Clinical signs and diagnostic methods
The timing of haematuria relative to urine voiding can aid in localising the source of bleeding (Table 5). Ideally both a free catch and cystocentesis sample would be assessed to determine the location. Blood throughout the urine stream, known as ‘total’ haematuria, can be found with pathology of the bladder, ureters and kidneys or systemic bleeding disorders. It results in pink coloured urine as seen in this case (Grauer 2009, Kenefick 2010). The dog was not demonstrating any other signs attributable to an underlying bleeding disorder; however haematology including a smear for platelet assessment and clotting times should be performed for completeness.
Table 5. Guide to timing and location of haematuria
| Timing of haematuria - the following explanations can be useful as a guide, but overlap occurs|| Possible origin of haematuria |
| Initial– blood seen at the start of urine voiding|| Lower urinary tract (bladder neck, urethra, vagina, vulva, penis or prepuce) Extra-urinary causes (proestrus, infection of uterus, prostatic disease or neoplasia of the genital tract)|
| Terminal– blood seen towards the end of urine voiding|| Upper urinary tract (bladder, ureters, kidneys – erythrocytes settle in bladder and are expelled towards the end of voiding)|
| Total– blood throughout urine voiding/pink urine||Bladder, ureters or kidneys|
A positive result on a urine dipstick may be due to pigmenturia other than blood (Kenefick, 2010), hence confirmation with urine microscopy in this case. Urine culture can be used to exclude chronic inflammation due to an underlying urinary tract infection as the cause of the haematuria. It is recommended that culture be performed on a sample obtained via cystocentesis since free catch samples may be contaminated. However, it is not uncommon for low numbers of red blood cells to be detected after collection of urine by cystocentesis.
Ultrasound has been recommended as the primary imaging modality for investigation of patients with haematuria or dysuria due to the ability to evaluate the majority of the urinary tract and it can also facilitate sample collection. When compared to intravenous urography and double-contrast cystography, it was the only imaging modality where bladder masses were detected in 100 per cent of dogs. However the limitations of not being able to fully evaluate the intra-pelvic urethra were acknowledged (Leveille et al., 1992). Where ultrasound is not available, radiography for positive and double-contrast retrograde urethrocystography can be utilised. Contrast cystography demonstrated a mass or filling defect in 96% of dogs with LUT tumours in one retrospective study, and was therefore considered a useful non-invasive diagnostic method (Norris et al., 1992).
Fine needle aspirate (FNA) of masses of the bladder, prostate or urethra is generally not recommended due to the potential for neoplastic seeding along the needle tract (Nyland et al., 2002). Obtaining a sample via ultrasound guided urinary catheter or cystoscopy is considered preferable (Webster, 2009).
Cystoscopy is a useful diagnostic procedure allowing visualisation of and biopsy collection from the lower urinary and genital tracts. Rigid cystoscopes are utilised in bitches whereas small flexible ‘scopes’ are available for use in male dogs. Cystoscopic biopsies have been shown to be of diagnostic quality in 65% of male dogs and 96% of female dogs compared to 100% with surgical cystotomy biopsies (Childress et al., 2011). However, since few general practices will possess a suitable flexible cystoscope to allow this technique to be performed in male dogs, referral should be considered.
Although urinary catheter samples are an accepted simple minimally invasive method of sample collection which do not require specialised equipment, the limitation of sample yield on accuracy of histological diagnosis has been noted (Lamb et al., 1996). In this case, the sample findings were suggestive of TCC but were insufficient to provide a definitive diagnosis since only cytological and not histological samples are obtained.
The majority of dogs have advanced disease at the time of diagnosis, and may not be surgical candidates (Henry, 2003). Metastatic disease (regional or distant) has been reported to be present in 11% (Henry, 2003) to 31% (Norris, 1992) of dogs at the time of diagnosis of malignant bladder tumours. Accurate histological diagnosis allows implementation of optimal treatment.
Alternative methods of diagnosis have been explored, including use of a ‘bladder tumour antigen test’ originally designed for use in humans. Although sensitivity was found to be good, specificity is low leading to false positive results especially in the presence of haematuria, making it unreliable in differentiating malignant and non-malignant lower urinary tract disease (Billet et al., 2002, Henry et al., 2003).
Management options, expected survival times and potential adverse effects need to be discussed with the owner. The literature reveals a number of methods of management of canine TCC that have been explored including: surgical (debulking, partial cystectomy, cystotomy tubes), radiation, chemotherapy including piroxicam, cisplatin, mitoxantrone and gemcitabine (Marconato et al., 2011), laser ablation (Cerf & Lindquist, 2012) or a combination of these techniques. Regardless of method, however, median survival times (MST) are generally less than a year.
The non-steroidal anti-inflammatory drug (NSAID) piroxicam has been reported to have antineoplastic properties, although uncertainty exists over the precise mode of action. Although generally well tolerated, piroxicam-induced gastrointestinal adverse effects and subclinical renal papillary necrosis are recognised complications (Knapp et al., 1992).
Complete remission, defined as disappearance of all clinical and radiographic evidence of tumour for a minimum of 30 days, was seen in 2 of 34 dogs treated with piroxicam in one study (Knapp et al., 1994), although MST was only 181 days. Piroxicam is not licensed for use in dogs and therefore other NSAIDS such as meloxicam could be considered initially as alternative treatments.
MST for piroxicam used in combination with mitoxantrone has been reported at 291 days which is longer than reported for piroxicam alone (Henry et al., 2003). Treatment with piroxicam and mitoxantrone in combination with coarse fraction radiation has been evaluated and found to be well tolerated (Poireir et al., 2004). It was concluded however, that since MST in this small pilot study was 326 days, this combination offered limited advantage over piroxicam and mitoxantrone alone.
Gemcitabine is reported to be a promising chemotherapeutic agent in human medicine and when used in dogs in combination with piroxicam an improvement in clinical signs was noted (Marconato et al., 2011). However, like many other treatments evaluated, the combination failed to significantly improve overall survival time.
Cisplatin administered in combination with piroxicam has been shown to induce remission more frequently than cisplatin alone. Renal toxicity was a dose-limiting factor due to the direct nephrotoxic effect of cisplatin in addition to NSAIDs induced negative effects (Knapp et al., 2000). Dogs with TCC are at risk of obstructive disease, which can contribute to renal failure (Henry et al., 2003). Monitoring of renal parameters in dogs receiving treatment for TCC is therefore advisable.
Advice from a clinical oncologist can be sought where appropriate. Oncologists currently consider treatment with piroxicam and mitoxantrone to be the primary standard of care providing a MST of 291 days and a 35% response rate, with other options being explored if response to treatment is poor.