Prostatic disease in the dog (Proceedings)

Benign Prostatic Hyperplasia

The most common prostatic disease in the dog is benign prostatic hyperplasia (BPH), which occurs in intact male dogs that are usually ≥ 2 years-of-age. Scottish terriers appear to be more severely affected than other dog breeds. The etiology is associated with altered androgen-estrogen ratios as the dog matures. Dogs with BPH can be asymptomatic or display clinical signs such as tenesmus (staining to defecate), hemorrhagic or clear urethral discharge, and hematuria. On prostatic palpation abdominally or rectally the prostate is nonpainful and often symmetrically enlarged. The presence of BPH predisposes the affected patient to developing prostatic cysts and bacterial prostatitis, which may produce additional clinical signs associated with those disorders. Data base results usually reveal an unremarkable CBC and biochemistry profile with a urinalysis indicating hematuria. Survey radiographs generally reveal prostatic enlargement, while abdominal ultrasonography indicates that the prostate has either normal echogenicity or is diffusely hyperechoic with small parenchymal cavities. Fluid obtained post-prostatic massage or semen post-ejaculation may be normal or have RBCs present.

Castration is the most effective treatment of BPH. Although treatment is only necessary if clinical signs are present, asymptomatic patients can still benefit from castration in regard to preventing the development of clinical signs. Involution of the gland begins shortly after orchiectomy is performed, reaching approximately 50% reduction in size by 3 weeks post-castration. If the patient with BPH is symptomatic but the owner rejects castration as a therapeutic option, medical intervention can be considered.

Hormonal therapy has long been recognized as a means to achieve reduction in the size of the enlarged prostate, but has many potential side effects. In addition, the hormones generally used in treatment affect the reproductive potential of the patient, limiting the usefulness of hormonal therapy in affected dogs that are kept intact for breeding purposes.

Estrogen depresses pituitary gonadotrophin secretion, reducing testicular androgen secretion which ultimately results in prostatic atrophy. Products used in BPH therapy include diethylstilbesterol (DES) administered at 0.2 – 1 mg PO q2 – 3 days for 3 - 4 weeks and Premarin, a conjugated estrogen product, administered at 0.312 – 0.625 mg/day PO for 5 days and then every 2 – 4 days for 3 weeks initially. A maintenance dose can then be established to control the dog's clinical signs over a longer period of time, if needed. Potential side effects from estrogen include bone marrow suppression (anemia, leucopenia, and thrombocytopenia), which can be permanent or require lengthy support for recovery. Paradoxically, use of estrogen products can eventually result in prostatic enlargement due to the induction of prostatic metaplasia, alterations in secretory status, and fibromuscular growth. These estrogen-induced changes can also predispose the patient to development of prostatic cyst formation and bacterial infection. In addition, reduction in the patient's libido can result from the administration of estrogen. Due to the many potentially undesirable side effects, estrogen therapy for BPH is not recommended.

Progestogens have also been used in the treatment of BPH, including megestrol acetate (0.5 mg/kg/day PO for 4 – 8 weeks) and medroxyprogesterone acetate (3mg/kg subQ). These progestogens decrease the number of prostatic androgen receptors and testosterone levels, competitively inhibits binding of dihydrotestosterone (DHT) to intracellular receptors, and inhibits 5-α-reductase, resulting in decreased DHT concentrations. As a consequence, decreased libido and fertility may develop. Several adverse effects may occur with the use of megestrol, including weight gain, lethargy, behavioral changes, mammary enlargement, diabetes mellitus, neoplasia, and adrenal suppression. Medroxyprogesterone acetate decreases testosterone levels and temporarily inhibits spermatogenesis. Many of the same adverse effects seen with megestrol can also be seen with medroxyprogesterone. Although some dogs with BPH receiving progestogens have been successfully bred, the adverse effects associated with these drugs make them undesirable for long-term therapy.

Finasteride and flutamide have been used successfully for the treatment of BPH in dogs. However, it should be remembered that both of these agents are expensive and must be given on a maintenance basis to sustain reduction in the size of the hyperplastic prostate.

Finasteride (Proscar®) is a 5-alpha reductase inhibitor which blocks conversion of testosterone to its active metabolite, dihydrotestosterone. The dose is 0.1 - 1 mg/kg PO daily for 1 – 4 months. Finasteride does not affect serum testosterone levels and has little effect on libido although it will decrease the prostatic portion of ejaculate. Clinical signs related to BPH generally begin to resolve approximately one week after the initiation of finasteride therapy and are often completely resolved within one month post-initiation. Once therapy with finasteride has been discontinued, the prostate will once again hypertrophy, reaching its pre-treatment size approximately 1 – 2 months after completion of finasteride administration. The drug is teratogenic and should not be administered by women of reproductive age. If used in dogs intended for breeding, it is recommended to discontinue use of finasteride temporarily 10 days prior to breeding and during the breeding period in order to minimize any risk to puppies produced and to restore the volume of prostatic fluid in the ejaculate.

Flutamide (Eulexin®) is an antiandrogenic agent that competes for dihydrotestosterone receptors in the prostate. The dose is 2.5 – 5 mg/kg/day PO for 4 – 6 weeks. Flutamide has few effects on testicular function, causing no change in the patient's libido, sperm production, or apparent fertility. However, hepatopathy as severe as liver failure has been documented in humans taking flutamide.

Chemical castration with subsequent resolution of BPH can be accomplished with the gonadotropin-releasing hormone (GnRH) agonists deslorelin (Suprelorin®) and nafarelin (Gonazon®) or the synthetic testosterone analogue osaterone acetate (Ypozone®). The GnRH agonists are used as subQ sustained release implants, achieving down regulation of GnRH receptors and subsequent suppression of testosterone an estradiol concentrations. The implants result in decreased size of both the prostate and testes of the patient for a period of 6 – 12 months. The patient is rendered infertile until the implant is removed. In contrast, osaterone acetate (0.25 – 0.5 mg/kg PO daily for 7 days), which has been marketed in Europe for treatment of BPH, competitively inhibits prostatic DHT receptors, resulting in decreased prostatic size and resolution of clinical signs without affecting sperm quality or the patient's fertility. Notable reduction in clinical signs occurs within two weeks of completion of administration and reduction in prostatic size is maintained for approximately 6 months. Potential adverse effects of osaterone include reduction in serum cortisol and adrenocortical insufficiency.

Bacterial Prostatitis

Bacterial prostatitis affects sexually mature dogs and is the second most common prostatic disease. Pathogenic organisms involved in the etiology include E. coli, Staphylococcus, Streptococcus, Pseudomonas, Proteus, Mycoplasma, and Brucella canis. Infection of the prostate most commonly occurs as the result of reflux of bacteria from the urinary bladder or ascending infection from the urethra although the route of infection can also be hematogenous . Castration is always recommended to facilitate resolution of prostatitis after antibiotics have been initiated and the patient is clinically stable.

Acute prostatitis can produce clinical signs such as sudden onset of lethargy, dysuria, fever, a painful and soft prostate on palpation, stiff rear limb gait, vomiting, and constipation. Abnormal laboratory values most commonly include a neutrophilic leukocytosis ± a left shift and hematuria, bacteriuria, and pyuria on urinalysis. Radiographically, the prostate is often normal except for an indistinct cranial border in some cases. Ultrasonographically, the prostate appears diffusely to focally hyperechoic. The bacteria involved may sometimes be cultured from the urine. Ultrasonography may also be used to aseptically obtain specimens for cytology and culture through a transabdominal approach. Due to the possible dissemination of bacteria prostatic massage is not recommended for collection of specimens. Acute prostatitis can lead to the development of chronic prostatitis and/or recurrent urinary tract infections. Antibiotic therapy is essential for treatment and supportive care is often needed as well. Parenteral antibiotic therapy is recommended initially followed by an extended course of oral antibiotic administration. Antibiotic therapy is best chosen by culture and sensitivity findings from prostatic fluid, prostatic FNA, brush sampling from the prostatic urethra,or, in some cases, urine. Ideally, culture and sensitivity should be performed on appropriate specimens initially and after the conclusion of a minimum of 3 – 4 weeks of antibiotic therapy. The follow-up appointment should also include a physical exam, urinalysis, and prostatic cytology, if possible. The most desirable antibiotics are those which will penetrate the prostatic-blood barrier such as erythromycin, clindamycin, trimethoprim-sulfa, chloramphenicol, and fluoroquinolones.

Chronic prostatitis is a more common entity in the dog than acute prostatitis. Unlike acute prostatitis, there are often no systemic signs of illness in patients with chronic signs of illness. The affected dog may have a history of recurrent urinary tract infection along with purulent or hemorrhagic urethral discharge, and/or dysuria. On palpation the prostate may not be enlarged or painful but frequently has an irregular contour. Data base analysis frequently reveals an unremarkable CBC and biochemistry profile, but the urinalysis commonly shows some combination of pyruia, hematuria, and bacteriuria. Abdominal radiographs may indicate mineralization of the prostate while ultrasonographic examination of the prostate often reveals focal to multifocal areas of increased echogenicity ± small intraparenchymal anechoic foci. Prostatic fluid collected post-prostatic massage or from ejaculate can be useful for cytologic examination and culturing microorganisms. If high numbers of gram negative or gram positive organisms with leukocytes are observed in the prostatic fluid, a diagnosis of prostatitis is supported. When collecting prostatic fluid, contamination with preputial discharge should be avoided. In addition, concurrent urinary tract infection complicates the evaluation of prostatic fluid in terms of establishing the presence of bacterial prostatic infection. However, any intact male dog with urinary tract infection should be assumed to be harboring microorganisms in the prostate. Prostatic specimens for cytology and culture may also be obtained ultrasonographically through FNA or biopsy performed via transabdominal technique aseptically. Therapy for chronic prostatitis includes eliminating any predisposing factors such as immunosuppressive medication or anatomic defects. Although antibiotic therapy is a cornerstone of treatment, parenteral administration initially is generally not necessary, unlike acute prostatitis. Treatment with an antibiotic with effective prostatic-blood barrier penetration for a minimum of 6 weeks is recommended. Success is best monitored by achieving two negative culture results from prostatic fluid/aspirate in a 30-day interval post-therapy. In some cases, long-term suppressive therapy may be needed, using once daily dosing of an antimicrobial that is well tolerated and appropriate for the organism cultured.

Prostatic Abscessation

Prostatic abscessation most commonly evolves from a chronic bacterial prostatitis and is characterized by the development of pockets of septic, purulent exudate within the prostatic parenchyma.

Clinical signs include dysuria, tenesmus, purulent or hemorrhagic urethral discharge, and an enlarged, painful, and asymmetrical prostate with varying consistency on palpation. Systemic signs may be present such as fever, pain, vomiting, and occasionally septic shock. Reviewing the data base most commonly reveals a neutrophilic leukocytosis ± a left shift, occasional liver enzyme elevation due to septicemia and endotoxemia, and an inflammatory urinalysis (hematuria, pyuria, bacteriuria). Abdominal radiographs often show enlargement of the prostate and an irregular contour. Ultrasonographic examination usually reveals a prostate with echogenicity ranging from normal to diffusely hyperechoic, parenchymal cavities, and an asymmetric shape. Prostatic massage and/or ejaculation are not advisable in obtaining samples. Aseptic, transabdominal, ultrasound-guided FNA of the prostate for cytology and culture may be helpful in establishing the presence of infection; however, care must be taken to prevent abscess rupture, seeding of bacteria, and subsequent peritonitis. Antibiotic therapy is essential, using an antibiotic with penetration across the prostatic-blood barrier for a minimum of 6 weeks. Selecting an antibiotic by culture and sensitivity of an appropriate specimen is highly desirable. Pathogenic organisms are usually aerobic but can sometimes be anaerobic. Ideally, the chosen antibiotic should have good penetration across the prostatic-blood barrier. Parenteral administration of antibiotics may be necessary initially if the patient is systemically ill. Supportive care is also generally required for such patients. When the patient is stable, progress is monitored by rechecking monthly until resolution of the abscess(es) is confirmed through ultrasonographic examination of the prostate, urinalysis, prostatic palpation rectally, and cytology and culture of prostatic fluid/FNA ± urine culture. After abscess resolution, rechecks should be scheduled every 3 – 6 months. Rechecks should include urinalysis and urine culture since asymptomatic, recurrent urinary tract infection is common. Surgical drainage of the abscess(es) may be necessary to achieve long-lasting resolution. Ultrasound-guided, percutaneous aspiration of abscesses can also be used in therapy. Long-term suppressive antibiotic therapy may be required, especially if surgical intervention is not elected. Prostatic abscessation which remains unresolved can result in the patient experiencing abscess rupture and/or septicemia. Castration of the stable, intact patient is recommended to facilitate control and resolution of infection.

Prostatic Neoplasia

Tumors affecting the prostate are usually malignant rather than benign and are most often primary in origin rather than metastatic. Malignant tumors found in the prostate include adenocarcinoma, transitional cell carcinoma, and leiomyosarcoma. Approximately 80% of prostatic neoplasms have already metastasized at the time of diagnosis. Breed predisposition for prostatic neoplasia includes the Shetland sheepdog, Scottish terrier, Airedale terrier, and Doberman pinscher. Unlike the majority of prostatic diseases, castration is not helpful in treatment or prevention of prostatic cancer. In fact, some studies have indicated that castrated male dogs are at greater risk for developing prostatic neoplasia and that castration favors tumor progression.

Adenocarcinoma is the most common primary prostatic neoplasm in the dog and generally is found in intact or neutered dogs > 6 years-of-age. Metastasis can occur to regional lymph nodes, periprostatic tissues, bladder, lung, and bone, especially the pelvis and vertebrae. Clinical signs can include hematuria, stranguria, tenesmus, hind limb weakness, and an enlarged, painful prostate on palpation. Data base findings may include neutrophilic leukocytosis, azotemia, hypercalcemia, hematuria, and pyuria. Specimens obtained from post-prostatic massage or FNA of the prostate may reveal abnormal epithelial cells. Radiographs may show enlargement of the prostate with an irregular contour, prostatic mineralization, bone lysis, and/or thoracic metastasis. Prostatic ultrasonography frequently reveals asymmetry and focal or multifocal hyperechoic areas in the parenchyma. Treatment is challenging and median survival time is often relatively short following diagnosis of malignancy with survival time of weeks to months. Total prostatectomy is associated with a high degree of morbidity and mortality. Partial prostatectomy of the rare benign tumor can be curative, but is of limited value otherwise. Stenting the prostatic urethra in case of obstruction resulting from neoplasia can improve the quality of the affected patient's life. Photodynamic therapy has shown promise in amelioration of clinical signs, but is not curative. Radiation therapy has not extended survival significantly although newer applications such as intensity-modulated radiation therapy may be more promising. Chemotherapy may have some benefit, using combinations of mitoxantrone or carboplatin plus piroxicam (0.3 mg/kg/day PO)as a cyclooxygenase-1 inhibitor. One study indicated that dogs with prostatic adenocarcinoma treated with piroxicam or carprofen alone survived significantly longer than untreated dogs (6.9 months versus 0.7 months).(Sorenmo, 2004) The use of biphosphonates is a palliative option for the management of patients with skeletal metastases and/or hypercalcemia.

Prostatic and Paraprostatic Cysts

Although uncommon, dogs can develop both prostatic cysts and paraprostatic cysts. Secondary bacterial infection may develop in some cysts, complicating clinical signs and treatment. Smaller prostatic cysts may develop diffusely within the gland in conjunction with BPH. Prostatic retention cysts are found within the parenchyma and usually communicate with the urethra. Paraprostatic cysts develop outside the parenchyma and typically communicate with or are attached to the prostatic gland. Cysts are thought to develop due to secretory stasis brought about by structural changes induced by hormonal influence and, in some cases, may develop from embryonic remnants associated with the prostate.

Clinical signs related to cysts associated with the prostate most often take the form of compression of the colon or urethra by larger cystic structures, producing tenesmus or dysuria ± urinary incontinence respectively. Urethral discharge may also occur in some cases, appearing hemorrhagic, serosanguineous, or purulent in character. Abdominal or rectal palpation may indicate the presence of a mass. Occasionally, indications of a perineal hernia may be found. Data base analysis may reveal a neutrophilic leukocytosis on the CBC and hematuria ± inflammation on the urinalysis. Abdominal radiographs most commonly show a mass effect and/or enlarged prostate which may displace the rectum dorsally and the bladder ventrally. Frequently, mineralization of the cyst is observed. If a large paraprostatic cyst is present, radiographs may give the impression that 2 bladders are present since two fluid-filled structures can be observed in the abdomen Contrast radiography may be needed to correctly identify the relationship of a cyst or cysts to other structures. Abdominal ultrasonography may reveal cysts as structures with a hyperechoic outer rim and hypo- or anechoic contents.

Larger cysts associated with the prostate may need to be surgically excised and/or drained. Surgical techniques may involve debridement, omentalization, marsupialization, and placement of drains. Drainage can also be accomplished by ultrasound-guided, percutaneous aspiration. The percutaneous drainage approach may be superior to surgical intervention, having the potential to cause less morbidity at a lower cost than tradtitional surgical techniques. Antibiotic therapy is indicated for those patients with secondary bacterial infection. Castration is also recommended for patients with cysts to aid in resolution and prevention of prostatic disease.