What is the recommended treatment approach for an older patient with bladder cancer, considering their overall health and potential comorbidities?

Treatment Approach for Older Patients with Bladder Cancer

For older patients with bladder cancer, age alone is not a contraindication to definitive treatment including radical cystectomy, though treatment selection must account for performance status, renal function, cardiac comorbidities, and disease stage to optimize survival while managing increased postoperative morbidity. 1

Initial Assessment and Staging

Before determining treatment, complete staging is essential:

• Perform cystoscopic examination with transurethral resection (TURBT) to obtain pathologic diagnosis and determine depth of invasion 1
• Obtain CT imaging of abdomen/pelvis and chest to detect enlarged lymph nodes (>8mm pelvic, >1cm abdominal) and distant metastases 1
• Assess for hydronephrosis, which predicts extra-vesical disease, node-positive disease, and poor clinical outcome 1
• Evaluate renal function (creatinine clearance), performance status (Karnofsky Performance Status), and cardiac function to determine treatment eligibility 1
• Document presence of visceral metastases, as this significantly impacts prognosis and treatment selection 1

Treatment by Disease Stage

Non-Muscle-Invasive Bladder Cancer (NMIBC)

Complete TURBT is the treatment of choice for initial bladder tumors, followed by risk-stratified intravesical therapy: 1

• For high-risk NMIBC (high-grade T1, carcinoma in situ), administer intravesical BCG therapy after complete resection 1
• Consider second TURBT within 4 weeks in high-risk tumors to ensure no residual disease 1
• If high-grade T1 or carcinoma in situ fails BCG therapy, recommend cystectomy due to high progression risk 1
• Multiple grade 3 T1 tumors with carcinoma in situ or increased depth of invasion represent very high-risk features warranting immediate cystectomy consideration 1

Muscle-Invasive Bladder Cancer (MIBC)

Radical cystectomy with extended bilateral pelvic lymphadenectomy preceded by neoadjuvant cisplatin-based chemotherapy is the standard of care for fit older patients with MIBC: 1, 2

• Administer 2-3 cycles of neoadjuvant cisplatin-based combination chemotherapy (gemcitabine/cisplatin or dose-dense MVAC) before surgery, which provides 5% absolute increase in 5-year overall survival 1, 2
• Extended lymphadenectomy (including common iliac, internal iliac, external iliac, and obturator nodes) is beneficial and potentially curative even with limited nodal involvement 1, 2
• Age is explicitly not a limiting factor for radical cystectomy, though postoperative morbidity increases with age 1
• Reconstruction options include ileal conduit or orthotopic bladder replacement depending on tumor characteristics and patient preference 1

Bladder Preservation as Alternative to Cystectomy

For older patients who refuse cystectomy or have prohibitive surgical risk, bladder preservation with trimodality therapy is a reasonable alternative with strict selection criteria:

Ideal candidates must meet ALL of the following: 2

• T2 tumor <5cm in size, solitary lesion 2
• No carcinoma in situ present 2
• No hydronephrosis (absolute contraindication) 2
• Visibly complete or maximal TURBT achievable 2
• Good performance status and adequate bladder capacity 2

Treatment protocol for bladder preservation: 2

• Maximal TURBT followed by concurrent chemoradiotherapy 2
• Cisplatin-based chemotherapy with radiation to 64-66 Gy total dose 2
• Mandatory cystoscopic restaging after induction therapy to assess response 1, 2
• If persistent disease at restaging, proceed immediately to salvage cystectomy 1, 2

Expected outcomes with bladder preservation: 2

• Complete response rate after induction: 70-87% 2
• 5-year overall survival: 50-67% 2
• Bladder-intact survival at 5 years: 40-54% 2

Metastatic Disease (Stage IVB)

For cisplatin-eligible patients with metastatic disease, gemcitabine/cisplatin or dose-dense MVAC with G-CSF support are preferred first-line regimens: 1, 3

• Cisplatin eligibility requires adequate renal function (GFR ≥60 mL/min), no significant cardiac disease, and good performance status 1, 3
• Median survival with platinum-based chemotherapy is 9-15 months, with 15% achieving long-term disease-free survival 1
• Patients with lymph-node-only disease have better outcomes (20.9% long-term survival) compared to visceral metastases (6.8%) 1

For cisplatin-ineligible older patients (GFR <60 mL/min, cardiac disease, poor performance status): 1

• Gemcitabine/carboplatin is the preferred alternative regimen, though less effective than cisplatin-based therapy 1
• Immune checkpoint inhibitors (atezolizumab, pembrolizumab) were previously approved for first-line treatment in cisplatin-ineligible patients, but FDA issued safety alerts in 2018 regarding their use in this setting 1
• For patients with performance status 2 or significant comorbidities, consider single-agent therapy or best supportive care 1

Critical Pitfalls to Avoid in Older Patients

Never attempt bladder preservation in patients with any degree of hydronephrosis, as this predicts extra-vesical disease and poor outcomes 1, 2

Do not substitute carboplatin for cisplatin in curative-intent settings (neoadjuvant therapy, bladder preservation) even with borderline renal function, as survival benefit is specific to cisplatin 1, 2

Avoid dismissing cystectomy based solely on age—postoperative morbidity increases with age but age itself is not a contraindication when performance status is adequate 1

Monitor renal function closely in elderly patients receiving cisplatin, as they are more susceptible to nephrotoxicity, and cisplatin is contraindicated with pre-existing renal impairment 3

Perform audiometric testing before each cisplatin dose in all patients, as ototoxicity is cumulative and may be severe 3

Do not give adjuvant chemotherapy after cystectomy if neoadjuvant chemotherapy was already administered 2

Special Considerations for Comorbid Conditions

Cardiac disease: 1, 3

• Avoid anthracycline-containing regimens (MVAC) in patients with significant cardiac dysfunction 3
• Consider gemcitabine/cisplatin as alternative if cardiac function precludes anthracyclines 1
• Cisplatin can cause electrolyte abnormalities requiring cardiac monitoring 3

Renal impairment: 1, 3

• Calculate creatinine clearance (not just serum creatinine) to determine cisplatin eligibility 3
• For GFR <60 mL/min, cisplatin is contraindicated and carboplatin-based regimens or immunotherapy should be considered 1, 3
• Aggressive hydration and mannitol diuresis are required with cisplatin to reduce nephrotoxicity 3

Poor performance status (KPS <80): 1

• Patients with KPS <80 have significantly worse prognosis (median survival 9.3 months with two risk factors vs 33 months with no risk factors) 1
• Consider palliative radiotherapy for symptom control (bleeding, pain) rather than aggressive systemic therapy 1
• Single-agent chemotherapy or best supportive care may be more appropriate than combination regimens 1

Follow-Up Protocols

After radical cystectomy: 2

• Urine cytology, liver function tests, creatinine, and electrolytes every 3-6 months for 2 years 2
• Imaging of chest, abdomen, and pelvis every 3-12 months for 2 years based on recurrence risk 2

After bladder preservation: 1, 2

• Cystoscopy with cytology every 3 months for first 2 years, then every 6 months thereafter 1, 2
• Upper tract imaging every 1-2 years for high-grade tumors 2
• Continued monitoring is mandatory as recurrence risk remains throughout life 1