What are the contraindications for bladder preservation therapy in patients with impaired renal function, significant bladder dysfunction, or a history of pelvic radiation or genetic syndromes?

Contraindications for Bladder Preservation Therapy

Bladder preservation therapy is contraindicated in patients with pre-existing renal impairment (as cisplatin cannot be safely administered), tumor-related hydronephrosis, extensive carcinoma in situ, poor bladder function, obstructed ureters, and tumors larger than 5 cm or multifocal disease. 1, 2

Absolute Contraindications

Renal Function Impairment

• Pre-existing renal impairment is an absolute contraindication because cisplatin, the cornerstone radiosensitizing agent for bladder preservation, cannot be used in patients with compromised kidney function 2
• The FDA drug label explicitly states that cisplatin is contraindicated in patients with pre-existing renal impairment, as it produces cumulative nephrotoxicity 2
• Carboplatin should not be substituted for cisplatin in the bladder preservation setting, as it lacks equivalent efficacy 3

Tumor-Related Factors

• Hydronephrosis is a contraindication to bladder preservation therapy, as it predicts poor outcomes and indicates advanced local disease 3, 1
• Extensive carcinoma in situ (CIS) associated with the muscle-invasive tumor excludes patients from bladder-sparing approaches 3, 1
• Tumors larger than 5 cm or multifocal lesions are not suitable for bladder preservation 1
• Palpable bladder mass on examination under anesthesia indicates locally advanced disease unsuitable for organ preservation 1

Bladder Function Issues

• Significant bladder dysfunction or inadequate bladder capacity precludes successful bladder preservation 1
• Patients must have good baseline bladder function to maintain quality of life after chemoradiotherapy 1

Relative Contraindications

Patient Performance Status

• Poor performance status makes patients unsuitable for the intensive trimodality approach requiring maximal TURBT, concurrent chemoradiation, and frequent monitoring 3
• Patients with extensive comorbid disease should be considered for alternative approaches such as TURBT alone, radiotherapy plus chemotherapy, or chemotherapy alone 3

Hematologic Factors

• Myelosuppression is a contraindication per the cisplatin FDA label, as patients cannot tolerate concurrent chemoradiation 2

Prior Pelvic Radiation

• Patients who have undergone full-course pelvic radiotherapy (>65 Gy) cannot receive additional radiation for bladder preservation 3
• Prior pelvic radiation limits the ability to deliver adequate doses for tumor control 3

Hearing Impairment

• Pre-existing hearing impairment is a contraindication to cisplatin use, as the drug causes cumulative ototoxicity 2
• Audiometric testing should be performed prior to initiating therapy 2

Disease Stage Considerations

Advanced Local Disease (T3b-T4)

• T3b and T4a disease with extensive extravesical extension has poor outcomes with bladder preservation, as the proportion rendered tumor-free is low 3
• T4b disease or positive lymph nodes should be managed with systemic chemotherapy rather than bladder preservation attempts 3

Inability to Achieve Complete TURBT

• Incomplete resection with residual visible tumor after maximal TURBT is a relative contraindication, as visibly complete resection with pT0 status is crucial for success 1
• Patients should undergo repeat TURBT if no muscle is present in the initial specimen or if resection is incomplete 3

Critical Pitfalls to Avoid

• Do not attempt bladder preservation in patients with any degree of hydronephrosis, as this consistently predicts treatment failure 3, 1
• Never substitute carboplatin for cisplatin in the bladder preservation setting, even with borderline renal function—consider split-dose cisplatin (35 mg/m² on days 1 and 2) instead, though efficacy is undefined 3
• Avoid bladder preservation in patients with diffuse CIS, as concurrent extensive CIS significantly reduces success rates 3, 1
• Do not proceed without confirming adequate bladder capacity and function, as patients must maintain quality of life with the preserved organ 1