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Prostatic Biopsy in selected Patients with Carcinoma in Situ of the Bladder: Preliminary Report
0022-534 7/84/1326-1117$02.0()/0 VoL
THE JOURNAL OF UROLOGY
Copyright© 1984 by The "\IVilliams & Wilkins Co.
Decembet in U.S.A.
PROSTATIC BIOPSY IN SELECTED PATIENTS WITH CARCINOMA IN SITU OF THE BLADDER: PRELI1VUNARY REPORT HARRY GRABSTALD* From the Division of Urology, University of South Florida Medical College and Veterans Administration Hospital, Tampa, Florida
ABSTRACT
Transitional cell carcinoma was found in biopsies of grossly normal-appearing prostates in 4 of 40 patients with recurrent carcinoma in situ of the bladder. In selected patients prostatic biopsy may be warranted if conservative therapy does not control the bladder tumors and if cystectomy is contemplated. A common problem concerning patients with recurrent multifocal carcinoma in situ is the difficult decision about whether to perform ablative surgery or to continue conservative measures, such as transurethral resection with or without intravesical chemotherapy. One fact seems readily apparent, that is patients with multifocal bladder cancers and involvement of the prostatic glandular substance should undergo cystoprostatectomy and, probably, urethrectomy. A biopsy is necessary to confirm or deny the presence of urothelial cancer in the prostate.
cancerous in at least one spot and it is atypical in others". Could this finding not have been primary carcinoma in situ of the bladder with secondary prostatic extension or multifocal disease? The capricious behavior and unpredictability of the natural history of carcinoma in situ of the bladder were described by Melamed and associates in a clinical study of 25 cases. 2 A variable latency period between diagnosis of carcinoma in situ and invasion was discussed, since the authors stated that "multiple sites of involvement were a frequent occurrence".
MATERIALS AND METHODS
INCIDENCE AND SIGNIFICANCE OF PROSTATIC INVOLVEMENT BY TRANSITIONAL CELL CANCER
The study included 40 consecutive, nonselected patients with recurrent carcinoma in situ of the bladder. Prostatic biopsy was performed transurethrally and by perineal punch. No effort was made to resect completely or even to channel the prostate. Biopsy consisted of a single loop bite from the neck to the verumontanum at the 5 and 7 o'clock positions. Perinea! punch biopsy included the right and left lobes, and posterior areas. There were no complications attributable to the biopsy. RESULTS
Of the first 20 patients 12 had multifocal carcinoma in situ (2 with associated transitional cell carcinoma in the prostate) and 8 had unifocal disease (1 with prostatic involvement). Thus, 3 of 20 patients (15 per cent) had transitional cell cancer in the prostate. Also, prostatic adenocarcinoma was detected in 1 patient. These findings are surprising, since the incidence of latent prostatic cancer with complete transurethral resection is only 5 to 7 per cent. I do not propose use of routine prostatic biopsy to detect unsuspected prostatic cancer. Of the next 20 patients transitional cell cancer was found in only 1 prostate. Regardless of whether the incidence is 3 of 20 or 4 of 40 patients, the numbers are not valid statistically. The fact is that the finding of unsuspected prostatic involvement is a possibility. Whether routine biopsies are worthwhile statistically remains to be determined by larger series. DISCUSSION
In l of the earliest references to carcinoma in situ of the prostate Ortega and associates reported extension into the urethra and bladder. 1 A bladder of "slightly reduced capacity, mild diffuse injection of the bladder mucosa, and an area of edematous reddening" was described. Today, we would suspect diffuse field carcinoma in situ of the bladder, as did Ortega and associates, since they mentioned later that microscopic examination of the bladder revealed that "the mucosa is cytologically Accepted for publication August 2, 1984. *Requests for reprints: Department of Urology, Beth Israel Medical Center, First Ave. and 16th St., New York, New York 10003.
Herr and associates studied 41 patients with multifocal flat carcinoma in situ treated by transurethral resection and intravesical bacillus Calmette-Guerin. 3 Of 30 patients who responded 4 suffered recognized carcinoma in situ in the prostatic urethra. Of 24 patients with carcinoma in situ treated by transurethral resection alone 12 underwent cystectomy and prostatic urethral cancer was found in 15 per cent. It is interesting that the incidence of prostatic involvement is the same in our series and that of Herr and associates. Beebe and Persky emphasized the "devastating effect" of transitional cell carcinoma in the prostate. 4 Lockhart and associates also suggested that tumor in the prostatic urethra indicates the presence of an aggressive tumor and that therapy should be instituted accordingly. They recommended that followup include cytology, cystoscopy and prostatic urethral biopsies.5 Prout has stated that radical cystectomy is indicated when the prostate is invaded in patients with multifocal carcinoma in situ. 6 · 7 This also has been my belief and the therapeutic philosophy of all urological oncologists with whom I have discussed the matter. Utz indicated that prostatic biopsy was important regardless of how it was done. 8 He emphasized the fact that intravesical chemotherapy should not be used unless one knows what the prostate shows. Utz stated, "If 40 percent of these people have cancer in the prostatic ducts as well as in the bladder, I think that we just have to know about it". In the same monograph Bonney and Prout emphasized the fact that a needle biopsy of both lobes of the prostate as well as collection of urine from both ureters might be worthwhile. 7 Mertz questioned whether Utz had ever found prostatic implants that were attributable to a urethral biopsy. 9 Utz indicated that there is no doubt that if the mucosa was violated the urothelium was more conducive to implantation but the studies to date had shown no implants following biopsy. Laor and associates compared the records of 137 patients who underwent simultaneous transurethral resection of bladder tumors and the prostate to those of 150 patients who underwent transurethral resection of bladder tumors only. The data pre-
1117
1118
GRABSTALD
sented no evidence that simultaneous resection of bladder tumors and the prostate adversely affects the incidence of tumor in the prostatic urethra. Io Seemayer and associates found that 5 of 7 patients with carcinoma in situ of the bladder had silent but extensive intraductal prostatic involvement, including 3 with microinvasion.11 All had symptoms that were characteristic of carcinoma in situ, which included dysuria and urgency. In 3 patients the prostatic involvement was diagnosed by transurethral resection and in 2 it was discovered only after cystectomy. They concluded that prostatic assessment was important in the evaluation of patients with carcinoma in situ.I 1 Schellhammer and associates correlated the pathological stage ofprostatic involvement with survival. When noninvasive cancer was observed the 5-year survival rate was 50 per cent (6 of 12 patients), while it decreased to 4 of 18 patients (22 per cent) with stromal invasion. 12 At a recent bladder cancer workshop Montie and associates described prostatic involvement in 27 of 183 cystectomies (19 per cent). 13 Of 27 patients 9 (33 per cent) had invasive cancer, which carries a worse prognosis, and 18 (67 per cent) had noninvasive cancer (carcinoma in situ). CONCLUSION
The fact that there is a great difference between a biopsy (how large and deep, how obtained and from where) and a cystectomy specimen is well recognized. Another fact must be considered. When transitional cell cancer is found in the prostate what are the variables? How many sections taken at what intervals are examined by what pathologists for how long an interval and so forth? The statistical limitations of interpretations of biopsy results compared to cystectomy results are obvious. Transitional cell cancer of the bladder does appear in the prostate. Since this fact may change the therapy the information is worth obtaining, especially when approaching a decision about whether to continue conservative therapy or to perform ablative surgery. REFERENCES 1. Ortega, L. G., Whitmore, W. F., Jr. and Murphy, A. I.: In situ carcinoma of the prostate with intraepithelial extension into the urethra and bladder; Paget's disease of the urethra and bladder. Cancer, 6: 898, 1953. 2. Melamed, M. R., Voutsa, N. G. and Grabstald, H.: Natural history and clinical behavior of in situ carcinoma of the human urinary bladder. Cancer, 17: 1533, 1964. 3. Herr, H. W., Whitmore, W. F., Jr., Sogani, P. C. and Pinsky, C. M.: Extravesical carcinoma in situ after intravesical bacillus Calmette-Guerin (ECG). Read at annual meeting of the American Urological Association, Las Vegas, Nevada, abstract 346, p. 178, April 17-21, 1983. 4. Beebe, D.S. and Persky, L.: Urethral extension ofvesical neoplasm. Surgery, 66: 687, 1969. 5. Lockhart, J. L., Chaikin, L., Bondhus, M. J. and Politano, V.
6.
7.
8. 9. 10. 11.
12. 13.
Prostatic recurrences in the management of superficial bladder tumors. J. Urol., 130: 256, 1983. Prout, G. R., Jr.: Personal communication. Weinstein, R. S.: Pathobiology of bladder carcinoma. In: AUA Monographs, Bladder Cancer. Edited by W.W. Bonney and G. R. Prout, Jr. Baltimore: The Williams & Wilkins Co., 1982. Bonney, W.W. and Prout, G. R., Jr.: Superficial urothelial cancer: discussion. In: AUA Monographs, Bladder Cancer. Baltimore: The Williams & Wilkins Co., chapt. 16, pp. 179-181 and 195, 1982. Utz, D.: Commentary. In: AUA Monographs, Bladder Cancer. Edited by W. W. Bonney and G. R. Prout, Jr. Baltimore: The Williams & Wilkins Co., 1982. Mertz, J.: Commentary. In: AUA Monographs, Bladder Cancer. Edited by W. W. Bonney and G. R. Prout, Jr. Baltimore: The Williams & Wilkins Co., 1982. 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. Seemayer, T. A., Knaack, J., Thelma, 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. 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. Montie, J., Mirsky, A. and Levin, H. S.: Prostatic involvement in patients with bladder cancer. Poster B-10. Tenth National Bladder Cancer Project Investigator's Workshop, Sarasota, Florida, January 1984. EDITORIAL COMMENT
This relatively small series of consecutive patients with carcinoma in situ of the bladder has an important message-prostatic involvement always must be considered in patients with multifocal carcinoma in situ. Involvement of the prostate and, specifically, invasion into the prostatic stroma have an ominous prognosis and would certainly militate against intravesical therapy opposed to more radical exenterative procedures. In this paper no definition of carcinoma in situ is given and one wonders whether this terminology does, in fact, represent high grade anaplastic carcinoma in situ or just various grades of stage 0 tumors. This point needs clarification between urologists and pathologists because of the implications of carcinoma in situ for further therapy. Most urologists use the term carcinoma in situ to mean only high grade (III/III) anaplastic cells that appear to be limited to the mucosa. There is no mention of the grade of the bladder tumors and no correlation with presence or absence of carcinoma in situ. There is no correlation of presence or absence of prostatic involvement with irritative symptoms or dysuria. Most importantly, there is no breakdown of prostatic involvement into intraductal surface changes versus stromal invasion. Despite these questions, the message upon which Doctor Grabstald has focused our attention is important and should not be overlooked in the decision for therapy of patients with multifocal carcinoma in situ. Jerome P. Richie Department of Urology Brigham and Women's Hospital Boston, Massachusetts
THE JOURNAL OF UROLOGY
Copyright© 1984 by The "\IVilliams & Wilkins Co.
Decembet in U.S.A.
PROSTATIC BIOPSY IN SELECTED PATIENTS WITH CARCINOMA IN SITU OF THE BLADDER: PRELI1VUNARY REPORT HARRY GRABSTALD* From the Division of Urology, University of South Florida Medical College and Veterans Administration Hospital, Tampa, Florida
ABSTRACT
Transitional cell carcinoma was found in biopsies of grossly normal-appearing prostates in 4 of 40 patients with recurrent carcinoma in situ of the bladder. In selected patients prostatic biopsy may be warranted if conservative therapy does not control the bladder tumors and if cystectomy is contemplated. A common problem concerning patients with recurrent multifocal carcinoma in situ is the difficult decision about whether to perform ablative surgery or to continue conservative measures, such as transurethral resection with or without intravesical chemotherapy. One fact seems readily apparent, that is patients with multifocal bladder cancers and involvement of the prostatic glandular substance should undergo cystoprostatectomy and, probably, urethrectomy. A biopsy is necessary to confirm or deny the presence of urothelial cancer in the prostate.
cancerous in at least one spot and it is atypical in others". Could this finding not have been primary carcinoma in situ of the bladder with secondary prostatic extension or multifocal disease? The capricious behavior and unpredictability of the natural history of carcinoma in situ of the bladder were described by Melamed and associates in a clinical study of 25 cases. 2 A variable latency period between diagnosis of carcinoma in situ and invasion was discussed, since the authors stated that "multiple sites of involvement were a frequent occurrence".
MATERIALS AND METHODS
INCIDENCE AND SIGNIFICANCE OF PROSTATIC INVOLVEMENT BY TRANSITIONAL CELL CANCER
The study included 40 consecutive, nonselected patients with recurrent carcinoma in situ of the bladder. Prostatic biopsy was performed transurethrally and by perineal punch. No effort was made to resect completely or even to channel the prostate. Biopsy consisted of a single loop bite from the neck to the verumontanum at the 5 and 7 o'clock positions. Perinea! punch biopsy included the right and left lobes, and posterior areas. There were no complications attributable to the biopsy. RESULTS
Of the first 20 patients 12 had multifocal carcinoma in situ (2 with associated transitional cell carcinoma in the prostate) and 8 had unifocal disease (1 with prostatic involvement). Thus, 3 of 20 patients (15 per cent) had transitional cell cancer in the prostate. Also, prostatic adenocarcinoma was detected in 1 patient. These findings are surprising, since the incidence of latent prostatic cancer with complete transurethral resection is only 5 to 7 per cent. I do not propose use of routine prostatic biopsy to detect unsuspected prostatic cancer. Of the next 20 patients transitional cell cancer was found in only 1 prostate. Regardless of whether the incidence is 3 of 20 or 4 of 40 patients, the numbers are not valid statistically. The fact is that the finding of unsuspected prostatic involvement is a possibility. Whether routine biopsies are worthwhile statistically remains to be determined by larger series. DISCUSSION
In l of the earliest references to carcinoma in situ of the prostate Ortega and associates reported extension into the urethra and bladder. 1 A bladder of "slightly reduced capacity, mild diffuse injection of the bladder mucosa, and an area of edematous reddening" was described. Today, we would suspect diffuse field carcinoma in situ of the bladder, as did Ortega and associates, since they mentioned later that microscopic examination of the bladder revealed that "the mucosa is cytologically Accepted for publication August 2, 1984. *Requests for reprints: Department of Urology, Beth Israel Medical Center, First Ave. and 16th St., New York, New York 10003.
Herr and associates studied 41 patients with multifocal flat carcinoma in situ treated by transurethral resection and intravesical bacillus Calmette-Guerin. 3 Of 30 patients who responded 4 suffered recognized carcinoma in situ in the prostatic urethra. Of 24 patients with carcinoma in situ treated by transurethral resection alone 12 underwent cystectomy and prostatic urethral cancer was found in 15 per cent. It is interesting that the incidence of prostatic involvement is the same in our series and that of Herr and associates. Beebe and Persky emphasized the "devastating effect" of transitional cell carcinoma in the prostate. 4 Lockhart and associates also suggested that tumor in the prostatic urethra indicates the presence of an aggressive tumor and that therapy should be instituted accordingly. They recommended that followup include cytology, cystoscopy and prostatic urethral biopsies.5 Prout has stated that radical cystectomy is indicated when the prostate is invaded in patients with multifocal carcinoma in situ. 6 · 7 This also has been my belief and the therapeutic philosophy of all urological oncologists with whom I have discussed the matter. Utz indicated that prostatic biopsy was important regardless of how it was done. 8 He emphasized the fact that intravesical chemotherapy should not be used unless one knows what the prostate shows. Utz stated, "If 40 percent of these people have cancer in the prostatic ducts as well as in the bladder, I think that we just have to know about it". In the same monograph Bonney and Prout emphasized the fact that a needle biopsy of both lobes of the prostate as well as collection of urine from both ureters might be worthwhile. 7 Mertz questioned whether Utz had ever found prostatic implants that were attributable to a urethral biopsy. 9 Utz indicated that there is no doubt that if the mucosa was violated the urothelium was more conducive to implantation but the studies to date had shown no implants following biopsy. Laor and associates compared the records of 137 patients who underwent simultaneous transurethral resection of bladder tumors and the prostate to those of 150 patients who underwent transurethral resection of bladder tumors only. The data pre-
1117
1118
GRABSTALD
sented no evidence that simultaneous resection of bladder tumors and the prostate adversely affects the incidence of tumor in the prostatic urethra. Io Seemayer and associates found that 5 of 7 patients with carcinoma in situ of the bladder had silent but extensive intraductal prostatic involvement, including 3 with microinvasion.11 All had symptoms that were characteristic of carcinoma in situ, which included dysuria and urgency. In 3 patients the prostatic involvement was diagnosed by transurethral resection and in 2 it was discovered only after cystectomy. They concluded that prostatic assessment was important in the evaluation of patients with carcinoma in situ.I 1 Schellhammer and associates correlated the pathological stage ofprostatic involvement with survival. When noninvasive cancer was observed the 5-year survival rate was 50 per cent (6 of 12 patients), while it decreased to 4 of 18 patients (22 per cent) with stromal invasion. 12 At a recent bladder cancer workshop Montie and associates described prostatic involvement in 27 of 183 cystectomies (19 per cent). 13 Of 27 patients 9 (33 per cent) had invasive cancer, which carries a worse prognosis, and 18 (67 per cent) had noninvasive cancer (carcinoma in situ). CONCLUSION
The fact that there is a great difference between a biopsy (how large and deep, how obtained and from where) and a cystectomy specimen is well recognized. Another fact must be considered. When transitional cell cancer is found in the prostate what are the variables? How many sections taken at what intervals are examined by what pathologists for how long an interval and so forth? The statistical limitations of interpretations of biopsy results compared to cystectomy results are obvious. Transitional cell cancer of the bladder does appear in the prostate. Since this fact may change the therapy the information is worth obtaining, especially when approaching a decision about whether to continue conservative therapy or to perform ablative surgery. REFERENCES 1. Ortega, L. G., Whitmore, W. F., Jr. and Murphy, A. I.: In situ carcinoma of the prostate with intraepithelial extension into the urethra and bladder; Paget's disease of the urethra and bladder. Cancer, 6: 898, 1953. 2. Melamed, M. R., Voutsa, N. G. and Grabstald, H.: Natural history and clinical behavior of in situ carcinoma of the human urinary bladder. Cancer, 17: 1533, 1964. 3. Herr, H. W., Whitmore, W. F., Jr., Sogani, P. C. and Pinsky, C. M.: Extravesical carcinoma in situ after intravesical bacillus Calmette-Guerin (ECG). Read at annual meeting of the American Urological Association, Las Vegas, Nevada, abstract 346, p. 178, April 17-21, 1983. 4. Beebe, D.S. and Persky, L.: Urethral extension ofvesical neoplasm. Surgery, 66: 687, 1969. 5. Lockhart, J. L., Chaikin, L., Bondhus, M. J. and Politano, V.
6.
7.
8. 9. 10. 11.
12. 13.
Prostatic recurrences in the management of superficial bladder tumors. J. Urol., 130: 256, 1983. Prout, G. R., Jr.: Personal communication. Weinstein, R. S.: Pathobiology of bladder carcinoma. In: AUA Monographs, Bladder Cancer. Edited by W.W. Bonney and G. R. Prout, Jr. Baltimore: The Williams & Wilkins Co., 1982. Bonney, W.W. and Prout, G. R., Jr.: Superficial urothelial cancer: discussion. In: AUA Monographs, Bladder Cancer. Baltimore: The Williams & Wilkins Co., chapt. 16, pp. 179-181 and 195, 1982. Utz, D.: Commentary. In: AUA Monographs, Bladder Cancer. Edited by W. W. Bonney and G. R. Prout, Jr. Baltimore: The Williams & Wilkins Co., 1982. Mertz, J.: Commentary. In: AUA Monographs, Bladder Cancer. Edited by W. W. Bonney and G. R. Prout, Jr. Baltimore: The Williams & Wilkins Co., 1982. 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. Seemayer, T. A., Knaack, J., Thelma, 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. 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. Montie, J., Mirsky, A. and Levin, H. S.: Prostatic involvement in patients with bladder cancer. Poster B-10. Tenth National Bladder Cancer Project Investigator's Workshop, Sarasota, Florida, January 1984. EDITORIAL COMMENT
This relatively small series of consecutive patients with carcinoma in situ of the bladder has an important message-prostatic involvement always must be considered in patients with multifocal carcinoma in situ. Involvement of the prostate and, specifically, invasion into the prostatic stroma have an ominous prognosis and would certainly militate against intravesical therapy opposed to more radical exenterative procedures. In this paper no definition of carcinoma in situ is given and one wonders whether this terminology does, in fact, represent high grade anaplastic carcinoma in situ or just various grades of stage 0 tumors. This point needs clarification between urologists and pathologists because of the implications of carcinoma in situ for further therapy. Most urologists use the term carcinoma in situ to mean only high grade (III/III) anaplastic cells that appear to be limited to the mucosa. There is no mention of the grade of the bladder tumors and no correlation with presence or absence of carcinoma in situ. There is no correlation of presence or absence of prostatic involvement with irritative symptoms or dysuria. Most importantly, there is no breakdown of prostatic involvement into intraductal surface changes versus stromal invasion. Despite these questions, the message upon which Doctor Grabstald has focused our attention is important and should not be overlooked in the decision for therapy of patients with multifocal carcinoma in situ. Jerome P. Richie Department of Urology Brigham and Women's Hospital Boston, Massachusetts