Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline

There are 79,030 new cases of bladder cancer and 16,870 bladder cancer deaths predicted for 2017 in the U.S.6 Approximately 25% of newly diagnosed patients have muscle-invasive disease,7,8 a rate that has not changed over the last 10 years based on data from the Surveillance, Epidemiology, and End Results (SEER) registry.9 In addition, up to 50% or more patients with high-risk non-muscle invasive bladder cancer (NMIBC) can progress to invasive disease.

In 2020 AUA, ASCO, ASTRO and SUO jointly released guidelines on Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer For the purposes of this guideline, clinical framework for the management of muscle-invasive urothelial bladder cancer. Topics covered include patient evaluation and counseling, as well as an in-depth discussion of treatment options, including chemotherapy, cystectomy, urinary diversion, lymphadenectomy, and variou bladder preserving treatment options.

Following are its major recommendations:

1. Prior to treatment consideration, a full history and physical exam should be performed, including an exam under anesthesia, at the time of transurethral resection of bladder tumor for a suspected invasive cancer. (Clinical Principle)

2. Prior to muscle-invasive bladder cancer management, clinicians should perform a complete staging evaluation, including imaging of the chest and cross sectional imaging of the abdomen and pelvis with intravenous contrast if not contraindicated. Laboratory evaluation should include a comprehensive metabolic panel (complete blood count, liver function tests, alkaline phosphatase, and renal function). (Clinical Principle)

3. An experienced genitourinary pathologist should review the pathology of a patient when variant histology is suspected or if muscle invasion is equivocal (e.g., micropapillary, nested, plasmacytoid, neuroendocrine, sarcomatoid, extensive squamous or glandular differentiation). (Clinical Principle)

4. For patients with newly diagnosed muscle-invasive bladder cancer, curative treatment options should be discussed before determining a plan of therapy that is based on both patient comorbidity and tumor characteristics. Patient evaluation should be completed using a multidisciplinary approach. (Clinical Principle)

5. Prior to treatment, clinicians should counsel patients regarding complications and the implications of treatment on quality of life (e.g., impact on continence, sexual function, fertility, bowel dysfunction, metabolic problems). (Clinical Principle)

6. Utilizing a multidisciplinary approach, clinicians should offer cisplatin-based neoadjuvant chemotherapy to eligible radical cystectomy patients prior to cystectomy. (Strong Recommendation; Evidence Level: Grade B)

7. Clinicians should not prescribe carboplatin-based neoadjuvant chemotherapy for clinically resectable stage cT2-T4aN0 bladder cancer. Patients ineligible for cisplatin-based neoadjuvant chemotherapy should proceed to definitive locoregional therapy or clinical trial. (Expert Opinion)

8. Clinicians should perform radical cystectomy as soon as possible following a patient's completion of and recovery from neoadjuvant chemotherapy (ideally within 12 weeks unless medically inadvisable). (Expert Opinion)

9. Eligible patients who have not received cisplatin-based neoadjuvant chemotherapy and have non-organ confined (pT3/T4and/or N+) disease at cystectomy should be offered adjuvant cisplatin-based chemotherapy. (Moderate Recommendation; Evidence Level: Grade C)

10. Clinicians should offer radical cystectomy with bilateral pelvic lymphadenectomy for surgically eligible patients with resectable non-metastatic (M0) muscle-invasive bladder cancer. (Strong Recommendation; Evidence Level: Grade B)

11. When performing a standard radical cystectomy with curative intent, clinicians should remove the bladder, prostate, and seminal vesicles in males; clinicians should remove the bladder in females and should consider removal of adjacent reproductive organs based on individual disease characteristics and need to obtain negative margins. (Clinical Principle)

12. Clinicians should discuss and consider sexual function preserving procedures for patients with organ-confined disease and absence of bladder neck, urethra, and prostate (male) involvement. (Moderate Recommendation; Evidence Level: Grade C)

13. In patients undergoing radical cystectomy, ileal conduit, continent cutaneous, and orthotopic neobladder urinary diversions should all be discussed. (Clinical Principle)

14. In patients receiving an orthotopic urinary diversion, clinicians must verify a negative urethral margin. (Clinical Principle)

15. Clinicians should attempt to optimize patient performance status in the perioperative setting. (Expert Opinion)

16. Perioperative pharmacologic thromboembolic prophylaxis should be given to patients undergoing radical cystectomy. (Strong Recommendation; Evidence Level: Grade B)

17. In patients undergoing radical cystectomy µ -opioid antagonist therapy should be used to accelerate gastrointestinal recovery, unless contraindicated. (Strong Recommendation; Evidence Level: Grade B)

18. Patients should receive detailed teaching regarding care of urinary diversion prior to discharge from the hospital. (Clinical Principle)

19. Clinicians must perform a bilateral pelvic lymphadenectomy at the time of any surgery with curative intent. (Strong Recommendation; Evidence Level: Grade B)

20. When performing bilateral pelvic lymphadenectomy, clinicians should remove, at a minimum, the external and internal iliac and obturator lymph nodes (standard lymphadenectomy). (Clinical Principle)

21. For patients with newly diagnosed non-metastatic muscle-invasive bladder cancer who desire to retain their bladder, and for those with significant comorbidities for whom radical cystectomy is not a treatment option, clinicians should offer bladder preserving therapy when clinically appropriate. (Clinical Principle)

22 In patients under consideration for bladder preserving therapy, maximal debulking transurethral resection of bladder tumor and assessment of multifocal disease/carcinoma in situ should be performed. (Strong Recommendation; Evidence Level: Grade C)

23. Patients with muscle-invasive bladder cancer who are medically fit and consent to radical cystectomy should not undergo partial cystectomy or maximal transurethral resection of bladder tumor as primary curative therapy. (Moderate Recommendation; Evidence Level: Grade C)

24. For patients with muscle-invasive bladder cancer, clinicians should not offer radiation therapy alone as a curative treatment. (Strong Recommendation; Evidence Level: Grade C)

25. For patients with muscle-invasive bladder cancer who have elected multi-modal bladder preserving therapy, clinicians should offer maximal transurethral resection of bladder tumor, chemotherapy combined with external beam radiation therapy, and planned cystoscopic re-evaluation. (Strong Recommendation; Evidence Level: Grade B)

26. Radiation sensitizing chemotherapy should be included when using multimodal therapy with curative intent. (Strong Recommendation; Evidence Level: Grade B)

27. Following completion of bladder preserving therapy, clinicians should perform regular surveillance with CT scans, cystoscopy, and urine cytology. (Strong Recommendation; Evidence Level: Grade C)

28. In patients who are medically fit and have residual or recurrent muscle-invasive disease following bladder preserving therapy, clinicians should offer radical cystectomy with bilateral pelvic lymphadenectomy. (Strong Recommendation; Evidence Level: Grade C)

29. In patients who have a non-muscle invasive recurrence after bladder preserving therapy, clinicians may offer either local measures, such as transurethral resection of bladder tumor with intravesical therapy, or radical cystectomy with bilateral pelvic lymphadenectomy. (Moderate Recommendation; Evidence Level: Grade C)

30. Clinicians should obtain chest imaging and cross sectional imaging of the abdomen and pelvis with CT or MRI at 6-12 month intervals for 2-3 years and then may continue annually. (Expert Opinion)

31. Following therapy for muscle-invasive bladder cancer, patients should undergo laboratory assessment at three to six month intervals for two to three years and then annually thereafter. (Expert Opinion)

32. Following radical cystectomy in patients with a retained urethra, clinicians should monitor the urethral remnant for recurrence. (Expert Opinion)

33. Clinicians should discuss with patients how they are coping with their bladder cancer diagnosis and treatment and should recommend that patients consider participating in cancer support groups or consider receiving individual counseling. (Expert Opinion)

34. Clinicians should encourage bladder cancer patients to adopt healthy lifestyle habits, including smoking cessation, exercise, and a healthy diet, to improve long-term health and quality of life. (Expert Opinion)

35. In patients diagnosed with variant histology, clinicians should consider unique clinical characteristics that may require divergence from standard evaluation and management for urothelial carcinoma. (Expert Opinion)

Note:

The AUA categorizes body of evidence strength as Grade A (well-conducted and highly-generalizable RCTs or exceptionally strong observational studies with consistent findings), Grade B (RCTs with some weaknesses of procedure or generalizability or moderately strong observational studies with consistent findings), or Grade C (RCTs with serious deficiencies of procedure or generalizability or extremely small sample sizes or observational studies that are inconsistent, have small sample sizes, or have other problems that potentially confound interpretation of data). A Clinical Principle is a statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature. Expert Opinion refers to a statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge, and judgment for which there is no evidence.

Reference:

Chang SS, Bochner BH, Chou R et al: Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO guideline. J Urol 2017; 198: 552.