Elective pelvic irradiation in stage A2, B carcinoma of the prostate: analysis of RTOG 77-06

0360s3016/88 $3.00 + .W Copyright Q 1988 Pergamon Press plc

Inr. J. Radiation Onco/ogyBio/. Phys..

Vol. 15. pp. 1307-1316 Printed in the U.S.A. All rights reserved.

??Original Contribution

ELECTIVE

PELVIC IRRADIATION IN STAGE AZ, B CARCINOMA PROSTATE: ANALYSIS OF RTOG 77-06

OF THE

S. 0. ASBELL, M.D.,’ J. M. KRALL, PH.D.,~ M. V. PILEPICH, M.D.,3 H. BAERWALD, M.D.,4 W. T. SAUSE, M.D.,5 G. E. HANKS, M.D.6 AND C. A. PEREZ, M.D.3 ‘Albert Einstein Medical Center, Philadelphia, PA; ‘RTOG Headquarters, Philadelphia, PA; 3Washington University, St. Louis, MO; 4Roswell Park Memorial Institute, Buffalo, NY; 5LDS Hospital, Salt Lake City, UT; and ‘Sutter Community Hospitals, Sacramento, CA From 1978 to 1983 the Radiation Therapy Oncology Group conducted a study to evaluate the role of elective pelvic lymph node irradiation in carcinoma of the prostate. Eligible patients were those with clinical Stage A2 (occult disease with more than 3 positive chips and poorly differentiated tumor) and Stage B without clinical (lymphangiogram) or biopsy evidence of lymph node involvement. The patients were randomized to receive 6.5 weeks of either prostatic bed irradiation only 6500 cGy at 180-200 cGy per treatment or pelvic node irradiation to 4500 cGy with a boost of 2000 cGy to the prostatic bed bringing the total dose to 6500 cGy. As of February, 1988, the median follow up has been 7 years and there were 445 analyzable cases who were evaluated for local control, incidence of distant metastases, ned (no evidence of disease) survival and survival. The results of the study revealed no statistically significant benefit of elective pelvic irradiation.

The recent improvement in radiographic and surgical technology has permitted a greater accuracy in determining tumor volume and extent and therefore staging.‘6322 Thus, with more accurate staging, more accurate assessment of the ability of radiation to sterilize the tumor bed can be made. Historically, except for Bagshaw,’ Paulson24 and a few others, the value of external radiotherapy was based on treatments given to clinically staged patients without knowledge of the status of pelvic lymph nodes from lymphangiograms (LAG), CAT scans or surgical investigation. 2oIf no assessment was made of lymph nodes, occult involvement of 14-28% would be anticipated in Stage A2 or B with as high as 50% pelvic nodal involvement in Stage B2 and a maximum of 82% in high Theoretically, if occult disease is degrade tumors. 6*‘0312 fined as that which is not found at LAG, then prophylactic treatment of lymph nodal areas of the pelvis will demonstrate radiation therapy’s ability to sterilize subclinical nodal involvement as well as truly limited prostatic cancer. A Phase III study, RTOG 77-06, was designed to determine the value of elective pelvic lymph nodal irradiation in the management of tumor clinically limited to the

INTRODUCIION de1 Regato,’ Bagshaw,’ and Buhraja’ were among the

first physicians of the radiotherapy community to introduce the safe and seemingly effective use of megavoltage external beam radiotherapy in the treatment of prostate cancer. The treatment then described was to a small volume, prostate and immediate paraprostatic tissue (the latter never fully described as to content). As the pathophysiology of progression of prostatic cancer and its metastatic pattern became clear, the staging systems changed to reflect an understanding of the disease process. l6 In an attempt to increase the cure rate, Bagshaw suggested the addition of radiation to the pelvic nodes as well as the previously described smaller volume of prostate and paraprostatic tissue.4 He began a study comparing local prostatic versus pelvic and prostatic irradiation. Support of this more aggressive therapy in another large series was published by McGowan in 198 1.” There has been continued controversy in the literature as to the need for elective pelvic lymph nodal irradiation in the control of what may appear to be tumor limited to the prostate.

Reprint requests to: S. 0. ASBELL, M.D., Albert Einstein Medical Center, N-Division, Department of Radiation Therapy, Old York & Tabor Roads, Philadelphia, PA 19141. Accepted for publication 29 June 1988.

Presented at the 28th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, November, 1986, Data updated February, 1988. Supported by grants CA22557 (Albert Einstein Medical Center), CA321 15 (RTOG Statistical), CA2166 1 (RTOG Headquarters), CA 12261 (Washington University), CA36766 (Sutter) and CA 17906 (LDS Hospital). 1307

I. J. Radiation Oncology 0 Biology 0 Physics

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Table 1. Institutional

December 1988, Volume 15, Number 6

case accrual C1977- 1983) with affiliates included

University of Rochester Washington University, St. Louis LDS Hospital Sutter Community Hospitals Methodist Medical Center of Illinois Albert Einstein Medical Center, N. Division Marshfield Clinic Loyola University Medical Center University of Washington Hospital Illinois Cancer Council Downstate Medical Center Indiana University Hahnemann Medical College and Hospital University of Pennsylvania University of California, San Francisco Mercy Hospital, Altoona Thomas Jefferson University Hospital

University of Puerto Rico Boston University Medical Center Medical College of Wisconsin University of Alberta Allegheny General Hospital Johns Hopkins University Rockford Memorial Hospital Columbia-Presbyterian Medical Center Hackensack Medical Center Maine Medical Center Northwest Washington CCOP, Tacoma Christ Hospital Ellis Fischel State Cancer Hospital Medical University of South Carolina St. Francis Hospital, Illinois St. Vincent’s Hospital CCOP, New York University of Texas

Table 2. RTOG 7706 prostate protocol: Analysis of treatment arms for balance of pretreatment Prostate only (N = 225)

Gleason

Stage

Race

Acid phosphatase (prostatic or total) TUR Tumor size

No. cases

%

111 88 24

(50)

114 85 20

(52) (39) (9)

No

35 144 39

(16)

(19)

No

;‘r:;

40 130 44

47 178

(21) (79)

37 183

(17) (83)

213 11

(95) (5)

204 14

White Black Other Not elevated Elevated Unknown ( 19)

205 17 3 189 29

(91) (8) (1)

203 15 2

(87) (13)

No Yes 5 1.OOcm2 1.Ol-9.00 cm2 9.01-25.00 cm2 25.01+ cm2 Unknown ( 147)

115 110

(51) (49)

27 104 19 4

(17) (68) (12) (3)

1 2 3-4 Unknown 2-5 6-7 8-10 Unknown

(3)

A2

No Yes Unknown

Mean age Method of nodal evaluation

&;

(13) No No

(3) No

181 27

(92) (7) (1) (87) (13)

111 109 23

(50) (50) (16)

No

99 20 2

:::; (1)

<60 61-70 71+ Laparotomy No laparotomy (lymphangiogram)

38 111 81 67.7 years

(15) (49) (36)

36 105 79 67.6 years

No

No

No

5.9 cm2

5.4 cm2

Mean size Age

Statistically significant difference?

%

B Prior hormones

Prostate + pelvic (N = 220)

No. cases

Factor Grade

factors

(15) (48) (36)

No

No

59

(25)

58

(26)

166

(74)

162

(74)

No

1309

Elective pelvic irradiation 0 S. 0. ASBELL etal. 100

75

DEAD/TOTAL (62/225) (59/220)

_ PROSTATEONLY ________ PROSTATE+ PELVlC

pns

225 D q 220 0

137 131

196 190 1

2

3

4

25

5

6

PROSTATEONLY PROSTATE+ PELW 6

7

9

10

YEARS FROM ONSTUDY

Fig. 1. RTOG 7706 prostate study, survival by treatment arm.

(Stage AZ, B), that is, without evidence of nodal involvement by lymphangiogram or at surgical staging. These data form the basis of this report.

prostate

METHODS AND MATERIALS Patients with clinical Stage A2 or B prostatic tumor according to Jewitt’s modification or Whitmore’s staging, l6 that is, without either radiographic or surgical evidence of lymph node involvement were studied. Patients with

100

previous radiation therapy or potentially curative surgery, and those with previous or concurrent cancers other than skin cancer were not eligible. The pretreatment work-up included history, physical examination, SMA 12, serum acid phosphatase, chest X ray, bone scan, intravenous pyelogram, and lymphangiogram or surgical staging of lymph nodes. There were 484 patients entered in RTOG 77-06 from March 1978 to August 1983 (See Table 1 for participating institutions) providing minimum follow-up of 4.5 years and median follow-up of 7 years.

---------________ -___ -‘---_______?~:_ ----------

----___

08% L

I-

;

i!

;

i

-.

--.________-__---

\

RECURRENCE/TOTAL (32/225) (25/220)

PROSTATEONLY ________ PROSTATE+ PELVlC

0

--__

;

6

;

;r

9

YEARS FROM ONSTUDY

Fig. 2. RTOG 7706 prostate study, local/regional

recurrence by treatment arm.

-

10

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December 1988, Volume 15, Number 6

100

75

50

PROSTATE ONLY __ _ _ _ _ _ _ PROSTATE + PELVIC

MEMSTASES/TOTAL (43/225) (47/220)

25

p=“*

I

0

0

1

2

3

4 MARS

5 6 FROM ONSTUDY

7

0

9

10

Fig. 3. RTOG 7706 prostate study, distant metastases by treatment arm.

For the purposes of this analysis, there were 3 1 patients excluded as ineligible, cancelled or not evaluable. Eight patients were excluded as they were non-randomized cancer control patients. This left 445 analyzable patients. There were 22 patients with major unacceptable protocol deviations and 10 who were not completely evaluable by the study chairman. Thus there were 413 patients treated per protocol for analysis. Stratification criteria included histological grade, absence or presence of hormonal manipulation (administration of estrogen or orchiectomy) and method of node

evaluation (lymphangiogram or laparotomy). The patients were randomized to either receive only prostate bed irradiation or pelvic irradiation and a boost to the prostatic bed. The treatment arms were checked for balance in pretreatment factors of cell differentiation, that is, grade, Gleason scores” (these were reviewed by a single pathologist, Dr. Roger Terry) stage, prior hormonal therapy, race, acid phosphatase, if diagnosis by TUR, tumor size, age and method of nodal staging. All were balanced, that is, without statistically significant difference (Table 2).

e ii

50-

5 * PROSTATE ONLY _ _ _ __ __ _ PROSTATE + PELVlC

FAILURE/TOTAL (93/225) (91/220) p=n*

25 -

0

;

i

;

i i 6 YEARS FROM ONStUDY

;

0

Fig. 4. RTOG 7706 prostate study, NED survival by treatment arm.

9

10

1311

Elective pelvic irradiation 0 S. 0. ASBELL etal.

Radiotherapy guidelines The prostatic and paraprostatic target volume included the gland with adequate margins encompassing at least a portion of the seminal vesicles. This volume was to receive a minimum of 6500 cGy in 6 1 to 7 weeks. The maximum dose was not to exceed 7200 cGy. Any technique delivering this dose to the prescribed target volume was acceptable although coplanar opposed antero-posterior fields were not to be permitted for the full course of treatment with megavoltage equipment. However, it was accepted in the early part of the study, in a few patients, for part of the course of therapy, provided rectal and bladder doses of 6500 cGy were not exceeded. The pelvic lymphatic target volume was defined as 1 cm beyond the bony pelvic wall on each side, superiorly at the interspace of the fifth lumbar and the first sacral vertebrae, inferiorly at the bottom of the ischial tuberosities. Rotation, four field box techniques or opposed anterior and posterior fields for energies greater than 10 MeV were permitted. The pelvic nodal target volume received was 4500-5000 cGy in 44-5 f weeks. The daily dose was between 180-200 cGy. Some patients were treated with a sandwich technique, that is, part of the pelvic nodes were treated with an interruption of 2 weeks while the prostate bed was treated before completion of the prescribed pelvic dose. This was designated as an acceptable

variation although the pelvic nodes then received 4500 cGy in 61 weeks. RESULTS Whether the 4 13 patients treated per protocol or the 445 evaluable patients were studied, the results were the same for local control, time to distant metastases, survival or disease free survival. Analysis of curves generated by the Kaplan-Meier method” with comparison of treatment arms by Mantel-Haenszel test” revealed no statistically significant difference between treatment arms (Figs. l-4). The crude 5-year survival was 80% for the prostate plus pelvic arm and 78% for the prostate only arm (Fig. 1). For the purpose of this analysis, local or regional failure is defined as either progression of measurable disease at any time or histological verification of tumor 2 years after completing radiotherapy. Progression of the primary tumor is defined as at least a 25% increase in the palpable tumor mass dimensions, quantified by the product of tumor dimensions. Persistence of tumor was defined as tumor which never completely disappeared at the end of treatment and is carried as treatment failure. Actuarial 5-year survival with local control was 88% in the prostate arm and 90% in the pelvic nodes with pros-

Table 3. RTOG 7706 prostate protocol: Analysis of treatment arms pretreatment Factor All patients Grade

: 3-4 2-5 6-7 8-10

Gleason score

Stage

A2

B No prior hormones White

Race Normal/low acid phosphatase High acid phosphatase No TUR TUR Tumor size

5100 cm’ 1.01-9.00 cm2 9.01 cm2+

Age

Laparotomy Lymphangiogram

160 years 6 l-70 years 71+ years only

* Mantel-Haenszel test. t Too few patients for reliable estimate.

factors for survival

Prostate only 5 yr rate %

Prostate + pelvic 5 yr rate %

Statistically significant difference*

78

80

No

82 77 70 88 80 67 86 76

82 83 58 81 86 59 86 78

No No No No No No No No

80

81

No

78

79

No

77

79

No

82 78 79

85 81 77

No No No

74 78 t 78 81 75 83 77

86 83

No No

t

No

79 83 76 91 76

No No No No No

p-value

p=.lO

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tate boost (Fig. 2). As of February 1988 there have been 32 local/regional failures in the group treated to the prostate only and 25 in the pelvic and prostate boost arm. Of those treated to the prostate alone 84% were free of distant metastases while 83% were disease-free for those treated to the lymph nodes and prostate (Fig. 3). Survival with no evidence of disease (NED) was found to be 67% at 5 years for those treated to only the prostate while 64% for those treated to the nodes as well (Fig. 4). The 445 analyzable patients were examined as subpopulations by the pretreatment factors of tumor grade, Gleason score, stage, hormonal therapy, race, acid phosphatase; if diagnosis by TUR, tumor size, age and method of nodal evaluation. In this way any treatment differences could be identified in either treatment arm. There was no statistically significant difference found in either treatment arm using a value ofp = .05 (Tables 36), with the exception of Stage AZ for distant metastases and NED survival. Since analysis of the morbidity of prostatic and pelvic radiation for this population of patients has already been the subject of several publications26,27,28 further details will not be presented. Note that 89% maintained the ability to have an erection on at least one follow-up visit, and 47% in their last follow-up.

December 1988, Volume 15, Number 6

DISCUSSION

AND CONCLUSION

Can we expect to control prostate cancer if there has already been spread to lymph nodes? “Since it is possible to relieve lymphatic obstruction with X ray therapy even late in the disease, the disease is radioresponsive. In addition, lymphangiogram after X ray therapy showed regression of affected lymph nodes. Whether complete sterilization occurs is difficult to ascertain as exploratory laparotomy is not routinely done post X ray therapy.“’ Bagshaw has shown that patients with involved lymph nodes develop subsequent bone metastases in 75-80% of cases but even at 12 years at risk 20% of these patients are alive and still disease-free.3 McGowan et al., also showed a statistical advantage to treating the pelvic lymph nodes when there was a high probability of involvement in this series of Stage B2 and C patients.*’ Perhaps our 77-06 protocol patients are so well staged, that is with a low probability of lymph nodal involvement, that only microscopic disease already distantly disseminated far from the local bed accounts for the equal rate of distant metastatic sites in both arms. Does elective radiation of the pelvic lymph nodes in patients with cancer of the prostate regionally control disease or prevent possible occult microscopic metasta-

Table 4. RTOG 7706 prostate protocol: Analysis of treatment arms by pretreatment factors for local/regional recurrence free

Factor All patients Grade 2 3-4 Gleason

Stage

2-5 6-7 8-10 A2 B

No prior hormones Race

White

Normal/low acid phosphatase Elevated acid phosphatase No TUR TUR Tumor size

Age

1.OOcm2 1.Ol-9.00 cm2 9.01 cm2+ 160 years 6 l-70 years 71+ years

5

Laparotomy Lymphangiogram only * Mantel-Haenszel test. t Too few patients for reliable estimate.

Prostate only 5 yr rate %

Prostate + pelvic 5 yr rate %

Statistically significant difference*

88 90 89

90 90 90

81 88 89 79 97 85

t 95 89 86

No No No No

94 89

No No

89

90

No

87

No

88

89 91

86

84

No

90 86

86 94

No No

90 83 t

No

:: 88 89

91 89 t 94 94 81 90

87

89

No

No No No

p-value

p= .15

No

p = .08

No No No No No No

p = .09

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Elective pelvic irradiation 0 S. 0. ASBELL etal.

Table 5. RTOG 7706 prostate protocol: Analysis of treatment arms by pretreatment

Factor All patients

factors for distant metastases

Prostate only 5 yr rate %

Prostate + pelvic 5 yr rate %

Statistically significant difference*

84

83

No

Grade

1 2 3-4

88 82 71

89 85 t

No No No

Gleason

2-5 6-7 8-10

91 89 63

86 87 66

No No No

Stage

A2

90 82

78 84

Yes No

85

83

No

83

85

No

84

84

No

81

72

No

87 80 92 81

90 75 81 87

No No No No

B No prior hormones Race

White

Normal/low acid phosphatase Elevated acid phosphatase No TUR TUR Tumor size

Age

5 1.OOcm* 1.Ol-9.00 cm* 9.01 cm’+ 560 years 6 l-70 years 7 I+ years

Laparotomy Lymphangiogram only

t

t

No

78 84 86

82 84 82

No No No

87 83

88 81

No No

p-value

p=.o3

* Mantel-Haenszel test. t Too few patients for reliable estimate.

ses from leading to dissemination of the disease? These questions have been posed for a number of years. So far our study shows no value of elective pelvic lymph node irradiation on local control or time to dissemination in Stage A and B. Similar results have been obtained by others. Hill et al., I3in a non-randomized trial found no advantage to prophylactic lymph-node radiation. It should be noted that their field sizes were large, similar to that utilized by our protocol. Ploysonsang noted no increased

survival in a non-randomized series of 38 patients Stage A2 and B when treated with prophylactic pelvic lymph node irradiation after 1975, compared to his series of patients prior to 1975 in which the prostatic field alone was treated.30 Bagshaw recently published and updated his prospective randomized study reporting on the largest group of irradiation patients, with an average follow-up beyond 5 years.’ He found in lymph node negative patients that the group who received prophylactic pelvic nodal irradiation had slightly longer survival. This group, however, was approaching a statistically significant difference from those who received prostatic bed irradiation alone.3 Why has there been no statistically significant difference between the elective use of pelvic radiation in our

study? The answer may be related to: (a) the radiation portal field size, (b) the degree of accuracy of the LAG (c) the equal risk of inaccuracy of clinical staging in both arms (d) the number of years the patients have been at risk, (e) the definition of failure (f) the equal use of hormonal manipulation in both arms. The prostatic field size for this protocol was originally small like that of Bagshaw, 6 X 6 cm-7 X 7 cm ports. However, as more about the disease process became evident, CAT scans permitted the visualization of the prostate and seminal vesicles, and clinical understaging was recognized, I8 the field sizes utilized for radiation of the prostatic bed alone approached more of that utilized for the pelvis. Field sizes of 9 X 9 cm-10 X 10 cm on AP portal similar to that utilized by Hussey,14 Neglia et al.,23 and Beiler et al7 were used for patients randomized to prostatic bed alone from 198 1 on to the conclusion of the study. This may be one of the reasons that we have found no significant statistical difference between the treatment arms at 5 years for survival or local control. The accuracy of lymphangiograms has been reported with the commonly accepted average of 80%.33 Thus, in approximately 20% of patients with negative LAG studies, there are involved lymph nodes found at staging lap-

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December 1988, Volume 15, Number 6

Table 6. RTOG 7706 prostate protocol: Analysis of treatment arms pretreatment

factors for NED survival

Prostate only 5 yr rate %

Prostate + pelvic 5 yr rate %

Statistically significant difference*

All patients

67

64

No

Grade

72 66

No No

77 71 48

69 67 t 74 74 49

79 64

68 64

Yes No

68

65

No

65

65

No

66

67

No

68

51

No

68 66

65 64

No

59 64 t 63 69 66 75

68 70 t 67 70 56 75

No

64

61

Factor

2 3-4 Gleason

Stage

2-5 6-7 8-10 A2

B No prior hormones Race

White

Normal/low acid phosphatase Elevated acid phosphatase No TUR TUR Tumor size

Age

1.OOcm2 1.01-9.00 cm2 9.01 cm*+ 5

560 years 6 l-70 years 71+ years

Laparotomy Lymphangiogram only

p-value

No No

No p = .05

No

No No No No

No No

* Mantel-Haenszel test. t Too few patients for reliable estimate.

arotomy.29,33 This means that there is only a small percentage of Stage A2 or B patients who might benefit from prophylactic irradiation afier negative staging laparotomy or lymphangiogram. Thus, we have not seen a difference yet in either arm. Also there is disagreement as to the value of lymphangiograms with some claiming that one of the most commonly involved lymph nodes, the obturator, is not seen. Zoretic et al., presented proof that the surgical obturator lymph node is visualized and removed at the time of lymphadenectomy.34 In many reported series, and in ours, this obturator lymph node has been included in even small field radiation directed to only the paraprostatic tissues, thus receiving in either arm of the study a minimum of 4500 cGy; we expected no difference and found none. Patients with clinical Stage A2 prostatic cancer has a 23% to 28% chance of having positive nodes if biopsied while Br 14-21% and B2 30-50%.12 Thus, if lymph node assessment was either surgically negative or questionably abnormal on LAG but biopsy was negative, the patient was probably a true Stage A or B. Thus the number of patients at risk of lymph nodal involvement are small and may require a longer period of observation to see any possible statistical difference in the treatment arms.

Note that our definition of local failure varies from other reports making verification of similarities of end points more difficult. Examples, of other definitions of local recurrence are as: (a) “local progressive enlargement of the primary prostate cancer with or without histologic confirmation of lymph nodal enlargement in the pelvis.“30 (b) “A clinical phenomena causes discrete signs or symptoms rather than abnormality on biopsy or rectal examination alone.“32 Our local control rate at 5 years was 89% but criteria of failure was different. Local failure was defined as progressive increase of measurable disease or biopsy proof of tumor 2 years beyond completion of radiotherapy. The definition of recurrence or the presence of metastasis has varied with the author. Paulson et al., did not permit patients to enter a randomized study comparing radiation and surgery in surgically lymph node staged patients 25 if the acid phosphatase (AP) were elevated. They assumed an elevated acid phosphatase (AP) at two follow-up visits as an indication of distant metastases. In our study we permitted an increased acid phosphatase or prostatic acid phosphatase on protocol entry (although the number of patients were small). This made comparison of our series with Paulson’s surgically staged and ra-

Elective pelvic irradiation 0 S. 0. ASBELL et al.

diation treated patients more difficult. Using this blood test as a method of determining recurrence or distant failure seems to have shown an earlier abnormality compared to our chosen end points which depend on more tumor burden for identification such as CAT scan, bone scan, or chest X ray. The literature has indicated the inaccuracies of clinical staging in carcinoma of the prostate especially in those with poor tumor differentiation. Lange et al.,‘* reported 68% of 72 patients clinically Stage A and B found at surgery to be Stage C. Despite this risk of understaging in both arms of our study (few were surgically staged) the average survival at 5 years equalled that of those surgically staged and treated by radiation in Paulson’s series.25 In this trial it is conceivable that the hormonal therapy may have masked early evidence of distant metastases. Scardino et aZ.32 stated that “difference in survival rates between different perspective groups of patients with prostatic cancer are not likely to become apparent for the first lo- 15 years if the patients are treated with hormone therapy.” Since our patients have been evaluated on the average of only 5 years, we may not have yet been able to detect any significant differences from the non-hormonally treated. However, since randomization was carried out with equal hormonal manipulation in both

1315

arms, one would not anticipate any statistical differences in the treatment arms as was evident in our series. In conclusion, in our series of over 400 patients with early carcinoma of the prostate, Stages A2 and B, there was a 5-year survival of 79% and disease free survival of 65%, comparable to other series in the literature.2**5,20*3’ If the definition of local recurrence and/or distant metastases is the same, our data supports similar time to distant metastases and local recurrence rates as that reported by other radiation oncologists. Staging, with the help of lymphangiogram, represented the majority of patients and was associated with a 5-year distant metastases free survival of 83% and local control rate of 89%. Our time to distant metastases differs from the more recent Paulson study of surgically staged and radiation treated patients. Reasons for these differences may be on the basis definition of end points, frequency of data collection, compliance, radiotherapy technique and randomization techniques. So far our data suggests that whether the prostatic bed or pelvic lymph nodes and prostatic bed are irradiated there is no statistical difference in the disease free and actuarial survival, nor time to distant metastases, nor local recurrence.

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Bagshaw, M.A.: Radiotherapeutic carcinoma

treatment of prostatic with pelvic node involvement. Ural. Clin. N.

Am. 11: 297-304,

1984.

2. Bagshaw, M.A.: Radiotherapy of prostatic cancer: Stanford University experience. Prog. Contro. Oncol. Ural. 493-512,1984.

3. Bagshaw, M.A.: Potential for radiotherapy alone in prostatic cancer. Cancer 55: 2079-2085, 1985. 4. Bagshaw, M.A., Pistenma, D.A., Ray, G.R. et al.: Evaluation of extended field radiotherapy for prostatic neoplasms. 1976 Progress Report. Cancer Treat. Rep. 61: 297306,1977.

5. Bagshaw, M.A., Ray, G.R., Pistemma, D.A., Castellino, R.A., Meares, E.M.: External beam radiation therapy of primary carcinoma of the prostate. Cancer 36: 723-728, 1975.

6. Barzell, W., Beam, M.A., Hilaris, B.S., Whitmore, W.F.: Prostatic adenocarcinoma: Relationship ofgrade and local extent to the pattern of metastases. J. Ural. 118: 276-282, 1977. 7. Beiler, D.D., Wright, J., Reddy, G.N.: Radical external radiotherapy for prostatic carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 7: 885-890, 198 1. 8. Budhraja, S.N., Anderson, J.C.: An assessment of the volume of radiotherapy in the management of cancer of the prostate. Br. J. Ural. 36: 535-540, 1964. 9. de1 Regato, J.A.: Radiotherapy in the conservative treatment of operable and locally inoperable carcinoma of the prostate. Radiology 88: 761-766, 1967. 10. Donohue, R.E., Mani, J.H., Whitesel, J.A., Mohr, S., Scanavino, D., Augspurger, R.R., Biber, R.J., Fauver, H.E., Wettlaufer, J.N., Pfister, R.R.: Pelvic lymph node dissection: Guide to patient management in clinically locally

confined adenocarcinoma of the prostate. Ural. 20: 559565, 1982. 11 Gleason, D.F., Mellinger, G.T., the Veterans Administration Cooperative Urological Research Group: Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J. Ural. 111: 5864, 1974. 12. Gothlin, J.H.: Protstatic carcinoma: Staging with percutaneous lymph node biopsy. Bull. Cancer 72: 462-466, 1985.

13. Hill, D., Crews, A.D., Jr., Walsh, P.C.: Prostate carcinoma: Radiation treatment of the primary and regional lymphatits. Cancer34: 156-159, 1974. 14. Hussey, D.H.: Experience with limited-field irradiation for adenocarcinoma of the prostate. In Cancer of the Genitourinary Tract, Johnson, D.E., Samuels, M.L. (Eds.). New York, Raven Press. 1979, pp. 2 17-228. 15. Jazy, F.K., Aron, B., Dettmer, C.M., Shehata, W.M.: Radiation therapy as definitive treatment for localized carcinoma of the prostate. Ural. 14: 555-560, 1979. 16. Jewett, H.J.: The present status of radical prostatectomy for stage A and B prostatic cancer. Ural. Clin. N. Am. 2: 105-124, 1975. 17. Kaplan, E.L., Meier, P.: Nonparametric estimation for incomplete observation. J. Am. Stat. Assoc. 53: 457-48 1, 1958. 18. Lange, P.H., Narayan, P.: Understaging and undergrading ofprostate cancer. Ural. 21: 113-l 18, 1983. 19. Lee, E.T.: Statistical Methods for Survival Data Analysis. Lifetime Learning Publications. Belmont, CA, Wordsworth, 1980. 20. Leibel, S.A., Hanks, G.E., Kramer, S.: Patterns of care outcome studies: Results of the national practice in adenocar-

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21.

22.

23.

24. 25.

26.

27.

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