Elsevier

European Urology

Volume 67, Issue 1, January 2015, Pages 74-82
European Urology

Platinum Priority – Urothelial Cancer
Editorial by David R. Yates on pp. 83–84 of this issue
Prognostic 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

https://doi.org/10.1016/j.eururo.2014.06.040Get rights and content

Abstract

Background

The impact of prognostic factors in T1G3 non–muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making.

Objective

To assess prognostic factors in patients who received bacillus Calmette-Guérin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment.

Design, setting, and participants

Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011.

Outcome measurements and statistical analysis

Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS).

Results and limitations

With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age ≥70 yr, size ≥3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients ≥70 yr with tumor size ≥3 cm and 13% otherwise.

Conclusions

T1G3 patients ≥70 yr with tumors ≥3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression.

Patient summary

Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guérin, there is a subgroup of T1G3 patients with age ≥70 yr, tumor size ≥3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

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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