PRIMARY ADENOCARCINOMA OF BLADDER TIMOTHY G. WILSON, M.D. T. RAND PRITCHETT, M.D. GARY LIESKOVSKY, M.D. NANCY E. WARNER, M.D. DONALD G. SKINNER, M.D.
From the Departments of Urology and Pathology, University of Southern California School of Medicine, and the Kenneth Norris Junior Cancer Hospital and Research Institute, Los Angeles, California
ABSTRACT--Between April 1983 and December 1987, we have treated and :followed 16 patients at the University o] Southern California ]or adenocarcinoma of the bladder. In 10 patients, the cancer originated # o m a nonurachal source; all underwent radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion. The other 6 patients had an apparent urachal origin of their cancer. Half of these patients were treated with radical cystectomy and urinary diversion and half were treated initially with segmental cystectomy. Presenting characteristics (age, sex ratio, and symptoms) were similar for both groups. Three-year adjusted actuarial tumor-free survival rates for the two groups were 48 percent and 31 percent, respectively. We advocate an aggressive approach ofradical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion for all invasive adenocarcinoma of the bladder, regardless of location.
prmary adenocarcinomas of the bladder are op from metaplasia of transit or neoplastic degeneration of it. Primary nonuraehal adenobladder is a rare lesion, oeeurnt to 2.0 percent of all epitheers.1 Histologically, it occurs in forms, though this seems unreaerally poor prognosis of all at etiologies have been theoesion is generally thought to ansitional epithelial metaplaon with ehronie irritation, inglandularis, and bladder exeseribed2 ,4 Loeareinoma is less c o m m o n nuraehal adenoeareinoma, ocpereent to 0.7 percent of all meies. It is thought to arise in a uraehal cyst remnant, ange of histologie differentiatssoeiated with cystitis glandu-
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laris.l.5 Controversy has revolved around treatment. 6 Anecdotal successes have been reported, but this tumor is generally unresponsive to radiation and chemotherapy. Best survival is reported with surgery, but superiority of segmental cystectomy versus radical cystectomy with urinary diversion is yet to be determined, v Because of this cancer's rarity and poor prognosis, study groups have been small, retrospective, and usually treated by multiple individuals over broad periods of time. This has made statistical analysis difficult and absolute conclusions impossible. Historically, it has been important to differentiate these two etiologies for invasive adenocarcinoma of the bladder because segmental cystectomy has been advocated by many previous investigators. In an attempt to better understand the success of contemporary treatment, we review our institution's recent experience at the University of Southern California.
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Material and Methods Between April 1, 1983 and December 31, 1987, 16 patients with nonmetastatie adenoeareinoma of the bladder were evaluated and treated with the intent to cure. All patients were found to have biopsy-proved muscle-invading bladder cancer without any evidence of metastatic disease prior to definitive surgery. Metastatic evaluation included a history and physical examination, blood serum chemistries, and chest x-ray film. Bone scans and computerized tomography (CT) scans were performed only w h e n physical examination or serum chemistries were suspicious for metastatic disease. All pathologic speeimens, either from transurethral reseetion or gross samples, were reviewed independently by a pathologist, both to eonfirm the diagnosis of adenoeareinoma and to exelude a nonbladder primary tumor. In addition, exclusion of a nonbladder primary adenoeareinoma ineluded both the preoperative evaluation and speeial histoehemieal stains when indieated. Follow-up and evaluation for metastatic disease ineluded periodic physieal examination, serum ehemistries, and ehest x-ray film for those patients having undergone radieal eysteetomy and urinary diversion; periodie eystoscopy was added to the follow-up evaluation for those patients having undergone segmental eysteetomy. All patients underwent either radical eysteetomy with bilateral pelvic lymph node dissection with urinary diversion or segmental eysteetomy as a primary mode of therapy. No patient in this series reeeived preoperative radiation or ehemotherapy. Criterion used for diagnosis of presumed uraehal adenoeareinoma was a muscle invasive adenoeareinoma in the dome of the bladder without assoeiated eystitis glandularis. The TNM system for pathologie staging of bladder eaneer was applied to all patients, s Adjusted actuarial survival tumor free rates were ealeulated for all groups. 9 Results Between April 1983 and December 1987, 462 patients underwent treatment for bladder cancer at the University of Southern California School of Medicine, Los Angeles, California. Ten of these patients (2.2%) had primary nonurachal adenocarcinoma, and all of these underwent radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion. 224
Six of these patients (1.3 % ) had uraehal adeno,: carcinoma. Three patients in this group underwent radical eysteetomy and urinary diversion; 2 underwent segmental eysteetomy; 1 patient u n d e r w e n t salvage eysteetomy and urinary diversion two months postoperative from his original segmental eysteetomy because pathologic margins were found to be positive for tu: mor. i~ Overall, the two groups were comparable in~ sex, age, and presenting symptoms. Of the 161~ patients, 11 were men and 5 were women. Theli age range was thirty-six to seventy-nine years{~ (mean age 63 years). Of these patient cent presented with hematuria, and had irritative symptoms. Only 1 pati palpable mass on pelvic examinat operatively. This was a fifty-six w o m a n with n o n u r a e h a l adenoe~ Stage P3BN +. Seven of 10 patients uraehal adenoeareinoma underwent tive intravenous pyelogram, and all were inte~ preted as being abnormal. Preoperative C~i scans were interpreted as positive (i.e., mass f~ the bladder or pelvic lymphadenopathy) in 3 ~ t 4 patients. Of the uraehal group, 3 Patients ha~ intravenous pyeli~grams, one o f ' an abnormal finding of bilateral sis. Two patients in this group ha, CT scans, one of which showed dome of the bladder: this patien~ six-year-old white man w h o segmental eysteetomy for Stage ] died of disease at sixteen mow tively. There were no intraoperat erative complications or death, these groups of patients. Overall, 7 of 14 patients who underwent rl ieal eysteetomy are eurrently alive, with foli~ up ranging from thirteen to forty-eight mon (median 22 months). Two of these patiei both in the nonuraehal adenoeareinoma g~ are alive with known pelvie recurrence of ease. One patient, a sixty-nine-year-old i with Stage P3BNO disease that was founJ reeur at sixteen months of follow-up is rently undergoing systemic ehemotherap~ seeond patient had tumor recurrence at t~i months, but has refused furthei I). Of the patients with ura einoma, neither of the 2 patie: went segmental eysteetomy alor died of disease at sixteen and ei respectively. The p a t i e n t th salvage eysteetomy two months
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TABLE I. ase 0.
Age/Sex
Lachal
1
Summary o] urachal and nonurachal cases o] adenocarcinoma
Stage
adenocarcinoma PINO PIS P3BN + 65/M PIS P1NO 64/F PIS PISNO 56/M P4N + 66/M PIS P3ANO* 79/M
52/M
2 :3 4 5 6 v i
57/M
P3ANO
8 9
59/F 69/M
P3BN + P3BNO
10
48/F
PINO PIS l~ lrachal adenocareinoma ;1: 78/M P2NO
~
I i: ~,: i3 4 5 .... :: 6.
Hist.
Therapy
Survival
Recurrence
MW Cis MW
R.Cx
D, 27 mos.
No
R.Cx
D O D , 3 mos.
Yes
Adeno. Cis Cis MW Cis PD
R.Cx
A, 26 mos.
No
R.Cx R.Cx
A, 22 mos. A, 20 mos.
R.Cx
D, 16 mos.
PD mucin signet cell MW PD signet cell Adeno. Cis
R.Cx
D, 12 mos.
No Yes, local 20 mos. Yes, local 8 mos. Yes, local 6 mos.
R.Cx R.Cx
D, 43 mos. A, 18 mos.
R.Cx
Other
•
o
Postop. chemo. EBR
Postop. cherno. 16 mos.
A, 41 mos.
No Yes, local 16 mos. No
R.Cx
A, 48 mos.
No
. .
Seg.Cx
A, 13 mos.
78/M
P4N +
MW Pap. MW
77/F
P2NO
PD
Seg.Cx
D, 22 mos.
62/M 71/F
P4N + P3ANO
R.Cx R.Cx
D, 8 mos. D
36/M
P4
PD • MW Pap. MW
Seg.Cx
D, 16 mos.
ros. marg., n o w l l mos. S/P salvage Cx Yes, local distant 19 mos. Yes, 4 rnos. No Yes
"" B
. . ..
Tx with chemo.
kEY; MW = moderately well-differentiated; PD = poorly differentiated; Cis = carcinoma in situ; R.Cx = radical cystectomy; ~.Cx = segmental cystectomy; EXR = external beam radiation; Pap = papillary; Chemo = chemotherapy. "~B2 adenocarcinoma prostate separate primary tumor.
)ecause pathologic margins were positive for :umor from the segmental cystectomy specihen, is currently alive at thirteen months of fol0wiup. Of the 3 patients with urachal adenoiareinoma who underwent radical cystectomy, Ii0ne is alive and free of disease at forty-eight ~n0nths of follow-up; one died, free of disease, ~ ! five months o f follow-up; and one died of dis~:~as~ at eight months of follow-up (Table I) Three-year actuarial tumor-free survival of overall is 43 percent. Three-year surs for the nonuraehal adenoeareinoma the uraehal adenoeareinoma group rcent and 31 percent, respectively. Comment 5, Mostofi, Thomson, and Dean 1° rearge retrospective study of 44 patients ~i with vesical adenocarcinoma treated with ~ ~'~~t!ple forms of therapy. These patients repre~nted those from the Armed Forces Tumor I~egistry prior to 1951 and were treated by •
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several different individuals. Overall five-year survival was 30 percent. Mostofi attributed the poor survival to lack of complete surgical resection. Thomas e t al. 1 reviewed 52 patients with vesical adenocarcinoma treated over a twentyone-year period. No survivors were reported in those treated with modalities other than surgery. A 17 percent five-year survival was reported in those treated with radical cystectomy. Stage of disease was not discussed. Subsequent reviews T M have found equally poor results regardless of the mode of therapy. However, these studies likewise have been retrospective in nature, covered long periods of time (10 to 50 years), and included patients from several different institutions. As a result, these groups do not represent good historic controis for our patients, but do confirm in general that primary nonurachal adenocarcinoma is aggressive and has a poorer prognosis than transitional cell carcinoma of the bladder. Based on previous work by Skinner and Lieskovsky, 14 a
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similar group of patients weighted by stage and treated in a similar manner for invasive transitional cell carcinoma would have an expected three-year survival of 62 percent. Our threeyear survival for nonurachal adenocarcinoma is 48 percent. Certainly, the data here are retrospective, the group is small, and follow-up is as yet relatively short. However, these data do represent a standardized group of patients treated in a consistent manner in the same institution. The history, management, and prognosis of patients with urachal adenocarcinoma are also not straightforward. Controversy has revolved mainly around treatment: radical cystectomy with urinary diversion versus segmental cystectomy. Mostofi et al. ~o reported a 16 percent fiveyear survival for those patients with urachal adenocarcinoma treated with a spectrum of therapy. Thomas, Ward, and Williams I reported 22 patients all treated with segmental cystectomy and found a 56 percent two-year survival and a 38 percent five-year survival. Johnson et al. in 1985, ~5 reviewed 14 cases of urachal adenocarcinoma treated over a tenyear period. Thirteen of these patients underwent segmental cystectomy. Most of these patients also received additional therapy with radiation or chemotherapy. Their reported fiveyear survival was greater than 50 percent. No study to date, however, compares segmental with radical cystectomy. Numbers in our group are small, but experience thus far indicates extremely poor survival of those patients treated with segmental cystectomy alone. Our only survivor underwent salvage cystectomy two months after his segmental cystectomy because margins were positive for tumor. Review of the literature, 7,~-2° indicates that urachal adenocarcinoma is more aggressive than primary nonurachal adenocarcinoma and recurrence usually occurs locally or in regional lymph nodes. This is presumably secondary to inadequate initial resection, or t u m o r spill during surgery. Hence, it seems puzzling that we might select a less aggressive form of therapy for a more aggressive disease. In this light, this seems especially apparent when the morbidity and mortality of radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion, is acceptably low. ~4 In addition, continent urinary diversion is currently a well accepted and applied modality; and these patients, specifically, may be well suited to performing a low-pressure reservoir (i.e., Kock
226
pouch) to urethral remnant anastomosis sine~ they should have no disease at the bladder nee[!i or urethra. In conclusion, we have treated 16 patient with invasive adenocarcinoma of the bladder a our institution. This cancer is rare and carries i poor prognosis. We advocate early aggressiv, surgery, i.e., radical cystectomy, bilateral pelvi lymph node dissection, and urinary diversio for this aggressive form of bladder cancer, ri gardless of etiology. Department of UroloI University of Southern Californ School of Medieii 1200 State Street, Suite 59( Los Angeles, California 900! (DR. WILSOr References 1. Thomas DG, Ward AM, and Williams JL: A study of~ cases of adenocarcinoma of the bladde 2. Abenoza P, Manivel C, and Frah cinoma of urinary bladder, Urology 2~ 3. Shaw JL, Gislason GJ, and Imbr titis glandularis to primary adenocarcir 79:815 (1958). 4. Darica PJ, MacKenzie F, Reed Ri adenovillons carcinoma of the bladder. 5. Lin JI, et ah Diffuse cystitis gl~ adenoeareinomatous change, Urology 6. Skinner DG: Management of inv~ pelvic node dissection can make a d (1982). 7. Sheldon CA, et ah Malignant ur~ (1984). 8. Union Internationale Centre le C of Malignant Tumors, ed 3, Geneva, 1 9. Kaplan EL, and Meier P: Nonp; incomplete observations, J Am Stat As 10. Mostofi FK, Thomson RV, and carcinoma of the urinary bladder, Car 11. Bennett JD, Wheatley JK, and \ rience with adenocarcinoma of the (1984). 12. Jacobo E, Loening S, Schmidt J adenocarcinoma of the bladder: a ret: tients, J Urol 117:54 (1977). 13.Krarner SA, et ah Primary nonu the bladder, J Urol 121:278 (1979). 14. Skinner DG, and Lieskovsky G: with pelvic node dissection compared therapy plus cystectomy in the manag cancer, J Urol 131:1069 (1984). 15. Johnson DE, Hodge GB, AbdulUrachal carcinoma, Urology 26:218 (. . . . j. 16. Nesbitt JA, and Walter PJ: Computed tomographi ing of microscopic dystrophic calcification in urachal ad cinoma, Urology 27:184 (1986). 17. Loening SA, Jacobo E, Hawtrey CE, and C~
Adenocarcinoma of the urachus, J Urol 119:68 (1978~ ~ 18. Kakizoe T, et ah Adenocarcinoma of urachus: rei~ cases and review of literature, Urology 21:360 (1983): 19. Jakse G, Schneider HM, and Jacob GH: Uracha ring cell carcinoma, a rare variant of vesical adeuocar~'~;~,~v incidence and pathological criteria, J Urol 120:764 (llJt~e~j 20. Hayman J: Carcinoma of the urachus, Patholo~
(1984).
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