Introduction
Malignant prostatic neoplasia is the most commonly reported disease affecting the prostate of castrated dogs.1 Clinical signs associated with prostatic neoplasia are often nonspecific, such as anorexia and weight loss. More specific signs, such as tenesmus, dysuria, stranguria, incontinence, and urethral discharge, can also be seen in dogs with prostatic neoplasia.2 Urethral obstruction can occur from prostatic compression of the urethral lumen, and subsequent urine retention can result.
The most commonly diagnosed neoplasms affecting the prostate in dogs include urothelial carcinoma, adenocarcinoma, and undifferentiated carcinoma.1,2 The prognosis associated with prostatic neoplasia in dogs is considered poor to grave because of the presence of extensive local disease at diagnosis.2 Additionally, high metastatic rates (eg, 61/76 [80%]3) have been reported.
Traditional treatment options for prostatic tumors in dogs generally fall into 3 major categories: surgery, radiotherapy, and chemotherapy. Several surgical options have been proposed for the treatment of prostatic neoplasia, and results have shown mixed success.2,4,5,6,7,8,9 In humans with localized prostatic disease, radiotherapy is a treatment option that has the potential to cure.10 Data on dogs with prostate neoplasia are limited, resulting in little information on which to base treatment; however, radiotherapy has been effective at palliating clinical signs associated with local disease of the prostate and skeletal metastases in dogs.4 Additionally, in a previous study,11 the use of an intensity-modulated and image-guided radiotherapy protocol had a 60% subjective response rate reported by owners of treated dogs with genitourinary carcinomas. Furthermore, chemotherapy with or without NSAIDs is often incorporated into the treatment regimen of prostate neoplasia for local and metastatic disease12; however, data about the impact of systemic chemotherapy on local prostatic disease are limited.
Transarterial embolization is a well-established treatment modality in humans, and the use of prostatic artery embolization (PAE) in the treatment of benign prostatic hyperplasia (BPH) in men has recently become a regularly pursued option.13,14,15,16 Embolization of the prostatic artery has been evaluated in a model for BPH in dogs.17 In this model, hormonal administration stimulated dogs to develop BPH, and after 3 months of hormonal treatment, 7 dogs underwent PAE. In 4 of those dogs, marked shrinkage of the prostate occurred after PAE. In the remaining 3 dogs, the prostate had increased in size; however, necropsy revealed that the increased size was secondary to the formation of large prostatic cysts.17
Poor response rates to currently available treatments for dogs with prostate neoplasia dictate the need for improved therapeutic options. The aims of the study reported here were to describe the procedure of PAE in dogs with naturally occurring prostatic carcinoma and to evaluate the short-term (30 days) outcome with respect to clinical signs and prostatic tumor volume in treated dogs. We hypothesized that PAE would be technically feasible to perform in a cohort of dogs with naturally occurring cancer of the prostate and that dogs undergoing PAE would demonstrate improvement in clinical signs and decreased prostate volume, including decreased prostatic tumor volume.
Materials and Methods
Animals
Client-owned dogs with naturally occurring prostate carcinoma presented to the University of California-Davis Veterinary Medical Teaching Hospital between May 2014 and July 2017 were eligible for prospective enrollment in the study. The study protocol was explained to the owners, and written informed consent was obtained prior to enrollment. The protocol was approved by the hospital Clinical Trials Review Board. A cytologic or histopathologic diagnosis of carcinoma in the prostate was required for enrollment. Dogs were excluded if they had complete urethral obstruction or urethral catheter dependence. Before PAE, each dog underwent thoracic radiography and abdominal ultrasonography, with specific focus on the urinary tract to determine whether ureteral obstruction was present.
PAE procedure
All dogs underwent general anesthesia for PAE, and the anesthetic protocols were individualized for patient needs as determined by the clinical anesthesiology service. Each dog received perioperative antimicrobials and was positioned in dorsal recumbency and aseptically prepared for PAE after being transported to our fluoroscopy (OEC 9900 Elite; GE Healthcare) suite. All PAE procedures were performed by the same author (WTNC), and the over-arching goal was to embolize the prostatic blood supply bilaterally when possible. Briefly, a 1- to 2-cm skin incision was made over the left carotid artery, and the subcutaneous tissues were bluntly and sharply dissected until the left carotid artery was visualized. The carotid artery was isolated with blunt dissection, and 2 strands of 3-0 polydioxanone (PDS; Ethicon Inc) were passed around the artery. An 18-gauge over-the-needle catheter (Becton, Dickinson and Co) was introduced into the carotid artery, and the needle was removed. A 0.035-inch × 180-cm-long hydrophilic guidewire (Infiniti Medical LLC) was introduced into the over-the-needle catheter, and the over-the-needle catheter was removed. A 5F vascular access sheath with a dilator (Infiniti Medical LLC) was introduced over the guidewire and into the carotid artery. The vascular access sheath was then sutured to the skin, and the dilator was removed. A 4F angled catheter (Berenstein; Infiniti Medical LLC) was introduced over the guidewire and advanced to the aortic trifurcation. The contrast medium iopamidol (Isovue-370) diluted 50% by volume with sterile saline (0.9% NaCl) solution was injected through the 4F angled catheter so that the vascular supply to the prostate and tumor could be identified fluoroscopically (Figure 1). The guidewire and angled catheter were advanced from the aorta to the internal iliac artery. The caudal aspect of the patient was then positioned into lateral recumbency, and an angiographic examination was performed to identify the blood supply to the prostate and the urinary bladder. A 0.014-inch microwire (RUNTHROUGH NS Microwire; Terumo Medical Corp) was introduced into a 1.8F to 2.8F microcatheter (SuperCross; Vascular Solutions Inc; ProGreat; Boston Scientific), and this combination was then introduced into the 4F angled catheter. The microwiremicrocatheter combination was advanced into the prostatic artery, and the microwire was removed. An injection of 100% contrast medium was performed for arteriography to identify the specific prostatic blood supply. The microwire-microcatheter combination was then advanced distal to the branch of the caudal vesical artery to avoid nontarget embolization of the blood supply to the urinary bladder. The microwire was subsequently removed.
Representative digital subtraction fluoroscopic angiographic images of 1 of the 20 client-owned dogs undergoing prostatic artery embolization (PAE) for treatment of prostatic carcinoma between May 2014 and July 2017. A—Evident are the distal portion of the aorta (a) and the internal iliac arteries (II). The dog is in dorsal recumbency and its head toward the top of the image. B through D—The dog's hind limbs, pelvis, and caudal portion of the abdomen have been rotated into left lateral recumbency, and its head is toward the right of the images. B—Arteriography is being performed with contrast medium injected through a micro-catheter that has been advanced into the internal pudendal (IP) artery. The prostatic artery (P) is seen branching off of the internal pudendal artery with blood supply to the uri-nary bladder (UB), prostate, and prostatic tumor (with contrast medium enhancement and a dashed outline). During PAE, the caudal vesical artery (CdV) should not be embolized because it provides arterial blood supply to the urinary bladder. C—The microcatheter has been advanced into the prostatic artery, and injected contrast medium shows the blood flow to only the prostate (caudal margin denoted by arrows). D—Contrast medium injected at the level of the internal pudendal artery (IP) after PAE shows blood flow through the caudal vesical artery (CdV) to the urinary bladder (UB) but no blood flow through the prostatic artery to the prostate.
Citation: Journal of the American Veterinary Medical Association 259, 10; 10.2460/javma.20.06.0324
Representative digital subtraction fluoroscopic angiographic images of 1 of the 20 client-owned dogs undergoing prostatic artery embolization (PAE) for treatment of prostatic carcinoma between May 2014 and July 2017. A—Evident are the distal portion of the aorta (a) and the internal iliac arteries (II). The dog is in dorsal recumbency and its head toward the top of the image. B through D—The dog's hind limbs, pelvis, and caudal portion of the abdomen have been rotated into left lateral recumbency, and its head is toward the right of the images. B—Arteriography is being performed with contrast medium injected through a micro-catheter that has been advanced into the internal pudendal (IP) artery. The prostatic artery (P) is seen branching off of the internal pudendal artery with blood supply to the uri-nary bladder (UB), prostate, and prostatic tumor (with contrast medium enhancement and a dashed outline). During PAE, the caudal vesical artery (CdV) should not be embolized because it provides arterial blood supply to the urinary bladder. C—The microcatheter has been advanced into the prostatic artery, and injected contrast medium shows the blood flow to only the prostate (caudal margin denoted by arrows). D—Contrast medium injected at the level of the internal pudendal artery (IP) after PAE shows blood flow through the caudal vesical artery (CdV) to the urinary bladder (UB) but no blood flow through the prostatic artery to the prostate.
Citation: Journal of the American Veterinary Medical Association 259, 10; 10.2460/javma.20.06.0324
Representative digital subtraction fluoroscopic angiographic images of 1 of the 20 client-owned dogs undergoing prostatic artery embolization (PAE) for treatment of prostatic carcinoma between May 2014 and July 2017. A—Evident are the distal portion of the aorta (a) and the internal iliac arteries (II). The dog is in dorsal recumbency and its head toward the top of the image. B through D—The dog's hind limbs, pelvis, and caudal portion of the abdomen have been rotated into left lateral recumbency, and its head is toward the right of the images. B—Arteriography is being performed with contrast medium injected through a micro-catheter that has been advanced into the internal pudendal (IP) artery. The prostatic artery (P) is seen branching off of the internal pudendal artery with blood supply to the uri-nary bladder (UB), prostate, and prostatic tumor (with contrast medium enhancement and a dashed outline). During PAE, the caudal vesical artery (CdV) should not be embolized because it provides arterial blood supply to the urinary bladder. C—The microcatheter has been advanced into the prostatic artery, and injected contrast medium shows the blood flow to only the prostate (caudal margin denoted by arrows). D—Contrast medium injected at the level of the internal pudendal artery (IP) after PAE shows blood flow through the caudal vesical artery (CdV) to the urinary bladder (UB) but no blood flow through the prostatic artery to the prostate.
Citation: Journal of the American Veterinary Medical Association 259, 10; 10.2460/javma.20.06.0324
An embolic slurry was prepared just prior to injection. Embolic beads (Bead Block; Boston Scientific Corp; 100 to 300 μm in size) were prepackaged in a syringe and suspended in saline solution. The syringe was held upright, allowing the beads to settle to the plunger end of the syringe, and all but approximately 1 mL of saline that contained the embolic beads was evacuated. The syringe of embolic beads and remaining saline solution was then attached to a 3-way stopcock to which a syringe containing 6 mL of contrast medium was also attached. The contents of the syringes were mixed together several times to form a slurry of embolic beads, saline solution, and contrast medium. Under fluoroscopy, the slurry was then administered by hand with the use of 1-mL syringes attached to the microcatheter to inject the slurry into the prostatic arterial supply until blood flow stasis was achieved, indicated by fluoroscopic cessation of contrast medium movement (Figure 1). After administration of the slurry, the microcatheter was removed and then diluted contrast medium (50% by volume with sterile saline) was administered through the 4F angled catheter so that angiography could be performed to assess for embolization of the prostatic artery and patency of nontarget vessels. Once no blood flow to the prostate was confirmed, all PAE catheters and the vascular access sheath were removed and the left carotid artery was ligated by securing the 3-0 polydioxanone sutures that were previously placed. The skin incision was closed in a routine manner.
For each dog, the procedural variables recorded included procedure duration (time from incision until closure of incision), total anesthesia duration (time from induction to extubation), accessibility of the right and left prostatic artery (yes or no), nontarget vessel embolization (yes or no), amount (milliliters) of embolic agent administered, and intra- and postprocedural complications grade (1 = treatment not needed, 2 = treatment needed, 3 = life-threatening complication or permanent disability, or 4 = death) on the basis of classification of intraoperative complications criteria.18,19 Technical success was considered embolization of all prostatic arterial supply detected with angiography.
Assessment of response by clinical signs
All owners were asked to complete an ad hoc questionnaire within 2 days before and again approximately 30 days after PAE to assess changes in clinical signs. Through the use of the questionnaires, owners were asked specific questions about their dog's clinical signs and assigned numerical scores to the severity of those clinical signs. Additionally, owners were asked to compare the water intake and frequency of urination by their dog with those of dogs they considered “normal” or without prostatic disease. Chemotherapy was not initiated during the study period for each dog; however, continued treatment with NSAIDs was allowed for dogs previously receiving such drugs.
Assessment of response by diagnostic imaging
All dogs underwent abdominal ultrasonographic (iE 33 ultrasound machine; Philips Healthcare Solutions) and CT (Lightspeed 16; GE Medical Systems) angiographic assessments before and after PAE. All ultrasonographic assessments of the prostates included color-flow and power Doppler ultrasonography and were performed and assessed 1 day before and 1 day after PAE by the same board-certified veterinary radiologist (EGJ). For each dog, results of subjective assessments of prostatic blood supply before versus after PAE were compared.
Each dog underwent CT angiography of the prostate 1 day before and approximately 30 days after PAE. Computed tomography following a clinical protocol of overlapping (0.625-mm continguous helical images) was performed before and after systemic IV administration of iodinated contrast medium (iopamadol, 2.38 mL/kg) with a pressure injector set to deliver 5 mL/s. The CT images were reconstructed in soft tissue (window width, 350 HU; window level, 40 HU) and bone (window width, 1,500 HU; window level, 300 HU) algorithms with a 2-mm slice thickness, and the prostate volume was determined by use of a commercially available imaging analysis software package (OsiriX version 4.1.2; Pixmeo).
Statistical analysis
Descriptive statistics were calculated, and the distribution of continuous variables was assessed with histograms and tests of skewness and kurtosis. A Wilcoxon matched-pairs signed rank test was used to compare results for prostatic volume before versus after PAE. The percentage and 95% CI for change in prostatic volume were calculated. The McNemar exact test for matched pairs was used to compare the results for clinical signs before versus after PAE. Population prevalence of clinical signs pre- and post-PAE was estimated by use of exact binomial 95% CI.
All tests were 2-sided, and values of P < 0.05 were considered statistically significant. Computer software (Stata Statistical Software release 14; StataCorp LLX) was used for analyses.
Results
Animals
Twenty dogs with carcinoma of the prostate met inclusion criteria and were enrolled in the study. No dogs met the exclusion criteria. The diagnosis of carcinoma was based on cytologic evaluation of fine-needle aspirate samples (n = 17) or samples collected from traumatic catheterization (3). All dogs had been castrated previously. Mean ± SD age and body weight were 9.6 ± 2.1 years and 20.1 ± 10.9 kg; 5 dogs weighed < 10 kg. Dogs included 3 Labrador Retrievers, 2 Dachshunds, and 1 each of Australian Shepherd, Basenji, Beagle, Bernese Mountain Dog, Boston Terrier, Cairn Terrier, Cavalier King Charles Spaniel, Chow Chow, French Bulldog, Jack Russell Terrier, Belgian Malinois, Scottish Terrier, Silky Terrier, West Highland White Terrier, and mixed breed.
Procedural outcome
The median duration for the PAE procedure (for bilateral treatment) was 99 minutes (range, 46 to 140 minutes), and the median duration of anesthesia was 180 minutes (range, 140 to 250 minutes). The median total volume of embolic slurry administered per dog was 1.9 mL (range, 0.6 to 7 mL). The body weights of the 4 dogs that received the greatest volume of embolic slurry (between 4.5 and 7 mL) were 9.2, 12.1, 14.4, and 22.2 kg. In the remaining 16 dogs, the largest volume of embolic slurry injected was 2.2 mL (range, 0.6 and 2.2 mL), and the mean body weight was 22.0 ± 11.6 kg. Despite the small size of the prostatic arteries, the flow of the embolic slurry was recognized with fluoroscopy in all dogs during injection, and catheter-induced occlusion was not appreciated. Additionally, blood flow through the caudal vesical artery to the urinary bladder was observed in all dogs during angiography immediately after PAE.
Four dogs had grade 1 intraprocedural complications. In 2 of these 4 dogs, presumed vascular spasm of one of the prostatic arteries occurred after catheterization with the microcatheter. This was assumed to have been vascular spasm because the prostatic arteries were initially visualized angiographically and then catheterized but did not show opacification on subsequent angiography. In both affected dogs, IV administration of lidocaine (1 mL through the micro-catheter) resulted in the opening of the prostatic arteries, which was confirmed with angiography, and then embolization of the prostatic blood supply was performed. A different dog had contrast medium extravasation from the prostatic artery during angiography to document vascular stasis after completion of the PAE. This dog was monitored for several minutes for any signs of complications; a subsequent angio-graphic study revealed cessation of contrast medium extravasation, and no further treatment was pursued. In the fourth dog with a grade 1 intraprocedural complication, only 1 prostatic artery was observed; therefore, unilateral PAE was performed. Vascular spasm was not assumed to have occurred in this dog because only the single prostatic artery was evident, even after terminal aortic injection at the beginning of the procedure. Catheterization of the internal pudendal artery in this dog further supported the uni-lateral lack of a prostatic arterial branch.
No dogs had high-grade intra- or post-PAE complications or postembolization syndrome. Overall, 39 of 39 prostatic arteries were successfully catheterized, allowing for PAE with a technical success rate of 100%.
After PAE, analgesics were administered for 2 to 4 days; however, antimicrobials were not administered unless indicated by results of bacterial culture of urine. No dogs required urethral catheterization after PAE. All dogs were observed to have urinated prior to hospital discharge, and all dogs were discharged the day following PAE.
Assessment of response by clinical signs
Clinical signs that were reported before PAE mostly pertained to the gastrointestinal tract (eg, tenesmus [n = 10], abnormal fecal shape [10], or hyporexia [3]) or urinary tract (eg, hematuria [7] or pollakiuria [7]; Table 1). Stranguria was reported for 10 dogs, with severity ranging from 2 to 8 (median, 5) on a scale of 1 to 10. Vomiting was reported for 3 dogs; however, this was thought to have been related to other preexisting gastrointestinal diseases in 1 of the 3 dogs. Additionally, 6 dogs had been lethargic. In contrast, 3 dogs had no abnormal clinical signs, with the prostate tumor found incidentally. In 1 dog, a prostatic mass was palpated during a routine rectal examination. In a second dog, a mineralized mass in the region of the prostate was noticed on abdominal radiography during the reevaluation of a previously placed gastrostomy tube. In the third dog, the prostate was identified as enlarged during splenectomy (splenic lipoma), and histologic examination of a fine-needle aspirate sample from the enlarged prostate revealed prostatic carcinoma.
Numbers and percentages (95% CIs) of 20 client-owned dogs with prostatic carcinoma for which owners had reported various abnormal clinical signs through completion of a questionnaire within 2 days before versus 30 days after dogs underwent PAE.
| Clinical sign | Before PAE | After PAE | P value | ||
|---|---|---|---|---|---|
| No. of dogs | Percentage (95% CI) | No. of dogs | Percentage (95% CI) | ||
| Abnormal fecal shape | 10 | 50 (27–73) | 4 | 20 (6–44) | 0.031 |
| Stranguria | 10 | 50 (27–73) | 1 | 5 (0–25) | 0.004 |
| Tenesmus | 9 | 45 (23–68) | 2 | 10 (1–32) | 0.016 |
| Hematuria | 7 | 35 (15–59) | 2 | 10 (1–32) | 0.125 |
| Pollakiuria | 7 | 35 (15–59) | 2 | 10 (1–32) | 0.125 |
| Nocturia | 6 | 30 (12–54) | 3 | 15 (3–38) | 0.375 |
| Lethargy | 6 | 30 (12–54) | 0 | 0 (0–17) | 0.031 |
| Abnormal fecal color | 3 | 15 (3–38) | 1 | 5 (0–25) | 0.500 |
| Vomiting | 3 | 15 (3–38) | 1 | 5 (0–25) | 0.500 |
| Hyporexia | 3 | 15 (3–38) | 0 | 0 (0–17) | 0.250 |
Approximately 30 days after PAE, tenesmus was still reported for 2 dogs that previously had tenesmus; however, the owners of both dogs reported improvement in the severity. The proportion of dogs with tenesmus was significantly (P = 0.016) lower after PAE (2/20 [10%]) versus before PAE (9/20 [45%]; Table 1). Additionally, the proportion of dogs with lethargy or abnormally shaped feces was significantly (P = 0.031) higher before PAE (6/20 [30%] and 10/20 [50%], respectively) versus after PAE (0/20 [0%] and 4/20 [20%], respectively), and all dogs had a clinically normal appetite after PAE. Furthermore, the proportion of dogs with stranguria before PAE (10/20 [50%]) versus after PAE (1/20 [5%]) significantly (P = 0.004) improved, and the 1 dog with stranguria after PAE had a decrease in severity score from 8 before PAE to 4 after PAE. Hematuria and pollakiuria also improved in all affected dogs, and only 2 of the 7 dogs with hematuria and pollakiuria before PAE still had these signs, but with less severity after PAE.
Before PAE, owners reported that their dog's water intake was less (n = 1 [5%]), more (2 [10%), or the same (17 [85%]) as that of other dogs. After PAE, all 20 dogs were reported to have relatively the same water intake as did other dogs; however, this change was not significant (P = 0.500). Another but not statistically significant (P = 0.063) change was in the frequency of urination. Owners reported that before PAE, the frequency that their dog urinated was less (n = 2 [10%]), more (5 [25%]), or the same (13 [65%]) as other dogs, whereas they reported the frequency of urination after PAE was more (1 [5%]) or the same (19 [95%]) as other dogs. No dogs developed new abnormal clinical signs after PAE that they did not have before PAE.
Assessment of response by diagnostic imaging
Ultrasonographic assessments revealed robust blood flow to the prostrate before PAE and subjectively decreased blood flow to the prostate 1 day after PAE in all 20 dogs (Figure 2). Although prostatic blood flow appeared dramatically decreased for most dogs after PAE, all dogs had some prostatic blood flow detected with ultrasonography after PAE. Additionally, a subjective increase in echogenicity of the periprostatic fat was noted in all dogs after PAE.
Representative transverse plane color-flow Doppler ultrasonographic images of the prostate and a prostatic carcinoma in a dog from the group of dogs described in Figure 1 at 1 day before (A) and 1 day after (B) PAE, showing decreased blood flow after PAE.
Citation: Journal of the American Veterinary Medical Association 259, 10; 10.2460/javma.20.06.0324
Representative transverse plane color-flow Doppler ultrasonographic images of the prostate and a prostatic carcinoma in a dog from the group of dogs described in Figure 1 at 1 day before (A) and 1 day after (B) PAE, showing decreased blood flow after PAE.
Citation: Journal of the American Veterinary Medical Association 259, 10; 10.2460/javma.20.06.0324
Representative transverse plane color-flow Doppler ultrasonographic images of the prostate and a prostatic carcinoma in a dog from the group of dogs described in Figure 1 at 1 day before (A) and 1 day after (B) PAE, showing decreased blood flow after PAE.
Citation: Journal of the American Veterinary Medical Association 259, 10; 10.2460/javma.20.06.0324
Also, on ultrasonography, tumor extending from the prostate into the bladder was evident in 4 of the 20 dogs. Urethral invasion, mineralization, or thickening was evident in 6 of the 20 dogs. No obvious tumor extension into the urethra or bladder was noted in 10 dogs; however, specific imaging analysis (eg, urethral distension during imaging or catheter placement to identify urethral lumen) to assess extension was not performed.
On the basis of CT findings, the median prostatic volume was significantly (P < 0.001) smaller after PAE (14.8 cm3; range, 0.4 to 48.1 cm3; inter-quartile [25th to 75th percentile] range, 6.7 to 19.5 cm3), compared with before PAE (21.7 cm3; range, 2.9 to 77.7 cm3; interquartile range, 11.0 to 35.1 cm3), and all dogs had a smaller prostate on CT performed a median of 30 days (range, 30 to 33 days) after PAE (Figure 3). Median percentage of prostatic volume loss was 39.4% (95% CI, 20.3% to 59.3%).
Transverse plane postcontrast CT images of prostatic carcinomas in 2 dogs (dog 1, A and B; dog 2, C and D) 1 day before (A and C) and 30 days after (B and D) treatment with PAE. For dog 1, the prostate (P) is large, highly contrast enhancing, and compressed to and bilaterally alongside the colon (Col) before PAE, whereas there is a lack of prostatic tissue and a noncompressed colon (at the level of the sacroiliac joint) 30 days after PAE. Similarly, for dog 2, the prostate is large and contrast enhancing before PAE, whereas it is substantially smaller and the urinary bladder is evident (at the level of midileum) 30 days after PAE. In each image, the dog's right side is toward the left. The images are displayed in a soft tissue window (window width, 350 HU; window level, 40 HU) with a 2-mm slice thickness.
Citation: Journal of the American Veterinary Medical Association 259, 10; 10.2460/javma.20.06.0324
Transverse plane postcontrast CT images of prostatic carcinomas in 2 dogs (dog 1, A and B; dog 2, C and D) 1 day before (A and C) and 30 days after (B and D) treatment with PAE. For dog 1, the prostate (P) is large, highly contrast enhancing, and compressed to and bilaterally alongside the colon (Col) before PAE, whereas there is a lack of prostatic tissue and a noncompressed colon (at the level of the sacroiliac joint) 30 days after PAE. Similarly, for dog 2, the prostate is large and contrast enhancing before PAE, whereas it is substantially smaller and the urinary bladder is evident (at the level of midileum) 30 days after PAE. In each image, the dog's right side is toward the left. The images are displayed in a soft tissue window (window width, 350 HU; window level, 40 HU) with a 2-mm slice thickness.
Citation: Journal of the American Veterinary Medical Association 259, 10; 10.2460/javma.20.06.0324
Transverse plane postcontrast CT images of prostatic carcinomas in 2 dogs (dog 1, A and B; dog 2, C and D) 1 day before (A and C) and 30 days after (B and D) treatment with PAE. For dog 1, the prostate (P) is large, highly contrast enhancing, and compressed to and bilaterally alongside the colon (Col) before PAE, whereas there is a lack of prostatic tissue and a noncompressed colon (at the level of the sacroiliac joint) 30 days after PAE. Similarly, for dog 2, the prostate is large and contrast enhancing before PAE, whereas it is substantially smaller and the urinary bladder is evident (at the level of midileum) 30 days after PAE. In each image, the dog's right side is toward the left. The images are displayed in a soft tissue window (window width, 350 HU; window level, 40 HU) with a 2-mm slice thickness.
Citation: Journal of the American Veterinary Medical Association 259, 10; 10.2460/javma.20.06.0324
Discussion
Prostatic artery embolization was successfully performed in all 20 dogs of the present study, and no serious procedural complications were encountered. Most of the pre-PAE clinical signs exhibited by these dogs were either improved or resolved after PAE, and no new signs attributed to treatment developed in any dog. Additionally, results of the diagnostic imaging assessments of response after PAE were highly promising because dogs had decreased prostatic volume and blood flow. These findings supported our hypothesis that PAE would be technically feasible to perform in a cohort of dogs with naturally occurring cancer of the prostate and that dogs undergoing PAE would demonstrate improvement in clinical signs and decreased prostatic volume, including decreased prostate tumor volume.
Embolization is a major component of oncological treatment in human patients and has been established as a mainstay treatment for liver neoplasia (primary and metastatic) because unique characteristics of hepatic blood supply allow for the specific targeting of hepatic tumoral vasculature and the sparing of normal hepatic vasculature.20,21 Additionally, embolization of tumors in a myriad of other organs has been described22,23,24,25 and is regularly part of the armamentarium of options offered to human patients with tumors. The major concept of PAE is that obstruction of the vascular supply to the prostate results in prostatic tissue and tumor ischemia, infarction, and cell apoptosis.13
Although PAE has been described most regularly for the management of BPH in men, recent work has evaluated this treatment for prostatic neoplasia.26,27,28 In a study28 that evaluated PAE for prostate neoplasia in men, chemotherapy was also added during the embolization. In the present study, chemotherapy was not included in the treatment of the dogs because 1 dog undergoing chemoembolization previously at our facility had substantial peri-urethral and ureteral inflammation and partial urinary bladder necrosis. In human patients, success has been reported for technical (eg, ability to perform bilateral embolization) and biochemical (eg, evaluating prostate-specific antigen concentration) aspects of PAE.28 The results were promising in that technical and midterm (12 to 18 months post-PAE) biochemical success were 80% (16/20) and 62.5% (10/16), respectively, and that patients with mid-term responses had a mean decrease in prostate volume of 29.4%.28
The assessment of prostatic volume has been performed in studies28,29,30 evaluating PAE of benign and malignant disease in men; however, data on PAE in dogs are limited. All dogs in the present study had statistically and clinically significant decreased prostate volume after PAE. Given that the recheck CT assessments were performed just 1 month after PAE, continued prostate volume decrease afterward could have occurred, further improving outcome.31 The assessment of tumor response to embolization is challenging, and tumor cell death may not always correspond to tumor size32; much still needs to be learned. Although Response Evaluation Criteria in Solid Tumors guidelines31,32 have been applied regularly to determine tumor response after varying treatments, these criteria may not be reliable when applied to patients undergoing embolization.32,33,34 Further investigation into other means of tumor response assessment, such as positron emission tomography, Doppler ultra-sonography, contrast-enhanced ultrasonography, and functional MRI, is well underway in human medicine and can also be considered in veterinary medicine.
Results of decreased prostatic volumes and blood flow after PAE indicated positive responses to PAE in dogs of the present study. Additionally, the post-PAE ultrasonographic finding of relatively increased echogenicity of the fat surrounding the prostate, compared with findings before PAE, has been associated with inflammation and gives further credence to an embolization response.35 Such inflammatory response is likely attributable to prostatic cellular hypoxia and subsequent cell death.
The goals of PAE in treating prostatic neoplasia would be to achieve local tumor control and to improve abnormal clinical signs secondary to prostatic enlargement or tumor invasion. Because prostatic carcinoma is highly metastatic, with common distant sites including lymph nodes, lungs, and bones and other reported sites including liver, colon, kidney, heart, adrenal gland, brain, and spleen,3 affected dogs would likely benefit from treatment with chemotherapy after PAE. Long-term evaluation is needed to assess the impact of PAE combined with chemotherapy on the overall survival time and other outcome measures in dogs with prostatic neoplasia.
The clinical signs associated with prostatic neoplasia are most commonly referable to the urinary tract and to alterations in defecation. In 1 study,3 62% (47/76) of dogs with prostatic carcinoma had clinical signs related to the urinary tract, including hematuria, stranguria, and incontinence. Between 22% (24/111) to 30% (23/76) of affected dogs have been reported to have tenesmus. Signs associated with systemic disease, such as anorexia, lethargy, and weight loss, are variably reported between 16% (18/111) to 42% (32/76).3,36 Similarly, the dogs of the present study most commonly had urinary or gastrointestinal signs, with stranguria or abnormal fecal shape each encountered in 50% of the dogs. Our results were encouraging in that significant improvements in urination and defecation were reported, particularly when owners evaluated for straining characteristics. Additionally, 6 dogs were lethargic before PAE, whereas none of the 20 dogs were lethargic at their 30-day evaluation after PAE.
None of the dogs in the present study were dependent on a urinary catheter when they underwent PAE. Historical treatment options for dogs with complete urethral blockage have included debulking procedures, cystostomy tube placement, urethral catheterization, decompressive cystocentesis, and urethral stent placement. We specifically excluded animals that had undergone these procedures because of reports29,30 that indicate worsening urinary retention in human patients. Nonetheless, future investigation into the use of PAE as a means of reversing catheter dependency37 or avoiding permanent urinary diversion or urethral stent placement should be performed because if successful, PAE could represent a major step forward in the management of affected patients.
There are several technical aspects of PAE that should be considered. An extensive understanding of the vascular supply of the prostate and lower uri-nary tract as well as the instrumentation that might be used for PAE is necessary. Nontarget embolization could include embolization of the blood supply to the urethra or bladder and has the potential to lead to urethral or bladder necrosis, and urine retention has been described in humans.14 Although nontarget embolization did not occur in the present study, it must be considered for all dogs undergoing PAE. Prostatic artery embolization is considered challenging to perform in human patients owing to the small diameter (0.5 to 2 mm) of the prostatic vessels, tortuosity and variable nature of the pelvic vasculature, and potential arteriosclerosis that is often encountered in older men.13,14,15,16 Similarly, PAE in dogs is challenging. Compared with other vascular procedures performed in companion animals, we believe PAE is more technically challenging. We used microcatheters (between 1.8F and 2.8F), and occlusion of vascular flow still occurred in some instances, requiring repositioning of the microcatheters. If a microcatheter becomes occlusive, preventing forward blood flow into the vessel containing the microcatheter, injection of embolic beads can still commence in most cases through slowly injecting and causing blood and embolic flow to continue. However, the presumed lack of underlying vascular disease in the dogs of the present study may have been an important factor in our high technical success rate. It is also important to consider that access to the carotid artery could lead to bleeding at the access site or generation of a blood clot that could migrate cranially to the head; care should be taken to prevent this by careful manipulation of the carotid artery and ligation around the access site.
Dog size did not appear to have been associated with the volume of embolic slurry needed for prostatic vascular stasis. Three of 4 dogs that received the largest volumes of embolic slurry (between 4.5 and 7 mL) had body weights between 9.2 and 14.4 kg, which were well below the overall mean body weight for the 20 dogs (20.1 kg), whereas dogs that received between 1 and 2.2 mL of embolic slurry had a mean body weight of 22 kg. Similar to the embolic beads use in the present study, those in the size range of 100- to 300-mm diameter are often used in men undergoing PAE.16,27,30 The ideal embolic particle size for the prostate in men and dogs remains to be determined. The advantage to the use of smaller beads is that, presumably, greater prostatic ischemia will occur, followed by greater decrease in prostate volume.
Access to the arterial system in dogs is most commonly achieved through either the carotid or femoral arteries. Common carotid artery access for the prostatic arterial blood supply for intra-arterial chemotherapy in dogs has been described previously.38 Common carotid artery access is considered safer in dogs than in humans owing to differences in cerebral blood flow and substantial collateral blood supply in the dog whereby occlusion of the carotid artery is tolerated in dogs.39,40,41 In humans, the prostatic arteries are accessed from the femoral arteries, potentially further increasing the challenge of the procedure.
A limitation of the present study was the small number of dogs included; however, each dog served as its own control for changes in prostate size and blood flow and clinical sign progression, allowing a direct measurement of response. Another limitation was that none of the dogs underwent biopsy sample collection and evaluation to differentiate between urothelial cell or prostatic glandular origin, which could respond differently to PAE. As further investigation into the impact of PAE on long-term survival time is conducted, such histologic information will become even more critical. Additionally, the impact of tumor extension into the urethra or bladder is not fully understood relative to long-term outcome in dogs undergoing PAE. Furthermore, the data reported here only reflect the short-term (approx 30 days after PAE) outcome. The impact that PAE may have on long-term improvement in clinical signs or survival time in dogs is unknown. Survival times of dogs with prostate tumors are variable on the basis of the treatments received, and comparisons with studies performed previously are challenging; prospective trials are needed to allow for a more direct comparison.
Our results indicated that the short-term response of prostatic neoplasia to PAE in dogs was promising. All dogs had decreased prostate volume (on the basis of results from CT performed before and 30 days after PAE) and improved clinical signs (on the basis of results from owner questionnaires completed before and 30 days after PAE). Although technically challenging, PAE was successfully performed for all 20 dogs and complications were uncommon. Further investigation into technical aspects of PAE, use of PAE in conjunction with other treatments (eg, chemotherapy), methods for response assessments, and long-term outcome assessments are needed.
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