High-Grade T1 Bladder Cancer: A Clinical Quandary
Daniel J. Canter, MD
Assistant Professor of Urology, Emory University
for
In 2010, there were an estimated 70,520 new cases of bladder cancer1 of which approximately 13,000 cases were diagnosed as clinical high-grade T1 bladder cancer.2 One of the key components of the evaluation of patients with high-grade T1 bladder cancer is the role of a re-resection or second TUR of the tumor bed 4-6 weeks after the initial diagnosis. This re-resection has both diagnostic and prognostic importance: (1) anywhere from 30-60% of patients will be upstaged to muscle-invasive disease3, and (2) the presence of residual T1 disease implies a 76% chance of progression to muscle-invasive disease4. This subset of patients represents a unique clinical challenge in that although technically these patients do not have muscle-invasive disease, the lamina propria—layer of extension of bladder tumors in T1 disease-is where the lymphatic and vascular channels responsible for tumor metastasis reside.5 According to the recent National Cancer Center Network (NCCN) Guidelines, the 5-year probability of recurrence in patients with high-grade T1 bladder cancer is 50-70%, and the risk of progression to muscle-invasive disease is “moderate to high”. According to the AUA Guidelines for the Management of Superficial Bladder Cancer, intravesical therapy with BCG is the recommended first-line treatment for high-grade T1 bladder cancer. However, some authors have shown that the increasing use of BCG in these patients is associated with worse recurrence-free and bladder-cancer specific survivals.6 Thus, there has been a growing sentiment that these patients should be offered an immediate/early cystectomy as their best chance for cure.
There have been a number of small, single institutional series that have demonstrated that patients with high-grade T1 bladder cancer have improved bladder cancer-specific survival if they undergo an immediate/early radical cystectomy.3,7-12 Table 1 summarizes the pathological and clinical outcomes of these radical cystectomy series for patients with high-grade T1 bladder cancer. Pathologic upstaging occurs in 26-50% of patients, and lymph node disease is found in 9-18% of patients. Bladder cancer-specific survival ranges from 69-93%. Thus, there appears to be a survival advantage from an early/immediate cystectomy in medically fit patients. Nevertheless, the concern exists that cystectomy over-treats these patients while subjecting them to the morbidity and potential mortality of this extirpative and reconstructive operation is real: post-operative complication rates range from 28.1-64%13-14 and 90-day mortality rates for patients after radical cystectomy range from 2.57-20.5%13,15. Due to these competing issues, many authors have tried to devise criteria to risk stratify high-grade T1 bladder cancer. Using this risk criteria, urologists, perhaps, can choose better which patients should be offered an early cystectomy. For example, large tumor size, multifocal disease, the concomitant presence of CIS, high-risk histology (micropapillary, adenocarcinoma, etc.), incomplete resection, difficult to access tumor, and the presence of lymphvascular invasion have all been proposed as high-risk criteria that would argue for an immediate/early cystectomy.16-17 Despite this push advocating for early cystectomy in patients with high-grade T1 bladder cancer, recent population-based data show that only 3.3% of patients with high-grade T1 bladder cancer underwent a cystectomy to treat their disease.18 This data is in stark contrast to the T1 renal mass and T1c prostate cancer where despite questionable impact on survival, patients with these cancers are routinely surgically treated.19-20 High-grade T1 bladder cancer has an aggressive biologic phenotype that, in the majority of cases, seems destined to progress. Thus, delaying definitive surgery, despite its inherent risks, may be ultimately more risky than proceeding with cystectomy. This dynamic of diagnosis and under-treatment is contrasted against early-stage renal and prostate cancers where diagnosis and over-treatment exists.
Table 1. Existing Single Institutional Radical Cystectomy Series Examining Pathologic and Survival Outcomes in Patients with Clinical High-Grade T1 Disease
Series / No. of patients / % Upstaging / LN + / Bladder-cancer survival / Overall survivalHerr and Sogani / 35 / NR / NR / 92% / NR
Dutta et al / 78 / 40 / 12 / 78% / 64
Thalmann et al / 29 / 41 / 14 / 69% / 54
Masood et al / 30 / 27 / NR / 88% / NR
Bianco et al / 66 / 27 / 9 / 78% / NR
Lambert et al / 104 / 40 / NR / 93% / 87
Gupta et al / 167 / 50 / 18 / 82% / 69
Denzinger et al / 54 / 26 / NR / 78% / NR
Total / 563 / 26-50% / 9-18% / 69-93% / 54-87%
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Daniel J. Canter, MD
Assistant Professor of Urology, Emory University