The role of CT Urography in the evaluation of Bladder Cancer

Milagros Otero-GarcíaComplexo Hospitalario Xeral Cíes. Vigo.SPAIN

milaotero@mundo-r.com

What is CT Urography (CTU)?

CTU is a term used to describe high-spatial-resolution imaging of the urinary tract by using contrast material administration, a multidetector CT scanner with thin collimation and imaging in the excretory phase *.

* Van Der Molen AJ. Eur Radiol. 2008 18: 4–17

CTU Indications

Hematuria

Patients at increased risk for having upper or lower tract

urothelial neoplasms

Urinary diversion procedures following cystectomy

Hydronephrosis, chronic symptomatic urolithiasis or planning of

percutaneous nephrolithotomy (PCNL)

Traumatic and iatrogenic uretheral injury, and complex urinary tract infections.

Nolte-Ernsting C. 2006: 16;2670-2686.

Caoili EM. Categorical Course in Diagnostic Radiology: Genitourinary Radiology 2006; pp 11–22.

Van Der Molen AJ. Eur Radiol. 2008 18: 4–17

CTU: Suspected malignant diseaseHow do we do it?

2 Phase- single bolus CTU: - Oral hydration (700 ml of water, 30 min ) - Low dose diuretic (Furosemide): 0.1mg/kg, 1-3 min, before CM - Single bolus of 100 -[320] IV CM - Nephrographic phase@ 100 sec 0,75 mm x16: Beam collimation - Excretory phase @ 12 min (7-15 min) 1/0.8 mm : Reconstruction

Unenhanced phase?

1.- Ultrasound is widely used in my country and normally the patients have undergone an US exploration before they are referred to our department.

2.-Using Furosemide there is an improvement in lithiasis diagnosis. Furosemide decrease the urine attenuation value (< 500 HU) *.

3.- There is not evidence considering unenhanced phase efficiency. What detects the unenhanced phase which is undetected by the nephrographic phase ?.

*Bellin MF, et al. Eur Radiol 2004; 14:2134-2140

Lithiasis HU

BrushiteCalcium oxalate monohydrateCalcium oxalate dihidrateCystineStruviteUric acid

1703+ 1611704+ 2381417 + 234711 + 228666 + 87

409 + 118

Portal versus nephrographic phase?

Bladder cancer tends to show peak enhancement with the 60- second (portal Phase) scanning delay *.

Portal phase CTU offers high accuracy detecting BC**:

- Sensitivity: 89%–92% in per lesion analysis 95% in per patient analysis

- Specificity: 88%– 97% in per lesion analysis 91%–93% in per patient analysis

* Kim JK. 2004;231(3): 725-731

* *Park SB. 2007;245:798-805

CTU: Image review, image reconstruction and reformatted images

CTU image review and postprocessing: Using a workstation and/or a picture archiving and communication system (PACS): Creation of multiplanar reformatted images and 3D reconstructed images by using:

- Maximum and average intensity projection techniques (MIP 5-50mm , AIP 5-10mm)

- Volume-rendering (VR 5-50 mm)

- Narrow and wide windows * ,** and thin sections with MPR and axial images review (improve the detection rate for tumors smaller than 5 mm) ***.

* Cohan R.H. AJR 2009; 192:1501-1508** Caoili EM. AJR Am J Roentgenol 2005; 184:1873–1881***Jinzaki Masahiro AJR 2007; 188:913-918

Homogeneous bladder opacification: Voiding the bladder before examination or mixing bladder contents: patient rolls over supine- prone on the CT table or walks around the CT room.

All the excretory system must be included in the exam: Since the urothelium of the entire urinary system is at risk of developing cancer.

CTU may allow staging of deeply invasive tumors, detection of metastases and other extra-genitourinary pathology.

Bladder cancer CTU

Bladder cancer

Background• Is the most common malignancy of the urinary tract. • Is a disease of older patients (>65).• Represents the 6.6% of the total cancers in men and

2.1% in women, with an estimated male-to-female ratio of 3.8:1*.

* Ferlay J. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 2007;18(3):581-592.

Bladder cancer

Risk factors• Cigarrete smoking: Smokers have a two to sixfold increased risk of

cancer compared to non-smokers. • Occupational exposures: Exposition to aromatic amines

(petrochemical, textile, printing industries), hairdressing, firefighting, truck driving, plumbing…

• Exposures to certains medications: Phenacetin, Cyclophosphamide.• Others: Arsenic in drinking water, prior pelvic irradiation and lower

urinary tract inflammation (schistosomiasis).

Steiner H. BJU Int 2008; 102; 291-296.

Jade J. Wong-You–Cheong. Radiographics, 2006.

Bladder cancer

Cell type

•I.- Epithelial tumors:•Urothelial (transitional cell) cancer (90%). Is the most common urinary tract cancer in the United States and Europe. • Has a propensity to be multicentric (30-40% ) with synchronous and metachronous bladder and upper tract tumors.

• Squamous cell (5-8 %)• Adenocarcinoma (2%)

•II.- Non-epithelial tumors: Leiomyosarcomas, lymphoma: Rare

Staging

Ta: Non invasive CIS: high- grade flat Urothelial cancer T1: Invade lamina propria

T2a and T2b: bladder wall musculature

T3a and T3b: perivesical space extension

T4: Adyacent organs or pelvic

sidewall invasion.

GRADE: Grade 1: Well differentiated: papillary/ superficial Grade 2: Poorly differentiated: infiltrative/Invasive

Husband J. Imaging in Oncology, Second edition, 2004

Symptoms

Microscopic or gross hematuria, but only 13-28% patients with gross hematuria have bladder cancer.

CTU Assesment in Bladder cancer

Tumor appearance

Tumor enhancement

CTU appearance of BC

Asymmetric diffuse or focal wall thickening

Male, 75 year-old.Tumor right bladder wall

Male 70 year old.Tumor at left UVJ

Focal enhancing masses

Small filling defects

Soft tissue window (W:400, L:40) Wide windows (W:1990, L:362)

Multiple enhancing and filling defects lesions

Studies evaluating ability of CTU to detect tumors in urinary system

Hematuria CTU/Cystoscopy Sens. Specif. PPV NPV

Turney BW, BJU Int 2006 Macroscopic hematuria(N:161)

Bladder cancer 93% 99% 98% 97%

Sung Big Park et al.Radiology 2007

Painless gross hematuria or repeated microscopic hematuria

Bladder cancer

- Lesions <10 mm

92%

83%

97%

Sudakoff GS et al. The Journal of Urology 2008

Macroscopic hematuria

Neoplasms detection 64% 98% 76% 96%

Muller-Lise UG.Eur Radiol 2007

Previous cancer and painless hematuria

Tumor detection 94% 78%

Cheryl A. Sadow Ch A. Radiology 2008

Hematuria or previous urothelial cancer (N: 779)

Bladder Cancer 79% 94% 75% 95%

Turney BW. BJU Int 2006

. Flexible cystoscopy would only be required in patients whose CTU findings are equivocal.

Sadow Ch A. Radiology 2008

. Forgot cystoscopy in low-risk patients with negative CTU .

. Reserve cystoscopy for patients with a history of urothelial cancer.

CTU and BC detection

CTU reasons for false positive diagnosis

Previous transurethral resection or anticancer drug instillation, related inflammation may suggest BC.

67 year-old man. Previous transurethral BC resection.CTU: Asymetric enhancing right wall thickeningCystoscopy: Fybrosis

CTU reasons for false negative diagnosis

Flat tumors Bladder lesions located at the bladder base

(near prostate and urethra) The most problematic group: Patients

have already undergone local treatment for non-invasive bladder tumors .

72 year-old man. CTU: Prostatic hypertrophy and diffuse wall thickening and small polipoid nodule in the posterior bladder wallCystoscopy: BC in small nodule

75 year-old man. Previous transurethral resectionCTU: Small bladder, diffuse wall thickening and small enhancing nodule at bladder domeCystoscopy: BC

Problematic group

Treated bladders develop areas of thickening and scarring:

These areas can show an abnormal enhancement that mimics tumor, false positive diagnosis

Also make any present cancers difficult to detect false negative diagnosis Cystoscopy is necessary

CTU for Local Staging of bladder cancer

• Low (40-60%)Staging

Accuracy

• cannot distinguish:• Non-muscle invasive/

muscle invasive: T1-T2• Perivesical infiltration:

T3a-T3b

Invasiveness and

perivesical spread

T3a or T3b ?

T4

CT Urography in the Diagnosis of Bladder Cancer Our experience

Purpose: To evaluate the efficacy of CT Urography (CTU) for the detection of bladder cancer in patients at high risk.

Materials and Methods: Retrospective study of 45 patients. The CTU studies were read in consensus by two observers with

varying levels of expertiseGold standard: Flexible cystoscopy (+biopsy) was performed

( within 1 month). Sensitivity, specificity, positive and negative predictive values.

Age, sex, type of hematuria and CTU result were evaluated as predictors for bladder cancer using McNemar test and multivariate logistic regression analyses. P < 0,05 was significant.

RISK FACTORS

Age > 40

Macroscopic hematuria or repeated microscopic hematuria (n:42): - Macroscopic (n:32): 76% - Repeated microscopic (n:10): 24%

Smokers (n:11): (24,4%)

Positive citology (n:35): (77,7%)

Previous TCC ( n:3): 6,6%

Results

Size MeanStd. DeviationMinimunMaximun

2.8 cm1.8 cm0.50 cm6 cm

CTU/CYST CYS + CYS - Total

CTU + 39 1 40

CTU - 1 4 5

Total 40 5 45

ResultsCTU/CYS: bladder cancer

McNemar Test CTU/Cystoscopy

Male/female 0.0001

Age ( > 60 y.) 0.0001

Macroscopic /microscopic hematuria

0.0002

CTU (+/_) 0.0001

Sens: 97% , Spec: 80% , PPV: 97% NPV: 80% .(P: 0.001)

Variables in the Equation

B S.E. Wald df Sig. Exp(B)

Step 1a CTU 5,050 1,509 11,206 1 ,001 156,000

Constant -8,713 2,314 14,185 1 ,000 ,000

Step 2b Gender -19,508 6756,488 ,000 1 ,998 ,000

CTU 21,993 6756,488 ,000 1 ,997 3,561E9

Constant -4,277 2,483 2,966 1 ,085 ,014

a. Variable(s) entered on step 1: CTU

b. Variable(s) entered on step 2: Gender.

Logistic Regression

Limitations:

- Few cases and therefore difficult to extrapolate results

- Few cases in the most problematic group: Patients with previous bladder cancer.

CONCLUSION

In patients at high risk testing positive on CTU, initial assessment by flexible cystoscopy can be replaced by direct referral to rigid cystoscopy for possible biopsy and transurethral resection.

Sunset at the Ria de Vigo