The value of a second transurethral resection for T1 bladder cancer

Authors

  • HARTWIG E. SCHWAIBOLD,

    1. Bristol Urological Institute, Southmead Hospital, Bristol, UK, and Department of Urology, Klinikum rechts der Isar der Technischen Universität München, Germany
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  • SIVAPRAKASAM SIVALINGAM,

    1. Bristol Urological Institute, Southmead Hospital, Bristol, UK, and Department of Urology, Klinikum rechts der Isar der Technischen Universität München, Germany
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  • FLORIAN MAY,

    1. Bristol Urological Institute, Southmead Hospital, Bristol, UK, and Department of Urology, Klinikum rechts der Isar der Technischen Universität München, Germany
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  • RUDOLF HARTUNG

    1. Bristol Urological Institute, Southmead Hospital, Bristol, UK, and Department of Urology, Klinikum rechts der Isar der Technischen Universität München, Germany
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Hartwig Schwaibold, Bristol Urological Institute, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK. e-mail: h.schwaibold@talk21.com

Abstract

OBJECTIVE

To evaluate a series of repeat transurethral resections (TURs) of tumour in patients with T1 bladder cancer, usually used to ensure a complete resection and to exclude the possibility muscle-invasive disease.

PATIENTS AND METHODS

In all, 136 consecutive patients had a second TUR because of a histopathological diagnosis of T1 transitional cell carcinoma (TCC) after their initial TUR. Of the 136 patients, 101 were first presentations and 35 had recurrent tumours. The second TUR was done 4–6 weeks later. The evaluation included the presence of previously undetected residual tumour, changes to histopathological staging/grading, and tumour location.

RESULTS

In all, 71 patients (52%) had residual disease according to findings from specimens obtained during the second TUR. The staging was: no tumour, 65 (48%); Ta, 11 (8%); T1, 32 (24%); Tis, 15 (11%); and ≥ T2, 13 (10%). Histopathological changes that worsened the prognosis (>T1 and or concomitant Tis) were found in 21% of patients. Residual malignant tissue was found in the same location as the first TUR in 86% of the patients, and at different locations in 14%. Overall, 28 patients (21% of the original 136) had a radical cystectomy as a consequence of the second TUR findings.

CONCLUSIONS

A routine second TUR should be advised in patients with T1 TCC of the bladder, to achieve a more complete tumour resection and to identify patients who should have a prompt cystectomy.

Abbreviations
TUR

transurethral resection

Cis

carcinoma in situ.

INTRODUCTION

The standard treatment for superficial (Ta, T1) TCC of the bladder is the endoscopic resection of all visible tumours, followed possibly by adjuvant intravesical therapy [1]. The macroscopic aspect of the tumour influences the endoscopic resection, so transurethral resection (TUR) might fail to control superficial disease, especially in patients with higher tumour stages (T1). Furthermore, if TUR is not complete, muscle-invasive disease might be overlooked and the result could be a decision to adopt a more conservative approach than is really warranted.

In our clinic we routinely use a second TUR in patients with T1 tumours, regardless of the pathological grade, multiplicity, or recurrence factor. We report our evaluation of a series of 136 consecutive patients with T1 bladder cancer who had a second TUR. The analysis includes the presence and location of previously undetected residual disease, changes to the histopathological staging/grading and therapeutic changes that resulted from this second TUR.

PATIENTS AND METHODS

From January 1992 to December 1998, 804 patients had 1201 TURs for superficial bladder cancer; of these, 149 patients showed T1 disease. In 13 of the 149 patients a second TUR was felt inappropriate on the grounds of age, comorbidity or the need for a radical cystectomy because of the extensive nature of their disease, based on initial resection. Patients were excluded based on age and comorbidities because it was felt that the results of the second TUR are unlikely to influence future treatment in these few patients. Thus only 136 patients finally had a second TUR because of the histopathological diagnosis of T1 bladder cancer after their first TUR.

The first TURs were fully standardized; the bladder was thoroughly examined endoscopically with a 70° lens. The location, number and size of bladder tumours were recorded on a cystoscopy diagram. Hot-loop TUR of all visible tumours was then done down to the lamina propria, and several deep muscular samples were also taken from the tumour base.

Before discharge from the hospital, all 136 patients were advised to have a second TUR 4–6 weeks after the first. Intravesical therapy was not administered after the first TUR, regardless of the histological results of this TUR. During the second TUR all visible tumours and previous resection scar or oedematous areas from initial biopsy sites were resected. Deep muscle specimens were taken, especially from the previous tumour areas. When the results of the histopathological evaluation of these specimens were available, the final treatment strategy was discussed with the patients.

For the statistical analysis we used Fisher’s exact probability test to evaluate the association of residual malignant disease with the characteristics of the primary tumour, with P < 0.05 considered to indicate a significant correlation between the groups.

RESULTS

Of the 136 patients who had a second TUR, 35 (26%) had recurrent disease, 59 (43%) had multifocal tumours (at least two tumour foci) and 129 (95%) were histopathologically confirmed as having high-grade disease (Table 1). After the second TUR, 71 (52%) showed residual disease in histopathological specimens; staging is also listed in Table 1. An increase in T stage or grade over that in the first TUR was found in 28 (21%) patients, including 11 (8%) with carcinoma in situ (Cis; Table 1).

Table 1.  Tumour characteristics and histopathological findings after the second TUR of the 136 patients with T1 bladder cancers who had a second TUR, and those with a subsequent worse prognosis
Characteristic or findingN or N (%)
First tumour 101
Recurrent tumour 35
Grade
 G1  7
 G2 81
 G3 48
Number of tumour lesions
 1 77
 >1 59
Concomitant Tis 21
Histopathology after second TUR
Tumour stage
 T0 65 (48)
 Ta  11 (8)
 T1 32 (24)
 ≥ T2 13 (10)
 Tis 15 (11)
Histopathology worsening prognosis after second TUR
Tumour stage/grade
 G3  4 (3)
 ≥ T2 13 (10)
 Tis  11 (8)
Total 28 (21)

Residual malignant tissue was found at the same location in 86% of the patients and at other locations in 14%. Residual tumours had a statistically significant correlation with multifocal disease (P < 0.05) but not with the grade or diameter of the initial tumour. The increase in T stage or grading after the second TUR, and the detection of extensive T1G3 disease or T1G3 disease with concomitant Cis, changed tumour treatment and led to radical cystectomy in 24 (18%) patients. The others had intravesical instillations with BCG. No significant morbidity was documented among the patients who had a second TUR.

DISCUSSION

Despite progress in therapy (e.g. early postoperative intravesical chemotherapy, hyperthermia, and laser surgery), TUR remains the standard treatment for bladder TCC that is not muscle-invasive. Accurate technical recommendations for TUR are desirable. Endoscopic tumour resection is obviously limited by the visual identification of the tumour. If the tumour had invaded the lamina propria, the radicality of TUR cannot be monitored during the TUR procedure. Tumour spreading towards the deep muscle bundles and beneath the urothelium can limit the success of this procedure. Several authors have recommended a second TUR in all cases of superficial bladder cancer. On the evidence of the first evaluation of a second TUR in T1 disease, by Klän et al.[2], we routinely used a second TUR in all patients with T1 disease in our clinic. In the present consecutive series there was residual tumour in 52% of the patients, with only 8% presenting as Ta tumours, while 44% showed T1, ≥ T2 or Tis disease. The present data are in close accordance with previous reports (Table 2) [2–11], which showed residual disease in up to 78% of patients.

Table 2.  Results of the second TUR in previous reports of patients with Ta and T1 bladder cancers
ReferenceN tumours and stage after first TUR% of residual tumour after second TUR
Klän et al. 1991 [2] 46 (T1)20
Köhrmann et al. 1994 [4] 75 (Ta)27
 76 (T1)34
Mersdorf et al. 1998 [6] 49 (Ta)45
 45 (T1)58
Vögeli et al. 1998 [5] 69 (Ta)37
 30 (T1)43
Herr 1999 [3] 18 (Ta)72
 58 (T1)78
Engelhardt et al. 1999 [8] 50 (Ta)22
 25 (T1)52
Brauers et al. 2001 [7] 42 (T1)64
Schips et al. 2002 [9] 31 (Ta)39
 76 (T1)33
Grimm et al. 2003 [10] 59 (Ta)27
 19 (T1)53
Zukirchen et al. 2004 [11] 99 (Ta)27
115 (T1)37

Herr [3] described the usual scenario of daily urological practice; 96 patients from all geographical regions in the USA had a second TUR after a first TUR revealed Ta, T1 or Tis bladder cancer. Almost 80% of the patients had significant residual tumour load. In 31% of the cases, the histopathological findings of the repeat TUR led to a change in treatment. Comparable data were published by other authors, mainly from Europe, who showed clearly the value of a second TUR. Köhrmann et al.[4] analysed 159 patients with superficial bladder cancer, all of whom had a second TUR. They found a 32% residual tumour rate, which correlated with the presence of Tis, high-grade or multifocal disease in the first TUR. They subsequently performed a third TUR in patients with residual tumour load and found additional tumour in 31% of the patients. They concluded that all patients with Ta, T1 tumours should have a second TUR. Similarly, Vögeli et al.[12] analysed 256 consecutive second TURs and found a high load of residual disease, which changed the therapeutic approach in 21% of Ta and 56% of T1 tumours. In a second prospective study [5], they evaluated 215 patients with Ta and T1 tumours, and confirmed their previous results with residual tumour rates of 37% and 43% for Ta and T1 tumours, respectively. The repeat TURs also revealed a higher tumour stage in 9% of the patients. Almost the same rates of residual disease were also reported Mersdorf et al.[6], with 40% positive results in the second TUR in T1 disease and 64% in a later series [7]. Similarly, there are other studies (Table 2) which show clearly a high load of superficial bladder cancer which will be insufficiently treated with only one TUR [8–11].

Recent literature reviews by both Miladi et al.[13] and Jakse et al.[14], evaluating the role of repeat TUR in superficial bladder cancer, came to the same conclusion; there is a potential role for the procedure in managing T1 bladder cancers, based on current evidence.

In addition to altering the histopathological staging of the cancer and subsequent treatment, a study by Grimm et al.[10] also suggested that the procedure might actually statistically improve recurrence-free survival in those having a repeat TUR. Unfortunately, there are shortcomings in that study, as there were few patients compared in the repeat TUR vs TUR-only groups, and the follow-up was rather short.

Whether the findings of residual tumour are due to a less aggressive TUR or simply to overlooked multifocal disease remains unclear. According to the present data, only 14% of the malignant tissue was at other locations outside the initial tumour resection area. It is unlikely that findings of residual tumour could be all due to incorrect endoscopy during the TUR. Nevertheless, other authors are seeking new technologies to improve the sensitivity and specificity of endoscopy, e.g. a multicentre randomized prospective study which included 165 patients showed a decrease in the rate of residual tumour by 21% through the use of fluorescence endoscopy during the first TUR of superficial bladder cancers. However, the percentage of residual tumour was still 38.5%, despite the use of endoscopy with 5-aminolaevulinic acid-induced fluorescence [15] during the first TUR.

The high rates of residual tumour reported previously might also be due to the level of experience of the operating surgeon; in most centres TURs are carried out by trainees. Zurkirchen et al.[11] addressed this specifically in their series of 214 patients who had a repeat TUR for Ta and T1 bladder cancers. They found no statistical difference in the residual cancer rates between the experienced urologist and trainee groups.

We feel that the value of a second TUR is considerable. The remaining tumour which might be the origin/source of recurrent disease can potentially be removed. The patient’s tumour load too will be diminished, and this could increase the effectiveness of any adjuvant intravesical instillation of BCG or chemotherapeutic drugs. In many patients, the second TUR might be the only way of revealing the ‘real’ tumour load, the presence of muscle-invasive disease or extensive T1G3 tumour, all of which could lead to a change in the eventual treatment strategy. We think that a second TUR should be a standard procedure in urological practice for T1 tumours, as recommended by the European Guidelines on Bladder Cancer [16].

In conclusion, most patients with T1 bladder tumours have a higher tumour load than initially suspected on the basis of a single TUR. A second TUR showed an increase in stage, grade or extent of disease in 21% of patients, and led to radical cystectomy in 18% of patients in the present series. A second TUR should be routinely advised in all patients with T1 bladder cancer, to achieve a complete tumour resection and to identify patients who may need to undergo a prompt radical cystectomy.

CONFLICT OF INTEREST

None declared.

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