What are the treatment options for bladder cancer?

Treatment Options for Bladder Cancer

Treatment of bladder cancer depends fundamentally on whether the tumor is non-muscle invasive (NMIBC) or muscle-invasive (MIBC), with transurethral resection forming the foundation for NMIBC and radical cystectomy with neoadjuvant chemotherapy being the standard for MIBC. 1

Non-Muscle Invasive Bladder Cancer (NMIBC)

Initial Management

• Complete transurethral resection of bladder tumor (TURBT) is the primary treatment for any initial bladder tumor, serving both diagnostic and therapeutic purposes 1, 2
• Multiple selective and/or random biopsies must be performed when carcinoma in situ is suspected or known 1
• Repeat TURBT is mandatory if no muscle is present in the specimen for high-grade disease, any T1 lesion is present, or the first resection does not allow adequate staging 1

Risk-Stratified Adjuvant Therapy

Low-Risk Tumors:

• Observation or single-dose intravesical chemotherapy within 24 hours of TURBT 1
• Cystoscopy follow-up at 3 months, then at increasing intervals 1

Intermediate-Risk Tumors:

• Multiple chemotherapeutic instillations with mitomycin 1

High-Risk Tumors:

• BCG intravesical therapy is the standard, preventing recurrences and reducing mortality by 23% 1

Muscle-Invasive Bladder Cancer (MIBC)

Standard Surgical Approach

Radical cystectomy with extended bilateral pelvic lymphadenectomy is the gold standard for MIBC 3, 1:

• In men: cystoprostatectomy including removal of prostate, seminal vesicles, proximal vas deferens, and proximal urethra 3
• In women: cystectomy with hysterectomy including uterus, ovaries, fallopian tubes, urethra, and part of vagina 3
• Pelvic lymph node dissection must include at minimum the common iliac, internal iliac, external iliac, and obturator nodes 1
• More extensive PLND may include lower para-aortic or para-caval nodes and is associated with better survival and lower pelvic recurrence rates 3

Urinary Diversion Options

• Ileal conduit (external collection) 3
• Continent pouch with drainage to abdominal wall 3
• Orthotopic neobladder (urethral drainage) - provides closest function to native bladder but carries increased risk of nighttime incontinence and urinary retention requiring intermittent self-catheterization 3
• Relative contraindications to urethral drainage include carcinoma in situ in prostatic ducts or positive urethral margin 3

Neoadjuvant Chemotherapy

Cisplatin-based combination chemotherapy before cystectomy is strongly recommended (Category 1 evidence) 1:

• Recommended regimens: DDMVAC, gemcitabine and cisplatin, or CMV 4
• Cisplatin is FDA-approved as a single agent for transitional cell bladder cancer no longer amenable to local treatments 5
• Cisplatin produces cumulative nephrotoxicity and should not be given more frequently than once every 3-4 weeks 5
• Contraindicated in patients with pre-existing renal impairment, myelosuppression, or hearing impairment 5

Adjuvant Therapy

• For pathologic T3, T4, or node-positive disease after cystectomy, adjuvant chemotherapy should be considered 4

Partial Cystectomy

Partial cystectomy is appropriate in <5% of cases 3:

• Solitary lesions in locations amenable to segmental resection with adequate margins 1
• No carcinoma in situ present elsewhere in the urothelium 1
• Most frequently recommended for lesions on the dome of the bladder 3
• Relative contraindications: lesions in the trigone or bladder neck 3

Bladder Preservation (Trimodality Therapy)

May be considered for highly selected patients 1:

• Initial T2 tumors <5 cm 1
• No carcinoma in situ 1
• Good performance status 1
• Consists of maximal TURBT, concurrent chemotherapy, and radiation therapy 3
• Radiation doses: 66-70 Gy to gross primary disease, 54-66 Gy to gross nodal disease 3
• Complete response rates of 70-80% are achieved, with 85% remaining free of invasive recurrence in the bladder 6
• Overall 5-year survival approximately 50%, with 40-45% maintaining intact bladder 6

Advanced/Metastatic Bladder Cancer

• Platinum-based combination chemotherapy (MVAC or gemcitabine-cisplatin) is first-line therapy (Category 1 evidence) 1
• Cisplatin is FDA-approved as monotherapy for advanced disease 5

Special Histologic Variants

Small Cell Carcinoma

Requires neoadjuvant chemotherapy using small cell lung cancer regimens (etoposide-cisplatin) followed by radical cystectomy or radiotherapy, regardless of stage 7:

• 4 cycles of platinum-based regimen before surgery 7
• Highly aggressive with high metastatic potential 7

Sarcomatoid Features

• Radical cystectomy with neoadjuvant cisplatin-based chemotherapy is standard 4
• Bladder preservation generally not recommended due to aggressive nature 4
• Delaying cystectomy beyond 3 months from diagnosis negatively impacts outcomes 4

Follow-Up Protocols

After Radical Cystectomy

• Urine cytology, creatinine, and electrolytes every 3-6 months for 2 years, then as clinically indicated 1, 7
• Imaging of chest, abdomen, and pelvis every 3-12 months for 2 years based on recurrence risk 1, 7

After Bladder Preservation

• Cystoscopy and urinary cytology every 3 months during first 2 years, then every 6 months 1, 7
• Upper tract imaging every 1-2 years for high-grade tumors 1

Critical Pitfalls to Avoid

• Understaging occurs in 42% of patients - clinical staging with cystoscopy, EUA, and TURBT has modest accuracy even with cross-sectional imaging 3
• Inadequate lymphadenectomy may miss occult nodal disease 4
• Incomplete initial TURBT is the major reason for high recurrence rates 2
• Extended TURBT with additional deep and marginal specimens reveals residual tumor in 38% of cases across all stages and 22% in non-muscle-invasive tumors 8