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 cancer 1 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 muscleinvasive 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 2650% of patients, and lymph node disease is found in 9-18% of patients. Bladder cancerspecific 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 overtreatment 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 % Upstaging
patients
LN +
Bladder-cancer
survival
Overall
survival
Herr 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%
References
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Jemal, A., Siegel, R., Xu, J. & Ward, E. Cancer statistics, 2010. CA Cancer J Clin 60,
277-300, (2010).
Strope, S. A., Ye, Z., Hollingsworth, J. M. & Hollenbeck, B. K. Patterns of care for
early stage bladder cancer. Cancer 116, 2604-2611, (2010).
Dutta, S. C. et al. Clinical under staging of high risk nonmuscle invasive urothelial
carcinoma treated with radical cystectomy. J Urol 166, 490-493, (2001).
Nepple, K. G. & O'Donnell, M. A. The optimal management of T1 high-grade
bladder cancer. Can Urol Assoc J 3, S188-192 (2009).
Stein, J. P. & Penson, D. F. Invasive T1 bladder cancer: indications and rationale
for radical cystectomy. BJU Int 102, 270-275, (2008).
Lambert, E. H. et al. The increasing use of intravesical therapies for stage T1
bladder cancer coincides with decreasing survival after cystectomy. BJU Int 100,
33-36, (2007).
Herr, H. W. & Sogani, P. C. Does early cystectomy improve the survival of
patients with high risk superficial bladder tumors? J Urol 166, 1296-1299, (2001).
Thalmann, G. N. et al. Primary T1G3 bladder cancer: organ preserving approach
or immediate cystectomy? J Urol 172, 70-75, (2004).
Masood, S., Sriprasad, S., Palmer, J. H. & Mufti, G. R. T1G3 bladder cancer-indications for early cystectomy. Int Urol Nephrol 36, 41-44 (2004).
Bianco, F. J., Jr. et al. Management of clinical T1 bladder transitional cell
carcinoma by radical cystectomy. Urol Oncol 22, 290-294, (2004).
Gupta, A. et al. Outcomes of patients with clinical T1 grade 3 urothelial cell
bladder carcinoma treated with radical cystectomy. Urology 71, 302-307, (2008).
Denzinger, S. et al. Early versus deferred cystectomy for initial high-risk pT1G3
urothelial carcinoma of the bladder: do risk factors define feasibility of bladdersparing approach? Eur Urol 53, 146-152, (2008).
Konety, B. R., Allareddy, V. & Herr, H. Complications after radical cystectomy:
analysis of population-based data. Urology 68, 58-64, (2006).
Shabsigh, A. et al. Defining early morbidity of radical cystectomy for patients
with bladder cancer using a standardized reporting methodology. Eur Urol 55,
164-174, (2009).
Aghazadeh, M. A. et al. Determining factors for hospital discharge status after
radical cystectomy in a large contemporary cohort. J Urol 185, 85-89, (2011).
Bochner, B. H. Optimal timing of radical cystectomy for patients with T1 bladder
cancer. Urol Oncol 27, 329-331, (2009).
Montgomery, J. S., Weizer, A. Z. & Montie, J. E. T1 bladder cancer: advocating
early cystectomy to improve oncologic control. Urol Oncol 28, 466-468, (2010).
Huang, G. J., Hamilton, A. S., Lo, M., Stein, J. P. & Penson, D. F. Predictors of
intravesical therapy for nonmuscle invasive bladder cancer: results from the
surveillance, epidemiology and end results program 2003 patterns of care
project. J Urol 180, 520-524; discussion 524, (2008).
19
20
Hollingsworth, J. M., Miller, D. C., Daignault, S. & Hollenbeck, B. K. Rising
incidence of small renal masses: a need to reassess treatment effect. J Natl
Cancer Inst 98, 1331-1334, (2006).
Eggener, S. E. et al. Predicting 15-year prostate cancer specific mortality after
radical prostatectomy. J Urol 185, 869-875, (2011).
Daniel J. Canter, MD
Assistant Professor of Urology, Emory University