Jovi Stuart
Welcome to this evening's webinar, Advances in Urology: Understanding Haematuria, PSA testing and BPH management. We are joined tonight by speakers, Dr Jinna Yao and Professor David Gillatt. My name is Jovi. I am the Projects and Events Officer for the New South Wales ACT faculty, and I am your host for this evening, your RACGP representative. Just before we get started, I would like to make an acknowledgement of country. We recognise the traditional custodians of the land and sea on which we live and work. We pay our respects to elders past, present and emerging. I would also like to acknowledge any Aboriginal and Torres Strait Islander colleagues who have joined us online tonight. I am joined from Cammeraygal Land on Sydney's North Shore.
I would like to introduce to you our speakers for this evening. We have got Dr Jinna Yao. She is a Fellow of the Royal Australasian College of Surgeons and obtained a Master of Surgery at the University of Sydney and underwent a six-year Advanced Surgical Training for Urology. Jinna went on to complete her post-fellowship training in kidney and pancreas transplantation where she gained skills in complex open and laparoscopic kidney surgery. Dr Yao then completed Robotic Urological Oncology Fellowship at Macquarie University Hospital where she underwent rigorous training in robotic surgery for kidney and prostate cancers. Welcome to Jinna. Professor David Gillatt is a Specialist Surgeon and Director of Medical Services at Macquarie University Hospital. David is recognised as one of the world's foremost robotic surgeons in the treatment of both prostate and bladder cancers. David also has expertise in the discovery and optimisation of biomarkers for early prostate cancer diagnoses and prognoses and in the effects of ketamine abuse on bladder function. Before joining MQ Health, David was Clinical Director of Urology at Southmead Hospital and Medical Director of the Bristol Urological Institute where he established the Prostate Cancer Care and Research Centre. Last, but not the very least, we have got Dr Natasha Feingold, a Sydney-based GP in Sydney. Natasha works for a specialised women's health clinic where she has special interest in chronic disease management. Natasha is committed to quality medical education for junior doctors and worked for many years as a lecturer at the University of Notre Dame School of Medicine. Additionally, Natasha has held a number of roles within the college such as an examiner for RACGP fellowship exams and as well as the chair of the New Fellows for the New South Wales ACT Faculty, which advocated for recently fellow GPs and organised wellbeing conferences for doctors and their families. Welcome to all of our speakers. I would like now to hand over to Natasha, who is going over the learning objectives. Thank you, Natasha.
Dr Natasha Feingold
Thank you, Jovi, for that warm welcome. I am very excited to be here today to talk about a very hot topic that we all come across in general practice. Our learning objectives for tonight are: Number 1, identify the potential causes of haematuria, enabling accurate diagnosis and appropriate management. Interpret PSA test results and guidelines and discuss how to investigate an abnormal result. Outline minimally invasive surgical treatments for BPH and describe the medical and surgical treatments for BPH. We might get right to it and we can hand over the presentation to Dr Jinna Yao. Thank you so much, Jinna.
Dr Jinna Yao
Thank you for that very nice introduction. Tonight, I am going to be talking about minimally invasive surgical treatments for BPH. I suppose it is quite relevant because more and more patients are walking into our consultation rooms asking and interested about these minimally invasive treatments. I have no disclosures. After introduction, we will talk about the evaluation of someone with BPH and low urinary tract symptoms. We will talk about the medical therapy and surgical treatment of BPH. The prevalence of BPH is increasing with an ageing population. It is an androgen-driven disease of the prostate gland and it causes benign enlargement. Treatment is with medications or surgery. What is minimally invasive surgery? This is a list but it is not exhaustive. It is constantly growing. The ones of note are the Rezum or the water vapour therapy, Urolift, the iTind, the aquablation, prostatic artery embolisation. I see minimally invasive surgical treatment as sort of a midway between medications and the traditional BPH surgery. There is an increasing demand for less invasive treatments compared to traditional surgery, and this is where the MIST treatments come in and fill this space. The choice, though needs to be balanced between less risk of complications and sexual dysfunction at the cost of a more modest outcome of BPH treatment. Over the recent years, there has been an increase in utilisation of these minimally invasive surgeries for BPH. You can see here that there is an increasing utilisation of prostatic Urolift, water vapour therapy or Rezum and the utilisation of the more traditional methods of surgery for BPH has been going down. TURP and also GreenLight laser has also been on a decline. Same kind of trend demonstrating in a different way. This is a paper looking at the Google search terms. You can see that there is an increasing interest in Urolift in recent years as well as HoLEP Rezum whereas the search term for TURP and GreenLight laser has stayed much the same over the last few years.
Let us start off with a case. A 52-year-old male patient called Ronny. He presents with a three-year history of weak stream, post-void dribbling. He is otherwise well, no history of trauma or surgery. Immediately in my mind, the differential diagnoses are urethral stricture or blood outlet obstruction. The initial evaluation includes a thorough history. I like to get them to do an International Prostate Symptom Score as well. This is just a quick way that the patient can complete these questionnaires in the waiting room while they are waiting to see you, goes through all the symptoms such as incomplete emptying, frequency, intermittency, urgency, weak stream, straining, nocturia, and also there is a quality of life question at the end as well. I do a urine M/C/S to make sure that they do not have infection that is causing the urinary tract symptoms. It can also be a relative contraindication for certain treatments such as Rezum for instance. I would like to know their kidney function to make sure that they do not have any upper tract compromise as a result of their bladder outlet obstruction. Any patients who are at increased risk of prostate cancer such as if they have family history of prostate cancer or if they are older than 55, then I do a PSA. I also do renal tract ultrasound and a Uroflow. Ronny's urine is unremarkable. His renal function is normal. His renal tract ultrasound is essentially normal except his prostate size is mildly enlarged. Normal size for a prostate is about 20 to 30 g. His is 40 g. Often patients are quite worried about a big prostate because they equate that with cancer. They are worried about it and they want treatment for it, but I am careful to tell them that just because their prostate size is enlarged does not mean that they are at increased risk of prostate cancer, and it does not mean that they have worsened symptoms as well. There is actually not much correlation between prostate size and symptoms. Just because they have a really big prostate does not mean they have a lot of symptoms, and just because they have a small prostate does not mean they do not have symptoms. His urine flow. This is a normal trace. His is a little bit blunted and more protracted. The maximum flow is what we look at. It is 7 mL/sec. Normal is more than 15 mL. Abnormal is less than 10 mL. We performed a cystoscopy on him. He actually does not have big protruding, obstructing prostatic lobes, but his bladder neck I found was a bit high and tight. I trialled him on tamsulosin 400 mcg and that actually significantly improved his symptoms. I think that using tamsulosin or an alpha-blocker to trial to see if that improves the lower urinary tract symptoms is actually quite useful diagnostic information because it is an alpha-blocker so it works on the bladder neck. If it works, then it implies that the pathology is at the level of the bladder neck and prostate. Medical therapy for BPH is broadly divided into two groups. There is alpha-blockers and 5-alpha reductase inhibitors. Alpha-blockers work by smooth muscle relaxation. The common ones that I use are tamsulosin and silodosin. Tamsulosin 400 mcg nocte, silodosin 4 to 8 mg nocte, use it at night because it causes postural hypotension, lightheadedness, so it is better if they take it before they go to sleep. For patients who have a lot of cardiac comorbidities and who are a bit more older and frail, I tend to start them with silodosin because it is the most selective for alpha-1A receptors, and they are the ones that are more specific for the bladder neck and prostate. There is less cardiovascular impact. The rate of postural hypotension is similar to placebo. They have the highest rate of retrograde ejaculation, which is what you would expect because they are the most selective. I do not tend to use them as much in younger men. If they have concurrent erectile dysfunction, then you could try using tadalafil as well. I warn them about the side effects such as hypotension and nasal congestion and retrograde ejaculation.
Dr Natasha Feingold
Jinna, there is a question in the chat box about trialling tamsulosin before cystoscopy while we are waiting to see the urologist. Is that appropriate?
Dr Jinna Yao
Oh, yeah. That is completely appropriate. Yes.
Dr Natasha Feingold
We also just were hoping to get a bit more of an explanation of uroflowmetry.
Dr Jinna Yao
Uroflow is where I explain it to the patients like we get them to drink a lot of water, hold their bladder and then pee into this funnel shaped machine, and then it spits out that little graph like I showed you before, and basically the useful information that we can gauge is the amount that they void, this runny voided almost 300 ml, and often we do a bedside ultrasound to see how much post-void residual they have afterwards, and then the important thing is the Q-Max or the maximum flow. If they have a low maximum flow, they may be obstructed but they may also have what is called detrusor failure. Their bladder is not pumping properly. They are either blocked off or the bladder is not pumping properly to generate enough pressure to push the urine past the blockage, but very reasonable to start empirical therapy with tamsulosin, or do a diet or something prior to referral to the the urologist. The other medical treatment for BPH is five-alpha-reductase inhibitor. That works by lowering the amount of testosterone because it is an androgen driven disease, and it causes a reduction in the prostate size. The more common one that we use is dutasteride. It takes six months for the minimum effect. That is why I guess it is often used in combination with tamsulosin, Duedate, because the Dutasteride component actually takes a lot longer to work. The studies indicate that it is more useful for prostates that are larger than 40 g in volume. It also halves your PSA artificially. Before I start, anyone on Dutasteride or Duedate, I will do a PSA, and then after six months of treatment, you would expect the PSA to halve. Then in order to get the true reading of the PSA, you need to double it. Side effects erectile dysfunction, low libido, low jack lip volume, gynecomastia. Combination therapy, five-alpha-reductase inhibitor and alpha-blocker like Duedate consisting of tamsulosin and dutasteride leads to greater improvement in symptom score and quality of life than either drug alone. It has been shown to reduce the rate of acute urinary retention, need for surgery, and symptom progression. You can also use like tamsulosin and alpha blocker with anticholinergics such as solifenacin or beta three agonists such as omega if they have mixed obstructive and irritative symptoms, and I think that is often useful because a lot of patients get bladder outlet obstruction and then over time the bladder becomes more sensitive, and there is activation of C fibres and things like that, and then that causes irritation of the bladder mucosa, and then subsequently they get overactive bladder symptoms like urinary frequency and urgency, and so they can have OAB secondary to their obstruction. There is a downside of long term medical therapies. I do not really like to put these patients forever and ever on long term medical therapy. Alongside the known side effects of alpha blockers such as, postural hypotension, ejaculatory dysfunction and five-alpha-reductase inhibitors such as erectile dysfunction and low libido. There are other side effects that we are starting to become more aware of as well, such as an increased risk of stroke, dementia, post finasteride syndrome as well, which is like a constellation of symptoms including irreversible sexual side effects and psychiatric side effects as well. Often I would put these patients on medical treatment for about a year or so, and then at the end of the year, we plan to take them off it and see if that causes their symptoms to return, and if it does, then I offer surgery because I see bladder outlet obstruction as a surgical problem, then we can actually fix the root cause of the issue, of course, that is in someone who is medically fit for surgery. Also keeping in mind that chronic bladder outlet obstruction can lead to complications as well, so even if you do not treat them or if you actively survey these patients or patients who are on long-term medical therapy, then we need to watch for these kinds of complications. As the bladder is obstructed, it causes hypertrophy of the bladder walls, and sometimes that is why you get the ultrasound report saying that there is thickened bladder wall and trabeculation. This is what it actually looks like on cystoscopy, and once it gets to this point then a lot of times the detrusor function has been irreversibly damaged, and so that is when you run into problems like chronic urinary retention and detrusor failure, and then their post-void residuals get higher and higher. Then that can have effects such as putting back pressure on the kidneys. You have bilateral hydronephrosis then and that causes renal impairment. It can cause diverticular formation and then stones forming because you have got stasis of urine and incomplete bladder emptying, you can have urinary tract infections because of incomplete bladder emptying and as the prostate hypertrophy, they get a lot of blood vessels. They can have haematuria, and also they can go into acute urinary retention as well. One alternative to surgery is intermittent self-catheterisation for people with chronic retention. These are the people with high post-void residuals and have problems like UTIs and things as a result. It maintains sexual function. You can use disposable catheters or your reusable catheters. Patients must be reliable, dexterous, and you cannot rely on a caregiver to do the catheterisation. So our patient, Ronny, six months later, he does not want to keep taking his medications because he had retrograde ejaculation. We talked about surgery. I talked to him about a MIST, either Urolift, Rezum, iTind versus bladder neck incision versus a TURP. To Ronny, preservation of sexual function is important, AND so out of the three he chose, iTind and post-operatively his Uroflow improved in terms of his maximum flow improved slightly from 7 to 10ml. Voiding time he stands up emptying his bladder at the toilet improved from 56 seconds to 42 seconds, and his post-void dribble also improved as well. When I am counselling these patients for minimally invasive treatments I say to them that the effectiveness of these minimally invasive surgery is about equivalent to the effect of medications. I see it as replacing the medications rather than competing with the classic surgery for BPH, which is TURP. The indications for surgery include renal insufficiency, urinary retention, recurrent UTIs, bladder stones, refractory haematuria. Relative indications include bothersome symptoms and not interested in taking medications long term, but I think that if you have any of these indications, then the classic textbook teaching is to go for a TURP rather than go for the minimally invasive surgery. This is basically a whole list of surgical options available for BPH. There is a lot it depends on prostate size. If you have a really large prostate, greater than 100g, then traditionally they say go for a simple prostatectomy or laser enucleation of the prostate either with holmium or thulium, but these days over 100g most people get a TURP I think. From average to small size prostate, then this is where the minimally invasive treatments come in. As we said before, the treatments for BPH and lower urinary tract symptoms include watchful waiting, medications and surgery, and now there is a growing market for minimally invasive treatments. Let us talk about surgery first. The two broad categories of surgical treatments for BPH is enucleation versus resection. Enucleation is where we actually enucleate the whole prostate adenoma as a whole, whereas resection is we take little chips out like a TURP. So simple prostatectomy I guess is the ultimate form of enucleation, and basically we take out the it. Traditionally it is done via a big open cut and then we use our fingers to claw out the middle of the prostate and enucleate it. These days, we can do it robotically too. This is a TURP. The TURP is considered a classic gold standard. Traditionally it's for prostates less than 100 g, but these days you can do 150 g TURPs and more even can be monopolar or bipolar. The idea is to basically open up that bladder neck there and keep resecting. I tell the patients like coring out the inside of an apple or turning a two lane highway into a four lane highway to increase the flow of urine. They have a catheter there for 48 hours. Complications include bleeding, TUR syndrome, retrograde ejaculation, erectile dysfunction, bladder neck contraction or stress incontinence. I think the differentiating risk factor in terms of making a decision as to which procedure to perform is the sexual side effects. By far and large, most people, if you do it properly, is probably going to get retrograde ejaculation because the bladder neck should be wide open after you perform a TURP on them, and so when they ejaculate, it goes backwards into the bladder rather than forwards, and this is not reversible, and I think that a lot of patients may underestimate the importance of this prior to their surgery. Transurethral incision of prostate. This is more ideal for smaller glands and higher bladder necks. There is less risk of sexual dysfunction, and basically, you just make incisions in the prostate most of the time at 5 o'clock and 7 o'clock to open things up. Laser treatment for BPH. You can use the laser either holmium, thulium or greenlight laser to enucleate or to vaporise prostate tissue. Advantages are that there is a lower risk of bleeding, shorter catheterisation time, but they may have more irritative symptoms postoperatively. The holmium or thulium laser enucleation of prostate that it follows natural planes of the prostate tissue in the what we call the anatomical plane of the prostate because it allows for less bleeding in that plane. It can do very big prostates, transient incontinence is common, usually for weeks, and usually it resolves with pelvic floor physio. Retrograde ejaculation is common competitor. There is a similar mid to longer term efficacy and longer operative times than a TURP. This is a greenlight laser. It works by selective absorption of laser energy by haemoglobin causing vaporisation, and so that is why it is so good for haemostasis, and it can be performed with patients on anticoagulation like warfarin or Plavix. Compared to TURP, similar efficacy in the short and medium term but maybe inferior longer term efficacy. It is more haemostatic, takes a little bit longer as well. You can see that the laser burns away at the bladder neck there, but the same kind of idea you just want to widen up that bladder neck. Post operatively, you can see that the urine is very clear in these cases, and sometimes you can just trial avoid them the next day or on the same day even. Let us talk about the minimally invasive treatments. I tend Urolift and Rezum. In general, they have less sexual side effects and reduced or no need for catheterization. The Urolift has been on the market for quite some time. It is a permanent nitinol and vicryl implant in the prostate. We insert this via cystoscopy and we put these pins into the prostate. It is for small to medium sized prostates. There is minimal recovery, no catheter required. There is a low risk of sexual dysfunction, and compared to TURP, they are similar results at two years, faster return to normal activities. There may be a higher reintervention rate at two years, but again, this is something that can be repeated as well with less side effects. Water vapour therapy is something that is becoming more and more popular. This is where we insert a cystoscopy in and then using the needles, we deliver steam into the prostate, and it causes necrosis and atrophy of the prostatic tissue, and because this process requires a while to occur, then we leave the catheter into 3 to 7 days. The improvement in voiding begin by two weeks, but may take months for maximum effect, and there is low risk of sexual side effect and some irritative symptoms is common in the first 4 to 6 weeks. ITind, it is a Nitinol device that we insert with a cystoscopy, and this basically exerts pressure on the prostate and slowly expands over the course of 5 to 7 days, and makes these deep incisions in the prostatic urethra, and then that device is retrieved 5 to 7 days later. There is less sexual and ejaculatory side effects, but they do get a bit of discomfort, especially during the first seven days while they have the device in place. Aquablation is something that is not available in Australia at the moment, but it is basically a robotic assisted prostate ablation using high pressure water jets and with leaving a catheter overnight. There is less sexual side effects again. There is a higher bleeding risk because there is no mechanism for haemostasis attached to the device, so you have to go back and use diathermy to coagulate everything. Basically, the treatment is planned using a rectal ultrasound so that that is the prostate there, and then basically you just press a button and then it like vaporises that tissue with a water jet. Prostatic artery embolisation, this is something that some patients ask about as well. This is where arterial catheters are inserted into the femoral or radial artery, and prostatic arteries are embolised, and then the cells die and then they slough away. Compared to a TURP, they are less effective. They have a high urinary retention rate, but they have a lower bleeding risk. It takes weeks to months for improvement. It is not currently recommended by the American European guidelines and it is reserved for co-morbid patients. In summary, there are a lot of ways to treat a large prostate. Evaluation should confirm obstruction and rule out infection and malignancy. The choice is dependent on the side effect profile and the risk tolerance to the patient. TURP is considered the gold standard for treatment for BPH, and there is an increasing demand for minimally invasive surgery for BVH. Men who are concerned about preserving sexual function should consider Urolift, Rezum, or iTiND, and laser treatment for BPH should be considered for men who are on anticoagulation. Thank you.
Dr Natasha Feingold
Thank you so much, Jinna. For the sake of time, we might just go ahead and move on to Professor David Gillatt. I know there are some questions in the chat box, but we might come back to those after Professor Gillatt talk, and Dr Yao will have you back on the panel for the Q&A as well. Thank you so much. David, over to you.
Professor David Gillatt
Thank you for asking me to talk about two things. Hopefully I have had time to talk about PSA and prostate cancer and then something about the management and investigation of haematuria. When I was training prostate cancer was like this. You had skeletons full of bony metastases, spinal metastases, blocked kidneys. Most people with prostate cancer tended to present with advanced disease. What prostate specific antigen has done since the late 80s early 90s is actually change the pattern of prostate cancer, hopefully mostly for the good. PSA has its challenges and problems, but it has been a good thing in terms of diagnosing disease earlier and enabling us to both monitor the disease but also cure it to where possible, whereas 35 years ago or 30 years ago, most prostate cancer was not curable. These x-rays all show advanced metastatic disease. Prostate cancer has gone from something that would be on the right of this where most people presented with locally advanced or metastatic symptomatic disease. We had acid phosphatase and that was about it to diagnose it to to the majority now presenting with localised disease and many appropriately having radical local treatment. Where we see metastatic disease it is often a progression from failed local treatment, and hopefully in the majority of cases, local treatment controls or cures the disease. PSA has shifted the pattern of prostate cancer from advanced symptomatic disease, which had a probably somewhere between 18-month and 30-month life expectancy on average to one where more most people are probably being diagnosed at a stage where curative therapy could be offered. It is important we emphasise to our men that as you get older, they need to keep checking themselves, just as women will check for breast and cervical changes. It is reasonable to suggest to our men as they get older, and probably be talking about from the late 40s into the 70s, that they need to check their prostates for signs of early prostate cancer. Just a few facts about process about PSA, PSA is a normal substance that is present in all men who have had normal hormones and have a prostate present. It is a protein that is probably responsible for delivering the sperm to the appropriate targets in the semen, but it can change. There are many facts that need to be known about it. We need to be aware that most of the time we are measuring the total PSA in the circulation. You can also measure free PSA, which is the PSA floating around without being attached to other proteins. Is there such a thing as a normal PSA? Well, it is partly age dependent. For example, a man in his 40s, you may not want to see a PSA much over 2. A man in his 80s, you may allow a PSA that is much higher than that to be considered the normal range. PSA tends to rise with age and enlargement of the benign prostate, and you can allow perhaps on average a 0.75 ng/ml rise per year just from benign change. If it is rising faster than that, you have to be suspicious that there is something else other than benign disease present. PSA can be affected by infection, occasionally very acute infection. If you choose to measure the PSA, which you probably should not, you can put the PSA up to very high levels, which subsequently should settle down to normal levels after treatment. Free PSA can be worth measuring. Lower levels indicate a higher risk of finding a significant cancer. Various papers might suggest less than 15, less than 13, less than 12% being the higher risk. The simple messages labs often quote over 25% as being normal. If it is getting into the 15% or less range, it just indicates the slightly higher risk that the PSA is indicative of an early prostate cancer. You also need to be aware that PSA can fluctuate. If it rises above benign levels, it can be worth repeating the PSA before further investigation. You do get some people whose PSA is all over the place. It can be up and down and that can be quite difficult to interpret. There is also a negative predictive value of PSA, a low level for example, less than 0.9 at the age of 60 confers a very low risk of cancer over the next ten years. PSA is a useful marker, but it will show that it is just hopefully the minute that it is just a test that allows you to decide whether further tests should be done. Saying that, if you actually get on to treatment either locally radical treatment or more advanced disease, PSA is a very good marker of disease response and progression. It has a different function there. It is used to indicate whether, for example, if you remove the prostate and the cancer entirely, the PSA should go to zero and stay there. If you treat an advanced cancer with hormone therapy androgen deprivation, the PSA should fall rapidly. If a patient is going to respond well, so it has another function. It is a monitoring of treatment marker as well as being a diagnostic marker. It is just a balance. The benefits of PSA I will show you in a second or that if you use it you will diagnose disease earlier. You will get patients with a lower metastatic burden or less with metastases at diagnosis, and there are studies that have suggested you can reduce mortality from prostate cancer, however, you will undoubtedly put people through unnecessary biopsies with overdiagnosis and certainly in the past less so now over treatment with more stratified treatment now depending on cancer aggressiveness, but undoubtedly certainly in the 90s a lot of men were very low grade cancer, were getting surgery and radiotherapy that may be now deemed less necessary and more appropriate for surveillance. There is a balance for PSA. It does overall in the population reduce mortality and improve the chances of finding earlier cancer, but you will undoubtedly put some men through biopsies that they could have avoided if you have not done a PSA. Just a little side issue. Who is at risk for prostate cancer? Well, if you look carefully, it is men who have the biggest risk for prostate cancer in the UK and the USA. Men of African heritage have a higher incidence of prostate cancer. Men with a family history of prostate cancer at usually a father, a brother, an uncle who are at a young age will be at a much higher risk of getting the disease themselves. Frequency of sexual function. The more often you do it, the less cancer you seem to get, but the one factor is that if you check your PSA and that tends to be more common in middle class and better off men then you will find prostate cancer at a curable stage, and therefore, one of the main risks for prostate cancer is getting your PSA checked, and we the people who tend not to do that are those from the less advantaged populations. I will just skip through that bit. What happens if you do PSA in a population? Well, these are quite old slides, but you can see for example PSA appeared in the USA in the late 1980s. Prostate cancer is on a slow upward trend there, and the lower graph on the left is the UK, England, Wales, anyway and you can see that resulted in an increase certainly falling more rapid in the US in diagnosis and more incidence of prostate cancer. The same happened in England and Wales, but PSA screening was much less penetration in the population in the UK. In fact, for many years, it was advised against in the UK by the NHS and by general practice groups. There was an increase which paralleled PSA introduction but it was not as marked as the US, you see on the right hand graph. However, the mortality from prostate cancer continued to rise during this time, although not as high as the incidence. PSA means you diagnose more prostate cancer and hopefully treating it and you can see the mortality in the mid 90s onwards started to fall for prostate cancer, hopefully due to better and earlier diagnosis. Should we therefore use PSA and screen for prostate cancer where there is evidence in favour of it? The European randomised study of screening which was across eight different countries and it was quite a large study of many tens of thousands of men. The initial findings were that if you screen in the screen group versus the non screen group, only 1% in the screen group presented with metastases compared to 24% who were not screened and just presented clinically, and most cancers diagnosed were deemed to be significant and not insignificant. You certainly reduced the number of advanced cancers diagnosed by using PSA. You also overall reduce the mortality of the disease. The screening group had a lower risk of dying of prostate cancer over 10 to 15 years than the control group. In that one study, it suggested that you reduce the amount of metastases at diagnosis and improve the mortality from prostate cancer by screening with PSA on a yearly basis compared to just waiting for patients to present clinically. I have to say there are other trials that disagree with that. There was one for the US that suggested that screening made no difference upon the prostate lung, colorectal ovarian cancer screening trial. However, this was quite contaminated in that about 50-60% of men who joined the trial had already been screened with PSA, so were not suitable because PSA screening was quite prevalent in America already. The European study suggests that you can benefit men by doing PSA screening if you want justification for doing it in your patients. The initial European study suggested that you probably have ever needed to treat 48 men to save one life. As the trials gone, and it suggested that it is about an 18:1 ratio. If you screen, you have a 20% risk reduction in deaths from prostate cancer in the screen group. As time goes by, it is an 18:1 ratio of treatment to life save, which is actually the same as breast cancer screening. This one study does suggest that advantage to using PSA screening in men between their late 40s and the late 60s. Should you do a DRE? Well, I think you should. It still has a role, certainly in urology. I think you occasionally put your finger in the man's rear end and you find something that does not correlate with the PSA level. Also I would talk to the patients and if they decline, which many do, an MRI adds more benefit than a DRE. DRE has its functions, but it is not, in my view, essential for every man. If you go on to a biopsy, I will come on to MRI in a second. We have moved away from transrectal biopsy. We still use a transrectal ultrasound probe to identify the prostate, but we do the biopsy through the perineum now, either under sedation or a brief general anaesthetic. It is, in my view, a cleaner, a less risky procedure. Transrectal biopsy was associated with a 3-5% risk of significant infection, even using prophylactic antibiotics. The perineal route is a little bit more fiddly, but it is less likely to be associated with infection, and it also allows access to anterior parts of the prostate that the transrectal route find difficult. I believe and it is quite prevalent in Australia and many parts of Europe, now that the transperineal route is the better way of biopsying the prostate. What about MRI scanning? You probably are all aware that MRI has sort of become part of the routine diagnosis investigation of men with a change in their PSA or a family history that indicates further investigation. Why? Well, in fact, in Australia now it is covered by Medicare because the evidence appears quite clear from initial studies out of London, for example, but if you use MRI, which has been around for 30 years, if you use it however with a number of different software mechanisms, you can identify abnormalities within the prostate that are consistent with a higher risk of those areas being significant areas of cancer rather than either benign disease or low-grade insignificant cancers, and the Promis study from the UK showed a 27% reduction in biopsies if you use MRI scanning alongside PSA as a way of determining who needs a biopsy. MRI has become standard if your PSA level indicates either because it is raised or rising that you should investigate further and probably you should review this MRI with the patient before deciding whether to do a biopsy or not. A more recent study from the UK suggested you probably do miss a very tiny number of significant cancer if you rely entirely on the PSA and the MRI being clear of abnormalities, but it is a pretty sensitive test for significant prostate cancer. I think in some men who got a rising PSA of the normal MRI, you may still consider biopsy, but MRI is the next stage in investigation. You see what you tend to find is a it is actually better. These slides with the red area show abnormalities in the prostate for example here is the pale white with the central part of the prostate and the arrows are pointing to abnormal areas. You can see the dark area on the left of the screen within the prostate, which is an area of mid to high grade cancer and a small less obvious area on the other side of the prostate. MRI first of all identifies abnormalities that have a chance of being cancer and allow you both to target those areas as well as differentiate those who definitely need a biopsy from those who you may consider not biopsying. The next stage in investigation of somebody with an abnormal PSA is a multiparametric MRI scan, and often you guys are organising them for us before we see the patient. It is certainly very helpful because you can then discuss with the patient the need for the biopsy, what you are biopsying and what the significance is, and you probably all know that the radiologists score these lesions in a system called the BI-RADS system, which is score from 1 to 5. 4 and 4 are a higher risk of finding significant cancer. 3 are mid risk when we are talking the high risk somewhere of 50-80% risk in those 4 and 5, but slightly lower for the mid risk. 1 and 2 probably a very low risk. We can determine from the MRI and the scoring system which patients are at risk of cancer and whether we should biopsy them and take that alongside the PSA behaviour. We tend to do MRI and ultrasound fusion targeted biopsies on the abnormal areas and the MRI and probably sample the rest of the prostate as well. Coming into the picture also is PSMA scanning. This is actually a vertebrae, but the PSMA is a different protein marker that is used with an isotope scan injected into the patient, and you can see there is a vertebrae here that has a slight abnormality that when PSMA scanning is done, lights up are showing prostate cancer in that vertebrae, and this has been used for staging for localised prostate cancer, and there are even trials going along side MRI scanning using PSMA scanning for diagnosis as well as staging. PSMA scanning is now available on Medicare for staging localised prostate cancer or looking for recurrent disease after localised treatment. It may well become part of a diagnostic pathway in some men, probably not everyone as data comes available about its utility in diagnosis, If we make a diagnosis, once we have had the biopsy, the MRI, the PSMA scan, I think we need to be aware that we need to stratify our cancers. Not all prostate cancers are dangerous. Some are best served by surveillance. What are they? Well, we base it on pathological grade, either Gleason score, which is a score looking at the architecture of the cancer within the prostate or grade grouping. Grade group 1 to 5, 1 being low grade, 5 being the highest grade of aggression. Gleason scoring more than 8 is quite aggressive, 6 is low grade and 7 in between is mid grade, but that is quite a large group of people, 7 being the commonest probably. You have got localised prostate cancer. It is useful to risk stratify your patients into low, intermediate and high risk because many low risk patients are probably best served by active surveillance, which is not ignoring it, but is a process of active monitoring to try and identify those patients who are showing signs of progression who may need treatment and leave alone the majority who probably do not need treatment because they never progress. This is a recommendation from NICE in the UK that men with low risk localised disease who are fit for radical treatment if they are very low risk, should be offered active surveillance. It caused a lot of controversy 15 years ago in the UK. People were getting quite upset about the suggestion that you should not immediately operate on people with prostate cancer, but in fact it has become in the meantime, standard management, low risk localised disease should almost certainly be offered active surveillance and only offer radical treatment to those who show signs of growth or progression of their cancer. What is low risk prostate cancer? Well, low grade 1, early 2 usually Gleason some 6 or maybe low volume 7 with a low PSA and low stage disease, probably also with a low number of positive biopsies. It is people with low grade low volume cancer essentially, and in some series, the risk of these actually going on to dying of their cancer for example in this study from Toronto, only 3% of these very low risk patients died over a ten year period of cancer. Some had treatment on the way. Some patients do not like surveillance and switched to active treatment even though their cancer is not progressing, but if you actually take overall a series of 450 odd patients over ten years on surveillance overall, and if you took this approach, only 3% died of prostate cancer because they are low risk, some probably need a treatment on the way. Most carried on with surveillance. Does the surgery make a difference to mortality or radiation in men with more aggressive disease? Well, there is only one proper biopsies two randomised trials. This is the Scandinavian one that compared radical prostatectomy against waiting and seeing, and it showed in higher risk disease that men actually benefited from surgery. There was overall 44% better survival at seven years in those who had surgery with higher risk disease. In other words, they got medium to high risk cancer compared to low risk disease over watchful waiting. So yes, there is evidence in favour of radical treatment in men with more aggressive cancers. There is a study out of the UK that I was involved with which compared surgery with radiation with watchful waiting, and again, it showed some advantage at ten years to surgery or radiation over active monitoring in people with moderate to high risk disease. and that was a study of over 2000 men. There are a couple of studies that suggest that radical treatment helps in the patients who have not got low risk disease. They have got medium to high risk disease. So yes, we can justify radical treatment. What is the benefit of active surveillance? Well, obviously active radical treatment has side effects, including effects on continence and potency, and if you could avoid that in a lot of men with low risk cancers, you avoid the side effects of radical treatment. You have to discuss what the with the patient, what the best way of following up is, and additionally, you may want to do the PSA to get an idea of its behaviour every three months for reducing the six monthly. Early guidelines suggest you should bypass the prostate every year or 18 months, but now MRI is coming to that space and most active surveillance protocols will include an MRI every one year, 18 months, and radical treatment would still be the standard treatment if those early low grade cancers started to show signs of changing. I think I am going to run out of time soon, so I am just going to move on to a little bit about haematuria, if that is okay, for five minutes if I can get this. So I am sure there are some questions about PSA. PSA is a good thing that has to be taken in context. I was also going to just briefly cover what we should do about blood in the urine haematuria, and by definition it is just the presence of blood in the urine. We should divide it into non-visible often in the past called microscopic haematuria and visible haematuria. The patient sees blood in the urine. It can be painless, which is often more concerning than painful. Painful may indicate infection or other disease, but these are useful ways of breaking down blood in the urine. Non-visible, people often say that the dipstick or stick testing is too sensitive, in fact, if you look at what is normal in the urine in terms of red cells, they are probably not sensitive enough. The normal level is actually lower than the 60 detection, but a lot of that is based on for example, the early studies were on 10,000 Israeli soldiers, the military in 1960s all in their teens and 20s, which probably is not representative of an older population, so you can get false positives. You get blood in the urine with exercise and contamination with menstruation. You can get false negatives in some drugs. Will give you a false negative in the urine, but overall, if you detect blood in the urine, it is worth having microscopy. You have got to remember if you do microscopy and send it to the lab, by the time he gets there, red cells may well have lysed. So a positive continuing or a continuous positive stick detection for blood probably should be investigated further. Guidelines often suggest you should investigate. Is any even a single episode of visible haematuria? and all macroscopic haematuria is certainly in older men, but even in younger ones if it is painless. Non-visible haematuria in men and women over 50, although some series suggest the pick up rate for significant pathology in microscopic haematuria is as low as 1%. It depends on the population you are looking at. One thing you have to be careful is young women with blood in the urine and UTIs or not getting UTIs. You do occasionally find that one of them has got a squamous cancer of the bladder. You do get some young women who have got a got squamous cancer of the bladder, which presents with pain and bleeding, and sometimes they are treated repeatedly as having urine infections if they get more than one, and with bleeding, it is probably worth considering whether you should at least have an ultrasound to check them out, and you should not blame anticoagulants for blood in the urine. They can make it more persistent, but you should not blame it for starting the blood. Investigation, urine dipstick blood pressure because some haematuria is due to renal disease and not urological disease. MSU for infection. I would always check the renal function, the blood count. PSA is arguable. You would probably do it in the man over 50, but it was prostate cancer. Early disease does not usually cause blood in the urine. Other tests. We do not do old fashioned IV use anymore, but the first test should probably be an ultrasound plus a CT IVU or CT urogram we used to call it in the UK. If somebody has got macroscopic visible haematuria and ultrasound and a CT, there was one paper written by an Australian, but it was in Newcastle in the UK that suggested if you just did one or the other, you missed tumours in the kidney, so you should do both a CT IVP and an ultrasound. Retrograde studies only if they succumb to cystoscopy. Outpatient flexible cystoscopy is reasonable in people who go to investigate under a local anaesthetic, although many patients or some patients may prefer a general anaesthetic but some form of cystoscopy to examine the bladder even. If all the other tests are normal. small bladder tumours may not show on a CT or an ultrasound, although imaging is becoming much better than it used to be. So I guess you are going to find most bladder tumours on some form of imaging.
Dr Natasha Feingold
We might have to wrap this up unfortunately, because we are running out of time. Are there any other pearls about haematuria.
Professor David Gillatt
I will just leave that one up just to say that we have got to remember even in older people with macroscopic haematuria probably for every ten people, one might have cancer and one might have a benign course. You might not find a cause in between 50-70% of them, but you are trying to exclude malignancy so males are more at risk than females. Smokers are at higher risk. The main urologist main aim in investigating visible haematuria is to exclude cancer and in non-visible haematuria in younger people to exclude renal disease. I will just leave that as my last comment that we are doing the tests for a reason but may not find a cause in many patients we are trying to exclude cancer and more serious disease in these patients.
Dr Natasha Feingold
Thank you so much, David, and Jinna has been very graciously answering a lot of your questions in the chat box, but we have one question, David, that I thought I could pass on to you, and this will be the unfortunately only question we have for the Q&A, but how do you teach patients to check their own prostates? Can you explain that?
Professor David Gillatt
I do not usually so there is the German habits. There were studies of self-examination of prostate that in Germany, but I think the best way of checking your own prostate is to go and get your PSA checked.
Dr Natasha Feingold
That sounds good. Well, thank you so much, both David and Jinna, that was so informative, and I think we are all going to walk away with a lot of great information that we can pass on to improving our patient outcomes. Jovi, is there anything else that you would like to say before we.
Jovi Stuart
Definitely. Thanks, Natasha. So I would also like to thank all our speakers and everyone that has joined us online tonight. We hope you enjoy the presentation. Just as a reminder that as this is a CPD accredited activity and to be allocated to your CPD hour, you must complete the survey following this webinar. If you have got any questions relating to this tonight, I will send through the copy of the presentation slides tomorrow morning to your emails and you can email through any questions as well. If you have missed any parts of this webinar also you can watch it on demand on our website in the next couple of days. Thanks everybody and hope you have a good evening.