Courtney:
Good evening everyone, and welcome to tonight’s webinar, A 2022 Update on Prostate Cancer Detection and Incidental Renal Mass. Tonight our presenters are Professor David Gillatt and Professor Howard Lau, and our facilitator is Dr Tim Senior.
Firstly, I would just like to make an Acknowledgement of Country. We recognise the traditional custodians of the land and sea on which we live and work, and we pay our respects to Elders past, present and emerging. I would also like to acknowledge any Aboriginal and Torres Strait Islander colleagues that have joined us online this evening.
So, Professor David Gillatt’s expertise is in the discovery and optimisation of biomarkers for early prostate cancer diagnosis and prognosis, and in the effect of ketamine use on bladder function. Before joining MQ Health, Professor Gillatt 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.
Professor Howard Lau’s special interests in urology are renal, adrenal and prostate diseases, both benign and malignant. He has performed a series of firsts in laparoscopic renal surgery since 1998. He has been appointed VMO at Macquarie University Hospital since its beginning. He also practices at Westmead Private Hospital, where he is the Chair of the MAC and Head of Urology. He is also the Head of Robotic Surgery at Westmead Hospital, both private and public, where he heads the surgical team in a series of successful robot assisted renal transplants.
Dr Tim Senior is a GP at Tharawal Aboriginal Corporation in South Western Sydney. Tim is also an RACGP Medical Advisor for the National Faculty of Aboriginal and Torres Strait Islander Health, and Senior Lecturer in General Practice and Indigenous Health at UWS, and an RACGP Medical Educator. And I will just hand over to Tim now, who will run us through our learning objectives for the evening.
Tim:
Thank you very much, Courtney. Good evening, everyone, I hope you are keeping well. These are our learning objectives for this evening. So, this is educational speak for what we hope to get out of the next hour or so. So, by the end of this online activity, we should all be able to appraise current evidence for prostate cancer detection and diagnosis, including PSA, free-PSA, novel markers such as MiCheck, and genetic markers. Outline the role of multiparametric MRI in investigating suspected prostate cancer and monitoring low risk prostate cancer. Discuss the difference in Simple (Bosniak 1) Cystic versus Complex renal cysts (Bosniak 2 to 4), and discuss the importance of nephron preservation, particularly in younger patients. And so I am going to hand over I think to Professor Gillatt.
Courtney:
That is correct.
Tim:
Thank you very much.
David:
Thank you, and thank you for the invitation again to talk to your group. My remit this evening is to discuss prostate cancer detection and diagnosis which has been a changing and shifting field over most of my career since finishing my training. I finished training in the late eighties. PSA was the subject of my thesis, and did not really exist in the clinical picture until the late eighties, early nineties in most western countries. We will talk through some of the changes that has made in the field of prostate cancer, and how modern diagnostics are maybe shifting a little to still include PSA, but to sit it alongside other biomarkers including MRI scanning.
This is prostate cancer when I was training in the eighties. Most men turned up because they had symptoms of metastatic disease. Acid phosphatase was the only marker available, and as you can see in the skeletal picture in the middle, it is a bone scan, all the dark areas are metastases everywhere. And the other scans, they give examples of spinal metastases or obstructed ureters, caused by relatively advanced disease, et cetera. And this was only in an 18 month period when I did my research in the late eighties, I managed to find 250 men with advanced disease. We saw very little early disease, and if you present with advanced metastatic prostate cancer, in those days the average life expectancy was something under two years. It is a little greater with new drugs now. It is three and a half, four years, perhaps, but it is essentially if you get to this stage, you are probably going to die of the disease, even if you are older.
So, what has changed? Well, the shifting pattern over time is that more men are being diagnosed earlier, and they are getting radical treatment. And this graph basically shows at the left hand of the graph, the majority are probably cured, but it is those that do present with metastatic disease are often those who have had failed local treatment, which then progresses locally and metastases. Some obviously do still progress to death. But some present at the right end, still present too late at the right end of the graph with metastatic disease, and are going to have controllable disease for a while but are probably not going to survive. So, ideally, we diagnose people with significant cancer early, and we would do so simply with good specificity, good positive predictive value tests, and we treat appropriately those that need treating to stop them developing metastases. So, it is a lot that I think has been partially achieved over the last 30 years, but we still have some way to go in terms of getting the diagnosis right and the appropriate treatment.
So, is this true, as you get older, should you keep checking? This has been a debate going on for the last 50 years. Is it right to check or screen for prostate cancer? And there have been studies I will refer to that suggest that it is, but certainly, if you do not look for it, as I said earlier, you will be too late often when the disease shows itself clinically. So, yes it probably is right that you should be checking yourself for prostate disease or prostate cancer as you get older.
The tests we have, PSA, prostate-specific antigen, it comes in some forms, the total prostate-specific antigen is the amount in your blood stream that you measure routinely. Free PSA is the free PSA that floats around without being attached to any other proteins in the blood. PSA normal substance in the prostate and in ejaculate, possibly responsible for delivering the sperm in a healthy manner to the appropriate target, but it leaks into the circulation with prostate abnormalities, and that can include benign change as well as malignant change. For those reasons, it does lack specificity, it can go up in benign enlargement of the prostate or inflammation or infection, and there are therefore a number of false positives. Its benefits are, I will come to this in a minute, that it will decrease the incidents of metastases and probably decrease the mortality from prostate cancer if you use it as an early detection test. The harms are that because of its lack of specificity, you may well end up doing a number of unnecessary investigations including invasive biopsies that result in over-diagnosis and maybe over-treatment of low risk disease, which has been a problem particularly in the US, but in most western countries in the nineties and naughties, but hopefully with better understanding of the disease, we are less likely to over-treat those that do not need treating. So, PSA has got a lot of benefits, however it also has resulted in some over-diagnosis and over-treatment of some cancers.
Just briefly, to look at the risks of prostate cancer. The main risk for being diagnosed with prostate cancer is actually getting your PSA checked. And that is why Australia in fact has one of the highest rates of PSA measurement and prostate cancer in the world, if not the highest. Other risk factors that you may bring into your calculation when deciding whether to test a man, are that African or indeed indigenous Australian heritage seems to give a higher risk of prostate cancer. It tends to be more aggressive disease. A family history. If your father or brother or uncle or first degree relative had prostate cancer fairly young, under 65, it doubles your own risk. If you have got two such relatives, it might put your risk up as high as times 11. And similar to breast cancer, there is a small relationship between breast cancer in families and prostate cancer, so these are the things we ask for in the history. Other things that are less relevant are sexual history, the more sexually active a man has been, the less likely he appears to get prostate cancer. Dietary change, men of Chinese or Japanese origin who move to the west, their children are starting to get more prostate cancer, probably due to environmental change. And PSA tends to get checked in the middle to wealthier classes, particularly in the US where white, middle class men are more likely to get prostate cancer and their PSA checked. So, I think family history is important, and ethnicity as well. In some cultures it is important to be more assiduous, and perhaps get in early with checking PSA. Normally I guess we would recommend PSA checks from the late forties onwards. You may come down a little bit in somebody with a strong family history for example.
There is often a question about this, so I just put this in, because there is often a question asked. Can we prevent prostate cancer? Well, maybe, maybe not. Identifying risk groups to target obviously you know, good things. Dietary prevention, perhaps. That has been looked at in terms of using for example, lycopene supplements and other supplements to see if we can reduce the risk of prostate cancer. And chemo prevention has been tried with drugs such as dutasteride, but none of these things have ever been shown to significantly reduce the risk of you getting prostate cancer.
So, what happened when PSA was introduced? PSA came in to the UK in about 89-90, I guess in Australia about the same time, and in the US it was slightly before that. What happened is particularly in the US there was a significant increase in the left-hand graph in the instance of prostate cancer. Interestingly, looking at the right-hand graph, there was a bit of an increase in the mortality which fell off as time went by with PSA, although the incidence then for mortality although it was not as marked for the increase in incidence which suggested in some areas that a lot of prostate cancer was being diagnosed that might not influence mortality, which means that one big focus in this disease has been trying to identify those patients that actually may have significant prostate cancer that threatens their health and therefore needs treating, and not identify those with insignificant cancers that are probably not going to impact on their lifespan. That is the important feature I think, understanding that not all prostate cancers are threatening and that by over-diagnosing them, you may do more harm to the patient than not diagnosing in the first place.
So, what about screening or early diagnosis? There have been several studies around the world. The European trial for example was a study with randomised PSA screening against just waiting and not screening, in quite a large population, based mostly in the Netherlands, Belgium and a separate bit in Scandinavia. The first finding was that if you use PSA screening, when patients are diagnosed, only 1% in the initial findings had metastases compared to 24% in the control group. In other words, you are going to diagnose the disease early before metastases have happened, which I guess intuitively, you would think would be a good thing that would help patients not die of the disease or get distressing symptoms. So by using PSA, you definitely diagnose the disease earlier.
This basically shows a similar thing. It shows that basically the control patients were more likely to have prostate cancer and go on and progress than those who were screened and diagnosed earlier. You can see the period of follow up was 11 or 12 years to show a difference, and early prostate cancer takes quite a few years before it metastasises and threatens people, but if you diagnose it earlier, there is definitely a point around 10 years where those who got early diagnosis start doing better than those who you just wait and deal with the disease if it shows itself symptomatically. So there is evidence that PSA usage earlier on can improve outcome. Interestingly, an American trial, a similar randomised trial, showed no difference between being screened and not screened, but the problem in America was that somewhat over half the men had already had their PSA checked, in other words, it was a flawed study, because you were actually including men who had already been screened effectively in a screening study. So people mostly discounted this study. So, there are other studies including the ProtecT study in the UK which I was involved with, and the European study that has shown benefit to early diagnosis. So, sort of in early conclusion from the European study, there was a 20% risk reduction in deaths from prostate cancer if you use PSA to screen men and diagnose the disease early. The American study was rather discounted because it was contaminated. It did initially show that you needed to treat 48 men for every prostate cancer life you would save, although with subsequent follow up, that number has come down to between 15 and 18 to one, which interestingly is the same as the breast cancer screening trials. And it is because of the long natural history of that disease, you have to follow men up for between 10 and 15 years to start showing an impact of the diagnosis and treatment. So PSA does save lives. Probably however I would say that at the beginning at the slight expense if you use it alone, of over-diagnosis and over-treatment of some cancers.
What about the DRE, is that dead? The examination. Well, I do not think it is. It is useful. I had a patient the other day who had a PSA, quite a young guy, I put my finger in his rear-end and he has very obvious prostate cancer. Now, I still think it is an essential part of work up, but obviously a lot of men do not like you doing it and never force it anybody, but a DRE I think is a useful test if probably not always tolerated by patients nowadays.
So, what do you do next? Well, until recently, the next thing you do if PSA came back, you got the man who was 52 and his PSA was six, and you repeated it at six, you might check the free PSA. The free PSA as you may know, the lower the free PSA, the more likely it is to be cancerous. If it is under 15%, there is a higher risk of that being a cancer present, than if it is for example over 25%. So the lower the free PSA as well, the useful test, they are more likely to have cancer. You biopsy the prostate, usually by the transrectal route, put an ultrasound probe in the rectum in clinic, patient on their side, local anaesthetic, you biopsy the rectal wall. Now, the problem with that technique, and it is still widely used in the US, is that the significant infection rate. Despite prophylactic antibiotics, it is about 5%. In other words, you can give them antibiotic, but you are biopsying through faecal material sometimes, and you are going to get a significant number of people with infections. This has been largely replaced in almost every country, again besides the USA, by the transperineal route, which means you still put an ultrasound probe in the rectum, but you pass the needles in the perineum between the scrotum and the anus, directly into the prostate. It is a clean field and a recent paper in fact published in the last couple of weeks has compared this with transrectal biopsy and shown the infection rate with the transperineal route is almost negligible. So, you can even do away with prophylactic antibiotics. In the early days, retention of urine was a worry with a transperineal route, but it is probably less than 1%. So, transperineal has taken over from transrectal. The only difference is that transperineal needs to be done in some form of operating theatre environment and usually under a brief general anaesthetic. It can be done under sedation, whereas the transrectal route could be done in clinic. So, I am sure Howard will agree later that the transperineal route has taken over from transrectal in any civilised society such as Australia. So, this is basically the ultrasound is used in the same way, just the needle is put in in a different place. And until recently, you would basically sample the whole prostate in a sort of a structured way using a template through the perineum.
What has changed in the last, well I guess five years of so, that has really taken off in Australia and the UK, probably first around the world, is the use of multiparametric MRI scanning, which basically uses MRI. It has been around for the prostate for 30 odd years, but only recently has the software been used to actually define what tissue changes are within the prostate, and the Promis study in the UK for example, or the first large study, showed that if you use the MRI and target abnormalities that might show significant cancer of the prostate, these red areas on the diagram on the right, you will reduce the number of unnecessary biopsies. Less needles will need to be put in, and the MRI only tends to show mid to high-grade cancers, and therefore you will decrease your low-grade, what we might term insignificant, cancers. So you will identify those men with a focal disease, with significant cancer, and biopsy them appropriately, with only a very small risk of missing significant cancer, and decrease your biopsies on benign disease or very low grade cancer that are a low threat to patients.
So, what is coming to this space over the last few years is the use of multiparametric MRI scanning, and a couple of years ago, it became covered by Medicare for diagnosis. It sits between PSA being done and the patient needing a biopsy. And that is the space it should sit in. It is a form of biomarker in its own right.
Imaging has changed immensely, just during my career from having plain x-rays and ultrasounds, through MRI and CT to now other imaging which I will also come onto. But MRI is now sitting firmly in the space of a biomarker imaging modality. Multiparametric MRI scan whereby you can help select your patients more accurately for needle biopsies, and those who do need biopsies, accurately try and target the areas that are likely to be bearing cancer. A great step forward. Now, some cost, but it is enormously expensive, four or five hundred dollars and Medicare covers the cost in most situations. These are some examples. I will come back to that, sorry. I will come back to a better one in a second.
But, multiparametric MRI scanning is basically a regular MRI scan which has three modes of software, evaluation of the prostate which a skilled radiologist, it is important that the radiologists are doing this regularly and have been appropriately trained, because you need to make sure they are not under or over-reporting the abnormalities. And bear in mind, the imaging department at Macquarie has got very skilled guys who do this sort of stuff. They have to be able to interpret the software changes, the images, and tell you where the abnormalities are, which are usually scored by the PI-RADS system, 1 to 5, a PI-RAD 4/5 lesion is extremely likely to contain significant cancer. A PI-RAD 3 lesion has a moderate risk, and a PI-RAD 1 and 2 are very low risk. A normal MRI is again, extremely low risk of having significant mid to high-grade cancer. So, that is what a multiparametric MRI scan is.
These are some examples. The red areas are examples at the front of the prostate which was quite difficult to get access to in the old days with scans, but these abnormalities suggest cancer present, and indeed it was in this case. There is an arrow pointing on the left side of the picture on both images to a dark area which is an area of cancer, showing quite clearly here. Again, biopsy showed Gleason 4+3 cancer, in other words, high mid-grade cancer in the prostate. So you know what to target, and there may also be occasional applications of more specific focal therapy in certain cancers rather than radical treatment, if you have a very focal, localised cancer that you can access in other ways. What we tend to use now is a fusion biopsy system, whereby we take an ultrasound machine, the probe in the rectum, we bring in the MRI image on top of the ultrasound so we can see where the abnormalities are, and this robot device is then used, it basically finds the lesion, points at it and tells us where to biopsy. And so basically, using MRI and ultrasound together to identify the abnormal lesions and point the urologist at the abnormal areas to biopsy with a small biopsy gun fired through the perineum.
The other imaging modality that has come into vogue is isotope based imaging, using PSMA, not PSA, prostate-specific membrane antigen, which sticks to prostate cells, either in the prostate or elsewhere. Now this is the picture of somebody’s spine with a positive PSMA scan, so that is a metastases. However it is being looked at increasingly for local staging and also for recurrent disease after previous treatment. If you had radiation and the PSA starts to rise again for example, or surgery and the PSA starts to rise, PSMA scanning can be a useful modality to identify cells outside the prostate field or indeed recurrence inside the prostate if it is still present. And it can also be useful for identifying metastatic disease that may not show easily on other more standard forms of imaging, such as CT or regular isotope bone scan. So PSMA scanning is now covered by Medicare for local staging and the identification of recurrent disease from the 1st July, I think. So, just a couple of weeks ago.
I am just going to briefly talk a bit the last few minutes about active surveillance. Not all prostate cancers are dangerous. It is a bit of a difficult feeling when you tell a patient that they have got cancer, but it is fine, it is not going to cause them any problems. I guess not diagnosing those cancers, would be, in fact there is even a debate going on in Twittersphere in the US about whether we should actually call low-grade prostate cancer at all, it does not behave very much like cancer, a Gleason 6 small volume cancer, the vast majority never progresses and threatens people’s lives or health. So, should we even call it cancer? It is still defined however as cancer, so if you diagnose it, you have to tell the patient you have a low-grade cancer, but it is probably not going to be a threat to you. So you have to have a strategy for dealing with it. We still use a pathological grade, and we also use grade groups, you know, one to five. The Gleason grade has been modified over the last decade or more. Gleason 3+3=6, is still low-grade. And if it is low volume with only a small amount present, it is a very small risk of ever progressing. As the grade goes higher, the risk of progression over time, and I have already shown a graph that shows that can be a decade or more, the higher the grade goes, the more likely progression is and the more rapid the progression may be. And Gleason 4+3 is worse than 3+4 .Gleason more than 8 is actually aggressive disease, and therefore more of a threat to a patient. So, all of us should always ask if a cancer is diagnosed, how far has it gone, and how aggressive and how threatening is it to me? Is it low risk or is it medium risk, or is it an aggressive one? You know, is it still in the prostate and curable and treatable? So we base this on the grade group, but also the Gleason pattern, which is demonstrated on the right. The Gleason pattern is basically a score for how far away from normal the architecture of the prostate has moved, and it is a score of two different areas within the cancer.
So, if you diagnose a cancer, does radical therapy increase survival? Well, unfortunately, the world’s literature, despite the fact that we have been looking at it for 30 years, there are very few randomised trials. The one that is often quoted is this one, which was radical prostatectomy versus surgery, sorry the Scandinavian Prostatic Cancer Group was a randomised trial of radical prostatectomy versus watch and waiting, which means waiting and dealing with the disease when it presents symptomatically, had showed significant improvement in survival with the surgical arm, except that most of these patients probably had at least mid to high-grade disease. They were not just low grade cancers, they were threatening ones. So, surgery in this group certainly by six years, gives a much better survival advantage than waiting and just dealing with it when it appears clinically. There are various other, at the bottom of the slide, observational studies, which suggest that surgery and radiotherapy have similar outcomes. The study I was involved with in the UK, ProtecT, at 10 years suggested surgery and radiotherapy had similar cancer-free survivals, and they also have a similar complication rates, just different types. So, radical treatment does increase survival, surgery being the preferred option in most western countries, although radiation does offer an option in men who are keen to avoid surgery, or if for some reason surgery is not a great option.
I only have a couple of minutes left, so I am just going to talk about active surveillance. Active surveillance is something you put people on because you think their disease is not an immediate or possibly a long term threat, with localised cancer. And this might occasionally even apply to some small mid-grade cancers. This is an active process, it is not ignoring them. So, interesting studies in the US have shown that active surveillance is eventually after about five or six years more expensive than active treatment, and in America anyway, and it also has a psychological burden on a small number of men. And there is similar work in breast cancer that has shown women under the surveillance do often suffer more anxiety than those who have actually had more aggressive disease and been treated. So, active surveillance is not easier for some men, but it is probably better than having treatment that might leave them with potency or urinary difficulties.
And basically, the statement should be that men with low risk localised disease who are at low risk from that disease, there may be suitable radical treatment, but the threat of their disease is low, and therefore active surveillance is entirely reasonable. And low risk disease Gleason sum 6 or less, or maybe grade group 1 or 2, a low PSA, impalpable disease T1c, but also low volume. If you have one or two biopsies out of 20 for example or 30, that is low volume. So, low volume, low grade disease. PSA and the clinical staging, give some indication of volume too, and of course, MRI and PSMA scanning, can also give some clue as to the stage of the disease as well, now that we have those available.
So, I am just going to briefly over the last slide or two, show you a couple of slides. This slide is a cohort of men under active surveillance from Toronto. At 10 years, 62% had had no intervention. Interestingly the other 38% had had intervention mostly because they got fed up with being on active surveillance, not because the disease had actually progressed. And if you look at the actual number of patients over 10 years out of 452 with very low risk disease who died of cancer, it was five out of 452. So, it is very low risk disease. The mortality from cancer is quite low. Some people have treatment because they prefer not to be under surveillance, but if you can get across the idea that the disease is of low threat, well this is a good management modality.
So, active surveillance may spare men with early prostate cancer side effects of treatment without compromising their survival. And the real question is, well, what is the best regime? It is going to be PSA maybe quite frequently to start with to get a trajectory, every three months. Most international guidelines indicate that you should do repeat biopsies, in the US every year, the UK said every two years. This may have been actually superseded by MRI scanning which has now been used in this space where you do MRI scans maybe every 18 months in appropriate people. Radical treatment is still the standard if the disease is progressive or suggesting it is not of the lowest risk. So, active surveillance is a process you have to buy into with a patient and follow up, including biomarkers, PSA, and maybe in the future, new biomarkers, probably now rather than regular biopsies, regular MRI scans with biopsies if there is a change in the PSA or the MRI suggests new lesions. I have run out of time, so I am going to probably stop at that point.
Howard:
Management of small renal masses has changed a lot in the last decade or so. Mainly because our understanding of renal mass has improved. The natural history, treatment modalities such as ablative treatment, and not the least, robotic partial nephrectomy, has changed the standard of care for small renal masses. And hopefully, in the next 20 minutes or so, we are going to be able to share some of the thinking behind the management of renal masses.
This is a very common clinical scenario. A healthy 60-year-old with a bit of comorbidity, incidental finding of a renal mass, and it does look like a renal tumour. What are we going to do to them? And when we talk about incidentally found renal mass, probably the most important thing is we determine whether this is a cystic or solid mass. Cystic mass or renal cyst are so common. Probably about 40% of people over 60 years of age would have some renal cysts. By far the majority, they are simple cysts, they are unilocular, they are round, they are thin-walled, they do not have any solid component, no septum, no calcification. They are always benign and they do not change. And they are classified as a grade 1 cyst. And when we see a grade 1 cyst of the kidney, nothing needs to be done, unless they are so big that they are actually causing some pressure effect and discomfort for the patient.
There are grade 2 cysts which have a bit of septum, maybe a little bit of focal thickening, and no enhancement, they are generally benign, and they need to be followed up.
Grade 3 and grade 4 cysts have varying components, solid components, there may be enhancement, and they are basically a lesion that has got a significant risk of being a renal tumour. Grade 3, probably about 30% or 40%. Grade 4 in some cases, up to 90% they have a renal tumour. So, a grade 3, grade 4 cyst, they need to be assessed properly. A grade 2 cyst, they should be followed up and the patient needs to be seen by a specialist, and I am hoping that it is not a common practice, but hoping that all radiologists will use a grading system to help patients to identify a cystic lesion and whether follow up is necessary. But simple cysts, we see a lot and they are very common.
To complete the list, a para-pelvic cyst is just another renal cyst. It is just around the renal pelvis. But there are unusual situations where we see unusual diagnoses, caliceal diverticulum, medullary sponge kidney, there is also cystic disease or autosomal dominant polycystic disease. They are something that deserve individual discussion which we will not have time for here.
Now, for the purpose of the talk, we are mostly concerned about renal tumours, and renal masses are most commonly either renal cell carcinoma, they could be the less common kidney tumours like a transitional cell tumour which originates from the renal collecting system, while the renal cell carcinoma is originally from the renal substance. And there are some benign tumours, such as the adenoma, oncocytoma and angiomyolipoma. But the patient usually presents with a renal mass, and it is up to us to determine what the significance of the renal mass is.
This is somewhat of a summary of angiomyolipoma. As its name suggests, there is fat components within it, and there is also angio, which is blood vessels and smooth muscle. It is the fat within this lesion that gives it its characteristic look on the ultrasound, which fat is hyper-reflective of sound, hyper-echoic, so shows up as bright on ultrasound, but very low density on CT scan. And so, it is actually dark on CT, bright on ultrasound, and based on this, we are actually confident enough to call this a fat containing renal tumour which is almost always an angiomyolipoma that is benign. And if that is the case, we are safe to watch, except when they are larger, for example when they are larger than 4 cm, the risks of a spontaneous rupture and haemorrhage in these patients are increased, particularly if they are pregnant. And if that is the case, some strategies such as embolization can be used to reduce the risk of this haemorrhage.
Now, back to renal cell carcinoma.
Courtney:
You are cutting in and out, Howard.
Howard:
The incidence of cancer within Australia, and by far the most common cancer in men is prostate, and the most common in females is breast. And kidney cancer rates around about 10.
In terms of prognosis, looking at all the different prognoses in general, all urological cancer tends to do pretty well. Among the urological cancers however, the five year survival of kidney cancer tends to be the worst. Testis are best, prostate is following second, closely, even bladder cancer is a little bit better than kidney cancer overall. And the prognostic factor for kidney cancer, most important, is stage. Stage correlates closely with size. So, the incidental renal masses are almost always stage 1, they are below 7 cm, and within stage 1, there is a subgroup of stage 1a, which behaves very well, highly curable, and they are usually less than 4 cm. Less than 4 cm in the TNM system is stage 1a, and up to 7 cm is 1b. And prognosis correlates well with the stage, which is size. A small renal tumour, the five years survival is approaching 100%, and highly treatable, but once this tumour metastasises, cure is generally not likely.
So, when we see a patient such as this, this is a clinical stage 1a tumour, highly curable, with need in a subsequent slide to have a look at the natural history of such a tumour, and that will help us decide what to do with the patient, how to advise the patient. Such small renal masses grow very slowly. On average, the growth rate is about 3-4 mm per year, not even half a centimetre per year. And with such small renal tumours, progression to metastasis rate is less than 1%. And we know that the actual incidence of renal tumour in the western world, in particular the US, with a lot of imaging modalities being used, the incidence of renal tumour has been increasing consistently for many years. And yet, the presentation of metastatic disease has remained unchanged. We are probably picking up a lot of indolent tumours.
And if the tumour, now we are talking about radiologically diagnosed tumours, or mass, is less than 1 cm, about 50% being malignant. If they are 2 or 3 cm in size, about 80% being malignant, and the larger they are, the more likely they are to be malignant. But there is no fool proof way to tell if these are malignant tumours or non-malignant tumours by imaging, whether it is CT, ultrasound or MRI. They all contribute in some way to determining the nature of the tumour, but none of them are fool proof. For these tumours, what is the metastatic potential? Less than 2 cm, almost zero percent metastatic rate. So, a small renal tumour, it can be observed without having to treat, and certainly not treat rapidly, not urgently. So the larger the tumour, the metastatic potential starts to increase. And so, if people have multiple familial cancer recurrence, we tend to wait till the tumour is about 3 cm or more before we consider treatment. It is almost like we are looking at a mango on a mango tree, when it turns yellow, we start to pluck it. When it is small, we leave it alone. So, when they are about 3 cm or more, then we will start to go in and remove all the tumours, the larger ones and the smaller ones as well. So you can see that the larger the tumour, the metastatic potential increases.
So when we see a small renal tumour in a patient, what are the options we can give the patient? We can observe them, very similar philosophy as active surveillance with a lower risk of prostate cancer. We can excise them, which is the gold standard of treatment. Once upon a time, always we treated the patient with radical nephrectomy, that is remove the whole kidney. But now we know that that is probably over-treating the patient, and a more appropriate choice would be just removing the tumour and leaving the kidney behind, and we will look at the reason why we do that. Ablative treatment, which is using energy to either freeze or burn them, and all of these options can be done with or without a needle biopsy.
So if we observe the patient, obviously the benefit is avoiding the morbidity associated with treatment. But there is always a risk the cancer will grow, but we know that the cancer, even if it is a proven cancer, it grows about 3 or 4 mm per year, and the metastatic potential of a very small tumour are small. So, it is reasonable, particularly for the older and less fit patients that we observe them and we will proceed with treatment if there is signs of progression.
Now, this is a very busy slide, so you do not have to read all of it, but it is a meta-analysis of all the active surveillance or observations for small renal mass. And most of them are up to about say four or five years follow up. You can see that the metastatic incidence are very low. Some of them, most of them, are zero percent, but in some isolated studies, it could be 7% or 8% metastatic rate. So, it is not completely without risks and the patient must be watched closely.
So, what about biopsy? Do we biopsy the tumour? Now the sensitivity and specificity test varies a lot between different units. Essentially, if you use a fine needle aspirate, it is neither very sensitive nor very specific. But if you use a core biopsy, you actually take a larger needle, a core, or multiple cores, it is very sensitive and very specific. But it is starting to become a bit more invasive. And we tend to only do this biopsy if it changes our management. For example, you see a young man, a 3 cm tumour, you are probably going to treat anyway, so I do not think you need to complicate matters by doing a biopsy. If there is other malignancy involved, particularly say, metastatic spread, possibly lymphoma, then a biopsy would be very useful in this situation. The question my patients always ask me, what about seeding? Seeding for renal tumour biopsy is exceedingly rare, with the exception of a transitional TCC. And the difference I explain to my patient, is a bit like (inaudible), the more aggressive tumour is like weeds, it can grow along the (inaudible).
Tim:
We seem to have lost Professor Lau.
Courtney:
Yes. I will stop his video and see if that helps his internet.
Tim:
Yes.
Courtney:
It is not letting me. Okay.
Tim:
I think he might disconnect and then come back on.
Howard:
I am back, I am sorry about that internet connection. I think my children are wanting to watch a few movies, that is fine. So, I will jump back onto the talk.
I think we are onto the important indication for nephron sparing surgery. And in the past, absolute indication was solitary kidney. Now we are seeing increasingly lots of people with impaired renal function, diabetes, hypertension, and these diseases can comprise renal function and reserve, so these patients, if they have a renal tumour, should be offered nephron sparing surgery. But increasingly, we are considering seeing patients with a completely normal kidney on the other side, good enough to be a renal donor, I think in these patients, the current standard of care is still nephron sparing surgery and we will explain why. Because, I think overall survival is better in these patients if they are treated with partial nephrectomy. The advantage of partial nephrectomy is that we know that 10, maybe 25% of patients with these small renal masses are benign. We know the oncological outcome for T1s disease whether they are treated with radical nephrectomy or partial nephrectomy, they have the same oncological survival. Three percent of the tumours can occur in the opposite side later on. The incidence of end stage renal failure is reduced if we preserve nephron, and there is increased evidence, particularly in the younger patient populations, the overall survival for other causes if better if you have better renal reserves. The disadvantage however, is that there is possible local recurrence. Technically, it is a more complex operation, particularly if you want to do a more invasive technique, and the complication rate in terms of transfusion is increased. But thankfully, these are old data. The newer data would be less than 2%.
I felt this was time for a little commercial. This is a news clip on a demonstration of partial nephrectomy robotically in this hospital about four years ago. So, talking about the different types of nephron sparing surgery, there is open surgery, there is laparoscopic and robotic surgery, which I think this hospital, Macquarie Hospital, is particularly in the forefront of the technical aspects of robotic partial nephrectomy and robotic surgery in general. There are other options for partial nephrectomies, for example as in this case, where the patient has a bilateral renal tumour. The larger tumour on the left is actually relatively easy to deal with. The central tumour on the right is much more difficult. And what I have done in here is, I used transplant technique, remove the kidney outside, take my time in removing the tumour as you can see, repair the kidney, and transplant it back into the patient. And you can give it back to the patient, or in situations where the patient does not want the kidney back anymore, you can actually use this kidney to transplant in someone who has kidney failure, in need of kidney transplant, particularly when the dialysis access is becoming increasingly difficult. They are older and they can actually have the risks of transplanting a kidney that has the tumour removed, and actually do very well. And Australia actually has the largest series of this type of transplant.
So, throughout the years, how small is a small renal mass? It has changed. We are now probably treating 7 cm tumours which is stage 1, as a small renal mass that we can treat with nephron sparing surgery. And we know that we spare nephrons. The blue line here is a patient treated with partial nephrectomy, the red dotted line is radical nephrectomy. If we use grade 3 chronic renal disease, you know, GFR 60, you can see quite a difference between the two. If we use 3b kidney disease, partial nephrectomy, almost always above 45 GFR. While radical nephrectomy is a significant proportion of patients are below that range. We know that better renal reserves will slow down the future renal deterioration because of hyperfiltration injury. Better renal reserves also leads to better overall survival. And this is supported in some of the patient retrospective studies, looking at patients treated with radical nephrectomy versus partial nephrectomy, and the advantage is most of the group where patients are younger than 65 years of age, radical nephrectomy treated patients have a two-fold increase risk of death from overall causes. So it is not insignificant, but they are retrospective studies. So if we can, we should consider nephron sparing treatment for patients who are younger in particular.
Ablation treatment, we can freeze the tumour, we can cook the tumour with microwaves, or we can use radiofrequency ablation, which also generates heat, and there are other ways to generate the energy. And probably the Nanoknife electroporation, which electrocutes the tumour basically, it is probably the way to go in the future. But we are not quite there yet. But we can only treat small tumours. The definition of success is a little bit different in the sense that the tumour carcass would still be there, and all we can say is that there is no blood flow into the tumour carcass, which means contrast study is necessary. And that of course, provides some disadvantage for the patient who has compromised renal function, you cannot really give them the contrast.
This is a meta-analysis looking at all the different treatments available. Active surveillance, cryotherapy, radiofrequency ablation, laparoscopic partial nephrectomy, open partial nephrectomy, open radical nephrectomy and laparoscopic radical nephrectomy. Looking at a tumour size, certainly the radical nephrectomy, larger tumour.
It is interesting to look at recurrence risks. Even using a different definition of no blood supply going to the carcass of the tumour, ablative treatments still have almost a 10% failure rate, whilst surgery has about a 1% to 2% failure rate. The complication of partial nephrectomy is higher, closely followed by ablation, so ablation is not without complication, and a well done radical nephrectomy is still a very safe operation. The problem is poor renal function.
Familial tumour, I have already touched on it a little bit. (Inaudible) and treat all the tumours in the same kidney. I think I can get to my last slide, and I have some case discussions if we have time to go through that. Simple renal cysts are common and benign. They do not require any specific treatment. Complex cysts, they need follow up. All solid renal masses, they need to be assessed by an urologist. Early stage renal cancer tends to progress very slowly, but we need to avoid metastatic development, because once this occurs, it is incurable. Nephron preservation should be considered in all suitable cases, and is likely to improve overall patient survival. And minimal invasive surgery is possible and feasible and it is the standard of care.
Actually, I am going onto case discussion, is everybody happy with that?
Tim:
That is good, you have got about, we have been answering the questions as we go which is really helpful, so you have got four minutes or so.
Howard:
Thank you. Five minutes. Okay, alright. So, this patient which we touched on a few times in the presentation, should they see an urologist? Yes, I think. Is it urgent? No, because it is a slow growing, early stage tumour, so we can reassure the patient of that. The metastatic potential? Very low, because it is well under 3 cm. Is it suitable for observation? I think it is an acceptable option. Is a biopsy reasonable? It is reasonable, but if we decide that we are going to observe or treat and we are not going to change our mind, probably not necessary, because unless it changes our approach, it is probably not necessary. Surgery would be the standard of care. A radical nephrectomy, definitely not appropriate because he has diabetes and he has hypertension, we should preserve nephrons, and I think most appropriately, we should do a partial nephrectomy. Ablation is reasonable. The patient seems quite young, fairly fit, they require very close follow up, and I think if the patient is fit enough, they should probably have the tumour removed, but ablation should be mentioned and discussed.
A different case. A 48-year-old man, already had two multiple partial nephrectomies and a contralateral radical nephrectomy for his familial disease which is Von Hippel-Lindau disease, giving him multiple renal tumours, and this is the third time he is having a partial nephrectomy in a solitary kidney, and this is basically what we can do, go in (inaudible).
Tim:
I do not know if you can hear us, Professor Lau, I have lost sound.
Howard:
I am the elephant. And my team is the elephant. Allow him to touch the sky. And the commissioning, the process of commissioning to paint this picture was far more extensive than my surgical fee.
Anyhow, a 60-year-old female, a bit of back pain. Ultrasound showed am 8 cm simple renal cyst. Quite a common scenario. What should we do? I think we should exclude all other causes of the pain, and if there is no other pathology, no other significant problem, the renal cyst can be safely observed. But if the pain is likely to be from the cyst, all we can do is, we can use radiological aspiration as an outpatient procedure and if the pain settles, then we know it is diagnostic for the original pain. The cyst is almost always likely to recur with simple aspiration, and if the pain recurs after a long time, we can either repeat the aspiration, and if it recurs quickly, we can consider de-roofing of the renal cyst.
I think we have a quick case of an AML. Risk of malignancy because of the pathognomonic sign of the fatty nature of the tumour, very reasonable to just watch. Risk of rupturing is to be discussed with the patient. And do we need to treat? If the patient is child-bearing age, we probably should consider embolization. I think that is all I have got.
Courtney:
There we go, the learning objectives are back up for everyone to see. So, I would just like to extend my thanks once again to David and Howard for presenting this evening, to Tim for facilitating, and also to everyone who joined us online. We do hope you enjoyed the session and the rest of your evening.