cultures. Despite the correlation of stone cultures and post-operative infection, their utilization in guiding clinical practice is limited in that it takes several days following the removal of the stone for cultures to results. They are most helpful following the development of UTI to help guide antibiotic choice.

Unfortunately we do not have a study showing the use of ureteric stent post URS reduces UTI as upper tract decompression using a stent would also play a part in reducing UTI.

Infective Issues in Extra-Corporeal Shock Wave Lithotripsy (ESWL)

In general, the incidence of urinary tract infection occurring after uncomplicated ESWL is less than 1%, rising to 2.7% for staghorn calculi. This risk of sepsis increases in the presence of bacteriuria prior to ESWL especially if there is distal obstruction.

Until recently, the practice of giving prophylactic antibiotics was controversial in patients undergoing ESWL with negative urine cultures. It has been reported that bacteriuria can develop in 5-6% of patients undergoing ESWL even in the presence of sterile urine prior to the procedure and the risk of clinical UTI can be seen in 2-3% subsequently.

The European Association of Urology guidelines on urological infections (updated in 2010) do not recommend prophylactic antibiotics in ESWL unless there are risk factors like ureteral stents, urinary catheters, nephrostomy tubes or infective stones1. More recently, in a meta-analysis reported in the Journal of Urology in 2012 covering 9 randomized trials of 1364 patients undergoing ESWL for urinary stones with sterile urine cultures2, Lu et al reported no significant differences between the prophylactic group and the control group in terms of symptoms, rate of fever, rate of positive urine culture and the incidence of urinary tract infection. They suggested that antibiotic prophylaxis is not necessary for ESWL in low risk patients.


The American Urological Association guidelines3 were recently updated in Jan 2014 and currently do not recommend antibiotic prophylaxis for patients undergoing ESWL with negative urine culture. In the light of more recent publications, prophylactic antibiotics are recommended only in high risk stone groups with infective stones, recent instrumentation, nephrostomy tubes, positive urine cultures and a history of recent UTI or sepsis. In addition, special considerations should also be given to high risk patient groups which the AUA defines as advanced age, anatomical anomalies of the urinary tract, poor nutritional status, chronic smokers, chronic steroid users, immunodeficiency, externalized catheters and prolong hospitalisation.

In general, ESWL should only be performed if the urine is sterile and when there is no distal obstruction to minimise infective complication. Currently, prophylactic antibiotics should be considered only in high risk patients.


The current guidelines and practice patterns pertaining to stone surgery have evolved based on emerging clinical data. These recommendations in conjunction with patients’ individual risk factors and culture data should help guide ongoing practice patterns.


1. Wolf, J. S., Jr., Bennett, C.J., Dmochowski, R.R. et al. : Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol, 179:1379,2008.

2. Grabe, M., Bjerklund-Johansen, T.E., Botto, H. et al.: Guidelines on Urological infections. European Association of Urology:79,2010.

3. Lu, Y., Tianyong, F., Ping, H. et al.: Antibiotic prophylaxis for shock wave lithotripsy in patients with sterile urine before treatment may be unnecessary: a systematic review and meta-analysis. J Urol, 188:441,2012.

4. Sohn, D. W., Kim, S. W., Hong, C. G. et al.: Risk factors of infectious complication after ureteroscopic procedures of the upper urinary tract. J Infect Chemother, 2013

5. Segura, J. W., Preminger, G. M., Assimos, D. G. et al.: Nephrolithiasis Clinical Guidelines Panel summary report on the management of staghorn calculi. The American Urological Association Nephrolithiasis Clinical Guidelines Panel. J Urol, 151: 1648, 1994

6. Gravas, S., Montanari, E., Geavlete, P. et al.: Postoperative infection rates in low risk patients undergoing percutaneous nephrolithotomy with and without antibiotic prophylaxis: a matched case control study. J Urol, 188: 843, 2012

7. Mariappan, P., Loong, C. W.: Midstream urine culture and sensitivity test is a poor predictor of infected urine proximal to the obstructing ureteral stone or infected stones: a prospective clinical study. J Urol, 171: 2142, 2004

You can read more about Michael Wong by clicking this link

Categories: Updates, Other


A Safer Way to Biopsy the Prostate

A Safer Way to Biopsy the Prostate

Jeremy Grummet is a Urological Surgeon with particular expertise in urological cancer. He has been instrumental in the introduction of transperineal prostate biopsy as an alternative to transrectal biopsy, to reduce infection rates after biopsy. Jeremy is conducting multiple clinical research projects on prostate biopsy and heads the Victorian Transperineal Biopsy Collaboration (VTBC) research group. In this article, Jeremy discusses the techniques and advantages of transperineal biopsy.

What’s wrong with the current standard method of prostate biopsy?

A biopsy is where a sample of tissue is taken for examination under a microscope, usually to determine if cancer is present. As you can see from the diagram below, the easiest way to access the prostate is via the rectum. That’s why we perform a rectal examination - so we can feel the back of the prostate for any suspicious lumps. Most prostate cancers are located towards the back of the prostate (peripheral zone), so a transrectal ultrasound-guided (TRUS) biopsy is a convenient way of sampling this area. Typically, at least 12 cores of tissue are taken during a TRUS biopsy.

TRUS biopsy

The other advantage of the TRUS biopsy is that it can be performed in just a few minutes by giving the patient intravenous sedation or using a local anaesthetic nerve block.

However, passing the needle of the biopsy gun through the wall of the rectum multiple times is problematic. As you’d expect from an organ that stores faeces, the rectum has a high concentration of bacteria. These bacteria don’t cause any problems as long as they stay in the rectum. However, passing the biopsy needle through the wall of the rectum allows these bacteria to access the prostate and its rich blood supply. This in turn can lead to a serious infection in the blood called septicaemia (sepsis). Septicaemia makes patients feel very unwell, requires hospitalization for intravenous antibiotic therapy, and can even be life-threatening.

This risk of sepsis in TRUS biopsy is well-recognised. It is therefore standard to use an antibiotic to help prevent such an infection. Unfortunately, the antibiotic doesn’t always work, so there is still a risk of sepsis, which has been measured at about 1-2%.

Today, there is the additional and growing problem of bacteria developing antibiotic resistance. This has been reported worldwide and was the subject of a major US Government report last year.

Our own research group, the Victorian Transperineal Biopsy Collaboration (VTBC), reviewed the scientific literature, finding that developing resistance is a particular problem for bacteria that live in the rectum, so that the antibiotics we would normally use, such as ciprofloxacin, can sometimes be rendered ineffective. This coincides with reports of increasing rates of TRUS biopsy sepsis even as high as 5%.

Our research has also found that, as a result of the above, some Australian and New Zealand urology practices have resorted to using big-gun broad-spectrum antibiotics on a regular basis to prevent TRUS biopsy sepsis. Whilst this may reduce sepsis for the individual patient, from a public health perspective, it is a step backwards, as widespread use of such antibiotics will lead to even more resistance. Unfortunately, we are already seeing this happening, with hospitals in Australia finding CRE (Carbapenem-Resistant Enterococci) in their wards.

What is transperineal biopsy, and why is it safer?

Fortunately, there is another approach to prostate biopsy which avoids perforation of the rectum altogether. Instead, the biopsy needle can be passed via the skin of the perineum. In men, the perineum is the part of the body between the scrotum and the anus.

TRUS biopsy

As shown in the diagram, the ultrasound probe is still passed into the rectum to provide an image of the prostate. But instead of the biopsy needle passing alongside the probe, it is passed through a grid, which itself is fixed against the probe outside the body. Prior to insertion of the ultrasound probe, the perineal skin is easily prepared in a sterile fashion, just as any other incision site is prepared before surgery to prevent wound infection. (Although worthwhile attempts have been made to sterilize the rectum, this has not been possible.)

Our group studied the experience of transperineal (TP) biopsy around the world and found that in over 6,600 patients, there were only 5 patients re-admitted to hospital for sepsis - a rate of just 0.076%, or less than 1 in a thousand. Furthermore, in our own published experience of 245 TP biopsies our rate of re-admission for infection was zero. (We have now performed over 400 TP biopsies, still without a single episode of infection.)

Based on the published scientific evidence to date then, it appears that TP biopsy is a safer option than TRUS biopsy due to its near-zero sepsis risk. It also gives the advantage of avoiding regular use of heavy-duty antibiotics, thereby avoiding promotion of resistant bacteria, now labelled by the US Government Center for Disease Control as a Serious Threat to population health worldwide. As a result, we now use TP biopsy routinely for all prostate biopsies.

Are there any downsides to the transperineal approach?

Looking at the diagram above, you would expect TP biopsy to be painful, which is why it is typically performed under a general anaesthetic (although methods of using local anaesthetic only have been reported). We routinely perform TP biopsy under GA. As a result, men experience no pain during the procedure, and very little afterwards, so that paracetamol is only required occasionally. Although a general anaesthetic is required, it is of a short duration only (less than 30 minutes) and is very safe.

Practitioners of TP biopsy initially reported a higher risk of acute urinary retention (unable to pass urine) with this approach. However, with further experience, and by deliberately avoiding the area around the urethra, this rate dropped so that it is now similar to the risk seen in TRUS biopsy (around 2%). Although a catheter has been used by some doctors, as shown in the diagram above, it is unnecessary.

Due to anecdotal experience, some urologists have been concerned that TP biopsy may lead to erectile dysfunction by damaging the erectile nerves or to more difficult surgery if cancer is found and the prostate needs to be removed. However, evidence to date, albeit scant, does not support either of these concerns.

Is it as good as TRUS at cancer detection?

According to the scientific literature, TP biopsy is at least equivalent to TRUS biopsy in its ability to detect cancer. Some research has also found improved detection of cancers at the front of the prostate (anterior). This may be due to the typically easy access TP biopsy provides to all areas of the prostate, particularly anteriorly. Conversely, it can often be difficult to reach the anterior prostate via TRUS biopsy, especially in large glands.

What other advantage might TP biopsy provide?

In TP biopsy, the ultrasound probe is stabilized by equipment that is fixed to the operating table. The grid through which the biopsy needle is passed is, in turn, stabilized against the ultrasound probe. This set-up permits accurate and reproducible biopsy needle placement.

In the past, TP biopsies were taken in a systematic fashion only, evenly sampling various areas of the prostate. Whilst this is still performed routinely, in addition we are now often performing targeted biopsies of suspicious lesions if found on a prostate MRI. The stable arrangement of TP biopsy therefore permits accurate targeting of such lesions, with the potential to further improve the accuracy of cancer detection.

You can read more about Jeremy Grummet by clicking this link

There is more information on transperineal biopsy on the AUA site.

And you can follow @JGrummet on Twitter.

Categories: Updates, Prostate Cancer, Prostate Surgery


Fight Bladder Cancer - the New(ish) Kid on the Block

Fight Bladder Cancer - the New(ish) Kid on the Block

Fight Bladder Cancer is a UK based charity that was formed to provide information and support to people affected by bladder cancer. The charity started life as a small local support group but has now grown to be a very effective organisation offering global support through its new website, online confidential forum and support for local groups and research projects.

Andrew Winterbottom, founder and director of the charity tells the story of its beginnings and it's vision for the future.

Fight Bladder Cancer - the New(ish) Kid on the Block

The first strange thing about being told you have bladder cancer is that you most probably have never heard of it before. Despite being the 6th or 7th most common cancer (depending on where you live) it is a cancer that hardly ever gets talked about. The next thing to hit you and your loved ones is that there is very little information and support out there. When I was diagnosed in 2009 there wasn't a single charity in the UK dedicated to bladder cancer. Yes, there was general information, a lot of it very good, on the websites of the large cancer charities but nowhere dedicated to bladder cancer.

Whilst I was being rushed into treatment after being diagnosed with a T4G3 cancer my wife was left at home trying to make some sense of the madness that is a cancer diagnosis. In the end it was the American Bladder Cancer Cafe site (set up by patients themselves) that was the most help. The next best thing we found was a small general chat room being run as part of the Macmillan charity website where people with all cancers could chat. This was a lifesaver and a sanity saver, which also gave us the opportunity to 'meet up' with people online who also had a bladder cancer diagnosis.

A new friend who went by the screen name of 'Mike on a bike', who had been diagnosed just 6 months before me, plus his wonderful wife, were there to answer all our questions and give us suggestions for the questions we just didn't know to ask. Without that contact with other people affected by bladder cancer it would had been a very lonely and scary time. And that was why, six months post RC we decided to set up our own support group for bladder cancer patients being treated at the local hospitals to where we lived. But it wasn't long before we realised that just a local group was not enough.

Another 28 people were being diagnosed with bladder cancer every day in the UK and there was almost nothing out there for them. This made us think of a way to offer support to a much bigger audience. With an estimated 100,000 people living every day with bladder cancer in the UK, we needed to change tactics and move to a national internet based service.

And so our national bladder cancer support charity was formed in 2010 with its main outlet being a confidential forum housed on Facebook. Starting with just a few of us we have been amazed as to how big it has grown in such a short period. Now with almost 400 current members the forum is active with people supporting each other whether they are the patient themselves, a carer or a loved one. And it's not just UK people who are using the forum as we now have many from around the globe, especially from the USA, Canada and Australia.

The big project Fight Bladder Cancer took on in 2013 was the writing, designing and building of our own website. Planned from the beginning to be made patient friendly, all the work has been carried out personally by the trustees of the charity. A task that has meant learning how to build websites and how to design them so that it was easy to navigate for a patient or carer searching for help during those late nights when sleep just wasn't possible.

Our site went live early in October 2013 and now, just 4 months later, we are surprised and delighted by how many visitors we have had with almost no publicity accept for traffic from our forum on Facebook and our presence on Twitter. Already people from more than 30 different countries have visited the site.

Long term objectives

So what are the long-term objectives of Fight Bladder Cancer? As a charity we have three simple objectives:

1. Provide support and information for people affected by bladder cancer

2. Raise awareness about bladder cancer, it's causes, treatments and quality of life issues

3. Support research into the cause and treatment of bladder cancer.

Providing support has been the main objective in these first few years of the charity. Building on the Internet based forum we are now starting to support the setting up of local groups so that it is easier for people to meet face to face, a bladder cancer buddy service is in it's early stages and we have started to arrange group get-togethers so that our forum members can meet each other in real life.

This year, with our website now up and running, Fight Bladder Charity is raising funds for a large national awareness campaign. The campaign has two main aims of raising awareness both with the public and within the medical profession. We are attending conferences and study days this year with urologists, specialist nurses and GPs to develop a dialogue with the medical profession and to make them aware that we exist so that they can signpost their patients to the support that we offer. All to help improve awareness about bladder cancer and get more professionals talking about it.

Alongside this we, once enough monies have been raised, intend to supply every hospital and every GP surgery in the country with posters and leaflets about bladder cancer so that patients don't feel alone and know where they can go to for information and support. This, we believe, will be the first national campaign in the UK solely dedicated to bladder cancer. A campaign that has been a long time coming.

What about social media?

Social media has helped massively in our work so far and we anticipate that it will be a key part if our campaigns in the future.

As well as running our confidential forum on Facebook, we also have an open information Facebook page where we post news articles and links to bladder cancer stories of interest. We keep this very much up to date and often have broken news here before it has reached either the mainstream media or even the specialist urology periodicals! On Twitter we have, we have been told, more followers than any other bladder cancer charity worldwide. Not bad for a very young and still very small charity! This is certainly a media route that works for us and has opened many doors for us into the mainstream media and also introduced us to urologists worldwide.

Up until now the trustees of Fight Bladder Cancer have funded most of the work of the charity but this year we have started to start fundraising with greater effort to allow ourselves to expand our work and, hopefully, to even start to look at helping to fund research.

The future?

That's simple. To do more of what we are good at and help to change bladder cancer from being the one that is just not talked about to one where outcomes are improving year on year.

If you want to find out more about Fight Bladder Cancer take a look at their website and get in touch.

Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Website: www.fightbladdercancer.co.uk

Twitter: @bladdercanceruk

Facebook: www.facebook.com/fightbladdercancer

Categories: Bladder Cancer


Prostate Cancer Smartphone Apps

Prostate Cancer Smartphone Apps

The first guest blog for February is by Jim Duthie, a Urologist in Tauranga, New Zealand. Jim has written two Apps to make it easier for patients to be actively involved in their prostate cancer management. One app helps track PSA over time along with a history of prostate biopsies and treatments. The other greatly helps consolidate treatment for patients who are on ADT (hormone treatment).

For any question, the clichéd answer is now “There’s an App for that”, referring to the ubiquitous mobile applications for smartphones that seem to solve many of our problems, real or imagined. For medical conditions, this is increasingly the case. The “Medical” category is currently the most rapidly growing domain in the Apple App store. You can now download anything from a nomogram for predicting your risk of heart disease, to the somewhat questionable App that can treat whatever ails you by using your iPhone torch as a form of phototherapy. For me, designing mobile Apps was an effective solution for specific problems facing Urology patients.

Androgen Deprivation Therapy App

The process began with a concern that men undertaking Androgen Deprivation Therapy (ADT) were poorly followed up in terms of the myriad potential side effects that this treatment causes, from bone density to dyslipidaemia, to depression, and hot flushes. It is unclear exactly how many men are receiving ADT, let alone what percentage receive adequate follow up care. As Urologists, we are not experts in managing the complexities of, for example, cardiac risk factors.

Despite best intentions, we also lack the time and expertise to manage depression and cognitive impairment. It makes sense for General Practicioners/Family Physicians (GPs/FPs) to coordinate this follow up, but the physiological effects may seem complex and intimidating for a non-specialist. Perhaps Endocrinologists may be better equipped, but not from the point of view of coordinating patient management, and again a GP/FP usually has a better understanding of psychosocial issues. With this lack of clarity around responsibility it is easy for uncomplaining patients to slip through the cracks. In practice, men receiving ADT may only attract medical attention after suffering a significant complication of their treatment.

To improve this situation, I considered that a centralized ADT database where men are recruited at the time of initiation of therapy, then sent reminders at regular follow up intervals would be ideal, and could additionally provide a bank of men available for clinical trials and retrospective study. Unfortunately, database creation and management is prohibitively expensive, and despite my best efforts such a structure is some way off yet.

I identified the core follow up issue as being getting the right investigations performed at the right time. To achieve this GPs/FPs need to be aware of the necessary tests, and patients informed about when to see their doctor for follow up. The ADT App attempts to achieve this with automated “push notifications” (alerts appearing on the smartphone) when they are due to see their GP, as well as listing recommended investigations according to the elapsed time since commencing treatment. The patient can also read about potential side effects by body system, and follow links for explanations about why the specific tests are required in terms of the physiological effects of androgen deprivation. This is an App aimed at patients, however the intention is that a GP/FP could also have this on their phone as a reference and educational aid.

PSA Manager App

This App addresses a broader group, any man either undertaking prostate cancer treatment or PSA screening. The idea of a “PSA Tracker” is not new. Before the advent of iTunes I encountered a retired accountant who had graphed his PSA over time by hand. An electronic equivalent is easy to achieve, but does it add much to the patient’s care? I thought that an “all in one” manager for prostate cancer screening and treatment would be more useful. The PSA Manager App allows the input of results of prostate biopsies, dates and modalities of treatment for cancer and benign prostate disease including surgery, radiation, and newer novel techniques, and results of imaging investigations such as CT, MRI, or bone scans with a facility for entering a free-text description of the results of these. The data are then presented on a graph with colour-coded markers to represent the timing of the interventions. PSA velocity and doubling time can also be calculated. The intention is to allow men a clear overview of their PSA changes during screening, and if applicable, the evolution and treatment of their prostate cancer.

Identifying barriers to care is an essential part of equitable health delivery, and something I considered at length. The first challenge I identified for men using these Apps, particularly the ADT App, was advanced age. We may think of men on ADT as being elderly, perhaps frail, and probably not expert in using technology. Firstly, this perception ignores the group of men receiving ADT as neoadjuvant/adjuvant treatment for radiation therapy, which constitutes a younger and healthier cohort of men. Secondly, many ADT patients attend clinic with a younger family member, and my experience has been that when I ask if anyone in the family has an iPod, iPad, or iPhone, the answer is usually yes. As long as one tech-savvy person can enter the data, the Apps work well by proxy. In designing the interface, details such as larger buttons to suit male fingers and presbyopic vision were considered.

Finally, any financial cost will constitute a barrier to some patients. The solution was the make the Apps free to download. This meant securing funding which was generously provided by unrestricted grants from Australian Prostate Cancer Research and Ipsen for the ADT and PSA Manager Apps respectively. Although I receive no reimbursement from the development of either App, I believe patients feel more confident in a product provided solely for their benefit, and I can promote the Apps to them and my colleagues with no financial conflict of interest.

Follow this link to download the ADT App

Follow this link to download the PSA App

Jim Duthie is a Urologist at Tauranga, New Zealand with an interest in Urologic Oncology, Robotic Surgery, and Medical Communication. You can follow @JamesDuthie1 on Twitter.

Categories: Updates, Prostate Cancer, Prostate Surgery


Radical Prostatectomy or Surveillance in Older Men – Which is Better?

Radical Prostatectomy or Surveillance in Older Men – Which is Better?

This is an abridged, written version of an invited lecture Nick Brook gave to the Clinical Oncology Society of Australia in November 2013. It covers a common clinical dilemma in a changing medical and surgical environment; the older man with organ confined prostate cancer….is surgery or surveillance the best option?

Has anyone noticed a storm of controversy surrounding the diagnosis and treatment of prostate cancer? This centres on concerns about the overtreatment of prostate cancer, and may have particular relevance in older men, who mostly have a shorter life expectancy than their younger counterparts. But men are living longer and in better health, perioperative management has advanced, and minimally invasive surgical treatments have lessened the acute physiological impact of treatment. Dogma has been that there should be a cut-off at 70 years of age when considering curative treatment for prostate cancer, but the tired catchphrase - ‘physiological not chronological age’ - is actually a very useful one, and has relevance to this topic.

Why worry?

It’s worth examining why we worry about treating localised prostate cancer with curative intent in older men. The reasons are four-fold:

  • These men may not benefit from treatment, as they may die of other causes before their prostate cancer becomes clinically relevant
  • Treatment may not be tolerated, and may cause morbidity and, rarely, mortality
  • Most men with curable disease who are left untreated do not die from prostate cancer within 10 years of diagnosis
  • For those who die within 10 years of diagnosis, the disease was probably incurable at diagnosis

These last two points are taken from a recent presentation by Patrick Walsh, and reflect an understanding of the natural history of prostate cancer, and its heterogeneity.

With changes in demographics and treatments, should we be pushing for surgical treatment in older men with localised prostate cancer, or is this overtreatment? Are these men better off on surveillance/watchful waiting? Before we can answer these questions, some basic points need reviewing:

Prostate cancer is not one disease

First, prostate cancer as a disease is heterogeneous in its classification and behavior. Gleason grading is absolutely central to determining how the cancer is likely to behave. We know that this classification trumps other variables in predicting outcomes, whether these are positive margin rates, extra-capsular extension, seminal vesicle invasion, lymph node status, recurrence after treatment, or prostate cancer mortality.

We can use the Albertson tables to indicate likely mortality from prostate cancer and non-prostate cancer causes over a period of time for a given Gleason score and age at diagnosis. It is really quite simple; when we ask “does it matter if we treat or not?”, we get an indication that a man in his early 60s with Gleason 6 disease has a very different proportional chance of dying from prostate cancer in the next 15 years than a man in his early 70s. Likewise, a man in his 70s with Gleason 7 (a weakness of the tables is that 3+4 and 4+3 are combined) is, of course, proportionally more likely to die of another cause than he is to die of prostate cancer, but this is not true for a man in his 60s at diagnosis.

Albertson Table

So, age and Gleason score are combined in these tables to give us a reasonably powerful tool when we grapple with the question of whether to treat or not. These Albertson tables have been around for a long time, have recently been updated, and are greatly underused.

Active surveillance or watchful waiting?

Second, the terms ‘surveillance’ and ‘watchful waiting’ are separate entities that are often confused.

Watchful waiting is based on the premise that some patients will not benefit from treatment of their primary cancer. The decision is made at the outset to forgo definitive treatment, and instead provide palliative intervention for local progression or metastasis if/when it occurs.

Active surveillance is very different, and is based on the understanding that some but not all patients may benefit from localised treatment. The idea is to monitor closely and

  1. identify those men with localised cancers that are likely to progress, providing timely treatment for them
  2. to avoid treatment and associated treatment-related complications in men with cancers that are unlikely to progress
Active surveillance or watchful waiting - Man at a microscope

If we consider again the Albertson tables, we can see why active surveillance makes sense for those cancers that are less likely to cause trouble, but also makes sense for older patients, perhaps with intermediate risk cancer.

A number of different active surveillance protocols are in use. They vary slightly (some have stricter criteria), and include the Johns Hopkins, Toronto, Miami, and UCSF protocols. The one we are encouraged to use in Australia as part of an international protocol study is PRIAS (Prostate Cancer Research International Active Surveillance).

Results of active surveillance

What do we know about outcomes from active surveillance? Klotz’s group in Toronto reported on 450 men followed with active surveillance, about 50% of whom were over 70 years at diagnosis, most with 3+3=6 but 17% of men had 3+4=7. Importantly 10-year cancer specific survival was 97%. There was no difference in prostate cancer mortality for those men on AS over or under 70 years of age at diagnosis. Obviously though, non-prostate cancer death in those over 70 at diagnosis and commencement of AS was much greater than those under the age of 70. This provides further evidence that age does matter; we already know our older patients are more likely to die of other causes. It also substantiates the idea that for carefully selected patients, AS is a sensible option.

What factors should we consider when choosing radical prostatectomy or ‘surveillance’ in older men?

When we are considering RRP in older men, there are three key questions we should consider:

  1. In this man’s lifetime, will cancer control be an issue, i.e. do we need to perform radical prostatectomy to control his cancer or will surveillance (or watchful waiting) suffice?
  2. Is the perioperative risk higher than is acceptable, and is it higher than in younger men? Does his age/co-morbidity preclude safe surgery?
  3. Is his risk of long-term side effects that affect quality of life (incontinence and erectile dysfunction) too high, and is this higher than in younger men?

Let’s look at some evidence for these three areas:

Cancer Control

The two randomised studies that we have were of watchful waiting (rather than surveillance) versus radical prostatectomy:

The Scandinavian Prostate Cancer Group 4 Study randomised 695 men, 75 years old or less, with localised prostate cancer to radical prostatectomy or watchful waiting (not surveillance). The intervention for progression in the WW group was hormone ablation. Median follow-up was 12.8 years. Briefly, compared to watchful waiting, radical prostatectomy reduced prostate cancer deaths in men under 65 years (51% RR reduction, p=0.008), but not in those over 65 years (17% RR reduction, NS). Likewise, occurrence of metastasis (itself, an important endpoint) was significantly reduced in the radical prostatectomy group in under 65s, but not in the over 65s. This randomised study suggests that age does matter when considering the effect of RRP on cancer control.

The PIVOT study (Prostate Intervention Versus Observation Trial) looked at a similar number of men, randomised to RRP or observation (essentially watchful waiting, with palliative therapy or chemotherapy on progression). At 12 year follow up, there was no benefit of radical prostatectomy over observation, and there was no age effect. This study has been heavily criticised as it was underpowered (the study was initially powered for 2000 men but only 731 were randomised), and for the very small number of prostate cancer deaths in each arm. There were far fewer deaths overall in PIVOT, and the men as a cohort had more co-morbid conditions than SPCG4. Difference in outcomes from the two studies may also be because the SPCG4 men were mostly PSA naïve, whereas the PIVOT cohort came from the early PSA testing era.

Perioperative risk in older men

Can we safely take older men through an operation and the perioperative period? Do the (generally) age-associated co-morbidities impart too much risk?

An excellent retrospective study from Ontario of 11,000 men who underwent RRP helps address this question. Importantly, it showed the following:

  • Increasing age is associated with increased medical/surgical complications
  • There is a small but significant increase in 30-day mortality with age, even when adjusted for comorbidity
  • The number of co-morbidities is more important than age in determining mortality risk.

My reading of this is that age does matter, but medical fitness is more important in determining post radical prostatectomy complications and death. Older men who are fit (with minimal co-morbidities) are low risk and can be considered for surgery.

Long term side effects that affect quality of life – continence and erectile function in older men.

Lets conclude by looking at the potential long-term side effects of radical prostatectomy (incontinence and erectile dysfunction) that can have a major impact on quality of life. Is there any evidence for an age effect?

Many of the papers reporting side effects from radical prostatectomy are set about with bias, uncertainties and confusing definitions of continence and erectile function. However, a stand out paper from Massachusetts General Hospital looked at 430 men treated for localised prostate cancer with different modalities, and reported pre- and 36-month post-treatment sexual and continence function. Importantly, the authors stratified post-op outcomes according to pre-treatment function. Looking at erectile function, for nerve sparing radical prostatectomy (the gold-standard for erectile preservation), we see a remarkable reduction in sexual function. For those men with normal erectile function pre-op, only 8% were normal 36 months post-operatively. 28% of men deteriorated from normal to intermediate function, and 64% went from normal to poor. If we look at those who were intermediate before surgery, the figures post-op figures are worse. The paper did not examine an age effect, but we can extrapolate from population studies of non-prostate cancer men. We know that erectile function deteriorates with age, and it is therefore likely that a cohort of older men will have worse pre-op function, and are therefore more likely to have worse post-surgery erectile function.

Illustration of a man's body with the prostate highlighted

Admittedly there are weaknesses in this argument; the extrapolation and presumption, and the possibility that men with poor erectile function pre-operatively may not be concerned about post-operative erectile function, i.e. that factor may not affect their quality of life.

The paper reports a much less severe reduction in continence after surgery. However, but the outcomes are poorer for men who had less-than normal continence pre-operatively.

Some recent data is available on the effect age on continence after robotic radical prostatectomy; this indicates that although early continence 3-6 months after surgery is slower to recover in men >70 years, after that time the results are equal to men <70 years.


This is a complex dilemma and a common clinical issue we struggle with regularly. As life expectancy increases, the likelihood of prostate cancer clinical progression increases. Less invasive surgery and improved perioperative management have expanded the pool of men that can be safely treated. We need to carefully examine the rationale for radical prostatectomy, watchful waiting and surveillance in this dynamic demographic of ‘older’ men, but we are becoming more sophisticated in our decision making in this area.

For cancer control, one randomised trial suggests that men over the age of 65 do not benefit from RRP compared to WW. In carefully selected men, true active surveillance seems safe, and it is likely to be particularly safe for men over 70. We may even be able to extend surveillance criteria in these older men. In terms of surgical safety, age does matter but it is not as important as co-morbidity. For those long-term side effects of radical prostatectomy that impact on quality of life, it is likely that older men have worse potency outcomes than younger men. Low-level evidence indicates that continence outcomes may be equivalent in older and younger men.

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Categories: Prostate Cancer


Salvage radical prostatectomy

Salvage radical prostatectomy

This is Professor David Gillatt's second blog on the site. Here, he talks about the indications for salvage radical prostatectomy for prostate cancer, its indications and some of the difficulties encountered in this rarely performed surgery.

David, can you explain what salvage prostate cancer surgery is?

As we all recognise, unfortunately, in a minority of cases treated for prostate cancer the disease will recur despite that treatment. When a man has had radiation treatment for what appears to be prostate cancer confined to the prostate or its immediate surrounds, some will in time show evidence of the cancer reappearing and starting to progress. This will also happen in the less common situation of the cancer being treated with other local therapies such as cryotherapy, high intensity focussed ultrasound or brachytherapy. The disease comes back either because the treatment failed to control the cancer within the prostate or there was disease already microscopically beyond the gland which will eventually lead to spread. If the recurrent cancer is still within the prostate and detected early it may still be at a curable stage. This is the point at which we can consider salvaging the situation by surgically removing the prostate and the recurrent cancer therein.

If a patient has failed another treatment, what are the factors determining suitability for salvage surgery?

Salvage surgery is a local therapy and as such it will only remove or cure a cancer if still within the prostate. Therefore a judgement needs to be made when recurrence has occurred as to whether the disease has a high likelihood of being localised or are there features that suggest the probability of at least micrometastatic cancer.

Recurrence usually is suspected because the serum PSA begins to rise after falling to low levels after initial therapy. A variety of definitions of recurrent cancer after radiation have been used; the ASCO (American Society of Clinical Oncology) defined failure as the lowest PSA (nadir) after therapy plus 2 units of PSA is the most commonly accepted. This is applied by many to all forms of local therapy, apart from surgery, for prostate cancer.

If recurrence is suspected in my view a thorough search for obvious metastatic disease, including CT chest/abdomen/pelvis, isotope bone scan and occasionally PET scanning is mandatory. MRI and occasionally Choline PET scanning may define local recurrence. Antibody labelled isotope scanning (Prostascint for example) has been evaluated but is not in routine usage. The presence of obvious metastatic disease or locally advanced T3/4 N+ cancer will usually be a contraindication to salvage surgery.

A biopsy is again essential to define local recurrence and may be done once imaging has confirmed that the disease has not obviously spread. Confirmation of local recurrence in the absence of spread may be an indication for salvage surgery.

One further factor that must be taken into account is the behaviour of the patient’s PSA. The PSA velocity or doubling time give an indication of how much risk of progression the cancer poses to the individual over their lifetime. A rapid doubling of PSA, less than every 3 months, confers a high risk of the cancer spreading and resulting in early death. A slow doubling, more than one to two years, indicates a risk as low as perhaps 10 % of the cancer progressing over the next 10 years or more. As with many stages of prostate cancer there is a balance between needing to treat successfully those at high risk of causing damage and death and not over treating those with a very low risk of progress.

In summary a man with prostate cancer previously treated with radiation with PSA evidence of recurrence requires specialist assessment. A variety of factors including the stage of the cancer, the PSA behaviour and the life expectancy of the individual need to be considered before embarking on salvage surgery.

Obviously, this is difficult surgery. Can you outline the side effects of the operation?

This type of surgery, whether performed by the open route, laparoscopically or with robotic assistance is undoubtedly far more difficult and complex than primary radical prostatectomy. The effect of radiation, or indeed HIFU or cryotherapy, results in marked tissue reaction around the prostate. The prostate lies very close to many important organs and the effect of radiation is to make dissection of these areas more difficult and the risk of injury to other structures much more likely. Even when injury does not occur the healing of tissues is less certain following radiation. Collateral radiation effects on the distal urethral sphincter, neurovascular bundles and bladder neck may also make functional recovery slower and long term side effects more likely.

The rectum lies close to the posterior prostate and will often be quite stuck after radiation. Surgical dissection needs to be very careful in this region as injury to the rectum increases the risk of infection, fistula (a connection between the bowel and bladder resulting in urine leaking into the rectum) and the need for a colostomy. While this complication is still uncommon it is more so than after radical prostatectomy with no prior radiation. Incontinence is common in the short term after radical prostatectomy, resolving relatively rapidly in most. After salvage radical prostatectomy, the risk of incontinence is much higher, the time to recovery longer and long-term problems more common. At least 30-40% of men may experience long-term continence issues, some requiring correction, after salvage prostatectomy.

Sexual dysfunction, mainly erectile problems, are very common after salvage prostatectomy as the bundles may well have been compromised by the radiation before embarking upon a difficult salvage procedure. Because of fibrosis (scarring) around the bladder neck subsequent contractures requiring dilatation are common and in some will further increase the chance of long-term continence problems.

Can the operation be performed by laparoscopic or robotic methods?

The answer is yes; salvage prostatectomy can be performed by any of the recognised methods of radical prostatectomy. Is there evidence in favour of one procedure over another? – There is no evidence as there have been no trials comparing the techniques in this situation. As with many difficult procedures the likelihood of a successful outcome will in large part depend upon the experience of the surgical team dealing with the operation.

You are a high volume prostate cancer surgeon, but this is quite a rare operation. How many of these salvage prostatectomy operations do you perform per year?

Salvage prostatectomy is an uncommon operation even in very large busy prostate cancer centres. Even in US centres where 3-6,000 or more robotic prostatectomies have been performed the number of salvage cases is often far less than 100. The Bristol experience has been around 2000 open radical prostatectomies of which around 65 were salvage and over 1000 robotic cases, in 21 cases these were salvage cases. Our outcomes including functional recovery have been very good. However as these numbers suggest, most specialist units are very selective about to whom they offer salvage radical prostatectomy.

One interesting question is should we be considering more men for salvage RP? Undoubtedly the answer is yes. The perceived morbidity of all salvage treatments and the uncertainty as to which men most benefit from this approach has led many oncologists to take an observational approach. It is the urological cancer surgeons’ role to convince our Medical and Radiation oncological colleagues that appropriate salvage surgery can deliver a high chance of cure to men with locally recurrent prostate cancer at risk of progression in their lifetime with acceptable functional outcomes. It is my belief that minimally invasive surgery, in particular robotically assisted LP, offers the opportunity for the experienced prostate cancer surgeon to deliver salvage surgery safely, effectively and with rapid recovery times.

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