0022-534 7/91/1465-1207$03.00/0 Vol. 146, 1207-1212, November 1991

THE JOURNAL OF UROLOGY

Printed in U.S.A.

Copyright© 1991 by AMERICAN UROLOGICAL ASSOCIATION, INC.

Review Article TRANSITIONAL CELL CARCINOMA OF THE PROSTATE HAIM MATZKIN,* MARKS. SOLOWAY*

AND

STEPHEN HARDEMAN

From the Department of Urology, University of Tennessee, Memphis and Baptist Memorial Hospital, Memphis, Tennessee KEY WORDS:

carcinoma, transitional cell; prostatic neoplasms

Transitional cell carcinoma of the prostate, once believed to be rare, is being diagnosed with increasing frequency. 1 In large part this may be due to the increasing use and efficacy of intravesical therapy for the treatment and prophylaxis of superficial bladder cancer. Finding transitional cell carcinoma in the prostate, an organ more commonly the site of adenocarcinoma, may come as a surprise to the clinician, who may be unsure of its etiology, treatment and prognosis. A review of the literature reveals a multiplicity of terms used to describe prostatic transitional cell carcinoma. Forty years ago, Melicow and Hollowell used the term Bowen's disease when they first described in situ carcinoma of the prostate coexistent with bladder transitional cell carcinoma. 2 Ortega et al alluded to the condition as Paget's disease because of the squamoid appearance of the cells and the intact appearing basement membrane. 3 Others named it intraepithelial carcinoma of the periurethral gland4 or intraductal carcinoma. 5 It was not until the mid 1970s that workers consolidated this knowledge, agreeing on the label of transitional cell carcinoma of the prostate for this disease entity. 6 HISTOGENESIS

Since transitional cell epithelium lines the prostatic urethra, it seems logical that the same etiological factors responsible for transitional cell carcinoma of the bladder should have the same effect on prostate urothelium. 7 Experimental and clinical observations have demonstrated that transitional cell carcinoma may be caused by carcinogens present in the urine. 8 In 1956 Franks and Chesterman suggested, from observations on a single patient with concomitant transitional cell carcinoma of the bladder and prostatic urethra, that the etiology of the 2 processes was the same. 9 Prostatic transitional cell carcinoma is almost always observed in individuals with concomitant bladder cancer. Ende et al hypothesized that transitional cell carcinoma of the prostate originates in the periurethral and prostatic ducts at the juncture of the columnar and transitional epithelium. 1° Karpas and Moumgis postulated that the hyperplastic transitional cells arise from indifferent or reserve cells, lying between the luminal epithelium and the basement membrane of the periurethral ducts.11 They analyzed 200 consecutive autopsies and found 4 cases with either periurethral duct hyperplasia or transitional cell carcinoma of the prostatic ducts. In these cases they found small, flattened, undifferentiated basal cells in addition to well defined columnar and transitional epithelium. These cells may show hyperplasia within periurethral ducts and may be the source of transitional cell carcinoma of the prostate. Ullmann and Ross described 9 cases of transitional cell hyperplasia in ducts of periurethral glands. 12 They support, in principle, the theory of Ende et al that invasive transitional cell carcinoma of the prostate is a tumor originating in the ducts of the mucosal or submucosal glands of the prostatic urethra, which have penetrated the basement membrane and secondarily invaded the prostatic stroma. 10 In a review of 20 cystoprostatectomy cases with prostatic * Current address·: Department of Urology, University of Miami School of Medicine, 1400 N.W. 10th Ave., Miami, Florida 33136.

involvement of bladder transitional cell carcinoma, Mahadevia et al described 2 modes of spread of urothelial cancer into the prostate: 1) tumor cells invade the wall of the ducts and infiltrate between the lining epithelium and the basal cells, and 2) tumor cells are intercalated with apparently normal epithelial cells, similar to Paget's disease of the nipple.13 Transitional cell carcinoma of the prostate may also originate from direct extension of bladder cancer or rarely by implantation from an upper tract transitional cell carcinoma. 7• 14 PATHOLOGY

As mentioned, early reports referred to these tumors by different names. Some even used the term mixed carcinoma,4· 15 describing adenocarcinoma and transitional cell elements together, causing further confusion. Tannenbaum first clarified the issue and provided a concise review of the pathological findings. 6 Although histologically transitional cell carcinoma and adenocarcinoma are distinct, they cannot be differentiated on gross examination. 16• 17 In the advanced stage both lesions produce an enlarged, hard, fixed irregular gland. However, in the earlier stage transitional cell carcinoma starts in the prostatic urothelium and progresses via the ductal system into the stroma. Adenocarcinoma of the prostate usually arises in glands in the peripheral zone of the prostate and only in later stages does it involve the urethra. Early reports failed to distinguish between primary and secondary transitional cell carcinoma of the prostate. Primary transitional cell carcinoma of the prostate implies no pre-existing bladder cancer. Most studies within the last 20 years do make a distinction between the 2 entities. 1a-2o Just as with neighboring bladder cancer, tumor grade is classified as well, moderately and poorly differentiated. 21 In the pathology report in situ involvement of the prostatic urothelium or ducts by transitional cell carcinoma must be differentiated from prostatic stromal invasion, 22 since they do not have the same prognosis. Once prostatic transitional cell carcinoma is diagnosed there must be sufficient tissue to determine the extent of tumor involvement. STAGING

There currently is no widely accepted staging system for prostate transitional cell carcinoma. According to the current Jewett-Strong and tumor, nodes and metastasis (International Union Against Cancer) classifications a patient with bladder cancer and transitional cell carcinoma of the prostate has stage Dl or T4 disease regardless of the depth of involvement of the bladder or prostate transitional cell carcinoma. This implies that transitional cell carcinoma of the prostate is an advanced tumor in all instances. There is no provision in these classifications for the different degrees of prostatic involvement ranging from carcinoma in situ to stromal invasion. The prognosis for carcinoma in situ and ductal involvement is not the same as for stromal invasion. 16 The extent of the prostatic tumor invasion may not correlate with the stage of the bladder tumor. There is a growing awareness that vesical and prostatic transitional cell carcinoma must be staged separately. However, there is no consensus on the proper staging of the latter disease.

1207

1208

MATZKIN, SOLOWAY AND HARDEMAN

Greene 23•24 and Kopelson4 et al staged transitional cell carcinoma of the prostate according to the system used to stage acinar adenocarcinoma of the prostate. With that classification Kopelson et al reported 10% of the tumors to be stage A, 3% stage B and 86% advanced (stages C and D) cancer. This classification is inappropriate because: 1) transitional cell carcinoma starts in the urothelium, while adenocarcinoma begins in the peripheral zone, 2) palpable changes are infrequent with transitional cell carcinoma but frequent with the adenocarcinoma, 3) diagnosis is made by a transurethral biopsy in prostatic transitional cell carcinoma and by transrectal or perineal biopsy in the case of adenocarcinoma, and 4) the staging in adenocarcinoma is primarily based on tumor volume, which correlates with prognosis. In transitional cell carcinoma the prognosis is based on the invasion through the ducts into the stroma. Chibber et al classified their patients into 3 subgroups: 1) carcinoma in situ involving the prostatic urethra and ducts (with or without similar bladder involvement), 2) noninvasive papillary tumor of prostatic urothelium or ductal involvement together with similar bladder tumor and 3) invasive tumor of the bladder base and neck with extensions into the prostate. 25 Among other problems with this classification is that it does not consider that the prognosis of transitional cell carcinoma of the prostate may be totally independent of the bladder tumor. Kirk et al divided their 33 patients into 4 groups: 1) direct extension of a bladder tumor into the prostate gland, 2) previous bladder tumor recurrent in prostate, 3) carcinoma in situ of the prostatic urethra and 4) apparent primary prostatic tumor. 26 Again, these investigators have artifically separated primary and secondary transitional cell carcinoma of the prostate, although there is no information that the prognosis is different. It seems appropriate to base the staging system on the integrity of the basement membrane. The classification used by Hardeman and Soloway does so accordingly and uses 3 subgroups: 1) tumor confined to the prostatic urothelium (carcinoma in situ), 2) invasion into ducts and acini but limited by the basement membrane and 3) stromal invasion. 21 · 27 This staging system does not differentiate primary from secondary prostatic transitional cell carcinoma. It also does not consider the tumor in the bladder. In a review of our experience in 35 men undergoing cystoprostatectomy with the aforementioned classification, 20% had carcinoma in situ in the urethra, a third had tumor involving the ducts and acini, and 46% had stromal invasion. Wishnow and Ro grouped their patients into only 2 categories: 77% had transitional cell carcinoma limited to the ducts and 23 % had stromal invasion. 28 While using similar subclassifications and excluding patients with direct invasion from muscle invasive bladder cancer, Wood et al reported that 39% of their patients had stromal invasion. 29 INCIDENCE

There are no large autopsy series that sought to define the incidence of prostatic transitional cell carcinoma. Several authors suggested that transitional cell carcinoma of the prostate is under-reported. 6· 12·19 Some believe that transitional cell carcinoma of the prostate is being diagnosed with increasing frequency. 1 A possible reason for this belief is the increasing use and success of intravesical therapy in patients with superficial bladder cancer. This might alter the natural history of lower urinary tract cancer. Most intravesical agents require direct contact with the tumor. The prostatic urothelium is less likely to be reached by these agents because of a competent bladder neck. The urothelium of the prostatic urethra continues to be exposed to carcinogens, possibly resulting in malignant transformation in an environment shielded from therapeutic agents.18, 21, 80, 31 Several studies have reported the incidence of prostate transitional cell carcinoma in conjunction with past or present bladder transitional cell carcinoma. In most of these reports

only select groups of patients with superficial bladder tumor, that is carcinoma in situ, had routine biopsies of the prostatic urothelium. Thus, the incidence remains unknown. The apparent incidence of prostatic transitional cell carcinoma may be increasing due to either an increased prevalence of bladder cancer or an increasing number of prostate biopsies in patients with bladder transitional cell carcinoma. Another possible explanation may be the increasing awareness of this entity among pathologists. Wood et al step-sectioned the prostate after 84 radical cystoprostatectomies performed for bladder transitional cell carcinoma. 29 Of the specimens 43 % had prostatic transitional cell carcinoma. In a previous review Montie et al identified a 20% incidence of prostatic involvement in surgical specimens. 32 In a review of 350 men who underwent cystoprostatectomy for bladder transitional cell carcinoma, Schellhammer et al reported that 12% had prostate transitional cell carcinoma. 22 Coutts et al reported 23% with transitional cell carcinoma of the prostate and an additional 28% with dysplasia. 33 Other publications based on surgical data estimated prostatic transitional cell carcinoma to vary between 10 and 51 %.8•13· 22· 29· 32-36 We reviewed 121 consecutive radical cystoprostatectomies performed for bladder cancer. A total of 37 men (31%) had prostatic transitional cell carcinoma. The variance of reported figures probably reflects different sampling methods, rather than true differences in incidence (see table).8· 13• 22· 29· 32, 33, 36-40 It has been suggested that patients with carcinoma in situ of the bladder are more likely to have prostatic involvement. In a review article from the Mayo Clinic 26% of the patients with carcinoma in situ of the bladder had prostatic transitional cell carcinoma. 19 The incidence was even higher if the trigone was involved. Seemayer et al found that 70% of their patients with carcinoma in situ of the bladder also had prostatic transitional cell carcinoma. 8 Prout20 and Coutts33 et al reported that the incidence of transitional cell carcinoma of the prostate was 68% and 80%, respectively, when bladder carcinoma in situ was found in the cystectomy specimen. Patients treated for carcinoma in situ and superficial bladder cancer unsuccessfully with intravesical chemotherapy appear to be at high risk for prostatic transitional cell carcinoma. 21 · 29•31· 35 In some instances, intravesical therapy eradicated or prevented bladder transitional cell carcinoma, with the site of treatment failure being the prostatic urethra. 27 Bretton et al reported a rather low 8. 7% incidence of prostatic urethral involvement among 264 patients with multifocal superficial bladder cancer.37 Admittedly, they performed biopsies only in patients with gross cystoscopic findings of prostate involvement rather than on a systematic basis. This again emphasizes the problems encountered in accurately estimating the true incidence of prostatic transitional cell carcinoma. Primary transitional cell carcinoma of the prostate is relatively rare. In the Mayo Clinic experience 161 of 5,700 men (2.8%) who presented with cancer of the prostate had transitional cell carcinoma. 19 Of the men 37 (23%) had no associated bladder or upper tract malignancy and, thus, they were classified as having primary transitional cell carcinoma of the prostate. Others suggested that the incidence of primary transitional cell carcinoma is low and that in most instances of primary transitional cell carcinoma careful examination of the bladder by means of multiple biopsies would have disclosed occult carcinoma in situ of the bladder.13· 16 SIGNS AND SYMPTOMS

Most men are asymptomatic. If transitional cell carcinoma of the prostate is associated with bladder cancer patients may have signs or symptoms related to the bladder cancer, for example, hematuria and vesical irritability .19· 22· 41· 42 Symptoms related to obstruction are infrequent and are virtually always associated with stromal involvement.

1209

TRANSITIONAL CELL CARCINOMA OF PROSTATE

Occurrence of prostate transitional cell carcinoma in reported series Type of Series

Reference

Radical cystoprostatectomy for bladder Ca in situ Radical cystoprostatectomy for bladder transitional cell Ca

Seemayer et al8 Schellhammer et al 22

Recurrent bladder Ca in situ, biopsies Radical cystoprostatectomy for bladder transitional cell Ca Radical cystoprostatectomy for bladder transitional cell Ca, whole mounts Radical cystoprostatectomy for bladder transitional cell Ca

Grabstald36 Coutts et al'" Montie et al

32

Mahadevia et al 13 Hillyard et al39 Wood et al

29

Bretton et al37 Terris et al

38

Hardeman and Soloway•

0

Superficial bladder transitional cell Ca, biopsies Radical cystoprostatectomy for bladder transitional cell Ca, whole mounts Multifocal superficial bladder transitional cell Ca, biopsies Radical cystoprostatectomy for bladder transitional cell Ca Radical cystoprostatectomy for bladder transitional cell Ca

DIAGNOSIS

Since the incidence of transitional cell carcinoma of the prostate is increasing and knowledge of its presence is necessary to make appropriate decisions, with regard to therapy of tran sitional cell carcinoma of the bladder a representative sample of the prostatic urothelium should be available for examination in any high grade bladder tumor. Several studies have dealt with the optimal method to biopsy the prostate in patients with bladder cancer. Wood et al compared the accuracy of prostate needle biopsy, fine needle aspiration and transurethral biopsy of the prostate to detect the presence of transitional cell carcinoma of the prostate in 25 men before radical cystoprostatectomy. 29 Of the 25 patients 10 had transitional cell carcinoma of the prostate. The accuracy rate was 20%, 40% and 90% for transrectal needle biopsy, fine needle aspiration and transurethral biopsy, respectively. Rubenstein and Rubnitz reported results similar to Wood et al, with a 90% positive rate for transurethral biopsy and 40% for transrectal biopsy. 17 Therefore, transurethral resection is the most appropriate method to establish the diagnosis. 9 • 33 The biopsy must provide sufficient material to allow one to examine not only the urothelium but the prostatic ducts. Thus, cold-cup biopsies are inferior to transurethral resection. 43 One might question the wisdom of violating the prostatic urethra in the presence of high grade transitional cell carcinoma of the bladder. Will this lead to tumor cell implantation? Laor et al compared 137 patients who underwent simultaneous transurethral resection of a bladder tumor and prostatic hyperplastic tissue to 150 patients who underwent transurethral resection of a bladder tumor only. 44 There was no evidence that simultaneous resection of bladder tumor and the prostate adversely affected the incidence of tumor in the prostatic urethra. Although this does not exclude the potential for implantation, we believe that the necessity to determine the presence or absence of transitional cell carcinoma of the prostate justifies this approach. Recently, Terris et al reported on the use of transrectal ultrasound in 58 men with bladder transitional cell carcinoma. 38 All patients underwent radical cystoprostatectomy and transitional cell carcinoma of the prostate was found in 20. In 10 men (50%) only urethral involvement was noted: 3 had ductal

No. Pts.

No. With Prostate Transitional Cell Ca(%)

7

5 (78)

350

42 (12)

40

4 (10)

43

22 (51)

141 85 62 20

27 24 25 9

(20) (28) (40) (45)

Details of Prostatic Involvement Highly select group 38 evaluable pts. (16 ductal or ductal plus acinar and 22 stromal) Not further specified 12 dysplasia, 6 Ca in situ and 4 frank Ca 1972-1981 1982-1984 1984-1985 7 focal in periurethral ducts, 2 extensive involvement Not further specified

28

7 (25)

84

36 (43)

14 stromal invasion

264

23 (8.7)

19 mucosa! and 4 ductal

58

20 (34)

86

30 (35)

10 prostatic urethra and 7 stromal invasion 8 urethral, 8 ductal and 14 stromal invasion

involvement and 7 (35%) had stromal invasion. As expected, those with carcinoma in situ had a normal transrectal ultrasound. Ductal involvement was not detected by transrectal ultrasonography. Of 7 men with tumor extending into the stroma 5 had hypoechogenic areas. All cases of periprostatic involvement were detectable. The authors concluded that transrectal ultrasound may enhance the surveillance of men with transitional cell carcinoma of the bladder. However, we believe that the low incidence of prostatic stromal transitional cell carcinoma in men with bladder cancer does not support routine transrectal ultrasonography. TREATMENT AND PROGNOSIS

There is a relative scarcity of information on different treatment strategies for patients with various stages of transitional cell carcinoma of the prostate. This is true especially when discussing the rather infrequent cases of primary prostate transitional cell carcinoma. The majority of men will have a history of transitional cell carcinoma of the bladder. In such cases the clinicians must consider the status of the bladder urothelium before a decision is made on treatment of the prostatic transitional cell carcinoma. Until recently the treatment of transitional cell carcinoma of the prostate was anecdotal and results of different therapeutic modalities were difficult to evaluate. The response of carcinoma in situ of the prostatic urethra to intravesical therapy has been investigated only recently. Bacillus Calmette-Guerin (BCG) has received the most attention. The mechanism of action of BCG is still not entirely elucidated. Although local surface contact with the prostatic urethra is of a short and limited duration (voiding time) it may be sufficient to treat carcinoma in situ. Droller commented on a theoretical basis that the BCG treatment might not be successful due to insufficient contact time of the drug. 45 Several studies have indeed reported that the prostatic urethra is a common site of recurrence after the use of BCG for bladder transitional cell carcinoma. 27 • 35• 46 Transurethral resection of the prostate performed before intravesical BCG instillation may partially or even totally remove the prostatic tumor, and the ensuing bladder neck incompetence may lead to sufficient contact time between the drug and the urothelium. There are a number of reports on the administration of BCG for carcinoma in situ of the prostate.

1210

MATZKIN, SOLOWAY AND HARDEMAN

Bretton et al performed transurethral resection followed by the administration of BCG in 23 men with multifocal superficial bladder cancer and concomitant carcinoma in situ of the prostatic urethra. 37 All but 4 men had tumor limited to the mucosa, while 48% remained free of disease after therapy. Ten patients (44 %) suffered either local or metastatic progression of the bladder cancer but none had progression in the prostatic urethra. Of the 10 men 7 eventually underwent cystectomy. Thus, the over-all cystectomy rate was 30%. The authors suggested that this mode of treatment is an alternative to immediate radical cystectomy. Hillyard et al treated 8 men in a similar fashion and 7 had a complete response. 39 Two patients had progression while on treatment (1 in the bladder and 1 in the prostate). Only 1 patient had invasive bladder and prostatic tumor 15 months after completion of BCG treatment and he underwent radical cystoprostatectomy. These authors also suggested that a trial of BCG is worthwhile before suggesting a radical operation. Recently, Siami et al added another well documented case successfully treated with BCG.47 In patients with more extensive involvement of the prostate, for example ductal or stromal transitional cell carcinoma, most clinicians would agree that intravesical treatment is contraindicated. 14· 19· 22· 25 Currently, few advocate transurethral resection as the only primary treatment. 25· 48 An exception is Chibber et al, who subgrouped their patients and, while suggesting a radical treatment for stromal involvement of the prostate, advocated transurethral resection when the tumor is confined to the mucosa or periurethral ducts. 25 In a review of 23 men with prostatic transitional cell carcinoma in the surgical specimen after radical cystoprostatectomy, Wishnow and Ro showed that radical surgery was curative in a high percentage of patients (16 of 18) with carcinoma in situ of the prostatic urethra. 28 During followup 11 % of the patients with carcinoma in situ of the prostatic ducts had metastasis compared to 100% who had invasion into prostatic stroma. They recommended that chemotherapy should be used in addition to radical surgery in patients with prostatic stroma invasion because of the poor prognosis of these patients. Schellhammer et al studied a group of 38 patients with prostatic transitional cell carcinoma. 22 Of these patients 22 had stromal invasion and were treated with preoperative adjunctive radiotherapy, radical cystoprostatectomy and bilateral lymph node dissection. They achieved a 20% 5-year disease-free survival rate. Zincke et al strongly advocated an aggressive approach consisting of radical cystoprostatectomy and concomitant urethrectomy, regardless of the depth of prostatic involvement.19 In their large series a conservative, nonradical operation was associated with early failure. Only 25% of their 80 men treated without a radical operation survived 5 years, compared to more than 50% of the 76 men treated with a radical operation. For patients undergoing radical cystectomy a preoperative diagnosis of transitional cell carcinoma of the prostate is significant in the decision concerning urethrectomy. In the past, some physicians recommended simultaneous urethrectomy for all patients undergoing cystectomy,19 while others disagreed. 26 A selective approach seems to be reasonable, one that would allow low risk patients to retain the urethra for potential bladder reconstruction. Hardeman and Soloway recently reviewed the clinical course of 86 men after radical cystoprostatectomy to determine who were at highest risk for urethral recurrence. 40 Of 30 patients with prostatic involvement 37% suffered urethral recurrence, compared to only 4% of patients with no prostatic involvement. They recommended prophylactic urethrectomy only in patients with prostatic transitional cell carcinoma. Radiotherapy is mentioned by some as therapy for stromal involvement of the prostate with transitional cell carcinoma. Chibber et al treated 12 men with grade 3 stromal involvement

with radical radiotherapy. 26 Only 3 patients had no evidence of disease with a mean followup of 20 months. Radiation therapy should be reserved for patients who are not medical candidates for or who refuse radical cystoprostatectomy. The response of transitional cell carcinoma to systemic chemotherapy has been reviewed. Methotrexate, vinblastine, doxorubicin and cisplatin comprise the most effective regimen for advanced urothelial cancer. One would assume it would be the chemotherapy regimen of choice for prostatic transitional cell carcinoma. However, this still remains to be proved. Doxorubicin, 5-fluorouracil, cyclophosphamide and cisplatin have been used in sporadic cases of prostate transitional cell carcinoma singly or in combination. 23· 26· 41· 49· 50 The longest clinical response achieved was 9 months. In a small group of patients with involvement of the prostate but with no metastases, Chibber et al used systemic chemotherapy as the initial treatment and none of the patients had progression. 25 Our recommendations regarding therapy depend on the depth of prostatic involvement and are summarized in figure 1. In all high grade bladder tumors transurethral resection sampling of the prostatic urethra should be performed. If positive, one can give a course of intravesical therapy or proceed with cystoprostatectomy and concomitant urethrectomy. The decision is based primarily on the depth of invasion in the prostatic biopsy. If no disease is present in the bladder and prostatic transitional cell carcinoma is confined to the urothelium a treatment course (6 to 8 instillations) of intravesical therapy is a reasonable choice. If BCG or other intravesical therapy fails to eradicate prostatic transitional cell carcinoma cystoprostatectomy with urethrectomy is the treatment of choice. For ductal involvement it is difficult to be certain that stromal invasion does not exist, and we recommend radical cystoprostatectomy and urethrectomy. For high grade stage T2 or greater bladder tumor and a positive prostatic biopsy cystoprostatectomy and urethrectomy are indicated. If the biopsy is negative concomitant urethrectomy is not critical. In the past most physicians who study this disease anticipated a grim prognosis for patients with prostate transitional cell carcinoma. 7· 51 There evidently is a different prognosis according to stage (depth of prostatic involvement). In patients with carcinoma in situ of the prostatic urethra the prognosis is not adversely affected by the prostatic tumor. 22 Prostatic stromal invasion in otherwise low stage bladder tumor decreases the survival anticipated from the bladder tumor alone. 52· 53 Among the 34 men with transitional cell carcinoma of the prostate in our series followed for a mean of 28 months after radical cystoprostatectomy 16 have died. Of 7 patients with carcinoma in situ of the prostatic urethra 6 are alive. The patient who died had a stage T3bN+ bladder tumor. Of the 9 men with ductal and acinar involvement with no penetration of the basement membrane 3 have no evidence of disease and

DIAGNOSTIC

BLAPPEO DISEASE

.EEl!llllUllE

High grade bladder TCC

Slages Ta, T1, CIS

"+

TBfAIMENT OPTIONS CIS only--TUR-P+lntravesical treatment

I

>

+ Ductal Only -

+ Slromal

Failure .j, ·Cystoprostatectomy+ Urethreclomy

Transurethral

resection biopsy ~:e:~~a.prosta\lic

I

High grade bladder TCC Stages T:1!2

... negative--Treat bladder tumor Irrespective of prostate

+ Any depth of prostatic -Cystoprostatectomy+Urethrectomy Involvement

- negative --Treat bladder tumor irrespective of prostate

Fm. 1. Algorithm of evaluation and treatment options. TCC, transitional cell carcinoma. CIS, carcinoma in situ. TUR-P, transurethral resection of prostate.

TRANSITIONAL CELL CARCINOMA OF PROSTATE 121

RCP for bladder TCC

I

37 (31%)

With prostatic involvement

Dead

Alive

I

16 (47%) follow up 28'

18 (53%) follow up 57•

~

with disease

I

3 (17%) follow up 12•

~Other

of disease

l'8)

\

15 (83%) follow up so•

\

11 (69%) follow up 36•

I

5 (31%) follow up 17.5'

'Mean follow up period in months 3 patients lost to follow up

FIG. 2. Description of study groups. RCP, radical cystoprostatectomy. TCC, transitional cell carcinoma. NED, no evidence of disease.

Gare dead (2 died of disease). Of the 16 patients with prostatic stromal invasion 8 (50%) were alive at the time of this report (3 with evidence of disease). All men who died did so secondary to tumor (fig. 2). In the rare case of primary transitional cell carcinoma of the prostate stromal invasion is present in most patients at diagnosis. Therefore, the prognosis is extremely poor. 17• 54 LaPlante and Brice found no 5-year survivors. 53 Kirk et al reported that these patients rarely survive longer than 2 years. 26 CONCLUSIONS AND RECOMMENDATIONS

Transitional cell carcinoma of the prostate has become a well recognized entity and may be increasing in incidence. Most cases are diagnosed in association with bladder cancer. Primary prostatic transitional cell carcinoma is rare. Staging presently is ill-defined, and no staging system is accepted by all involved in the diagnosis and treatment of this disease. There seems little doubt that a reason for the increase in the incidence of prostatic transitional cell carcinoma is a growing awareness of and search for the disease. In patients with bladder cancer, especially in the presence of carcinoma in situ, an independent evaluation of the prostate is important before any therapeutic decision. We recommended transurethral biopsies of the gland and encourage others to consider on a routine basis the assessment of the prostate in patients with high grade, multifocal bladder tumors, including carcinoma in situ. A positive cytology study in the absence of an identifiable bladder tumor also is an indication for a transurethral resection biopsy of the prostatic urothelium. Various treatment options have been presented. Aggressiveness of therapy should be based on staging (depth of invasion). REFERENCES

1. Wendelken, J. R., Schellhammer, P. F., Ladaga, L. E. and E!-

Mahdi, A. M.: Transitional cell carcinoma: cause of refractory cancer of prostate. Urology, 13: 557, 1979. 2. Melicow, M. M. and Hollowell, J. W.: Intra-urothelial cancer: carcinoma in situ, Bowen's disease of the urinary system: discussion of thirty cases. J. Urol., 68: 763, 1952. 3. Ortega, L. G., Whitmore, W. F., Jr. and Murphy, A. I.: In situ carcinoma of the prostate with intra-epithelial extension into the urethra and bladder; Paget's disease of the urethra and bladder. Cancer, 6: 898, 1953. 4. Kopelson, G., Harisiadis, L., Romas, N. A., Veenema, R. J. and Tannenbaum, M.: Periurethral prostatic duct carcinoma: clinical features and treatment results. Cancer, 42: 2894, 1978.

1211

5. Rhamy, R. K., Buchanan, R. D. and Spalding, M. J.: Intraductal carcinoma of the prostate gland. J. Urol., 109: 457, 1973. 6. Tannenbaum, M.: Transitional cell carcinoma of prostate. Urology, 5: 674, 1975. 7. Johnson, D. E., Hogan, J. M. and Ayala, A. C.: Transitional cell carcinoma of the prostate: a clinical and morphological study. Cancer, 29: 287, 1972. 8. Seemayer, T. A., Knaack, J., Thelmo, W. L., Wang, N.-S. and Ahmed, M. N.: Further observations on carcinoma in situ of the urinary bladder: silent but extensive intraprostatic involvement. Cancer, 36: 514, 1975. 9. Franks, L. M. and Chesterman, F. C.: Intra-epithelial carcinoma of prostatic urethra, periurethral glands and prostatic ducts. (Bowen's disease of urinary epithelium.) Brit. J. Cancer, 10: 223, 1956. 10. Ende, N., Woods, L. P. and Shelley, H. S.: Carcinoma originating in ducts surrounding the prostatic urethra. Amer. J. Clin. Path., 40: 183, 1963. 11. Karpas, C. M. and Moumgis, B.: Primary transitional cell carcinoma of prostate gland: possible pathogenesis and relationship to reserve cell hyperplasia of prostatic periurethral ducts. J. Urol., 101: 201, 1969. 12. Ullmann, A. S. and Ross, 0. A.: Hyperplasia, atypism and carcinoma in situ in prostatic periurethral glands. Amer. J. Clin. Path., 47: 497, 1967. 13. Mahadevia, P. S., Koss, L. G. and Tar, I. J.: Prostatic involvement in bladder cancer. Prostate mapping in 20 cystoprostatectomy specimens. Cancer, 58: 2096, 1986. 14. Thelmo, W. L., Seemayer, T. A., Madranas, P., Mount, B. M. M. and MacKinnon, K. J.: Carcinoma in situ of the bladder with associated prostatic involvement. J. Urol., 111: 491, 1974. 15. Bates, H. R., Jr. and Thornton, J. L.: Carcinoma of the prostate ducts. Amer. J. Clin. Path., 45: 96, 1966. 16. Sawczuk, I., Tannenbaum, M., Olsson, C. A. and deVere White, R.: Primary transitional cell carcinoma of prostatic periurethral ducts. Urology, 25: 339, 1985. 17. Rubenstein, A. B. and Rubnitz, M. E.: Transitional cell carcinoma of the prostate. Cancer, 24: 543, 1969. 18. Wolfe, J. H. N. and Lloyd-Davies, R. W.: The management of transitional cell carcinoma of the prostate. Brit. J. Urol., 53: 253, 1981. 19. Zincke, H., Utz, D. C. and Farrow, G. M.: Review of Mayo Clinic experience with carcinoma in situ. Urology, suppl. 4, 26: 39, 1985. 20. Prout, G. R., Jr., Griffin, P. P., Daly, J. J. and Heney, N. M.: Carcinoma in situ of the urinary bladder with and without associated vesical neoplasms. Cancer, 52: 524, 1983. 21. Hardeman, S. W. and Soloway, M. S.: Transitional cell carcinoma of the prostate: diagnosis, staging and management. World J. Urol., 6: 170, 1988. 22. Schellhammer, P. F., Bean, M. A. and Whitmore, W. F., Jr.: Prostatic involvement by transitional cell carcinoma: pathogenesis, patterns and prognosis. J. Urol., 118: 399, 1977. 23. Greene, L. F., O'Dea, M. J. and Dockerty, M. B.: Primary transitional cell carcinoma of the prostate. J. Urol., 116: 761, 1976. 24. Greene, L. F., Mulcahy, J. J., Warren, M. M. and Dockerty, M. B.: Primary transitional cell carcinoma of the prostate. J. Urol., 110: 235, 1973. 25. Chibber, P. J., McIntyre, M.A., Hindmarsh, J. R., Hargreave, J. B., Newsam, J.E. and Chisholm, G.D.: Transitional cell carcinoma involving the prostate. Brit. J. Urol., 53: 605, 1981. 26. Kirk, D., Hinton, C. E. and Shaldon, C.: Transitional cell carcinoma of the prostate. Brit. J. Urol., 51: 575, 1979. 27. Hardeman, S. W., Perry, A. and Soloway, M. S.: Transitional cell carcinoma of the prostate following intravesical therapy for transitional cell carcinoma of the bladder. J. Urol., 140: 289, 1988. 28. Wishnow, K. I. and Ro, J. Y.: Importance of early treatment of transitional cell carcinoma of prostatic ducts. Urology, 32: 11, 1988. 29. Wood, D. P., Jr., Montie, J. E., Pontes, J. E., Vanderburg Medendorp, S. and Levin, H. S.: Transitional cell carcinoma of the prostate in cystoprostatectomy specimens removed for bladder cancer. J. Urol., 141: 346, 1989. 30. Catalona, W. J., Hudson, M.A., Gillen, D. P., Andriole, G. L. and Ratliff, T. L.: Risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer. J. Urol., 137: 220, 1987.

1212

MATZKIN, SOLOWAY AND HARDEMAN

31. Droller, M. J. and Walsh, P. C.: Intensive intravesical chemotherapy in the treatment of flat carcinoma in situ: is it safe? J. Urol., 134: 1115, 1985. 32. Montie, J. E., Mirsky, H. and Levin, H. S.: Transitional cell carcinoma of the prostate in a series of cystectomies: incidence and staging problems. J. Urol., part 2, 135: 243A, abstract 557, 1986. 33. Coutts, A. G., Grigor, K. M. and Fowler, J. W.: Urethral dysplasia and bladder cancer in cystectomy specimens. Brit. J. Urol., 57: 535, 1985. 34. Wood, D. P., Jr., Montie, J. E., Pontes, J. E. and Levin, H. S.: Identification of transitional cell carcinoma of the prostate in bladder cancer patients: a prospective study. J. Urol., 142: 83, 1989. 35. Lockhart, J. L., Chaikin, L., Bondhus, M. J. and Politano, V. A.: Prostatic recurrences in the management of superficial bladder tumors. J. Urol., 130: 256, 1983. 36. Grabstald, H.: Prostatic biopsy in selected patients with carcinoma in situ of the bladder: primary report. J. Urol., 132: 1117, 1984. 37. Bretton, P.R., Herr, H. W., Whitmore, W. F., Jr., Badalament, R. A., Kimmel, M., Provet, J., Oettgen, H.F., Melamed, M. R. and Fair, W.R.: Intravesical bacillus Calmette-Guerin therapy for in situ transitional cell carcinoma involving the prostatic urethra. J. Urol., 141: 853, 1989. 38. Terris, M. K., Villers, A. and Freiha, F. S.: Transrectal ultrasound appearance of transitional cell carcinoma involving the prostate. J. Urol., 143: 953, 1990. 39. Hillyard, R. W., Jr., Ladaga, L. and Schellhammer, P. F.: Superficial transitional cell carcinoma of the bladder associated with mucosal involvement of the prostatic urethra: results of treatment with intravesical bacillus Calmette-Guerin. J. Urol., 139: 290, 1988. 40. Hardeman, S. W. and Soloway, M. S.: Urethral recurrence following radical cystectomy. J. Urol., 144: 666, 1990. 41. Alexander, S. J., Lee, S. S. and Bekhrad, A.: Transitional cell carcinoma of the prostate: response to treatment with cisplatinum and cyclophosphamide. J. Urol., 131: 975, 1984.

42. Bates, H. R., Jr.: Transitional cell carcinoma of the prostate. J. Urol., 101: 206, 1969. 43. Rikken, C.H. M., van Helsdingen, P. J. R. 0. and Kazzaz, B. A.: Are biopsies from the prostatic urethra useful in patients with superficial bladder carcinoma? Brit. J. Urol., 59: 145, 1987. 44. Laor, E., Grabstald, H. and Whitmore, W. F.: The influence of simultaneous resection of bladder tumors and prostate on the occurrence ofprostatic urethral tumors. J. Urol., 126: 171, 1981. 45. Droller, M. J.: Bacillus Calmette-Guerin in the management of bladder cancer. J. Urol., 135: 331, 1986. 46. Herr, H. W., Pinsky, C. M., Whitmore, W. F., Jr., Sogani, P. C., Oettgen, H.F. and Melamed, M. R.: Long-term effect of intravesical bacillus Calmette-Guerin on flat carcinoma in situ of the bladder. J. Urol., 135: 265, 1986. 47. Siami, P., Ray, V., Chinn, S., Rubenstein, M., Clayton, M. and Guinan, P.: BCG in management of transitional ceU carcinoma invasive to prostate. Urology, 34: 381, 1989. 48. Shenasky, J. H., II and Gillenwater, J. Y.: Management of transitional cell carcinoma of the prostate. J. Urol., 108: 462, 1972. 49. Dexeus, F. H., Logothetis, C. J., Samuels, M. L., Ayala, A.G. and Hossan, E.: Complete responses in metastatic transitional cell carcinoma of the prostate with cisplatin regimens. J. Urol., 137: 122, 1987. 50. Taylor, H. G. and Blom, J.: Transitional cell carcinoma of the prostate: response to treatment with adriamycin and cis-platinum. Cancer, 51: 1800, 1983. 51. Lemberger, R. J., Bishop, M. C., Bates, C. P., Blundell, W. and Ansell, I. D.: Carcinoma of the prostate of ductal origin. Brit. J. Urol., 56: 706, 1984. 52. Whitmore, W. F., Jr. and Marshall, V. F.: Radical total cystectomy for cancer of the bladder: 230 consecutive cases five years later. J. Urol., 87: 853, 1962. 53. LaPlante, M. and Brice, M., II: The upper limits of hopeful application of radical cystectomy for vesical carcinoma: does nodal metastasis always indicate incurability? J. Urol., 109: 261, 1973. 54. Bodner, D.R., Cohen,J. K. and Resnick, M. I.: Primary transitional cell carcinoma of the prostate. J. d'Urol., 91: 157, 1985.

Transitional cell carcinoma of the prostate.

0022-534 7/91/1465-1207$03.00/0 Vol. 146, 1207-1212, November 1991 THE JOURNAL OF UROLOGY Printed in U.S.A. Copyright© 1991 by AMERICAN UROLOGICAL...
221KB Sizes 0 Downloads 0 Views