|Year : 2002 | Volume
| Issue : 2 | Page : 136-139
Carcinoma-in-situ bladder -an early indication for cystectomy?
V Kumar, AH Lawson
Harrogate Health Care, Lancaster Park Road, Harrogate, United Kingdom
12A, Swanston Grange, Shakespeare Road, Luton, LU4 OHF
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Carcinoma in situ bladder is a high grade and aggressive manifestation of transitional cell carcinoma of bladder that has highly variable course. The purpose of this study is to analyse how this serious disease is dealt with, most effective treatment option available and its clinical progression inspite of intervention.
All patients diagnosed to have CIS bladder histologically in Harrogate District Hospital from August 94 to August 99 were included in the study. All data concerning the management, treatment and subsequent follow-up were collected from the patients' records and analysed in a systematic way. A total of 20 patients were included in the study. Analysis showed that there was no age or sex predilection and the age group ranged from 36 to 75. It occurs either alone or with papillary bladder tumour. It is found to be poor prognostic indicator for subsequent ttunour recurrence. Mitomvcin was the least effective and BCG is the most effective form of intravesical treatment. Failure on BCG therapy is an earlvpredictorforaggressive treatment i.e. Radical Cystectomy. Eventually 1/3 of all patients diagnosed to have CIS progressed to muscle invasive disease requiring radical treatment.
Keywords: Carcinoma in situ Bladder; Bladder Tumour; Hematuria; Cytology; Intravesical Treatment.
|How to cite this article:|
Kumar V, Lawson A H. Carcinoma-in-situ bladder -an early indication for cystectomy?. Indian J Urol 2002;18:136-9
| Introduction|| |
Transitional cell carcinoma is situ of the bladder is a pathobiologic paradox that continues to challenge pathologists, researchers and urologists. Although CIS generally is considered an aggressive form of transitional-cell carcinoma, the clinical course is highly variable and unpredictable, creating a management dilemma for urologists. Carcinoma in situ bladder was first described in 1952 by Melicow. The diffuse nature of CIS extending from renal pelvis to penile urethra was subsequently documented by Melicow et al; they also pointed that CIS is a frank maligancy rather than precancerous condition. Figures of overall incidence are not available. The best data comes from Utz et al in a review of 2454 patients with newly diagnosed bladder cancer, of whom 250 (10.2%) had CIS.
| Materials and Methods|| |
All patients diagnosed to have CIS from August 1994 to 1999 at Harrogate District Hospital were included in the study. Meticulous record collection is made from the general computerised patient records and each subject was crossverified with histology report and looking at individual patient records. Further information was collected from each patient's record including personal data, mode of presentation, treatment intervention and its efficacy. Further data was collected regarding cystoscopic findings, biopsy results and treatment strategies. The major purpose of this study is to analyse the behaviour, clinical course and progression of CIS bladder over a period of time. Follow-up data was available from 1 year to 6 years from the diagnosis. This study is a combined retrospective and prospective study. Patients with follow-up less than one year were excluded from the study.
| Results|| |
Total number of patients with CIS bladder was 20.
Of the 20 patients 11 had CIS in isolation unassociated with papillary tumour. The remaining 9 had CIS in association with papillary tumour. The age group ranged from 36 to 75 with a mean age of 62. Frank hematuria was the presenting feature in 55% of cases. 15% presented with microscopic hematuria. 20% presented with irritative bladder symptoms. 10% were referred for abnormal urine cytology. A total of 90% of patients had urine cytology positive (18/20 cases).
Cystoscopically no consistent or specific features were noted.  At times, the bladder appeared to be normal, but more commonly, mucosal erythema or granularity suggesting inflammation was seen. The most common affected sites were trigone or floor of the bladder, including the periurethral areas and bladder neck. Multiple sites of involvement were frequent.
Analysis of intravesical treatment response revealed significant results. 18 patients received mitomycin as a first line of intravesical treatment. 12 had recurrence of CIS within 6 months. 4 patients were diagnosed to have recurrence between 6 and 12 months [Table - 1].
12 patients had intravesical epirubicin. Epirubicin was used as second line of therapy. Of the 12 patients 6 had recurrences within six months.
lntravesical BCG was used in 12 patients. 2 patients received it as first line, 4 had it as second line following mitomycin failure. Six patients had it as third line following failure of both epirubicin and mitomycin. Only 3 patients had recurrence following BCG treatment within 12 months. Follow-up was with regular cystoscopy and bladder biopsy. Follow-up data was available from the time of diagnosis up to the present time (1 to 6 years). Some of the cases had over five years follow-up now. 33% of patients (6 subjects) developed muscle invasive recurrence over the period of follow-up all qualifying for more radical treatment. 4 patients had standard treatment of radical cystectomy. 1 patient was subjected to radiotherapy in view of his poor general condition. Only palliative treatment could be offered to 1 patient as he presented with extensive metastatic disease. Of the 6 patients who developed muscle invasive disease, 3 developed within two year period (50%).
| Discussion|| |
The histopathological definition of carcinoma in situ on the urinary tract has been discussed by many authors. , The lack of cohesiveness observed in the epithelial cells of the biopsy fragments is reflected in the cases in which cytological examination of urine revealed cancer cells.
Riddle et a1  have identified significant differences in the extent of disease depending on the type of presentation. They concluded that patients presenting either with dysuria or obstructive symptoms had widespread disease. There was no predictability from the mode of presentation in this study. This might be due to the fact that urologists at present time have high index of suspicion and bladder biopsies are more frequently carried out at the slightest suspicion. Routine use of urine cytology as a part of hematuria investigation has improved the detection rate for this malignancy. The methodology of near and far biopsies along with tumour resection have improved the pick-up rate for this potentially serious disorder. Mitomycin was found to be least effective in achieving response. Only 2 patients remained recurrence free after 12 months ie. 9% of them. Fourteen series reporting the response to mitomycin treatment of CIS are available. In individual series the complete response rates range from 0% to 100%. Meta analysis by Donald et all showed an overall response rate of 53% [Table - 2]. No data was available from use of epirubicin from previous studies. This study demonstrated that 50% of the epirubicin group remained recurrence free for over 12 months. More published experience is available in doxorubicin treatment for CIS than others. In eight previous studies a response rate of 48% was noted [Table - 3].
BCG was the most effective in preventing recurrence in 75% of cases at 12 months in this study. The success of BCG immunotherapy for CIS heralds a new era in the management of this disease. Response data are available from 18 series [Table - 4]. The complete response rate averaged 70%. In the southwest oncology group study of 64 patients treated with Connaught BCG, 70% of the patients had a complete response, and the median duration of response was 39 months. In this study the response ranged from 1 year to 5 years with median duration of 34 months. In the above randomised comparison with doxorubicin, 45% of patients treated with BCG were disease free for 5 years compared with 18% of those treated with doxorubicin. But at follow-up for 5 years 30% of cases had progressed to muscle invasive disease. 50% of them occurred within 2 years of first diagnosis. All of them are patients who showed recurrence with BCG treatment.
Fourteen series evaluating the natural history of CIS are available [Table - 5]. No randomised study is available and the incidence of subsequent muscle invasive disease is quite variable. No major study could be cited in assessing the progression of subjects who failed to respond to BCG. In the present study a definite trend is identified with BCG failure meaning a more aggressive tumour. The progression occurred within 2 years in 3 subjects (50%). 1 of them presented with extensive metastatic disease. Utz et all have identified that in cystectomy specimens of patient who had radical cystectomy, 34% was associated with microinvasive cancer and the occurrence of metastatic disease despite early cystectomy in 6% of cases. This stresses the increased importance of early cystectomy to achieve cure from this notorious disease. There is an early indication from this study to consider cystectomy if there is failure of BCG therapy, as all the BCG failures progressed to muscle invasive disease eventually.
Further, patients need to be counselled from the time of first diagnosis about the poor prognosis and that they may eventually require radical treatment in spite of rigorous surveillance.
| Conclusion|| |
CIS is a definitive indicator of early recurrence. A high index of suspicion is required to diagnose this problem early. Low threshold for bladder biopsies of suspicious areas should be recommended. BCG is to be used as first line of treatment. If BCG fails to prevent recurrence radical cystectomy has to be offered to the patient even without muscle invasive disease. Even if BCG prevents recurrences strict, frequent, prolonged follow-up is required. Randomised prospective control trials are required to quantify the duration of protection offered by BCG and survival advantage following early cystectomy at first post BCG recurrence.
| Acknowledgements|| |
We thank Mr.G.Sarin, Staff grade Urology department, Harrogate District Hospital, for his continued support. We also thank pathologist and I&T staff for their support in our study.
| References|| |
|1.||Mellicow MM. Hollowell JW : Intra-urothelial cancer-Carcinoma in situ. Bowen's disease of urinary system. Discussion of 30 cases. J Urol 1952; 68: 763. |
|2.||Melamed MR. Voustsa NG, Grabstald H. Natural history and clinical behavior of in situ carcinoma of the human urinary bladder. Cancer 1964: 17: 1533. |
|3.||Riddle PR, Chisholm GD, Trott PA, Pugh RCB. Flat carcinoma in situ of bladder. Br J Urol 1976:, 47: 829-833. |
|4.||Lamm DL. Carcinoma in situ. Urol Clinic of North Am 1992; 19: 499-508. |
|5.||Utz PC, Farrow DM. Carcinoma in situ of the urinary tract. Urol Clin North Am 1984: 11: 735. |
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]