- Email: [email protected]
Localized advanced carcinoma of the prostate: Radiation therapy versus hormonal therapy
hf.
J. R&bn
Oncology
Bid.
Phys.,
1976. Vol.
1. pp. 1043-1048.
Papamon
Press.
Printed
in the U.S.A.
??Original Contributions LOCALIZED ADVANCED CARCINOMA OF THE PROSTATE: RADIATION THERAPY VERSUS HORMONAL THERAPY BRIGITVAN DER WERF-MESSING,M.D.,? VERA SOUREKZIKOVA, M.D.S and DIRK I. BLONK,
M.D.§
Rotterdamsch Radio-Therapeutisch Instituut, Groene Hilledijk 301, Postbus 5201, Rotterdam, The Netherlands Since 1%7,% patients with prostatic eaneer T,,,N& have been treated by eastration and estrogens; 30 patients received additional radiotherppy, 30 patients were submitted to radietherapy only. Four year survival was best if radiotherapy only was tbe initial treatment
though hormone treatmmt might be necemaq during follow-up period. A low degree of dffkentiation of tbe growth worsens prognoh aign&antiy. kradWoncumplicat&nscanbe reduced to an acceptable percentage. Trcmsrectai prostatic~pepirrrtioniIlordertopssess tbepreaeWofane&rogene&ct-oritsdisappearrrnee andattbesametimerearerppeprpnceof hormonetreatmentandfu cancerc&3-m@btbeausefultooliopredictingfailureof indfcathg local radiotherapy as a second attempt of ‘kuatfve” treatment. Radiation therapy, Prostatic cancer, Estrogens, Hormone treatment.
of worthwhile life. Some relevant features of the four groups are analyzed.
INTRODUCTION
In about 1967 the Rotterdam Radiotherapy Institute joined the American Cooperative Study Group on treatment of prostatic cancer. ‘Patients with histologically proven prostatic cancer in stage C (III), (carcinoma infiltrating beyond the capsule of the prostate without demonstrable metastases) or according to the U.I.C.C.‘-classification 1974 category T,N,M, and T,N,M,, were randomized into either the treatment modality estrogens and castration or the combination of radiotherapy, estrogens and castration. Since 1971-with increasing confidence of urologists in radiotherapy-a series has been built up of carcinoma stage C (III) patients treated by radiotherapy only. A fourth group of 21 patients was referred to the Radiotherapy Institute after failure of hormone treatment, hoping that radiotherapy of the primary could substantially contribute to the chance of local control and to prolongation
METHODS AND MATERIALS
All patients were submitted to prostatic biopsy for histological typing of the growth. Each patient underwent bimanual rectal palpation, complete clinical examination, laboratory tests including serum acid phosphatase and serum prostatic acid phosphatase (during the last 2 years bone marrow serum acid phosphatase and serum globuline were assessed), radiological investigations (skeletal chest X-ray, intravenous survey, pyelography), bone marrow biopsy and transrectal prostatic thin needle cytology. During the last 2 years a skeletal scan and lymphography have been added as diagnostic tools. At regular intervals all patients were seen for follow-up examination; during the last 3 years, wherever possible, a transrectal cytology from
tconsultant Radiotherapist, Department of Radiotherapy, Rotterdam Radiotherapy Institute and Professor and Chairman of Clinical Radiotherapy, Erasmus University Rotterdam. SConsultant Radiotherapist, Department of
Radiotherapy, Rotterdam Radiotherapy Institute. Konsultant Cytologist, Rotterdam Radiotherapy Institute. Reprint requests to: Prof. B. van der WerfMessing, M.D.
1043
1044
Radiation Oncology 0 Biology 0 Physics
the prostate was repeated at 6 or 12 months’ intervals. Twenty-six patients were treated by castration followed by estrogen therapy (1 mg ethynyloestradiol daily by mouth). Thirty patients received the same treatment and additional radiotherapy (7000 rad in 7 weeks delivered by two opposing antero-posterior fields or by one anterior and two oblique posterior fields; the prostatic area with a wide margin of healthy tissue was included in the irradiation field). Thirty patients were admitted to radiotherapy only; 6500-7000 rad in 6.5-7 weeks; three treatment fields, covering the prostatic area with a wide margin of healthy tissue; in case of complaints a “split period” of 3-4 weeks was given after 4000 rad. Twenty one patients received palliative radiotherapy to the primary after failure of hormone treatment elsewhere. They were submitted to transrectal prostatic thin needle biopsy in order to assess the estrogen effect. The same investigation was performed in 27 patients of the U.S.A. Trial Group. RESULTS The uncorrected actuarial survival of patients belonging to the three curative treatment modalities is presented in Fig. 1, which shows that prognosis after 4 years is best after radiotherapy only. The small difference in survival between the two other treatment modalities (hormonal treatment only or irradia-
November-December
1976. Vol. 1. No. I1 and No. 12
tion + hormonal treatment) is of no statistical significance. Three patients belonging to the group “hormones and radiotherapy” stopped their hormone treatment and are still doing well. Figure 2 shows that the average age of patients treated with hormones only is significantly lower than the average age of the two other groups. The degree of differentiation of the growths in the three treatment modalities is presented in Table 1; the percentage of patients with a low degree of differentiation is significantly higher in the group treated with estrogens and radiotherapy as compared with the group treated by estrogens only. Figure 3 presents the actuarial survival of all patients belonging to the U.S.A.-trial group (hormonal treatment vs hormones + radiotherapy) according to the degree of differentiation of the growth: prognosis in case of medium degree or high degree of dBerentiation is significantly better than in case of low degree of differentiation. Figure 4 shows the influence of degree of differentiation on prognosis in case of radiotherapy combined with hormonal treatment: during the first year, patients with low
PROSTATIC CANCER
T3,4NxM0
(86)
AVERAGE AGE (WITH 95% CONFIDENCE LIMITS OF AVERAGE) ACCORDING TO TREATMENT 3”
09
PROSTATIC CANCER TJ,~N~M~(861 ACTUARIALSURVIVALACCORDING TOTREATMENT
b0 66
YEARS
b5 i b4
.ESTROGEN1301
63 62
i
bl-
Fig. 1. Up to 4 years after therapy, patients treated by X-ray only have a significantly better prognosis than those treated with estrogens or with irradiation and estrogens. The prognostic difference between the two latter groups is of no statistical significance. (W, Irradiation only; O--O, estrogen; u, Irradiation+estrogen).
TRIAL
60 TREATMENT NUMBER
1
ESTROGEN
IRRADIATION + ESTROGEN
IRRADIATIOh
26
30
30
Fig. 2. Patients treated with estrogens only were significantly younger than those treated with estrogens and radiotherapy.
advanced carcinoma of the prostate 0 B. VAN DER WERF-MESSING et al.
Localii
1045
Table 1. Prostatic Cancer T3cNx M, Degree of differentiation High + Medium No. %
Treatment Hormonal Radiation therapy + hormonal therapy Radiation therapy only
TRIAL PROSTATIC CANCER T14~X~D
Low No. %
23 19
88 63
3 11
12 37
26 30
100 loo
22
73
8
27
30
100
156)
PROSTATIC CANCER
T3,4NxMo
(30)
ACTUARIAL SURVIVAL AFTER EXTERNAL IRRADIATION ONLY ACCORDING TO DEGREE OF DlFFERENTlATlON
ACTUARIAL SURVIVAL ACiORDIiG TO DEGREE OF DIFFERENTIATION
IOG
‘::I?*+
Total No. %
----
~MD.HDIP2, '0.jf-‘--
60' i
--=.
4oj
'\,. --v- ----__----__* tlD,lo,
204 i
(ii
0
/
!
I
/
I
1
I
,
2
3
4
5
t
7
,
8
YEARS
Fig. 3. In the total trial group patients with a carcinoma of medium or high degree of differentiation (U, MD+HD) had a significantly better prognosis than those with a carcinoma of low degree of diff erentiation (O---O, LD).
Fig. 5. In the case of radiotherapy only, 100% of the patients with medium or high degree of differentiation (O--O, MD+HD) survived 4 years (O---O, LD; U-I, total).
TRIAL PROSTATIC CANCER T3,4~X~0 1301 ACTUARIAL SURWAL AFTERIRRADIATION+ESlROGEN ACCORDING TO DEGREE OF DIFFERENTIATION
1
?01 0:
I
c
/
I
I
1
3
h
5
b
I
1
7
8
YEARS
Fig. 4. In the group treated with estrogens and radiotherapy, patients with a carcinoma of medium or high degree of differentiation (U, MD+HD) had a better prognosis during the first 2 years. After that period, the differences shade off. (The small number of low degree of differentiation (O---O. LD) growths’ in the “hormonally-only” treated group did not permit assessing prognosis according to degree of differentiation).
degree of differentiation growths fare worse, but the difference is effaced within 3 years. Figure 5 shows prognosis after radiotherapy only, according to degree of differentiation: the
follow-up period is too short to allow conclusions. The causes of death are shown in Table 2. The complications following radiotherapy in the two treatment modalities radiotherapy + hormones and radiotherapy only are presented in Table 3. Of 48 patients treated with hormones with or without radiotherapy transrectal prostatic cytology could be performed in order to assess the estrogen effect (squamous cell metaplasia of the prostate epithelium) and the presence of tumor cells: those who were clinically well showed either a distinct estrogen effect” or they had also been irradiated to the primary.3 In 6 instances the estrogen effect was not assessable in the slide. All patients with progressive disease had no demonstrable estrogen effect, three of whom with a local recurrence without evidence of distant metastases could subsequently be treated successfully by irradiation (Table 4).
1046
Radiation Oncology 0 Biology 0 Physics
Table
2. Prostatic
cancer
November-December
T,,,NxMO causes treatment
of death
to type of
Irradiation only (30)
None
1
None
3
6
None
None None 5
21 1t 5
None None None
IO/26
15/30
I/30
2(;la$er)
Second cancer Suicide Radiation damage Cardiovascular accident Total tBefore
according
Irradiation + hormones (30)
Hormonal (26) Local recurrence + metastases Metastasis without local recurrence
1976, Vol. I, No. II and No. 12
1970.
Table 3. Prostatic cancer T,,N,M,
Irradiation complications
treated by irradiation (2 estrogen) (60)
7000 rad/7 weeks (+ estrogen) (30)
Blood in stools Chronic proctitis Urethra stricture Chronic cystitis Radiation necrosis (plastic surgery) Perineal abscess Edema of penis Total
650&7000 rad/6-7 weeks with or without split (no estrogen) (30)
1 1 1 1 1
None
1 1
None None
7130 (23%)
3130 10%
2t
None 2t
None
t 1 same patient. Table 4. Estrogen effect in cytology of prostatic cancer in relation to clinical findings and degree of differentiation (48); Trial irradiation + estrogens (13); Trial estrogens only (14); Failures after hormonal treatment elsewhere (21)
Estrogen effect HD+MD LD
Estrogen effect + HD+MD LD ClinicalIy welI Clinically progressive
16 None
2 None
3” 12.
“3 from trial irradiation + hormone. .2 from trial hormone only; 3 received curative
DISCUSSION Survival rates after hormone treatment combined with radiotherapy and after hormone treatment only are comparable, however the group of combined treatment modality
None 9
Estrogen effect not assessable HD+MD LD 2 3
1 None
local irradiation.
consisted of significantly more patients with a growth of low degree of differentiation, a feature which is related to a poor prognosis.‘*‘.’ The group treated by irradiation only had the best prognosis up to 4 years. However, 5
Localized advanced carcinoma of the prostate 0 B. VAN DERWERF-MESSINGet 01.
patients received estrogens during the follow-up period, as metastases or local discomfort developed! Perhaps local radiotherapy only postpones the necessity of hormone treatment, thus prolonging the total period of effective treatment. Patients treated with hormones and irradiation suffered both from the sequelae of hormonal treatment (cardiovascular accidents) and from irradiation sequela (one radionecrosis with infection leading to death; two suicides, probably the result of hormone treatment-related depression, enhanced by the knowledge of the diagnosis “cancer”, when radiotherapy was given). The group treated with radiotherapy only after 1971 was thoroughly supported by a psychologist, moreover radiation complications could be
1047
reduced due to acquired experience during the past years Disappearance of the estrogen effect in patients treated with hormones only might predict imminent resistance to hormone treatment. The finding that absence of estrogen effect is more frequent in case of low degree of differentiation (9 out of 11) than in case of high or medium degree of differentiation (12 out of 3 1) is in agreement with the fact that a lower degree of differentiation is related to a poor prognosis. Careful examination for reappearance of local tumor gives the possibility to install curative radiotherapy in case no distant metastases have developed. The results of R.R.T.I.-treatment are comparable with those published in literature (Table 5).
Table 5. Prostatic cancer T,,N,M, survival in literature % Survival 10yr 5 yr
Author
Treatment
No.
Bayard et al. (1974)*/ Veterans administration (1%7)9 Stage C
Placebo Estrogen Orchidectomy + Placebo Orchidectomy + Estrogen Irradiation well differentiated poorly differentiated Irradiation well differentiated poorly differentiated Irradiation
248 251 256
55 55 50
237
45
53 70 20 180 60 30 185
50
40
29
60
36
45
147
60
131 265 73
68 55 11
Perez et al. (1974)’ Stage C Cantril et al. (1974)’ Stage C Bagshaw and Ray (1974)’ Stage C Edsmyr et al. (1974)4 Stage C
Flocks (1972)O Stage C Esposti (1971)’ All stages
Irradiation + hormonal treatment poorly differentiated irradiation after failure of hormones Radical surgery + interstitial irradiation after failure of hormones Hormones: high differentiation medium differentiation low differentiation
35 18 106 71
45
18-25
30
REFERENCES 1. Bagshaw, M.A., Ray, G.R.: Carcinoma of the prostate; the place of radiotherapy. In Radiology ; Proc. 13th Int. Cong. Radiol., Vol. 2,
Madrid,
15-20 October
1973, ed. by Gomez Excerpta
Lopez, J. Bonmati, J. Amsterdam, Medica,
1974, pp. 67-72.
1u4x
Radiation Oncology 0 Biology 0 Physics
2. Bayard, S., Greenberg, R., Showalter, D., et al.: Comparison of treatments for prostatic cancer using an exponential-type life model relating survival to concomitant information. Cancer Chemother. Rep. 58: 845-859, 1974. 3. Cantril, S.T., Vaeth, J.M., Green, J.P., et al.: Radiation therapy for localized carcinoma of the prostate; correlation with histopathological grading. Front. Radiat. Ther. Oncol. 9: 274-294, 1974. 4. Edsmyr, F., Esposti, P.L., Littbrand, B., Almgard, L.E.: Carcinoma of the prostate; the place of radiotherapy. In Radiology; Proc. 13 th Ink Cong. Radiol., vol. 2, Madrid, 15-20 October 1973, ed. by Gomez Lopez, J. Bonmati, J. Amsterdam, Excerpta Medica, 1974, pp. 67-72. 5. Esposti, P.L.: Cytologic malignancy grading of prognostic carcinoma by transrectal aspiration biopsy; a five year follow up study of 469
November-December
6.
7.
8.
9.
1976. Vol. 1. No. 11 and No. 12
hormone-treated patients. &and. J. Ural. Nephrol. 5: 199-209, 1971. Flocks, R.H.: The treatment of stage C prostatic cancer with special reference to combined surgical and radiation therapy. Trans. Am. Assn. Genitourin. Surg. 64: 5840, 1972. Perez, C.A., Ackerman, L.V., Silber, I. et al.: Radiation therapy in the treatment of localized carcinoma of the prostate. Preliminary report using 22 MeV-photons. Cancer 34: 1059-1068, 1974. Union Internationale Contre le Cancer: TNM Classification of Malignant Tumors, Geneva, UICC, 2nd Edn, 1974, pp. 8&87. Veterans Administration Cooperative Urological Research Group: Treatment and survival of patients with cancer of the prostate. Surg. Gynecol. Obstet. 124: 1011-1017, 1967.
J. R&bn
Oncology
Bid.
Phys.,
1976. Vol.
1. pp. 1043-1048.
Papamon
Press.
Printed
in the U.S.A.
??Original Contributions LOCALIZED ADVANCED CARCINOMA OF THE PROSTATE: RADIATION THERAPY VERSUS HORMONAL THERAPY BRIGITVAN DER WERF-MESSING,M.D.,? VERA SOUREKZIKOVA, M.D.S and DIRK I. BLONK,
M.D.§
Rotterdamsch Radio-Therapeutisch Instituut, Groene Hilledijk 301, Postbus 5201, Rotterdam, The Netherlands Since 1%7,% patients with prostatic eaneer T,,,N& have been treated by eastration and estrogens; 30 patients received additional radiotherppy, 30 patients were submitted to radietherapy only. Four year survival was best if radiotherapy only was tbe initial treatment
though hormone treatmmt might be necemaq during follow-up period. A low degree of dffkentiation of tbe growth worsens prognoh aign&antiy. kradWoncumplicat&nscanbe reduced to an acceptable percentage. Trcmsrectai prostatic~pepirrrtioniIlordertopssess tbepreaeWofane&rogene&ct-oritsdisappearrrnee andattbesametimerearerppeprpnceof hormonetreatmentandfu cancerc&3-m@btbeausefultooliopredictingfailureof indfcathg local radiotherapy as a second attempt of ‘kuatfve” treatment. Radiation therapy, Prostatic cancer, Estrogens, Hormone treatment.
of worthwhile life. Some relevant features of the four groups are analyzed.
INTRODUCTION
In about 1967 the Rotterdam Radiotherapy Institute joined the American Cooperative Study Group on treatment of prostatic cancer. ‘Patients with histologically proven prostatic cancer in stage C (III), (carcinoma infiltrating beyond the capsule of the prostate without demonstrable metastases) or according to the U.I.C.C.‘-classification 1974 category T,N,M, and T,N,M,, were randomized into either the treatment modality estrogens and castration or the combination of radiotherapy, estrogens and castration. Since 1971-with increasing confidence of urologists in radiotherapy-a series has been built up of carcinoma stage C (III) patients treated by radiotherapy only. A fourth group of 21 patients was referred to the Radiotherapy Institute after failure of hormone treatment, hoping that radiotherapy of the primary could substantially contribute to the chance of local control and to prolongation
METHODS AND MATERIALS
All patients were submitted to prostatic biopsy for histological typing of the growth. Each patient underwent bimanual rectal palpation, complete clinical examination, laboratory tests including serum acid phosphatase and serum prostatic acid phosphatase (during the last 2 years bone marrow serum acid phosphatase and serum globuline were assessed), radiological investigations (skeletal chest X-ray, intravenous survey, pyelography), bone marrow biopsy and transrectal prostatic thin needle cytology. During the last 2 years a skeletal scan and lymphography have been added as diagnostic tools. At regular intervals all patients were seen for follow-up examination; during the last 3 years, wherever possible, a transrectal cytology from
tconsultant Radiotherapist, Department of Radiotherapy, Rotterdam Radiotherapy Institute and Professor and Chairman of Clinical Radiotherapy, Erasmus University Rotterdam. SConsultant Radiotherapist, Department of
Radiotherapy, Rotterdam Radiotherapy Institute. Konsultant Cytologist, Rotterdam Radiotherapy Institute. Reprint requests to: Prof. B. van der WerfMessing, M.D.
1043
1044
Radiation Oncology 0 Biology 0 Physics
the prostate was repeated at 6 or 12 months’ intervals. Twenty-six patients were treated by castration followed by estrogen therapy (1 mg ethynyloestradiol daily by mouth). Thirty patients received the same treatment and additional radiotherapy (7000 rad in 7 weeks delivered by two opposing antero-posterior fields or by one anterior and two oblique posterior fields; the prostatic area with a wide margin of healthy tissue was included in the irradiation field). Thirty patients were admitted to radiotherapy only; 6500-7000 rad in 6.5-7 weeks; three treatment fields, covering the prostatic area with a wide margin of healthy tissue; in case of complaints a “split period” of 3-4 weeks was given after 4000 rad. Twenty one patients received palliative radiotherapy to the primary after failure of hormone treatment elsewhere. They were submitted to transrectal prostatic thin needle biopsy in order to assess the estrogen effect. The same investigation was performed in 27 patients of the U.S.A. Trial Group. RESULTS The uncorrected actuarial survival of patients belonging to the three curative treatment modalities is presented in Fig. 1, which shows that prognosis after 4 years is best after radiotherapy only. The small difference in survival between the two other treatment modalities (hormonal treatment only or irradia-
November-December
1976. Vol. 1. No. I1 and No. 12
tion + hormonal treatment) is of no statistical significance. Three patients belonging to the group “hormones and radiotherapy” stopped their hormone treatment and are still doing well. Figure 2 shows that the average age of patients treated with hormones only is significantly lower than the average age of the two other groups. The degree of differentiation of the growths in the three treatment modalities is presented in Table 1; the percentage of patients with a low degree of differentiation is significantly higher in the group treated with estrogens and radiotherapy as compared with the group treated by estrogens only. Figure 3 presents the actuarial survival of all patients belonging to the U.S.A.-trial group (hormonal treatment vs hormones + radiotherapy) according to the degree of differentiation of the growth: prognosis in case of medium degree or high degree of dBerentiation is significantly better than in case of low degree of differentiation. Figure 4 shows the influence of degree of differentiation on prognosis in case of radiotherapy combined with hormonal treatment: during the first year, patients with low
PROSTATIC CANCER
T3,4NxM0
(86)
AVERAGE AGE (WITH 95% CONFIDENCE LIMITS OF AVERAGE) ACCORDING TO TREATMENT 3”
09
PROSTATIC CANCER TJ,~N~M~(861 ACTUARIALSURVIVALACCORDING TOTREATMENT
b0 66
YEARS
b5 i b4
.ESTROGEN1301
63 62
i
bl-
Fig. 1. Up to 4 years after therapy, patients treated by X-ray only have a significantly better prognosis than those treated with estrogens or with irradiation and estrogens. The prognostic difference between the two latter groups is of no statistical significance. (W, Irradiation only; O--O, estrogen; u, Irradiation+estrogen).
TRIAL
60 TREATMENT NUMBER
1
ESTROGEN
IRRADIATION + ESTROGEN
IRRADIATIOh
26
30
30
Fig. 2. Patients treated with estrogens only were significantly younger than those treated with estrogens and radiotherapy.
advanced carcinoma of the prostate 0 B. VAN DER WERF-MESSING et al.
Localii
1045
Table 1. Prostatic Cancer T3cNx M, Degree of differentiation High + Medium No. %
Treatment Hormonal Radiation therapy + hormonal therapy Radiation therapy only
TRIAL PROSTATIC CANCER T14~X~D
Low No. %
23 19
88 63
3 11
12 37
26 30
100 loo
22
73
8
27
30
100
156)
PROSTATIC CANCER
T3,4NxMo
(30)
ACTUARIAL SURVIVAL AFTER EXTERNAL IRRADIATION ONLY ACCORDING TO DEGREE OF DlFFERENTlATlON
ACTUARIAL SURVIVAL ACiORDIiG TO DEGREE OF DIFFERENTIATION
IOG
‘::I?*+
Total No. %
----
~MD.HDIP2, '0.jf-‘--
60' i
--=.
4oj
'\,. --v- ----__----__* tlD,lo,
204 i
(ii
0
/
!
I
/
I
1
I
,
2
3
4
5
t
7
,
8
YEARS
Fig. 3. In the total trial group patients with a carcinoma of medium or high degree of differentiation (U, MD+HD) had a significantly better prognosis than those with a carcinoma of low degree of diff erentiation (O---O, LD).
Fig. 5. In the case of radiotherapy only, 100% of the patients with medium or high degree of differentiation (O--O, MD+HD) survived 4 years (O---O, LD; U-I, total).
TRIAL PROSTATIC CANCER T3,4~X~0 1301 ACTUARIAL SURWAL AFTERIRRADIATION+ESlROGEN ACCORDING TO DEGREE OF DIFFERENTIATION
1
?01 0:
I
c
/
I
I
1
3
h
5
b
I
1
7
8
YEARS
Fig. 4. In the group treated with estrogens and radiotherapy, patients with a carcinoma of medium or high degree of differentiation (U, MD+HD) had a better prognosis during the first 2 years. After that period, the differences shade off. (The small number of low degree of differentiation (O---O. LD) growths’ in the “hormonally-only” treated group did not permit assessing prognosis according to degree of differentiation).
degree of differentiation growths fare worse, but the difference is effaced within 3 years. Figure 5 shows prognosis after radiotherapy only, according to degree of differentiation: the
follow-up period is too short to allow conclusions. The causes of death are shown in Table 2. The complications following radiotherapy in the two treatment modalities radiotherapy + hormones and radiotherapy only are presented in Table 3. Of 48 patients treated with hormones with or without radiotherapy transrectal prostatic cytology could be performed in order to assess the estrogen effect (squamous cell metaplasia of the prostate epithelium) and the presence of tumor cells: those who were clinically well showed either a distinct estrogen effect” or they had also been irradiated to the primary.3 In 6 instances the estrogen effect was not assessable in the slide. All patients with progressive disease had no demonstrable estrogen effect, three of whom with a local recurrence without evidence of distant metastases could subsequently be treated successfully by irradiation (Table 4).
1046
Radiation Oncology 0 Biology 0 Physics
Table
2. Prostatic
cancer
November-December
T,,,NxMO causes treatment
of death
to type of
Irradiation only (30)
None
1
None
3
6
None
None None 5
21 1t 5
None None None
IO/26
15/30
I/30
2(;la$er)
Second cancer Suicide Radiation damage Cardiovascular accident Total tBefore
according
Irradiation + hormones (30)
Hormonal (26) Local recurrence + metastases Metastasis without local recurrence
1976, Vol. I, No. II and No. 12
1970.
Table 3. Prostatic cancer T,,N,M,
Irradiation complications
treated by irradiation (2 estrogen) (60)
7000 rad/7 weeks (+ estrogen) (30)
Blood in stools Chronic proctitis Urethra stricture Chronic cystitis Radiation necrosis (plastic surgery) Perineal abscess Edema of penis Total
650&7000 rad/6-7 weeks with or without split (no estrogen) (30)
1 1 1 1 1
None
1 1
None None
7130 (23%)
3130 10%
2t
None 2t
None
t 1 same patient. Table 4. Estrogen effect in cytology of prostatic cancer in relation to clinical findings and degree of differentiation (48); Trial irradiation + estrogens (13); Trial estrogens only (14); Failures after hormonal treatment elsewhere (21)
Estrogen effect HD+MD LD
Estrogen effect + HD+MD LD ClinicalIy welI Clinically progressive
16 None
2 None
3” 12.
“3 from trial irradiation + hormone. .2 from trial hormone only; 3 received curative
DISCUSSION Survival rates after hormone treatment combined with radiotherapy and after hormone treatment only are comparable, however the group of combined treatment modality
None 9
Estrogen effect not assessable HD+MD LD 2 3
1 None
local irradiation.
consisted of significantly more patients with a growth of low degree of differentiation, a feature which is related to a poor prognosis.‘*‘.’ The group treated by irradiation only had the best prognosis up to 4 years. However, 5
Localized advanced carcinoma of the prostate 0 B. VAN DERWERF-MESSINGet 01.
patients received estrogens during the follow-up period, as metastases or local discomfort developed! Perhaps local radiotherapy only postpones the necessity of hormone treatment, thus prolonging the total period of effective treatment. Patients treated with hormones and irradiation suffered both from the sequelae of hormonal treatment (cardiovascular accidents) and from irradiation sequela (one radionecrosis with infection leading to death; two suicides, probably the result of hormone treatment-related depression, enhanced by the knowledge of the diagnosis “cancer”, when radiotherapy was given). The group treated with radiotherapy only after 1971 was thoroughly supported by a psychologist, moreover radiation complications could be
1047
reduced due to acquired experience during the past years Disappearance of the estrogen effect in patients treated with hormones only might predict imminent resistance to hormone treatment. The finding that absence of estrogen effect is more frequent in case of low degree of differentiation (9 out of 11) than in case of high or medium degree of differentiation (12 out of 3 1) is in agreement with the fact that a lower degree of differentiation is related to a poor prognosis. Careful examination for reappearance of local tumor gives the possibility to install curative radiotherapy in case no distant metastases have developed. The results of R.R.T.I.-treatment are comparable with those published in literature (Table 5).
Table 5. Prostatic cancer T,,N,M, survival in literature % Survival 10yr 5 yr
Author
Treatment
No.
Bayard et al. (1974)*/ Veterans administration (1%7)9 Stage C
Placebo Estrogen Orchidectomy + Placebo Orchidectomy + Estrogen Irradiation well differentiated poorly differentiated Irradiation well differentiated poorly differentiated Irradiation
248 251 256
55 55 50
237
45
53 70 20 180 60 30 185
50
40
29
60
36
45
147
60
131 265 73
68 55 11
Perez et al. (1974)’ Stage C Cantril et al. (1974)’ Stage C Bagshaw and Ray (1974)’ Stage C Edsmyr et al. (1974)4 Stage C
Flocks (1972)O Stage C Esposti (1971)’ All stages
Irradiation + hormonal treatment poorly differentiated irradiation after failure of hormones Radical surgery + interstitial irradiation after failure of hormones Hormones: high differentiation medium differentiation low differentiation
35 18 106 71
45
18-25
30
REFERENCES 1. Bagshaw, M.A., Ray, G.R.: Carcinoma of the prostate; the place of radiotherapy. In Radiology ; Proc. 13th Int. Cong. Radiol., Vol. 2,
Madrid,
15-20 October
1973, ed. by Gomez Excerpta
Lopez, J. Bonmati, J. Amsterdam, Medica,
1974, pp. 67-72.
1u4x
Radiation Oncology 0 Biology 0 Physics
2. Bayard, S., Greenberg, R., Showalter, D., et al.: Comparison of treatments for prostatic cancer using an exponential-type life model relating survival to concomitant information. Cancer Chemother. Rep. 58: 845-859, 1974. 3. Cantril, S.T., Vaeth, J.M., Green, J.P., et al.: Radiation therapy for localized carcinoma of the prostate; correlation with histopathological grading. Front. Radiat. Ther. Oncol. 9: 274-294, 1974. 4. Edsmyr, F., Esposti, P.L., Littbrand, B., Almgard, L.E.: Carcinoma of the prostate; the place of radiotherapy. In Radiology; Proc. 13 th Ink Cong. Radiol., vol. 2, Madrid, 15-20 October 1973, ed. by Gomez Lopez, J. Bonmati, J. Amsterdam, Excerpta Medica, 1974, pp. 67-72. 5. Esposti, P.L.: Cytologic malignancy grading of prognostic carcinoma by transrectal aspiration biopsy; a five year follow up study of 469
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