DIAGNOSIS & THE ROLE OF DIAGNOSIS & THE ROLE OF SURGERY IN TTC OF SURGERY IN TTC OF

BLADDERBLADDER

Dr. Homayoun Abbasi, MDDr. Homayoun Abbasi, MD

Isfahan Fertility and Infertility Center Isfahan Fertility and Infertility Center

Key Points: Detection of Urothelial Key Points: Detection of Urothelial CancerCancer

• Painless gross hematuria occurs in 85% of patients with bladder cancer and requires a complete evaluation that includes cystoscopy, urine cytology, CT scan, and a PSA

blood test.

• Patients with microscopic hematuria require a full evaluation, but low-risk patients do not require repeat

evaluations. High-risk individuals primarily are those with a smoking history and should be evaluated every 6 months.

• White light cystoscopy with random bladder biopsies is the gold standard for tumor detection, but blue light cystoscopy

may be an adjunct.

• There are various urine markers that evaluate secreted proteins or shed cells in the hope of noninvasively detecting bladder cancer. To date, none of these markers have a high enough sensitivity or specificity to replace office cystoscopy

High-Risk Characteristics of Patients withHigh-Risk Characteristics of Patients withMicroscopic HematuriaMicroscopic Hematuria

• Smoking history• Occupational exposure• History of gross hematuria• Greater than age 40 years• Previous urologic surgery• Irritating voiding symptoms• History of urinary tract infections• Analgesic abuse• History of pelvic radiation• Previous cyclophosphamide therapy

From Grossfeld GD, Litwin MS, Wolf JS Jr, et al. Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy—part II: patient evaluation, cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow-up. Urology 2001;57(4):604–10.

Cystoscopy

• The main diagnostic test for bladder cancer is cystoscopy and biopsy. White light cystoscopy (WLC) is the gold standard, and flexible office cystoscopy is as reliable as a rigid endoscopy (Grossfeld et al, 2001). White light cystoscopy has an excellent sensitivity and specificity for papillary tumors but is relatively poor for CIS. Cystoscopy with porphyrin dye (commonly referred to as blue light cystoscopy) may be more sensitive in the detection of CIS (Fradet et al, 2007; Grossman et al, 2007).

• Porphyrininduced fluorescence cystoscopy uses photoactive porphyrins,such as hexaminolevulinate, that accumulate preferentially in neoplastic tissue and emit red fluorescence under blue-wavelength light. This may improve the detection of small papillary lesions and CIS.

• Narrow-band imaging (NBI) is an endoscopic optical image enhancement technique that enhances the contrast between mucosal surfaces and microvascular structures without the use of dyes. The depth of light penetration into the bladder wall increases with increasing wavelength. NBI illuminates the mucosal surface with light of a narrow bandwidth in the blue (415 nm) and green (540 nm) light spectrum, which are strongly absorbed by hemoglobin. Consequently, the vascular structures appear dark brown or green against a pink or white mucosal background.

Urinary Markers

Sensitivity and Specificity of Urinary Markers in the Detection of Urothelial Cancer

MARKER MEDIAN SENSITIVITY(%)

RANGE (MINIMUM %–MAXIMUM %)

MEDIANSPECIFICITY (%)

RANGE (MINIMUM%–MAXIMUM %)

BTA stat BTAtrak NMP22 FDP ImmunoCyt Cytometry Quanticyt Hb-dipstickLewis XFISH Telomerase Microsatellite CYFRA21-1 UBC Cytokeratin BTA TPSCytology

706973618360595283847591947891507248

24-8957-7947-10052-8150-10045-8345-6941-9580-8973-927-10083-9574-9966-8782-9628-8064-8831-100

756580798080798285958694869184867894

52-9348-9556-9575-9669-9036-8770-9368-9380-8692-10024-9389-10067-10080-9767-9766-9555-9562-100

From van Rhijn BW, van der Poel HG, van der Kwast TH. Urine markers for bladder cancer surveillance: a systematic review. Eur Urol 2005;47(6):736–48.

• The primary concern is missing tumor cells by relying on the urinary marker. None of the currently available urinary markers meet this 90% sensitivity on a reliable basis, and therefore a combination of cystoscopy with urine markers, in select situations, is appropriate for surveillance of patients with non–muscle-invasive bladder cancer.

Random Biopsy

• For patients with concurrent bladder tumors, a random biopsy will detect dysplasia or CIS in up to 23% of cases (Mufti and Singh, 1992). It is reasonable to perform random biopsies in high-risk individuals, such as for those given postintravesical therapy or for those with a positive cytology and an endoscopically negative bladder.

• On the basis of the understanding that CIS can exist in normalappearing urothelium, some authors advocate the use of random biopsies to identify CIS in otherwise normal-appearing mucosa. This remains controversial.

• The current consensus is that random biopsies are not indicated in low-risk patients

Urine Cytology

Poor cellular cohesion in high-grade Poor cellular cohesion in high-grade tumors, especially CIS, enhances the tumors, especially CIS, enhances the

yield. Its high specificity is the most yield. Its high specificity is the most important feature of cytology because a important feature of cytology because a

positive reading regardless of cystoscopic positive reading regardless of cystoscopic or radiographic findings suggests the or radiographic findings suggests the

existence of malignancy in the vast existence of malignancy in the vast majority of patients.majority of patients.

• Overall, the sensitivity and specificity for cytology in detecting bladder cancer is 40% to 62% and 94% to 100%, respectively (van Rhijn et al, 2005; Volpe et al, 2008).

ENDOSCOPIC SURGICALENDOSCOPIC SURGICALMANAGEMENTMANAGEMENT

• When bladder cancer is identified during office-based cystoscopy, the location, number, and nature of tumors are recorded, as is involvement of areas likely to reflect extravesical extension such as the ureteral orifices and bladder neck/prostatic urethra. Urinary cytology is obtained as a baseline and to establish the likelihood of high-grade disease. Positivity will encourage random bladder biopsy at the time of TUR as discussed later.

• TUR of bladder tumor (TURBT) under regional or general anesthesia is the initial treatment for visible lesions and is performed to (1) remove all visible tumors and (2) provide specimens for pathologic examination to determine stage and grade.

Repeat Transurethral Resectionof Bladder Tumor

• Complete tumor removal is not always possible, whether due to excessive tumor volume, anatomic inaccessibility, medical instability requiring premature cessation, or risk of perforation.

• However, even in the absence of these circumstances repeat TUR is often indicated. When repeat TUR is performed within several days to several weeks of the original resection, residual tumor is identified at the site of the initial resection at least 40% of the time (Klan et al, 1991; Mersdorf et al, 1998; Vogeli et al, 1998).

• Repeat TURBT is usually appropriate in the evaluation of T1 tumors because a repeat TUR can demonstrate worse prognostic findings in up to 25% of specimens (Schwaibold et al, 2000).

• This is especially likely if no muscle is identified on initial pathology, which can occur in almost half of cases. The Vanderbilt University group reported a 64% risk of understaging T1 lesions when muscle was absent, compared with 30% when muscle was present in the specimen

• Consensus is that patients with pT1 and high-grade Ta tumors merit repeat resection.

• Radical Transurethral Resection of Bladder Tumor (TURBT)

• For selection of candidates, strict criteria are required and include (1) initial occurrence of bladder cancer; (2) no CIS; (3) size less than or equal to 3 cm; (4) stage T2 (no palpable mass); and (5) not in the dome or high posterior wall because of the risk of bowel injury.

When these criteria are used, long-term When these criteria are used, long-term survival is comparable with that of radical survival is comparable with that of radical

cystectomy for the small fraction of cystectomy for the small fraction of potentially eligible patients.potentially eligible patients.

• All patients must undergo re-resection 3 months after radical TURBT, and if tumor persists at this time, radical cystectomy or radiation is considered.

Partial CystectomyPartial Cystectomy

• The indications for partial cystectomy are similar to those for radical TURBT with one exception—the location. Tumors must be in a location suitable for bladder preservation—usually on the dome and away from the ureteral orifices.

• Bilateral pelvic lymphadenectomy is performed at the time of surgery for pathologic staging of the nodes.

• In the unique situation of urachal adenocarcinoma, partial cystectomy with en bloc resection of the urachus is the preferred surgical method for local control

Laser TherapyLaser Therapy

• Laser coagulation allows minimally invasive ablation of tumors up to 2.5 cm in size. The neodymium : yttrium-aluminum-garnet (Nd : YAG) laser has the best properties for use in bladder cancer.

• The most significant complication of laser therapy is forward scatter of laser energy to adjacent structures, resulting in perforation of a hollow, viscous organ such as overlying bowel.

• limiting energy to 35 W precludes exceeding 60° C on the outer bladder wall, minimizing the risk of perforation (Hofstetter et al, 1994). The most efficient delivery appears to be an end-fire noncontact fiber with a 5- to 15-degree angle of divergence, which allows variable penetration depth up to 5 mm

• Laser therapy can be more expensive than resection due to the cost of laser fibers, but bleeding is negligible and there is no risk of obturator reflex. Small lesions can be treated easily using intravesical anesthesia. Because there is no tissue available for pathologic inspection, the optimal candidate for laser therapy is the patient with recurrent, low-grade lesions whose biology is already known.

• Holmium : yttrium-aluminum-garnet (YAG), argon, and potassium titanyl phosphate (KTP) lasers ablate tissues by cutting (vaporization) and thus have limited applicability due to lack of deep coagulation (Johnson et al, 1991; Benson, 1992; Holzbeierlein and Smith, 2000). The carbon dioxide laser is completely absorbed by fluid, so it is not appropriate for use in the treatment of bladder cancer (Benson, 1992).

Thank you for your time -Thank you for your time -much appreciated!much appreciated!