Prof Lukas Lusuardi joins A/Prof Joseph Ischia and co-host Dr Nicholas Campbell as they discuss the ins and outs of performing a transurethral resection of the bladder, TURBT. Lukas Lusuardi is Professor and Chairman of the Department of Urology at PMU University Hospital in Salzburg, Austria. He completed his medical degree and urology residency at Università degli Studi di Verona, Italy and is the author of over 100 peer-reviewed publications.
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Talking Urology podcast transcript
So You’re Gonna ... do a TURBT
JOSEPH: Hi there and welcome. I’m Joseph Ischia. This is our new podcast series called So You’re Gonna and it’s from the team at Talking Urology where we are helping doctors and allied practitioners develop a deeper understanding of the literature to ensure we apply the right evidence to the right patient. So You’re Gonna do a transurethral resection of a bladder tumour or TURBT for short! Today, Nicholas Campbell and I, with the help of international TURBT expert Dr Lukas Lusuardi are going to bring the literature to life and take a look at all the latest evidence around the TURBT and give you some key numbers that you can use when chatting to your next patient or performing what is a very common urological procedure.
NICHOLAS: Thanks, Joseph. I’m Nick Campbell, a urologists from Melbourne with a special interest in bladder cancer. It’s a pleasure to be here chatting TURBTs with you today. And, let’s introduce our international special guest.
LUKAS: I am Lukas Lusuardi working at the University hospital in Salzburg, it’s called Paracelsus Medical University.
JOSEPH: Thanks, Lukas. We will hear some great tips and tricks from Lukas throughout the podcast. There’s lots to cover in this podcast and we hope as usual that we keep it interesting enough to keep you awake on your drive to or from work. These podcasts are only possible with the support of our sponsors. This TURBT podcast is brought to you by Karl Storz and we will be back after a quick word.
PODCAST SPONSOR AD.
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JOSEPH: So, listeners, where and when did it all begin with the endoscopic management of bladder tumours?…..Well, we are used to the Americans telling us that they invented everything, and this case, they actually did. A gentleman called Edwin Beer was born in 1876 and grew up in The Big Apple, New York City, before studying in Prague, Vienna and Berlin. After his European adventures he finally returned home and settled down to become the Chief of GU Surgery at Mount Sinai in New York. Edwin made several important contributions to urology throughout his illustrious career but none more valuable than his landmark study on the fulguration of papillary bladder tumours published way back in 1908. That’s the same year they started construction on the Titanic, but unlike, the Titanic, the TURBT has avoided all obstacles and is now more than 100 years old!
NICHOLAS: I think that we would all acknowledge that Edwin deserves to be commended because cystoscopic fulguration of bladder tumours, using high frequency diathermy, is still practiced today in urology worldwide.
JOSEPH: I think we would all agree that transurethral resection is an essential endoscopic urological procedure for diagnosis, staging and treatment of bladder cancer and in this podcast we are going to very quickly recap the goals and key steps in performing a TURBT, and something that I think is very important which is a good operation report which I think of all the operatios we do, the TURBT report is probably the most important that we do for reasons we will elaborate on, and then we can get on to the interesting stuff of the new technologies and enhanced imaging modalities that are out there to help us improve our TURBTs. So let’s get started.
JOSEPH: The most recent EAU guidelines also go into some detail on useful techniques and strategies for resecting different size tumours during a TURBT. If possible, a papillary tumour <1cm should be resected in one piece, or an en bloc resection.. For tumours that are >1cm this isn’t always possible but there are advocates out there who are doing it. Lukas is a big proponent of the en bloc resection and he thinks it has a big future:
LUKAS: When I find that the en-block procedure which is not a new procedure has now the potential to replace the conventional TURBT for smaller lesion. And when I say small, it’s under 5cm in diameter.
NICHOLAS: So, Joseph do you have any tips for preventing the scary obturator reflex or ‘jerk’ as it’s referred to by our North American colleagues?
JOSEPH: That’s right, you don’t want a jerk at each end of the resectoscope so let’s look at some tricks that we can use to minimise risks on the bladder side. Firstly, 3 useful evidence-based preventative surgical techniques were described in a recent review by Panagoda and are as follows:
- Reduce the diathermy current used during resection
- Use bipolar diathermy current instead of monopolar current
- A distended bladder brings the lateral bladder wall closer to the obturator nerve so avoid over-filling of the bladder
Other Level 4 evidence strategies based on expert opinion, or probably more accurately, bitter experience, have also been suggested and include resecting the tumour on thinner slices, laser resection, staccato resection applying the energy in small bursts, reversing the polarity of the diathermy current, and changing the site of the inactive electrode, ie, the diathermy plate to the opposite hip or leg.
JOSEPH: This issue of mono-polar vs bipolar is certa polarising debate (bad joke sound effect). We asked Lukas if he thought there was any difference.
LUKAS: Well it’s very drastic. I think Monopolar should already been ???? because especially for bladder cancer with the new generator we have on the market we just cut simply better with Bipolar we are much more in control of our resection and that means also the pathology is going to be happier because your histology is going to look better.
NICHOLAS: And does it reduce the risk of obturator kick?
LUKAS: The kick is still there, it’s probably a little bit reduced. What has been proven by many studies and it’s already in the guidelines, is that it is probably producing less complication. By saying complication I’m talking about bleeding, blood retention, clots and probably less perforation.
NICHOLAS: Ok. Those are the surgical manoeuvres, but now let’s take a look at the evidence based anaesthetic techniques to reduce the risk of obturator jerk. These include:
- The use of neuromuscular blockade, which necessitates the need for a general anaesthetic with an endotracheal tube to secure the airway
- Selective blockade of the obturator nerve by using either non-depolarising or depolarising neuromuscular blocking agents.
JOSEPH: That’s a nice list for the exam and a good refresher for the rest of us still learning in the training course of life. Now, let’s get on to one of the hottest topics in the field of modern TURBT and ask the big question, “what are the practical advantages of the enhanced endoscopic visualisation techniques compared to standard white light cystoscopy to help detect urothelial cancers?” We have all heard about techniques like blue light cystoscopy (also known as photodynamic diagnosis), or narrow band imaging, and now the new spectral enhancement systems, but, Nick, what are the practical real world advantages?
NICHOLAS: In brief, photodynamic diagnosis or blue light cystoscopy is performed using violet light after intravesical instillation of 5-aminolaevulinic acid (ALA) or hexaminolaevulinic acid or HAL. An important advantage with HAL, is that an instillation time of only 1 hour before cystoscopy is required, compared with 2–4 hours for 5-ALA and both agents are equally effective. A meta-analysis in European Urology by Burger et al in 2013 showed that HAL-assisted blue light cystoscopy detected 15% more Ta tumours compared with white light alone.
JOSEPH: One important note here is that blue light cystoscopy should be used in conjunction with white light cystoscopy, not as a replacement.
NICHOLAS: Absolutely right. We also know that fluorescence-guided biopsy and resection are more sensitive than while light cystoscopy for CIS. One meta-analysis showed that photodynamic diagnosis had a higher sensitivity than white light endoscopy for detecting bladder cancer at biopsy at 93% for blue light compared to 65% for white light. I think that these percentages definitely show a clear advantage with fluorescence cystoscopy compared to normal white light cystoscopy.
JOSEPH: There appear to be a lot of advantages to the use of PDD with blue light cystoscopy but I know that the number of centres that use it routinely would be in the minority. We asked Lukas what he thought on photodynamic diagnosis?
LUKAS: Well I love PDD, I have been using PDD in the last 15 years and it has been improving in quality and technology, now we have a very good product on the market and you just see lesions better. We know that with white light cystoscopy we miss up to 20% of the tumours. We miss CIS, possibly and that’s already proven that PDD is more sensitive to detect CIS and we probably reduce our recurrences. So why not use it?
JOSEPH: 15 years! Lukas is well and truly ahead of the pack. But even he doesn’t use it for every case because the dye is actually quite expensive in a busy bladder cancer practice. Therefore, we asked Lukas what cases does he think we could get the greatest value for our PDD?
LUKAS: I will tell you what I do in my department. I use it when I meet a patient for the first time with his 1st tumour in order to check if he has other areas besides the tumour which is probably also clear with white light. I want to exclude other lesions and then I re-use PDD in all situations when I have multi-focal tumour. Because it’s very easy if you have many tumours to miss some areas. You wont see them because you have so much tissue floating around the bladder, probably you get confused by many pieces floating and you can miss.
JOSEPH: When do you think we don’t need PDD?
LUKAS: Probably if it’s low grade, low recurrence tumour, singular tumour, recurring after 2-3 years, which has always been the same in the last decade, I would say. Probably there you don’t need PDD, you don’t need detrusor, but how often is this situation.
NICHOLAS: Now moving on to narrow band imaging or NBI…NBI is different to blue light cystoscopy in that it is an optical image enhancement technology that depends on the use of two short wavelength light beams of 415 nm (blue) and 540 nm (green). The light penetrates the superficial bladder tissues and is strongly absorbed by haemoglobin, so it greatly increases the visibility of capillaries and delicate tissue surface structures by reinforcing contrast of the bladder surface of tissues. Back in 2008, Herry Herr compared the effectiveness of NBI with conventional white light cystoscopy in 103 patients with recurrent superficial bladder cancer. He found that the detection rate of recurrent bladder tumour was 87.4% with white light cystoscopy compared to 100% with NBI cystoscopy.
JOSEPH: So we are looking at a 13% improvement for narrow band imaging. The big advantage here is that it is logistically easier than PDD. You don’t have to have to give an expensive dye 1 hour before your operation. Another great new technology that does not require early preparation with a dye is specific to the Karl Storz equipment. They have developed the Image 1s.
NICHOLAS: The addition of different colours like orange or violet to the image obtained by reflected blue- and green-spectrum light offers three different viewing options depending on needs in various clinical situations.
JOSEPH: There are 4 different modes you can use; standard which is white light; chroma which enhances the colour differences in the image; and then spectra A and B. Spectra A mode is based mainly on the green and blue wavelengths, and Spectra B which is similar to Spectra A with a reduction in the dominance of the red wavelengths. It sounds like a new band of superheroes. We asked Lukas what he used.
LUKAS: Well actually, I prefer spectra B because I mainly use this image 1S technology when I am doing en-block resection because I want to see the margins of the tumour. Obviously I do a white light cystoscopy, if I have PDD then I do PDD enough on the suspicious area I also look with image 1S. Especially using spectra B because I see vascularity better so pathologic vascularity helps us to detect areas and especially if you want to do an en-block, you need to be sure that you start your resection in a healthy part of the mucosa. So vascularity is very important, you have to understand it very good.
JOSEPH: Thanks, Lukas. They are some great tips. Image 1s is currently at the early clinical study stage of investigation so I’m looking forward to seeing how their results turn out! We have now finished performing our perfect TURBT: we looked good with the resectoscope, there we no jerks apart from the ones we already knew about, and we didn’t miss a tumour with our optimised visualisation techniques. But then how often do we let ourselves down with a poor operation report. How many times have you been sitting in your multidisciplinary meeting or tumour board and you are trying to decide what to do next when you bring up the operation report. It says: bladder cancer right wall. TURBT. 20 Fr catheter. Then there you are in the MDM trying to risk stratify the patient and guessing the size, the multiplicity, were there other red patches suspicious for CIS, was resection complete etc. I don’t think there is any operation in Urology where the operation report is more important to help direct further management. So Nick, tell us what are the 10 key points we should all be noting in our operation reports.
NICHOLAS: According to the godfather of bladder cancer, Harry Herr, a high quality TURBT operation report should include the following 10 essential pieces of information:
- Number of tumours
- A description of the largest tumour
- The characteristics of each tumour (sessile/ papillary)
- Recurrent versus primary tumour
- Presence of CIS or not
- Tumour stage clinically
- Bimanual findings
- Whether the resection was complete on visual inspection
- Whether there is detrusor muscle visible in the resection base
- Whether there is evidence of a bladder perforation
JOSEPH: That is great and I think a lot of us have room for improvement here, or it could be just me. Now listeners, we are almost there. The perfect operation has been performed; you have written an operation report that are some are calling the 155th Shakespearean sonnet, and now you have to decide whether you are going to give post-operative intravesical chemotherapy like Mitomycin-C or gemcitabine after a TURBT?
NICHOLAS: Well Joseph, it is widely believed that tumour cell implantation immediately after TURBT is responsible for many early recurrences and this has been used to explain why initial tumours are usually found on the floor and lower side walls of the bladder, but recurrences are often found near the dome. For this reason, intravesical chemotherapy to kill bladder cancer cells before implantation is especially recommended; typically, with Mitomycin C or Gemcitabine. Joseph when do you usually give Mitomycin after a TURBT?
JOSEPH: Good question Nick, a single dose of immediate postoperative intravesical Mitomycin, epirubicin, thiotepa or doxorubicin for superficial bladder cancer is associated with a recurrence rate of 37% after 3.5 years compared to a recurrence of 48% without In statistical terms, this equates to a 12% absolute risk reduction and 39% relative risk reduction in favour of immediate instillation of chemotherapy [Sylvester Meta-analysis (2004) (n=1476)]. So listeners, make sure to get that Mitomycin in quickly…unless of course you have concerns about a bladder perforation or heavy haematuria! These 2 scenarios are contraindications for instilling mitomycin into the bladder….. For intravesical gemcitabine it is interesting to note that Messing et al published on RCT in May 2018 in JAMA to determine whether immediate post-TURBT intravesical instillation of gemcitabine reduces recurrence of suspected low-grade non-muscle-invasive urothelial cancer compared with saline in 383 patients. Their findings showed that 35% of patients in the gemcitabine group had a recurrence within 4 years compared to 47% in the saline group. Our astute listeners would note that that is also a 12% reduction with a number needed to treat to prevent one recurrence of 8. So it would appear we have made our way from the start to the end of the TURBT but there is one more area I want to cover before we sign off, and that is the issue of the positive cytology but negative imaging and cystoscopy. We know that the specificity of cytology is almost 100% so we know that there is something there but we cannot see it yet. Where do we go looking? The great inner torment of out time:
- TUR BT or not TUR BT, that is the question:
- Whether ’tis nobler in the mind to suffer
- The slings and arrows of podium presentation questions,
- Or to take arms against a sea of peer reviewers
- And by opposing publish. To comfort—to cut,
- No more; and by a cut to say we end
- The heart-ache and the thousand natural shocks
- That flesh is heir to (ie reduce recurrences,progressions,death): ’tis a consummation
- Devoutly to be wish’d. To comfort, to cut;
- To cut, perchance to cure—ay, there’s the rub:
NICHOLAS: Poor Shakespeare. But let’s get back to our modern day anthology of poetry, the EAU guidelines in this situation. As recommended, I take biopsies from normal-looking mucosa (trigone, bladder dome, and right, left, and anterior and posterior bladder walls) when urine cytology is positive or when high-risk exophytic tumour is expected. If equipment is available, I use fluorescence-guided biopsies. I also biopsy the prostatic urethra in cases of bladder neck tumour, when bladder CIS is present or suspected, when there is positive cytology without evidence of tumour in the bladder, or when abnormalities of the prostatic urethra are visible.
Joseph: Ok, all very good points. But in the scenario of the prostatic urethra does it matter where the biopsy is performed, or can it be done in any location?
NICHOLAS: the guidelines suggest that the biopsy is taken from any abnormal areas in the prostatic urethra and from the precollicular area, which is between 5 and 7 o’clock positions (for those that are rusty on their anatomy!), using a resection loop. In non–muscle-invasive tumours when stromal invasion is not suspected a cold-cup biopsy with forceps is sufficient. It is also important to refer the specimens from different biopsies and resection fractions to the pathologist in separate containers and to label them separately.
JOSEPH: I completely agree Nick.
NICHOLAS: Now Joseph, I think we should discuss the situations and after what timeframe that a second TURBT should be performed?
JOSEPH: EAU guidelines recommend a second TURBT in the following situations….If the initial TURBT is incomplete, if there is no muscle in the specimen after an initial resection with the exception of TaG1 tumours and primary CIS. A second TURBT should also be performed for all T1 tumours and for all high grade tumours. In terms of timing….I usually stick with EAU recommendations and perform a second TURBT within 2–6 weeks of the initial resection. During my second resection I always make sure to resect the primary tumour site. Nick, do you have any data on the evidence for performing a second TURBT because a second anaesthetic after such a short period can be quite difficult in patients with comorbidities?
NICHOLAS: Persistent disease after resection of T1 tumours is found in 33–55% of patients. In patients with an initial diagnosis of TaG3 disease; tumour is found in approximately 40% of cases at second TURBT. These findings clearly demonstrate that the tumour is often understaged at initial resection. In terms of muscle invasion at second TURBT, the likelihood of an initial T1 tumour ranges from 4-25% and increases to 45% if there was no muscle in the initial resection. Additional caveats worth mentioning on the merits of a second TURBT are increased recurrence-free survival, improved outcomes after BCG treatment and provision of additional prognostic information. Based on these facts and figures I think we can safely say that, a second TURBT is definitely recommended in these cases!
JOSEPH: Good numbers to know for your next multidisciplinary meeting. It is worth noting that some of those number ranges are pretty broad, and it has to do with the experience of the urologist doing the first resection. If you are doing one or two TURBTs per year, your risk of persistent disease after resecting a T1 tumour is 55%, if you do more than 50 per year, it drops to 33%. Same for the range of upstaging to muscle invasion with a range of 4% to 25% for the less experienced. I have to admit, that the one exception I make to the automatic re-resection is the small single high grade Ta tumour where I am confident that I have completely resected the entire tumour. I do not perform a repeat TURBT in this instance because my pickup of persistent cancer is almost zero. Admittedly, I do more than 2 TURBTs per year and as Nathan Lawrentschuk often feels the need to remind me after a good outcome, it is better to be lucky than good. Well we are almost done and we appreciate those of you who could not find the skip button on your smart phone. So let’s finish by asking Lukas what is his number one tip he would give training urologists for a TURBT?
LUKAS: Well I would absolutely, especially if one resident is learning, absolutely use the technological imaging we have on the market. Whatever company. I think it’s very important because, we know that experienced probably miss less tumours with white light. They are not having 100% but probably they are close to that. Especially if they are very experienced, they wont miss great problems. But, a resident without help, has absolutely to pick up all technologies, all helps that are available in order to start getting better and improve the quality of his skills.
NICHOLAS: What’s the number 1 mistake that you think urologists regularly make?
LUKAS: For bladder cancer – to use Monopolar firstly, I am very critical I know. The second one is probably to overfill the bladder while doing resection. These are the 2 classical problems we see nowadays. But, if you adopt Bipolar you are never having a very filled bladder and so you work with very good quality.
JOSEPH: What do you think is going to be the biggest change in TURBT over the next 10 years or what would you like to see?
LUKAS: What I personally would love to see better vasculature, we see better neoplastic area because they capture Hexvix, so we see them with PDD, my wish would be to see the mucosa with three dimensional system, in order not only to see the vasculature but also the architecture of the tumour. I am sure three dimension would help in bladder cancer and in the treatment of that.
NICHOLAS: So Lukas sees a day when we have an US in the tip of the resectoscope.
JOSEPH: So, listeners I think we’ve covered quite a lot in this podcast. We touched on Edwin Beer’s pioneering TURBT that took place way back in 1908, we went through technological advances for diagnosing bladder cancer and also discussed the role of post-operative intravesical chemotherapy. Other important topics that were covered were the 10 key points in the operation report, ‘TUR BT OR NOT TUR BT!’ and when to perform a re-resection after initial TURBT. So to recap our fast five facts for TURBT:
- The improved detection of cancers compared to white light with the advanced imaging: a 28% improvement from 65% up to 93% with photodynamic diagnosis with the dyes, and a 13% improvement with narrow band imaging from 87% to 100%.
- A single post-operative instillation of MMC or gemcitabine reduces recurrence by an absolute value of 12%.
- The second TURBT detects persistent disease in around 40% of high grade Ta, and up to 50% in T1.
- Second TURBT upstages initial T1 to muscle invasion in 4-25% of T1 disease, and up to 45% if there was no muscle in the initial specimen.
- Remember, always look good when holding a resectoscope.
You’ve been listening to Joseph Ischia, Nicholas Campbell and our special guest, Lukas Lusuardi. Written by Mark Quinlan (Specialist in Chronic Orchalgia and Prostatitis), Prof Niall Davis, and Joseph Ischia. Produced by Joseph Ischia and Cara Webb. And a special thanks to our sponsor of this episode….’Karl Storz’, it’s German for 20/20 vision.
NICHOLAS: It’s really not but they do make some nice scopes.