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Risk Factors for Perineal Seeding of Prostate Cancer after Needle Biopsy
0022-534 7/89/1421-0086$02.00/0 Vol. 142, July
THE ,JOURNAL OF UROLOGY
Copyright© 1989 by Williams & Wilkins
Printed in U.S.A.
RISK FACTORS FOR PERINEAL SEEDING OF PROSTATE CANCER AFTER NEEDLE BIOPSY JUDD W. MOUL,* BRIAN J. MILES,t STEVEN J. SKOOG AND DAVID G. McLEOD From the Urology Service, Walter Reed Army Medical Center, Washington, D. C.
ABSTRACT
Between 1975 and 1986, 2,107 perineal prostate biopsies were performed at our institution with 502 (23.8 per cent) positive for prostate cancer. Among this group there were 5 cases (1.0 per cent) of perineal seeding. These 5 cases along with a case referred to our institution represent cases 14 to 19 in the literature. All 19 cases are reviewed to elucidate risk factors for the development of perineal seeding. Biopsy of large volume local tumors appears to be the greatest risk factor associated with 18 of the 19 cases. Technique of biopsy appears to be important in that removal of the Tru-Cut:j: sheath and obturator may expose the perineum to a greater risk of seeding. Other factors discussed include histology, hormonal responsiveness and radiotherapy technique. Distant metastases were discovered simultaneouly or within 16 months of the perineal seeding in every case, and all patients died at a median of 36 months after initial diagnosis. Perineal seeding after prostatic needle biopsy is uncommon but its occurrence suggests a poor prognosis. (J. Ural., 142: 86-88, 1989) Since the early 1960s needle biopsy by the transperineal or transrectal route has been used to obtain histological tissue for suspected prostate cancer.' Advocates of the transrectal route contend that more accurate needle placement is possible but the risk ofbacteremia is increased significantly. 2 Transperineal biopsy has a lower complication rate but there has been a theoretical concern of needle tract seeding of carcinoma. 3 Since 1953, 13 cases of perineal seeding after transperineal biopsy have been reported.4- 15 Previous investigators have suggested that anaplastic or hormone-resistant tumors were risk factors for perineal seeding; however, radiotherapy was believed to sterilize the perineum and eliminate these potential risks. 6 - 9 A variety of therapies has been used to treat perineal seeding but long-term followup is sporadic and few conclusions regarding risk factors, therapy or prognostic significance of perineal seeding can be ascertained from the literature. We report 6 cases of perineal seeding with long-term followup on all patients, including autopsy data on 3. We hope to define this potential complication more clearly by presentation of these cases with a review of the literature.
lobes in the majority of the patients. Prophylactic oral antibiotics generally were used. Prostate cancer was graded with the Mostofi grading system and staging was based on the American Urological System (stages A to D). 16' 17 RESULTS
Between 1975 and 1986, 502 of 2,107 perineal prostate biopsies (23.8 per cent) were positive for adenocarcinoma. Of these 502 cases there were 5 (1.0 per cent) of perineal seeding, while 1 was referred to our institution with perineal involvement. Our results were divided into 2 time frames. Between 1975 and 1980, 166 of 716 biopsies (23.2 per cent) were positive for prostate cancer, including 4 of 166 (2.4 per cent) with perineal seeding. The 2.4 per cent incidence of perineal seeding between 1975 and 1980 is statistically significant (p = 0.043, Fisher's exact test) compared to the 0.3 per cent rate during the latter period. In the second half of the study (1981 to 1986) 336 of 1,391 biopsies (24.2 per cent) were positive for prostate cancer, and only 1 of the 336 (0.3 per cent) demonstrated perineal seeding. Our increased incidence of perineal seeding may be explained in part by biopsy technique. During 1975 to 1980 most surgeons would completely remove the Tru-Cut sheath and obturator with each pass, while during the second period most surgeons left the sheath of the biopsy needle in place while only removing the obturator with each core. While there was not a strict protocol regarding biopsy technique the majority of biopsies during the first half of the study were performed as above and by the latter method during the second half. Perhaps removal of the entire needle and sheath provides for greater seeding. All patients were white and the average patient age at presentation was 61 years. Four patients had only 1 biopsy while 1 had 2 separate biopsies. The stage, grade and treatment of the primary disease are outlined in the table. All patients had at least clinical stage C disease and all had received definitive primary radiotherapy. There was a mean of 16 months from biopsy until the diagnosis of perineal seeding. The perineal masses ranged from 1.5 x 1.0 to 5.5 x 4.0 cm. Of 6 patients 5 presented with a tender, painful perineal mass and in 1 the mass was discovered incidently at a "channel" transurethral prostatectomy. The grade and therapy of the perineal seeding also are shown in the table. All patients died of prostate cancer
MATERIALS AND METHODS
Records of all patients who underwent a perineal prostate biopsy between January 1975 and December 1986 were reviewed. All cases of perineal seeding seen at our institution during this period were reviewed, including a case referred in which the initial biopsy was performed elsewhere. Perineal biopsy was performed with digital rectal guidance with the patient in the lithotomy position under local anesthesia and with a 14 gauge Tru-Cut needle. Most surgeons left the Tru-Cut sheath in place while removing the obturator with each core biopsy specimen. However, in earlier years most removed the entire obturator and sheath with each pass. Two or 3 core samples were obtained from the right and left prostatic Accepted for publication January 6, 1989. The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. *Requests for reprints: Urology Service, Walter Reed Army Medical Center, Washington, D. C. 20307-5001. t Current address: Urology Service, Henry Ford Hospital, Detroit, Michigan 48202. :j: Travenol Laboratories, Inc., Deerfield, Illinois.
86
RISK
FACTORS FOR
PEHJNEAL
SEEDING OF PROSTATE CANCER
AFTER l"lEEDLE
87
BIOPSY
Current patient profiles Perinea! Seeding
Primary Tumor
Pt.-Age Stage
Grade
Therapy
Mos. to Diagnosis
LF-45
Clinical C
Not stated
Radiotherapy (7,064 rad)
25
WM-62
Pathological DI (pos. lymphadenectomy) Clinical C (neg. lymph-
Moderately differentiated
Diethylstilbestrol (5 mg.), or-
16
EM-68
Grade
Therapy
Interval to Distant Metastasis
Mos. to Death After Initial Diagnosis
Poorly differentiated Poorly differentiated
Wide excision
16 mos. (orchiectomy)
156
No
Wide excision, radiotherapy (3,000 rad)
Simultaneous
20
No
18
Not stated
Wide excision
12 mos. ((orchiectomy)
40
Yes (residual perineal disease) Yes (residual perineal disease) Yes (residual perineal disease)
chiectomy,
Well differentiated
radiotherapy (5,000 rad) Radiotherapy (6,560 rad)
adenec-
80-61
KF-65
JB-65
tomy) Clinical C
Clinical C (neg. lymphadenectomy) Clinical DI (pos. computerized
Autopsy
Moderately differentiated
Radiotherapy (6,527 rad)
10
Well differentiated
Wide excision
12 mos. (orchiectomy)
38
Well differentiated
Radiotherapy (6,900 rad)
15
Moderately differentiated
Wide excision
8 mos. (orchiectomy)
33
Poorly differentiated
Orchiectomy, radiotherapy (6,590 rad)
13
Poorly dif-
Biopsy, obser-
6 mos.
22
feren-
No
vation
tiated
tomogra-
phy scan)
at a mean of 52 months (median 36 months) from initial diagnosis. Autopsies performed in 3 of 6 cases demonstrated widespread metastases. Residual perinea! disease was present despite previous wide local excision. DISCUSSION
Our 1.0 per cent incidence of perinea! seeding is higher than that of other series. Burkholder and Kaufman reported only a 0.15 per cent incidence among 1,351 patients,6 while Blackard and associates had a 0.2 per cent incidence among 2,086 biopsies.8 Emtage and Perez-Marrero reported a 0.17 per cent incidence ofperineal seeding in a series of 575 biopsies but they calculated incidence by dividing the single occurrence by the total number of biopsies rather than the total number of positive biopsies, which is the more appropriate denominator. 14 The 13 cases of perinea! seeding previously reported in the literature are all single case reports except for that of Thompson and associates, who reported 2 cases from the same institution.4· L, Their patients had an average age of 65.8 years, and most striking is the fact that all but 1 had locally advanced disease (stage C or Dl) at biopsy diagnosis. Only Desai and Woodruff reported on a stage B cancer patient who underwent prostatectomy as initial therapy. 10 Combining our experience with all other reported cases, 18 of 19 patients had locally advanced disease, which suggests that biopsy of high volume local tumor is a risk factor for perinea! seeding. In 10 of the 13 patients reported on in the literature undifferentiated histological findings were present in the primary tumor,4· 11 • 13 • L, while the remaining 3 had well or moderately differentiated disease. 12 • 14 • 15 Combining our cases with those reported previously, 11 of 19 (58 per cent) had undifferentiated primary tumors. Regarding the grade of the perineal seeding, 11 of 19 (58 per cent) had undifferentiated disease. However, in 3 cases perineal seeding grade was not stated and 2 showed a more differentiated grade in the seeding. Previous investigators have suggested that grade is a definite risk factor for perineal seeding. Burkholder and Kaufman stated that highly
anaplastic tumors are most likely to seed. 6 Blackard and associates went a step further and advocated closer followup of poorly differentiated patients after biopsy. 8 Recently Brausi and associates again reaffirmed that patients with poorly differentiated tumors should be followed carefully on a monthly basis for 1 year after perinea! biopsy. 13 Undifferentiated primary tumor also appears to be a substantial risk factor for perinea! seeding. However, any grade of tumor can manifest perinea! seeding as demonstrated from our experience. Based upon our observations we would not advocate closer followup of patients with poorly differentiated tumors but would look for perineal seeding at followup in all patients. In only 5 of the 13 previous cases was radiotherapy used to treat the primary tumor. Despite this limited experience previous investigators have postulated that radiotherapy of the primary tumor would sterilize the perineum, thereby lowering the clinical incidence of perinea! seeding. Labardini and Nesbit stated that radiation therapy maintained the seeding in a subclinical state of remission,7 and Puigvert and associates believed that seeding of tumor cells is common but that radiotherapeutic measures eradicated the perinea! seeding. 9 Emtage and Perez-Marrero contended that the true incidence of needle tract seeding cannot be ascertained, since radiotherapy makes small subclinical seedings disappear. 14 Addonizio and Kapoor reported that a 500 rad boost of radiation to the perineum in their patient did not prevent perinea! seeding but they advocated a sterilizing perinea! dose of radiation after perinea! biopsy of poorly differentiated tumors. 11 Warden and associates presented a patient with well differentiated carcinoma in whom perinea! seeding developed despite radiotherapy. 12 They found that the isodose curve did not adequately treat the perineum and they modified the technique to assure full perineal dosage. All of our patients received primary external beam radiotherapy. Two patients received cobalt therapy through a 15 x 15 cm. field of 4,000 rad and then a prostate boost to the final dose. The remaining patients received megavoltage therapy through a 10 x 10 cm. field of 4,500 rad and then an additional
88
MOUL AND ASSOCIATES
prostatic boost. None was given a specific additional boost to the perineum. The calculated maximum isodose curve to the perineum in these patients was 20 per cent. Certainly, radiation did not sterilize perineal seeding in these patients but it is not known whether this dose would sterilize occult seeding in others. When one considers the other risk factors, especially tumor volume, and that perineal seeding is rare, we do not advocate changing the radiotherapy technique to include a perineal boost. Hormonal resistance as a precipitating factor in perineal seeding was suggested previously by Labardini and Nesbit, 7 and Puigvert and associates. 9 In 7 of 13 previous reports•- 7 , 9 , rn, 14 and 9 of 19 patients (47 per cent) over-all perineal seeding developed after hormonal therapy had been instituted. Of our 6 patients 4 had perineal seeding evident before any hormonal manipulation. Hormonal therapy or resistance does not appear to be a risk factor for seeding. The interval to the appearance of perineal seeding in the literature averaged 15.6 months, which is similar to our experience and patients presented with a tender perineal mass. The diameter of the excised perineal masses ranged from 3 mm. to 5 cm.4· 5 Treatment for perineal seeding has included radiotherapy, hormonal therapy and either simple excision or aggresive wide local excision. The efficacy of any treatment has been unclear due to inadequate followup. In only 6 of the 13 previous reports was any followup given and the exact interval to death was available only for 3 cases (18, 6 and 3 months, respectively, after initial diagnosis). 6 ' 9 ' 15 Wide excision has been the mainstay of treatment but in the aforementioned 3 cases and in our series excision did not eradicate local disease or alter disease progression. Distant metastases were discovered simultaneously or within 16 months after presentation with perineal seeding in our 6 patients. Seeding should signify a careful evaluation for metastatic disease. Thus, local therapy appears to be useful only as a palliative measure. In conclusion, perineal seeding portends a poor prognosis; all of our patients have died of disease at a median of 36 months from the initial diagnosis. While 1 young patient (L. F.) achieved survival in excess of 12 years, the mean survival of the remaining 5 was 30 months. This survival time is less than the expected survival for comparable stage cancer patients with seeding who are treated with radiotherapy. 18 • 19 REFERENCES 1. Kaufman, J. J. and Schultz, J. I.: Needle biopsy of the prostate: a re-evaluation. J. Ural., 87: 164, 1962. 2. Thompson, P. M., Pryor, J. P., Williams, J. P., Eyers, D. E.,
3. 4.
5. 6.
7.
8.
9.
10. 11. 12.
13.
14.
15.
16.
17.
18.
19.
Dulake, C., Scully, M. F. and Kakkar, V. V.: The problem of infection after prostatic biopsy: the case for the transperineal approach. Brit. J. Ural., 54: 736, 1982. Rinker, J. R. and Shuman, W. G.: Perinealpunch biopsy of prostate with statistical analysis. J. Ural., 67: 709, 1952. Clarke, B. G., Leadbetter, W. F. and Campbell, J. S.: Implantation of cancer of the prostate in site of perinea! needle biopsy: report of a case. J. Ural., 70: 937, 1953. Goldman, E. J. and Samellas, W.: Local extension of carcinoma of the prostate following needle biopsy. J. Ural., 84: 575, 1960. Burkholder, G. V. and Kaufman, J. J.: Local implantation of carcinoma of the prostate with percutaneous needle biopsy. J. Ural., 95: 801, 1966. Labardini, M. M. and Nesbit, R. M.: Perinea! extension of adenocarcinoma of the prostate gland after punch biopsy. J. Ural., 97: 891, 1967. Blackard, C. F., Soucheray, J. A. and Gleason, D. F.: Prostate needle biopsy with perinea! extension of adenocarcinoma. J. Ural., 106: 401, 1971. Puigvert, A., Elizalde, C. and Matz, J. A.: Perinea[ implantation of carcinoma of the prostate following needle biopsy: a case report. J. Ural., 107: 821, 1972. Desai, S. G. and Woodruff, L. M.: Carcinoma of prostate. Local extension following perinea! needle biopsy. Urology, 3: 87, 1974. Addonizio, J. C. and Kapoor, S. N.: Perinea! seeding of prostatic carcinoma after needle biopsy. Urology, 8: 513, 1976. Warden, S.S., Schellhammer, P. F. and el-Mahdi, A.: Well differentiated carcinoma of the prostate seeding a perinea! needle biopsy tract. Brit. J. Ural., 56: 436, 1984. Brausi, M., Latini, A. and Palladini, P. D.: Local seeding of anaplastic carcinoma of prostate after needle biopsy. Urology, 27: 63, 1986. Emtage, J. B. and Perez-Marrero, R.: Extension of carcinoma of prostate along perinea! needle biopsy tract. Urology, 27: 548, 1986. Thompson, I. M., Baikadi, M., Berchmans, J., Berkland, M. and Ortiz, R.: Perinea[ recurrence of adenocarcinoma of prostate following radiation therapy. Urology, 31: 198, 1988. Harada, M., Mostofi, F. K., Corle, D. K., Byar, D. P. and Trump, B. F.: Preliminary studies of histologic prognosis in cancer of the prostate. Cancer Treat. Rep., 61: 223, 1977. Murphy, G. P., Gaeta, J. F., Pickren, J. and Wajsman, Z.: Current status of classification and staging of prostate cancer. Cancer, 45: 1889, 1980. Bagshaw, M. A.: Radiation therapy of prostatic cancer. In: Genitourinary Cancer Surgery. Edited by E. D. Crawford and T. A. Borden. Philadelphia: Lea & Febiger, chapt. 47, pp. 405-411, 1982. Pilepich, M. V., Zinniger, M., Johnson, R. J., Sause, W. T., Perez, C. A., Hanks, G. E., Krall, J.M., Martz, K. L. and Russ, H. H.: Prognostic significance of nodal involvement in locally advanced (stage C) carcinoma of the prostate-RTOG experience. Urology, 30: 535, 1987.
THE ,JOURNAL OF UROLOGY
Copyright© 1989 by Williams & Wilkins
Printed in U.S.A.
RISK FACTORS FOR PERINEAL SEEDING OF PROSTATE CANCER AFTER NEEDLE BIOPSY JUDD W. MOUL,* BRIAN J. MILES,t STEVEN J. SKOOG AND DAVID G. McLEOD From the Urology Service, Walter Reed Army Medical Center, Washington, D. C.
ABSTRACT
Between 1975 and 1986, 2,107 perineal prostate biopsies were performed at our institution with 502 (23.8 per cent) positive for prostate cancer. Among this group there were 5 cases (1.0 per cent) of perineal seeding. These 5 cases along with a case referred to our institution represent cases 14 to 19 in the literature. All 19 cases are reviewed to elucidate risk factors for the development of perineal seeding. Biopsy of large volume local tumors appears to be the greatest risk factor associated with 18 of the 19 cases. Technique of biopsy appears to be important in that removal of the Tru-Cut:j: sheath and obturator may expose the perineum to a greater risk of seeding. Other factors discussed include histology, hormonal responsiveness and radiotherapy technique. Distant metastases were discovered simultaneouly or within 16 months of the perineal seeding in every case, and all patients died at a median of 36 months after initial diagnosis. Perineal seeding after prostatic needle biopsy is uncommon but its occurrence suggests a poor prognosis. (J. Ural., 142: 86-88, 1989) Since the early 1960s needle biopsy by the transperineal or transrectal route has been used to obtain histological tissue for suspected prostate cancer.' Advocates of the transrectal route contend that more accurate needle placement is possible but the risk ofbacteremia is increased significantly. 2 Transperineal biopsy has a lower complication rate but there has been a theoretical concern of needle tract seeding of carcinoma. 3 Since 1953, 13 cases of perineal seeding after transperineal biopsy have been reported.4- 15 Previous investigators have suggested that anaplastic or hormone-resistant tumors were risk factors for perineal seeding; however, radiotherapy was believed to sterilize the perineum and eliminate these potential risks. 6 - 9 A variety of therapies has been used to treat perineal seeding but long-term followup is sporadic and few conclusions regarding risk factors, therapy or prognostic significance of perineal seeding can be ascertained from the literature. We report 6 cases of perineal seeding with long-term followup on all patients, including autopsy data on 3. We hope to define this potential complication more clearly by presentation of these cases with a review of the literature.
lobes in the majority of the patients. Prophylactic oral antibiotics generally were used. Prostate cancer was graded with the Mostofi grading system and staging was based on the American Urological System (stages A to D). 16' 17 RESULTS
Between 1975 and 1986, 502 of 2,107 perineal prostate biopsies (23.8 per cent) were positive for adenocarcinoma. Of these 502 cases there were 5 (1.0 per cent) of perineal seeding, while 1 was referred to our institution with perineal involvement. Our results were divided into 2 time frames. Between 1975 and 1980, 166 of 716 biopsies (23.2 per cent) were positive for prostate cancer, including 4 of 166 (2.4 per cent) with perineal seeding. The 2.4 per cent incidence of perineal seeding between 1975 and 1980 is statistically significant (p = 0.043, Fisher's exact test) compared to the 0.3 per cent rate during the latter period. In the second half of the study (1981 to 1986) 336 of 1,391 biopsies (24.2 per cent) were positive for prostate cancer, and only 1 of the 336 (0.3 per cent) demonstrated perineal seeding. Our increased incidence of perineal seeding may be explained in part by biopsy technique. During 1975 to 1980 most surgeons would completely remove the Tru-Cut sheath and obturator with each pass, while during the second period most surgeons left the sheath of the biopsy needle in place while only removing the obturator with each core. While there was not a strict protocol regarding biopsy technique the majority of biopsies during the first half of the study were performed as above and by the latter method during the second half. Perhaps removal of the entire needle and sheath provides for greater seeding. All patients were white and the average patient age at presentation was 61 years. Four patients had only 1 biopsy while 1 had 2 separate biopsies. The stage, grade and treatment of the primary disease are outlined in the table. All patients had at least clinical stage C disease and all had received definitive primary radiotherapy. There was a mean of 16 months from biopsy until the diagnosis of perineal seeding. The perineal masses ranged from 1.5 x 1.0 to 5.5 x 4.0 cm. Of 6 patients 5 presented with a tender, painful perineal mass and in 1 the mass was discovered incidently at a "channel" transurethral prostatectomy. The grade and therapy of the perineal seeding also are shown in the table. All patients died of prostate cancer
MATERIALS AND METHODS
Records of all patients who underwent a perineal prostate biopsy between January 1975 and December 1986 were reviewed. All cases of perineal seeding seen at our institution during this period were reviewed, including a case referred in which the initial biopsy was performed elsewhere. Perineal biopsy was performed with digital rectal guidance with the patient in the lithotomy position under local anesthesia and with a 14 gauge Tru-Cut needle. Most surgeons left the Tru-Cut sheath in place while removing the obturator with each core biopsy specimen. However, in earlier years most removed the entire obturator and sheath with each pass. Two or 3 core samples were obtained from the right and left prostatic Accepted for publication January 6, 1989. The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. *Requests for reprints: Urology Service, Walter Reed Army Medical Center, Washington, D. C. 20307-5001. t Current address: Urology Service, Henry Ford Hospital, Detroit, Michigan 48202. :j: Travenol Laboratories, Inc., Deerfield, Illinois.
86
RISK
FACTORS FOR
PEHJNEAL
SEEDING OF PROSTATE CANCER
AFTER l"lEEDLE
87
BIOPSY
Current patient profiles Perinea! Seeding
Primary Tumor
Pt.-Age Stage
Grade
Therapy
Mos. to Diagnosis
LF-45
Clinical C
Not stated
Radiotherapy (7,064 rad)
25
WM-62
Pathological DI (pos. lymphadenectomy) Clinical C (neg. lymph-
Moderately differentiated
Diethylstilbestrol (5 mg.), or-
16
EM-68
Grade
Therapy
Interval to Distant Metastasis
Mos. to Death After Initial Diagnosis
Poorly differentiated Poorly differentiated
Wide excision
16 mos. (orchiectomy)
156
No
Wide excision, radiotherapy (3,000 rad)
Simultaneous
20
No
18
Not stated
Wide excision
12 mos. ((orchiectomy)
40
Yes (residual perineal disease) Yes (residual perineal disease) Yes (residual perineal disease)
chiectomy,
Well differentiated
radiotherapy (5,000 rad) Radiotherapy (6,560 rad)
adenec-
80-61
KF-65
JB-65
tomy) Clinical C
Clinical C (neg. lymphadenectomy) Clinical DI (pos. computerized
Autopsy
Moderately differentiated
Radiotherapy (6,527 rad)
10
Well differentiated
Wide excision
12 mos. (orchiectomy)
38
Well differentiated
Radiotherapy (6,900 rad)
15
Moderately differentiated
Wide excision
8 mos. (orchiectomy)
33
Poorly differentiated
Orchiectomy, radiotherapy (6,590 rad)
13
Poorly dif-
Biopsy, obser-
6 mos.
22
feren-
No
vation
tiated
tomogra-
phy scan)
at a mean of 52 months (median 36 months) from initial diagnosis. Autopsies performed in 3 of 6 cases demonstrated widespread metastases. Residual perinea! disease was present despite previous wide local excision. DISCUSSION
Our 1.0 per cent incidence of perinea! seeding is higher than that of other series. Burkholder and Kaufman reported only a 0.15 per cent incidence among 1,351 patients,6 while Blackard and associates had a 0.2 per cent incidence among 2,086 biopsies.8 Emtage and Perez-Marrero reported a 0.17 per cent incidence ofperineal seeding in a series of 575 biopsies but they calculated incidence by dividing the single occurrence by the total number of biopsies rather than the total number of positive biopsies, which is the more appropriate denominator. 14 The 13 cases of perinea! seeding previously reported in the literature are all single case reports except for that of Thompson and associates, who reported 2 cases from the same institution.4· L, Their patients had an average age of 65.8 years, and most striking is the fact that all but 1 had locally advanced disease (stage C or Dl) at biopsy diagnosis. Only Desai and Woodruff reported on a stage B cancer patient who underwent prostatectomy as initial therapy. 10 Combining our experience with all other reported cases, 18 of 19 patients had locally advanced disease, which suggests that biopsy of high volume local tumor is a risk factor for perinea! seeding. In 10 of the 13 patients reported on in the literature undifferentiated histological findings were present in the primary tumor,4· 11 • 13 • L, while the remaining 3 had well or moderately differentiated disease. 12 • 14 • 15 Combining our cases with those reported previously, 11 of 19 (58 per cent) had undifferentiated primary tumors. Regarding the grade of the perineal seeding, 11 of 19 (58 per cent) had undifferentiated disease. However, in 3 cases perineal seeding grade was not stated and 2 showed a more differentiated grade in the seeding. Previous investigators have suggested that grade is a definite risk factor for perineal seeding. Burkholder and Kaufman stated that highly
anaplastic tumors are most likely to seed. 6 Blackard and associates went a step further and advocated closer followup of poorly differentiated patients after biopsy. 8 Recently Brausi and associates again reaffirmed that patients with poorly differentiated tumors should be followed carefully on a monthly basis for 1 year after perinea! biopsy. 13 Undifferentiated primary tumor also appears to be a substantial risk factor for perinea! seeding. However, any grade of tumor can manifest perinea! seeding as demonstrated from our experience. Based upon our observations we would not advocate closer followup of patients with poorly differentiated tumors but would look for perineal seeding at followup in all patients. In only 5 of the 13 previous cases was radiotherapy used to treat the primary tumor. Despite this limited experience previous investigators have postulated that radiotherapy of the primary tumor would sterilize the perineum, thereby lowering the clinical incidence of perinea! seeding. Labardini and Nesbit stated that radiation therapy maintained the seeding in a subclinical state of remission,7 and Puigvert and associates believed that seeding of tumor cells is common but that radiotherapeutic measures eradicated the perinea! seeding. 9 Emtage and Perez-Marrero contended that the true incidence of needle tract seeding cannot be ascertained, since radiotherapy makes small subclinical seedings disappear. 14 Addonizio and Kapoor reported that a 500 rad boost of radiation to the perineum in their patient did not prevent perinea! seeding but they advocated a sterilizing perinea! dose of radiation after perinea! biopsy of poorly differentiated tumors. 11 Warden and associates presented a patient with well differentiated carcinoma in whom perinea! seeding developed despite radiotherapy. 12 They found that the isodose curve did not adequately treat the perineum and they modified the technique to assure full perineal dosage. All of our patients received primary external beam radiotherapy. Two patients received cobalt therapy through a 15 x 15 cm. field of 4,000 rad and then a prostate boost to the final dose. The remaining patients received megavoltage therapy through a 10 x 10 cm. field of 4,500 rad and then an additional
88
MOUL AND ASSOCIATES
prostatic boost. None was given a specific additional boost to the perineum. The calculated maximum isodose curve to the perineum in these patients was 20 per cent. Certainly, radiation did not sterilize perineal seeding in these patients but it is not known whether this dose would sterilize occult seeding in others. When one considers the other risk factors, especially tumor volume, and that perineal seeding is rare, we do not advocate changing the radiotherapy technique to include a perineal boost. Hormonal resistance as a precipitating factor in perineal seeding was suggested previously by Labardini and Nesbit, 7 and Puigvert and associates. 9 In 7 of 13 previous reports•- 7 , 9 , rn, 14 and 9 of 19 patients (47 per cent) over-all perineal seeding developed after hormonal therapy had been instituted. Of our 6 patients 4 had perineal seeding evident before any hormonal manipulation. Hormonal therapy or resistance does not appear to be a risk factor for seeding. The interval to the appearance of perineal seeding in the literature averaged 15.6 months, which is similar to our experience and patients presented with a tender perineal mass. The diameter of the excised perineal masses ranged from 3 mm. to 5 cm.4· 5 Treatment for perineal seeding has included radiotherapy, hormonal therapy and either simple excision or aggresive wide local excision. The efficacy of any treatment has been unclear due to inadequate followup. In only 6 of the 13 previous reports was any followup given and the exact interval to death was available only for 3 cases (18, 6 and 3 months, respectively, after initial diagnosis). 6 ' 9 ' 15 Wide excision has been the mainstay of treatment but in the aforementioned 3 cases and in our series excision did not eradicate local disease or alter disease progression. Distant metastases were discovered simultaneously or within 16 months after presentation with perineal seeding in our 6 patients. Seeding should signify a careful evaluation for metastatic disease. Thus, local therapy appears to be useful only as a palliative measure. In conclusion, perineal seeding portends a poor prognosis; all of our patients have died of disease at a median of 36 months from the initial diagnosis. While 1 young patient (L. F.) achieved survival in excess of 12 years, the mean survival of the remaining 5 was 30 months. This survival time is less than the expected survival for comparable stage cancer patients with seeding who are treated with radiotherapy. 18 • 19 REFERENCES 1. Kaufman, J. J. and Schultz, J. I.: Needle biopsy of the prostate: a re-evaluation. J. Ural., 87: 164, 1962. 2. Thompson, P. M., Pryor, J. P., Williams, J. P., Eyers, D. E.,
3. 4.
5. 6.
7.
8.
9.
10. 11. 12.
13.
14.
15.
16.
17.
18.
19.
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