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Letter to the Editor
E U R O P E A N U R O L O G Y 5 8 ( 2 0 1 0 ) e 2 1 – e 2 2
ava i lable at www.sciencedirect .com
journal homepage: www.europeanurology.com
Re: Derya Tilki, Oliver Reich, Pierre I. Karakiewicz, et al.
Validation of the AJCC TNM Substaging of pT2 Bladder
Cancer: Deep Muscle Invasion Is Associated with
Significantly Worse Outcome. Eur Urol 2010;58:112–7
Pooling data from a large international cohort of patients,
Tilki and colleagues validated pathologic substaging of
muscle invasive (pT2) bladder cancer [1]. The authors found
that patients whose tumors invaded the deep muscle (pT2b)
had worse outcomes than patients whose tumors were
confined to the superficial muscle (pT2a), independent of
lymph node or lymphovascular status. Pathologic T2b
tumors have more occult nodal and distant metastases
than pT2a tumors, accounting for subsequent relapse and
reduced survival despite cystectomy.
In 1944, Jewett first presented to members of the
American Association of Genito-Urinary Surgeons the
results of a landmark autopsy analysis of 107 patients
who died with bladder cancer [2]. He found that of 89
patients with perivesical fat infiltration, 52 (58%) had
metastases compared with only 1 of 15 whose tumors were
confined to the muscle, indicating that depth of invasion of
the primary tumor correlated with the incidence of
extravesical disease and metastases. Jewett and Lewis later
suggested that muscle-invasive (stage B) bladder tumors be
subdivided into superficial (B1) and deep (B2), stating that
‘‘regardless of histologic pattern and degree of malignancy,
tumors which have infiltrated less than half way through
the muscularis are usually confined to the bladder wall
and tumors that have infiltrated more deeply usually
have spread beyond’’ [3]. Although only 5 patients
had superficial muscle (B1) invasion, 4 survived after
cystectomy compared with only 1 of 13 with deep muscle
(B2) invasion [4]. In 365 additional cases, Jewett et al
confirmed that depth of bladder wall penetration was the
most important feature determining outcome, besides
lymphatic permeation, tumor grade, and pattern, and
that deeply infiltrating (B2) tumors behaved more like
extravesical (C) disease than superficial muscle-invasive
(B1) tumors [5]. After surgery, 10 of 16 patients (63%) with
B1 tumors survived compared with 6 of 37 (16%) with B2
tumors. Although Jewett studied fewer patients than Tilki
et al, the patients were better characterized, and he firmly
DOI of original article: 10.1016/j.eururo.2010.01.015
0302-2838/$ – see back matter # 2010 European Association of Urology. Publis
established predictability of metastases based on local
tumor stage.
Although the data reflect pathologic staging determined
by cystectomy specimens, that does not help the patient
whose bladder has been removed. The real value in
substaging muscle-invasive tumors is its clinical relevance
to patient treatment. Because prognosis is determined more
by the extent of the tumor than by the extent of surgery,
patients whose tumors minimally invade the muscle are
predicted to have fewer metastases, and they should
survive equally well after local tumor excision or cystec-
tomy. That is exactly what we found in selected patients
with muscle-invasive tumors who survived with the
bladder after a complete transurethral resection (TUR)
[6]. Moreover, 15% of patients who undergo cystectomy for
a muscle-invasive tumor will have no residual tumor (pT0)
in the bladder [7]. Because 85% of these patients survive,
presumably they were cured by TUR alone.
More than a half century ago, Jewett taught us that not all
muscle-invasive (stage B, pT2) bladder tumors behave alike.
Tilki et al remind us of that lesson and recommend that pT2
substaging be maintained in the American Joint Committee
on Cancer’s TNM system because it ‘‘may help in the
application of future therapeutic approaches.’’ It remains for
us, today’s urologists, to identify patients with nonmetastatic
invasive bladder cancers and to make that lesson a reality.
Conflicts of interest: The author has nothing to disclose.
References
[1] Tilki D, Reich O, Karakiewicz PI, et al. Validation of the AJCC TNM
substaging of pT2 bladder cancer: deep muscle invasion is associated
with significantly worse outcome. Eur Urol 2010;58:112–7.
[2] Jewett HJ, Strong GH. Infiltrating carcinoma of the bladder: relation
of depth of penetration of the bladder wall to incidence of local
extension and metastases. J Urol 1946;55:366.
[3] Jewett HJ, Lewis E. Infiltrating carcinoma of the bladder; curability
by total cystectomy. J Urol 1948;60:107–18.
[4] Jewett HJ. The historical development of the staging of bladder
tumors: personal reminiscences. J Urol 1977;27:37–40.
[5] Jewett HJ, King LR, Shelley WM. A study of 365 cases of infiltrating
bladder cancer: relation of certain pathological characteristics to
prognosis after extirpation. J Urol 1964;92:668–78.
hed by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2010.04.023
E U R O P E A N U R O L O G Y 5 8 ( 2 0 1 0 ) e 2 1 – e 2 2e22
[6] Herr HW. Conservative management of muscle-infiltrating bladder
cancer: prospective experience. J Urol 1987;138:1162–3.
[7] Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant
chemotherapy plus cystectomy compared with cystectomy alone
for locally advanced bladder cancer. New Engl J Med 2003;349:
859–66.
Harry W. Herr
Memorial Sloan-Kettering Cancer Center, New York, NY, USA
E-mail address: [email protected]
April 14, 2010
Published online on April 23, 2010