What is the recommended initial management for a patient with non‑invasive high‑grade papillary urothelial carcinoma (Ta, high‑grade)?

Treatment for Non-Invasive High-Grade Papillary Urothelial Carcinoma (Ta, High-Grade)

For patients with non-invasive high-grade papillary urothelial carcinoma (Ta, high-grade), perform a repeat transurethral resection within 2-6 weeks if no muscle was present in the initial specimen or if resection was incomplete, followed by intravesical BCG therapy (6-week induction plus maintenance for 1-3 years). 1

Initial Surgical Management

Repeat TURBT Indications

A repeat TURBT should be strongly considered within 2-6 weeks for all high-grade Ta tumors, particularly when: 1, 2

• No muscularis propria is present in the initial specimen - this represents the highest priority indication, as 49% of patients will be understaged without muscle in the specimen 3
• The initial resection was incomplete (visible residual tumor or uncertain margins) 1
• Large or multifocal high-grade lesions are present 1

The repeat resection should specifically target the original tumor site and include deep tissue to ensure adequate muscle sampling. 3 Even when muscle was present in the original resection, restaging TURBT detected residual disease in 27% of patients with Ta tumors. 3

Intravesical Therapy

Primary Treatment Recommendation

After complete resection, intravesical BCG is the preferred adjuvant treatment over mitomycin C for high-grade Ta lesions. 1

BCG Induction Protocol

• Administer a 6-week induction course of BCG for newly diagnosed high-grade Ta urothelial carcinoma 1
• BCG is given as weekly instillations for 6 weeks 1
• Four meta-analyses confirm that BCG after TUR is superior to TUR alone or TUR with chemotherapy in preventing recurrences 1

BCG Maintenance Protocol

For high-risk patients (including high-grade Ta), continue maintenance BCG for 1-3 years as tolerated: 1

• Maintenance consists of weekly instillations for 3 weeks at 3,6,12,18,24,30, and 36 months 1
• Three-year maintenance BCG significantly reduces the risk of recurrence compared with 1-year maintenance (HR 1.61,95% CI 1.13-2.30, P = 0.01) in high-risk tumors 1
• For intermediate-risk high-grade Ta tumors, 1 year of maintenance BCG may be sufficient 1

Alternative to BCG

If BCG is contraindicated or not tolerated, mitomycin C may be administered as an alternative intravesical chemotherapy agent. 1 However, this is considered a second-line option for high-grade disease.

Surveillance Protocol

After treatment, implement the following surveillance schedule: 1

• Cystoscopy and urinary cytology every 3 months for the first 1-2 years 1
• Repeat at increasing intervals over the next 2 years 1
• Annual surveillance thereafter 1
• Upper tract imaging should be considered every 1-2 years for high-grade tumors 1

Management After BCG Treatment

12-Week Evaluation

At the 12-week evaluation after BCG induction: 1

• If no residual disease is found: Continue with maintenance BCG as outlined above 1
• If persistent high-grade Ta disease is present: Consider a second induction course of BCG (no more than 2 consecutive induction courses should be given) 1

BCG-Unresponsive Disease

For patients with BCG-unresponsive disease (persistent high-grade disease at 6 months despite adequate BCG, or recurrence within 6 months of last BCG), radical cystectomy should be offered. 1 BCG-unresponsive disease carries a high risk of progression and warrants definitive surgical management. 1

Role of Radical Cystectomy

Early radical cystectomy should be considered in very high-risk scenarios: 1

• Persistent high-grade T1 disease on repeat resection (though this is technically beyond Ta disease) 1
• BCG-unresponsive high-grade Ta disease 1
• Patient preference after thorough discussion of risks and benefits 1

However, for Ta high-grade disease without these features, cystectomy is rarely considered initially, and bladder-sparing modalities should be attempted first. 1

Critical Pitfalls to Avoid

Do not assume adequate staging without muscle in the specimen - this represents a 49% risk of understaging and mandates repeat resection. 3 The absence of muscularis propria in the initial specimen is the single most important indication for repeat TURBT.

Do not use BCG for low-grade Ta tumors - BCG is not recommended for low-grade disease due to the low risk of progression and should be reserved specifically for high-grade lesions. 1, 4

Do not delay repeat resection beyond 6 weeks - optimal timing is 2-6 weeks after initial TURBT to maximize therapeutic benefit. 1, 3, 2

Do not discontinue maintenance BCG prematurely - while toxicity may limit duration, the full 3-year maintenance course provides superior recurrence prevention in high-risk patients compared to 1-year maintenance. 1

Do not skip the 12-week evaluation - this critical assessment determines response to BCG and guides subsequent management decisions. 1