Urological cancers Flashcards
LO:
This session aims to discuss the risk factors, common histological subtype, clinical features, investigations and treatments for:
- Kidney cancer
- Bladder cancer
- Prostate cancer
This session mainly relates to the following TILOs:
- 1-BRS-URO-3: Genitourinary disorders: Summarise the pathology and pathophysiology of genitourinary disorders.
- 1-BRS-URO-4: Genitourinary disorders: Describe the clinical features and treatment options of genitourinary disorders.
Session plan:
Kidney cancer-epidemiology and types and aetiology
- Risk factors: Smoking, Renal failure and dialysis, obesity, hypertension(2)
- Genetic predisposition with Von Hippel-lindau syndrome (50% of individuals will develop RCC within lifetime)(2)
Kidney cancer: Clinical features
Haematuria (blood in urine) is a red flag for all urological cancers
Can be physical, ie you can see it. This was historically called macroscopic haematuria
Or it can be non-visible, ie can’t see it-microscopic haematuria
Cause of haematuria can be from cancer, infection or inflammation of these regions: kidney, bladder, ureter or urethra.
Infection and inflammation can be causes of haematuria but they cause pain. It is more worrying if there is painless haematuria especially visible haematuria, needs to be investigated as this is suggestive of cancer. Anyone with persistent microscopic haematuria would also require investigation.
Bone pain-if spread to bone or haemoptysis if spread to lungs
Kidney cancer: Investigations
Anyone with painless visible haematuria requires a flexible cystoscopy, and that essentially involves looking at the bladder with a telescope through the urethra.
We would also have to rule out any cancer in the kidney and ureter, and for this patients undergo a CT urogram, and that essentially gives a good detailed view of both these regions.
Would also do a blood test to check renal function-this not only provides prognostic info but also in order to do CT scan need to check that kidneys can survive a contrast insult.
In patients with persistent non-visible haematuria, ie people who have had their urine checked via dipstick and have found to have microscopic haematuria. They would also require a flexible cystoscopy to look at the bladder.
But to look at the kidneys we tend to do an ultrasound of the kidneys, ureter and bladder, because non-visible haematuria is less associated with cancer than physical haematuria.
If on the CT scan or ultrasound of the kidney there is suggestion that there might be a kidney lesion. You can characterise it better with a CT renal triple phase scan. And this essentially involves a delayed scan with contrast, so that you have better characterisation of the lesion.
Also would want to perform a Staging scan to check if any lesions within the chest region, and if they are complaining of any bone pain, do a bone scan to check for obvious mets within their skeleton.
Kidney cancer: staging and grading
Were you to find a lesion, the next logical step would be to stage it:
Staging-uses TNM for RCC, gives an idea of size of lesion and whether it has spread
Grading is different to staging-this is when they have histology and they look under a microscope at the histology and they characterise how abnormal/poorly differentiated the cells are within the lesions compared to normal cells.
1-3 based on nuclear size , 4 = presence of sarcomatoid/rhabdoid differentiation
Kidney cancer: Management
First looks at patients factors, ie are they fit enough:
ASA-physical status classification. The American Society of Anesthesiologists (ASA) Physical Status Classification System is often used by UK anaesthetists to establish a person’s functional capacity. ASA grades are a simple scale describing a person’s fitness to be given an anaesthetic for a procedure.
Then look at the lesion itself, how aggressive does it look on the scan, what staging has it got, is there any metastases.
If the patient is fit and it looks to be an intermediate or aggressive cancer, the gold standard would ideally be a radical nephrectomy-take whole kidney out along with ureter.
But if there is concern that this patient has only got 1 functioning kidney or there are tumours in both kidneys or have genetic cause eg Von Hippel-Lindau syndrome so is likely to develop a further tumour in the future or can’t survive with one kidney as other if not effective then may have to do partial nephrectomy-so don’t take whole kidney out, you just excise the lesion in the kidney.
(Von Hippel-Lindau syndrome (VHL) is a hereditary condition associated with tumors arising in multiple organs. VHL-related tumors include hemangioblastomas, which are blood vessel tumors of the brain, spinal cord, and retina. People with von Hippel-Lindau syndrome commonly develop cysts in the kidneys , pancreas , and genital tract. They are also at an increased risk of developing a type of kidney cancer called clear cell renal cell carcinoma and a type of pancreatic cancer called a pancreatic neuroendocrine tumor.)
There will be cases where patients are unfit for surgery
Cryosurgery-minimally invasive approach that involves freezing the lesion in the hope of stopping the cancer progression.
In patients with metastatic disease we tend to use Tyrosine kinase receptor inhibitors:
Receptor tyrosine kinase inhibitors essentially block the cell signalling pathways so there will be less angiogenesis within the tumour, so it is less likely to progress or spread further.
What is the most common histological subtype for kidney cancer?
=adenocarcinoma
Transitional cell carcinoma is the next most common
Bladder Cancer-epidemiology, types and aetiology (risk factors)
-In some countries particularly Eygpt they had SCC more common due to schistosomiasis being endemic there. But in UK transitional cell carcinoma is more common.
Risk factors:
Smoking, occupational exposure( aromatic hydrocarbons), chronic inflammation of bladder (bladder stones, schistosomiasis, long term catheter), drugs (cyclophosphamide=chemotherapy drug), Radiotherapy
Bladder cancer: Clinical features
Tends to be more concerning if it is visible painless haematuria.
You would follow the same route as before:
- Flexible cystoscopy to look into the bladder
- CT urogram to check the kidneys and ureter
Additional features that you might seen in bladder cancer that you wouldn’t necessarily see in kidney cancer are shown.
- suprapubic pain because the cancer itself can elicit localised pain.
- lower urinary tract symptoms-can affect voiding (increased frequency, sometimes pain, but this is more relective of a UTI)
- Again can get metastatic disease and thus associated symptoms. If spread to lymph nodes can get lower limb swelling
Bladder cancer: Investigations
Investigations are very similar to kidney cancer.
Flexible cystoscopy to look in bladder
If finding of Flexible cystoscopy shows lesion of bladder, patient can be given general anaesthetic and they will do a rigid cystoscopy (similar to flexible cystoscopy, but they use a bigger telescope to enter the bladder) and from that telescope, they take a biopsy of that lesion to provide histology and also in most cases get rid of the lesion by using heat to excise that lesion. So provides histology and treatment. This is crucial, as you can identify whether it is cancer, or whether it is a benign phenomenon, eg maybe some inflammation related to past infection. This investigation will help define the further management the patient will need.
Bladder cancer: staging and grading
Like kidney cancer we try and stage the bladder cancer using the TNM staging system, depending on how invasive it is to the bladder mucosa. Any lesion that invades the muscle is much more worrying than any sort of flat lesion.
Also, the more poorly differentiated the lesion the more abnormal it looks compared to normal bladder cells-this is another poor prognostic sign.
Cystoscopy + transurethral resection of bladder lesion
Management Protocol for bladder cancer
If lesion found to invade muscle, then most appropriate treatment is to have bladder out, assuming they are fit enough for this to be done, as there is such a high risk of it spreading and the prognosis is very poor unless the patient undergoes very radical treatment such as a cystectomy)
However if the tumour is not invading the muscle of the bladder, ie it is a small lesion with a stalk and its low grade and there is no concern of any carcinoma insitu, which is essentially red patches within the bladder which are a poor prognostic factor, then one can consider regular cystoscopic surveillance. And if any new lesions pop up then using heat and cautery to excise that lesion. You can also use chemotherapy within the bladder, including BCG, which is the same as the TB vaccine but they just put it in the bladder because it elicits an inflammatory response, which is shown to reduce the risk of a progression of any sort of bladder lesion.
Which is not a recognised risk form of bladder cancer?
=alcohol
(note: risk factors: smoking (most common risk factor), UTIs (through chronic inflammatory process) and working in the dye industry. Working in the dye industry is less of an issue though nowadays due to better regulations put in place)
Prostate cancer-epidemiology, types, aetiology and clinical feature
-More common than the other cancers. Most common in men
Prostate cancer investigations
-Main way to diagnose is in PSA blood test which is specific to prostate and can be done in community
(but can get raised PSA in absence of cancer eg UTI or inflammatory process of porstate caused by prostatitis)
- Historically patients were diagnosed incidentally or with a PSA blood test, and most patients underwent a prostate biopsy, however in the last 10 years or so there has been a real shift to perform imaging of these patients, particularly multiparametric MRI before biopsy. Because no only do you get a better understanding of the cancer, but you can target specific lesions in biopsies that you are concerned by. In some cases you may not even proceed to a biopsy, but historically everyone got a biopsy, and actually there was a huge overdetection of low grade cancers which were clinically insignificant and unlikely to affect the man in his lifetime. Also if just randomly biopsy prostate you are more likely to underdetect high grade lesions as you are doint it blindly, but in imaging you can target specific worrying lesions.
- Historically to biopsy prostate cancer it used to always be transrectal, so that involves taking biopsies within the rectum, but now most centres use transperineal (this is now goldstandard for prostate biopsy), so you target the prostate from the transperitoneal region-area below the scrotum and above the anus (better as can access all areas of the prostate, whereas through a transrectal approach it is harder to target certain areas and get samples such as in apical regions. Also it has been shown to have less infection rates as you are avoiding the rectum and therefore faecal contamination.
Prostate cancer: staging and grading
TNM is the staging method for all urological cancers
Prostate cancer is graded via Gleason score-looks at how normal the cells of the prostate look compared to a normal person. Tend to take 2 scores as there is such a variability, and add them together. Anything below 6 is a good prognostic sign as well differentiated, but anything further has a poor prognosis.
Prostate cancer - Management
Dependent on patient and cancer itself.
Young and fit:
- Young and fit-prostatectomy, which involves taking out the prostate through either a laparoscopic or robotic approach. You can consider radiotherapy also.
- However this aggressive intervention such as radical prostatectomy whilst it has a high cure rate, it also comes with a high risk of side effects as there are a lot of nerves surrounding the prostate so can cause erectile dysfunction or urinary incontinence etc. Therefore in a patient who is young and fit who has a low grade cancer, you may wish to just survey it and perform regular PSAs, and also an MRI, and try if possible and avoid having to do an operation, if that cancer stays at a low grade.
- In anyone who has had a prostatectomy, they are still at risk of prostate cancer recurrences, because you have these micrometastases, so you have to keep an eye on their PSA. Initially it should be undetectable or less than 0.01, however if it becomes greater than 0.2 then we consider this a biochemical relapse and they need further treatment.
Old or unfit:
- If old or unfit and high grade or metastatic disease (usually presents with bone pain)-give androgen deprivation therapy, essentially this lowers their testosterone level, because that’s the main fuel for the prostate cancer. Hormone therapy also has lots of side effects eg gynecomastia etc.
- If low grade, again probably just watch the patient and monitor PSA, and when it does progress to high grade metastatic disease perform hormone therapy. (unsuitable to give them hormone therapy straight away ie for low grade as no point having side effects for this when prostsate probs won’t be the thing that kills them anyway.)
- The prostate contains the proximal sphincteric unit, which controls some degree of urinary continence. Prostatectomy removes the proximal urethral sphincter and there is a risk of inadvertent damage to the cavernous nerve to the prostate (which provides neural innervation to the bladder and urethra) resulting in bladder function being affected(3). Moreover, urethral length changes during the operation which can also affect continence(3). The main treatment for this type of incontinence is building the pelvic floor muscles through exercises but should this fail there is an option for an artificial urinary sphincter device.
- PSA should be undetectable or <0.01 ng/ml. Patients should undergo PSA testing 6 monthly and a biochemical relapse is defined as a PSA >0.2ng/ml.
Treatment side effects
Prostate is important in terms of voiding. It contains the proximal urethral sphincter, and when you perform a prostatectomy you remove that. And also by taking some of the urethra you also manipulate the length. There is a high chance of damaging the cavernous nerves which provide innervation to the bladder and urethra, and so patients who have a prostatectomy are at high risk of urinary incontinence and erectile dysfuction.
Management of this:
urinary incontinence-manin management would be undertaking pelvic floor exercises, but in some cases can perform an operation and put in an artificial urethral sphincter to replace this.
Damage to caverous nerves causes erectile dysfunction, to treat this can use medical management so PDE5 inhibitors (eg sildenafil (Viagra)) and then move onto injections in the penis such as prostaglandin E1. Both of those actually work by causing vasodilation so increasing the blood flow to the penis. In some cases where patients are refractory to those treatments, you can even put a penile prosthesis in.
Which statement is false?
=Prostate cancers should only be treated with radical prostectomy
There are other therapies including radiotherapy, surveillance etc.
Session Summary
Q and A
Von Hippel-Lindau syndrome-autosomal dominant disorder characterised by lesions in the retina, CNS and also patients develop recurrent RCC. Due to a mutation in the tumour supressor gene.
CIS=carcinoma in situ, flat lesion of bladder so not structural lesion that you can see but more a change in colour of the muscosa. It isn’t a cancer but it has a high progression rate to cancer. If take biopsy and see CIS then must treat it as it has a high progression rate.
Rigid cystoscopy-General anaesthetic given and put telescope through urethra into bladder and can take biopsy of any lesions in bladder and can cauterise lesion in the bladder (use heat).
Flexible cystoscope-used as screening for everyone, much smaller scope so don’t need general anaesthetic.
Staging-size and spread of tumour
Grading-microscopic description of how differentiated the cells are, so how similar they are to normal tissue.
Schisctosomiasis-tropical parasitic infection. Causes SCC of the bladder, but tends to be less of a cause nowadays.
When take bladder out:
- Can create a stoma: so take bladder out and then you take some bowel and plug in both ureters from the kidneys and then you bring it out as a stoma bag, and they urinate into this bag to be emptied.
- Another method is to create a neo bladder- take some bowel and make a fake bladder. They have to put catheter in to empty that neobladder but don’t need stoma bag.
To prevent urinary incontinence, can work on strengthening the pelvic floor muscles or if this doesn’t work they can insert an Artificial urinary sphincter in. Patient’s have control of thisdevice and have a button to open and close this themselves when they want to wee.
Prostate cancer tends to be multifocal, so several sites are involved. So they take 2 scores rather than just one score, and both scores are put together to give a more accurate reflection of overall what the prostate is like.
Tyrosine kinase inhibitor for RCC (if someone has metastatic disease you are less likely to do a nephrectomy to take out the kidney)-works because kidney cancer needs tyrosine kinase to make new blood vessels so by giving them inhibitors you stop the formation of blood vessels so block the blood supply of these metastatic deposits by preventing angiogenesis.
Macroscopic haematuria is more worrying as it tends to be correlated with cancer.
CT renal triple phase: different from a normal CT scan because it has several different phases all related to the contrast that is given. Because as the contrast is given, it is filtered through the kidney at different time points. So it is a lot longer scan because they have different phases, one looking at the kidney parenchyma, one looking at the collecting system and one looking at the ureter. The reason they do this is so you get a better appreciation of the kidney lesion enhancement, so gives better idea of if its cancer and also its staging.
