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    Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer (beta)

    Based on guidelines from AUA, ASCO, ASTRO, and SUO.

    Strength
    Strong recommendation
    Moderate recommendation
    Conditional recommendation
    Evidence
    Grade A quality evidence
    Grade B quality evidence
    Grade C quality evidence
    Clinical principle
    Expert opinion

    Initial Evaluation and Counseling

    Evaluation
    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.
    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).
    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).
    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.
    Counseling
    1. 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).

    Treatment

    Neoadjuvant/Adjuvant Chemotherapy
    1. Utilizing a multidisciplinary approach, clinicians should offer cisplatin-based neoadjuvant chemotherapy to eligible radical cystectomy patients prior to cystectomy.
    2. 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.
    3. Clinicians should perform radical cystectomy as soon as possible following a patient’s completion of and recovery from neoadjuvant chemotherapy.
    4. 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.
    Radical Cystectomy
    1. Clinicians should offer radical cystectomy with bilateral pelvic lymphadenectomy for surgically eligible patients with resectable non-metastatic (M0) muscle-invasive bladder cancer.
    2. When performing a standard radical cystectomy, clinicians should remove the bladder, prostate, and seminal vesicles in males and should remove the bladder, uterus, fallopian tubes, ovaries, and anterior vaginal wall in females.
    3. 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.
    Urinary Diversion
    1. In patients undergoing radical cystectomy, ileal conduit, continent cutaneous, and orthotopic neobladder urinary diversions should all be discussed.
    2. In patients receiving an orthotopic urinary diversion, clinicians must verify a negative urethral margin.
    Perioperative Surgical Management
    1. Clinicians should attempt to optimize patient performance status in the perioperative setting.
    2. Perioperative pharmacologic thromboembolic prophylaxis should be given to patients undergoing radical cystectomy.
    3. In patients undergoing radical cystectomy µ-opioid antagonist therapy should be used to accelerate gastrointestinal recovery, unless contraindicated.
    4. Patients should receive detailed teaching regarding care of urinary diversion prior to discharge from the hospital.
    Pelvic Lymphadenectomy
    1. Clinicians must perform a bilateral pelvic lymphadenectomy at the time of any surgery with curative intent.
    2. When performing bilateral pelvic lymphadenectomy, clinicians should remove, at a minimum, the external and internal iliac and obturator lymph nodes (standard lymphadenectomy).

    Bladder Preserving Approaches

    Patient Selection
    1. 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.
    2. 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.
    Maximal TURBT and Partial Cystectomy
    1. 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 (TURBT) as primary curative therapy.
    Primary Radiation Therapy
    1. For patients with muscle-invasive bladder cancer, clinicians should not offer radiation therapy alone as a curative treatment.
    Multi-Modal Bladder Preserving Therapy
    1. 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 reevaluation.
    2. Radiation sensitizing chemotherapy regimens should include cisplatin or 5-fluorouracil and mitomycin C.
    3. Following completion of bladder preserving therapy, clinicians should perform regular surveillance with CT scans, cystoscopy, and urine cytology.
    Bladder Preserving Treatment Failure
    1. 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.
    2. 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.

    Surveillance and Follow Up

    Imaging
    1. 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.
    Laboratory Values and Urine Markers
    1. 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.
    2. Following radical cystectomy in patients with a retained urethra, clinicians should monitor the urethral remnant for recurrence.
    Patient Survivorship
    1. 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.
    2. 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.
    Variant Histology
    1. In patients diagnosed with variant histology, clinicians should consider unique clinical characteristics that may require divergence from standard evaluation and management for urothelial carcinoma.
    What do the icons mean?  
    Research PaperChang SS, Bochner BH, Chou R, et al. Treatment of Nonmetastatic Muscle-Invasive Bladder Cancer: American Urological Association/American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Urologic Oncology Clinical Practice Guideline Summary. J Oncol Pract. 2017;13(9):621-625.