SCIENTIFIC ARTICLES

RADICAL PROSTATECTOMY AFTER DEFINITIVE RADIATION THERAPY FOR PROSTATE CANCER* PETER LINK, M.D. FUAD S. FREIHA, M.D. From the Division of Urology, Stanford University Medical School, Stanford, California

~rostatectomy was performed in 14 patients following local failure of radiaarcinoma of the prostate. Ten patients were treated with external beam and ~,ion. The interval from beginning radiation therapy to biopsy-proved residwas twenty-four to one hundred fourteen months (mean 61 months). Ten anterior and lateral fibrosis. Five patients had loss of tissue planes between ;, however, no rectal injuries occurred. Estimated blood loss was 300-8,000 )perative time was one hundred ten to three hundred seventy-five minutes Significant late complications are impotence (100%) and incontinence '~as 1.1-27.2 cc (mean 11.1 cc). Seven patients had seminal vesicle involvelpsule penetration, and 6 had positive surgical margins. Follow-up ranges vwnths (median 18 months). Currently, 6 patients are clinically without prostate-specific antigen (PSA) of O.0 ng/mL. Four patients have no clinical do have detectable serum PSA, and 4 patients have evidence of metastatic an with elevated serum PSA levels. Radical prostatectomy following radiaeter immediate morbidity or mortality compared with radical prostatectomy m and takes only slightly longer to perform. However, there is a marked nce and incontinence. More patients followed for a longer time are needed to !ical prostatectomy on survival of patients who fail radiation therapy.

curative intent has been ~rtant modality in the vith localized adenoearThe reported five-, tenil are 81 percent, 60 perpercent, respectively. 1 however, show a signifiits have failure of local an increased risk of dis',se patients, if they have tie disease, pose a thera,tment options include en ablation, radical eysdieal prostateetomy. At offering salvage radical ' ,'eted subset of these pand Methods 84 and December 1988, ?al prostatectomies have

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been performed at Stanford for prostate cancer. Of these, 14 patients had previously been treated with radiation therapy, 10 with 7,000 rad of external beam therapy, and 4 with implantation of Iodine-125 seeds. Thirteen patients presented with a new or enlarging prostatic nodule on routine physical examination. The interval from initiating radiation therapy to biopsy-proved residual or recurrent disease ranged between twenty-four months and one hundred fourteen months (mean 61 mos). The remaining patient had a positive prostate biopsy showing residual disease fifty-nine months after initiation of radiation therapy with no changes on rectal examination. Patients were restaged with prostate biopsy, serum prostate-specific antigen (PSA) determined by the Yang assay, 4 and bone scans.

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Supported by a grant from The Richard M. Lueas Foundation.

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TABLE I.

Initial stage and treatment

--Initial Pt. Stage Grade A B C D

C D1 B1 B1

E F G H

B2 B2 B2 C

I J K L M

B1 A2 B1 C C

N

B1

2+2 2 +3 3+2 "well diff." 3 +3 3+3 3+4 "mod. diff." N.A. 3+4 3+4 2+3 "well diff." 3+3

Mode of Radiation

Recurrence* (mos)

7,000 ext. beam 7,000 ext. beam 125Iseeds 7,000 ext. beam

24 51 61 105

7,400 ext. beam 125Iseeds 125Iseeds 7,000 ext. beam

114 44 58 59

Incontinence in patients followed at least six months

TABLE II.

Pt.

Preop

A B

None None

C D E

None None Minor

F G

None None

beam beam

83 56 37 35 48

H I J

None None None

7,000 ext. beam

51

K

None

7,000 ext. 7,000 ext. 125Iseeds 7,000 ext. 7,000 ext.

beam beam

Additional Procedure

Postop

Currefit ~ IneonL:~

Severe Severe

•• Severe Stricture Severe :i!I~ dilatation x 3 ;~ Mod. . . Mod. None •• None Severe Artificial uriNone nary sphine. Min. •• Minimal Severe Artificial uriNone nary sphine. None •• None :: Min. •• Minirn~ Severe Cystectomy + ., ileal loop None . . None i l

*Biopsy-proved.

Pelvic computerized t o m o g r a p h y (CT) scans w e r e also done in 5 patients. Clinical d a t a on each patient are listed in Table I. All patients w e r e a d m i t t e d one day prior to surgery for a limited bowel p r e p a r a t i o n with soap suds e n e m a and a 500 ec n e o m y c i n enema. Patients w e r e given gentamicin and cefoxitin perioperatively, and w o r e thigh-high support hose. Radical r e t r o p u b i c p r o s t a t e c t o m y a n d pelvic l y m p h node sampling w e r e p e r f o r m e d via a low midline incision. A urethral catheter was left to closed drainage for two to three weeks, postoperatively, and a negative pressure pelvic drain was left in the space of Retzius until drainage stopped. One patient (K) underw e n t a scheduled a b d o m i n a l aortic aneurysm repair u n d e r the same anesthetic.

neurovascular bundles in p a r t se( loss of n o r m a l tissue planes. M, time was one h u n d r e d eighty-five p a r e d w i t h one h u n d r e d sevent fourteen r a n d o m l y selected radio mies p e r f o r m e d by the same tear over the same time period. Blood loss. T h e m e d i a n est loss was 1,000 cc (300-8,000 cc) lost 8,000 cc primarily from tt plexus w h i c h was difficult to con to apical fibrosis. This patien d y n a m i c a l l y stable t h r o u g h o u t course. The m e d i a n blood loss tients w h o h a d not had prior 1,100 ec.

Results

T h e r e w e r e 6 early postopert tions, one of w h i c h required sm tion. In this patient gross hem~ retention developed fifteen d~ tively secondary to radiation e? t i n u e d aspirin use. H e faile( management with bladder i aminocaproie acid. Cystoscopy w i t h radiation cystitis and ble~ trolled w i t h 2 % formalin instill tient continued to have severe incontinence, retention, urgenc bladder capacity. F o u r months a e y s t e e t o m y w i t h ileal loop done. T h e five minor eompli( eases of ileus for eight days, 1 eas 1 calf deep vein thrombosis, an~ sistent u r i n e l e a k f r o m t h e

T h e r e 'were no o p e r a t i v e d e a t h s or intraoperative complications. The average hospital stay was six days, w h i c h is similar to that of patients w h o have h a d a radical p r o s t a t e c t o m y w i t h o u t prior irradiation.

Operative findings Significant fibrosis w i t h obliteration of normal tissue planes was found in 10 patients. There was difficulty dissecting the prostate off the r e c t u m in 5 patients, but no rectal injury occurred. T h e incidence of difficulty w i t h the rectal dissection in patients treated with interstitial seeds (1 of 4) was no greater t h a n patients w h o h a d external b e a m irradiation (4 of 10). T h e r e was no a t t e m p t m a d e to s p a r e t h e

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Early morbidity

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TABLE III. [;

: Preop. PSA (ng/mL) 13.4 56.8 3.4 14.9 26.5 10.0 26.2 •

.

14.6 4.5 42.2 4.5 73.4 1.3

Pathology and current status

Tumor Vol. (ce)

Level III Capsular Penetration (cm)

SV

Margin

10.5 20.4 7.3 19.0 27.2 2.4 19.8 2.8 1.9 10.6 17.4 4.9 1.1 10.7

13.4 6.0 1.5 0 7.5 0 6.5 1.4 0 9.5 2.2 0 0.1 0

+ + + + + + + -

+ + + + + + -

ich resolved spontaneously after

n m o r b i d i t y occurring in this se: are impotence, incontinence, aaotie stricture. All patients h a d function prior to beginning ra: At the time of surgery, 6 paal erections, an additional 2 pa'teased f u n c t i o n , a n d 6 w e r e atients are impotent postoperaents have h a d a penile prosthesis ,~ellent results. ;rol during t h e r a p y is s h o w n in ~atients r e p o r t e d incontinence on therapy, and only 1 patient ntinenee preoperatively. All of ave m o d e r a t e to severe ineonm m e d i a t e postoperative period. ,~nts w h o have been followed a x months after surgery, 5 have urinary incontinence, 1 patient montinenee and uses four to five nd 5 patients have severe ineon!the five have subsequently h a d •inary sphincter placed a r o u n d hra and are n o w continent. O n e cent the previously m e n t i o n e d ~'omparison, 4 percent of the pa'e h a d a radical p r o s t a t e e t o m y radiation t h e r a p y are ineonti-

Current Status PSA elevated + bone scan PSA elevated NED + bone scan PSA elevated NED NED NED + bone scan + bone scan NED PSA elevated NED

Months of Follow-up 26 24 28 12 20 11 30 52 6 24 15 4 3 1

viously described. 5 Average t u m o r v o l u m e was 11.1 cc. Level III capsule p e n e t r a t i o n was present in 9 patients. Seven patients h a d positive seminal vesicles and 6 patients had positive surgical margins. These findings and current status are listed in Table III. Current status

All patients are followed at t h r e e - m o n t h intervals w i t h physical examination and serum PSA determination. Bone scans are obtained every six months. Three (C, F, G) of the 4 patients w h o h a d prior interstitial seeds h a d an additional 5,000-6,000 rad of external b e a m radiation t h e r a p y to the pelvis w h e n their serum PSA failed to go to zero after surgery or b e c a m e detectable w i t h no evidence of metastatic disease. Two patients (B, J) have h a d bilateral orc h i e c t o m y after d e v e l o p m e n t of multiple sympt o m a t i c b o n e metastases. Currently, 6 patients are clinically diseasefree and have no detectable serum PSA at one to fifty-four m o n t h s p o s t o p e r a t i v e l y (median 9 months). F o u r patients have d o c u m e n t e d bone metastases on bone scans obtained six months postoperatively. Their serum PSA at that time w e r e 23.7, 21.9, 0.8, and 26.7 n g / m L , respectively. F o u r patients w h o are at three, fifteen, eleven, and twenty-six months postoperatively, respectively, have detectable serum PSA levels w i t h equivocal or negative bone scans. Comment

: ology adieal p r o s t a t e e t o m y specimens w e r e exned by the 3 - m m step section technique pre-

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The a p p r o p r i a t e t r e a t m e n t of patients with local failure of definitive radiation t h e r a p y w h o are otherwise healthy and have no evidence of

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metastatic disease is not known. Alternatives inelude observation, androgen ablation, braehytherapy, or surgical resection either by radical prostateetomy or eystoprostateetomy with urinary diversion. Several reports have been published addressing the role of salvage prostateetomy and its morbidity and mortality. Mador et al. ~ reported 4 patients who had salvage prostateetomy and 3 who had eystoprostatectomy after local failure following external beam radiation therapy. There were two intraoperative rectal injuries. Among the prostatectomy patients, the average operative time was 4.75 hours and average postoperative hospitalization was 7.6 days. The average total transfusion was 4.7 units. There was one immediate postoperative death from pulmonary edema. The remaining 3 patients have had no significant complications and are all continent. Thompson et al.7 reported on 5 patients who had salvage prostateetomy. Two had had braehytherapy in addition to external beam radiation. Postoperative complications included one myocardial infarction and one anastomotie stricture. One patient had a nerve-sparing proeedure and is now potent. Only 1 patient is continent. The other 4 patients have some degree of stress urinary incontinence, one of whom is using an external collecting device. Neerhut, Wheeler, and Seardino8 described their experience with 16 patients who had salvage prostateetomy after definitive radiotherapy. Fifteen had had interstitial radioactive gold seeds in addition to external beam irradiation. Mean operative time was 4.4 hours and mean estimated blood loss was 900 ce. There were three intraoperative rectal injuries which were closed primarily. In one of these patients a vesieourethral reetat fistula subsequently developed which required a diverting eolostomy and subsequent fistula repair. One patient had a ureteral transection which was recognized intraoperatively and successfully reimplanted. A ureteral stenosis developed in 1 patient which required ureteral reimplantation. Three patients had prolonged anastomotie leakage, and 4 patients later underwent internal urethrotomies for strictures. All of their patients are impotent and 4 (25 %) had urinary incontinence one year after surgery. Eleven (63 %) of their patients had seminal vesicle involvement and 12 (75 %) had some extraeapsular extension. Six specimens had tumor at the surgical margin. Only 12 percent of these pa192

tients have had metastatic bo at twelve months postoperati all median follow-up of twel In the present series of traoperative rectal injury dil ever, 55 percent of the patiel and 100 percent are impote had seminal vesicle invasion surgical margins. Only six t main without evidence of dis, period of follow-up, ineluc eeived additional radiation prostatic bed. Patients' clinical stage 1; therapy and their preoperat not correlate with clinical salvage prostateetomy in thi there is an apparent eorrel volvement of seminal vesiel{ come evident with even a s] low-up with 5 of 7 patient: seminal vesicles currently w disease (NED). Only 1 of 7 volved seminal vesicles is Nf went additional postoperat light of this, we are now perf ultrasound-guided s e m i n a l identify those patients with volvement and to exclude th aggressive surgical therapy. a role for radical prostateei healthy patients who haw therapy and have no evident seminal vesicles. A longer pe~ needed before the potential J termined. Stanford, California 9 4 8 0 5 ~ (DR Li Referenees 1. Bagshaw MA: Management Hosp Praet 21:73 (1986). 2. Freiha FS, and Bagshaw M~ results of post-irradiation biopsy, P 3. Seardino PT: The prognostie radiotherapy for prostate caneer, S 4. Liedtke RJ, and Batjer JD: 1 eifie antigen by radioimmunoassay 5. McNeal JE, et ah Patterns of Lancet 1:60 0986). 6. Mador DR, Huben RP, Wajsn surgery following radical radiother~ prostate, J Urol 133:58 (1985). 7. Thompson IM, Rounde JB, S? Salvage radieal prostatectomy for tate, Cancer 61:1464 (1988). 8. Neerhut GJ, Wheeler MC, an prostateetomy for radiorecurrent ac J Urol 140:544 (1988).

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