THE
Vol. 115, May Printed in U.S.A.
JOURNAL OF UROLOGY
Copyright© 1976 by The Williams & Wilkins Co.
LOCALIZED URETERAL FIBROSIS: AN UNRECOGNIZED COMPLICATION OF RADIATION THERAPY FOR PROSTATIC CARCINOMA JOSEPH A. JACOBS, RONALD S. ROSENTHAL
AND
JOHN L. SHAW
From the Department of Surgery, Division of Urology, Abington Memorial Hospital, Abington, Pennsylvania
ABSTRACT
Complications of radiation therapy for prostatic carcinoma are frequent but usually minor. A patient is described in whom localized ureteral fibrosis developed following curative radiation therapy, which subsequently required a reconstructive operation. An analogous situation regarding patients with carcinoma of the cervix is examined and possible etiologies are discussed. This complication should be recognized so that proper management can be instituted. Radiation therapy has become an accepted form of treatment for prostatic carcinoma in selected patients. Although this is associated with numerous well known complications, most are minor. Herein we describe a patient who had localized ureteral fibrosis, a previously undocumented complication.
Differential diagnosis at this time included a lucent calculus, primary ureteral tumor, extrinsic mass, metastatic prostatic carcinoma and radiation effect. Operative intervention was considered mandatory to disclose the nature of the obstructing ureteral lesion. Exploration of the right distal ureter was performed through a hockey-stick incision. The ureter was dilated proximal to a small, intrinsic mass 5 cm. from the bladder. A ureterotomy was performed above the mass and a biopsy was obtained. The biopsy revealed fibrosis and evidence of chronic inflammation
CASE REPORT
A 59-year-old man was hospitalized because of distal right ureteral obstruction discovered on a routine annual excretory urogram (IVP) (fig. 1, A).
FIG. 1. A, IVP shows hydronephrosis and hydrometer on right side down to right sacral wing on 1-hour film. B, normal IVP on 10-minute film. C, right retrograde ureterogram demonstrates lucent filling defect in right ureter 5 cm. from catheter tip.
A year prior to the aforementioned IVP the patient had had a transurethral resection of the prostate gland for stage C adenocarcinoma. The preoperative IVP at that time was normal (fig. 1, B). Postoperatively he received a course of cobalt therapy at which time 6,000 rads were delivered to an 8 by 10 cm., 360-degree rotational field centered over the prostatic fossa. Mild cystitis developed during the 6-week. treatment period but cleared rapidly with appropriate medication. The post-radiation course was uneventful and the patient was asymptomatic when rehospitalized 1 year later. Physical examination revealed a healthy, white man with a small, firm prostatic fossa. Laboratory studies, including blood urea nitrogen, creatinine, acid phosphatase, electrolytes, urinalysis, chemistry studies, and liver and bone scans, were within normal limits. Cystoscopy revealed a normal bladder with normally positioned ureteral orifices. A right retrograde pyelogram was attempted but the ureteral catheter could not be negotiated by an obstruction noted 5 cm. proximal to the right ureterovesical junction. A bulb ureterogram showed an obstructive filling defect and proximal dilatation (fig. 1, C). Accepted for publication October 31, 1975.
(fig. 2). The fibrotic segment of ureter was excised and a ureteroneocystostomy was accomplished. A ureteral stent was left indwelling and appropriate drains were inserted. Convalescence was uneventful and the patient was discharged from the hospital 10 days postoperatively in excellent condition. A repeat IVP 3 months later was normal (fig. 3). DISCUSSION
Radiation therapy has been shown repeatedly to be an effective adjunct to operation in the treatment of prostatic carcinoma in all stages. More recently, several groups have used radiation therapy as the primary, curative treatment for stages A, B and C prostatic carcinoma and have shown satisfactory results. 1-• Numerous complications have been described secondary to radiation therapy but most are minor, self-limited or easily treated. Mollenkamp and associates recently described the more common complications. 1 Vesical, rectal and urethral irritation are most often encountered but they usually resolve with therapy within a short time. A decreased libido and impotency were also common sequelae. Loh and associates reported a high incidence of urethral and
610
611
LCCALIZ€D URETERAL FIBROSIS
anal strictures. 3 also noted that more than 80 per cent of their patients were impotent post-therapy. Other reports fail to support this result. Ureteral injury has never been reported with radiation therapy alone in the treatment of prostatic carcinoma. Flocks described ureteral damage in 4 of 345 patients but all had undergone extensive radical operation (perinea! or retropubic) combined with irradiation. 5 The etiology of radiation-induced ureteral stricture is poorly understood. Although frequently exposed to high doses of radiation the ureter is rarely injured. 6 With radiation therapy for carcinoma of the cervix, ureteral injury is well documented and is postulated to be caused by tumor necrosis with subsequent parametrial fibrosis. 7 Localized ischemia also has been proposed as a possible cause of stricture formation. It is noteworthy that structural damage to the ureter by telecobalt therapy occurs equally with high and low doses of radiation. 8 Nonetheless, the etiology of this stricture formation remains unknowno However, regardless of the cause a tissue diagnosis is imperative in all similar cases to ensure proper management of this benign but potentially deleterious complication. Ureteral fibrosis must now be included in the expanding list of complications of radiation therapy for prostatic carcinoma, which unfortunately, is not minor or easily treatedo REFERENCES
1. Mollenkamp, J. S., Cooper, J. F. and Kagan, A. R.: Clinical
2. FIG. 2. Biopsy of mass of right ureter reveals infiltration of chronic inflammatory cells into fibrous connective tissue. There is no evidence of tumor. Reduced from x430.
3.
4.
5.
6.
7.
8.
experience with supervoltage radiotherapy in carcinoma of the prostate: a preliminary report. J. Uro!., H3: 374, 1975. Grout, D. C., Grayhack, J. T., Moss, W. and Holland, J. M.: Radiation therapy in the treatment of carcinoma of the prostate. J. Urol., l05: 411, 1971. Loh, E. S., Brown, H. E. and Beiler, D. D.: Radiotherapy of carcinoma of the prostate: preliminary report. J. Urol., 106: 906, 1971. Carlton, C. E., Jr., Dawoud, F., Hudgins, P. and Scott, R., Jr.: Irradiation treatment of carcinoma of the prostate: a preliminary report based on eight years of experience. J. Urol., 108: 924, 1972. Flocks, R. H.: The treatment of stage C prostatic cancer with special reference to combined surgical and radiation therapy. J. Uro!., 109: 461, 1973. Shingleton, H. M., Fowler, W. C., Jr., Pepper, F. D. and Palumbo, L.: Ureteral strictures following therapy for carcinoma of the cervix. Cancer, 24: 77, 1969. Slater, J.M. and Fletcher, J. H.: Ureteral strictures after radiation therapy for carcinoma of the uterine cervix. Amer. J. Roentgen., lH: 269, 1971. Moss, W. T., Brand, W. N. and Battifora, H.: Radiation Oncology, Rationale, Technique, Results, 4th ed. St. Louis: The C. V. Mosby Co., p. 378, 1973.
COMMENT Ureteral obstruction as a complication of irradiation therapy is well recognized in the management of cervical carcinoma. The authors present the first documented case in prostatic cancer. As the authors have noted histological confirmation must be obtained in all cases since a repeat course of irradiation, if recommended, will not relieve the stricture and carries a high risk of producing fistulas. The ureters like the bladder are lined by transitional stratified epithelium but are less sensitive to radiation than the bladder epithelium. This seems inexplicable but may relate to 2 factors: 1) less blood supply and 2) great distensibility. High dose total pelvic irradiation may cause massive fibrosis throughout the pelvis, affecting the ureters and bladder as well as other organs. Localized areas of cicatricial stenosis owing to post-radiation fibrosis occur either following surgical trauma or successfully treated cancer infiltrated hollow organs. Ascending infection and obstruction owing to scarring of the intravesical portion of the ureters are also causes of ureteral obstruction following pelvic irradiation. FIG. 3. Normal IVP 3 months post-reimplantation on 5-minute film.
Tapan Hazra The Johns Hopkins Hospital Baltimore, Maryland
Vol. 115, May Printed in U.S.A.
JOURNAL OF UROLOGY
Copyright© 1976 by The Williams & Wilkins Co.
LOCALIZED URETERAL FIBROSIS: AN UNRECOGNIZED COMPLICATION OF RADIATION THERAPY FOR PROSTATIC CARCINOMA JOSEPH A. JACOBS, RONALD S. ROSENTHAL
AND
JOHN L. SHAW
From the Department of Surgery, Division of Urology, Abington Memorial Hospital, Abington, Pennsylvania
ABSTRACT
Complications of radiation therapy for prostatic carcinoma are frequent but usually minor. A patient is described in whom localized ureteral fibrosis developed following curative radiation therapy, which subsequently required a reconstructive operation. An analogous situation regarding patients with carcinoma of the cervix is examined and possible etiologies are discussed. This complication should be recognized so that proper management can be instituted. Radiation therapy has become an accepted form of treatment for prostatic carcinoma in selected patients. Although this is associated with numerous well known complications, most are minor. Herein we describe a patient who had localized ureteral fibrosis, a previously undocumented complication.
Differential diagnosis at this time included a lucent calculus, primary ureteral tumor, extrinsic mass, metastatic prostatic carcinoma and radiation effect. Operative intervention was considered mandatory to disclose the nature of the obstructing ureteral lesion. Exploration of the right distal ureter was performed through a hockey-stick incision. The ureter was dilated proximal to a small, intrinsic mass 5 cm. from the bladder. A ureterotomy was performed above the mass and a biopsy was obtained. The biopsy revealed fibrosis and evidence of chronic inflammation
CASE REPORT
A 59-year-old man was hospitalized because of distal right ureteral obstruction discovered on a routine annual excretory urogram (IVP) (fig. 1, A).
FIG. 1. A, IVP shows hydronephrosis and hydrometer on right side down to right sacral wing on 1-hour film. B, normal IVP on 10-minute film. C, right retrograde ureterogram demonstrates lucent filling defect in right ureter 5 cm. from catheter tip.
A year prior to the aforementioned IVP the patient had had a transurethral resection of the prostate gland for stage C adenocarcinoma. The preoperative IVP at that time was normal (fig. 1, B). Postoperatively he received a course of cobalt therapy at which time 6,000 rads were delivered to an 8 by 10 cm., 360-degree rotational field centered over the prostatic fossa. Mild cystitis developed during the 6-week. treatment period but cleared rapidly with appropriate medication. The post-radiation course was uneventful and the patient was asymptomatic when rehospitalized 1 year later. Physical examination revealed a healthy, white man with a small, firm prostatic fossa. Laboratory studies, including blood urea nitrogen, creatinine, acid phosphatase, electrolytes, urinalysis, chemistry studies, and liver and bone scans, were within normal limits. Cystoscopy revealed a normal bladder with normally positioned ureteral orifices. A right retrograde pyelogram was attempted but the ureteral catheter could not be negotiated by an obstruction noted 5 cm. proximal to the right ureterovesical junction. A bulb ureterogram showed an obstructive filling defect and proximal dilatation (fig. 1, C). Accepted for publication October 31, 1975.
(fig. 2). The fibrotic segment of ureter was excised and a ureteroneocystostomy was accomplished. A ureteral stent was left indwelling and appropriate drains were inserted. Convalescence was uneventful and the patient was discharged from the hospital 10 days postoperatively in excellent condition. A repeat IVP 3 months later was normal (fig. 3). DISCUSSION
Radiation therapy has been shown repeatedly to be an effective adjunct to operation in the treatment of prostatic carcinoma in all stages. More recently, several groups have used radiation therapy as the primary, curative treatment for stages A, B and C prostatic carcinoma and have shown satisfactory results. 1-• Numerous complications have been described secondary to radiation therapy but most are minor, self-limited or easily treated. Mollenkamp and associates recently described the more common complications. 1 Vesical, rectal and urethral irritation are most often encountered but they usually resolve with therapy within a short time. A decreased libido and impotency were also common sequelae. Loh and associates reported a high incidence of urethral and
610
611
LCCALIZ€D URETERAL FIBROSIS
anal strictures. 3 also noted that more than 80 per cent of their patients were impotent post-therapy. Other reports fail to support this result. Ureteral injury has never been reported with radiation therapy alone in the treatment of prostatic carcinoma. Flocks described ureteral damage in 4 of 345 patients but all had undergone extensive radical operation (perinea! or retropubic) combined with irradiation. 5 The etiology of radiation-induced ureteral stricture is poorly understood. Although frequently exposed to high doses of radiation the ureter is rarely injured. 6 With radiation therapy for carcinoma of the cervix, ureteral injury is well documented and is postulated to be caused by tumor necrosis with subsequent parametrial fibrosis. 7 Localized ischemia also has been proposed as a possible cause of stricture formation. It is noteworthy that structural damage to the ureter by telecobalt therapy occurs equally with high and low doses of radiation. 8 Nonetheless, the etiology of this stricture formation remains unknowno However, regardless of the cause a tissue diagnosis is imperative in all similar cases to ensure proper management of this benign but potentially deleterious complication. Ureteral fibrosis must now be included in the expanding list of complications of radiation therapy for prostatic carcinoma, which unfortunately, is not minor or easily treatedo REFERENCES
1. Mollenkamp, J. S., Cooper, J. F. and Kagan, A. R.: Clinical
2. FIG. 2. Biopsy of mass of right ureter reveals infiltration of chronic inflammatory cells into fibrous connective tissue. There is no evidence of tumor. Reduced from x430.
3.
4.
5.
6.
7.
8.
experience with supervoltage radiotherapy in carcinoma of the prostate: a preliminary report. J. Uro!., H3: 374, 1975. Grout, D. C., Grayhack, J. T., Moss, W. and Holland, J. M.: Radiation therapy in the treatment of carcinoma of the prostate. J. Urol., l05: 411, 1971. Loh, E. S., Brown, H. E. and Beiler, D. D.: Radiotherapy of carcinoma of the prostate: preliminary report. J. Urol., 106: 906, 1971. Carlton, C. E., Jr., Dawoud, F., Hudgins, P. and Scott, R., Jr.: Irradiation treatment of carcinoma of the prostate: a preliminary report based on eight years of experience. J. Urol., 108: 924, 1972. Flocks, R. H.: The treatment of stage C prostatic cancer with special reference to combined surgical and radiation therapy. J. Uro!., 109: 461, 1973. Shingleton, H. M., Fowler, W. C., Jr., Pepper, F. D. and Palumbo, L.: Ureteral strictures following therapy for carcinoma of the cervix. Cancer, 24: 77, 1969. Slater, J.M. and Fletcher, J. H.: Ureteral strictures after radiation therapy for carcinoma of the uterine cervix. Amer. J. Roentgen., lH: 269, 1971. Moss, W. T., Brand, W. N. and Battifora, H.: Radiation Oncology, Rationale, Technique, Results, 4th ed. St. Louis: The C. V. Mosby Co., p. 378, 1973.
COMMENT Ureteral obstruction as a complication of irradiation therapy is well recognized in the management of cervical carcinoma. The authors present the first documented case in prostatic cancer. As the authors have noted histological confirmation must be obtained in all cases since a repeat course of irradiation, if recommended, will not relieve the stricture and carries a high risk of producing fistulas. The ureters like the bladder are lined by transitional stratified epithelium but are less sensitive to radiation than the bladder epithelium. This seems inexplicable but may relate to 2 factors: 1) less blood supply and 2) great distensibility. High dose total pelvic irradiation may cause massive fibrosis throughout the pelvis, affecting the ureters and bladder as well as other organs. Localized areas of cicatricial stenosis owing to post-radiation fibrosis occur either following surgical trauma or successfully treated cancer infiltrated hollow organs. Ascending infection and obstruction owing to scarring of the intravesical portion of the ureters are also causes of ureteral obstruction following pelvic irradiation. FIG. 3. Normal IVP 3 months post-reimplantation on 5-minute film.
Tapan Hazra The Johns Hopkins Hospital Baltimore, Maryland
