Is a Second Transurethral ResectionNecessary for Newly Diagnosed pT1 Bladder Cancer?Taner Dıvrık,* Umıt Yildirim, Askin Eroglu, Ferruh Zorlu and Haluk ÖzenFrom the Department of Urology, SSK Tepecik Teaching Hospital, Izmir (TD, UY, AE, FZ), and the Department of Urology, HacettepeUniversity, Ankara (HO), Turkey

Purpose: We evaluated the potential benefit of a second transurethral resection in patients with newly diagnosed pT1transitional cell carcinoma of the bladder.Materials and Methods: Between January 2001 and May 2003, 80 patients with stage T1 bladder cancer were includedin this protocol in which all patients prospectively received second TUR within 2 to 6 weeks following the initialresection. Patients with incomplete resections were excluded from study. The pathological findings of the second TURwere reviewed.Results: Of the 80 patients who underwent second resection, 18 (22.5%) had macroscopic tumors before resection. However,with the addition of microscopic tumors, overall residual disease was determined in 27 (33.8%) patients. Of the 27 patients7 had pTa, 14 had pT1, 3 had pT1�pTis and 3 had pT2 disease. Residual cancers were detected in 5.8%, 38.2% and 62.5%in G1, G2 and G3 tumors, respectively. The risk of residual tumor directly correlated with the grade of the initial tumor(p � 0.009).Conclusions: Although second TUR dramatically changed the treatment strategy in a small percentage of cases, we stronglyrecommend performing second TUR in all cases of primary pT1 disease, especially in high grade cases.

Key Words: mycobacterium bovis, bladder neoplasms

Transurethral resection of bladder tumors is the main-stay approach in the diagnosis and the treatment ofbladder cancer. The first and the most important rule

is the complete resection of the superficial bladder cancer.This procedure is not only mandatory for adequate stagingbut also serves as the completion of TURB for most of thesuperficial tumors. Recent studies have suggested that ini-tial TURB may be incomplete in a significant number ofcases.1–6 In this prospective study we evaluated the neces-sity of a second TUR in patients with newly diagnosed pT1bladder cancer.

MATERIALS AND METHODS

From January 2001 to May 2003, a total of 80 patients withnewly diagnosed T1 tumors underwent second TUR andprospectively evaluated to document the number of the pa-tients with residual tumors and adequacy of clinical stagingin our institution. The mean age was 62.2 years (range 37 to87, SD 10.4) and 7 of all patients were women. The initialresection of all cases was performed in our institution by 4experienced surgeons. Patients who were considered to haveundergone incomplete resection and specimens of patientsnot having muscle tissue to evaluate tumor invasion wereexcluded from this study. During this period we have ex-

Submitted for publication January 17, 2005.Nothing to disclose.* Correspondence: 1394 Sk. No: 11/13, Alsancak-Izmir, Turkey

(telephone: �90 232 4650888; FAX: �90 232 4646050; e-mail:t.divrik@superonline.com.tr, tdivrik@hotmail.com.tr).

0022-5347/06/1754-1258/0THE JOURNAL OF UROLOGY®

Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATION

1258

cluded 26 patients from this study, 22 because of the lack ofmuscle tissue in the specimen and an additional 3 patientswith incomplete resection and a further patient with perfo-ration. All visible tumors, tumor bed and the margins wereresected separately. Cold cup biopsies from normal mucosawere not routinely obtained. All of the tumors were depictedon a bladder map by the surgeon immediately after theoperation. Second TUR was routinely performed within 2 to6 weeks following the initial resection if the histopathologi-cal evaluation revealed T1 tumor. Tumors were classifiedaccording to the TNM system of the UICC7 and were gradedaccording to the WHO classification. If there were no resid-ual tumor or it was superficial intravesical chemotherapywas planned. However, if muscle invasive residual tumor orTis were detected subsequent treatment strategy wasplanned as radical cystoprostatectomy or intravesical bacil-lus Calmette-Guerin treatment, respectively. Statisticalevaluation was performed using the Pearson chi-square test.Informed consent for the treatment strategy was obtainedfrom each patient.

RESULTS

Of 80 patients with primary T1 tumor, 18.8% were solitaryand less than 3 cm and the rest (81.2%) were multiple and/or

Editor’s Note: This article is the first of 5 published inthis issue for which category 1 CME credits can beearned. Instructions for obtaining credits are given

with the questions on pages 1582 and 1583.

Vol. 175, 1258-1261, April 2006Printed in U.S.A.

DOI:10.1016/S0022-5347(05)00689-0

SECOND TRANSURETHRAL RESECTION FOR NEWLY DIAGNOSED pT1 BLADDER CANCER 1259

more than 3 cm in diameter (table 1). Regarding the gradingof the tumors resected by the first TURB, 21.3%, 68.7% and10% had G1, G2 and G3 transitional cell carcinoma, respec-tively.

Cystoscopy performed 2 to 6 weeks after initial resectionshowed that 18 (22.5%) patients had visible tumors. Ourprotocol dictated TUR of the previously resected areas evenif there were no macroscopic abnormalities. As a result re-sidual cancer was detected in 14.5% (9 of 62) of such pa-tients. Since transitional cell carcinoma was found to bepresent in all of the cases who had visible tumor, residualcancer was detected histopathologically in a total of 27 pa-tients (33.8%) of our group. In 12 of these patients the tumorwas detected at the primary site, whereas in 11 patientstumor was detected elsewhere. The remaining 4 patientshad residual tumors at the site of the first TUR and inanother site. Of these 27 patients with residual cancer, in 3(3.75%) disease was up staged to pT2 and an additional 3patients had Tis in conjunction with residual pT1 disease.Therefore, second TURB definitely resulted in a majorchange in the treatment strategy of 3 patients. Intravesicalbacillus Calmette-Guerin treatment became almost manda-tory in an additional 3 patients in whom Tis was discoveredin the second TURB. The distribution of stage as assessedduring second TUR is given in table 2.

While of 15 patients who had solitary, less than 3 cmtumors, 3 (20%) had residual tumors at the second TUR,24 (37%) of 65 patients with multifocal and/or more than3 cm tumors were found to have residual tumors (p�0.05). After initial TUR residual cancers were detectedin 5.8%, 38.2% and 62.5% in G1, G2 and G3 tumors,respectively (table 3). The risk of having a residual tumordirectly correlated with the grade of the initial tumor (p �0.009). Second TURB was performed without a majormorbidity on 80 patients with primary T1 transitional cellcarcinoma. Minor complications included prolonged bleed-ing managed conservatively in 3, and epididymitis andtransient urinary retention in 1 each.

DISCUSSION

Although complete TUR of the bladder tumors is the firstand the most important aspect in the treatment of almost all

TABLE 1. Solitary and multifocality after initial TUR, percentresidual tumor at second TUR

Macroscopic AppearanceNo. After Initial

TUR (%)

No. ResidualTumor After

Second TUR (%)

Solitary, less than 3 cm 15 (18.8) 3 (20)Solitary, greater than 3 cm 27 (33.8) 24 (37)Multifocal, less than 3 cm 22 (27.5)Multifocal, greater than 3 cm 16 (20.0)

TABLE 2. Stage distribution as assessed during second TUR

Histological Results of Second TUR No. Pts (%)

No residual tumor 53 (66.25)pTa 7 (8.75)pT1 14 (17.50)pT1 � pTis 3 (3.75)

pT2 3 (3.75)

stages of the disease, relatively little significance is given toimprove the surgical skills of the residents. This fact hasbeen extensively studied by Brausi et al, who showed thatthe quality of TUR had a major impact on recurrence rates.8

The positive effect of an excellent resection is especiallyevident in superficial disease. Even in this group of patientsa type of intracavitary treatment modality deserves moreinterest than surgical technique. In published reports his-topathologically confirmed residual tumors have been re-ported in 28% to 74% of patients with newly diagnosed orrecurrent pT1 bladder cancer at the second TUR.1–4,6,9–14

To minimize the effect of inadequate skill, we designed ourprotocol such that TURB was performed by 4 senior, expe-rienced surgeons.

Early recurrence especially high grade and T1 diseasehas been shown to be one of the most important prognosticfactors in regard to recurrence and progression.15,16 To havean evidenced based therapy plan for patients with superfi-cial tumors, it is crucial to differentiate a patient with anearly recurrence from those who has residual tumor due toincomplete resection.

In our prospective study residual tumors were detected in27 (33.8%) of 80 patients with newly diagnosed G1-3 pT1bladder cancers at the second TUR. It must be stressed that14.5% of the patients with normal cystoscopy ended up hav-ing residual cancer after resection of the previously resectedarea. This fact was also reported by several investigators.17

After the first TUR residual cancers were found in 1 of 17(5.8%) G1, 21 of 55 (38.2%) G2 and 5 of 8 (62.5%) G3 tumors(p � 0.009).

Klän et al reported a residual tumor rate of 50% inpatients with G2-3 pT1 tumors.1 Mersdorf et al detectedresidual tumors in 58% (26 of 45 patients) of patients withG2-3 pT1 tumors.2 This new information has been reportedto alter the proposed therapeutic regimen in 2% (11) ofpatients. Herr reported a rate of 74% residual tumors in 58patients with G2-3 pT1 bladder cancer, but informationregarding whether tumor resection was complete or incom-plete at the first TUR was not available.3 Furthermore, inthe aforementioned study 23 of 58 patients with pT1 tumorhad no muscle tissue in the specimen at initial TUR toevaluate the invasion.3 The relatively low incidence of resid-ual tumors and residual muscle invasive tumors in ourstudy may be attributed to the strict inclusion criteria. Re-view of the published reports on this issue is shown in table4. As can be recognized, second TUR certainly detected asignificant percentage of residual tumors and, among themTis and muscle invasive disease rates were reported with arange of 6% to 24% in different studies.2,4,10,13,14 In ourseries Tis and muscle invasive disease were detected in 7.5%

TABLE 3. Grade distribution as assessed during first andsecond TUR

No. AfterFirst TUR (%)

No. AfterSecond TUR (%)

G1 17 (21.3) 1 (5.8)G2 55 (68.7) 21 (38.2)G3 8 (10.0) 5 (62.5)Overall 80 (100) 27 (33.8)

p � 0.009.

of patients.

TA

BL

E4.

Rev

iew

ofpu

blis

hed

repo

rts

(sel

ecte

don

lypT

1bl

add

erca

nce

r)

Ref

eren

ces

No.

Pts

.N

o.N

ewly

Dia

gnos

ed%

Mu

ltif

ocal

(No.

)W

ith

Con

com

itan

tC

ain

Sit

u(%

)

No.

Wit

hV

isib

leR

esid

ual

Tu

mor

atR

epea

tT

UR

/Tot

alN

o.(%

)%

Res

idu

alG

1pT

1T

um

or%

Res

idu

alG

2pT

1T

um

or%

Res

idu

alG

3pT

1T

um

or%

Res

idu

alG

1-3p

T1

Tu

mor

%A

lter

atio

nin

Th

erap

euti

cR

egim

en(N

o.)

län

etal

146

4652

.2(2

4)N

o16

/46

10/4

0(2

5)�

34.5

58.8

50.0

*U

nkn

own

ersd

orf

etal

245

Un

know

nU

nkn

own

No

Un

know

n�

Un

know

nU

nkn

own

58.0

24(1

1)er

r358

87%

Rec

urr

ent

Un

know

nN

oU

nkn

own

�P

osP

os74

.0U

nkn

own

†h

ips

etal

476

7639

.5(3

0)Y

es(3

.9)

Un

know

nP

osP

osP

os32

.97.

9(6

)ri

mm

etal

619

19U

nkn

own

No

Un

know

n�

33.3

85.7

53.0

Un

know

nge

liet

al9

3030

Un

know

nN

oU

nkn

own

Un

know

nU

nkn

own

Un

know

n43

.0U

nkn

own

auer

set

al1

042

4211

.9(5

)Y

es(U

nkn

own

)U

nkn

own

�P

osP

os64

.024

(10)

ake

etal

11

4444

52.0

(23)

Yes

(39)

Un

know

n�

�30

.0�

Un

know

nak

eet

al12

123

123

40.0

(50)

Yes

(22)

Un

know

nU

nkn

own

Un

know

nU

nkn

own

28.0

Un

know

nje

aC

alvo

etal

13

32U

nkn

own

Un

know

nN

oU

nkn

own

5744

.053

.16.

0(2

)ga

ud

etal

14

5252

Un

know

nN

oU

nkn

own

Un

know

nU

nkn

own

Un

know

n36

.57.

7(4

)es

ent

stu

dy80

8047

.5(3

8)‡

No

18/8

0(2

2.5)

5.8

38.2

62.5

33.8

7.5

(6)

In40

ofth

e46

pati

ents

no

tum

orw

asvi

sibl

eto

the

oper

atin

gsu

rgeo

ns

atth

een

dof

init

ial

TU

Ran

dco

mpl

ete

rese

ctio

nw

asre

port

ed.

Info

rmat

ion

rega

rdin

gw

het

her

tum

orre

sect

ion

was

com

plet

eor

inco

mpl

ete

was

usu

ally

not

avai

labl

e,23

of58

pati

ents

wit

hpT

1tu

mor

had

no

mu

scle

insp

ecim

enat

init

ial

TU

R.

Mu

ltif

ocal

and

soli

tary

but

grea

ter

than

3cm

:81

.2(6

5).

SECOND TRANSURETHRAL RESECTION FOR NEWLY DIAGNOSED pT1 BLADDER CANCER1260

CONCLUSIONS

Second TUR is beneficial because in a certain percentageof the patients this additional surgery results in a majorchange in treatment strategy. Furthermore, true recur-rence can be identified by this approach since convention-ally residual tumors may be falsely defined as recurrence.This will save the patient from receiving unnecessarytreatments. This approach might also have an effect onprogression and, thus, bladder preservation. However,these 2 latter arguments will be addressed in a subse-quent prospective controlled study with long followup.Our data indicate that it is necessary to perform secondTUR in patients with newly diagnosed, high grade (G2-3),stage T1 bladder cancer for true staging and completeresection.

Abbreviations and Acronyms

TURB � transurethral resection of bladder tumorsTUR � transurethral resection

REFERENCES

1. Klän, R., Loy, V. and Huland, H.: Residual tumor discovered inroutine second transurethral resection in patients with stageT1 transitional cell carcinoma of the bladder. J Urol, 146:316, 1991

2. Mersdorf, A., Brauers, A., Wolff, J. M., Schneider, V. and Jakse,G.: 2nd TUR for superficial bladder cancer: a must? J Urol,suppl., 159: 143, abstract 542, 1998

3. Herr, H. W.: The value of a second transurethral resection inevaluating patients with bladder tumors. J Urol, 162: 74,1999

4. Schips, L., Augustin, H., Zigeuner, R. E., Galle, G., Habermann,H., Trummer, H. et al: Is repeated transurethral resectionjustified in patients with newly diagnosed superficial bladdercancer? Urology, 59: 220, 2002

5. Dalbagni, G., Herr, H. W. and Reuter, V. E.: Impact of a secondtransurethral resection on the staging of T1 bladder cancer.Urology, 60: 822, 2002

6. Grimm, M.-O., Steinhoff, C., Simon, X., Spiegelhalder, P., Ack-ermann, R. and Vögeli, T. A.: Effect of routine repeat trans-urethral resection for superficial bladder cancer: a long-termobservational study. J Urol, 170: 433, 2003

7. Sobin, L. H. and Wittekind, Ch.: Urinary bladder. In: TNMClassification of Malignant Tumours, 5th ed. InternationalUnion Against Cancer (UICC). New York: Wiley-Liss, p. 187,1997

8. Brausi, M., Collette, L., Kurth, K., van der Meijden, A. P.,Oosterlinck, W., Witjes, J. A. et al: Variability in the re-currence rate at first follow-up cystoscopy after TUR instage Ta T1 transitional cell carcinoma of the bladder: acombined analysis of seven EORTC studies. Eur Urol, 41:523, 2002

9. Vögeli, T. A., Grimm, M.-O. and Ackermann, R.: Prospectivestudy for quality control of TUR of bladder tumors by routine2nd TUR (ReTUR). J Urol, suppl., 159: 143, abstract 543,1998

10. Brauers, A., Buettner, R. and Jakse, G.: Second resection andprognosis of primary high risk superficial bladder cancer: is

cystectomy often too early? J Urol, 165: 808, 2001K M H S

cG V

öB

rB

rB

rO R

iP

r

* † ‡

SECOND TRANSURETHRAL RESECTION FOR NEWLY DIAGNOSED pT1 BLADDER CANCER 1261

11. Brake, M., Loertzer, H., Horsch, R. and Keller, H.: Recurrenceand progression of stage T1, grade 3 transitional cell carci-noma of the bladder following intravesical immunotherapywith bacillus Calmette-Guerin. J Urol, 163: 1697, 2000

12. Brake, M., Loertzer, H., Horsch, R. and Keller, H.: Long-termresults of intravesical bacillus Calmette-Guerin therapy forstage T1 superficial bladder cancer. Urology, 55: 673, 2000

13. Ojea Calvo, A., Nunez Lopez, A., Alonso Rodrigo, A., RodriguezIglesias, B., Benavente Delgado, J., Barros Rodriguez, J. M.et al: Value of a second transurethral resection in the assess-ment and treatment of patients with bladder tumor. ActasUrol Esp, 25: 182, 2001

14. Rigaud, J., Karam, G., Braud, G., Glemain, P., Buzelin, J. M.and Bouchot, O.: T1 bladder tumors: value of a second endo-

scopic resection. Prog Urol, 12: 27, 2002

15. Kurth, K. H., Schroeder, F. H., Debruyne, F., Senge, T., Pavone-Macaluso, M., de Pauw, M. et al: Long-term follow-up in super-ficial transitional cell carcinoma of the bladder: prognosticfactors for time to first recurrence, recurrence rate, and sur-vival. Final results of a randomized trial comparing doxorubicinhydrochloride, ethoglucid, and transurethral resection alone.EORTC Genitourinary Tract Cancer Cooperative Group. ProgClin Biol Res, 303: 481, 1989

16. Fitzpatrick, J. M., West, A. B., Butler, M. R., Lane, V. andO’Flynn, J. D.: Superficial bladder tumors (stage pTa, grades1 and 2): the importance of recurrence pattern followinginitial resection. J Urol, 135: 920, 1986

17. Jakse, G., Algaba, F., Malmstrom, P. U. and Oosterlinck, W.: Asecond-look TUR in T1 transitional cell carcinoma: why? Eur

Urol, 45: 539, 2004