Platinum Priority – Urothelial CancerEditorial by David R. Yates on pp. 83–84 of this issuePrognostic Factors and Risk Groups in T1G3 Non–Muscle-invasive Bladder Cancer Patients Initially Treated with Bacillus Calmette-Guérin: Results of a Retrospective Multicenter Study of 2451 Patients
Introduction
T1G3 is considered to be a high-risk subgroup of non–muscle-invasive bladder cancer (NMIBC). Its natural history suggests an unfavorable long-term outcome, as documented by early untreated series reporting 27–65% disease progression rates [1] and a 34% cancer-specific death rate [2].
Bacillus Calmette-Guérin (BCG) is currently viewed as the gold standard conservative treatment option for T1G3 tumors [3], [4]. This policy is based on several inconsistent retrospective series reporting a 5-yr disease-specific survival of up to 80% [5]. Meta-analyses including relatively small numbers of T1G3 patients have reached conflicting conclusions concerning the ability of BCG to reduce the risk of progression [6], [7]. One-third of T1G3 patients will eventually progress under BCG [5] with a considerable risk of dying of their disease because of delaying radical surgery [8]. Early cystectomy, advocated by some authors as an alternative to BCG, has shown long-term survival rates not exceeding 80% [9], meaning that it does not guarantee cure for T1G3 tumors. The current understanding of T1G3 disease suggests that BCG is a feasible first-line treatment option, while cystectomy should be recommended in the presence of unfavorable prognostic factors [3], [4], [10], [11]. Integrating prognostic factors to develop risk groups would be particularly helpful in clinical decision making for T1G3 patients. Current scoring systems that predict clinical outcomes in NMIBC [12], [13] are inadequate for this purpose because of the low rate of T1G3 patients in these series.
The aim of the current study is to assess outcome-related prognostic factors in a large cohort of patients who received BCG as initial treatment of T1G3 tumors and to identify subgroups of high-risk patients who should be considered for more aggressive treatment.
Section snippets
Study design
This is a multicenter retrospective study including patients from 23 different centers.
Inclusion criteria
Patients who have histologically confirmed T1G3 tumors (World Health Organization [WHO] 1973) or T1 high-grade tumors (International Society of Urological Pathology 1998/WHO 2004) on bladder biopsy or transurethral resection (TUR) and who received at least an induction course of BCG as their initial intravesical treatment for a T1G3/high-grade tumor from 1990 to 2011 were eligible. Patients with a previous
Results
In November 2010, 25 centers agreed to take part in the study. Individual patient data from each center were checked electronically, and queries were sent back to investigators to provide missing data and correct inconsistencies. All patients from two centers were excluded for quality control reasons. Patients from 23 centers were retained for the study, with between 9 and 396 patients per center, for a total of 2451 patients who met the eligibility criteria (Supplemental Table 1).
Discussion
In the largest-ever reported series of T1G3 patients receiving BCG as primary intravesical treatment, with a median follow-up of 5.2 yr and a maximum follow-up of 18.7 yr, 19% of patients progressed and 9% died because of BCa, with 37% of progressing patients dying because of malignant disease or its treatment. Seventy-nine percent of patients retained their bladders. These favorable outcomes are comparable to recent smaller series of conservatively managed T1G3 patients [5], [11], [14] and
Conclusions
T1G3 patients treated with at least an induction course of BCG show excellent long-term CSS, with 79% of patients retaining their bladders. The simultaneous presence of three adverse prognostic factors—age ≥70 yr, tumor size ≥3 cm, and concomitant CIS—identifies a subgroup of patients with an unfavorable outcome who should be considered for more aggressive treatment.
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