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Management of Urologic Malignancies

Bladder carcinoma presentation, diagnosis and staging

Joseph W. Basler and Christopher Magee

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4 Management of Urologic Malignancies

Bladder carcinoma presentation, diagnosis and staging

Algorithm
Transitional cell carcinoma
Diagnosis

Signs: Hematuria Symptoms: Irritative voiding Dysuria Frequency Nocturia Urgency Flank pain Abdominal pain Weight loss None

Evaluation: History Physical examination Urinalysis Urine culture Cytology NMP-22, BTA IVP renal US, CT Cystoscopy

Staging

Confirmatory testing: CT + contrast Magnetic resonance Retrograde pyelography Bladder wash Bladder biopsy Transurethral resection

Staging

Clinical: Bimanual examination Thickened bladder Mass (size) Mobile Fixed Cystoscopic biopsy multiple (multifocal, and erythematous areas for ? CIS)

Pathological: Initial microscopic evaluation Associated CIS Lamina propria invasion Muscle invasion Perivesical fat

Staging (AJCC) Stage 0 0a 0is I II Primary tumor (T) Tx T0 Ta Tis T1 T2 Regional nodes (N) Nx N0 N1 Solitary node, < 2 cm N2 Total nodes < 5 cm N3 Total nodes > 5 cm Distant metastases Mx M0 M1 any metastases Grade Gx G1 well G2 moderate G3 poor

III

IV

non-invasive, papillary carcinoma in situ subepithelial connective tissue muscle invasion T2a inner _ detrussor T2b outer _ detrussor T3 perivesical tissue T3a microscopic T3b macroscopic T4 adjacent structures T4a prostate, uterus, vagina T4b pelvic/abdominal wall

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Interpreting the test results

Presentation
Most bladder tumors are discovered during a routine evaluation for haematuria or irritative voiding symptoms (frequency, urgency, nocturia, dysuria) although many remain asymptomatic for months prior to discovery. Eighty per cent of patients with bladder cancer have painless, intermittent hematuria as the primary symptom1. Often the initial episodes of intermittent gross hematuria were either not evaluated or were treated as presumed urinary tract infections or passed stones. Unfortunately, in some cases urinary tract infections or stone disease may co-exist and confuse or delay the diagnosis. The amount of hematuria varies from microscopic to frank blood but is not reliably related to amount of tumour, therefore, all hematuria warrants thorough investigation (see Hematuria algorithm). Irritative voiding symptoms such as dysuria, urgency or frequency may be associated with CIS or invasive cancer. For tumors overlying the ureteral orifice the presenting symptom may be flank pain or pyelonephritis from obstruction. These findings are also suggestive of invasive cancer. Symptoms of advanced disease such as pain, abdominal mass or weight loss may be present as well. The differential diagnosis includes urinary calculi, urinary tract infections (including tuberculosis), benign prostatic hypertrophy, prostate cancer, trauma and renal tumors.

and guide further work if positive but may fail to predict the presence of well to moderately differentiated tumors. False positive cytology occurs occasionally especially if obtained after contrast agents have been instilled into the urinary tract. Other urine-based tests (Table 4.1) are not indicated for initial evaluation but may be helpful in follow up of patients treated for transitional cell carcinoma of the bladder. Filling defects on IVU not corresponding to calcifications on plane films (Figure 4.1) are differentiated into:
Table 4.1 Partial list of some currently available tests for detection of bladder cancer
Test Cytology BTA BTAstat BTA trak NMP-22 Measures Nuclear morphology Bladder tumor associated analyte Compliment factor H-related protein Bladder tumor antigen Nuclear matrix protein Indication Diagnosis, Follow up Follow up Follow up Follow up Follow up

Diagnosis
The standard evaluation for hematuria and irritative voiding includes urine culture, cytology, intravenous urography (IVU) and cystoscopy. In some patients with renal insufficiency, significant proteinuria or contrast allergy, a renal ultrasound and cystoscopy with retrograde pyelography is indicated. Recent studies of immediate day-case outpatient screening of patients with hematuria have demonstrated that renal ultrasound and cystoscopy alone may be adequate evaluation leaving IVU and other imaging modalities in a confirmatory role 2. While spiral CT and MRI imaging may be helpful for finding gross lesions or differentiating soft tissue masses from stones, their role in the initial management should be limited due to their insensitivity to subtle urothelial lesions. A new technique utilizing MR (MR urogram) may eventually be useful for evaluating urothelium, especially in dilated ureters and full bladders.

Interpreting the test results

While usually negative, a positive urine culture should not necessarily preclude further evaluation with upper tract imaging and cystoscopy after the urine has been sterilized with antibiotic therapy. Cytologic evaluation can be helpful

Fig. 4.1 IVU demonstrating filling defect in the bladder that

was later found on cystoscopy to be a small pedunculated bladder tumor. Tumors in the bladder are best detected on drainage films and often appear as dark defects with a rim of contrast surrounding them.

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Bladder carcinoma presentation, diagnosis and staging

bladder tumor, clot, fungal ball, lucent stones (urate), etc. A filling defect over a ureteral orifice with obstruction of the ureter suggests muscle invasive disease around the trigone and possibly ureteral tumors3. In general, ultrasonography is insensitive to all but the most prominent bladder tumors, but recent advances in technology may cause this to change. A finding of hydronephrosis should be further evaluated with IVU and/or retrograde pyelography. Cystoscopic evaluation is usually carried out in the office setting unless there is evidence on IVU that biopsy or transurethral resection of bladder tumor may be needed. Cystoscopy using a rigid 17Fr cystoscope or a flexible cystoscope with 2% lidocaine jelly as a local anesthetic should be performed on all patients with hematuria. The flexible cystoscope is more comfortable for the patient and allows for better inspection of the dome and bladder neck; however, visibility is poor when there is gross hematuria. In these cases the rigid cystoscope using 30 and 70 lenses and sterile water irrigant provides better visualization of the bladder mucosa. It is important to inspect the mucosa in a systematic fashion so that small papillary tumors or areas of potential CIS are not overlooked. Patients with other identified causes of hematuria (stones, UTI, etc.) should still undergo cystoscopy to look for concominant disease. Patients found to have tumors should then be scheduled for resection. If no cause for the hematuria can be identified, urinalysis is performed at 36 months and complete evaluation repeated if hematuria persists. Cystoscopy may reveal the classic flat velvety lesion of carcinoma in situ (CIS) (Figure 4.2a) or easily distinguished frondular transitional cell carcinoma (Figure 4.2b). Often, CIS and papillary lesions coexist (Figure 4.2c). Invasive carcinomas will often have a sessile appearance with infiltration into the surrounding bladder wall (Figure 4.3). Diagnosis is made by cold-cup biopsy or transurethral resection of the lesion(s). Additionally, biopsies of other suspicious bladder lesions as well as the prostatic fossa (male) should be made. The utility of random or site-directed biopsies of normal appearing areas of mucosa is not well supported but is advocated by some. Some other benign lesions such as squamous metaplasia, cystitis cystica, cystitis glandularis and unusual tumors such as nephrogenic adenoma and inflammatory pseudotumor are sometimes confused with carcinoma. Adenocarcinoma, carcinosarcoma and other unusual bladder malignancies are usually discrete sessile lesions. Prostatic carcinoma may be visualized as a diffuse infiltrative lesion originating at the bladder base often with a nodular, friable surface caus-

Fig. 4.2 a. Red, velvety patch of carcinoma in situ. b. Multiple

frondular tumor excrescences along the bladder base. c. Frondular transitional cell carcinoma with a few satellite lesions.

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References

Table 4.2 TNM classification system

TIS Ta T1 T2 T3 T4 Nx N0 N1 N2 N3 Mx M0 M1 Carcinoma in situ Papillary tumor not invading lamina propria Papillary tumor invading basement membrane Papillary tumor invading true lamina propria Tumor invading superficial (inner half) detrusor Tumor invading deep (outer half) detrusor Tumor invading perivesical fat microscopically Tumor invading perivesical fat macroscopically Tumor invading prostate stroma, vagina, uterus Tumor invading pelvic or abdominal sidewall Not assessed No nodal metastases Single nodal metastasis (<2 cm) Multiple nodal metastases (<5 cm) Multiple nodal metastases (>5 cm) Presence of distant metastases not assessed No distant metastases Distant metastases

T1a T1b T2a T2b T3a T3b T4a T4b

Fig. 4.3 A large sessile transitional cell carcinoma with fresh (red) and old superficial areas of hemorrhage.
ing anatomical distortion and may invade the trigone and obstruct the ureter as it invades along the ureteral sheath.

Staging
There is not a uniformly accepted staging regimen for all types of bladder tumors. Superficial tumors and CIS generally require only the findings at cystoscopy, the results of upper tract imaging and the pathologic evaluation of the specimen. However, general guidelines for evaluation of invasive tumors would include the findings at cystoscopy, pathologic findings, examination under anesthesia, upper tract imaging and, depending on the depth of penetration of the tumor, CT scan of the chest, abdomen and pelvis. Bone scan may be helpful in situations where metastases are suspected due to an elevated serum alkaline phosphatase (an unproven but widely used indicator of bone activity) or bony pain. MRI may be helpful for determining the depth of penetration of the tumor and to assess the regional lymph nodes but usually offers little advantage over CT scan. If invasive tumor is suspected, CT or MRI imaging may be more useful for staging purposes prior to

System used for all histologic types of bladder cancer (transitional cell, squamous cell, adenocarcinoma, other carcinoma) but not tumors that invade or metastasize to the bladder secondarily (prostate, lymphoma, etc.) Primary vesicle melanoma or pheochromocytoma without other extravesicle lesions are rare exceptions.

resection to eliminate the post-resection inflammatory artefact that may produce bladder wall thickening and perivesical inflammation. The TNM classification system for bladder carcinoma is presented in Table 4.2.

References
1. Cummings KB, Barone JG, Ward WS. Diagnosis and staging of bladder cancer. Urologic Clinics of N Am 1992; 3: 455465. 2. Yip S, Peh W, Tam P, Li J, Lam H. Day case hematuria diagnostic service: use of ultrasonography and flexible cystoscopy. Urology 1998; 52 (5):762766. 3. Haleblian G, Skinner E, Dickinson M, Lieskovsky G, Boyd S, Skinner D. Hydronephrosis as prognostic indicator in bladder cancer patients. J Urol 1998;160(6 part 1):20112014. 4. Fleming ID et al: AJCC Cancer Staging Manual / American Joint Committee on Cancer, 5th edn. Philadelphia: Lippincott-Raven, 1997.

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