0022-5347/92/1471-0092$03.00/0 THE JOURNAL OF UROLOGY Copyright© 1992 by AMERICAN UROLOGICAL ASSOCIATION, INC.
Vol. 147, 92-95, January 1992 Printed in U.S.A.
TRANSITIONAL CELL CARCINOMA OF THE PROSTATE IN PATIENTS UNDERGOING RADICAL CYSTOPROSTATECTOMY JEFFREY H. REESE,* FUAD S. FREIHA, ARNOLD B. GELB, BERT L. LUM
AND
FRANK M. TORTI
From the Division of Urology, Department of Pathology and Medicine, Stanford University School of Medicine, Stanford, California
ABSTRACT
To assess the impact of prostatic involvement with transitional cell carcinoma we reviewed the clinical outcome of 49 patients with transitional cell carcinoma of the prostate. In addition, 115 step-sectioned cystoprostatectomy specimens removed for bladder transitional cell carcinoma were studied to determine the true incidence of secondary prostatic involvement by transitional cell carcinoma. Specimens from 300 prostates removed for prostatic adenocarcinoma also were reviewed to investigate the presence of incidental transitional cell carcinoma arising within the prostate. Transitional cell carcinoma was found in 29% of the step-sectioned specimens and in none of the radical prostatectomy specimens. The presence of prostatic invasion either into the stroma or involving prostatic ducts and acini only had no adverse effect on outcome. Lymph node status and bladder stage, and not prostatic invasion were the determining factors of survival. The presence of seminal vesicle involvement or prostatic stromal invasion appeared to predict for lymph node involvement. With a mean followup of more than 3 years 75% of our patients who had negative lymph nodes and low stage bladder lesions are alive without evidence of disease. In our series prostatic involvement by transitional cell carcinoma did not impact on survival when patients were treated aggressively with radical cystoprostatectomy. KEY WORDS: carcinoma, transitional cell; prostatic neoplasms; prostatectomy
Transitional cell carcinoma of the prostate is believed to arise as a primary lesion within prostatic ducts or acini, or in association with a bladder tumor. Stromal invasion may be present with either form. The primary form is rare, reported to account for 2 to 4% of all prostate cancers, 1-5 while secondary involvement of the prostate is common, occurring in 7 to 43% of men with transitional cell carcinoma of the bladder.6• 7 Whether primary or secondary, transitional cell carcinoma of the prostate has traditionally been believed to have a poor prognosis.8• Furthermore, when present in association with bladder cancer the disease has been classified as stage D irre spective of the extent of the bladder lesion. The records of 49 patients who presented with either primary or secondary tran sitional cell carcinoma and who underwent radical cystopros tatectomy as the definitive therapy were studied in an effort to determine the incidence of primary and secondary transitional cell carcinoma of the prostate, clarify the prognosis of patients with prostatic stromal versus duct/acinar invasion, and identify the role of nodal status and bladder stage as prognostic indi cators in patients with transitional cell carcinoma of the pros tate gland.
Correlations were made between the presence and extent of transitional cell carcinoma in the prostate, and survival, stage of bladder tumor, preoperative intravesical chemotherapy, sem inal vesicle invasion and lymph node metastasis. All patients were followed for a minimum of 18 months postoperatively. To investigate the presence of incidental transitional cell carci noma arising within the prostate 300 radical prostatectomy specimens removed for adenocarcinoma of the prostate that were step-sectioned at 3 mm. intervals were reviewed for evi dence of transitional cell carcinoma. Statistical analyses. The association between prostatic trans itional cell carcinoma invasion and various pathological fea tures was tested for significance with the chi-square 2 X 2 contingency tables with Yates' correction for continuity of data or Fisher's exact test when sample sizes were small.10 Standard univariate logistic regression analyses were used to evaluate tumor and patient characteristics that predicted for the devel opment of metastases to lymph nodes. To define further the importance of each covariable to predict independently for lymph node metastases in the presence of other variables, multivariate analyses were performed. Since the dependent variable, lymph node metastases, was a binary variable, a multiple logistic regression model was chosen.11 Cumulative proportions of patients surviving as a function of time were estimated with the Kaplan-Meier method 12 and differences between survival of groups with and without lymph node me tastases were compared with Gehan's generalization of the Wilcoxon test.13
9
MATERIALS AND METHODS
Between 1975 and 1988, 209 cystoprostatectomies were per formed in men with transitional cell carcinoma of the bladder and/or prostate gland. Of these 209 men 49 had prostatic involvement by transitional cell carcinoma. Of the latter 49 operations 6 were salvage procedures for failure of definitive external beam radiation therapy in which the regional lymph nodes were not removed. Patient age ranged from 39 to 84 years. In 115 of the 209 specimens the prostate glands were step-sectioned at 3 mm. intervals allowing for a detailed analy sis of the true incidence of transitional cell carcinoma involving the prostate. The pathological diagnosis in all patients in this series was reviewed and confirmed by 1 of us (A. B. G.).
RESULTS
Of the 209 patients 49 (23%) had transitional cell carcinoma involving the prostate gland: 29 had stromal invasion and 20 had transitional cell carcinoma in the prostatic ducts only. The regional lymph nodes were removed at operation in 43 of the 49 patients. A total of 6 patients whose lymph node status was unknown was excluded from over-all survival analysis. Over all survival analysis was based on the remaining 43 patients. Survival data also were analyzed as disease-specific survival (3 patients dying of other causes were eliminated). Two patients
Accepted for publication May 10, 1991. * Requests for reprints: Division of Urology, Stanford University School of Medicine, Santa Clara Valley Medical Center, 751 South Bascom Ave., San Jose, California 95128. 92
93
TRANSITIONAL CELL CARCINOMA OF PROSTATE
with positive lymph nodes had recurrence and were salvaged with chemotherapy, and they were alive at 30 and 45 months, respectively. Incidence of prostatic transitional cell carcinoma. To deter mine the true incidence of transitional cell carcinoma involving the prostate in our population, we separately examined the step-sectioned prostates in 115 of the 209 patients. Of the 115 step-sectioned glands 33 (29%) were involved with transitional cell carcinoma: 17 had duct/acinar involvement and 16 had stromal invasion. To determine the incidence of incidental transitional cell carcinoma arising in the prostate step-sec tioned specimens from 300 radical prostatectomies in patients without a history of transitional cell carcinoma were examined. No focus of transitional cell carcinoma was found. Furthermore, only 2 patients underwent cystoprostatectomy for what was believed to be a primary transitional cell carcinoma of the prostate (in these patients the tumor was believed to originate within the prostate itself). Neither patient had a history of transitional cell carcinoma and both had bladder involvement at the pathological examination. One patient died of the disease at 15 months, while 1 had recurrence, was salvaged with chemo therapy and was without evidence of disease at 30 months. Strama versus duct/acinar involvement. The survival curves comparing degree of prostatic invasion with lymph node status demonstrate a strong statistical association between lymph node status and survival. When survival is compared to the degree of prostatic invasion, regardless of the nodal status, the curves are similar and no statistical association exists (fig. 1). For patients without lymph node involvement the disease specific survival rate was 73% (8 of 11) in those with stromal invasion and a mean followup of 50 months, and 75% (9 of 12) in those with duct/acinar invasion with a mean followup of 38 months (table 1). Similarly, for patients with lymph node involvement the disease-specific survival was 31% (4 of 13) for those with stromal invasion and a mean followup of 36 months, and 50% (2 of 4) for those with duct/acinar invasion and a mean followup of 18 months. When analyzed by bladder stage at cystectomy the disease specific survival was almost identical, stage for stage, between patients with stromal invasion versus those with duct/acinar invasion (table 2). When lymph node involvement and bladder stage were considered survival was not associated with the degree of prostatic involvement (stroma versus duct/acinar). Several differences were noted among patients with stromal versus duct/acinar invasion, although these differences did not (8)
1.0---�:(12) '--- ______ Q O) 0.9 , : (9)
i
'-----------------------------1----------���.;;;
0.8
I
0 >-
J
o.7 o.s
I
;(8)
(7) 1-
( 5)
--1 I (1 ) I Ductal Node Positive N•4 I
(2)
0.5
0.4
N Negative ��1�
(2)
Ductal Node Negative N•13
(2)
0.3
· · · · · 'SfrO�a· NOde Positive N•14
0.2 0.1 10
20
30
40
50
60
70
Time (Mos)
FIG. 1. Kaplan-Meier curves comparing over-all survival based on nodal status and degree of prostatic invasion. Numbers in parentheses represent patients at risk. Surviv�l comparisons were stroma i:t�de positive versus stroma node negative p = 0.009, duct node pos1t!ve versus duct node negative p = 0.02, node positive or node negative versus degree of invasion (stroma/duct) p = not significant (Gehan's generalized Wilcoxon test).
TABLE 1. Disease-specific survival and importance of nodes at
diagnosis
Node pos. all pts.: Yes No Stromal-node pos.: Yes No Duct-node pos.: Yes No Stroma versus duct: Node pos.: Stroma Duct Node neg.: Stroma Duct
No. Pts.
No Evidence of Disease No.(%)
17 23
6 (35) 17 (74)
13
11
4 (31) 8 (73)
4 12
2 (50) 9 (75)
13 4
4 (31) 2 (50)
11
8 (73) 9 (75)
12
Three patients dying of other causes were eliminated.
impact on survival (table 3). In particular, carcinoma in situ was found in the bladder in 14 of 20 patients (70%) with duct acinar invasion compared to only 6 of 29 (22%) with stromal invasion. Additionally, for 8 patients who underwent an oper ation for refractory carcinoma in situ all but 1 had duct/acinar invasion only. Seminal vesicle invasion also was noted in 8 patients with stromal invasion compared to only 3 with duct/ acinar invasion (table 3). Although seminal vesicle invasion was a poor prognostic indicator, this was due primarily to the close association of seminal vesicle invasion with the presence of lymph node metastases (table 4). Lymph node involvement. Lymph node metastases were found in 14 of 26 patients (54%) with stromal invasion com pared to 4 of 17 (24%) with duct/acinar involvement. The survival figures for node-positive stromal and duct/acinar can cer patients were nearly identical (table 1). Survival was strongly associated with lymph node status (fig. 2). A number of factors were examined to identify features associated with the presence of lymph node metastases (table 4). Only the presence of stromal prostatic invasion and seminal vesicle involvement were associated with the presence of lymph node metastases. Although stromal invasion showed a strong trend, it did not reach statistical significance in predicting nodal metastases. Seminal vesicle invasion, however, was as sociated significantly with and predictive of lymph node me tastases (table 4). The disease-specific survival rate for seminal vesicle invasion was 30%. This figure is nearly identical to the survival rate seen in patients with lymph node metastases, and is to be expected considering the close association between nodal status and seminal vesicle invasion. Bladder stage. Disease-specific survival was examined based on bladder stage alone (lymph node status was not considered). This evaluation did include 6 patients, previously excluded from survival analysis, in whom the nodal status was unknown. Of these 6 patients 3 died of other causes and were not included in the disease-specific survival analysis. Bladder stage corre lated well with survival (table 2)" Thus, for patients who had either no residual bladder tumor (stage PO), superficially invad ing tumor (stage Pl) or carcinoma in situ (stage PIS) the survival rate was excellent. Only 3 patients with positive nodes were in these favorable categories: 1 had recurrence and was salvaged with chemotherapy, and the other 2 were alive at 18 and 42 months. Patients in these favorable categories were equally distributed between those with stroma or duct/acinar invasion. The data in table 2 again emphasize the point that by itself the degree of prostatic involvement by transitional cell carcinoma does not impact on survival. DISCUSSION
Transitional cell carcinoma involving the prostatic urethra and prostatic ducts has been recognized as a clinical entity
94
REESE AND ASSOCIATES TABLE 2. Prostatic invasion related to bladder stage and to disease-specific survival
Bladder Tumor Stage P2/P3A Pl PIS PO* No,/Total (%) No./Total (%) No./Total (%) No./Total (%) 3/7 (43) 2/3 (67) 2/2 (100) Strama 4/4 (100) 2/3 (66) 4/5 (80) 2/3 (67) 4/4 (100) Duct 5/10 (50) 4/5 (80) 6/8 (75) All pts. 8/8 (100) Includes 3 patients in whom the nodal status was not known. A total of 3 patients dying of other causes was eliminated. * No tumor was found in the bladder on pathological review. Pathological features associated with prostatic invasion No. With Total No. Invasion P Value Finding Pts. OA62* 49 29 Stromal Al! pts. 20 Duct 0.096* 6 20 Strama! Ca in situ 12 Duct 0.739* 8 Strama! 18 Intravesical chemotherapy Duct 10 8 0.086t Seminal vesicle 11 Stromal 3 Duct * Chi-square test. t Fisher's exact test. TABLE 3.
TABLE 4.
Univariate and multiple logistic regressions for factors at diagnosis associated with node positive status P Value Variable Univariate logistic regression
0.5561 0.4460 0.0292 0.8477 0.062
Primary transitional cell Ca Ca in situ Seminal vesicle invasion Intravesical chemotherapy Strama! invasion Multiple logistic regression
0.031 0.067
Seminal vesicle invasion Strama! invasion
1.0 0.9-
--···-··1
(24) (17) ·····-----, (12) l..-------···-·-·-···--··-··-·· (16) 1. !11) ..
L ___ __ __
0,8 0.7 ·;;:
"'
0.6
,..
0.5
0
:g
) J�O
(7
l--·-····· Node Negative N•25
(13)
)
prostate has been estimated at 1 to 4% of prostatic carcino mas.1-5 These figures were derived from retrospective analysis of large series of prostatic carcinomas in which the presence or absence of a synchronous bladder tumor was, in virtually all instances, made on either history or cystoscopic examination alone. Only 1 study has examined autopsy prostates for the presence of transitional cell carcinoma. These physicians seri ally sectioned 400 autopsy prostates and found 3 cases of hyperplasia and only 1 grade 1 transitional cell carcinoma.14 We have step-sectioned and examined in detail the prostates of 300 men undergoing radical prostatectomy for adenocarci noma of the prostate during the last 4 years. No focus of transitional cell carcinoma involving the prostate has been found. Furthermore, in all cases in which the transitional cell carcinoma appeared to arise within the prostate an associated transitional cell carcinoma of the bladder or carcinoma in situ of the bladder was found after cystectomy. It is possible that much of what has been called primary transitional cell carci noma of the prostate in the literature may have represented cases of associated unrecognized bladder transitional cell car cinoma. Although transitional cell carcinoma may arise de novo within the prostatic ducts, our data and those of others suggest it is a rare event.14 Estimates of the incidence of transitional cell carcinoma involving the prostate in association with bladder transitional cell carcinoma range from 5 to 43%. Our results are roughly similar (29%) to those reported by Wood et al, who found a 43% incidence of transitional cell carcinoma of the prostate in carefully studied step-sectioned cystoprostatectomy speci mens.7 The minimal discrepancy, if real, probably is due to differences in patient population and sample size. Whether as a primary transitional cell carcinoma of the prostate or in association with bladder disease, the prognosis for patients with transitional cell carcinoma involving the prostate has been poor.8• Since primary transitional cell carcinoma has been viewed in the past as a variant of prostatic carcinoma, a variety of therapeutic modalities have been used to treat this disease. Local resection and hormonal therapy are ineffective treat ments for this disease. No long-term survivors have ever been reported and few patients survived as long as 2 years.1· 3• 15 There is no evidence to suggest that hormonal therapy is effective in the treatment of transitional cell carcinoma of the prostate. Neither does radiation therapy alone cure this disease. Johnson et al had 1, 5-year survivor in their series.15 The remaining 13 patients treated with radiation alone died within 36 months. Of 9 patients treated with radiation therapy alone Greene et al found a mean survival of 26 months with no long term survivors.16 They did show some increased survival in patients treated with radiation therapy compared to hormones or no therapy. Kopelson et al reviewed 58 cases and showed improved local control for patients treated with radiation ther apy.17 It is apparent that radiation therapy alone is beneficial in obtaining local control of the disease but it is unlikely to produce long-term cures. Surgery alone appears to offer some survival advantage over the aforementioned therapeutic modalities. Although some physicians have reported equally poor survival with surgery alone,8 others have reported long-term survivors when an op eration was the primary means of treatment.16· 18 In the largest 9
p
Vol. 147, 92-95, January 1992 Printed in U.S.A.
TRANSITIONAL CELL CARCINOMA OF THE PROSTATE IN PATIENTS UNDERGOING RADICAL CYSTOPROSTATECTOMY JEFFREY H. REESE,* FUAD S. FREIHA, ARNOLD B. GELB, BERT L. LUM
AND
FRANK M. TORTI
From the Division of Urology, Department of Pathology and Medicine, Stanford University School of Medicine, Stanford, California
ABSTRACT
To assess the impact of prostatic involvement with transitional cell carcinoma we reviewed the clinical outcome of 49 patients with transitional cell carcinoma of the prostate. In addition, 115 step-sectioned cystoprostatectomy specimens removed for bladder transitional cell carcinoma were studied to determine the true incidence of secondary prostatic involvement by transitional cell carcinoma. Specimens from 300 prostates removed for prostatic adenocarcinoma also were reviewed to investigate the presence of incidental transitional cell carcinoma arising within the prostate. Transitional cell carcinoma was found in 29% of the step-sectioned specimens and in none of the radical prostatectomy specimens. The presence of prostatic invasion either into the stroma or involving prostatic ducts and acini only had no adverse effect on outcome. Lymph node status and bladder stage, and not prostatic invasion were the determining factors of survival. The presence of seminal vesicle involvement or prostatic stromal invasion appeared to predict for lymph node involvement. With a mean followup of more than 3 years 75% of our patients who had negative lymph nodes and low stage bladder lesions are alive without evidence of disease. In our series prostatic involvement by transitional cell carcinoma did not impact on survival when patients were treated aggressively with radical cystoprostatectomy. KEY WORDS: carcinoma, transitional cell; prostatic neoplasms; prostatectomy
Transitional cell carcinoma of the prostate is believed to arise as a primary lesion within prostatic ducts or acini, or in association with a bladder tumor. Stromal invasion may be present with either form. The primary form is rare, reported to account for 2 to 4% of all prostate cancers, 1-5 while secondary involvement of the prostate is common, occurring in 7 to 43% of men with transitional cell carcinoma of the bladder.6• 7 Whether primary or secondary, transitional cell carcinoma of the prostate has traditionally been believed to have a poor prognosis.8• Furthermore, when present in association with bladder cancer the disease has been classified as stage D irre spective of the extent of the bladder lesion. The records of 49 patients who presented with either primary or secondary tran sitional cell carcinoma and who underwent radical cystopros tatectomy as the definitive therapy were studied in an effort to determine the incidence of primary and secondary transitional cell carcinoma of the prostate, clarify the prognosis of patients with prostatic stromal versus duct/acinar invasion, and identify the role of nodal status and bladder stage as prognostic indi cators in patients with transitional cell carcinoma of the pros tate gland.
Correlations were made between the presence and extent of transitional cell carcinoma in the prostate, and survival, stage of bladder tumor, preoperative intravesical chemotherapy, sem inal vesicle invasion and lymph node metastasis. All patients were followed for a minimum of 18 months postoperatively. To investigate the presence of incidental transitional cell carci noma arising within the prostate 300 radical prostatectomy specimens removed for adenocarcinoma of the prostate that were step-sectioned at 3 mm. intervals were reviewed for evi dence of transitional cell carcinoma. Statistical analyses. The association between prostatic trans itional cell carcinoma invasion and various pathological fea tures was tested for significance with the chi-square 2 X 2 contingency tables with Yates' correction for continuity of data or Fisher's exact test when sample sizes were small.10 Standard univariate logistic regression analyses were used to evaluate tumor and patient characteristics that predicted for the devel opment of metastases to lymph nodes. To define further the importance of each covariable to predict independently for lymph node metastases in the presence of other variables, multivariate analyses were performed. Since the dependent variable, lymph node metastases, was a binary variable, a multiple logistic regression model was chosen.11 Cumulative proportions of patients surviving as a function of time were estimated with the Kaplan-Meier method 12 and differences between survival of groups with and without lymph node me tastases were compared with Gehan's generalization of the Wilcoxon test.13
9
MATERIALS AND METHODS
Between 1975 and 1988, 209 cystoprostatectomies were per formed in men with transitional cell carcinoma of the bladder and/or prostate gland. Of these 209 men 49 had prostatic involvement by transitional cell carcinoma. Of the latter 49 operations 6 were salvage procedures for failure of definitive external beam radiation therapy in which the regional lymph nodes were not removed. Patient age ranged from 39 to 84 years. In 115 of the 209 specimens the prostate glands were step-sectioned at 3 mm. intervals allowing for a detailed analy sis of the true incidence of transitional cell carcinoma involving the prostate. The pathological diagnosis in all patients in this series was reviewed and confirmed by 1 of us (A. B. G.).
RESULTS
Of the 209 patients 49 (23%) had transitional cell carcinoma involving the prostate gland: 29 had stromal invasion and 20 had transitional cell carcinoma in the prostatic ducts only. The regional lymph nodes were removed at operation in 43 of the 49 patients. A total of 6 patients whose lymph node status was unknown was excluded from over-all survival analysis. Over all survival analysis was based on the remaining 43 patients. Survival data also were analyzed as disease-specific survival (3 patients dying of other causes were eliminated). Two patients
Accepted for publication May 10, 1991. * Requests for reprints: Division of Urology, Stanford University School of Medicine, Santa Clara Valley Medical Center, 751 South Bascom Ave., San Jose, California 95128. 92
93
TRANSITIONAL CELL CARCINOMA OF PROSTATE
with positive lymph nodes had recurrence and were salvaged with chemotherapy, and they were alive at 30 and 45 months, respectively. Incidence of prostatic transitional cell carcinoma. To deter mine the true incidence of transitional cell carcinoma involving the prostate in our population, we separately examined the step-sectioned prostates in 115 of the 209 patients. Of the 115 step-sectioned glands 33 (29%) were involved with transitional cell carcinoma: 17 had duct/acinar involvement and 16 had stromal invasion. To determine the incidence of incidental transitional cell carcinoma arising in the prostate step-sec tioned specimens from 300 radical prostatectomies in patients without a history of transitional cell carcinoma were examined. No focus of transitional cell carcinoma was found. Furthermore, only 2 patients underwent cystoprostatectomy for what was believed to be a primary transitional cell carcinoma of the prostate (in these patients the tumor was believed to originate within the prostate itself). Neither patient had a history of transitional cell carcinoma and both had bladder involvement at the pathological examination. One patient died of the disease at 15 months, while 1 had recurrence, was salvaged with chemo therapy and was without evidence of disease at 30 months. Strama versus duct/acinar involvement. The survival curves comparing degree of prostatic invasion with lymph node status demonstrate a strong statistical association between lymph node status and survival. When survival is compared to the degree of prostatic invasion, regardless of the nodal status, the curves are similar and no statistical association exists (fig. 1). For patients without lymph node involvement the disease specific survival rate was 73% (8 of 11) in those with stromal invasion and a mean followup of 50 months, and 75% (9 of 12) in those with duct/acinar invasion with a mean followup of 38 months (table 1). Similarly, for patients with lymph node involvement the disease-specific survival was 31% (4 of 13) for those with stromal invasion and a mean followup of 36 months, and 50% (2 of 4) for those with duct/acinar invasion and a mean followup of 18 months. When analyzed by bladder stage at cystectomy the disease specific survival was almost identical, stage for stage, between patients with stromal invasion versus those with duct/acinar invasion (table 2). When lymph node involvement and bladder stage were considered survival was not associated with the degree of prostatic involvement (stroma versus duct/acinar). Several differences were noted among patients with stromal versus duct/acinar invasion, although these differences did not (8)
1.0---�:(12) '--- ______ Q O) 0.9 , : (9)
i
'-----------------------------1----------���.;;;
0.8
I
0 >-
J
o.7 o.s
I
;(8)
(7) 1-
( 5)
--1 I (1 ) I Ductal Node Positive N•4 I
(2)
0.5
0.4
N Negative ��1�
(2)
Ductal Node Negative N•13
(2)
0.3
· · · · · 'SfrO�a· NOde Positive N•14
0.2 0.1 10
20
30
40
50
60
70
Time (Mos)
FIG. 1. Kaplan-Meier curves comparing over-all survival based on nodal status and degree of prostatic invasion. Numbers in parentheses represent patients at risk. Surviv�l comparisons were stroma i:t�de positive versus stroma node negative p = 0.009, duct node pos1t!ve versus duct node negative p = 0.02, node positive or node negative versus degree of invasion (stroma/duct) p = not significant (Gehan's generalized Wilcoxon test).
TABLE 1. Disease-specific survival and importance of nodes at
diagnosis
Node pos. all pts.: Yes No Stromal-node pos.: Yes No Duct-node pos.: Yes No Stroma versus duct: Node pos.: Stroma Duct Node neg.: Stroma Duct
No. Pts.
No Evidence of Disease No.(%)
17 23
6 (35) 17 (74)
13
11
4 (31) 8 (73)
4 12
2 (50) 9 (75)
13 4
4 (31) 2 (50)
11
8 (73) 9 (75)
12
Three patients dying of other causes were eliminated.
impact on survival (table 3). In particular, carcinoma in situ was found in the bladder in 14 of 20 patients (70%) with duct acinar invasion compared to only 6 of 29 (22%) with stromal invasion. Additionally, for 8 patients who underwent an oper ation for refractory carcinoma in situ all but 1 had duct/acinar invasion only. Seminal vesicle invasion also was noted in 8 patients with stromal invasion compared to only 3 with duct/ acinar invasion (table 3). Although seminal vesicle invasion was a poor prognostic indicator, this was due primarily to the close association of seminal vesicle invasion with the presence of lymph node metastases (table 4). Lymph node involvement. Lymph node metastases were found in 14 of 26 patients (54%) with stromal invasion com pared to 4 of 17 (24%) with duct/acinar involvement. The survival figures for node-positive stromal and duct/acinar can cer patients were nearly identical (table 1). Survival was strongly associated with lymph node status (fig. 2). A number of factors were examined to identify features associated with the presence of lymph node metastases (table 4). Only the presence of stromal prostatic invasion and seminal vesicle involvement were associated with the presence of lymph node metastases. Although stromal invasion showed a strong trend, it did not reach statistical significance in predicting nodal metastases. Seminal vesicle invasion, however, was as sociated significantly with and predictive of lymph node me tastases (table 4). The disease-specific survival rate for seminal vesicle invasion was 30%. This figure is nearly identical to the survival rate seen in patients with lymph node metastases, and is to be expected considering the close association between nodal status and seminal vesicle invasion. Bladder stage. Disease-specific survival was examined based on bladder stage alone (lymph node status was not considered). This evaluation did include 6 patients, previously excluded from survival analysis, in whom the nodal status was unknown. Of these 6 patients 3 died of other causes and were not included in the disease-specific survival analysis. Bladder stage corre lated well with survival (table 2)" Thus, for patients who had either no residual bladder tumor (stage PO), superficially invad ing tumor (stage Pl) or carcinoma in situ (stage PIS) the survival rate was excellent. Only 3 patients with positive nodes were in these favorable categories: 1 had recurrence and was salvaged with chemotherapy, and the other 2 were alive at 18 and 42 months. Patients in these favorable categories were equally distributed between those with stroma or duct/acinar invasion. The data in table 2 again emphasize the point that by itself the degree of prostatic involvement by transitional cell carcinoma does not impact on survival. DISCUSSION
Transitional cell carcinoma involving the prostatic urethra and prostatic ducts has been recognized as a clinical entity
94
REESE AND ASSOCIATES TABLE 2. Prostatic invasion related to bladder stage and to disease-specific survival
Bladder Tumor Stage P2/P3A Pl PIS PO* No,/Total (%) No./Total (%) No./Total (%) No./Total (%) 3/7 (43) 2/3 (67) 2/2 (100) Strama 4/4 (100) 2/3 (66) 4/5 (80) 2/3 (67) 4/4 (100) Duct 5/10 (50) 4/5 (80) 6/8 (75) All pts. 8/8 (100) Includes 3 patients in whom the nodal status was not known. A total of 3 patients dying of other causes was eliminated. * No tumor was found in the bladder on pathological review. Pathological features associated with prostatic invasion No. With Total No. Invasion P Value Finding Pts. OA62* 49 29 Stromal Al! pts. 20 Duct 0.096* 6 20 Strama! Ca in situ 12 Duct 0.739* 8 Strama! 18 Intravesical chemotherapy Duct 10 8 0.086t Seminal vesicle 11 Stromal 3 Duct * Chi-square test. t Fisher's exact test. TABLE 3.
TABLE 4.
Univariate and multiple logistic regressions for factors at diagnosis associated with node positive status P Value Variable Univariate logistic regression
0.5561 0.4460 0.0292 0.8477 0.062
Primary transitional cell Ca Ca in situ Seminal vesicle invasion Intravesical chemotherapy Strama! invasion Multiple logistic regression
0.031 0.067
Seminal vesicle invasion Strama! invasion
1.0 0.9-
--···-··1
(24) (17) ·····-----, (12) l..-------···-·-·-···--··-··-·· (16) 1. !11) ..
L ___ __ __
0,8 0.7 ·;;:
"'
0.6
,..
0.5
0
:g
) J�O
(7
l--·-····· Node Negative N•25
(13)
)
prostate has been estimated at 1 to 4% of prostatic carcino mas.1-5 These figures were derived from retrospective analysis of large series of prostatic carcinomas in which the presence or absence of a synchronous bladder tumor was, in virtually all instances, made on either history or cystoscopic examination alone. Only 1 study has examined autopsy prostates for the presence of transitional cell carcinoma. These physicians seri ally sectioned 400 autopsy prostates and found 3 cases of hyperplasia and only 1 grade 1 transitional cell carcinoma.14 We have step-sectioned and examined in detail the prostates of 300 men undergoing radical prostatectomy for adenocarci noma of the prostate during the last 4 years. No focus of transitional cell carcinoma involving the prostate has been found. Furthermore, in all cases in which the transitional cell carcinoma appeared to arise within the prostate an associated transitional cell carcinoma of the bladder or carcinoma in situ of the bladder was found after cystectomy. It is possible that much of what has been called primary transitional cell carci noma of the prostate in the literature may have represented cases of associated unrecognized bladder transitional cell car cinoma. Although transitional cell carcinoma may arise de novo within the prostatic ducts, our data and those of others suggest it is a rare event.14 Estimates of the incidence of transitional cell carcinoma involving the prostate in association with bladder transitional cell carcinoma range from 5 to 43%. Our results are roughly similar (29%) to those reported by Wood et al, who found a 43% incidence of transitional cell carcinoma of the prostate in carefully studied step-sectioned cystoprostatectomy speci mens.7 The minimal discrepancy, if real, probably is due to differences in patient population and sample size. Whether as a primary transitional cell carcinoma of the prostate or in association with bladder disease, the prognosis for patients with transitional cell carcinoma involving the prostate has been poor.8• Since primary transitional cell carcinoma has been viewed in the past as a variant of prostatic carcinoma, a variety of therapeutic modalities have been used to treat this disease. Local resection and hormonal therapy are ineffective treat ments for this disease. No long-term survivors have ever been reported and few patients survived as long as 2 years.1· 3• 15 There is no evidence to suggest that hormonal therapy is effective in the treatment of transitional cell carcinoma of the prostate. Neither does radiation therapy alone cure this disease. Johnson et al had 1, 5-year survivor in their series.15 The remaining 13 patients treated with radiation alone died within 36 months. Of 9 patients treated with radiation therapy alone Greene et al found a mean survival of 26 months with no long term survivors.16 They did show some increased survival in patients treated with radiation therapy compared to hormones or no therapy. Kopelson et al reviewed 58 cases and showed improved local control for patients treated with radiation ther apy.17 It is apparent that radiation therapy alone is beneficial in obtaining local control of the disease but it is unlikely to produce long-term cures. Surgery alone appears to offer some survival advantage over the aforementioned therapeutic modalities. Although some physicians have reported equally poor survival with surgery alone,8 others have reported long-term survivors when an op eration was the primary means of treatment.16· 18 In the largest 9
p
