Re: Derya Tilki, Oliver Reich, Pierre I. Karakiewicz, et al. Validation of the AJCC TNM Substaging...

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: herrh@mskcc.org

April 14, 2010

Published online on April 23, 2010