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Withrow > Chapter 29 - Tumors of the Urinary System > Flashcards

Chapter 29 - Tumors of the Urinary System Flashcards

1
Q

Canine urinary bladder accounts for ___ % of all reported cancer in dogs.

A

2%

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2
Q

What is the most common bladder cancer in dogs and what is the most common histologic form? What is the most common location?

A

TCC
Intermediate to high grade papillary infiltrative
Trigone

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3
Q

What % of bladder TCC’s involve the urethra and prostate?

A

60% urethra
30% prostate

78% are T2 - invade the bladder wall
20% are T3 - invade nearby organs like prostate, uterus

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4
Q

What % of dogs with TCC have regional and distant metastasis at diagnosis? Overall metastatic rate at death? What % has regional and distant mets?

A

At diagnosis:
16% LN
14% distant

At death:
70% overall
30% LN
60% distant (50% lungs, 11% bone)

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5
Q

What are risk factors for the development of TCC in dogs (7)? What has been found to help reduce the risk?

A 
Older generation flea/tick control products
Lawn chemicals (ex. 2,4-D)
Obesity in females
Cyclophosphamide exposure
Female sex
Neutered status
Breeds

Scottish Terriers that ate vegetables at least 3 times per week had reduced risk (OR 0.3). Carrots were most commonly used. Green leafy veggies or yellow orange veggies. NOT cruciferus.

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6
Q

Neoplastic cells can be present in the urine in up to ___% of dogs with TCC.

A

30%

Often indistinguishable from reactive epithelial cells

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7
Q

Urine antigen tests for TCC are ___ but not ___.

A

Sensitive (88%), but not specific.

Lots of false positives from RBC and WBC

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8
Q

What marker is used to identify urinary transitional epithelium?

Where is it expressed?

How can this marker be helpful?

This marker is expressed in more than ___% of TCCs.

Is it a sensitive or specific marker?

A

Uroplakin III (UPIII)

A transmembrane protein expressed in superficial transitional epithelial cells of the urinary tract

Helpful to differentiate TCC origin from other types of carcinoma

> 90%

It is a specific marker for TCC epithelium/cells

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9
Q

What is the most common bone metastasis site in dogs with TCC? What % has more than 1 bone lesion?

A

Vertebrae
35%
Majority are lytic

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10
Q

What are 3reasons surgery for dogs with TCC is indicated?

A
  • To obtain tissue for dx
  • To attempt to remove the tumor if the lesion is away from the trigone
  • To maintain or restore urine flow

3%

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11
Q

Why is complete surgical excision usually not possible for dogs with TCC?

What % of dogs with TCC are able to have their tumors completely excised?

A

Trigone location, urethral involvement, metastasis

3%

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12
Q

What is the field effect and how does it apply to TCC?

A

Field effect of cancer - entire area, in this case lining, is thought to undergo malignant change in response to carcinogens present in the urine

In TCC, the cancer is sometimes thought to be multifocal

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13
Q

TCC control is usually achieved in ___ of dogs. How are MST?

A

75% stable, reduction in size

They can extend well over 1 year

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14
Q

Is there a benefit in combining chemotherapy drugs in dogs with TCC?

A

Has not been proven
Also, potential development of resistance to multiple drugs at the same time could limit the options for subsequent therapy

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15
Q

ORR, OBA, and MST of piroxicam when used as a single agent in dogs with urogenital carcinoma?

A

ORR - 18% (6% CR, 12% PR)
OBA - 74% (including SD in 53%)
MST 6m

*non COX selective

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16
Q

PR, SD, PFS, and MST of deracoxib when used as a single agent in dogs with urogenital carcinoma?

A

17% PR, 71% SD
PFS 4.5m
MST 10.7m
GI AE 19%

COX-2 selective*

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17
Q

PR, SD, PFS, and MST of firocoxib when used as a single agent in dogs with urogenital carcinoma?

A

20% PR, 33% SD
PFI 3.5m
MST 5m

COX-2 selective*

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18
Q

ORR, biological response, PFI, and MST for dogs with bladder TCC treated with mitoxantrone and piroxicam?

A

ORR 35%
Biological response 75%
PFI 3.5 to 6.4m
MST 10m

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19
Q

ORR, PFI, MST for dogs with bladder TCC when treated with carboplatin and piroxicam? What if treated with carbo alone?

A

ORR 38%
PFI 2.4m
MST 5.3m

If carbo alone, 0% - NADA!!!

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20
Q

What was the major finding in a randomized phase III clinical trial comparing first line carbo vs mito in combination with piroxicam for dogs with bladder TCC? What was a negative prognostic indicator identified?

A

No difference in ORR or PFI

Dogs with prostatic involvement had a shorter MST compared to urethral, trigonal, or apically located tumors

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21
Q

What is the ORR, biological response rate and MST of dogs with bladder TCC when treated with gemcitabine and piroxicam?

A

ORR 26%
Biological response 76%
MST 7.6m

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22
Q

What is the ORR, biological response rate, PFI, and MST of dogs with bladder TCC when treated with vinblastine every 2 weeks? What % required dose reductions? DLT?

A 
ORR 36%
Biological response 86%
PFI 4m
MST 5m
60% required dose reductions due to neutropenia
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23
Q

What are localized therapies studied in dogs with TCC of the bladder?

A

Intravesicual mitomycin C and photodynamic therapy

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24
Q

What is the most serious complication seen with intravesical therapy with mitomycin?

A

Severe myelosuppression and marked GI upset; systemic absorption was suspected
Also severe irritation for 1 to 2 days post therapy

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25
Q

PDT in dogs with TCC has been evaluated with what compound? What is the photoactive metabolite when this compound is used?

A

5-aminolevulinic acid (ALA); converted to active protoporphyrin IX only in the bladder mucosa

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26
Q

In a series of 20 cats with TCC, what % of cats had a concurrent UTI? Cats in this study had a combination of surgery, chemo and piroxicam. What was the MST?

A

75%261 daysClinical signs, treatments, and outcome in cats with transitional cell carcinoma of the urinary bladder: 20 cases. JAVMA, 2007.

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27
Q

What are the 2 most common urethral tumors?

A

TCC and SCC

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28
Q

How is the response to therapy in dogs with urethral epithelial tumors when compared to bladder TCC?

A

Similar

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29
Q

What is more common in the canine kidneys, primary or metastatic tumors?

A

Metastatic

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30
Q

Primary renal tumors in dogsmake up ___ % of all canine cancers.

A

<2%

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31
Q

Most common primary renal tumor in dogs?

A

Renal cell carcinoma (50-65%)

32
Q

Lymphoma and RCC usually occur ____.

A

Bilaterally

33
Q

How does hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis (RCND) manifests in GSD? This condition is similar to which condition in humans?

A

Consists of slow growing dermal fibrosis and fibromas, concomitant renal cystadenocarcinoma, and uterine tumors if females. Results from a dominantly inherited mutation in folliculin, a tumor suppressor gene.Has a dominant patternof expression.

Birt-Hogg-Dube syndrome

34
Q

Which renal tumor may occur at any age in dogs?

A

Nephroblastoma

35
Q

What % of dogs with renal tumors have proteinuria?

A

50%

36
Q

How can the HCT be affected in dogs with renal tumors?

A

Anemia, polycythemia

37
Q

What 5 IHC stains have been reported to be useful in dogs with renal cell carcinomas?

A

c-Kit, vimentin, uromodulin, cytokeratin, Pax8 (80%)

Vimentin and cytokeratin suggest distal convoluted tumor origin

38
Q

What is the tx of choice for unilateral renal tumors with no mets in dogs? MST?

A

Nephrectomy with removal of associated ureter
MST 16m

Unless its lymphoma, however, lymphoma is usually bilateral

39
Q

What percentage of dogs with renal tumors have metastasis at the time of diagnosis and at the time of death?

A

Diagnosis - up to 34%
Death - up to 88%

Carcinoma - 70%
Nephroblastoma 75%
Sarcoma 88%

40
Q

In dogs with renal cell carcinoma, what is the MST post nephrectomy?

1 and 2 year survival rates?

Time to recurrence or metastasis?

A

MST 1.5yrs
1-yr SR 43%
2-yr SR 25%
Time to recurrence/mets 8.5m post sx

use of adjuvant therapy did not improve prognosis, but 6 dogs with distant mets were treated with chemo and had an MST of 14m

41
Q

What are the negative prognostic indicators for ST identified in dogs with renal cell carcinoma (10)?

A 
Age <6yrs
Presence of hematuria
Presence of cachexia
Metastasis at dx
Clear cell subtype
Histologic vascular invasion
Fuhrman nuclear grade (grade 4 MST 87d, grade 3 MST 379d, grade 2 MST 1065d)
14-3-3o IHC protein expression
COX-2 expression
MI (>30 MST 120-187d HR 12, 10-30 MST 452d, <10 MST 1184d)
42
Q

In a study of dogs with renal HSA treated with nephrectomy and +/- chemotherapy, the MST was ___ m.

Negative PI for ST (1)?

A

9.2m

Dogs with hemoabdomen had a shorter ST (2m)

43
Q

What can be said about bladder tumors in humans as opposed to animals?

A

2/3 are superficial low grade tumors and respond well to sx

44
Q

What breeds are at increased risk for developing TCC (8)?

A 
Scotties (OR 18-21)
Eskimo dogs (OR 6.5)
Shelties (OR 6)
Westies (OR 5.8)
Keeshonds (OR 4.2)
Samoyed (OR 3.4)
Beagle (OR 3)
Dalmatian (OR 2.4)
45
Q

What is Sanguer sequencing?

A

Gold standard for detecting a single nucleotide substitution, but requires a 10-20% fraction of mutated allele for reliable detection - therefore low sensitivity leading to false negatives. Can be used in tissue or urine.

46
Q

BRAF mutations are present in what % of dogs with urothelial and prostatic carcinoma? Overall?

A

Overall - 80% (20% do NOT posses the mutation)
Urothelial - 67%
Prostatic - 78%

47
Q

Describe the BRAF mutation in dogs with urogenital TCC. What is the equivalent mutation in humans?

A

BRAF gene in chromosome 16, exon 15, codon 450 or 595

Results in a T -> A transversion that causes aa substitution of valine for glutamic acid

Humans, V600E

48
Q

Sensitivity and specificity of Sanger sequencing and ddPCR for detecting BRAF mutations in tissue and urine samples from dogs with TCC?

A

Sanger sensitivity:
Tissue - 71%
Urine - 61% of UC, 100% of PC

ddPCR sensitivity:
Tissue: 79%
Urine: 85%

BOTH are 100% specific! ddPCR more sensitive than Sanger for both tissue and urine

49
Q

Advantages of ddPCR over Sanger for BRAF mutation detection?

A

ddPCR much more sensitive; able to detect mutation when present at levels as low as 0.005% (1 in 10,000 alleles)

Sanger requires a 10-20% fraction of mutated allele for reliable detection - therefore low sensitivity leading to false negatives.

50
Q

How does uroplakin III expression differ in dogs with TCC vs those with polyps?

A 
Polyps = staining confined to superficial layer
Carcinoma = random expression, can be patchy, and sometimes decreased in higher grade tumors
51
Q

What % of dogs with bladder/prostate cancer have a concurrent UTI?

Is it more common in dogs with a specific signalment (2)?

Cats?

A

Overall 55%
Females 80% vs males 30%
Urethral involvement 75% vs w/o 30%
Cats 67-75%

52
Q

What is the MST in dogs with TCC that have mets to the skin?

A

2-3m

53
Q

What is the MST, recurrence rate, TTF, and median PFS in dogs with TCC treated with partial cystectomy, an NSAID and +/- chemotherapy?

A

MST 11.6m
Recurrence rate 76%
TTF 100d
PFS 7.8m

Dogs receiving partial cystectomy (vs full thickness) and daily piroxicam MST 2.1yr in 1 study

43% developed post-op complications with incontinence being the most common one

54
Q

What is the MST in dogs with trigonal TCC treated with radical cystectomy and cutaneous ureterostomy (4 cases only)?

A

MST 9.3m

No major complications, but all dogs developed minor complications like bleeding and edema at ureterostomy site

55
Q

What is the MST in dogs with TCC that undergo ureterocolonic anastomosis? Complications (5)?

A

MST 7d to 5m

Complications:
Azotemia due to intestinal recycling of urea in all dogs, hyperchloremic metabolic acidosis, pyelonephritis, hyperammonemia, neuro signs

Not recommended due to morbidity and limited ST

56
Q

What % of dogs with TCC experience relief of UO with urethral stent placement?

A

98-100%

57
Q

What % of dogs with TCC experience incontinence, UTIs, stranguria, and re-obstruction after urethral stent placement?

A

Incontinence 37-64%; severe in 26%
UTI 35%
Re-obstruction 22% at median of 90d
Stranguria 4.7%

58
Q

What is the MST in dogs with TCC when treated with urethral stent?

What has been shown to prolong the MST in these dogs? MST?

A

MST 20d to 2.6m (therefore mostly palliative)

Tx with an NSAID for >4 weeks prior to stent and chemotherapy post stent; MST 8.3m

59
Q

How is the response of hypofractionated RT combined with piroxicam and mitoxantrone when compared to medical therapy alone in dogs with urogenital carcinoma?

A

No improvement vs mito + NSAID alone

AE in 40%

60
Q

How is the a/b ratio of bladder carcinomas?

Increased incidence of late AE is seen with total doses higher than ___Gy.

A

Low a/b ratio - means a higher dose per fraction is probably more important for cell kill

> 30Gy; increased incidence of ureteral fibrosis and stenosis

61
Q

What is the subjective response rate, median event-free ST, and MST in dogs with urogenital carcinoma when treated with IMRT (55-58 Gy over 20 fractions)? Late AE?

A

ORR 60%
Median event-free survival time 10.5m
MST 1.8yrs
20% late grade 3 GI or UG toxicosis

62
Q

What are some recommendations for RT protocols for dogs with urogenital carcinoma (4)?

A
  • Position in lateral recumbency
  • Use PTV of >1cm if not using IMRT
  • Limit dose per fraction to <3Gy to minimize late AE
  • Consider RT field size; inclusion of LN may increase risk of colitis and recta, ureteral, and urethral stricture; bladder size also influences field, so better to treat small bladders
63
Q

What is the biological response rate, PFI, and MST of dogs with bladder TCC when treated with chlorambucil?

A

Biological response rate - 70% (SD in 67% - highest one reported)
PFI 4m
MST 7.4m

Dose 4mg/m2 PO q 24hrs

64
Q

ORR, biological response rate, and MST of cisplatin and Tavocept for dogs with bladder TCC?

Only ___% developed elevated creatinine vs ___ to ___% of historical dogs treated with cisplatin.

A

ORR 27%
Biological response rate 91%
MST 8.4m (comparable to historical controls)
21% had elevated creatinine vs 50 to 86% previously

65
Q

ORR, biological response rate, and MST of dogs with bladder TCC when treated with 5-azacytidine?

A

ORR 26%
Biological response rate 72%
MST 6.7m

66
Q

ORR, biological response rate, PFI, and MST of dogs with bladder TCC when treated with vinorelbine?

A

ORR 15%
Biological response rate 78%
PFI 3m
MST 6m

67
Q

Clinical response rate, PFI, MST of dogs with bladder TCC when treated with doxorubicin, piroxicam, and +/- surgery?

A

Biological response rate 70%
PFI 3.5m
MST 5.6m

68
Q

Identified prognostic factors in dogs with TCC?

A
  • TNM stage
  • Tumor location: urethral (worse prognosis) and prostatic involvement
  • Dogs receiving 3+ chemo drugs had a longer MST compared to those receiving 1-2 chemo drugs
  • Daily piroxicam had a longer PFS and MST
69
Q

In humans, bladder cancer is risked to what?

A

Cigarette smoking

70
Q

What form of bladder carcinoma is similar to TCC in dogs?

A

The invasive form; accounts for 20% of human bladder cancers

71
Q

What % of bladder TCC in cats occur away from the trigone?

A

55%

72
Q

Overall MST in cats with bladder TCC when treated with a combination of surgery, chemotherapy, and an NSAID?

A

8.7m

73
Q

Clinical response and mean survival time of cats with bladder TCC when treated with meloxicam? Any prognostic indicators?

A

Clinical response in 90%
Mean ST 10m
COX+ tumors had a shorter ST (123d) vs COX- (375d)

74
Q

What % of cats with urethral stent develop incontinence and UTIs?

A

Incontinence - 50%

UTI - 25%

75
Q

First and second most common kidney tumor in cats?

A

Lymphoma #1

Tubular renal cell carcinoma #2; IHC CK7, CK20, KIT, CD10

76
Q

Most common renal tumor in children and humans?

A

Children - Wilm’s tumor (nephroblastoma)

Adults - renal cell carcinoma >90% of caricnomas

77
Q

Approximately how many cats with non-lymphomatous renal tumors have metastasis at dx?

A

Majority

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