prescribed testosterone therapy despite no clinical or labora-
tory diagnosis of hypogonadism. This study provides clear
evidence that guidelines for testosterone therapy initiation
are seldom followed, and in the United States, the lack of
adherence to guidelines has led to an overabundance of
potentially unnecessary testosterone prescriptions.
Another alarming trend highlighted in the study is that in
10% of men initiating testosterone therapy
are within their reproductive years. Practitioners often, do
not consider the inhibitory effect of exogenous testosterone
on a male’s reproductive potential. In fact, a 2010 survey of
American Urological Association members found that up to
25% of urologists would prescribe testosterone therapy for
idiopathic male infertility
, suggesting that the impact
on fertility often is not only ignored but also incorrectly
understood. A survey of Canadian men presenting at a male
infertility clinic between 2008 and 2012 found that an
alarming 39% of the men on testosterone therapy received
the prescription from either an endocrinologist or a urologist
. This finding suggests that a large group of men desiring
fertility are receiving testosterone supplementation from
practitioners outside the fields of endocrinology or urology
and that some endocrinologists or urologists are not
appropriately considering the ramifications of exogenous
testosterone on fertility. The reported discrepancy between
adequate testing and new testosterone prescriptions high-
lights the need for increased physician education and the
proper management of these patients by practitioners
trained in appropriately diagnosing and treating male
Conﬂicts of interest:
Larry I. Lipshultz is a clinical trials participant,
consultant, speaker for Auxilium and Endo. Ranjith Ramasamy is an NIH
K12 Scholar supported by a Male Reproductive Health Research Career
Development Physician-Scientist Award (HD073917-01) from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development Program. Jason M. Scovell has nothing to disclose.
Baillargeon J, Urban RJ, Ottenbacher KJ, Pierson KS, Goodwin JS.
Trends in androgen prescribing in the United States, 2001 to 2011.
JAMA Intern Med 2013;173:1465–6.
Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy
in men with androgen de±ciency syndromes: an Endocrine Society
clinical practice guideline. J Clin Endocrinol Metab 2010;95:
Ko EY, Siddiqi K, Brannigan RE, Sabanegh Jr ES. Empirical medical
therapy for idiopathic male infertility: a survey of the American
Urological Association. J Urol 2012;187:973–8.
Samplaski MK, Loai Y, Wong K, Lo KC, Grober ED, Jarvi KA. Testos-
terone use in the male infertility population: prescribing patterns
and effects on semen and hormonal parameters. Fertil Steril 2014;
Jason M. Scovell, Ranjith Ramasamy, Larry I. Lipshultz
Department of Urology, Baylor College of Medicine, Houston, TX, USA
*Corresponding author. 6624 Fannin Street, #1700, Houston,
TX 77030, USA.
Re: Prognostic Interest in Discriminating Muscularis
Mucosa Invasion (T1a vs T1b) in Nonmuscle Invasive
Bladder Carcinoma: French National Multicenter Study
with Central Pathology Review
ˆt M, Seisen T, Compe
´rat E, et al.; Comite
´rologie de l’Association Franc
¸ aise d’Urologie
J Urol 2013;189:2069–76
In a recent multicenter study, Roupre
ˆt et al. included 587
patients diagnosed with primary T1 non–muscle-invasive
bladder cancer (NMIBC) between 1994 and 2010. Six French
hospitals participated in this landmark study. Muscle in the
specimen was required, but a standard repeat resection was
not. All T1 tumors were substaged as follows: above or into
(T1a) or beyond (T1b) the muscularis mucosa (MM), a thin
layer within the lamina propria of the bladder. The prognostic
value of substage was investigated. T1a was reported in 388
patients (66%) and T1b in 199 (34%). After central review, 94
cases (16%) were reclassified. Median follow-up was 35 mo.
The 5-yr recurrence-free survival (RFS), progression-free sur-
vival (PFS), and cancer-specific survival (CSS) rates were all
significantly better for T1a cases compared with T1b. Cystec-
tomy was required in 45 T1b patients (23%) and 54 T1a
patients (14%). Significant predictors in multivariable analyses
for worse RFS were multiplicity, tumor size
1 cm, and T1b.
Significant predictors in multivariable analyses for worse PFS
were tumor size
1 cm, T1b, and grade 3. Significant predic-
tors in multivariable analyses for worse CSS were T1b and
higher age. The authors advocated the use of substage to
assess prognosis of T1 NMIBC.
The stakes are high in T1 bladder cancer, as standardized
treatment is lacking. Conservative management with bacillus
´rin may lead to progression and possibly death.
Alternatively, radical cystectomy with obvious impaired qual-
ity of life may be overtreatment for nonprogressive T1 NMIBC.
Hence, there is a need for an easy-to-use substaging system
that provides useful prognostic information. Roupre
ˆt et al. are
not the first to investigate substage using the MM (T1ab). In
fact, its prognostic value has been proven significant by sev-
eral previous studies
. However, the study by Roupre
ˆt et al.
is the largest study so far and the first multicenter study with
central pathology review showing a highly significant prog-
nostic value for T1 substage. This study provided a clear
rationale that substage is important in T1 NMIBC. Neverthe-
less, T1a/b substage has been not been adopted in clinical
guidelines or staging systems [1,2]. The main reason was lack
of consensus among pathologists regarding the identification
of the MM at the site of the invading front of the tumor.
Indeed, T1a/b substaging rates ranged from 58% to 100% in 15
previously reviewed original reports
. In 2004, substage
EUROPEAN UROLOGY 66 (2014) 784–789