0360-3016/84 503.00 + [email protected]
0 1984 Pergamon Press Ltd.
TRIPLE COURSE EXTERNAL BEAM RADIOTHERAPY FOR CARCINOMA OF THE PROSTATE ANAS M. EL-MAHDI, M.D., Sc.D.,* CORNELIUS I. C. TURALBA, M.D.,* PAUL F. *HELLHAMMER, M.D.? AND WILLIAM J. PEEPLES, M.D. EasternVirginiaMedicalschool/MedicalCenterHospitals,600 GreshamDrive,Norfolk,VA 23507 In 1976 we began using a tripl~urse tecbniiw of external beam irradiation for lomlked carcinoma of the prostate. Tbe treament consisted of 2 coursesof20Gyin2weekstotbepelvisandatbirdcourseof2045Gy in 2-2H weeks as a boost to tbe prostate. A 2 week rest followed tbe iirst and second courses. Tbe results of this treatment tecbniqne are reported on the fkst SOpatknts wbo bad been followed for at kast 3 years. Altbough 96% of these patknts developed bladder and/or bowel rea&ons, tbe majority of the symptoms were in tbe very mild to mild category, with only 2%severeractions referrabk to each organ. Tbe incideace of late annplkatkms in this aerks compnred favorably to those reported by other ~utbors. Clinkalloal controlwas 96%wbik posttreatment needle biopsy performed on 22/50 patknts yielded a negative rate of 86%. Those with Stages A pad B dkeaw bad a aegative biopsy rate of 94%. Tbre+yeu WNXWKCW disease-free survival for the wbok group was 54%. This study has shown tlut with triple coarse external bum irradiation, excelknt control of loaliz.ed carcinoma of the prostate an be achkved with minimal acute morbidity. Prostatk cancer, Triple course irradiation, Complications, Local control.
INTRODUCI’ION Substantial data have accumulated over the last 2 decades concerning the effectiveness of external beam irradiation in the treatment of local&d carcinoma of the prostate I-13,15.16,18-26.29-32.35.37,3.5 Theearlierstudieswerebased
uniformity in the definition and classification of morbidity related to radiation treatment of prostatic carcinoma and proposed a grading system for these complications to allow better correlation of their incidence and severity with the treatment used. Indeed, as the curative potential of radiation therapy in prostatic cancer treatment becomes more accepted, attention will focus more on techniques that can maintain a high cure rate while lessening morbidity. In 1976 we began a pilot study of a planned triple course, external beam technique (Table 1) in the curative treatment of localized prostatic carcinoma, with the aim of reducing the severity of acute reactions and, hopefully, lessening the risk of late complications while achieving adequate loco-regional control. This paper presents our early experience with this technique.
on small patient populations, with a predominance of patients not suitable for curative resection, i.e., Stage C.4*7*9~” More recent reports, however, have shown an apparent increase in the proportion of Stage A and B patients being treated with radiation, suggesting greater acceptance of this modality as a definitive treatment for these smaller lesions.6*‘9,29*~ Long term survival data are now available supporting the claim that external beam irradiation is curative for inoperable prostatic carcinoma* and is an alternative to radical prostatectomy’93s~30in patients with disease limited to the prostate. Moreover, radiation offers the advantage of preserving potency in at least 53% of patients.lZ Various treatment techniques have been used with the aim of delivering an optimum dose to the prostate and minimizing complications particularly related to the rectum and urinary bladder. L*7.9*26 Modifications in the treatment schedule have also been reported to achieve the latter goal. ‘*29Pilepich et aL2* underscored the lack of
METHODS AND MATERIALS From 1976 to 1981, 353 patients with carcinoma of the prostate were seen in the Department of Radiation Oncology and Biophysics at the Eastern Virginia Medical School. Two hundred and twenty-nine were candidates for curative treatment with either Iodine 125 ( 125-I) im-
* Departmentof RadiationOncologyand Biophysics. t Departmentof Urology. Reprintrequeststo: Anas M. El-Mahdi,M.D., Sc.D., De-
partmentof RadiationOncologyandBiophysics,600 Gresham Drive,Norfolk,Virginia23507. Acceptedfor publication22 November1983. 541
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Table 1st course 20 Gyl2
Gy~2 - 2
I 2 wks
~2 wk rest* (whole
plantation and pelvic node dissection (93 patients) or external beam irradiation ( 136 patients). The rest were referred only for palliation of symptomatic distant metastasis or extensive pelvic disease. During this period. the preferred treatment in our institution for localized disease in low surgical risk patients was 125-I implantation and pelvic node dissection. Hence, patients entered in this study were those who could not have the latter procedure for one of the following reasons: (a) not medically fit for surgery, (b) refused 125-L (c) had a recent transurethral resection of the prostate (TURP) with minimal tissue left for an adequate implant or (d) had extensive Stage C disease for which an implant was not felt applicable. The.study population comprised the first 50 patients treated with a curative intent using the triple course technique and had been followed for at least 3 years. Thirtysix (72%) patients were white and 14 (28%) were black. They ranged in age from 50 to 82 years with a median age of 73 years. Routine pre-treatment work-up included the following diagnostic procedures: I.
*Prostate only III patients with Stage AZ1 well differentiated
2. 3. 4. 5. 6. 7. 8. 9.
z 2 wk
CBC Serum acid and alkaline phosphatase Bun, Creatinine Urinalysis Chest X ray Intravenous pyelogram Cystoscopy Biopsy either by TURP or needle biopsy or both Bone scan Bone marrow biopsy
Lymphangiography was not done routinely and only 1 patient had lymphadenectomy. Histopathologic diagnosis was established by TURP in 15 patients, needle biopsy in 28 and both TURP and needle biopsy in 7. Slides from outside hospitals were reviewed by one of our pathologists and tumor grade was recorded in each case. All patients had adenocarcinoma, 22 (44%) of which were well differentiated, 8 ( 16%) moderately differentiated, and 20 (40%) poorly differentiated. Clinical staging was done according to the system shown on Table 2. Patient distribution by stage was as follows: A7 = 5 (10%); B, = 9 (18%); B? = 12 (24%): C = 23 (46%) and D, = 1 (2%). Fifty-six percent (13/23) of the Stage C patients had poorly differentiated tumors. Ail patients received supervoltage linear accelerator
of the prostate __~
mlcroscoplc carcinoma* Multifocal microscopic carcinoma* Isolated nodule or involvement limtted to the confines 01’ one prostatic lobe B2 More than one lobe involved but tumor 15 \IIII confined to the prostate C Extracapsular extension of invasion of the seminal vesicle DI Metastatic involvement of regional pelvtc node? Obturator. hypogastric. external iliac D2 Metastatic involvement of distant sites: extra regional nodes. osseous. pulmonary A
therapy according to the schedule shown on Table I. The borders of the whole pelvic field were the top of the 5th lumbar vertebra superiorly. 1 cm outside the pelvic walls laterally and the ischial tuberosities inferiorly. This field measured 15 cm wide and 18 cm long on the average. The reduced prostatic field usually measured 8 X 8 cm. Six patients with treated with 4 MV photons using parallel opposing anterior and posterior fields for the whole pelvis and 360” rotational technique for the boost to the prostate. The rest were treated with 10 MV photons using a 4 field technique for the whole pelvis and the same rotational technique for the prostatic boost. The antero-posterior portals were as described for the 2 field technique. The lateral field usually measured 9 cm X 18 cm. with the anterior border at the level of the anterior edge of the pubic symphysis and the posterior border at the level of the mid-rectum. All fields were treated daily. The daily dose for the pelvic treatment was 2 Gy while the boost was given at 1.9 to 2 Gy a day. Everyone in this study received 40 Gy to the pelvis. The prostatic boost was only 20 Gy in the first 7 patients but the rest received 25 Gy. The 2 week rest period was given after each 20 Gy course whether or not the patient had any treatmentrelated symptoms. Patients were examined once a week while under treatment. All acute reactions were recorded according to the criteria listed on Table 3. Follow-up was done jointly by the referring urologist and the radiation oncologist. Each patient was re-examined a month after completion of treatment. then every 3 months for 2 years, after which the return visits were extended to every 6 months. Observations on delayed symptoms were made using the same criteria for acute reactions. Prostatic response was recorded on each visit. Repeat
Radiotherapy for carcinoma of the prostate 0 A. M. EL-MAHDI er (11
Table 3. Crlterla for determining complications related to prostatic I. Very
severity of side effects or irradiatron
Slight urinary frequency or dysuria or soft stools (rlxlday-not requiring medications Transient dysutia or diarrhea requiring medication; intermittent hematuria or occasional blood streaked stools Sustained dysutia, tenesmus or rectal discomfort or other symptoms requiring interruption of treatment (other than planned break) or minor surgical correction (e.g. dilatation for outlet obstruction.) Rectal symptoms requiring steroid preparations included in this category Intractable bladder pain or hematuria, rectal pain or diarrhea, or other symptoms requiring hospitahzation and/or major surgical intervention (e.g. cystectomy, urinary diversion, or colostomy)
biopsy of the prostate was done by the referring urologist, when possible, 12 months or longer after treatment. Biopsies earlier than 12 months were done only if there was a suspicion of persistent or recurrent disease. All repeat biopsies were reviewed by the same pathologist who interpreted the pre-treatment slides. Follow-up acid phosphatase determinations were done on most patients but bone scans and appropriate X rays were ordered only in symptomatic cases. Hormonal therapy was not given unless the patient developed clinical local recurrence or distant metastasis. Sexual potency was not routinely recorded as the majority of the patients were sexually inactive due to age or medical problems. needle
Table Reaction Dysuna Hematurla Diarrhea Nausea/vomitmg Total symptoms
reactions Mild 6 2 23 I 32
31 0 9 0 40
Forty-eight of the 50 patients (96%) developed reactions referrable to the bladder, or the bowel or both (Table 4). Everyone completed the prescribed treatment without significant deviation except for 2 patients who developed severe reactions and required hospitalization during the treatment period. The one who had severe hematuria was hospitalized for continuous bladder irrigation and removal of blood clots during the second and third courses. while the other who developed severe diarrhea needed intravenous therapy for dehydration during the 4th week of treatment. Nevertheless. the latter completed his treatment with only a few days delay as he was on his planned treatment break during most of his hospital stay. The acute reactions which typically developed around the end of each whole pelvic course. generally lasted 3 to 4 days and those who needed medications took them only sparingly. Many of the patients who had mild diarrhea reported taking, at the most. 2 to 3 tablets of Lomotil a day. Five patients with moderate diarrhea occasionally required steroid suppositories for rectal discomfort. A salient feature of this treatment technique was the shortening of the symptomatic period and allowing more convenient self-care with the patients mostly resting at home at the peak of their symptoms. This technique greatly benefited the elderly patients. many of whom had inadequate domiciliary help. and those who used public transportation or commuted during treatment. Table 5 shows the incidence of late bladder and rectal complications. Of the 3 patients who developed urethral strictures . 2 had TURP before radiotherapy. One patient
(48150 patients) Moderate
0 0 5 0 5
37/SO (74) 3/SO (6) 38 ‘50 (76) l,!SO (2) 79
5. Late complications Mild
Total (“,) 13.50 (26)
I 7( 34)
Total (“J ‘Required +Requlred
urinary diversion colostomy.
I so (2) 3:SO (6) 16,‘50(32) I ‘SO (2)
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developed a posterior rectal wall ulcer a year after treatment but this healed with the use of low residue diet and steroid suppositories. Of the 2 patients who had severe urinary complications by our criteria. one had severe cystitis with incontinence requiring a right nephrostomy and left ureterostomy while the other had a uretero-ureterostomy for bladder contraction and distal ureteral obstruction. Severe rectal complications also occurred in 2 patients, both requiring a diverting colostomy for progressive rectal stricture preceded by symptoms of proctitis. All these severe complications developed between 7 months and a year after treatment. There was no definite direct relationship between the acute reactions and late complications. Of the 4 patients with severe late complications. one was the patient who had severe hematuria during irradiation. Two had only mild acute reactions while the 4th patient was symptom free during treatment. On the other hand, the patient who was hospitalized for severe diarrhea during his radiation course developed no late complications. Tumor regression assessed by periodic rectal examination was gradual in every case but complete in most patients by one year after treatment. Based on the absence of clinically demonstrable prostatic disease, local control was documented in 96% (48/50) of patients 3 years post irradiation. One patient with Stage C disease developed symptomatic local recurrence with distant metastasis 8 months after treatment. The other patient also had Stage C disease, involving the bladder. His periodic rectal examinations revealed no significant enlargement of the prostate but 2 years after treatment he developed hematuria. At cystoscopy, fibrotic changes were noted in the prostatic region but tumor was noted in the bladder invading the ureteral orifices. Biopsy of the bladder lesion showed recurrent prostatic carcinoma but needle biopsy of the fibrotic prostate was nondiagnostic. Review of the portal films revealed that not all of the involved portion of the bladder had been included in the boost field. Four years after treatment, repeat biopsy of the prostate revealed recurrent carcinoma, suggesting retrograde invasion of the prostate by the persistent disease in the bladder. Ureteral stents were inserted but no systemic treatment was
Table 6. Results of
repeat biopsy distributed
given. This patient died of a cerebrovascular accident a year later. Post-treatment needle biopsies had been performed on __ 7’ patients from 6 months to 4 years after irradiation. The median time of repeat biopsy was 16 months. with only 3 patients having the biopsy less than 12 months after treatment. The rebiopsies were done by random selection. although in these 3 patients and the one with bladder invasion the prostatic biopsy was done to rule our recurrence in the primary site. While the prostate in the latter case showed no tumor, we reported this as positive because of the persistent bladder tumor. Table 6 shows the results of the initial post treatment biopsies. classified by stage and tumor differentiation. There was a high index of consistency in these biopsies as all were done by one urologist (P.S.) and all the slides were reviewed by one pathologist. Eighty-six percent of the biopsies were negative for tumor, including 2 of the 3 biopsies done during the first year. While the numbers were small. there was a trend towards a higher negative rate with early stage lesions. Taking only the patients with Stage A and B disease. the negative biopsy rate was 94%’ ( 15/ 16). All these patients with negative biopsies had no evidence of disease at the time of analysis. No definite influence of the tumor grade was evident in the biopsy results. Only 3 patients had a second biopsy. Two were done at 22 and 36 months respectively, and no tumor was found in each case. The third case was the patient with known bladder involvement whose biopsy at 48 months converted to positive. Five additional patients had pathologic examination of the prostate: 3 at autopsy (2 negative and 1 positive for tumor) and 2 by TURP (I negative and I positive). The patient who had a positive TURP was the one who had recurrence 7 months after treatment. Overall, 27/50 patients had histologic confirmation of prostatic response and 82% (22/27) had no tumor in the prostate. Incidentally, the patient whose prostate showed tumor at autopsy and the 3 others who had positive needle biopsies had clinically normal prostates. All 5 patients with persistent prostatic disease had distant metastasis as well.
by stage and grade of tumor
Tumor grade Stage
617 (86) 616 ( 100)
Radiotherapy for carcinoma of the prostate 0
DISCUSSION Regardless of technique. local control of prostatic carcinoma with external beam irradiation gauged by clinical observation and periodic examination of the prostate has been reported to be in the range of 83-98%.‘~~‘y~“‘~~” The clinical local control rate of 96% in our series compares favorably with these results. On the other hand. results of post-irradiation biopsy of the prostate have not been as encouraging. Rhamy 01al.“’ reported on the first series of planned prostatic biopsies after irradiation of 15 patients with presumably resectable prostatic carcinoma. They found persistent tumor in 87?F of these biopsies and observed a 2.5% incidence of distant metastasis 3 years after treatment. These findings raised doubts over the curative efficacy of high dose irradiation for this tumor?’ A follow-up study of the same patients by Sewell (11al.” revealed a drop in the positive biopsy rate to 65%’ at S years. Other investigators have reported positive bibut opsy rates ranging widely from 0 to 7 1‘%4-f’~‘5~‘y~1’~23~26 a few of these reports involved only small numbers of patients. Some authors’“.‘x.” suggested an adverse effect of persistent prostatic tumor on disease free survival: however. the studies of Cox and Stoffel” and Leach ef ul. ” did not support this observation. These authors found no prognostic significance for positive or negative biopsies in terms of clinical local control or survival. The difficulty in comparing these different studies because of differences in various parameters was underscored by Herr and Whitmore’J in their review of this controversial topic. Our findings with the triple-course technique may further fuel this controversy. Histologic examination of the
prostate was done in nearly half of the patients in this series with a median interval of I6 months after treatment, and a negative rate of 86% was obtained. This rate was even higher (94%) in patients with Stage A and B lesions. This is in sharp contrast to that obtained by Rhamy et al.” and is more in keeping with the findings of Carlton ct u/.~ of a higher negative biopsy rate in patients with Stage B disease than those with Stage C (70 versus 57%’ respectively). Hill et a/.15 obtained a negative biopsy rate of 76% at I year or longer after irradiation and observed a clinical local control rate of 91% at 5 years. Other aUthors4.&.‘X.‘hhave also observed that negative biopsies correlated well with disease-free survival. In our series. all patients with negative needle biopsies had no evidence of local recurrence or distant metastasis at a minimum follow-up of 3 years. A dose-response relationship was suggested by Mollenkamp CI~1.” with the observation of a higher negative biopsy rate (53a.) in patients receiving a prostatic dose of 70 to 75 Gy compared to 26%’in those receiving lower doses. This was not supported by the high rate of negative biopsies with doses of only 60 to 65 Gy in our series. A possible explanation for this discrepancy could be the predominance of early cases in our series which presumably have less tumor burden and therefore would not require as high a dose as those with more advanced lesions. The morbidity associated with pelvic irradiation is well recognized and it appears that the severity of reactions or injuries is related to the size of the daily fractions and treatment volume although such factors as previous pelvic surgery. total dose. and technique of beam delivery are contributory as we11.X~“~“‘.‘h.~‘.~0.3K Transient bladder and/ or bowel symptoms occurring during the course of treatment are quite common. affecting up to 83% of patients’” although not all symptomatic patients necessarily develop reactions referrable to both organs. While some authors do not attribute much significance to these acute reactions.‘7.‘X evidence suggests that patients tolerate the radiation treatments better if these reactions are minimized. The split course technique which has known effectiveness in other sites73.34has been reported to achieve this goal in prostatic carcinoma as well.‘.h~‘vUsing extended fields and higher doses. the triple course approach was also employed by Cosgrove of ~1.~While they did not report on the complications. George. one of the other authors.
Absolute survival at 3.yeai-s follow-up is shown in Table 7. As expected. survival correlated well with disease stage: i.e.. the more advanced the stage. the poorer the survival. No firm conclusions could be made on 5 year survival. with only 7 patients at risk for 5 years at the time of analysis. all of whom had Stage C lesions. Of these 7 patients. S are dead. 2 of prostatic carcinoma, I of a second: primary in the lung and 2 of intercurrent disease. The 2 remaining patients are alive with distant metastasis. The 3 year absolute survival in our series compares well with other reported data.“‘.‘4.‘v.‘”
A. M. EL-MAHDI
of the prostate:
Dead of Intercurrent disease (“/,)
Dead of disease (“,)
Total no. patients
Alive without disease (U<)
Alive with disease (“J
A2 BI B2 C DI
5 9 12 23 1
4(80) 6(67) 9(75) 8(35) 0
0 I(111 0 5(22) l(lOO)
0 2(22) 2( 17) 5(22) 0
I(20) 0 I(R) 5(22) 0
Radiation Oncology 0 Biology 0 Physics
observed good tolerance of the treatment with marked regression of bulky tumors in some patients after each treatment break (oral communication. April 1980). Our data show that giving a treatment break at a time when the symptoms begin to occur not only diminishes the severity of the symptoms. but shortens the symptomatic period as well. This information is only partially reflected in our tabulation of these acute reactions (Table 4) which affected 96% of our patients. It should be emphasized for future reference. that we recorded all symptoms regardless of intensity. An attempt to compare our observations with other reports without the benefit of uniform criteria is shown in Tables 8 and 9. The disparity in the incidence of acute reactions or late complications are obvious. Further comparison of the late complications in our study with the results of Pilepich et ~1.” whose
Table 8. Comparison
McGowan’” (W. W. Cross) Phillips and Lattimei’ (ColumbiaPresbyterian) Pino y Torres er al.” (Johns Hopkins) Ray et al.‘” (Stanford) Taylor et al.” (Virginia Mason) This series (EVMS)
grading system (Table 10) is similar to ours revealed more comparable figures. Their grade 2 categor) was equivalent to the moderate symptoms in our criteria and they observed an incidence of 99 GI and 105’ GU symptoms. which are comparable to the 807rGI and 13 GU symptoms in our series. Our severe complication rate of 4’; GI and 4°C GU are slightly higher than the grade 3-4 complications of 2% Cl and 0.4% GU that they observed. On the other hand. Neglia (‘I al ” reported a 7.8? major complication rate, of which 5.8% were rectosigmoid injuries requiring a colostomy. In their series. the incidence of major complications was found to be influenced b) the treatment volume and total dose. but such was not observed in our series or that of Pilepich et al.‘” where there was little variation in these two factors. Recognizing these differences. the use of a standardized classification
of acute reactions
in our series with other All Acute reactions
Total no. pts.
In our series with other
NS = Not stated.
Table 9. Comparison
of late or chrome
Late or chronic complications Series
Total no. pts.
McGowan” (W. W. Cross) Pino y Torres et al.”
34( I I )
Ray et al.” (Stanford) This series (EVMS) NS = Not stated.
Radiotherapy for carcinoma of the prostate 0 A. M. EL-MAHDI et al Table IO. Grading system of complications
used by Pilepich
(‘I (II.‘8 Grade 1. Minor. transient symptoms responding to simple outpatient management. The majority of treatment-related symptoms occuring during radiation and immediately after completion oftreatment belong to this category. Grade 2. Distressing, persistent or recurring symptoms. requiring prolonged medical treatment, occasionally necessitating brief hospitalization for diagnosis and/ or minor surgical interventions (such as urethral dilatations). Grade 3. Complications requiring major surgical procedures (laparotomy. colostomy, cystectomy) or continued . hospitahzatton (over one month). Grade 4. Fatal complications.
Reprinted with permission from Pilepich, M.V., Perez, C.A., Walz, B.J. and Zivnuska, F.R.: Complicatrons of definitive radiotherapy for carcinoma of the prostate, Inr. J. Rudior. Oncol. B&j.- Phys. Vol. 7 1981, Pergamon Press, Ltd.
or grading system for complications would eliminate one important variable when comparing the different reports on the radiotherapeutic management of prostatic cancer. The results of this study indicate that with triple course irradiation excellent local control of prostatic carcinoma can be achieved with minimal acute morbidity and not much greater risk of late complications than that obtained with an uninterrupted course. We have been encouraged by these results and have continued to use this technique in our institution. We have decreased the daily fractions to 1.8 Gy and switched to a 24ateral arc rotation for the prostatic boost utilizing CT scanning for better localization. Our preliminary results indicate a further shift of the symptoms to the very mild category with no patient developing any severe complications. We are hoping that the improved dosimetry of the prostatic boost would decrease the incidence of late complications as well
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Radlauon Oncolog) 0 Biology 0 Phycs
26. Perez, C.A.. Ackerman. L.V.. Silber. I.. Rokce. R.K.: Radiation therapy in the treatment of localized carcinoma of the prostate: Preliminan report using X-MeV photons. C‘utwr 34: IO59- 1068. 1974. 17. Phillips. N.B.. Lattimer. J.K.: Complications and regression of primary tumor size with radiotherapy in prostatic cancer. J. C’rol. 108: 91 I-923. 1972. 28. Pilepich. M.V.. Perez. C.A.. Walz. B.J.. Zivnuska. F.R.: Complications of definitive radiotherapy for carcinoma of the prostate. In/. J. Rudiur. Oncol. Bid fhjx 7: 134 I1348.
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-\pnl 1984. Volume IO. Number 4 32. Rhamy. R.K.. Wilson. S.K.. Caldwell. W.L.: Blops)-proicti tumor following definitive irradiation for resectable carclnoma of the prostate. J. C.rol. 107: 617-630. 1971. 33. Sambrook. D.K.: Split-course radiation therapy m malignant tumors. .4ttI J. Romr,cynol. 91: 37-45. 1964. 34. Scruggs. H.. El-Mahdi. A.. Marks. R.D.. Constable. W.C’ The results of split-course radiation therapv in cancer ot 121: the lung. .-irn. J. Roenr~~enol. Rudiwn Tlwr .<~rcL .\/d 754-760. 1974. 35. Sewell. R.A.. Braren. V.. Wilson. SK.. Rhamk. R.K.: Extended biopsy follow-up after full course radiation for resectable prostatic carcinoma. J. C’rol. 113: 37 I-373. 1975. 36. Scardino. P.T.. Carlton. Jr.. C.E.: Combined interstitial and external irradiation for prostatic cancer. In Principlet utd .\lunugcwwnr o/‘C’rokt,~ic~ Chnwr. 2nd edition. N. Javadpour ied.). Baltimore. Williams and Wilkins. 1983. pp. 392-408. 37. Skinner. D.G.: Current concepts concerning carcinoma ot the prostate. .Slrrcq. .-inn. 5: 393-406, 1973. 38. Taylor. W.J.. Richardson. R.G.. Hafermann. M.D.: Radiation therapy for localized prostate cancer. C’urrcrr 13: 1113-l 127. 1979.