23 | Confused about urinary tumours? You need to read this

PodcastUrinaryOncology
Written By Laura Jones

Urinary tract tumours are an important cause of lower urinary tract signs in older patients.

 

These patients benefit from extensive nursing care—not just at the time of diagnosis but for the rest of their lives, too, to give them the best possible quality of life for as long as possible. 

Today, I’m joined by Inge Breathach DipVN, DipAVN(Small Animal), PGCertAVN(Oncology) RVN. Inge has a wealth of oncology experience, currently works as the oncology nurse at Bristol Veterinary Specialists, and will shortly sit her VTS(Oncology) exam.

Together, we’ll look at what these tumours are, the signs they cause in our patients, and the treatment and nursing care these patients need.

What is urinary neoplasia, and what patients are affected?

Neoplasia of the lower urinary tract - the ureters, bladder and urethra - is uncommon in dogs and much rarer in cats. 

We don’t completely understand why the incidence of these tumours is much lower in cats. We suspect it’s due to a difference in how they metabolise tryptophan, an amino acid required for the normal maintenance of muscles, proteins, enzymes and neurotransmitters.

Some metabolites of tryptophan are carcinogenic, and since cats have lower concentrations of these in their urine, they have a lower incidence of urinary neoplasia.

What tumours commonly affect the urinary tract?

Primary tumours affecting the lower urinary tract are far more likely to be malignant than benign.

Benign tumours, such as papillomas, fibromas, leiomyomas and haemangiomas, are reported but very rarely. Malignant tumours that can affect the lower urinary tract include squamous cell carcinomas, adenocarcinomas, fibrosarcomas, leiomyosarcomas, and haemangiosarcomas.

But by far, the most common type of tumour we see in the lower urinary tract is transitional cell carcinoma, aka urothelial carcinoma or TCC, which accounts for 2% of all canine cancer.

TCC is a tumour of the epithelial cells that line the urinary bladder. These cells stretch as the bladder fills and function to protect the body from the caustic urine within the bladder.

These tumours can be solitary masses or a collection of finger-like projections emerging from the mucosa of the urethra, ureter or urinary bladder. They can also affect the prostate gland in male dogs and cats.

They are highly invasive and frequently metastasise, most commonly to the lungs, regional lymph nodes and bone - especially the pelvic bone surrounding the urinary bladder and urethra.

They can also cause chronic partial obstruction to urinary flow, resulting in increased pressure within the kidneys and subsequent hydronephrosis and AKI. They’re also a common cause of acute urinary obstruction in older pets and commonly cause secondary bacterial infections.

What causes TCC in cats and dogs?

The cause of TCC is likely multifactorial and not yet completely understood. Risk factors that have been identified include:

  • Exposure to topical insecticides

  • Exposure to plant material sprayed with certain herbicides/insecticides

  • Obesity

  • Cyclophosphamide administration

  • Female sex in dogs

  • Male sex in cats

  • Certain breed associations

Some studies have also shown a correlation between the level of environmental pollution and the development of bladder cancer in both dogs and humans - showing that areas with higher industrial activity were associated with a higher incidence of bladder cancer.

We know that female dogs get TCC more than male dogs - presumably because they display less urine marking behaviour, so they store their urine within the bladder for longer. In cats, however, it’s the reverse - male cats have an increased risk over females.

We also know that breed plays a big role in a patient’s TCC risk level. Shetland sheepdogs, Westies, Beagles and Scottish terriers all seem to be predisposed. We don’t know exactly why these breeds are at increased risk since there’s not been any association between tumour behaviour in these breeds vs other breeds found. However, we think it reflects a different genetic predisposition to bladder cancer - for example, due to changes in the pathways that process carcinogens in the body.

There is also evidence to suggest that cyclophosphamide administration increases TCC risk. In fact, in humans, cyclophosphamide increases the risk of bladder cancer by 9 times.

We suspect that chronic bladder irritation from cyclophosphamide administration could be a cause. Sterile haemorrhagic cystitis is a known complication of cyclophosphamide administration - in fact, that’s why we tend to give furosemide alongside this drug to make our patients urinate. There is some suggestion that TCC could be more likely in patients receiving chronic oral cyclophosphamide than injectable doses, as this causes higher metabolite concentrations in the bladder.

Regardless of the cause, TCC is a disease of older pets. In dogs, it’s typically diagnosed at around 11 years old, and in cats, at 15 years old.

What signs do we see in TCC patients?

The most common signs we see include haematuria, dysuria, stranguria and pollakiuria since the tumour interferes with urination, causing at least partial urinary obstruction.

If the tumour causes a complete urinary obstruction, patients will often present with abdominal pain, a palpably enlarged bladder, and potentially enlarged and painful kidneys if hydronephrosis is present.

Systemic signs of acute kidney injury may also be present, including inappetence, anorexia, nausea, vomiting and dehydration.

Physical exam may also reveal a thickened bladder wall. It’s also really important to perform a rectal examination in these patients - the urethra is palpable rectally, as is the prostate gland in male dogs. The urethra often feels thickened or cord-like, with a palpable mass or masses, and the prostate gland may be enlarged, irregular and asymmetrical (as we discussed in episode 22 on prostatic disease).

How do we diagnose TCC?

Most of our diagnostic approach will be the same as other lower urinary tract diseases since our lower urinary patients often present with the same clinical signs.

We’ll likely perform some bloodwork ahead of urine analysis, diagnostic imaging, and other specific tests.

Let’s talk bloods

We don’t see specific biochemical or haematological changes in TCC patients - instead, we’re using our bloods to assess overall health (remember, these are senior patients), evaluate renal function (looking for evidence of AKI) and look for things like evidence of haemoconcentration (due to fluid balance changes) or infection/inflammation - as well as assess suitability for chemotherapy where appropriate.

What about urine analysis?

Urine analysis is vital in investigating any urinary tract disease, and TCC is no exception. 

Before we get into what tests to run, I want to get on my soapbox for a moment—don’t cysto these patients! The last thing we want is to seed those tumour cells into different areas in the body, and performing a cystocentesis can do just that—drag those tumour cells through the body wall and cause secondary masses to form.

Instead, collect a free catch sample if possible or take a urinary catheter sample. That catheter will also come in handy for sampling the mass, but more on that later.

Urine analysis often reveals haematuria and, potentially, evidence of secondary infection. Sediment examination can reveal neoplastic cells in some cases (though the absence of these doesn’t exclude a tumour).

Urine should also be submitted for genetic PCR testing - also known as the BRAF test.

BRAF is a gene which encodes a protein called B-raf. This protein plays an important role in cell growth by promoting cell division. 

BRAF gene mutations are present in approximately 80% of dogs with TCC, and the BRAF test detects this mutation in epithelial cells that have shed into the urine.

It’s a highly specific test, so a positive BRAF mutation in a patient with lower urinary tract signs suggests TCC. However, it’s less sensitive - meaning that false negatives can be seen because around 20% of TCCs do not possess the BRAF mutation.

Blood, bacteria, or protein in the urine don’t affect the test - so if your patient has a concurrent UTI, you can still submit that same sample for analysis. You just need to ensure you’ve got enough urine - at least 5-10mls will be needed.

And then there’s imaging

As we discussed in episode 20, various imaging techniques can be used to investigate bladder tumours, including ultrasound, CT, and contrast X-ray studies.

We can also scope these patients to visualize the lower urinary tract. Cystoscopy is a relatively uncommon endoscopic procedure performed mostly in dogs since cats are too small for the endoscopes we commonly use.

In female dogs, a rigid endoscope is inserted into the urethra and advanced into the urinary bladder. In male dogs, a flexible urethrocystoscope is required. These are basically the same as a bronchoscope but much narrower—they usually have a maximum diameter of 3mm.

Cystoscopy must be performed as a sterile procedure, with sterile scopes and kit, and performed in a clean procedure area (we often will perform ours in theatre).

In addition to visualising the urethra and urinary bladder, we can collect guided biopsies of the urethra and bladder for histopathology and culture.

Let’s talk sampling

Sampling of the affected area is required for definitive diagnosis. We can collect this endoscopically if you’re scoping your patient or via urinary catheter under ultrasound guidance.

Traumatic catheter biopsy, or suction catheter biopsy, is an advanced skill we can assist with in these patients. It essentially involves placing a rigid urinary catheter as you normally would and then advancing it into the bladder mass under ultrasound guidance. You then apply suction to collect a small sample of tissue into the catheter lumen, then withdraw your catheter and sample.

Then pop this in formalin if you’re sending it for histology, or an EDTA tube with some saline if you’re sending it for cytology, or a plain pot with some saline if you’re sending it for culture. Repeat as needed until you’ve got all the samples you need.

So you’ve diagnosed your patient - but how will you treat them?

The most common urinary tumour we are likely to see in our veterinary patients is invasive urothelial carcinoma, which is also known as invasive transitional cell carcinoma (TCC). 

In terms of treatment of this tumour, it does depend on whether the tumour is resectable or not, whether the tumour has metastasized, and whether we are trying to achieve remission, or whether palliation is the goal. 

Let’s talk surgery

First of all, surgery may be an option for some of these patients. Surgery might be carried out initially to obtain a tissue sample, which we can then send for histopathology to achieve a definitive diagnosis. 

With benign or smooth muscle malignancies, we may be able to resect the tumour surgically with clear margins by performing a partial cystectomy. This may still be possible with urothelial carcinoma, although it is less likely and depends on whether the mass is located in an area away from the trigone, as these areas are more amenable to resection. 

Another option is to perform palliative surgery to debulk the tumour and relieve obstruction of the urinary tract. This will alleviate the patient’s clinical symptoms.  

Surgery does, however, carry some risks. 

Urothelial carcinoma tends to be aggressive, and recurrence is very common, not just in the area of the tumour but in the entire urothelium. This recurrence is usually not due to poor surgical technique but occurs because even the tissue of the urinary tract that appears normal may contain neoplastic cells. 

When we perform surgery, there is also a high risk of tumour seeding in the structures around the bladder, and it’s vital to communicate these risks to the pet carer. Total cystectomy has been described but has extremely high complication rates, and it is not commonly performed. 

Other surgical techniques which are more palliative include placing cystotomy catheters or low-profile cystotomy tubes, which will bypass the urinary obstruction. Complications of these procedures include urine leakage, tumour seeding, infection, tube displacement and self-trauma by the patient, causing tube damage. 

Urethral or ureteral stents may also be placed using minimally invasive techniques, which again will relieve urinary obstruction. However, lower urinary tract signs such as stranguria may persist in patients with stents, with between 25 and 39% of dogs in studies reported as being incontinent. This is significant from a health and safety point of view, as many of these patients will also need adjuvant chemotherapy. 

Laser ablation or debulking of the tumour obstruction can also be performed. Again, this is often a palliative measure. Significant side effects are associated with this procedure in neoplastic tissue, such as the risks of perforation, urethral stenosis, infection, and seeding of tumour cells. A lesser side effect is transient haematuria or stranguria post-procedure. 

What about chemotherapy?

Due to the high metastatic and recurrence rate of urothelial carcinoma, even with successful surgery, it is wise to follow up with adjuvant chemotherapy. Systemic chemotherapy is also the standard of care for patients where surgery is not performed.

Although chemotherapy is not a cure, patients can achieve stable disease or remission, with treatment well-tolerated and providing a good quality of life. 

Chemotherapy is usually given alongside cyclo-oxygenase (COX) inhibitors, with a variety of different chemotherapy drugs used, depending on the patient’s response. 

Chemotherapy drugs commonly used include vinblastine, mitoxantrone, carboplatin, metronomic chlorambucil and toceranib. 

Vinblastine is most commonly administered, as it has a good effect against these tumours and tends to have few adverse effects, providing good quality of life for these patients. 

Some studies do show long survival times with drugs such as cisplatin but with the risk of more severe adverse effects such as renal toxicity, gastrointestinal upset and bone marrow toxicity. 

For patients where a single-agent COX inhibitor such as piroxicam is used alone, remission is achieved in 15-20% of patients, with stable disease in 55% of patients. 

With the addition of cytotoxic chemotherapy drugs, tumour growth can be controlled in 75-80% of dogs. Median survival times are over a year, and dogs have a good quality of life throughout. 

Monitoring progression or treatment failure may be difficult, as clinical signs may not necessarily be seen with tumour growth. It is recommended that tumour sizes be measured prior to treatment and re-measured at 4-8 weekly intervals, which will then dictate whether treatment is continued or if the patient' changed. 

Secondary urinary tract infections are also common and may need to be treated with an appropriate oral antibiotic. 

And then there’s radiotherapy…

Radiotherapy may also be an option for patients alongside chemotherapy. Historically, hypofractionated protocols were utilised, which resulted in high incidences of side effects such as chronic colitis,  cystitis and urethral strictures.

However, with more targeted treatments and more accurate megavoltage machines now more readily available, acute side-effects are reported to be milder, with fewer late side-effects such as strictures also reported. Palliative radiotherapy may also be useful for analgesic purposes, as well as to reduce the rate of growth or size of the tumour. 

And what about cats?

For feline patients with invasive urothelial carcinoma (which tends to be rare), more than half of the cases reported were away from the trigone, making them more suitable for surgical resection. Studies show that treatments are similar to those used for canine urothelial carcinoma, with surgery, cytotoxic chemotherapy, COX inhibitors, and a combination of the above used. Median survival times were between 261 and 311 days for these feline cases. 

How do we nurse patients with bladder tumours?

Our nursing considerations for these patients vary depending on whether they’re showing signs of acute obstruction and whether they are in the hospital or receiving outpatient treatment.

Let’s start with inpatient care

These patients are not usually hospitalised for long. Most of our inpatient treatment aims to support an obstructed patient, provide symptomatic care, and assist with diagnostics alongside general nursing care.

Assessing and managing fluid balance, pain management, and monitoring for signs of obstruction are all important considerations for patients with suspected bladder neoplasia.

When anaesthetising these patients for diagnostics, there aren’t any specific anaesthesia considerations to be aware of. 

However, if they’ve got evidence of AKI and hydronephrosis due to their obstruction, be careful with fluid rates and ensure your patient’s blood pressure remains above 90-100mmHg systolic (60mmHg mean) throughout GA. This will ensure they have sufficient renal perfusion and prevent worsening (or developing) acute kidney injury.

What about long term?

Special care should be taken with patients who are receiving cytotoxic chemotherapy drugs. 

Many of these patients are incontinent or urinate inappropriately, and care should be taken that humans in contact with the patient are not exposed to cytotoxic metabolites in the urine. 

Any staff or family member who is pregnant, trying to become pregnant, immunosuppressed or under 18 should restrict contact with the patient. 

Gloves should be worn to clean up cytotoxic urine or to bathe the patient, with aprons and protective face shields needed for bathing in case urine splashes onto the face.

Incontinence pads can be useful to allow elimination for a patient who might not otherwise be able to hold their urine until they get outside. 

Chemotherapy side effects should be reported to the treating oncologist, with the aim of providing supportive care, or reducing the dose or changing drugs if they are severe. 

Our aim is always quality of life in chemotherapy patients. If we are not providing this, then we need to reevaluate our drug regimen and patient goals. It is vital to monitor QoL in these patients on an ongoing basis.


So there you have it - a medicine and oncology approach to nursing patients with bladder tumours! Though we don’t see them very often, when we do, they’re likely to be malignant and require intensive management, especially with things like regular chemotherapy administration alongside in-hospital care where needed.

The vet nurse plays an absolutely vital role in delivering this care. Key areas for us to be involved in include administering chemotherapy, providing client support, and maintaining quality of life.

Did you enjoy this episode? If so, I’d love to hear what you thought - screenshot it and tag me on Instagram (@vetinternalmedicinenursing) so I can give you a shout-out and share it with a colleague who’d find it helpful!

Thanks for learning with me this week, and I’ll see you next time!

References and Further Reading

Laura Jones
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