Adenocarcinoma of bladder

European Journal of Surgical Oncology 1997; 23:157-160

Adenocarcinoma of bladder Niteen P. Dandekar, Amish V. Dalai, Hemant B. Tongaonkar and Murali R. Kamat

Department of Uro-oncology, Tata Memorial Hospital, Dr E. Borges Road, Parel, Bombay 400012, India

Forty-eight patients with adenocarcinoma (21 urachal and 27 non-urachal) of the bladder were treated at the Tata Memorial Hospital between 1976 and 1992. The study group consisted of 32 men and 16 women. The urachal tumours were more common in younger patients (mean age: 49 years) than were non-urachal tumours (mean age: 58 years). The overall 5-year survival in this series was 37%. Stage and grade were powerful predictors of outcome. Patients with nonurachal tumours showed an overall survival rate of 29.9% compared with 45.7% in patients with urachal turnouts (P = 0.14). Radical cystectomy was the most common treatment modality in patients with non-urachal turnouts and yielded an overall 5-year survival of 35%. Patients with uraehal tumours were treated with either partial cystectomy or radical cystectomy. The 5-year survival following partial cystectomy was 56.3% compared with 25.9% following a radical cystectomy and the difference between the two was not statistically significant (P = 0.76).

Key words: bladder neoplasm; adenocarcinoma; nrachal; partial cystectomy.

Introduction

Primary adenocarcinomas are uncommon tumours of urinary bladder accounting for 0.5%--2% of all bladder malignancies. So far, about 400 cases have been reported in the literature, resulting in a paucity &material for review. Those tumours arising from the bladder mucosa make up approximately two-thirds of cases, while those of urachal origin make up almost one-third. Although rare, 80% of the malignant cancers with complicated exstrophy have been adenocarcinomas. ~ Some cases are associated with schistosomiasis,-''3endometriosis, 4 bladder augmentation 5 or other chronic irritative conditions, 6 such as exist in paraplegic patients. 7 We report our experience with 48 cases seen at the Tata Memorial Hospital over a 17-year period.

Patients and methods

Forty-eight patients with adenocarcinoma of the bladder were treated at the Tata Memorial Hospital between 1976 and 1992. In all cases the initial diagnosis ofadenocarcinoma was established following cystoscopic bladder biopsies. Only those patients with adenocarcinoma arising primarily in the bladder were included in this study. In those where the tumour was thought to be secondary to invasion from surrounding organs, a full gastrointestinal and gynaecological evaluation was performed to rule out such a possibility. Clinically staging was done by bimanual examination under anaesthesia and was supported in some Correspondence to: Dr A. V. Dalai, 61-B., Bhulabhai Desai Road, Mumbai-400 026, India. 0748-7983/97/020157 + 04 $12.00/0

patients with computerized tomography. Chest X-ray and isotope bone scan was carried out in all patients to rule out metastatic disease. Of the forty-eight cases studied, 21 patients had tumours confined to the dome of the bladder, i.e. urachal tumours, and 27 had tumours primarily in the lower half of the bladder, i.e. non-urachal. The study group comprised 32 men and 16 women aged 28-70 years (mean: 54 years). When comparing the urachal and the non-urachal group there were differences in the male-female ratio, 9:12 for urachal and 23:4 for non-urachal, and in the mean ages, 49 years for urachal and 58 years for non-urachal. Haematuria, with or without irritative bladder symptoms, was the primary presentation in most of the patients (n =40). History of smoking was available in 10 of 21 patients with urachal tumours and 19 of 27 with non-urachal tumours. All patients had single tumours. The stagewise distribution of patients with non-urachal tumours showed two patients with stage A disease (Ta/T1); four with stage B (T2/T3a); nine with stage C (T3b); and 12 with stage D (T4/N +). Twenty-two patients had poorly differentiated tumours, and five had moderately differentiated tumours. Sixteen patients were treated with radical cystectomy, seven with pre-operative radiotherapy and nine without it. Adjuvant radiotherapy was given in eight patients and adjuvant 5-Fluorouracil-based chemotherapy was given to five patients for nodal metastases on viewing the histopathology results. Radiotherapy alone was used in six patients and a combination of radiotherapy and chemotherapy in three other patients. Two patients underwent a transurethral resection alone (Stage A). The stagewise distribution of patients with urachal tumours included nine stage B; l0 stage C and two stage © 1997W.B. SaundersCompany Limited

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I00

Table 1. Characteristics of patients in both the urachal and nonurachal groups Characteristic

Urachal (n=21)

Non-urachal (n=27)

9 12 49

23 4 58

8O "~ 60

Sex

Males Females Mean age Stage A B

C D Grade II III Treatment (a) Surgery Transurethral resection PC Pre-operative RT + PC RC Pre-operative RT + RC (b) Radical RT (c) RT + CT (d) No treatment Overall survival

0

2

9

4

10 2

9 12

5 16

5 22

19 0 5 5 9 0 0 0 2 45.7%

18 2 0 0 9 7 6 3 0 29.9%

PC, partial cystectomy; RT, radiotherapy; RC, radical cystectomy; CT, chemotherapy. D. Sixteen patients had poorly differentiated tumours and five had moderately differentiated tumours. Ten patients underwent a partial cystectomy, five with pre-operative radiotherapy and five without. Nine patients underwent radical cystectomy. Two patients' disease was too advanced for any therapy. The demographics of both these groups have been summarized in Table 1. Our treatment groups are heterogeneous as was expected from a series spanning 17 years and examirling an uncommon pathology. The extent of surgery and the use of radiotherapy and/or chemotherapy was dependent on the extent of the disease. Adjuvant chemotherapy was used in the initial period of the series. Those with more extensive local disease, especially if it was extending into the lower half of the bladder, underwent a radical cystectomy and those with disease limited to the dome of the bladder underwent a partial cystectomy. After completion of primary treatment the patients were followed up at 3-monthly intervals for 2 years, 6-monthly from the third to the fifth year, and thereafter annually with clinical and radiological evaluation as necessary at each visit. Actuarial survival rates were calculated using the Kaplan-Meir product limit method and differential survival curves compared with the SPSS+ and surreal software package.

Results

The overall 5-year survival in this series was 37% (Fig. 1). Non-urachal

The overall 5-year survival in patients with non-urachal tumours was 29.9%. The stagewise survival was 100% for

E lit L11 I

I II

I II

I

I

m ~.Of 20 I

I

1

2

I

I

3 4 Time (years)

I

I

5

6

7

Fig. 1. Overall survival in patients (n=48) with adenocarcinoma of the bladder.

stage A, 75% for stage B, 20.8% for stage C. and 8.3% for stage D (P=0.019). Grade-wise survival also showed a significant correlation (P=0.003). The 5-year survival in patients treated with radical cystectomy was 35%. There were three post-operative deaths and one patient in this group died after 30 months of myocardial infarction. Overall, six patients relapsed between 4 months and 16 months after radical cystectomy with regional or distant metastases (three pelvic and inguinal, three liver metastasis). Of these, five died and one is alive with disease at 26 months. Two patients who underwent a transurethral resection only for stage A turnouts are alive at 51 months and 61 months, respectively. There were no long-term survivors in patients treated with radiotherapy and/or chemotherapy. Only one patient is alive with disease at 8 months, and eight patients died of progressive disease between 1 and 9 months (mean: 4.3 months). We have not attempted to correlate the survival data to treatment as the number of patients treated with any one modality was small.

Urachal

The overall 5-year survival in patients with urachal tumours was 45.7%. The stagewise survival was 88.9% for stage B, and 31.3% for stage C (P=0.012). Grade-wise survival also showed a significant correlation (P=0.002). Of the 10 patients who underwent a partial cystectomy, four died of distant metastases (three liver and one multiorgan), one patient required salvage cystectomy for local recurrence and is alive at 29 months giving an overall survival of 56.3%. Of the nine patients who underwent a radical cystectomy four died, two after developing pelvic relapses and two with distant liver metastases giving overall survival of 25.9%. Comparison of the partial cystectomy group with the radical cystectomy group is probably not appropriate as radical cystectomy was advised for the more locally advanced tumours. There was no significant difference between the survival of patients with urachal cancer and the survival of those with non-urachal cancer ( P = 0.14) (Fig. 2).

Adenocarcinoma o f bladder

100 80 -~ 6O

E

,

,

,

L

,Uraehal

m 40

II

II

I

I

Non-urachal

20 I

I

1

2

I

I

3 4 Time (years)

I

I

5

6

Fig. 2. Survival in patients with urachal cancer (n---21) compared with those with non-urachal cancer 01= 27). Chi-squared =2.156; P--0.142.

Discussion

Adenocarcinomas account for 0.5-2% of primary bladder cancers, s'9 Those tumours arising from the bladder mucosa make up approximately two-thirds of cases, while those of urachal origin account for almost one-third. 9 Rare tumours with complicating exstrophy and endometriosis account for the remaining cases. The histological subtypes of adenocarcinoma of the bladder include: enteric, mucinous, signet ring, clear cell and mixed. Adenocarcinomas of the bladder arise in two common sites: (a) the bladder base area, including the trigone and the immediately adjacent lateral walls; and (b) the dome of the bladder. These tumours develop in response to chronic inflammation and irritation. 6'7 The question whether it is valid or necessary to separate adenocarcinomas into urachal or non-urachal type is debatable. Most authors agree that both these tumours probably have, in most instances, the same pathogenesis-metaplastic transformation to a glandular type of epithelium and ultimately to adenocarcinoma. Features that have been suggested as necessary for diagnosis of urachal cancer are: location in the dome; absence of cystitis cystica or cystitis glandularis; primary invasion of muscle or deeper structures; an intact or ulcerated epithelium; presence of a suprapelvic mass; a sharp demarcation between tumour and normal surface epithelium; presence of urachal remnants; and tumour growth in the bladder wall branching into space of RetziusJ 2'~3 We have used these criteria in our series to separate the patients into their respective groups. Less restrictive criteria have been described by others to separate urachal from non-urachal tumoursJ 4 Immunohistochemistry has not been valuable in making this distinction? Besides the criteria outlined clinically there appear to be differences between the two. In our series the urachal tumours arose in younger patients (49 years vs 58 years) at a male to female ratio close to 1 (4:3). In this series, as in others, haematuria was the most frequent presenting symptomJ 5 ,7 This was associated with irritative voiding symptoms in a significant number of patients with non-urachal adenocarcinoma.

159

The strongest reason for distinguishing the two types of tumours lies in the significant treatment differences between them. Most authors agree that for tumours localized to the dome, partial cystectomy with removal of the urachal tract and umbilectomy is the treatment of choice, t3-~5 Few, however, argue in favour of radical cystectomy for all patientsfl 2, In contrast, for localized non-urachal adenocarcinoma radical cystectomy is the treatment of choiceJ 5'~9The overall survival in this series was 37%. The 5-year survival rates in patients with urachal and nonurachal tumours were 45.7% and 29.9%, respectively, and the differences between the two were not statistically significant (P=0.14). The 5-year survival in patients with urachal tumours treated with partial cystectomy and radical cystectomy was 56.3% and 25.9%, respectively (P=0.76). Whitehead and Tesslerz2 reported a 25% 5-year survival rate with partial cystectomy and en-bloc excision of the umbilicus. Kakizoe et al.~9 recommended total cystectomy after they noted a local recurrence rate of 51% (37 of 72 patients). However, in their series, survival was similar in patients who underwent either partial or radical cystectomy. Henley et al. 23 reported on 38 patients of urachal cancer of whom 30 underwent a partial cystectomy with a 43% 5year survival, although 13 patients had local recurrence. The local relapse rate in our series of urachal tumours after a radical cystectomy was 22% compared to 10% after a partial cystectomy reflecting the fact that the choice of radical cystectomy in our series was based on the stage at presentation. Despite this, the above figures seem to suggest that outcome in terms of survival and local relapses is related more to the stage of disease at diagnosis than the extent of surgical procedure. More recently Herr ts reported excellent results following partial cystectomy for urachal cancer in 12 patients. The principle of wide pelvic dissection to encompass the umbilicus, tumour and entire urachal achieving negative soft tissue and bladder margins has been stressed to achieve cure. Certain biological features of urachal cancers, like protrusion into the bladder lumen without invasion of the wall, sharp demarcation between the tumour and adjacent bladder epithelium facilitates wide, safe and sure excision margins of normal bladder. Furthermore, urachal tumours usually extend superiorly within the urachal remnant and remain confined for a long time before they produce local invasion and distant metastases. All these features combined with an early diagnosis may improve prognosis of urachal neoplasms. Chemotherapy has been reported to have some presumptive advantage in the setting of metastatic disease. -'4'25We have no experience, however, with chemotherapy in urachal tumours. The role of adjuvant radiotherapy was unclear in our series. In contrast with urachal tumours, primary non-urachal adenocarcinomas characteristically occur on the base and the lateral walls of the bladderJ Most of these tumours are at an advanced stage at presentation. The site of these tumours and their high stage at presentation make them less amenable for conservative surgery. The 5-year survival of patients following radical cystectomy was 35%. We have not been able to match the 80% 5-year survival reported by Malek et a1.16 or the 100% 5-year survival rate reported by Jones et al. ~2Our experience with adjuvant therapy has been

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poor. Eight patients who received adjuvant radiotherapy and five patients who received adjuvant chemotherapy did not show any additional survival benefit. In conclusion, primary non-urachal adenocarcinoma is an aggressive tumour. The stage at presentation and the grade are powerful predictors of outcome. Additionally, Song et al.26 have recommended flow cytometric assessment of nuclear deoxyribonucleic acid ploidy pattern as a routine test to predict prognosis. In their series of 38 patients there was a significant difference in survival between diploid and non-diploid tumours, irrespective of grade of tumour. Radical cystectomy is the treatment of choice for nonurachal tumours due to their peculiar location in the bladder which precludes a conservative resection. In contrast, partial cystectomy in the initial management of urachal cancer may be considered in selected cases as this can enhance qualityof-life without necessarily influencing survival. Rather, the disease outcome seems more dependent on the stage at presentation. The role of adjuvant radiotherapy and chemotherapy is unclear at this time. It seems that prognosis of these cases will depend on earlier diagnosis and an effective systemic treatment programme which is currently unavailable.

8.

9. 10. I1. 12. 13. 14. 15. 16. 17. 18. 19.

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Accepted for publication 16 January 1997