Atezolizumab translates into survival benefit for bladder cancer patients with ctDNA positivity

 

 

Researchers who treated a group of post-surgery bladder cancer patients with the immunotherapy drug atezolizumab have found that patients whose blood contained circulating tumour DNA (ctDNA), responded very well to the treatment.   The study is presented today at the European Association of Urology Annual Congress (EAU22), in Amsterdam.   The research was part of a larger Phase III trial, IMvigor010, which looked at whether giving atezolizumab for up to one year to patients following bladder removal surgery improved the patients’ survival prospects, compared to a group that received no further treatment after surgery but placed in an observation group. Part of that trial involved patients’ levels of ctDNA being measured after surgery, and during further treatment or observation.   Although the trial found no significant difference in overall survival between the two groups in the intention-to-treat population, researchers noticed that a subgroup of patients who were ctDNA positive showed a marked improvement when they were given atezolizumab. These benefits included significantly higher disease-free survival, and significantly higher overall survival, than the observation group. This effect wasn’t seen in ctDNA negative patients.   In addition, the researchers also found that patients who were ctDNA positive, but subsequently changed to became ctDNA negative after treatment with atezolizumab, ultimately had a particularly good prognosis.    ctDNA comprises fragments of DNA shed from cancerous cells and tumours that are found in the bloodstream. Sometimes known as a ‘liquid biopsy’, it has emerged as a promising, minimally invasive biomarker in clinical oncology, but isn’t yet widely used as part of a standard detection and treatment tool for any cancers. It involves tumour specific gene sequencing for every patient, so is time-consuming and, at present, relatively expensive.   Professor Gschwend, Munich (DE), Chairman of the Department of Urology at the Technical University of Munich, said: “We already knew that patients who are ctDNA positive have a poor prognosis compared to those who are ctDNA negative. But this is the first time we’ve been able to show that with immunotherapy we can actually change the course of the disease depending on a patient’s ctDNA status.”   He continued: “If we can prove that consequent drug activity is linked to ctDNA status, and that high-risk patients will benefit, that could in time change the standard treatment pathway – and ultimately bring down the average cost of ctDNA analysis.”   Professor Morgan Rouprêt, Paris (FR), Chairman of the European Section of Onco-Urology of the EAU (ESOU), said: “The field of personalised medicine, using not only clinical but molecular indicators, is just around the corner. So, analysing ctDNA is very interesting. It is relatively easy to do with new technology and it means we can select a subset of patients who are likely to respond.”   The next step will be the upcoming IMvigor 011 study, which has been redesigned as a consequence of these results. With 500 participants, the trial will further evaluate the use of ctDNA sampling, and will compare atezolizumab against placebo in only ctDNA-positive patients, post-surgery.   Professor Rouprêt added: “Unlike in prostate cancer, where we can measure PSA as a marker of the cancer, until now we haven’t had anything we can use for bladder cancer. But these robust findings show that ctDNA has great potential as a sophisticated tool to monitor patients and choose their most effective treatment. The progress of the IMvigor 011 study will be watched closely by specialists for a greater assessment of the use of atezolizumab in bladder cancer patients.”

New imaging technology less accurate than MRI at detecting prostate cancer, trial shows

A team of researchers in Australia and New Zealand has found that MRI scans can detect prostate cancer more accurately than the newer, prostate-specific -PSMA PET/CT scanning technique. 

The findings are being presented today at the European Association of Urology’s Annual Congress( EAU 22 ) in Amsterdam. 

 Prostate-specific membrane antigen (PSMA) PET/CT scans, approved by the US FDA in 2020, use a radioactive dye to ‘light up’ areas of PSMA, which is found on the surface of prostate cancer cells. They are presently used to manage prostate cancer, as they can accurately measure the progression or recurrence of the disease. So, in this trial the researchers set out to find if they could be used to diagnose prostate cancer as well. 

The PEDAL trial recruited 240 patients across five hospital groups who were at risk of prostate cancer. Every patient was given both an MRI scan and a PSMA PET/CT scan. If imaging suggested the presence of prostate cancer, a biopsy was performed by the patient’s urologist. 

The MRI scans picked up abnormalities in 141 patients, while the PSMA PET/CT scans picked up abnormalities in 198 patients. A total of 181 patients (75%) underwent a prostate biopsy, and subsequently 82 of those patients were found to have clinically significant prostate cancer. 

Since each patient had both types of scans, the researchers could assess which type had more accurately detected those patients who had prostate cancer. The researchers found that MRI scans were significantly more accurate at detecting any grade of prostate cancer than the PSMA PET scans (0.75% for MRI vs 0.62% for PSMA PET). 

Associate Professor Lih-Ming Wong, Consultant Uro-oncologist at St Vincent’s Hospital in Melbourne (AU) headed the research team. He said: “Our analysis found that MRI scans were better than PSMA-PET for detecting any grade of prostate cancer. When we looked only at clinically significant prostate cancers, there was no difference in accuracy. As this study is one of the first to explore using PSMA-PET to diagnose cancer within the prostate, we are still learning and adjusting how to improve using PSMA-PET in this setting.

Although detection thresholds will be fine-tuned as diagnostic use develops, Associate Professor Wong believes the trial has important lessons for clinicians.  

He says: “This study confirms that the existing ‘gold standard’ of pre-biopsy detection – the MRI – is indeed a high benchmark. Even with fine-tuning, we suspect PSMA PET/CT won’t replace the MRI as the main method of prostate cancer detection. But it will likely have application in the future as an adjunct to the MRI, or for people for whom an MRI is unsuitable, or as a single combined "diagnostic and staging” scan for appropriately selected patients.”

He continues: “This is why these types of robust studies are crucial so we can better understand the part these technologies can play at every stage of the cancer journey, and progress the management of prostate cancer.”

Professor Peter Albers, Düsseldorf (DE) of the European Association of Urology’s Chief Scientific Office, comments: “New diagnostic tools need to be tested as carefully as new drugs, so we welcome the findings of this remarkable Phase III trial, which showed that MRI was superior in the detection of any prostate cancer. 
 
“It also showed that PSMA PET/CT was not inferior to MRI in the detection of clinically significant cancers (ISUP 2 and higher); and since the ultimate goal of primary staging will be to detect only the more aggressive cancers and avoid unnecessary biopsy, this is not the end of the story. More research will be needed to explore the PSMA PET/CT correlation between the standard uptake value (SUV) and cancer aggressiveness, but the first steps down the road in finding the best diagnostic approach to clinically significant prostate cancer have been taken.” 

Even younger nightshift workers shown to need to pee more, worsening quality of life

Millions of people work nights, but increasingly scientists are finding that night work is associated with health problems. Now a group of Italian scientists has found that nightshift workers also need to pee more, leading to a deteriorating quality of life for many workers, including care workers. This is also true of younger subjects, who would not normally be expected to report an overactive bladder. This work is reported at the European Association of Urology Congress in Barcelona. Researchers from the Sant’Andrea Hospital in Rome surveyed 68 men and 68 women between March and October 2018. All were workers in the Italian National Health System, with 66 of the volunteers working nightshifts, on average, 11 hours per night shift. The 70 day workers worked an average of 9.1 hours/day. The researchers found that the night shift workers reported a significantly higher rate of overactive bladder, and a poorer quality of life when compared with day shift workers. All the workers were under 50 years old. Using the generally accepted Overactive Bladder Questionnaire*, they found that those on night shift reported an average total score of 31, as against a score of 19 for those working day shifts. They also found that night workers scored a significantly worse quality of life (measured using the OAB QL score and the EORTC QLQ-30 score), with scores of 41 against 31 with day shift workers (see abstract for ranges). Research leader, Dr Cosimo De Nunzio said: “We know that long-term night work is stressful, and is associated with increased levels of health problems. This work shows that constant night workers may have a higher urinary frequency as well as a decline in their own quality of life. Furthermore, we have measured these changes in health workers, who are themselves responsible for looking after the well-being of patients. If they feel bad themselves, then this will inevitably lead to poorer patient care. The same is probably true in many other occupations. One of the most concerning things about this work is everyone in our sample was under 50. We normally expect bladder problems with older people, but here we have younger people expressing a deteriorating quality of life.” Background In many countries, night shift work is increasing to cope with the demands of the 24-hour economy. In the UK one worker in 8 works night shift (2017 figures; that’s 3.2 million, a 250,000 increase in the previous 5 years), with one in 6 black workers working night shifts. In the USA, nearly 9 million people work night shifts. In general, night shift workers are concentrated in poorer manual or service jobs, such as security, transport, cleaning, maintenance, etc. Night work has been shown to put stresses on health, with night workers showing greater levels of depression, cardiovascular disease, and certain cancers***. Commenting, Professor Jean-Nicolas Cornu (Rouen, France ) said: “Increased urinary frequency is an issue for millions of people worldwide. In nightshift workers, the present work highlights the importance of this issue regarding quality of life. Whether the changes described in this study depend on confounding factors (modification of drinking habits, caffeine intake, etc.) and/or modification of urinary production by the kidney cannot be assessed. A lot of work remains needed to understand what happens in those cases.” This is an independent comment; Professor Jean-Nicolas Cornu was not involved in this work The researchers note that this is a modest sample size, so the work needs to be reproduced in a larger study, with a longer-term follow-up.

Study suggests personality tests may improve care for prostate cancer patients

Scientists have found that men with high neuroticism – between a quarter and a fifth of men in developed countries – are significantly more likely to suffer from adverse events such as erectile dysfunction and incontinence, which may put their recovery from prostate cancer surgery at risk. The researchers say that this means cancer teams may need to consider testing for personality types to try to ensure that patients being treated for prostate cancer receive the best care. This work is presented at the European Association of Urology Congress in Barcelona. The researchers surveyed 982 men who had undergone prostate surgery (radical prostatectomy) at the University Hospital in Oslo, Norway. 761 of the respondents reported on their recovery from the surgery while also self-reporting on neuroticism with a standard questionnaire. 22% of the men scored high for neuroticism, which is in line with the prevalence of high-neurotic personality in national surveys in Norway (22 %,) and other countries such as the Netherlands (25%). These men showed significantly worse scores when surveyed on their recovery from radical prostatectomy (*See below for notes on questionnaires). Lead researcher, Dr Karol Axcrona (from Akershus University Hospital, Norway) said: “Around a fifth of the men scored highly for neuroticism, which is pretty much what would be expected. These men showed significantly more adverse effects after prostate cancer surgery. We use a standard questionnaire to measure the Quality-of-Life in men after prostate cancer surgery, and on average the highly neurotic patients scored around 20% worse than the non-neurotic patients on a variety of side effects, including erectile dysfunction, urinary leakage, and bowel problems. This mirrors work which has shown the effect of personality on disease recovery in general, but we still need to see this work replicated in other studies.” Until now differences in outcomes from prostate cancer surgery had been thought to be largely due to differences in surgical technique and the circumstances of the prostate cancer. This work shows that personality may also be a contributory factor to surgical outcomes. Dr Axcrona continued: “Neuroticism is not an illness, but a basic personality trait, like extraversion or openness; we all have some degree of neuroticism. What we found was that those patients who show a greater tendency towards neuroticism have worse outcomes 3 years after prostate cancer surgery. This is a real effect, and doctors need to take account of this, in the same way that we would take physical factors into account before and after cancer treatment. This means we may need better advance personality testing for identification and counselling, and perhaps a more specialised follow-up of those men who might be at risk of poorer outcomes. We believe the increased risk of adverse events is likely to impede the overall patient recovery, although the study was not designed to measure that." Commenting, Director of the European Association of Urology Scientific Office, Professor Arnulf Stenzl (Tuebingen, Germany) said: “This is interesting and novel work. It would be very valuable for those affected, but it may be difficult to test all patients; so in practical terms, we may need to pre-select those who are at most at risk. We know that roughly one out of five will tend to neuroticism, but we need to be more sure how this translates into postoperative clinical or psychological effects, so more we need more data.”  This is an independent comment; Professor Stenzl was not involved in this work. *Adverse events after surgery were measured using the EPIC-26 questionnaire https://medicine.umich.edu/sites/default/files/content/downloads/EPIC%20Short%20Form_0.pdf. Personality was measured using the Eysenck Personality Questionnaire, see Grav S, Stordal E, Romild UK, et al. The relationship between neuroticism, extraversion, and depression in the HUNT study: in relation to age and gender. Issues Ment Health Nurs 2012;33:777-785

Almost 1/3 of infertile men at increased risk of metabolic diseases as they age

Men with fertility problems are at increased risk of metabolic diseases as they age, according to work being presented at the European Association of Urology conference in Munich(* see publication details, below).

Around fifteen percent of all couples experience infertility, and in around half of these cases this is due to male infertility. Men with poor semen quality have been shown to have a decreased life expectancy, but the cause are unknown and no biochemical markers or prevention strategies have been developed. Now a group of Swedish researchers have measured the levels of sex hormones and other biochemical parameters in infertile men, and have shown that many of them are at risk of hypogonadism (low levels of sex hormones) as well as signs of metabolic disease and osteoporosis.

The group took 192 men with a low sperm count, who were attending the Reproductive Medicine Centre at Skåne University Hospital, Malmö, and compared them with 199 age-matched controls. They compared sex hormone  levels between the groups, as well as other markers such as bone mineral density (which indicates risk of osteoporosis) and HbA1c (a biomarker for diabetes).

They found that one third of men under 50 with fertility problems, had biochemical signs of low sex hormone levels (e.g. low testosterone), which is known as hypogonadism.  This was 7 times as common as amongst controls. These men also had low bone density – especially in men with low testosterone - leaving them at increased risk of fractures and osteoporosis. Hypogonadal men also showed biochemical signs of elevated glucose (with elevated HbA1c), and greater signs of insulin resistance – indicating a tendency towards diabetes.

According to study leader Dr Aleksander Giwercman (Skåne University Hospital, and Lund University, Malmö, Sweden):

“We found that a significant proportion of men from infertile couples show biochemical signs of hypogonadism. This may be affecting their fertility, but they can also serve as early warning signs for metabolic diseases in later life, such as osteoporosis or diabetes. We would recommend that levels of reproductive hormones should be checked in all men seeking advice for fertility problems. Those at risk of serious disease should be followed after the completion of fertility treatment. ”

Commenting, Professor Jens Sønksen (Copenhagen) of the European Association of Urology Scientific Congress Office said

“This study is very interesting, as is the question it poses; whether infertility in men below the age of 50 years might be used as a predictor for development of metabolic diseases including diabetes and osteoporosis later in life. There is a significant need for more studies in this field”.

New results suggest combining MRI with conventional prostate surveillance may give a generally effective prostate screening system

Initial results from the Göteborg randomised screening trial indicates that using MRI (Magnetic Resonance Imaging) alongside conventional prostate cancer screening seems to offer improved cancer detection and can help avoid unnecessary biopsies.

Prostate cancer is the third most common male cancer in Europe, accounting for over 92,000 deaths in 2012 (9% of male deaths).* Screening for prostate cancer is a controversial issue, with until recently, little clear evidence that existing screening procedures, using PSA (to be followed by biopsies), were effective. In general, either the screening has tended to miss many cancers, or to give false positives, meaning that many men are subject to invasive testing and perhaps treatment which was just not necessary.

The Göteborg Trial is the Swedish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC), which is the largest randomized prostate cancer screening trial in the world. In 2014 results from this trial showed a significant mortality reduction with prostate-specific antigen (PSA) screening for men aged 55-69 years of age. Now new work, presented at the European Association of Urology Conference in Madrid, shows that using MRI may further improve the accuracy of prostate cancer screening. This research has been awarded the EAU’s First Prize for the Best Abstract by a Resident

A group of Swedish researchers, led by Prof Jonas Hugosson took 384 patients attending the Göteborg trial, and asked 124 of these to go for an MRI prior to having a biopsy. Those with a suspicious MRI, or with a PSA > 3 ng/ml, were referred for biopsy. These biopsies were both standard samples, where 10 tissue samples are taken at random from the prostate, and targeted biopsies, where samples were taken from the suspicious areas seen on the MRI.

The results showed that the combining PSA and MRI, followed by MRI-targeted biopsy only in men with suspicious MRI gave better prostate cancer detection (as confirmed by biopsy) than PSA scores alone followed by standard random biopsy (7.0% versus 5.2%). The results also showed that more significant (potentially aggressive) cancers were detected with PSA + MRI combined compared with using PSA as a stand-alone test in screening.

Analysing the results, the Göteborg group suggests that this combination may point to a strategy to maximise success in prostate cancer screening.

According to researcher, Dr Anna Grenabo-Bergdahl:

“From these initial results it looks like we can combine PSA levels with MRI scans to give more accurate screening results. This strategy would allow us to take men with lower PSA scores, and give them MRI scans, to confirm whether or not a biopsy is absolutely necessary. Another benefit is that the MRI helps us locate the suspect area, meaning that if we have to do a confirmatory biopsy, we have a much better idea of where the problem might be. This avoids patient stress, and means we are less likely to miss cancers”.

She continued:

“These results from the pilot study are very encouraging, but now they need to be confirmed. We are starting a trial of 40,000 patients in the Göteborg area. If we can replicate the results from our pilot study this may lead to a paradigm shift in future screening and fundamentally change the way we handle early detection of prostate cancer”.

Commenting, European Association of Urology Treasurer, Professor Manfred Wirth (Dresden) said:

“These initial results, which confirm some of the work we have been doing here in Dresden, show that MRI-targeted biopsy has the potential to change how we diagnose prostate cancer. There are still real issues to address; for example MRI is currently not cost-effective to use in routine screening. As the authors say, we are still some way off considering using MRI for routine screening, and we need a bigger study to validate these results. But this is a positive proof of principle, and certainly merits more investigation”.

Cost of dealing with incontinence after prostate operation averages €210 per year

Incontinence is a common side-effect in men after treatment for prostate cancer. Now a new study not only confirms the high rates of post-operation incontinence, but also for the first time details some of the significant economic costs facing men – on average €210 per year after surgery, in some cases rising to as much as €283 in the first year. This work is presented at the European Association of Urology conference in Madrid.

Prostate cancer is the most common cancer in men, with around 360,000 new cases every year in Europe – making it about as common as breast cancer is in women. Often the cancer can be removed by surgery, which takes out the whole prostate. But there are very common side effects, notable erectile dysfunction (impotence) and urinary incontinence. This is because the nerves which surround the prostate are often damaged during the operation, and these nerves control the ability to have an erection and to control incontinence

Now a team of doctors from the University of Nijmegen (Netherlands), in collaboration with researchers from a Dutch insurance company, have used health insurance data to reveal the extent of post-operative incontinence, and the costs of dealing with it. The team reviewed data from the Achmea Health Insurance Database, which contains information on 17% of Dutch men. With this database, they were able to review data for 2834 men who had been treated for prostate cancer. They were able to correlate the surgical procedure with post-operative incontinence, and also with the resultant insurance costs which the men claimed for incontinence material (incontinence pads/diapers).

The researchers found that on average each incontinent man spent €210 in absorbent pads, every year, with a range of €112 to €283. In the second year, the mean cost of continuing incontinence remained high, at €219 per person.

They also found that the percentage of men suffering from incontinence in the first year after a urology procedure or follow-up varied from 8% of those undergoing conservative treatment (‘watchful waiting/active surveillance’)  to 80% for those undergoing laproscopic surgery (removal of the prostate via keyhole surgery). The overall mean incontinence rate was 22.6%. In the second year after treatment, incontinence still persisted in 40% of those who had undergone a laproscopic prostatectomy.

As lead researcher Dr Maarten de Rooij said:

“It can be very distressing to suffer from incontinence, and erectile dysfunction, after a cancer operation. Our work shows that, on top of this, it can have real economic costs as well – an average of €210 per person in our study in the first year. These are continuing costs for many men whose incontinence doesn’t improve over time. In the Netherlands for example, this side-effect of prostate cancer treatment could cost up to €800,000 per year, for only the newly treated men, and we would guess that other countries would have similar costs in proportion to their population.

The work also confirms the extent of the problem of incontinence after prostate cancer treatment. Given the size of the problem, we need to attach increasing importance to making sure that patients are not treated unnecessarily, while at the same time missing as few real cancers as possible”.

Commenting for the EAU, Professor James N'Dow (University of Aberdeen), Chair of the Guidelines Office Board at the EAU said:

“The cost of incontinence after prostate cancer surgery is a neglected topic and therefore this study is important and timely as it brings back into the public domain the critical issue of the wider costs of treating prostate cancer.   The cost for incontinence quoted in this study however is an underestimate of the true cost to the patient, his family and society at large.  The MAPS study published in the Lancet confirmed that the 20 year additional cost of incontinence for a man after prostate surgery is closer to Euro € 50,000 each.  This has to change and we must do better.  The EAU is ideally placed to lead the way in doing something about this costly problem through unrivalled science, innovation and advocacy”. 

Smokers at twice risk of prostate cancer recurring after surgery‏

 Current smokers, and those who have quit smoking less than 10 years previously, have twice the risk of a recurrence of prostate cancer after surgery, according to new research presented at the European Association of Urology conference in Madrid.

Prostate cancer is the third most common male cancer in Europe, accounting for over 92,000 deaths in 2012 (9% of male deaths). Around 30% of all prostate cancer patients treated with radical prostatectomy experience biochemical recurrence (defined by an increase in PSA, prostate specific antigen) within 10 years after surgery

An international group of scientists and clinicians from the USA and Europe retrospectively looked at biochemical prostate cancer recurrence - in 7191 men who had had their prostate removed by radical prostatectomy.  Of these men, roughly a third were never smokers (2513, or 34.9%), a third were former smokers (2269, or 31.6%) and a third were current smokers (3409, or 33.5%). These patients were followed up for an average of 28 months.

The results showed that after a median of 28 months, current smokers had around double (HR 2.26) the chance of the cancer recurring than did patients who had never smoked (see abstract below for full results). Even those who had quit smoking within the last 10 years still had a significantly higher risk of cancer recurrence, at about the same level (HR 2.03) as that for current smokers. It wasn’t until 10 years after a patient had quit smoking that the risk of cancer recurrence dropped significantly.

According to lead researcher Dr Malte Rieken (University Hospital, Basel, Switzerland):

“This is a new analysis, but it seems to confirm results we have seen in many other types of cancer:  basically, smoking increases the risk of cancer recurrence after initial treatment. Prostate cancer mortality varies widely throughout Europe. The fact that cancer recurrence can vary so dramatically due to smoking is probably one of the factors which may contribute to differences in prostate cancer mortality. It’s just another reason not to smoke at all, but the fact that the risk drops after 10 years means that anyone who has prostate cancer, would be well advised to quit immediately”.

Commenting former EAU Secretary-General, Per-Anders Abrahamsson (Malmo, Sweden) said:

“Prostate cancer is a leading cause of cancer death for man in the western world. A number of studies have addressed how diet and environmental factors affect the risk of prostate cancer. This is the first report that clarifies that smoking increases the risk of prostate cancer recurring after surgery and, therefore, a major step forward to advise our patients to stop smoking when diagnosed with prostate cancer”.

Changes in surgery methods significantly reduces antibiotic resistance

A new study shows how changing working methods in surgery can significantly reduce bacterial resistance to antibiotics, while maintaining protection against infection and reducing costs by up to 60%.  This work is being presented at the European Association of Urology conference in Madrid.

Antibiotic resistance is one of the most important medical problems facing the 21st century, with the medical world acknowledging a lack of new antibiotics in development. In the absence of new drugs in the worldwide pharmacopeia and in the pharmaceutical pipelines, the only way to contain the development of resistance is by changing the way we use antibiotics. However, too often it is easier just to carry on using antibiotics as before. Now a new multi-centre study shows that adherence to guidelines can significantly reduce bacterial resistance in urology surgery.

Antibiotic use is common in urological surgery. In 2010 the European Association of Urology introduced new guidelines* on urological infection in the hope of containing some of the problems associated with antibiotic resistance. In early 2011 an international group of clinicians from Italy, Germany, Norway, and the UK began to work strictly to these new guidelines, with a view to testing just how effective the procedures might be.

Over a period of 33 months they measured outcomes of 3,529 urological procedures (including open, laparoscopic, endoscopic and robotic surgery) which took place under strict adherence to the EAU Guidelines. The results were compared with 2,619 similar procedures from 2006-8 carried out before the new guidelines were implemented.  They found that the rate of infections was similar in the two periods. However, the costs of the antibiotic drugs, and other indirect costs, were significantly lower in the period the guidelines were followed. The antibiotic resistance rates also dropped significantly.

Lead researcher Dr Tommaso Cai (Santa Chiara Hospital, Trento, Italy), commented:

“The changes we made were fairly significant, and required monthly audits to ensure that we were sticking to the new system. For example, under the old system it was standard practice to give a patient who was having an operation** for benign prostatic hyperplasia, the antibiotic ciprofloxacin  both before surgery, and then for 7 days afterwards. But when we adhered to the guidelines we only gave the antibiotic prior to the surgery”.

“We were pleased to find that infection rates did not change between the ‘before’ and ‘after’ periods. However, we also saw significant costs savings, and perhaps most importantly we were able to show a significant decrease in bacterial resistance. For example, E.Coli resistance to ciprofloxacin  decreased by around 15% after we adopted rigorous adherence to the guidelines”.

The reduction in drug-related costs was highly significant: cost-per-procedure was €46.90 in the ‘before guideline’ period, but these dropped to €18.77 when working to the guidelines, a drop of 60%.

Professor Robert Pickard (Professor of Urology, Newcastle University, UK), Chair of the EAU Guideline Panel on Urological Infections (and a co-author of the study) said:

“The main bacterium that causes all types of urinary infection, Escherichia coli (E.coli), is becoming increasingly resistant to treatment using the antibiotics we have available in 2015. This antibiotic resistance is a major health threat, particularly to countries in the EAU community with our advanced healthcare systems. The only proven way to reduce the threat is by antibiotic stewardship to control the overuse and misuse of antibiotics in healthcare. This study shows that by following a few simple rules hospital usage of antibiotics can be dramatically reduced without affecting patient safety, and results in lower resistance and reduced costs”.

*See current EAU guidelines http://uroweb.org/guideline/urological-infections/

**The example given is for a TURP (Transurethral resection of the prostate) operation for BHP. Standard procedure before guideline implementation would be to give 400 mg ciprofloxacin before the operation, then 2 tablets a day for 7 days afterwards. After guideline implementation this changed to only 400 mg ciprofloxacin before the operation.

Study shows regaining normal sexual functioning is “rare” after prostate operations

Regaining normal erectile function is rare after the most common prostate operation, radical prostatectomy. This is the main result of a new study which is presented at the European Association of Urology Congress in Madrid.

Radical Prostatectomy is the removal of the prostate gland during a prostate cancer operation. This can often remove the cancer, but there is a major possible side-effect*, erectile dysfunction – the inability to have an erection. This is because the nerves which surround the prostate are often damaged during the operation, and these nerves control the ability to have an erection. In many cases, this improves with time, but now new research indicates that achieving an erection of the same quality as before the operation is rare, and may have been significantly overestimated by doctors.

The standard way of measuring erectile function is via a questionnaire, the International Index of Erectile Function (IIEF), but this is not specifically aimed at prostate cancer patients. Some researchers had felt that the questionnaire did not take account of the special circumstances of a sudden change in erectile function brought on by surgery, or allow comparison with sexual activity prior to the operation (the IIEF questions only deal with sexual activity within the previous four weeks).

A group led by Dr Mikkel Fode, from the Herlev Hospital in Copenhagen, asked 210 patients to complete the IIEF questionnaire, around 23 months after Radical Prostatectomy surgery. However they added an additional question: “Is your erectile function as good as before the surgery (yes/no)”. Only 14 patients (6.7% of respondents) reported that their erections were as good as before surgery. This compared with 49 patients (23.3%) who showed no decline in the in the IIEF score.

As Mikkel Fode said:

“The occurrence of sexual dysfunction after prostate cancer surgery is well known but our method of evaluating it is new. What this work shows is that having an erection as good as before surgery is a rare event, with the vast majority of men, more than 93% in our sample, experiencing some sexual problems after prostate cancer surgery. Fundamentally, we may have been asking patients the wrong question, but of course we really need bigger trials to confirm this.  We think that this work gives a more realistic, idea of the real problems which most men have after prostate surgery.

This is important to know before deciding on undergoing the treatment as your choice might be affected. For men who have already undergone surgery it is important to know that they are not alone in the situation and that their physician will likely be able to help if they discuss the problem”.

Commenting, Professor Francesco Montorsi, Chair Department of Urology, Vita Salute San Raffaele University, Milan, Italy and Editor Emeritus European Urology said:

“As the average age of patients undergoing radical prostatectomy is decreasing, maintaining the ability to have an erection after an operation is increasingly important to men facing surgery. This is the first study of its kind, so we need to confirm the findings but above all to learn from problems which can face patients after prostate cancer operations. We need to look more closely at nerve sparing techniques, and ensure that good post-operative care is available for each patient”.

 *Incontinence is also a possible side-effect, but this is less common.

Major new study suggests younger men need to review priorities with time after surgery for high-risk prostate cancer

Does age affect the outcomes of men after radical prostatectomy for high-risk prostate cancer? Does a long post-operative cancer specific survival make a difference in outcomes in such patients? A major new study suggests that both the age of the patient and the time survived since the operation have a significant impact in terms of cause of death. In practical terms this means that, for young men with high-risk prostate cancer, doctors may have to re-evaluate long-term clinical priorities with increasing time since surgery. This study is being presented at the European Association of Urology conference in Madrid.

These conclusions are based on the efforts of a multi-institutional international collaboration (the EMPACT group) developed to record long-term outcomes of patients classified as having “high-risk” prostate cancer (see below for definition*) and treated with radical prostatectomy. The study team was able to compile a database of 7650 patients from 14 different tertiary care centres in Italy, the USA, France, Belgium, Germany, Poland, Switzerland, and the Netherlands. Within this population, they were able to identify 612 patients treated with radical prostatectomy (RP) over a 26 year period, from 1987 to 2013 who were under the age of 60. The median follow up time was of 89 months. For each patient the number of cancer-specific related deaths (CSM) were recorded, and compared with the number of non-cancer related deaths (OCM).

They found that in patients younger than 60 years of age, there was a higher probability of dying of prostate cancer than of other causes in the first 10 years after a radical prostatectomy operation. However, after that initial period, cancer deaths diminish and other causes of death become more significant. This means that with increasing time since radical prostatectomy, care for these patients should gradually shift from prioritising prostate cancer towards prioritising other health risks (such as heart disease), even though regular urological check-ups should continue.

	Probability of succumbing to Prostate cancer after 5 yrs from last assessment  (CSM)	Probability of succumbing to other causes (OCM) after 5 yrs from last assessment
Time of last assessment	-	-
After 5 years from surgery	7.3%	2.6%
After 8 years from surgery	6.7%	5.8%
After 10 years from surgery	5.3%	9.9%

Commenting, lead author Dr Marco Bianchi (Ospedale San Raffaele, Milano, Italy) said:

“These results confirm that if you are under 60 when you undergo a radical prostatectomy you need close follow-up, concentrating on possible cancer recurrence for the first 10 years. After that time, patients should worry less about prostate cancer and priorities may need to shift to other health risks, even though regular urological check-ups should be continued.

What this means in practice is that each patient needs close, personalised regular monitoring, where the urologist should not focus only on prostate cancer features, but also on the general health status of the patients. This is particularly important especially with increasing time after surgery, since new comorbidities, such heart disease, may develop and become a more immediate risk to the patient’s health”.

*High risk was defined according to the D’Amico criteria (PSA>20 and/or cT3 or higher and/or biopsy Gleason sum 8-10).