Bladder Cancer - non muscle invasive

Question 1

Diagnosis

Answer 1

• At the time of resection of suspected bladder cancer, a clinician should perform a thorough cystoscopic examination of a patient’s entire urethra and bladder that evaluates and documents tumor size, location, configuration, number, and mucosal abnormalities. (Clinical Principle)
• At initial diagnosis of a patient with bladder cancer, a clinician should perform complete visual resection of the bladder tumor(s), when technically feasible. (Clinical Principle)
• A clinician should perform upper urinary tract imaging as a component of the initial evaluation of a patient with bladder cancer. (Clinical Principle)
• In a patient with a history of NMIBC with normal cystoscopy and positive cytology, a clinician should consider prostatic urethral biopsies and upper tract imaging, as well as enhanced cystoscopic techniques (blue light cystoscopy, when available), ureteroscopy, or random bladder biopsies. (Expert Opinion)

Question 2

Variant Histology

Answer 2

• An experienced genitourinary pathologist should review the pathology of a patient with any doubt in regards to variant or suspected variant histology (e.g., micropapillary, nested, plasmacytoid, neuroendocrine, sarcomatoid), extensive squamous or glandular differentiation, or the presence/absence of lymphovascular invasion. (Moderate Recommendation; Evidence Strength: Grade C)
• If a bladder sparing approach is being considered in a patient with variant histology, then a clinician should perform a restaging TURBT within four to six weeks of the initial TURBT. (Expert Opinion)
• Due to the high rate of upstaging associated with variant histology, a clinician should consider offering initial radical cystectomy. (Expert Opinion)

Question 3

Urine Markers after Diagnosis of Bladder Cancer

Answer 3

• In surveillance of NMIBC, a clinician should not use urinary biomarkers in place of cystoscopic evaluation. (Strong Recommendation; Evidence Strength: Grade B)
• In a patient with a history of low-risk cancer and a normal cystoscopy, a clinician should not routinely use a urinary biomarker or cytology during surveillance. (Expert Opinion)
• In a patient with NMIBC, a clinician may use biomarkers to assess response to intravesical BCG (UroVysion® FISH) and adjudicate equivocal cytology (UroVysion® FISH and ImmunoCyt™). (Expert Opinion)

Question 4

TURBT/re-resectino: timing, technique, goal, indication

Answer 4

• In a patient with non-muscle invasive disease who underwent an incomplete initial resection (not all visible tumor treated), a clinician should perform repeat transurethral resection or endoscopic treatment of all remaining tumor if technically feasible. (Strong Recommendation; Evidence Strength: Grade B)
• In a patient with high-risk, high-grade Ta tumors, a clinician should consider performing repeat transurethral resection of the primary tumor site within six weeks of the initial TURBT. (Moderate Recommendation; Evidence Strength: Grade C)
• In a patient with T1 disease, a clinician should perform repeat transurethral resection of the primary tumor site to include muscularis propria within six weeks of the initial TURBT. (Strong Recommendation; Evidence Strength: Grade B)

Question 5

Intravesical therapy;BCG maintenance; chemo/BCG combo

Answer 5

• In a patient with suspected or known low- or intermediate-risk bladder cancer, a clinician should consider administration of a single postoperative instillation of intravesical chemotherapy (e.g., mitomycin C or epirubicin) within 24 hours of TURBT. In a patient with a suspected perforation or extensive resection, a clinician should not use postoperative chemotherapy. (Moderate Recommendation; Evidence Strength: Grade B)
• In a low-risk patient, a clinician should not administer induction intravesical therapy. (Moderate Recommendation; Strength of Evidence Grade C)
• In an intermediate-risk patient a clinician should consider administration of a six week course of induction intravesical chemotherapy or immunotherapy. (Moderate Recommendation; Evidence Strength: Grade B)
• In a high-risk patient with newly diagnosed CIS, high-grade T1, or high-risk Ta urothelial carcinoma, a clinician should administer a six-week induction course of BCG. (Strong Recommendation; Evidence Strength: Grade B)
• In an intermediate-risk patient who completely responds to an induction course of intravesical chemotherapy, a clinician may utilize maintenance therapy. (Conditional Recommendation; Evidence Strength: Grade C)
• In an intermediate-risk patient who completely responds to induction BCG, a clinician should consider maintenance BCG for one year, as tolerated. (Moderate Recommendation; Evidence Strength: Grade C)
• In a high-risk patient who completely responds to induction BCG, a clinician should continue maintenance BCG for three years, as tolerated. (Moderate Recommendation; Evidence Strength: Grade B)

Question 6

BCG relapse and salvage regimens

Answer 6

• In an intermediate- or high-risk patient with persistent or recurrent disease or positive cytology following intravesical therapy, a clinician should consider performing prostatic urethral biopsy and an upper tract evaluation prior to administration of additional intravesical therapy. (Conditional Recommendation; Evidence Strength: Grade C)
• In an intermediate- or high-risk patient with persistent or recurrent Ta or CIS disease after a single course of induction intravesical BCG, a clinician should offer a second course of BCG. (Moderate Recommendation; Strength of Evidence C)
• In a patient fit for surgery with high-grade T1 disease after a single course of induction intravesical BCG, a clinician should offer radical cystectomy. (Moderate Recommendation; Evidence Strength: Grade C)
• A clinician should not prescribe additional BCG to a patient who is intolerant of BCG or has documented recurrence on TURBT of high-grade, non-muscle-invasive disease and/or CIS within six months of two induction courses of BCG or induction BCG plus maintenance. (Moderate Recommendation; Evidence Strength: Grade C)
• In a patient with persistent or recurrent intermediate- or high-risk NMIBC who is unwilling or unfit for cystectomy following two courses of BCG, a clinician may recommend clinical trial enrollment. A clinician may offer this patient intravesical chemotherapy when clinical trials are unavailable. (Expert Opinion)

Question 7

Role of cystectomy in NMIBC

Answer 7

• In a patient with Ta low- or intermediate-risk disease, a clinician should not perform radical cystectomy until bladder-sparing modalities (staged TURBT, intravesical therapies) have failed. (Clinical Principle)
• In a high-risk patient who is fit for surgery with persistent high-grade T1 disease on repeat resection, or T1 tumors with associated CIS, LVI, or variant histologies, a clinician should consider offering initial radical cystectomy. (Moderate Recommendation; Evidence Strength: Grade C)
• In a high-risk patient with persistent or recurrent disease within one year following treatment with two induction cycles of BCG or BCG maintenance, a clinician should offer radical cystectomy. (Moderate Recommendation; Evidence Strength: Grade C)

Question 8

Enhanced cystoscopy

Answer 8

• In a patient with NMIBC, a clinician should offer blue light cystoscopy at the time of TURBT, if available, to increase detection and decrease recurrence. (Moderate Recommendation; Evidence Strength: Grade B)
• In a patient with NMIBC, a clinician may consider use of NBI to increase detection and decrease recurrence. (Conditional Recommendation; Evidence Strength: Grade C)

Question 9

Risk adjusted strategies and followup strategies

Answer 9

• After completion of the initial evaluation and treatment of a patient with NMIBC, a clinician should perform the first surveillance cystoscopy within three to four months. (Expert Opinion)
• For a low-risk patient whose first surveillance cystoscopy is negative for tumor, a clinician should perform subsequent surveillance cystoscopy six to nine months later, and then annually thereafter; surveillance after five years in the absence of recurrence should be based on shared-decision making between the patient and clinician. (Moderate Recommendation; Evidence Strength: Grade C)
• In an asymptomatic patient with a history of low-risk NMIBC, a clinician should not perform routine surveillance upper tract imaging. (Expert Opinion)
• In a patient with a history of low-grade Ta disease and a noted sub-centimeter papillary tumor(s), a clinician may consider in-office fulguration as an alternative to resection under anesthesia. (Expert Opinion)
• For an intermediate-risk patient whose first surveillance cystoscopy is negative for tumor, a clinician should perform subsequent cystoscopy with cytology every 3-6 months for 2 years, then 6-12 months for years 3 and 4, and then annually thereafter. (Expert Opinion)
• For a high-risk patient whose first surveillance cystoscopy is negative for tumor, a clinician should perform subsequent cystoscopy with cytology every three to four months for two years, then six months for years three and four, and then annually thereafter. (Expert Opinion)
• For an intermediate- or high-risk patient, a clinician should consider performing surveillance upper tract imaging at one to two year intervals. (Expert Opinion)

Question 10

NMIBC treatment algorithm

Answer 10

Question 11

Risk stratification of NMIBC

Answer 11

Question 12

Risk stratification - low risk

Answer 12

• LG solitary <= 3 cm
• PUNLMP (papillary urothelial neoplasm of low malignant potential)

Question 13

Risk stratification - Intermediate Risk

Answer 13

• Recurrence within 1 year, LG Ta
• Solitary LG Ta >3 cm
• LG Ta, multifocal
• HG Ta = 3 cm
• LG T1

Question 14

Risk stratification - High risk

Answer 14

• HG T1
• any recurrent HG Ta
• HG Ta > 3 cm or multifocal
• CIS
• BCG failure in a HG patient
• Variant Histology
• LVI
• HG Prostatic urethral involvement