Local Failure After Definitive Therapy for Prostatic Cancer

0022-6347/87 /137 4-0613$02.00/C THE JOURNft_L OF UE:0:)LOG'!

Copy1~ight © 1987 by The ·vVilliar.r:s & VVilki:ns Co.

eview Article LOCAL FAILURE AFTER DEFINITIVE THERAPY FOR PROSTATIC CANCER EDWIN L. ROBEY

AND

PAUL F. SCHELLHAMMER

From the Department of Urology, Eastern Virginia Medicine School, Norfolk, Virginia

The efficacy of local definitive treatment is measured by its success in achieving local tumor control. Herr studied the incidence of local failure after treatment of carcinoma of the prostate and he concluded that local failure was similar whether radical surgery or radiotherapy was used. 1 He analyzed 3 series that used radical prostatectomy, and 1 series each that used external beam and interstitial radiotherapy. Other reviews of local failure following external beam radiation have been reported. 2· 3 However, documentation of local failure has not been a standard practice when results are reported after treatment of adenocarcinorna of the prostate. In an effort to focus attention on this parameter of treatment response, we reviewed the literature for pertinent information regarding the incidence of local failure, significance of positive biopsies after irradiation and the management of local failure of pr,ost;at1tc adenocarcinoma. MATERIALS AND METHODS

We reviewed the literature for reports of definitive therapy ofprostatic cancer between 1954 and 1985. Series were selected that contained information concerning the incidence of local failure. Local failure was segregated when possible by stage and grade of disease. Information pertaining to the time of initiation of hormonal therapy was recorded, and those series withholding hormonal therapy until either local or distant failure were separated from those series initiating hormonal therapy before treatment failure. The duration of followup after therapy was tabulated. Series reporting patients with positive biopsies but no clinical evidence of local failure were not included in the tabulations, although the relationship of positive biopsy after treatment to subsequent failure is discussed, RESULTS

Radical prostatectomy. Local failure radical prostatectomy with no hormonal therapy until treatment failure or with hormonal therapy before treatment failure is reviewed in tables 1 and 2. 4 - 18 Complete information beyond 10 years was available in 3 series. Jewett reported local failure in 16 cent of 86 patients with pathological stage B neoplasms. Walsh and Jewett subsequently reported a 12 per cent local failure rate in 57 patients with clinical stage B disease. 10 In these 2 series all patients were followed for at least 15 years. We reported a 15-year followup in 9 patients with clinical stage Bl, 17 with clinical stage B2, 23 with pathological stage B and 13 with pathological stage C lesions. 11 The local failure rates were 11, 16, 17 and 31 per cent, respectively. Culp reported local failure in 26 per cent of 123 patients with clinical stage B lesions who were followed for 1 to 15 years. 4 Few patients with clinical or pathological stage C disease have been treated by radical prostatectomy without concomitant adjunctive hormonal therapy. Belt and Schroeder reported experience with 452 patients, of whom 299 had received adjunctive hormonal therapy. 12 They detected local failure in 6 613

per cent of the patients with pathological stage B and 22 per cent of those with pathological stage C lesions after 1 to 20 years of followup. Myers and Fleming reported local failure in 10 per cent of 562 patients with combined pathological stages Band C lesions treated by radical prostatectomy. 17 Adjunctive hormonal therapy was used in 21 per cent of these patients. External beam therapy. Information regarding local failure in patients treated by external beam radiation therapy who were followed for longer than 10 years was not available. In addition, adjunctive hormonal therapy often was used in the external beam series. The majority of patients treated with external beam radiation had clinical staging. Local failure occurred in 5 per cent of the patients with clinical stage B disease and in 8 to 22 per cent of those with clinical stage C disease without hormonal therapy until treatment failure (table 3). 19- 24 With hormonal therapy, local failure was 3 to 13 per cent in patients with stage B lesions and O to 34 per cent in patients with stage C lesions (table 4). 2 - 20 , 25- 31 Many series combined clinical stages B and C lesions, and reported local failure rates of 12 to 14 per cent in patients with no hormonal therapy (table 3) 22 - 24 and 2 to 40 per cent in those with hormonal therapy (table 5). 3•30• 32 - 39 Analysis by differentiation of neoplasm demonstrates increasing incidence of local failure for progressively less differentiated disease whether or not hormonal therapy was used (tables 6 and 7). 21 • 27 • 28 , 40- 43 Interstitial therapy. Followup was less than 10 years in series reporting results of interstitial implantation with 125iodine ( 125 I), 198gold (198Au) or 192 iridium (192Ir) (table 8). 44- 49 Local failure occurred in 14 to 19 per cent of the patients with stage A2, 15 per cent with stage Bl, 17 to 35 per cent with stage B2 1 of these and 20 to 42 per cent with stage C lesions. In series was hormonal therapy used before treatment failurn. 48 Flocks and associates reported local failure of less than 5 per cent in patients with stage C ~Anlcwnoo who were treated with

TABLE

1. Radical prostatectomy without hormonal therapy No. With Local Failure/Total No.(%)

Reference

Stage A Culp'·* Gibbons and associates 5 ' * Jewett6 ·t McCullough and Leadbetter7• * Puntenney and Lamson8·t Tomlinson and associates'· t Walsh and Jewett10·* Schellhammern, * Schellhammern, t

* Clinical staging.

Stage B

Stage C

33/123 (26.8) 10/195 (5.1) 14/86 (16.3) 0/1 (0.0) 0/10 (0.0)

t Pathological staging.

0/15

(0.0)

1-15 1-15 6/14 (42.9)

15 1-14

0/3

1-8

(0,0)

2/24 (8.3) 7/57 (12.3) 4/26 (15.4) 4/23 (17.4)

Followup (yrs.)

2-14 15

4/13 (30.7)

15 15

614

ROBEY AND SCHELLHAMMER TABLE 2.

Radicalprostatectomy with hormonal therapy No. With Local Failure/Total No. Pts. (%)

Reference Stage B

Stage A Belt and Schroeder12• * Nichols and associates 13• t Scott1 4·t Spaulding and Whitmore 15• t Whitmore and MacKenzie 16• *

Stage C

12/185 (6.5)

59/267 (22.1)

3/33 (9.1) 1/2 (50.0)

3/9 4/7

7/29 (24.1) 13/24 (54.2) 3/7 (42.9)

(33.0) (57.0)

Followup (yrs.) 1-20 5-10 >5 1-20 5

Combined stages B and C Myers and Fleming17• * Vickery and Kerr 18' t

55/562 (9.8) "Uncommon" /187

1-15 1-12

* Pathological staging. t Clinical staging.

TABLE 3.

External beam without hormonal therapy

TABLE

5. External beam and hormonal therapy-combined staging No. With Local Failure/Total No. Pts. (stage)

No. With Local Failure/Total No. Pts. (%) Reference

Followup Stage A

Gibbons and associates 19 Neglia and associates20 Turalbaand associates21

Stage B

Stage C 17 /209 (8.1)

0/19 (0.0)

0/3

(0.0)

4/75

(5.3)

>2 yrs.

(9.2)

2-8 yrs.

16/72 (22.2)

1-5 yrs.

7/76

Combined stages Cupps and associates22 Green and associates 23 Grout and associates 24

TABLE

20/142 (14.1)

133 B and C

>5 yrs.

4/32 (12.5)

Mostly Band C

1-6 yrs.

6/41 (14.6)

39 Band C

4-53 mos.

Reference Hafermann3 Lipsett and associates30 Bagshaw and associates 32 Duttenhaver and associates33 Harisiadis and associates34 Hill and associates36 Leach and associates36 McGowan37 Mollenkamp and associates38 Pino y Torres and associates39

%

Followup (yrs.)

24/172 (A to C) 1/23 (A and B)

14.0 4.3

1-10

48/430 (Band C)

11.2

5-10

16/180 (153 T2-T3) 9/146 (133 Band C) 2/23 (A to C) 7/159 (Band C) 10/86 (B and C) 36/88 (B and C) 2/84 (A to C)

8.9

?

>5

6.2

1-5

8.7 4.4 11.6 40.9

>5 5-10 >2 >1

2.4

1-5

4. External beam with hormonal therapy No. With Local Failure/Total No. Pts. Stage A

Cox and Stoffel2 Neglia and associates20 Del Regato 25 Jazy and associates 26 Jones and associates 27 Kurupand associates28 Leibel and associates29 Lipsett and associates30 Pilepich and associates31

Followup (yrs.)

(%)

Reference

Stage B

1/15 (6.7)

0/24 (0.0) 2/56 (3.6)

No. With Local Failure/Total No. Pts. (%)

(0.0)

2/38 (5.3) 14/74 (18.9)

4* 2-8

6/60 (10.0)

0/59 (O.O) 14/41 (34.1)

1-10 1-5

7/53 (13.2)

16/58 (27.6)

2*

(3.1)

9/74 (12.2)

2-7

33/291 (11.3)

53/268 (19.8)

1-5

8/56 (14.3)

1-10

0/1

2/65

3/45

(6.7)

6. External beam without hormonal therapy

TABLE

Stage C

25/155 (16.1)

Reference

Moderately Differentiated

Poorly Differentiated

6/63 (9.5)

1/59 (1.7)

10/47 (21.3)

1-5

0/4 (0.0)

3/10 (30.0)

4/8 (50.0)

3-14

Turalba and associates21 Lupu and associates40

TABLE 7.

radical prostatectomy and colloidal 198Au, with a followup of 5 years. 50 A more recent experience with 198Au seeds rather than colloidal 198Au has been reported by Rosenberg and associates (table 9). 51 Cryosurgery. Local failure following definitive therapy with cryosurgery in patients with stages B to D lesions has been approximately 60 per cent without hormonal therapy and 40 per cent with adjunctive hormonal therapy (table 10). 52 DISCUSSION

Accurate staging of any neoplasm is critical in the subsequent assessment of treatment results. Clinical staging uses the information obtained from physical, radiological and serological examination. Surgical staging adds information gained at laparotomy with regard to involvement of adjacent organs, regional lymph nodes and other viscera. Pathological staging provides information with regard to microscopic extension of the tumor beyond the primary organ site, and information concerning

Radiation therapy with hormonal therapy No. With Local Failure/Total No. Pts. (%)

Reference

5*

* Median.

Followup (yrs.)

Well Differentiated

Jones and associates27 Rurup and associates28 DeMilelenaere and Sandison 41 Edsmyrand associates42 Perez and associates43

Model'at.elv Poorly Well Differentiated Differentiated Differentiated

Followup (yrs.) 2*

3/25 (12.0)

4/16 (25.0)

12/47 (25.5)

1/64 (1.6)

6/69 (8.7)

4/27 (14.9)

0/13 (0.0)

1/3 (33.0)

4/10 (40.0)

>2

31/107 (29.0)

>5

4/33 (12.1)

6/39 (15.4)

8/25 (32.0)

2-7

1-5

* Median.

microscopic nodal and visceral involvement. Autopsy staging provides the most complete information concerning the local and distant extent of disease. In the case ofprostatic cancer the majority of patients treated definitively undergo clinical staging. In some patients who undergo external beam radiation therapy and in the majority who undergo interstitial implantation the disease is staged surgically. Pathological staging is possible only in patients who undergo radical prostatectomy. If failure occurs after definitive treatment followup staging redefines the extent of disease. The

615

LOCAL FAILURE AFTER DEFINITIVE THERAPY FOR PROSTATIC CANCER

Interstitial implants-no hormones

TABLE 8.

No. With Local Failure/Total No. Pts. (%) Reference

Radiotherapy

Surgical Stage A2

Surgical Stage Bl

Surgical Stage B2

Surgical Stage C

Au

19/103 (19.0) 1/7 (14.3)

24/152 (15.8) (0.0) 0/7

21/98 (22.0) 6/35 (17.1)

41/99 (42.0) 3/15 (20.0)

(0.0)

0/12 (0.0) 9/58 (15.5)

0/16 (0.0) 70/199 (35.2)

(0.0) 0/6 40/106 (37.7)

Scardino44 Schellhammer and associates45 Syed and associates46 Herr and Whitmore47

198

Abadir and associates48 Goffinet49

125

1251

192Ir

0/6

1251

Followup 1-12 yrs. 5 yrs. 18 mos. (median) 19-179 mos.

Combined stages

I/external beam ,..1

0/20 (0.0)* 2/61 (3.3)t

6-25 mos. 1-54 mos.

* Stage Tl to T3 and includes 5 with hormonal therapy. t Stage Al to C.

TABLE 9.

Combined therapy (radical prostatectomy and 198Au) No. With Local Failure/ Total No. Pts. (%)

Reference

Stage B

15/335 (4.5)

Flocks and associates60 Rosenberg and associates51

1/34 (2.9)

TABLE 10.

Followup

Stage C

2/25 (8.0)

5 yrs. 40 mos. (av.)

Cryosurgery-combined stages B to D

Reference Bonney and associates:52 Without hormonal therapy With hormonal therapy

No. With Local Failure/Total No. Pts. (%)

Followup (yrs.)

35/57 (61.4) 54/135 (40.0)

2-10 2-10

failure may be local, regional or distant. In the case of carcinoma of the prostate the site of failure too often is not noted. Specifically, local failure is not identified. 53- 56 Local failure reflects the effectiveness of a treatment modality in controlling the primary tumor and it is a critical parameter in the followup assessment. A uniform definition of local failure after treatment for carcinoma of the prostate is not available. Some regard a palpable abnormal prostate or an irregular fossa as evidence of local failure, while others require evidence of progressive change in prostatic contour and still others include enlarging pelvic nodes and/or ureteral obstruction and/or urethral obstruction. Another problem that requires consideration is the histolog-· ical demonstration of carcinoma within biopsies obtained after radiation therapy when there is no digital evidence of abnormality at biopsy. These patients usually have not been considered as local failures. This assumption was supported by the study of Cox and Stoffel, who suggested that the incidence of positive biopsies would decrease with time after definitive radiotherapy, and that there was no relationship between positive biopsies and disease recurrence. 2 Others, however, have suggested that a positive biopsy after radiation therapy represents treatment failure, and predict an increased risk of local recurrence and/or distant metastases during followup of these patients. 57- 62 In a study of 64 patients Freiha and Bagshaw found that 25 per cent with negative biopsies 18 months after external beam radiation therapy had either local or distant failure compared to 84 per cent with positive biopsies.60 Scardino reported that of 147 patients who routinely underwent biopsy annually after combination therapy with 198Au implantation and external beam radiation therapy 80 per cent with any positive biopsies suffered local recurrence within 10 years. 61 In addition, his review of 81 patients with a palpable normal prostate showed a significantly higher risk of tumor progression in those with a positive biopsy compared to those with a negative biopsy.

Schellhammer and associates reported similar findings in 103 patients with palpable evidence of regression on examination after 1251 implantation or external beam radiation. 62 Of the patients with a negative biopsy 18 months or more after treatment 9 per cent had evidence of local recurrence on followup compared to 46 per cent of those with a positive biopsy. These reports provide strong evidence that a positive biopsy after radiotherapy has a high risk of local failure, especially if more than 18 months has elapsed since treatment. Certain variables make the evaluation of local failure after definitive surgical therapy or radiation therapy difficult. Most series report followup of less than 10 years, and combine various stages and grades of neoplasms. Results often include patients receiving hormonal therapy before treatment failure (local or metastatic) and, thus, they do not give an accurate indication of the effect of the definitive therapy alone. A retrospective comparison of patients undergoing external beam radiation therapy alone to those patients undergoing adjunctive hormonal therapy suggested less frequent local failure in the latter patients. 30 However, a randomized trial comparing radiation alone and with hormonal therapy for stages B and C neoplasms showed no statistically significant difference in local control or survival, 20 although the 5 mg. dose of diethylstilbestrol used may have biased adversely the survival results of radiation and hormonal therapy owing to increased cardiovascular deaths. An unanswered question pertaining to hormonal therapy is whether its administration simultaneously with radiation therapy has a different impact than when given some time after the completion of radiation therapy but before failure. Different staging techniques may affect the incidence of local failure. Series reported before routine bone scanning and pelvic lymphadenectomy would be expected to include patients with undetected distant metastases or nodal disease. These patients would be at higher risk for death of disease before the detection of local failure and at the time of distant failure they would receive hormonal therapy that possibly would alter the manifestation of local failure. Causes of local failure. After radical prostatectomy, local failure must reflect incomplete resection of neoplastic cells. In a recent review Catalona and Dresner reported positive surgical margins in 18 per cent of clinical stages A and Bl lesions, and 50 and 57 per cent of clinical stage B2 lesions removed by a standard radical retropubic prostatectomy or the nerve-sparing prostatectomy, respectively. 63 Eggleston and Walsh used the nerve-sparing technique and reported extensive periprostatic spread in 17 per cent of clinical stage A, 24 per cent stage BlN, 38 per cent stage Bl and 68 per cent stage B2 lesions. 64 However, surgical margins were positive in 17 per cent of clinical stage A, 0 per cent of stage Bl and 18 per cent of stage B2 lesions. The method of pathological examination may explain the difference in positive surgical margins between the 2 series. For instance, in a re-evaluation of an earlier study of 21 therapeutic failures Jewett and associates found that examination of a larger number of sections revealed partial or complete capsular penetration in 15 patients ratlier than the 6

616

ROBEY AND SCHELLHAMMER

found by routine random sections. 65 Thus, patients with extraprostatic tumor but negative margins may well have unrecognized areas of residual tumor and be at higher risk for local failure. Belt and Schroeder provided information regarding local failure in a large group of such patients. 12 In their series 22 per cent of 267 patients with histological evidence of extracapsular extension (some receiving hormonal therapy before failure) had local failure after radical prostatectomy. In our experience 31 per cent of the patients with pathological stage C lesions had local failure. 11 Even when lesions are confined histologically to the prostate local failure can be expected in 16 to 17 per cent of the patients after 15 years of followup. 6·11 This rate probably reflects unrecognized local extension or incomplete resection of the prostatic capsule containing tumor cells. 65 Little information is available to predict the risk of clinical local or distant failure in those patients with capsular invasion, penetration or perforation, and negative surgical margins and negative seminal vesicles. In addition, a clear distinction between partial capsular involvement and full thickness penetration is not a routine feature ofhistopathological study. A limited number of patients with capsular involvement were studied in the Johns Hopkins series and little adverse impact on prognosis was noted. 10• 65 Fowler and Mills reported no distant failures associated with tumors that were entirely intracapsular, whereas 17 per cent of the tumors that invaded and 16 per cent of those that penetrated the capsule were associated with distant metastases, and 55 per cent of the tumors with seminal vesicle invasion were associated with metastases. 66 Myers and Fleming noted no difference in projected local progression between cases without capsular invasion and those with penetration of the capsule. 17 However, perforation of the capsule was associated with a shorter time to local progression. The systemic progression rate at 10 years without capsular invasion was 10 per cent, whereas it was 45 per cent with capsular penetration. Byar and Mostofi reported a 7-year survival of 69 per cent when the capsule was invaded versus 33 per cent when the capsule was penetrated.67 Careful prospective histological studies are needed to determine the prognostic importance of capsular involvement and the significance of tumor invasion compared to perforation or penetration of the capsule. After radical prostatectomy the risk for local failure with seminal vesicle invasion was 44 per cent in our series. 11 The risk for local failure with seminal vesicle invasion without capsular penetration is not available, since most patients with seminal vesicle invasion also have capsular involvement.11· 67 Culp documented the interval to local failure after radical prostatectomy for lesions confined clinically to the prostate. 4 Tvvo-thirds of 33 patients: h:ul loc11l failure within the first 5 years after therapy but 15 per cent did not have local failure until after 10 years. That study demonstrates the need for prolonged followup before local tumor control can be assured. The cause of local failure after radiation therapy is more complex. Failure may result from clones of cells totally resistant to radiation and surviving its effect, clones of cells that undergo sublethal damage and are able, subsequently, to recover and resume growth or the development of new tumors in an organ at risk left in situ. In addition, inadequate external beam treatment portals may result in radiological "misses" so that cells outside the field are untreated and, subsequently, progress to local failure. 29·68 A similar problem exists with the use of interstitial implants when inadequate radiation delivery secondary to faulty seed distribution may occur. Since any of these factors potentially is the source of local failure, it appears that the potential for local failure is higher with radiation modalities. Short followup makes the evaluation of results following radiation therapy difficult. The largest series with the longest followup after external beam radiation grouped stages B and C neoplasms and included many patients who received hormonal therapy before treatment failure. Furthermore, the incidence

of local failure in this series has not been updated beyond 5 years of followup. 69 Treatment of local failure. The issue of local failure can be addressed either by attempts at prevention in patients at high risk for local failure or by treatment when digital detection of progressive enlargement, or evidence of bladder neck or ureteral obstruction occurs. Preventive therapy has consisted of extended excision by prostatocystectomy or pelvic exenteration,7· 15 preoperative radiotherapy followed by radical prostatectomy,59·70 sandwich radiotherapy around radical prostatectomy,71 radiotherapy after radical prostatectomy72 - 75 and regional intra-arterial chemotherapy. 61 Spaulding and Whitmore, 15 and McCullough and Leadbetter7 demonstrated that extended excision can be performed in patients with locally advanced disease with reasonable morbidity. However, this therapy should be considered only when a long interval of clinical observation has identified a tumor that has remained confined locally. Spaulding and Whitmore suggested that extended total excision be used only after "other therapeutic options were exhausted ... " to identify the small subset of patients determined not to have disseminated disease. 15 Carson and associates reported the results of radical retropubic prostatectomy and pelvic lymphadenectomy 4 to 8 weeks after planned preoperative external beam radiotherapy in 9 patients. 7°Followup ranged from 18 months to 11 years, during which time 3 patients had metastatic disease. The postoperative morbidity rate was not worsened by the radiation therapy. Gill and associates reported the use of radical retropubic prostatectomy and retroperitoneal lymphadenectomy for lesions downstaged to stage B from stage C by external beam radiotherapy. 59 Both cases reported were followed by prolonged suprapubic urinary drainage but otherwise the subsequent radical prostatectomy did not seem to be complicated by the radiotherapy that was administered 7 and 9 months preoperatively. Subsequently, Gill and associates suggested delivering 3,000 rad preoperatively and 4,500 rad to the pelvis and prostate after radical retropubic prostatectomy. 71 In addition, 4,500 rad were delivered to para-aortic lymph nodes postoperatively. Their experience included 15 patients with pathological stage C lesions followed for 6 to 66 months. Lymphadenectomy was not done in 14 patients. Prostatectomy was performed without difficulty 3 weeks after irradiation. Stress incontinence developed in 6 of 15 patients and 2 intraoperative rectal injuries occurred. No recurrent tumor had been detected in these patients at the time of their report. Lange and Narayan, 72 Ray and associates, 73 Skinner and Lieskovsky, 74 and Gibbons and associates 75 reported the use of prophylactic external b_e11m radiation after radical pros_tatectomy in patients believed to be at risk for local failure. Lange and Narayan treated patients with capsular or seminal vesicle invasion, or tumor invasion at the bladder neck or urethral anastomosis with 6,000 rad postoperative radiotherapy. 72 The treatment was tolerated well. Ray and associates used 7,000 rad in patients with capsular penetration, seminal vesicle invasion or tumor invasion of the bladder neck. 73 Local control was achieved in 77 per cent with up to 10 years of followup and the treatment was tolerated well. Skinner and Lieskovsky used 4,000 to 5,000 rad postoperatively in patients with capsular penetration, positive surgical margins or seminal vesicle in volvement. 74 They reported 1 local recurrence in 45 patients receiving postoperative radiotherapy. They also reported that impotence was more common among those who had a nervesparing radical prostatectomy and postoperative irradiation than those undergoing the same operation but without subsequent radiation. Gibbons and associates reviewed the results of therapy in patients with tumor extension through the capsule, into the seminal vesicles or at the surgical margins following radical perineal prostatectomy. 75 Of 45 patients 22 received radiotherapy within 6 weeks postoperatively. After 5 years of followup local failure occurred in only 1 patient. In contrast,

LOCAL FAILUR,E A.FTER DEFIN"ITIVE TI-iER.APY FOH. PROST_..t,_TIC CAI }CER 1

local failure appeared in 7 of the 23 ,rnr.H•,rn.;; who did :not receive adjuvant postoperative radiation. these 7 patients 6 then received external beam irradiation following local failure and 5 died subsequently of distant metastases. Gibbons and associates did find a higher incidence of severe complications when patients were irradiated shmtly after radical prostatectomy but they believed that much was owing to the 60 cobalt source used in the earlier patients. 75 Scardino reported the investigational use of cisplatin intra-arterial regional infusion of the prostate following a positive post-radiation biopsy. 61 The treatment of patients who have clinical evidence of local failure includes radical prostatectomy or extended excision after radiotherapy failure, 15• 70 • 76 external beam radiation after radical prostatectomy failure, 73 • 75 125I implants aftel' external beam radiation failure 77 and/or hormonal manipulation. Spaulding and Whitmore reported the use of prostatocystectomy or pelvic exenteration in 6 patients who had local failure after radiotherapy and found the procedures to be tolerated fairly well. 15 Survival or local recurrence results for these 6 patients were not reported separately from the total group of 37 patients undergoing extended total excision. Carson and associates performed radical prostatectomy in 7 patients 4 to 72 months after radiation therapy because of suspected residual tumor. 70 The complication rate was considered to be acceptable. Mador and associates reported on the use of salvage surgery involving either radical prostatectomy or cystoprostatectomy in 7 patients with local failure after radiotherapy. 76 They suggested that there was "substantial morbidity" with much fibrotic reaction following prior irradiation, making rectal injury a "significant risk". Ray 73 and Gibbons 75 and their associates used external beam irradiation for treatment of local failure after radical prostatectomy and found the therapy to be tolerated well with modern treatment sources. Local control was achieved in 58 per cent of the patients. However, survival free of disease was only 20 per cent at 6 years after irradiation in the series of Ray and associates, and Gibbons and associates found that 5 of 6 patients died of metastatic disease. Finally, Goffinet and associates implanted 125! seeds in patients with local failme after external beam irradiation. 77 They found a lower complication rate with lower intensity 125I seed implants in prostatic volumes less than 50 cc. After 6 to 36 months of followup clinical local control was obtained in 11 of 14 patients.

pr
prostate cancer: stages Bl and B2. Prostate, 4: 447, 1983. 2. Cox, J. D. and Stoffel, T. J.: The significance of needle biopsy after irradiation for stage C adenocarcinoma of the prostate. Cancer, 40: 156, 1977. 3. Hafermann, M. D.: External radiotherapy. Urology, suppl. 4, 17: 15, 1981. 4. Culp, 0. S.: Radical perinea! prostatectomy: its past, present and possible future. J. Urol., 98: 618, 1968. 5. Gibbons, R. P., Correa, R. J., Jr., Brannen, G. E. and Mason, J. T.: Total prostatectomy for localized prostatic cancer. J. Urol., 131: 73, 1984. 6. Jewett, H.J.: The present status of radical prostatectomy for stages A and B pl'ostatic cancer. Urol. Clin. N. Amer., 2: 105, 1975. 7. McCullough, D. L. and Leadbetter, W. F.: Radical pelvic surgery 8.

9. 10.

11. 12.

13. 14.

CONCLUSION

Our purpose was not to compare the local failure rate among various treatment groups. The in staging, in the use of adjunctive hormonal treatment, in tre,quten,cy method and dmation of followup, and the lack of a accepted definition of local failure make such a comparison invaiid. However, it is apparent that local failure is not rare after radical prostatectomy and it may occur even when the tumor is reported to be confined to the prostate by histological examination. Patients with seminal vesicle invasion, positive surgical margins or capsular penetration with negative margins must be considered to be at increased risk for later development of clinical local recurrence. Local failure occurs commonly after radiation therapy modalities, and positive biopsies obtained more than 18 months after the completion of radiation therapy imply a high risk for subsequent development of clinical local and distant failure. The use of postoperative irradiation in patients at increased risk for clinical local failure who have no evidence of pelvic lymphatic or distant spread of tumor after radical prostatectomy seems to be appropriate, although further evaluation of this treatment is needed. The appropriate treatment of patients with clinical local failure following initial therapy with either

15. 16.

17.

18.

19.

20. 21.

22.

for locally extensive carcinoma of the prostate. J. UroL, HIS: 939, 1972. Puntenney, R. E. H, and Lamson, B, G.: Cancer of the prostate gland: a clinical and pathological evaluation of patients treated by radical prostatectomy. J. UroL, 85; 649, 1961. Tomlinson, R. L., Currie, D. P. and Boyce, W. H.: Radical prostatectomy: palliation for stage C carcinoma of the prostate. J. Urol., 117: 85, 1977. Walsh, P. C. and Jewett, H, J.: Radical surgery for prostatic cancer. Cancer, 45: 1906, 1980. Schellhammer, P. F.: Radical prostatectomy for carcinoma of the prostate and 15 year analysis of survival and local control. J. Urol., part 2, 135: 247A, abstract 574, 1986. Belt, E. and Schroeder, F. H.: Total perinea! prostatectomy for carcinoma of the prostate. J. Urol., 107: 91, 1972. Nichols, R. T., Barry, J.M. and Hodges, C. V.: The morbidity of radical prostatectomy for multifocal stage I prostatic adenocarcinoma. J. UroL, 117: 83, 1977. Scott, W. W.: An evaluation of endocrine control therapy plus radical perinea! prostatectomy in the treatment of selected cases of advanced carcinoma of the prostate followed five or more years. J. Urol., 77: 521, 1957. Spaulding, J. T. and Whitmore, W. F., Jr.: Extended total excision of prostatic adenocarcinoma. J. Urol., 120: 188, 1978. Whitmore, W. F., Jr. and MacKenzie, A. R.: Experiences with various "v""'";-;,,,, procedures for the total excision of p:rostatic 12: 396, 1959. cancer. Myers, R, P. Fleming, T. R.: Course of localized adenocarcinorna of the prostate treated by radical prostatectomy. Prostate, 4: 1983. Vickery, L., Jr. and Kerr, W. S., Jr.: Carcinoma of the prostate treated by radical prostatectomy. A clinicopathological survey of 187 cases followed for 5 years and 148 cases follo,,ved for 10 years. Cancer, 16: 1598, 1963. Gibbons, R. P., Mason, J. T., Correa, R. J., Jr,, Cummings, K. B., Taylor, W. J., Hafermann, M. D. and Richardson, R. G.: Carcinoma of the prostate: local control with external beam radiation therapy. J. Urol., 121: 310, 1979. Neglia, W. J., Hussey, D. H. and Johnson, D. E.: Megavoltage radiation therapy for carcinoma of the prostate. Int. J. Rad. Oncol. Biol. Phys., 2: 873, 1977. Turalba, C. I. C., El-Mahdi, A. M., Higgins, E. M. and Schellhammer, P. F.: Six-year experience with triple course irradiation for carcinoma of the prostate. Int. J. Rad. Oncol. Biol. Phys., 10: 158, abstract 1024, 1984. Cupps, R. E., Utz, D. C., Fleming, T. R., Carson, C. C., Zincke, H. and Myers, R. P.: Definitive radiation therapy for prostatic

618

ROBEY AND SCHELLHAMMER

carcinoma: Mayo Clinic experience. J. Urol., 124: 855, 1980. 23. Green, N., Melbye, R. W., George, F. W., III and Morrow, J.: Radiation therapy of inoperable localized prostatic carcinoma: an assessment of tumor response and complications. J. Urol., 111: 662, 1974. 24. Grout, D. C., Grayhack, J. T., Moss, W. and Holland, J. M.: Radiation therapy in the treatment of carcinoma of the prostate. J. Urol., 105: 411, 1971. 25. Del Regato, J. A.: Long-term curative results of radiotherapy of patients with inoperable prostatic carcinoma. Radiology, 131: 291, 1979. 26. Jazy, F. K., Aron, B., Dettmer, C. M. and Shehata, W. M.: Radiation therapy as definitive treatment for localized carcinoma of prostate. Urology, 14: 555, 1979. 27. Jones, D. A., Eckert, H. and Smith, P. J.B.: Radical radiotherapy in the management of carcinoma of the prostate. Brit. J. Urol., 54: 732, 1982. 28. Kurup, P., Kramer, T. S., Lee, M. S. and Phillips, R.: External beam irradiation of prostate cancer. Experience in 163 patients. Cancer, 53: 37, 1984. 29. Leibel, S. A., Hanks, G. E. and Kramer, S.: Patterns of care outcome studies: results of the national practice in adenocarcinoma of the prostate. Int. J. Rad. Oncol. Biol. Phys., 10: 401, 1984. 30. Lipsett, J. A., Cosgrove, M. D., Green, N., Casagrande, J. T., Melbye, R. W. and George, R. W., III: Factors influencing prognosis in the radiotherapeutic management of carcinoma of the prostate. Int. J. Rad. Oncol. Biol. Phys., 1: 1049, 1976. 31. Pilepich, M. V., Perez, C. A. and Bauer, W.: Prognostic parameters in radiotherapeutic management of localized carcinoma of the prostate. J. Urol., 124: 485, 1980. 32. Bagshaw, M. A., Ray, G. R., Pistenma, D. A., Castellino, R. A. and Meares, E. M., Jr.: External beam radiation therapy of primary carcinoma of the prostate. Cancer, 36: 723, 1975. 33. Duttenhaver, J. R., Shipley, W. U., Perrone, T., Verhey, L. J., Goitein, M., Munzenrider, J. E., Prout, G. R., Parkhurst, E. C. and Suit, H. D.: Protons or megavoltage x-rays as boost therapy for patients irradiated for localized prostatic carcinoma. An early phase I/II comparison. Cancer, 51: 1599, 1983. 34. Harisiadis, L., Veenema, R. J., Senyszyn, J. J., Puchner, P. J., Tretter, P., Romas, N. A., Chang, C. H., Lattimer, J. K. and Tannenbaum, M.: Carcinoma of the prostate: treatment with external radiotherapy. Cancer, 41: 2131, 1978. 35. Hill, D.R., Crews, Q. E., Jr. and Walsh, P. C.: Prostate carcinoma: radiation treatment of the primary and regional lymphatics. Cancer, 34: 156, 1974. 36. Leach, G. E., Cooper, J. F., Kagan, A. R., Snyder, R. and Forsythe, A.: Radiotherapy for prostatic carcinoma: post-irradiation prostatic biopsy and recurrence patterns with long-term followup. J. Urol., 128: 505, 1982. 37. McGowan, D. G.: Radiation therapy in the management of localized carcinoma of the prostate: a preliminary report. Cancer, 39: 98, 1977. 38. Mollenkamp, J. S., Cooper, J. F. and Kagan, A. R.: Clinical experience with supervoltage radiotherapy in carcinoma of the prostate: a preliminary report. J. Urol., 113: 374, 1975. 39. Pino y Torres, J. L., Lee, D. J., Leibel, S. A., Wharam, M. D., Cantrell, B. B., Bross, D. S. and Order, S. E.: Local control and reduced complications in split course irradiation of prostatic cancer. Int. J. Rad. Oncol. Biol. Phys., 7: 43, 1981. 40. Lupu, A. N., Petrovich, Z., Corvalan, J., Katske, F. A. and Kaufman, J. J.: Teletherapy for stage C adenocarcinoma of the prostate. J. Urol., 128: 75, 1982. 41. DeMuelenaere, G. F. G. 0. and Sandison, A. G.: Treatment of locally advanced prostatic carcinoma. Brit. J. Rad., 49: 944, 1976. 42. Edsmyr, F., Esposti, P. L. and Andersson, L.: External irradiation therapy in carcinoma of the prostate. Scand. J. Urol. Nephrol., suppl., 55: 213, 1980. 43. Perez, C. A., Bauer, W., Garza, R. and Royce, R. K.: Radiation therapy in the definitive treatment of localized carcinoma of the prostate. Cancer, 40: 1425, 1977. 44. Scardino, P. T.: Personal communication, 1985. 45. Schellhammer, P. F., El-Mahdi, A. E., Ladaga, L. E. and Schultheiss, T.: 125Iodine implantation for carcinoma of the prostate: 5-year survival free of disease and incidence of local failure. J. Urol., 134: 1140, 1985. 46. Syed, A. M. N., Puthawala, A., Tansey, L. A., Shanberg, A. M.,

47. 48. 49. 50. 51.

52.

53. 54. 55. 56. 57. 58. 59.

60. 61. 62.

63. 64. 65. 66.

67.

68. 69. 70. 71.

72.

Neblett, D., Mendez, R., Barloon, J. W., Ingram, J.E., Naftel, W. T. and McNamara, C.: Management of prostate carcinoma. Combination of pelvic lymphadenectomy, temporary lr-192 implantation, and external irradiation. Radiology, 149: 829, 1983. Herr, H. W. and Whitmore, W. F., Jr.: Personal communication, 1985. Abadir, R., Ross, G., Jr. and Edwards, F. M.: Combined 1'25 seed implant and external irradiation for carcinoma of prostate. J. Canad. Ass. Rad., 31: 190, 1980. Goffinet, D. R.: 125! seed prostate implants. Contemp. Surg., 22: 61, February 1983. Flocks, R. H., O'Donoghue, E. P. N., Milleman, L. A. and Culp, D. A.: Surgery of prostatic carcinoma. Cancer, 36: 705, 1975. Rosenberg, S. J., Loening, S. A., Hawtrey, C. E., Narayana, A. S. and Culp, D. A.: Radical prostatectomy with adjuvant radioactive gold for prostatic cancer: a preliminary report. J. Urol., 133: 225, 1985. Bonney, W.W., Fallon, B., Gerber, W. L., Hawtrey, C. E., Loening, S. A., Narayana, A. S., Platz, C. E., Rose, E. F., Sall, J. C., Schmidt, J. D. and Culp, D. A.: Cryosurgery in prostatic cancer: elimination of local lesion. Urology, 22: 8, 1983. Bagshaw, M. A.: External beam radiation therapy of prostatic carcinoma. AUA Prostate Cancer Videoconference, p. 15, 1982. Boxer, R. J., Kaufman, J. J. and Goodwin, W. E.: Radical prostatectomy for carcinoma of the prostate: 1951-1976. A review of 329 patients. J. Urol., 117: 208, 1977. Hodges, C. V., Pearse, H. D. and Stille, L.: Radical prostatectomy for carcinoma: 30-year experience and 15-year survivals. J. Urol., 122: 180, 1979. Veenema, R. J., Gursel, E. 0. and Lattimer, J. K.: Radical retropubic prostatectomy for cancer: a 20-year experience. J. Urol., 117: 330, 1977. Nachtsheim, D. A., Jr., McAninch, J. W., Stutzman, R. E. and Goebel, J. L.: Latent residual tumor following external radiotherapy for prostate adenocarcinoma. J. Urol., 120: 312, 1978. Kiesling, V. J., McAninch, J. W., Goebel, J. L. and Agee, R. E.: External beam radiotherapy for adenocarcinoma of the prostate: a clinical followup. J. Urol., 124: 851, 1980. Gill, W. B., Marks, J.E., Straus, F. H., Sylora, H. 0. and Diamond, H. M.: Radical retropubic prostatectomy and retroperitoneal lymphadenectomy following radiotherapy conversion of stage C to stage B carcinoma of the prostate. J. Urol., 111: 656, 1974. Freiha, F. S. and Bagshaw, M. A.: Carcinoma of the prostate: results of post-irradiation biopsy. Prostate, 5: 19, 1984. Scardino, P. T.: The prognostic significance of biopsies after radiotherapy for prostate cancer. Sem. Urol., 1: 243, 1983. Schellhammer, P. F., El-Mahdi, A. E., Higgins, E. M., Schultheiss, T. E., Ladaga, L. E. and Babb, T. J.: Prostate biopsy after definitive treatment by interstitial I' 25 implant or external beam radiation therapy. J. Urol., in press. Catalona, W. T. and Dresner, S. M.: Nerve-sparing radical prostatectomy: extraprostatic tumor extension and preservation of erectile function. J. Urol., 134: 1149, 1985. Eggleston, J. C. and Walsh, P. C.: Radical prostatectomy with preservation of sexual function: pathological findings in the first 100 cases. J. Urol., 134: 1146, 1985. Jewett, H.J., Eggleston, J.C. and Yawn, D. H.: Radical prostatectomy in the management of carcinoma of the prostate: probable causes of some therapeutic failures. J. Urol., 107: 1034, 1972. Fowler, J. E., Jr. and Mills, S. E.: Operable prostatic carcinoma: correlations among clinical stage, pathological stage, Gleason histological score and early disease-free survival. J. Urol., 133: 49, 1985. Byar, D. P. and Mostofi, F. K.: Carcinoma of the prostate: prognostic evaluation of certain pathological features in 208 radical prostatectomies. Examined by the step section technique. Cancer, 30: 5, 1972. Catalona, W. J.: Radiation therapy. In: Prostate Cancer. Orlando, Florida: Grune & Stratton, Inc., chapt. 8, p. 117, 1984. Bagshaw, M. A.: Personal communication, 1984. Carson, C. C., III, Zincke, H., Utz, D. C., Cupps, R. E. and Farrow, G. M.: Radical prostatectomy after radiotherapy for prostatic cancer. J. Urol., 124: 237, 1980. Gill, W. B., Schoenberg, H. W., Banno, J. J. Sutton, H. G. and Straus, F. H.: Sandwich radiotherapy (3,000 and 4,500 rads) around radical retropubic prostatectomy for stage C prostatic carcinoma. Urology, 16: 470, 1980. Lange, P.H. and Narayan, P.: Understaging and undergrading of

:LiJ-Ci~L FAILUilE AFTER DE:f'Il'-JIT!VE: Tl1ERA!"Y FOR PRJ)STAT[C CAl'JCER prostate can,ce:r. Argurnent for postoperative radiation as adjuvant therapy. 21: 113, 1983. 73. Ray, G. R., Bagshaw, and Freiha, F.: External beam radiation salvage for residual or recurrent local tumor following radical prostatectomy. J. Urol., 132: 926, 1984. 74. Skinner, D. G. and Lieskovsky, G.: Carcinoma of the prostate: an opinion on management of early stage disease with a commentary on the meaning of capsular penetration. J. Urol., 134: 1183, 1985. 75. Gibbons, R. P., Cole, B. S., Richardson, R. G., Correa, R. J., Jr.,

Brannen, G. Mason, J. T., Taylor, W. J. and Hafermann, IvL D.: Adjuvant following radical prostatectomy: :results and complications. UroL, 135: 65, 1986. 76. Mador, D.R., Huben, R. P., Wajsman, Z. and Pontes, J.E.: Salvage surgery following radical radiotherapy for adenocarcinoma of the prostate. J. Urol., 133: 58, 1985. 77. Goffinet, D. R., Martinez, A., Freiha, F., Pooler, D. M., Pistenma, D. A., Cumes, D. and Bagshaw, M.A.: 125 Iodine prnstate implants for recurrent carcinomas after external beam irradiation: p~eliminary results. Cancer, 45: 2717, 1980.