New Canine Prostatic Carcinoma

PASE Oncology
By: Lillie Davis DVM, DACVIM (Oncology)
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Your pet has been diagnosed with prostatic cancer, specifically prostatic carcinoma.

Canine prostate tumors are uncommon, with a prevalence of 0.2-0.6%. However, the dog is one of the few domestic species to develop spontaneous prostate cancer. An analysis of 3 studies of canine prostate disease revealed prostatic adenocarcinoma was diagnosed in 7-16% of patients with prostatic disease. When evaluating intact dogs, prostatic cysts and prostatitis were the most common diseases of the prostate. When evaluating castrated dogs, prostatic adenocarcinoma was the most common disease of the prostate. The average age of dogs affected with prostate cancer is 10 years. The majority of canine prostate cancers are carcinomas, primarily adenocarcinomas. Transitional cell carcinoma, which arises from the cells lining the urinary tract and is most commonly found in the urinary bladder, may arise in prostatic urethra and affect the prostate. Other tumor types are rare to affect the prostate. Benign tumors of the prostate are extremely rare, as is metastasis to the prostate from other body systems. The cause of prostate cancer in dogs is currently unknown. Castration has been found to be a risk factor in some studies, however more recent reports have described prostatic adenocarcinoma more frequently in intact dogs than historically described. Breeds at increased risk of developing prostate cancer include bouvier des flandres, doberman pinscher, shetland sheepdog, scottish terrier, beagle, miniature poodle, german shorthaired pointer, airedale terrier, and norwegian elkhound.

Prostatic carcinomas are aggressive cancers. They are both locally invasive and have high rates of regional and distant metastasis (spread) to lymph nodes, lungs, bone, and other organ systems. At the time of death, 80-100% of dogs with prostate carcinoma have evidence of measurable metastatic disease, with lymph nodes, lungs, and bones (lumbar vertebrae and pelvis) being the most common sites.

Clinical signs and history are generally variable and may be related to the local disease in the prostate and/or metastatic disease. Most common findings attributable to the loco-regional disease include bloody urine, straining to urinate, difficulty urinating, urinary tract infection, difficulty defecating, straining to defecate, or flattened or ribbon shaped stool. These tumors and/or their metastatic lymph nodes may result in inability to urinate and/or defecate as they continue to grow. Clinical signs may partially improve with treatment for prostatitis (bacterial infection of the prostate), but as this is only treating secondary bacterial infection the improvement is generally only transient or partial. Secondary bacterial urinary tract/prostate infections are common with prostatic cancers. Prostates in intact male dogs can become mineralized due to many of the different disease processes that affect the prostate, aside from prostatic cancer.

A diagnosis of prostatic carcinoma or TCC requires histopathologic confirmation from a tissue biopsy sample. Although cancerous cells may be present in the urine of 30% of dogs with TCC, cancerous cells often are indistinguishable from reactive epithelial cells associated with inflammation. Urine antigen tests for TCC have been found to be sensitive, but a high number of false-positive results limits the value of these tests. Methods for obtaining tissue for histopathologic diagnosis include cystotomy (surgical biopsy), cystoscopy (biopsies obtained with a scope), and traumatic catheterization (obtaining samples cancer cells broken off the tumor when a urinary catheter is passed into the bladder). It is recommended to avoid fine needle aspirates or biopsies obtained through the skin (percutaneously) as this can be associated with seeding of cancer cells along the needle or biopsy tract through the body walland abdominal cavity.

The majority of dogs with primary prostatic cancer such as prostatic adenocarcinoma are unfortunately diagnosed with advanced disease. Prostatic carcinoma in the dog is considered to have a poor prognosis. The average survival times reported without further therapy is less than 1 month. Due to the locally invasive nature of this cancer and the high rates of metastasis, therapy is focused on local and systemic treatment. However, unfortunately therapy is largely considered to be palliative and no standard-of-care consensus therapy exists.

Castration can result in involution of non-cancerous prostatic tissue, however it does not alter the progression of the tumor and is considered palliative. Surgical removal of the prostate (prostatectomy), if pursued, is generally restricted to dogs with early stage disease that is still confined to the capsule of the prostate. Total surgical removal of the prostate is generally not recommended however, as it is associated with a high rate of postoperative complications, with over 90% of dogs developing complete urinary incontinence, and a survival benefit has not been definitively demonstrated. If a partial prostatectomy can be performed in an attempt to remove a tumor for dogs with early stage disease that has not invaded beyond the prostate capsule, the average survival time may increase to 3-4 months and have decreased rates of complications. Surgery is generally not a viable option for dogs with prostatic cancer. However, newer studies (2018, 2020) have shown that dogs with prostate carcinoma who successfully receive total prostatectomy had a median survival time of 231 days. These studies also revealed that approximately 35% of these dogs experienced urinary incontinence. Those dogs who were treated with surgery and medical management (i.e. chemotherapy or NSAIDs) did better than those dogs who just received surgery.

Chemotherapy can still be used to slow the progression of disease and delay the onset of metastasis. Chemotherapy is indicated regardless of other therapies that are used as this tumor has a metastatic potential and chemotherapy is the only treatment that addresses metastasis. Alone, it is indicated when surgery is not possible. Survival times differ depending on the protocol chosen, typically ranging from 6 months to 12 months. Systemic medical therapy is another mainstay of prostatic cancer treatment in dogs and usually consists of chemotherapy, cyclooxygenase (COX) inhibitors (non-steroidal anti-inflammatory or NSAID medications), and combinations of these. Although medical therapy is not usually curative, several different drugs can lead to remission or stable disease of prostatic carcinoma, and most therapies are well tolerated. COX inhibitors are beneficial in the treatment of a large percentage of carcinoma due to the high frequency of COX expression in these tumors.

The majority of patients with prostatic carcinoma or TCC are treated with a few chemotherapeutic drugs: mitoxantrone, vinblastine, or carboplatin along with a non-steroidal anti-inflammatory drug (NSAID) or COX inhibitor, like piroxicam, deracoxib or carprofen. Mitoxantrone is a chemotherapy given intravenously every 21 days for 4-5 treatments. NSAIDs (COX inhibitors) are most commonly used to reduce inflammation and pain associated with arthritis. However, they have recently been shown to also have anti-cancer properties. Adverse side effects, again, are rare but may include gastrointestinal upset (anorexia, vomiting, diarrhea) and/or black tarry stools due to stomach ulceration and bleeding. Less common side effects include liver or renal toxicity. We monitor the effectiveness of these drugs with physical examinations, bloodwork, and periodic imaging (abdominal ultrasound and chest x-rays). A recent study (2018) regarding dogs with prostatic carcinoma treated with NSAIDs and/or chemotherapy revealed that dogs who received NSAIDs and chemotherapy had a longer median survival time (106 days) compared to dogs who only received NSAIDs alone (51 days). The overall median survival time for dogs in this study was 82 days.

Typically chemotherapy is most effective in the microscopic disease setting and treatment of prostate tumors has been impaired by the relatively non-surgical nature of most tumors. If the tumor is located in an area where surgical excision is possible, this treatment, followed by chemotherapy, may result in the longest survival times. Radiation therapy has also been reported and the minimal studies thus far show it to be well tolerated with comparable response and survival times to other treatment modalities (3-4 months average survival time). Chemotherapy may be useful as this tumor has a high metastatic potential. Alone, chemotherapy may be used when surgery is not possible or radiation therapy effects are unacceptable. Survival times reported are scant. In two studies, average survival was 3-5 months. A recent study reported that dogs with prostatic tumors treated with an NSAID COX inhibitor had a median survival time of 7 months on this therapy, likely attributable to a majority of prostate carcinomas demonstrating high expression levels of the COX-2 enzyme.

Costs of chemotherapy vary depending on the protocol, but are commonly $500-800 a visit, with visits varying from 1-4 times a month for 4-6 months, though some patients are treated longer depending on the chemotherapy protocol and their disease status. Average total cost for chemotherapy protocols used to treat prostatic cancer range from $5000-7000 for the chemotherapy itself, not including repeat imaging (abdominal ultrasound and chest x-rays) which are necessary to track efficacy of chemotherapy.

In general terms, chemotherapy is different in our pets than humans.The toxicities in our pets re less because we use lower doses than those used in humans. We do this because our goal in veterinary oncology is to preserve a good quality of life while extending survival time. Chemotherapy is designed to kill rapidly dividing cancer cells but in doing so also kills normal cells that are rapidly dividing. This is where most of the side effects of chemotherapy come from. Normal cells that are killed include those that line the intestines, bone marrow and hair follicles. Side effects that could occur are vomiting and diarrhea, low white cell count (from bone marrow suppression) and occasionally, hair loss. The low white cell count can result in an infection that your pet cannot fight off. If this happens hospitalization for intravenous fluids and antibiotics will be required. It is extremely rare for an animal to have a fatal reaction to chemotherapy. The majority of our patients tolerate chemotherapy very well and they have a great quality of life while undergoing therapy. Less than 20% of our patients get sick and about 5% need to stay in hospital due to the abovementioned side effects. Less than 1% of patients will have a fatal side effect from chemotherapy.

Radiation therapy is another treatment option. We discussed the option of a form of therapy called stereotactic radiosurgery. This is a very special form of radiation therapy that is delivered by a piece of equipment called a Cyberknife. Rather than many small doses of radiation given over the course of four weeks, a few very large doses of radiation are delivered precisely to the tumor itself, often with the ability to spare important structures in the region. The treatment is usually completed within a few days. This treatment is only available in a few places across the country for animals. There happens to be a facility very close by, located in Malvern, PA. The estimated cost for this treatment would be about $12,000 if you pursue all three treatments. An alternative to Cyberknife radiation is a RT method called IMRT (palliative radiation therapy), which is usually the preferred radiation option. This is still very specialized and precise radiation, but allows a little larger of a margin around the tumor to hopefully catch any tumor cells that are extending out beyond the mass itself into surrounding tissue. This may allow for better longer term tumor control by catching a larger proportion of tumor cells. This form of therapy is delivered daily Monday through Friday for about 3.5-4 weeks. A recent (2020) study looking at 18 dogs with prostatic carcinoma who underwent IMRT found that they had a good overall median survival time of 563 days (1.5 years) with a moderate risk of toxicity. In this same study, dogs who were symptomatic for their prostatic carcinoma had shorter survival times (220 days) than those dogs who had incidental prostatic carcinoma and were asymptomatic.

Overall, I recommend a multi-modal approach of treatment with any combination of NSAIDs (piroxicam), chemotherapy, and/or radiation therapy. I find that radiation therapy followed by chemotherapy tends to allow for better quality of life for these patients. However, the overall survival time of these patients (as illustrated above) is highly variable.