Vol. 118, November Printed in U.S.A
THE JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
URETERAL OBSTRUCTION FROM PROSTATIC CARCINOMA: RESPONSE TO ENDOCRINE AND RADIATION THERAPY STEPHEN MICHIGAN
AND
WILLIAM J. CATALONA*
From the Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, Maryland
ABSTRACT
Ureteral obstruction occurred in 10 per cent of the patients treated for prostatic carcinoma and most often was associated with poorly differentiated tumors. The response of ureteral obstruction to different forms of therapy was evaluated. Obstruction diminished in 22 of 25 orchiectomized patients (88 per cent) but in only 1 of 6 patients receiving estrogen or antiandrogen therapy alone (17 per cent). Patients who responded favorably to therapy had a significantly better survival than did non-responders. Patients treated early in the course of ureteral obstruction responded better than those treated late, while neither tumor stage nor grade correlated with response to therapy. Radiation therapy for endocrine-resistant ureteral obstruction was effective in only 2 of 8 cases (25 per cent). The literature on ureteral obstruction from prostatic carcinoma and its treatment is reviewed. Patients with ureteral obstruction secondary to adenocarcinoma of the prostate often present the urologist with a difficult decision as to which form of treatment is most appropriate. Endocrine therapy, radiation therapy and supravesical urinary diversion all have been used as methods of palliation. Although the efficacy of endocrine therapy as treatment for advanced prostatic cancer is well known, only a few attempts have been made to characterize the response of ureteral obstruction to either estrogen therapy or castration. 1- 3 A few cases have been reported in which ureteral obstruction subsided after endocrine therapy"· 5 but there have been no studies that have defined clearly the nature or range of responses that may occur when patients with ureteral obstruction receive endocrine therapy. Radiation therapy has been evaluated more thoroughly in this setting and has been reported to yield favorable initial results.B-8 However, longterm followup is lacking. Our study was undertaken to characterize· further the response to medical (estrogen or antiandrogen) and surgical (orchiectomy) endocrine therapy in patients with ureteral obstruction from prostatic cancer and to determine the prognosis after such therapy. We also report on a small number of patients with endocrine-resistant ureteral obstruction who received radiation therapy. PATIENTS AND METHODS
The charts of 1,065 patients treated for prostatic cancer at our hospital from 1952 to 1976 were reviewed. Of these patients 110 (10 per cent) had evidence of unilateral or bilateral upper urinary tract obstruction. Records for these patients were analyzed to select those individuals in whom the response to a single form of treatment, whether endocrine or radiation therapy, could be definitely established. Thirtyfive such patients were found and constitute the basis for this report (table 1). The remaining patients were excluded from consideration for a variety of reasons (table 1). A number of patients in whom ureteral obstruction did diminish were excluded beAccepted for publication December 17, 1976. Read at annual meeting of Mid-Atlantic Section, American Urological Association, Dorado Beach, Puerto Rico, September 26-0ctober 1, 1976. * Current address: Division of Urology, Washington University, 4960 Audubon Ave., St. Louis, Missouri 63110.
cause they simultaneously received more than 1 form of therapy and the relative contribution of each mode of treat-ment could not be determined. Patients in whom retention could not be eliminated as the cause of nephrosis also were excluded and, in several of these resolution may have been owing either to surgical relief bladder outlet obstruction or to endocrine therapy. Two tients who were terminally ill when first seen died weeks of the initiation of therapy and were believed not to have had time to demonstrate a response, which often takes more than 2 weeks to become apparent. The presence or absence of a response to therapy was, for the most part, judged radiographically. Excretory (IVPs) and/or retrograde ureteropyelograms were for 27 patients. Official x-ray reports were used for the remaining 8 cases, in which the x-rays could not be recovered. Renal units were judged to be either normal, minimally hydronephrotic, moderately hydronephrotic, markedly hydronephrotic or non-visualizing. In patients with bilateral ureteral obstruction and azotemia serial serum urea nitrogen or creatinine determinations were helpful in assessing the response to therapy. Autopsy findings also were taken into consideration. Of the 31 patients selected for analysis of endocrine therapy, 6 had medical therapy only, 4 with 3 mg. diethylstilbestrol per day and 2 with 200 mg. cyproterone acetate per day; 11 were treated with orchiectomy alone and 14 received orchiectomy and estrogen therapy. Of the latter 2 groups those patients treated with orchiectomy alone fared slightly better (table 2) but the difference was not statistically significant and, therefore, results for all 25 patients treated with orchiectomy are combined for all further considerations. Some patients eventually were lost to followup but all were followed at least long enough to evaluate the initial response to therapy. In 9 patients receiving endocrine therapy transurethral resection of obstructing prostatic tissue was done at about the same time that endocrine therapy was begun but there was sufficient evidence either by cystoscopy, IVP or postmortem examination to document the presence of true ureteral obstruction. Five of these patients responded to therapy and 4 did not. Of 2 patients undergoing unilateral nephrostomy and endocrine therapy 1 responded to and the nephrostomy was removed, while the other did not respond and died 12 months later. Three patients had received radiation therapy well in advance of the onset of ureteral 733
734
MICHIGAN AND CATALONA
obstruction. Two of these patients responded to endocrine therapy and 1 did not. The results of radiation therapy for ureteral obstruction could be evaluated in 8 patients: 4 who had been castrated prior to becoming obstructed, 2 who were irradiated after failure to respond to estrogen therapy and 2 who had responded initially to orchiectomy with complete radiographic resolution of obstruction but were irradiated after a relapse. The latter 4 patients also have been included in the figures evaluating primary endocrine therapy. One patient who responded to radiation therapy also underwent transurethral prostatic resection but had definite radiographic evidence of ureteral obstruction. RESULTS
Characteristics ofpatient population. In 19 patients ureteral obstruction was present when prostatic cancer was diagnosed and 16 of these had bilateral involvement. Sixteen patients had a previous diagnosis of prostatic cancer with normal upper tracts documented at or after the time of diagnosis. In all, 26 patients (74 per cent) had bilateral ureteral obstruction and only 9 (26 per cent) had unilateral obstruction. Eight patients (23 per cent) had serum urea nitrogen greater than 40 mg. per cent and an additional 10 patients (29 per cent) were mildly azotemic. Of the obstructive lesions 84 per cent were at the level of the ureterovesical junction and an additional 12 per cent were in the distal third of the ureter. One patient had extrinsic compression of the upper ureter and 1 had multiple strictures along the entire length of both ureters. At operation the left ureter of the latter patient was found to be diffusely involved with adenocarcinoma up to and including the renal pelvis. Thirty patients (86 per cent) had stage D disease, including 17 with elevation of the serum acid phosphatase. No acid phosphatase determinations were available in 3 cases. Tumor grade was available in 25 patients. In 18 patients (72 per cent) the tumor was poorly differentiated and the remaining 1. Patient selection of110 patients with ureteral obstruction from prostatic carcinoma (10 per cent of 1,065 cases reviewed)
TABLE
No. Pts. Suitable for analysis: Endocrine therapy Medical 3 mg. diethylstilbestrol daily 200 mg. cyproterone acetate daily Surgical- orchiectomy Combined- orchiectomy plus 3 mg. diethylstilbestrol daily 1 mg. diethylstilbestrol daily ? mg. diethylstilbestrol daily 25 mg. chlorotrianisene daily 40 mg. polyestradiol phosphate biweekly
4* 2 11* 6
1 5
1 1* 31
Radiation therapy Orchiectomy preceded obstruction No response to estrogen therapy Relapse after response to orchiectomy
4
2t ~ 8
Unsuitable for analysis: Insufficient records No treatment given Inadequate followup Concurrent bladder outlet obstruction Simultaneous therapies Endocrine plus radiation Endocrine plus nephrostomy Nephrostomy only Early death (less than 2 weeks after treatment) Orchiectomy and radiation preceded obstruction Miscellaneous
13 14 13 10 4 3 3 2 3 10
75
* 1 Patient received radiation before obstruction. t Patients also included in endocrine therapy data.
TABLE
2. Comparison of orchiectomy alone to orchiectomy plus
estrogen or antiandrogenic therapy Orchiectomy Alone No. Pts. Favorable responses 1-yr. survival* 2-yr. survival* Average survival (mos.)t
10/11 6/7 2/3 26
Orchiectomy Plus Medical Therapy No. Pts.
(%)
(91) (86) (67) (2 pts.)
(%)
12/14 (86) 9/11 (82) 6/10 (60) 34 (8 pts.)
* Among patients who died or were followed for a sufficient interval. t Among patients followed until they died.
TABLE
3. Response to endocrine therapy in patients with ureteral obstruction Favoi;able Response No Response No. Pts.
Orchiectomy Diethylstilbestrol or cyproterone acetate alone Total endocrine
(%)
No. Pts.
22 1
(88) (17)
3
23
(74)
8
5
patients had only moderately well differentiated lesions. In no case was the tumor well differentiated. Response to endocrine therapy. Of 31 patients receiving endocrine therapy 23 (74 per cent) responded with a decrease in ureteral obstruction (table 3). Of those with favorable responses 22 had undergone orchiectomy and the other patient had received cyproterone acetate. In all, 22 of 25 patients (88 per cent) improved after orchiectomy, while only 1 of 6 patients (17 per cent) treated with diethylstilbestrol or cyproterone acetate responded to treatment. In most instances there was reason to believe that the non-responders were taking their medication: 1 had gynecomastia, another had gynecomastia and a decrease in serum acid phosphatase and a third had diminished bone pain. The average survival of the 8 responders followed until they died was 37 months (table 4). The longest survival was 115 months in a patient with unilateral obstruction. Eight patients were lost to followup at an average of 20 months and 7 patients continue to be followed. One-year survivorship among those patients who died or were followed for a sufficient period was 15 of 16 (94 per cent) and the 2-year survivorship was 7 of 10 (70 per cent). Average survival in the patients not responding to therapy was 12 months, with the longest survival being 47 months in a patient with unilateral obstruction. Two patients died within 2 months, 3 of 8 (38 per cent) survived for at least 1 year and only 1 of 8 (13 per cent) survived for 2 years. Among the patients treated with orchiectomy the average survival was 34 months, the 1-year survivorship was 15 of 18 patients (83 per cent) and the 2-year survivorship was 8 of 14 patients (57 per cent). Those treated medically had an average survival of 9 months, a 1-year survivorship of 3 of 6 (50 per cent) and a 2-year survivorship of 1 of 6 (17 per cent), with the longest survival being 15 months after the diagnosis of ureteral obstruction. Considering the entire group of patients treated with endocrine therapy as a whole, the average survival was 25 months, the 1-year survivorship was 18 of 24 patients (67 per cent) and the 2-year survivorship was 8 of 19 patients (42 per cent). The interval between orchiectomy and the onset of clinical response is variable. In 1 patient with bilateral ureteral obstruction and azotemia the serum urea nitrogen began to decrease 2 days postoperatively. In non-uremic patients the rapidity of improvement is more difficult to judge retrospectively, depending on the timing of whatever radiographic studies were obtained. In 1 patient there was no improvement seen on an IVP 1 month after orchiectomy but subsequent improvement was noted. In another patient gradual improve-
URETERAL OBSTRUCTION FROM PROSTATIC CARCINOMA TABLE
4. Suruiual after endocrine therapy of patients with ureteral obstruction
Responders No. Longest survival (mos.) 1-Yr. survival* 2-Yr. survival* Av. survival (mos.)t
Non-Responders No.
(%)
47 3/8 1/8
115
15/16 7/10 37
(94) (70)
(8 pts.)
* Among patients who died or were followed for
12
(%) (38) (13)
(8 pts.)
Orchiectomy No. 115 15/18
8/14 34
(%)
(83) (57)
(10 pts.)
Diethylstilbestrol or Cyproterone Acetate Alone No. 15 3/6 1/6 9
(%)
Total Endocrfr1_e (%) -~~---·-·-
No. 115 18/24 8/19
(50) (17)
(6 pts.)
25
(67) (42) (16 pts.)
a sufficient interval.
t Among patients followed until they died.
TABLE 5. Relationship between changes in serum acid phosphatase ment continued for more than 4 months. In 6 patients had response to endocrine therapy evidence of improvement within 1 week, an additional 5 had - - - - - - - - -and --------------··------evidence of improvement within 1 month and 2 more improved Pre-Treatment Favorable Post-Treatment No Acid Phosphatase Acid Phosphatase Response Response within 2 months. Rapidity of response to therapy could not be ] Elevated (16 pts.) Further increased estimated accurately in the remaining patients. 2 Unchanged 2 The duration of remission was equally difficult to judge Decreased 9 since a relapse of obstruction frequently was not accompanied Normal (12 pts.) Normal 4 8 clinical symptoms and often was not discovered until a Not known (3 pts.J ? 3 0 scheduled followup IVP revealed marked obstruc2 patients had a documented relapse during the tion. first year after therapy, 5 relapsed during the second postopResponse to radiation therapy. Patients were treated with erative year, 6 had no evidence of relapse after at least 14 4,000 to 5,500 rads during a period of 4 to 5½ weeks. months and 2 had no evidence of relapse at 4 years. One of patients, receiving 4,000 and 4,400 the latter patients had reobstruction demonstrated 99 months proved and both had been castrated before after orchiectomy. structed. None of the patients who failed on endocrine The response of an initially elevated seru1u ;;cid phospha- for ureteral obstruction or who had a after an tase to endocrine therapy frequently was of the favorable response to endocrine therapy 1mnr,·mc•n response of the ureteral obstruction (table 5). Sixteen patients tion therapy. treated with endocrine therapy had an initial elevation of Of the 2 patients who improved 1 with unilateral obstruction acid phosphatase values. A decline was observed in 10 patients became re-obstructed at 18 months but survived 39 months after orchiectomy and 9 of them (90 per cent) had a reduction and the other with bilateral obstruction had a normal PIP in the degree of the ureteral obstruction. Only 3 of 6 patients months after treatment and died of a infarction (50 cent) in ~horn the acid phosphatase did not decrease months after therapy. The average survival among the a lessening of hydronephrosis. Twelve patients had an responders was 7.5 months. There were 2, initially normal acid phosphatase and all remained normal and the longest documented survival after therapy. Eight of these individuals (67 per cent) had a ers was 14 months, the other patient lessening of ureteral obstruction. 13 months. The average survival for A correlation was found between the response to therapy patients treated with radiation was 13 months, with and whether or not prostatic cancer had been known to year survivors (50 per cent) and 1 of 7, survivors (1 1.'. antedate the development of ureteral obstruction. Eleven of per cent). Both responders had grade 3 12 "°""""·"""' (92 per cent) known to have prostatic cancer the onset of ureteral obstruction responded to endocrine non-responders, 1 had a grade 2 whereas only 12 of 19 patients (63 per cent) initially grade 3 disease. Two of these patients had up with ureteral obstruction responded to therapy. and 4 had stage D. Both patients who '""'"'"rmr,on to radiation Tumor stage and grade did not appear to have a great therapy were known to have nr,,,or,cin cancer before prognostic significance. Three of 4 patients (75 per cent) with of ureteral obstruction as were 4 of the stage C and 20 of 27 patients with stage D (74 per cent) patients. Two patients, neither of whom diseases responded to endocrine therapy. Ten of 14 patients to radiation therapy, had chemical and with 3 (71 per cent) and 3 of 6 patients with grade 2 (50 of increasing obstruction beginning within per cent) diseases responded to therapy. There was no substan- initiation of treatment. Both of these tial difference in the percentage of patients responding to serum urea nitrogen elevation of 40 to 50 in the unilaterally and bilaterally obstructed groups their base line values, with maximum (67 76 per cent, respectively) but there was a tendency tween 25 and 28 days of treatment. After radiation toward a longer survival in the group with unilateral obstruc- was terminated the serum urea nitrogen in both gradually returned toward the pre-treatment levels. tion. Relationship of response to degree obstruction. An Several miscellaneous observations were of interest. Three 1-'""''co,,n.o were on estrogen therapy when ureteral obstruction ysis was made on all 35 patients of the and they still responded to orchiectomy. Another of obstructed renal units to therapy patient been known to have hydroureteronephrosis for 28 pre-treatment obstruction (table 6). In months before orchiectomy and still responded favorably. In 4 eral obstruction only 1 of 12 (8 per cent) normal renal units patients there was evidence of increasing bony metastases at deteriorated after therapy. Of 4 minimally dilated renal the same time that ureteral obstruction was diminishing and 3 (75 per cent) returned to normal and 1 (25 per cent) 1 patient had a decrease in ureteral obstruction in the face of worse. Twelve of 15 (80 per cent) moderately dilated an increasing serum acid phosphatase level. Conversely, 1 systems improved, including 7 (47 per cent) that reverted more patient had a decrease in acid phosphatase while on estrogen normal, while 3 (20 per cent) became therapy and a second patient experienced diminished bone dilated. Of 25 markedly dilated collecting systems 15 (60 after orchiectomy- but neither had a reduction in the cent) improved, including 4 (16 per cent) that became while 4 (16 per cent) had no response and 6 (24 per of obstruction. -
aUGH'V"v
THE JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
URETERAL OBSTRUCTION FROM PROSTATIC CARCINOMA: RESPONSE TO ENDOCRINE AND RADIATION THERAPY STEPHEN MICHIGAN
AND
WILLIAM J. CATALONA*
From the Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, Maryland
ABSTRACT
Ureteral obstruction occurred in 10 per cent of the patients treated for prostatic carcinoma and most often was associated with poorly differentiated tumors. The response of ureteral obstruction to different forms of therapy was evaluated. Obstruction diminished in 22 of 25 orchiectomized patients (88 per cent) but in only 1 of 6 patients receiving estrogen or antiandrogen therapy alone (17 per cent). Patients who responded favorably to therapy had a significantly better survival than did non-responders. Patients treated early in the course of ureteral obstruction responded better than those treated late, while neither tumor stage nor grade correlated with response to therapy. Radiation therapy for endocrine-resistant ureteral obstruction was effective in only 2 of 8 cases (25 per cent). The literature on ureteral obstruction from prostatic carcinoma and its treatment is reviewed. Patients with ureteral obstruction secondary to adenocarcinoma of the prostate often present the urologist with a difficult decision as to which form of treatment is most appropriate. Endocrine therapy, radiation therapy and supravesical urinary diversion all have been used as methods of palliation. Although the efficacy of endocrine therapy as treatment for advanced prostatic cancer is well known, only a few attempts have been made to characterize the response of ureteral obstruction to either estrogen therapy or castration. 1- 3 A few cases have been reported in which ureteral obstruction subsided after endocrine therapy"· 5 but there have been no studies that have defined clearly the nature or range of responses that may occur when patients with ureteral obstruction receive endocrine therapy. Radiation therapy has been evaluated more thoroughly in this setting and has been reported to yield favorable initial results.B-8 However, longterm followup is lacking. Our study was undertaken to characterize· further the response to medical (estrogen or antiandrogen) and surgical (orchiectomy) endocrine therapy in patients with ureteral obstruction from prostatic cancer and to determine the prognosis after such therapy. We also report on a small number of patients with endocrine-resistant ureteral obstruction who received radiation therapy. PATIENTS AND METHODS
The charts of 1,065 patients treated for prostatic cancer at our hospital from 1952 to 1976 were reviewed. Of these patients 110 (10 per cent) had evidence of unilateral or bilateral upper urinary tract obstruction. Records for these patients were analyzed to select those individuals in whom the response to a single form of treatment, whether endocrine or radiation therapy, could be definitely established. Thirtyfive such patients were found and constitute the basis for this report (table 1). The remaining patients were excluded from consideration for a variety of reasons (table 1). A number of patients in whom ureteral obstruction did diminish were excluded beAccepted for publication December 17, 1976. Read at annual meeting of Mid-Atlantic Section, American Urological Association, Dorado Beach, Puerto Rico, September 26-0ctober 1, 1976. * Current address: Division of Urology, Washington University, 4960 Audubon Ave., St. Louis, Missouri 63110.
cause they simultaneously received more than 1 form of therapy and the relative contribution of each mode of treat-ment could not be determined. Patients in whom retention could not be eliminated as the cause of nephrosis also were excluded and, in several of these resolution may have been owing either to surgical relief bladder outlet obstruction or to endocrine therapy. Two tients who were terminally ill when first seen died weeks of the initiation of therapy and were believed not to have had time to demonstrate a response, which often takes more than 2 weeks to become apparent. The presence or absence of a response to therapy was, for the most part, judged radiographically. Excretory (IVPs) and/or retrograde ureteropyelograms were for 27 patients. Official x-ray reports were used for the remaining 8 cases, in which the x-rays could not be recovered. Renal units were judged to be either normal, minimally hydronephrotic, moderately hydronephrotic, markedly hydronephrotic or non-visualizing. In patients with bilateral ureteral obstruction and azotemia serial serum urea nitrogen or creatinine determinations were helpful in assessing the response to therapy. Autopsy findings also were taken into consideration. Of the 31 patients selected for analysis of endocrine therapy, 6 had medical therapy only, 4 with 3 mg. diethylstilbestrol per day and 2 with 200 mg. cyproterone acetate per day; 11 were treated with orchiectomy alone and 14 received orchiectomy and estrogen therapy. Of the latter 2 groups those patients treated with orchiectomy alone fared slightly better (table 2) but the difference was not statistically significant and, therefore, results for all 25 patients treated with orchiectomy are combined for all further considerations. Some patients eventually were lost to followup but all were followed at least long enough to evaluate the initial response to therapy. In 9 patients receiving endocrine therapy transurethral resection of obstructing prostatic tissue was done at about the same time that endocrine therapy was begun but there was sufficient evidence either by cystoscopy, IVP or postmortem examination to document the presence of true ureteral obstruction. Five of these patients responded to therapy and 4 did not. Of 2 patients undergoing unilateral nephrostomy and endocrine therapy 1 responded to and the nephrostomy was removed, while the other did not respond and died 12 months later. Three patients had received radiation therapy well in advance of the onset of ureteral 733
734
MICHIGAN AND CATALONA
obstruction. Two of these patients responded to endocrine therapy and 1 did not. The results of radiation therapy for ureteral obstruction could be evaluated in 8 patients: 4 who had been castrated prior to becoming obstructed, 2 who were irradiated after failure to respond to estrogen therapy and 2 who had responded initially to orchiectomy with complete radiographic resolution of obstruction but were irradiated after a relapse. The latter 4 patients also have been included in the figures evaluating primary endocrine therapy. One patient who responded to radiation therapy also underwent transurethral prostatic resection but had definite radiographic evidence of ureteral obstruction. RESULTS
Characteristics ofpatient population. In 19 patients ureteral obstruction was present when prostatic cancer was diagnosed and 16 of these had bilateral involvement. Sixteen patients had a previous diagnosis of prostatic cancer with normal upper tracts documented at or after the time of diagnosis. In all, 26 patients (74 per cent) had bilateral ureteral obstruction and only 9 (26 per cent) had unilateral obstruction. Eight patients (23 per cent) had serum urea nitrogen greater than 40 mg. per cent and an additional 10 patients (29 per cent) were mildly azotemic. Of the obstructive lesions 84 per cent were at the level of the ureterovesical junction and an additional 12 per cent were in the distal third of the ureter. One patient had extrinsic compression of the upper ureter and 1 had multiple strictures along the entire length of both ureters. At operation the left ureter of the latter patient was found to be diffusely involved with adenocarcinoma up to and including the renal pelvis. Thirty patients (86 per cent) had stage D disease, including 17 with elevation of the serum acid phosphatase. No acid phosphatase determinations were available in 3 cases. Tumor grade was available in 25 patients. In 18 patients (72 per cent) the tumor was poorly differentiated and the remaining 1. Patient selection of110 patients with ureteral obstruction from prostatic carcinoma (10 per cent of 1,065 cases reviewed)
TABLE
No. Pts. Suitable for analysis: Endocrine therapy Medical 3 mg. diethylstilbestrol daily 200 mg. cyproterone acetate daily Surgical- orchiectomy Combined- orchiectomy plus 3 mg. diethylstilbestrol daily 1 mg. diethylstilbestrol daily ? mg. diethylstilbestrol daily 25 mg. chlorotrianisene daily 40 mg. polyestradiol phosphate biweekly
4* 2 11* 6
1 5
1 1* 31
Radiation therapy Orchiectomy preceded obstruction No response to estrogen therapy Relapse after response to orchiectomy
4
2t ~ 8
Unsuitable for analysis: Insufficient records No treatment given Inadequate followup Concurrent bladder outlet obstruction Simultaneous therapies Endocrine plus radiation Endocrine plus nephrostomy Nephrostomy only Early death (less than 2 weeks after treatment) Orchiectomy and radiation preceded obstruction Miscellaneous
13 14 13 10 4 3 3 2 3 10
75
* 1 Patient received radiation before obstruction. t Patients also included in endocrine therapy data.
TABLE
2. Comparison of orchiectomy alone to orchiectomy plus
estrogen or antiandrogenic therapy Orchiectomy Alone No. Pts. Favorable responses 1-yr. survival* 2-yr. survival* Average survival (mos.)t
10/11 6/7 2/3 26
Orchiectomy Plus Medical Therapy No. Pts.
(%)
(91) (86) (67) (2 pts.)
(%)
12/14 (86) 9/11 (82) 6/10 (60) 34 (8 pts.)
* Among patients who died or were followed for a sufficient interval. t Among patients followed until they died.
TABLE
3. Response to endocrine therapy in patients with ureteral obstruction Favoi;able Response No Response No. Pts.
Orchiectomy Diethylstilbestrol or cyproterone acetate alone Total endocrine
(%)
No. Pts.
22 1
(88) (17)
3
23
(74)
8
5
patients had only moderately well differentiated lesions. In no case was the tumor well differentiated. Response to endocrine therapy. Of 31 patients receiving endocrine therapy 23 (74 per cent) responded with a decrease in ureteral obstruction (table 3). Of those with favorable responses 22 had undergone orchiectomy and the other patient had received cyproterone acetate. In all, 22 of 25 patients (88 per cent) improved after orchiectomy, while only 1 of 6 patients (17 per cent) treated with diethylstilbestrol or cyproterone acetate responded to treatment. In most instances there was reason to believe that the non-responders were taking their medication: 1 had gynecomastia, another had gynecomastia and a decrease in serum acid phosphatase and a third had diminished bone pain. The average survival of the 8 responders followed until they died was 37 months (table 4). The longest survival was 115 months in a patient with unilateral obstruction. Eight patients were lost to followup at an average of 20 months and 7 patients continue to be followed. One-year survivorship among those patients who died or were followed for a sufficient period was 15 of 16 (94 per cent) and the 2-year survivorship was 7 of 10 (70 per cent). Average survival in the patients not responding to therapy was 12 months, with the longest survival being 47 months in a patient with unilateral obstruction. Two patients died within 2 months, 3 of 8 (38 per cent) survived for at least 1 year and only 1 of 8 (13 per cent) survived for 2 years. Among the patients treated with orchiectomy the average survival was 34 months, the 1-year survivorship was 15 of 18 patients (83 per cent) and the 2-year survivorship was 8 of 14 patients (57 per cent). Those treated medically had an average survival of 9 months, a 1-year survivorship of 3 of 6 (50 per cent) and a 2-year survivorship of 1 of 6 (17 per cent), with the longest survival being 15 months after the diagnosis of ureteral obstruction. Considering the entire group of patients treated with endocrine therapy as a whole, the average survival was 25 months, the 1-year survivorship was 18 of 24 patients (67 per cent) and the 2-year survivorship was 8 of 19 patients (42 per cent). The interval between orchiectomy and the onset of clinical response is variable. In 1 patient with bilateral ureteral obstruction and azotemia the serum urea nitrogen began to decrease 2 days postoperatively. In non-uremic patients the rapidity of improvement is more difficult to judge retrospectively, depending on the timing of whatever radiographic studies were obtained. In 1 patient there was no improvement seen on an IVP 1 month after orchiectomy but subsequent improvement was noted. In another patient gradual improve-
URETERAL OBSTRUCTION FROM PROSTATIC CARCINOMA TABLE
4. Suruiual after endocrine therapy of patients with ureteral obstruction
Responders No. Longest survival (mos.) 1-Yr. survival* 2-Yr. survival* Av. survival (mos.)t
Non-Responders No.
(%)
47 3/8 1/8
115
15/16 7/10 37
(94) (70)
(8 pts.)
* Among patients who died or were followed for
12
(%) (38) (13)
(8 pts.)
Orchiectomy No. 115 15/18
8/14 34
(%)
(83) (57)
(10 pts.)
Diethylstilbestrol or Cyproterone Acetate Alone No. 15 3/6 1/6 9
(%)
Total Endocrfr1_e (%) -~~---·-·-
No. 115 18/24 8/19
(50) (17)
(6 pts.)
25
(67) (42) (16 pts.)
a sufficient interval.
t Among patients followed until they died.
TABLE 5. Relationship between changes in serum acid phosphatase ment continued for more than 4 months. In 6 patients had response to endocrine therapy evidence of improvement within 1 week, an additional 5 had - - - - - - - - -and --------------··------evidence of improvement within 1 month and 2 more improved Pre-Treatment Favorable Post-Treatment No Acid Phosphatase Acid Phosphatase Response Response within 2 months. Rapidity of response to therapy could not be ] Elevated (16 pts.) Further increased estimated accurately in the remaining patients. 2 Unchanged 2 The duration of remission was equally difficult to judge Decreased 9 since a relapse of obstruction frequently was not accompanied Normal (12 pts.) Normal 4 8 clinical symptoms and often was not discovered until a Not known (3 pts.J ? 3 0 scheduled followup IVP revealed marked obstruc2 patients had a documented relapse during the tion. first year after therapy, 5 relapsed during the second postopResponse to radiation therapy. Patients were treated with erative year, 6 had no evidence of relapse after at least 14 4,000 to 5,500 rads during a period of 4 to 5½ weeks. months and 2 had no evidence of relapse at 4 years. One of patients, receiving 4,000 and 4,400 the latter patients had reobstruction demonstrated 99 months proved and both had been castrated before after orchiectomy. structed. None of the patients who failed on endocrine The response of an initially elevated seru1u ;;cid phospha- for ureteral obstruction or who had a after an tase to endocrine therapy frequently was of the favorable response to endocrine therapy 1mnr,·mc•n response of the ureteral obstruction (table 5). Sixteen patients tion therapy. treated with endocrine therapy had an initial elevation of Of the 2 patients who improved 1 with unilateral obstruction acid phosphatase values. A decline was observed in 10 patients became re-obstructed at 18 months but survived 39 months after orchiectomy and 9 of them (90 per cent) had a reduction and the other with bilateral obstruction had a normal PIP in the degree of the ureteral obstruction. Only 3 of 6 patients months after treatment and died of a infarction (50 cent) in ~horn the acid phosphatase did not decrease months after therapy. The average survival among the a lessening of hydronephrosis. Twelve patients had an responders was 7.5 months. There were 2, initially normal acid phosphatase and all remained normal and the longest documented survival after therapy. Eight of these individuals (67 per cent) had a ers was 14 months, the other patient lessening of ureteral obstruction. 13 months. The average survival for A correlation was found between the response to therapy patients treated with radiation was 13 months, with and whether or not prostatic cancer had been known to year survivors (50 per cent) and 1 of 7, survivors (1 1.'. antedate the development of ureteral obstruction. Eleven of per cent). Both responders had grade 3 12 "°""""·"""' (92 per cent) known to have prostatic cancer the onset of ureteral obstruction responded to endocrine non-responders, 1 had a grade 2 whereas only 12 of 19 patients (63 per cent) initially grade 3 disease. Two of these patients had up with ureteral obstruction responded to therapy. and 4 had stage D. Both patients who '""'"'"rmr,on to radiation Tumor stage and grade did not appear to have a great therapy were known to have nr,,,or,cin cancer before prognostic significance. Three of 4 patients (75 per cent) with of ureteral obstruction as were 4 of the stage C and 20 of 27 patients with stage D (74 per cent) patients. Two patients, neither of whom diseases responded to endocrine therapy. Ten of 14 patients to radiation therapy, had chemical and with 3 (71 per cent) and 3 of 6 patients with grade 2 (50 of increasing obstruction beginning within per cent) diseases responded to therapy. There was no substan- initiation of treatment. Both of these tial difference in the percentage of patients responding to serum urea nitrogen elevation of 40 to 50 in the unilaterally and bilaterally obstructed groups their base line values, with maximum (67 76 per cent, respectively) but there was a tendency tween 25 and 28 days of treatment. After radiation toward a longer survival in the group with unilateral obstruc- was terminated the serum urea nitrogen in both gradually returned toward the pre-treatment levels. tion. Relationship of response to degree obstruction. An Several miscellaneous observations were of interest. Three 1-'""''co,,n.o were on estrogen therapy when ureteral obstruction ysis was made on all 35 patients of the and they still responded to orchiectomy. Another of obstructed renal units to therapy patient been known to have hydroureteronephrosis for 28 pre-treatment obstruction (table 6). In months before orchiectomy and still responded favorably. In 4 eral obstruction only 1 of 12 (8 per cent) normal renal units patients there was evidence of increasing bony metastases at deteriorated after therapy. Of 4 minimally dilated renal the same time that ureteral obstruction was diminishing and 3 (75 per cent) returned to normal and 1 (25 per cent) 1 patient had a decrease in ureteral obstruction in the face of worse. Twelve of 15 (80 per cent) moderately dilated an increasing serum acid phosphatase level. Conversely, 1 systems improved, including 7 (47 per cent) that reverted more patient had a decrease in acid phosphatase while on estrogen normal, while 3 (20 per cent) became therapy and a second patient experienced diminished bone dilated. Of 25 markedly dilated collecting systems 15 (60 after orchiectomy- but neither had a reduction in the cent) improved, including 4 (16 per cent) that became while 4 (16 per cent) had no response and 6 (24 per of obstruction. -
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