Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer

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 mabnormalities.

2. At initial diagnosis of a patient with bladder cancer, a clinician should perform complete visual resection of the bladder tumor(s), when technically feasible.

3. A clinician should perform upper urinary tract imaging as a component of the initial evaluation of a patient with bladder cancer.

4. 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.

5. At the time of each occurrence/recurrence, a clinician should assign a clinical stage and classify a patient accordingly as “low-,” “intermediate-,” or “high-risk.”

6. 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 LVI.

7. 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.

8. Due to the high rate of upstaging associated with variant histology, a clinician should consider offering initial radical cystectomy.

9. In surveillance of NMIBC, a clinician should not use urinary biomarkers in place of cystoscopic evaluation.

10. 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.

11. 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).

12. 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.

13. 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.

14. 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.

15. 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 (eg, gemcitabine, mitomycin C) within 24 hours of TURBT. In a patient with a suspected perforation or extensive resection, a clinician should not use postoperative intravesical chemotherapy.

16. In a low-risk patient, a clinician should not administer induction intravesical therapy.

17. In an intermediate-risk patient, a clinician should consider administration of a six week course of induction intravesical chemotherapy or immunotherapy.

18. 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.

19. In an intermediate-risk patient who completely responds to an induction course of intravesical chemotherapy, a clinician may utilize maintenance therapy.

20. In an intermediate-risk patient who completely responds to induction BCG, a clinician should consider maintenance BCG for one year, as tolerated.

21. In a high-risk patient who completely responds to induction BCG, a clinician should continue maintenance BCG for three years, as tolerated.

22. 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.

23. 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.

24. 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.

25. 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.

26. In a patient with persistent or recurrent high-grade NMIBC within 12 months of completion of adequate BCG therapy (two induction courses or one induction course plus one maintenance cycle) who is unwilling or unfit for cystectomy following two courses of BCG, a clinician may recommend clinical trial enrollment, an alternative intravesical therapy (ie, nadofaragene [firadenovec-vncg]) or alternative intravesical chemotherapies (ie, gemcitabine/docetaxel). A clinician may also offer systemic immunotherapy with pembrolizumab to a patient with carcinoma in situ (CIS) within 12 months of completion of adequate BCG therapy.

27. 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.

28. 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.

29. 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.

30. In a patient with NMIBC, a clinician should offer blue light cystoscopy (BLC) at the time of TURBT, if available, to increase detection and decrease recurrence.

31. In a patient with NMIBC, a clinician may consider use of narrow-band imaging (NBI) to increase detection and decrease recurrence.

32. 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.

33. 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.

34. In an asymptomatic patient with a history of low-risk NMIBC, a clinician should not perform routine surveillance upper tract imaging.

35. 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.

36. 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.

37. 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.

38. For an intermediate- or high-risk patient, a clinician should consider performing surveillance upper tract imaging at one to two year intervals.