Tumors of the Urinary Tract

Question 1

Incidence of canine urinary bladder tumors?

Answer 1

2%

Question 2

List 7 risk factors associated with canine bladder tumors?

Answer 2

exposure to flea control (old versions), lawn chemicals and cytoxan, obesity, female gender, neuter status, and a very strong breed predisposition on (OR vs mixed breed: Scotties 21x, Eskimo 6.6x, Shelties 6x, Westies 5.8x).

Question 3

What can lower the risk for bladder tumors?

Answer 3

Eating vegetables (>3x/week).

Question 4

Most common bladder tumor?

Other less common bladder tumors?

Answer 4

invasive urothelial carcinoma (iUC) or iTCC is the most common canine UB cancer

less frequent tumors - SCC, adenocarcinoma, undifferentiated carcinoma, rhabdomyosarcoma, LSA, HSA, fibroma and sarcomas.

Question 5

What is the proposed tumor grade for TCC?

Answer 5

High or 3=70%, intermediate or 2=29%, and low or 1=1% (n=232 iUCs, Knapp, ILAR J, 2014)

Question 6

What % of tumors extend to urethra and prostate?

Answer 6

56%, 29%

Question 7

What % have regional LN and distant mets at time of diagnosis?

Answer 7

16%, 14%

Question 8

What % have mets to lungs?

Answer 8

50%

Question 9

Other locations of metastasis for TCC?

Answer 9

liver, adrenals, spleen, heart, GI tract, brain and bone (9-14%), +/- skin (seeding or extension).

Question 10

Why do TCC patients have elevated BUN?

Answer 10

Abnormal urea transporters in the tumor

Question 11

BRAFv5952 mutation is present in the urine of ___% of canine iUC ?

Answer 11

>80% (19/23 iUC vs 0/37 normal UB or cystitis)

Question 12

List 5 other DDx to consider for common presenting clinical signs for iUC?

Answer 12

chronic bacterial, granulomatous or polypoid cystitis, urethritis, calculi or other neoplasia

Question 13

What are 2 IHC markers for iUC?

Answer 13

Uroplakin II +/-GATA-3 can be used to define urothelial origin.

Question 14

What % of bladder can be safely resected?

Answer 14

50%

Question 15

Important studies:

n Marvel, et al VCO 2017: n=37 dogs - partial cystectomy + NSAID +/- chemo, DFI=235 (8 mo) and MST=348 days (12 mo). Subset of n=22 dogs - surgery + piroxicam SID +/- chemo, MST=722 days (24 mo)

Knapp, et al ILAR J2014: n=9 dogs 4 surgery (3=complete margins) + deracoxib SID, MST=749 days.

Upton, et at JAVMA 2006: Transurethral CO2 laser ablation + NSAID + chemo, outcome not better than medical therapy alone and risks include urethral perforation and stenosis.

Question 16

What is the MST with stent placement?

Answer 16

Variable. MST=20-78 days (2-536) from urethral stent placement in one study of iUC and prostatic carcinoma, and MST=57 days in one study with ureteral stents.

Follow up with adjuvant therapy (NSAID, chemo, RT) is strongly recommended and has been noted to improve MST=251 (8-536) (Blackburn, JAVMA 2013).

Question 17

What is the main complication associated with stent placement and is seen in what % of dogs ?

What are the other complications?

Answer 17

Mainly incontinence in 25-39% of dogs,

Stent migration, collapse or blockage from tumor growth; also lower urinary signs (hematuria) may not resolve

Question 18

RT and iUC

lower rates of adverse events, with acute side effects being mild and transient (colitis, stranguria, erythema) and late side effects being less common. (urinary or rectal stricture, <10%). A PFI— 317 and MST=654 days was reported in one study with IMRT, and an ORR=61% and SD=38% in another study with 2.7Gy x 10 daily treatments

Question 19

What is the RR for VBL + piroxicam and MST?

VBL alone?

Answer 19

VBL + Piroxicam (58%, 199 days) > VBL alone (22%, 143 days), but MST was higher for VBL alone Piroxicam alone (531 days) > VBL + Piroxicam (299 days). (Knapp et al, Bladder Cancer, 2016).

Question 20

ORR for mitoxantrone + piroxicam? MST?

Answer 20

Mitoxantrone + Piroxicam: ORR=35%, PFI=194 and MST=291 days (Fulkerson et al, Vet J, 2015).

Question 21

ORR for carboplatin + piroxicam? MST?

Answer 21

Carboplatin + Piroxicam: ORR=38%, MST=161 days. Tends to be thought as more effective but less tolerated than mitoxantrone combination (Fulkerson et al, Vet .I, 2015).

Question 22

Low dose metronomic chemotherapy for iUC and MST?

Answer 22

Leukeran, n=31 heavy treated dogs, resulted in 3% PR and 67% SD, PFI-119 and MST=221 days (Schremp et al, JAVMA, 2013). Good quality of life, but risk of chronic myelosuppression.

Question 23

ORR for single agent COX inhibitor?

Answer 23

ORR=15- 20% (1%PRs) and SD=55% of dogs with iUC. Knapp (ILAR J 2014): n=94 iUC dogs on piroxicam, CR=3%, PR=18%, SD=59%, PFI=120 and MST=244 days, toxicity (grade 1 or 2 GI)=31% PPIs can increase GI toxicity.

Question 24

List 4 reasons female dogs (especially with urethral disease) are more predisposed to UTIs with iUC?

Answer 24

1) urine retention, 2) acquired anatomical defects due to tumor, 3) damaged urothelium, and 4) +/- compromised immunity.

Question 25

Most common uropathogens in iUC are?

Answer 25

E. coli and Staph spp.

Question 26

List some negative prognostic factors for canine iUC?

Answer 26

Advanced TNM stage at diagnosis, and factors associated with it, such as younger age (Trisk of LN mets), prostate involvement (Trisk of distant mets), higher T stage (Trisk ofLN and distant mets).

Question 27

List the most common feline UB tumor?

Other 2 tumors?

Answer 27

· Incidence: rare, most common UB tumor is iUC, followed by sarcomas and LSA.

Question 28

Where are most tumors located in feline bladder?

What do these tumors express?

Answer 28

Away from the trigone

Express COX- l and -2

Question 29

Bommer et al study, n=11 cats treated with meloxicam, MST=311 days, MST of COX-2+ cats was 123 days vs 375 days for COX-2- cats; Wilson et al study, n=20 cats, MST=261 days; Griffin et al study, n=118 cats, MST=155 days; 46 days for untreated cats, 176 days for cats treated medically vs 294 days for cats treated with partial cystectomy +/- medically.

Question 30

6 canine renal tumors?

2 conditions commonly seen in GSD? What causes this disease?

Answer 30

Renal cell carcinoma (RCC), adenocarcinoma, iUC, LSA, sarcomas (e.g., HSA) and nephroblastomas

Renal cystoadenocarcinoma and nodular dermatofibrosis, due to a dominantly inherited mutation on the TSG FLCN that codes for the protein folliculin

Question 31

Behaivour for canine renal tumors

Renal epithelial tumors and sarcomas are mostly seen in ____ dogs?

Nephroblastome is seen in ____ to ______ dogs?

Gender predisposition?

Answer 31

older dogs

younger and middle-aged dogs

males has been reported

Question 32

Metastatic rate at diagnosis for canine renal tumors?

Answer 32

Metastasis is noted at diagnosis (radiographs) in 16-34% of dogs

at necropsy in 88% of sarcomas, 75% of neprhoblastomas and 69% of carcinomas

Question 33

3 common clinical sign for canine renal tumors?

Answer 33

hematuria, pain at the area of the kidneys and palpable abdominal mass

Question 34

Common labwork abnomalities with canine renal tumors?

Answer 34

anemia or paraneoplastic polycythemia (secondary to erythropoietin production by tumor cells), paraneoplastic leukocytosis/neutrophilia (GM-CSF production by tumor cells), azotemia, TALP, iCa

Question 35

List negative prognostic factors for canine renal tumors?

Answer 35

mitotic index (MST for <10=1184 days or 40 mo, 10-30=452 or 15 mo and >30=187 or 6 mo),

COX-2 expression

Fuhrman nuclear grade in RCC (histological grade based on nuclear and nucleoli features, grade 1=MST not reached, 2=1065 days or 3 yr, 3=379 or 1 yr, 4=87 or 3 mo),

Specific histologic subtypes

Question 36

MST for canine RCC?

renal sarcoma?

Nephroblastoma?

Answer 36

MST=16 months for RCC (n=49)

MST=9 months for renal sarcomas (n=28)

MST=6 months for nephroblastoma (n=5)

Question 37

renal cystoadenocarcinoma and nodular dermatofibrosis in GSD is similar to Birt-Hogg-Dube syndrome in humans. Fuhrman nuclear grade is prognostic for both species

Question 38

List of feline renal tumors?

Answer 38

LSA, RCC (tubular, tubulepapillary -most common- and sarcomatoid), adenoma, adenocarcinoma, iUC, SCC, leiomyosarcoma, HSA, nephroblastoma.

Question 39

Most common clinical sign in cats with renal tumors?

Answer 39

most commonly weight loss, 1 report of HO

Question 40

Most common abnormality in feline renal tumor?

Answer 40

Polycythemia (which in two cats resolved with nephrectomy)

Question 41

Prognosis for cats with renal tumors?

Answer 41

Limited information on OS is unknown, but most reports note short ST.