Primary Non-Urachal Adenocarcinoma of the Bladder

0022-5347/79/1213-0278$02. 00/0 Vol. 121, March

THE JOURNAL OF UROLOGY

Printed in U.S.A.

Copyright © 1979 by The Williams & Wilkins Co.

PRIMARY NON-URACHAL ADENOCARCINOMA OF THE BLADDER STEPHEN A. KRAMER, JACQUES BREDAEL, BRYON P. CROKER, DAVID F. PAULSON JAMES F. GLENN*

AND

From the Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina

ABSTRACT

The clinical course of 34 patients with non-urachal adenocarcinoma of the bladder was reviewed and compared to the world experience. The 5-year survivorship was 19 per cent, with only 1 patient being free of disease. Metaplasia witH formation of glandular elements reflects the unstable potential of the transitional cell and may be associated with the biologic aggressiveness of the tumor. The association of diffuse uroepithelial changes and vesical malignancy is well documented. 1• 2 The appearance of cellular disorganization characterized by atypia, dysplasia and carcinoma in situ at locations adjacent to non-invasive transitional cell carcinoma enhances the probability of delayed invasive recurrence. 3 The ability of transitional epithelium to undergo metaplastic change with formation of either squamous or glandular elements is well documented and it is now believed that non-urachal adenocarcinoma of the bladder arises from transitional metaplasia. 4--7 Mostofi has analyzed the metaplastic potential of transitional urothelium and described 2 distinct patterns. 7 There can be progressive invagination of hyperplastic epithelial buds into the lamina propria (Brunn's nests), which becomes increasingly cystic and forms cystitis cystica. Metaplasia of the urothelium lining these cysts to columnar mucin-producing cells results in cystitis glandularis, a pre-malignant entity.s--io Secondly, cuboidal or.columnar metaplasia of the surface epithelium can occur without downward invagination. These metaplastic changes correlate well with the presence of chronic vesical irritation, infection and obstruction. 4, 5 • 8 • 11• 12 Progressive metaplasia would explain the coexistence of squamous, transitional and glandular epithelium in a single bladder. The association of unstable urothelium and biologically aggressive urothelial malignancy has been documented. 3 The metaplastic potential of urothelium is believed to document further the unstable potential of transitional urothelium. 4--7 Our study was undertaken to determine if the clinical course of patients with non-urachal adenocarcinoma of the bladder was in keeping with the postulated biologic aggressiveness of cells whose histology reflected an alteration of internal metabolic control. MATERIALS AND METHODS

Between 1930 and 1977, 34 patients with non-urachal adenocarcinoma of the bladder were seen at our medical center. The histologic character and clinical course of these patients were reviewed and the disease progression was compared to the published experience (table 1). 4--37 RESULTS

The patients ranged in age from 38 to 80 years old, with an average of 59 years (table 2). Male patients predominated 2.3 to 1.0. The tumor was confined to a single site in 56 per cent of Accepted for publication May 12, 1978. Read at annual meeting of American Urological Association, Washington, D. C., May 21-25, 1978. * Requests for reprints: P.O. Box 3707, Duke University Medical Center, Durham, North Carolina 27710. 278

the patients, with 44 per cent demonstrating multiple areas of involvement (table 3). Neoplastic involvement of the trigone was present in 40 per cent of the patients and tumors involved the dome in 16 per cent. Histology, grading and staging were in accordance with the classification of the World Health Organization. No correlation existed between mucin production or cystitis cystica with surgical stage or survivorship. More than 90 per cent of the patients presented with infiltrative lesions (table 4). Fifteen patients (44 per cent) underwent radical cystectomy, with or without radiation therapy. The remaining 19 patients (56 per cent) had other treatment modalities, including transurethral resection of the bladder tumor, radiation therapy, chemotherapy or combination therapy. After 2 years 28 patients were evaluable, with the over-all survival being 57 per cent with 32 per cent free of tumor. After 5 years 26 patients were evaluable, with the over-all survivorship being 19 per cent with only 1 patient (4 per cent) free of tumor (table 5). This single patient free of tumor had surgical stage A disease initially. Radical cystoprostatectomy increased survivorship minimally (2 of 12 or 17 per cent) over non-surgical treatment (1 of 11 or 9 per cent) in our series but no difference could be detected when the series were pooled. DISCUSSION

The observations that transitional epithelium presents a continuous epithelial diathesis and that the identification of unstable epithelium indicates a high risk for invasion are supported amply by the observed clinical course of patients with adenocarcinoma of the bladder. The metaplasia of transitional epithelium to glandular epithelium represents cellular instability and the subsequent clinical behavior of these tumors indicates their great biologic potential for damage. The 5-year survivorship figures documented in our series do not reflect cure but the ability of the biologic host to tolerate malignant disease. The accumulated survivorship figures and the documented 4 per cent rate free of tumor indicate that the methodology for control of adenocarcinoma of the bladder remains undeveloped. The enhanced survivorship seen after radical pelvic operations is believed, in retrospect, to reflect patient selection and the relative benefits of local disease control and the postponing of death from ureteral obstruction, bleeding and sepsis. Although an operation was beneficial in controlling local disease the high death rate indicates the degree of distant spread at the time of local control. The clinical course of patients with non-urachal adenocarcinoma of the bladder reflects the potential biologic aggressiveness of cells whose etiology reflects an alteration of internal metabolic controls.

279

PRIMARY NON-URACHAL BLADDER ADENOCARCINOMA

1. Non-urachal adenocarcinoma of the bladder SurgCystoscopy ical Grade Pathology Stage

TABLE

Pt. -Age-Sex

Symptoms

RM-48-M

Frequency

AW-55-M

Hematuria, frequency

LS-75-M

Terminal hematuria

FP-66-M

Duration

?

Treatment

Mos. Survival

Large tumor at trigone and dome 2 yrs. Large papillary tumor, ant. and rt. lat. wall 6 mos. Rt. post. lat. wall and neck

D

Well diff.

Infiltrating adenoca.

Palliative, radiotherapy

41

C

Mod. diff.

Infiltrating adenoca.

60

B

Mod. cliff.

Infiltrating adenoca.

Dysuria

3 mos. Multiple lesions on trigone and posterior wall

D

Poorly diff.

Infiltrating adenoca.

TW-66-M

Gross heme

1 mo.

C

Mod. diff.

Infiltrating adenoca.

EM-71-M

Painless heme

Extensive, lt. lat. wall, cystitis cystica 5 wks. Papillary, post. wall

Rad. cystectomy, chemotherapy, radiotherapy to meta. Transurethral resection of bladder tumor, radon seeds Transurethral resection of bladder tumor, preop. radiotherapy, ileal loop, no cystectomy Ilea! loop, no cystectomy

C

Mod./poorly diff.

Infiltrating adenoca., glandular meta.

AH-47-M AB-38-F

Hematuria Pyuria, microheme

7 mos. Exstrophy 1 yr. Dome

B C

Well diff. Mod. diff.

IB-71-F

Gross heme, frequency

7 mos. Rt. sup. lat. wall

C

Mod. diff.

RB-75-M

Gross heme, dysuria

3 mos. Rt. ant. lat. wall and neck

C

Mod. diff.

AH-65-F

Dysuria, quency

Papillary, rt. teral orifice

C

Mod. diff.

ME-80-F

Gross heme

2 mos. Rt. lat. wall

B

Well cliff.

SW-55-M

Gross heme

3 wks. Dome

B

Mod. diff.

GS-46-M

Terminal heme

1 yr.

Large, lt. lat. wall and floor

B

Well diff.

Hematuria

1 yr.

Large, sessile, across trigone

D

Mod. cliff.

Mucus in urine

3 mos. Extensive all quadrants and dome

B

Well diff.

EW-59-M

Gross heme

6 mos. 2

A

Well diff.

JD-62-M

Impotence

?

cm., papillary above rt. ureteral orifice Trigone

A

Well diff.

LW-55-M

Terminal heme

B

Mod. diff.

LG-62-M

Intermittent gross heme

C

Mod. diff.

CW-41-F

C

Mod. diff.

2 mos. Large, It. lat. wall

D

Poorly diff.

CV-77-M

Terminal heme, urgency, frequency Vesical irritation, heme Gross heme

6 mos. Sessile It. ureteral orifice, It. lat. wall 5 mos. Rt. ureteral orifice, rt. hemitrigone and neck, cystitis cystica 2 mos. Lt. hemitrigone, post. wall

3 mos. 3 cm., rt. ureteral orifice, rt. lat. wall

A

Mod. diff.

EJ-50-F

Gross heme

4 mos. Bladder neck, dome

B

Mod. diff.

PH-68-M

Gross heme, irritation

6 mos. Sessile, rt. lat. wall

B

Mod. diff.

Vesical tion

2 yrs.

B

Well diff.

WB-51-M PB-74-F

RB-50-M

MBS-48-F

fre-

irri ta-

3 yrs.

ure-

Sessile, rt. post. lat. wall

36, lost to followup 2 (widespread meta.)

Transurethral resection 8 of bladder tumor, radium, cutaneous loop ureterostomies Rad. cystectomy Papillary adenoca. 72 20 Mucinous adenoca., Transurethral resection of bladder tumor, parcystitis cystica, transitional cell Ca tial cystectomy, postop. radiotherapy Infiltrating adenoca., Preop. radiotherapy, rad. 25 cystitis cystica, cystectomy/loop glandular meta. 10, lost to folInfiltrating adenoca. Transurethral resection lowup of bladder tumor, partial cystectomy, postop. radiotherapy Infiltrating mucinous Transurethral resection 15 adenoca., glanduof bladder tumor, ralar meta. diotherapy, cutaneous ureterostomy Infiltrating papillary Transurethral resection 15 adenoca., follicular tumor, of bladder chemotherapy, radiocystitis therapy 26 Infiltrating mucinous Radium, partial cystecadenoca. tomy 18, lost to folTransurethral resection Mucinous adenoca. lowup of bladder tumor, radiotherapy 37 Infiltrating mucinous Preop. radiotherapy, rad. adenoca., cystitis cystectomy/loop, postcystica op. chemotherapy 2, lost to folInfiltrating papillary Transurethral resection adenoca., follicular lowup of bladder tumor, rad. cystitis cystectomy Papillary mucinous Transurethral resection 144 adenoca., glanduof bladder tumor lar meta. Adenoca., glandular Transurethral resection 31 of bladder tumor meta. Infiltrating mucinous Preop. radiotherapy, rad. adenoca. cystectomy Infiltrating adenoca., Transurethral resection 22 of bladder tumor, rad. follicular cystitis, glandular meta. cystectomy, postop. radiotherapy Infiltrating mucinous Transurethral resection 8 adenoca. tumor, of bladder postop. radiotherapy Infiltrating adenoca. Rad. cystectomy, postop. 6 radiotherapy Adenoca., cystitis Transurethral resection 60 cystica, squamous of bladder tumor, segmeta. mental cystectomy Infiltrating adenoca., Transurethral resection 11 glandular meta. of bladder tumor, rad. cystectomy Infiltrating mucinous Transurethral resection 31 adenoca., cystitis of bladder tumor, rad. cystica cystectomy Infiltrating adenoca., Transurethral resection 48 follicular cystitis, of bladder tumor, parglandular meta. tial cystectomy, transurethral resection of bladder tumor, rad. cystectomy

280

KRAMER AND ASSOCIATES TABLE

Duration

Pt. -Age - Sex

Symptoms

LD-56-M

Gross heme, vesical irritation Heme, frequency

BC-53-M

Surf 1ca Stage

Cystoscopy

2mos. Lt. lat. wall, trigone lOmos. Lt. ureteral orifice

I-Continued Grade

Pathology

Treatment

Mos. Survival

Transurethral resection of bladder tumor, rad. cystectomy Transurethral resection of bladder tumor, rad. cystectomy Transurethral resection of bladder tumor, radiotherapy Preop. radiotherapy, rad. cystectomy Radiotherapy

20, lost to followup

B

Mod. cliff.

Infiltrating adenoca., transitional cell Ca

C

Mod. diff.

Papillary adenoca., follicular cystitis

JS-77-M

Frequency, passage of tissue

2wks. Extensive, post. wall

C

Well cliff.

Infiltrating adenoca.

CJ-68-M

Suprapubic pain

?

Lt. lat. wall

C

Mod. diff.

JW-39-M

Irritation

lmo.

Bladder neck

B

Mod. diff.

CCG-50-M

Gross painless heme

7 days Bladder neck

B

Well diff.

Infiltrating mucinous adenoca. Mucinous adenoca., cystitis glandularis Mucinous adenoca., follicular cystitis

JS-45-F

Suprapubic pain

3wks. Dome, large

D

Well diff.

Infiltrating mucinous adenoca.

MM-63-M

Hematuria, obstruction

7mos. Large, lat. walls and trigone

D

Well diff.

Infiltrating mucinous adenoca.

TABLE

Current series 1977 Thomas and associates" Mostofi and associates•

34 28 27

Jacobo and associates13 Johnson and associates 14 Combined series

20 17 126

TABLE

TABLE

Male/Female Ratio 25/9 = 2.3:1 24/4 = 6:1 20/6 = 3.3:1 (1 unknown) 13/7 = 1.85:1 14/3 = 4.6:1 96/29 = 3:1

Age Range (av.) 38-80 (59) 54-78 (65) 18-77 (51) 36-80 (62.3) 38-78 (55) 18-80 (58)

3. Location of tumor on cystoscopy

Current series Thomas and associates" Mostofi and associates• Jacobo and associates13 Johnson and associates 14

Trigone No.(%)

Single Site No.(%)

Multiple Sites No.(%)

Dome Involved No.(%)

8/32 (40) (21) (24) (42) (29)

18/32 (56)

14/32 (44) (29) (36) (53) (24)

5/32 (16) (0) (16) (37) (47)

(71)

(64) (47) (76)

4. Histologic findings in surgically staged patients

Stage

Grade

MucinProducing

Associated Cystitis Cystica

A

Well diff., 2 Mod. diff., 1 Well diff., 6 Mod. diff., 7 Well diff., 1 Mod. diff., 11 Well diff. , 3 Mod. diff., 1 Poorly diff., 2

1

2

6

7

4

7

3

1

B C D

TABLE

5. Five-year survivorship-surgical staging Duke Series-34 Pts. No.(%)

Over-all Stage A StageB Stage C StageD

5/26 2/3 1/7 1/11 1/5

(19) (66.7) (15) (9) (20)

* Not all patients in total series were staged.

6 40 39, lost to followup 5 days 72, lost to followup 5, lost to followup

REFERENCES

2. Age and sex ratios

No. Pts.

Transurethral resection of bladder tumor, rad. cystectomy Preop. radiotherapy, bilat. ureterosig., no cystectomy, postop. radiotherapy Transurethral resection of bladder tumor, radiotherapy

39

Total Series-126 Pts. No.(%) 18/106* 2/3 4/7 1/26 2/25

(17) (66.7) (15) (4) (8)

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