GUIDEDBRACHYTHERAPYFORTREATMENTOF CONFINEDPROSTATECANCER JOSEPH B. PRIESTLY, JR., M.D. DAVID C. BEYER, M.D.

From the Walter 0. Boswell Memorial Hospital, Sun City, Arizona ABSTRACT-A total of 133 patients underwent transperineal ultrasoundguided iodine 125 seed implantation for Stages A and B prostate cancer with a twenty-seven-month follow-up. There has been no mortality and our morbidity is no more than experienced after transurethral resection of the prostate. By using a Mick applicator our operating time is well under one hour, and our patients go home the same day without a Foley catheter. Our results indicate that patients with PSA values of less than 20 ng/mL (Yang method) and/or Gleason scores of 6 or less are excellent candidates for brachytherapy. By subdividing the percentage of normal PSA values in the follow-up periods according to the patient’s original PSA value, further credence is given to the PSA value as a strong aid in staging when the Gleason score is 6 or less. Although the follow-up at twenty-seven months is small, our preliminary results indicate that brachytherapy is a viable option to radical surgery in those patients who are not good candidates for surgery or who prefer nonsurgical treatment.

Ultrasound-guided brachytherapy for confined prostate cancer was introduced by Holm et al.’ and popularized by Blasko, Ragde, and Schumaker2 and is becoming increasingly popular. The manufacturer of the iodine 125 seeds reported they shipped 13,000 seeds in May 1991 (JE Henderson, Mediphysics-Amersham Company, personal communication, 1991), indicating that between 130 and 140 cases are being performed monthly. Between November 1988 and June 1991, 157 transperineal ultrasound-guided radioactive seed implantations were performed at Boswell Memorial Hospital, utilizing a single team of urologist and radiation oncologist. Both lz51 and palladium 103 have been used, but herein we present our findings in 133 cases of implantations with 1251.

(ERT), and no patient had ERT with or after the implant. All patients were evaluated with digital rectal examination (DRE), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), transrectal prostatic ultrasound (TRUS), bone scan, and skeletal survey. A number of patients had computerized tomography (CT) scans of the pelvis. The diagnosis was established by ultrasound-guided biopsy in 124 patients and by transurethral prostatectomy (TURP) in 9 patients . B-94(4.5%)7

r55-64 (8.3%)

Material and Methods Figure 1 shows the age distribution of our patients with 86 percent between 65 and 84 years old. The youngest patient was fifty-nine, the oldest was ninety, and the mean was 73.5 years. No patient had prior external beam radiation

UROLOGY

i JULY 1992 I

VOLUME40,NUMBERl

Youngest 59 FIGURE 1.

lation.

Age

Oldest 90

Mean 73.5

distribution of patient (132)

popu-

27

Largest 74.8 gms

Smallest 11 gms

FIGURE2. Prostate size (g) determined

Mean 34

on original

ultrasound.

ng/ml (Yang-normal~2.5)

FIGURE 4. Original PSA values prior to implant. O-3 cm3 (55.1%)

Smallest 38 cm3

Largest 40.32 cm3

Mean 3.98 cm3

FIGURE 3. Sizeof lesion (cm”) on original ultrasound.

Selection criteria

Our selection criteria consisted of patients with Stages A and B tumors as determined by a PSA value of less than 20 ng/mL and normal findings on PAP, bone scan, skeletal survey, and CT scan. We attempted to limit the Gleason score to 6 and the prostate size to 60 g or less. Exceptions to these criteria were due to patient pressures. Clinical data

Twenty-two patients had no clinical symptoms of voiding difficulties, and only 2 presented with hematuria. Twenty-one patients had normal DRE results with no prostate irregularity, asymmetry, nodules, and only modest enlargement. Figure 2 illustrates the proportion of prostate sizes as determined by the ultrasound stepping procedures. The majority of cases had prostates between 29-39 g, not particularly large. The smallest gland was 11 g and the largest 74.8 g (mean 34 g). The lesion sizes as measured by ultrasound are depicted in Figure 3: 55 percent were 3 cm3 or less, while another 29 percent were between 3.1 and 6 cm3. The smallest lesion was 0.38 cm3, and the largest was 40.32 cm3 (mean 3.98 cm3). The original PSA values of the patients are shown in Figure 4. A total of 85 patients had PSA values between O-10 ng/mL, while 29 pa-

Normal PSA 2.5 @ml

FIGURE 5. Abnormal

PAP values in 13 pat’iknts.

tients had values between 11-20 ng/mL, or a total of 88 percent had PSA of 20 ng/mL or less. Thirteen patients had elevated PAP at presentation Figure 5 shows that 3 with abnormal PAP values had normal PSA; 4 with abnormal PAP level had PSA between 11-20 ng/mL; and 6 with elevated PAP level had PSA greater than 20 ng/mL. The Gleason scores of patients are shown in Figure 6. We divided the Gleason scores into high, medium, and low for easier representation. A total of 83 percent of patients had low or medium Gleason scores of 6 or under, and 17 percent had high Gleason scores of between 7 and 9. Our clinical staging of patients is shown in Figure 7. Elevations of PSA and PAP were not used to upstage patients with normal findings on bone and CT scans. Diagnosis of Stage A disease in patients was based on the usual definition of Stage Al disease: less than 5 percent

UROLOGY

/ JULY1992 / VOLUME40,NUMBERl

Low 2-3 Medium 4-6 High 7-9

1 Numberof patients ( FIGURE 6.

Gleason scores in patient population.

S@eS

FIGURE 7.

Chart showing clinical stage of disease.

prostate chips and Gleason score of under 4, and for Stage A2 disease, prostate chips more than 5 percent and Gleason score greater than 4. Stage B disease was divided by the biopsy results obtained on the six follow-up biopsies of the gland using Stamey et al3 description. A Bruel & Kjaer ultrasound 7 and 4 MHz axial and sag&al transducers were used in the TRUS, the ultrasound-guided biopsies with the Biopty gun, the stepping procedures, and the actual seed implantation. Our technique of seed implantation has been previously described.4 We use the Mick applicator and place all needles into the prostate starting in the center of the gland and working circumferentially. The prostate is secured without lateral holding needles, and we are able to leverage the gland downward if needed to place anterior needles and thus

UROLOGY

/ JULY1992 / VOLUME40,NUMBERl

avoid drilling into the symphysis. The preplanned peripheral tumor dose was 16,000 rad or 160 cGy with a total implanted activity of 1647 mCi (mean 29 mCi). Our operating time is well under one hour. All procedures are done as outpatients, and patients go home without a Foley catheter. Orthogonal films two weeks after the procedure indicate an excellent correlation with the preplan. The implanted volume is lo-25 percent greater than the measured prostate size. All TRUS measurements were performed by a single observer, and all PSA and PAP determinations were performed by the Yang method with normal values of 2.5 ng/mL. Postoperative

complications

The major postoperative complication is difficulty with urination. Simply, if the patient has significant obstructive symptoms prior to the procedure, he will have more of the same afterward. As a result, we do not hesitate to perform a transurethral prostatectomy (TURP) prior to the implantation and then follow with the implant in six to eight weeks. Patients will have minor dysuria and some hematuria after the procedure, but generally less than after TURP Proctitis has not been a problem, and only in 1 patient did a superficial ulcer of the rectal mucosa develop one and one-half years after the procedure. This healed with local steroid therapy without complications. Early in our experience in 1 patient urinary retention developed which was resistant to all treatment. We performed a successful balloon dilatation of the prostatic urethra four months after the implants5 One of the great attributes of this procedure is the patients feel so well afterward that they tend to be too active. We have noted that in a number of patients symptoms very similar to prostatitis, which we have called radiation prostatitis, developed when they play golf, ride bicycles, or undergo prolonged automobile riding or driving too soon after the implant. As a result of this experience, we severely restrict our patient’s activities for four to six weeks, restrictions similar to those post TURP We have not had any significant long-term complications, and our incidence of impotency is less than 10 percent. Results Our follow-up protocol consists of DRE, PSA, PAP, and TRUS every three and nine

29

Months after Implant I~DRE~TRU

Percent Shrinkage ]

FIGURE 8. Comparison of DRE and TRUS percentage decrease in prostate at three- and ninthmonth post implant.

FIGURE 10. Percentage mined by ultrasound.

shrinkage

of lesion deter-

PercentShrinkage m

FIGURE 9.

Month 3 m

Month 9

Percentage shrinkage and nine months post implant.

Months following implant

of prostate three

Percentage of normal PSA values post implant (original PSA O-10 ng/mL).

months from the implant and then DRE, PSA, and PAP every six months. Figure 8 is a comparison of DRE and TRUS percentage decrease in gland volume at three- and nine-month post implant. Excellent correlation exists between these two modalities with both showing more than 80 percent and 90 percent improvements at three- and nine-month tests, respectively. Beyond fifteen months, very little change was detected on DRE. Figure 9 delineates the actual percentage of shrinkage of the glands shown on TRUS at three and nine months in categories of up to 20 percent, 21 to 39 percent, and greater than 40 percent. By nine months, 56 percent of the glands had shrunk by 20 to 39 percent, but only 12 percent reduced in size by 40 percent or more. In contrast, a similar breakdown of percentage of shrinkage of lesions recorded on TRUS

shows only 21 percent of lesions shrunk 20 to 39 percent at nine months (Fig. 10). However, a much higher percentage of patients showed a 40 percent or more reduction in lesion size, i.e., 45 percent. This seems to confirm that the effects of radiation on benign prostatic tissue are different from effects on malignant tissue. As a result, shrinkage of the lesion is expected to have more prognostic value than reduction in size of entire gland. Little controversy exists as to the value of PSA in following the results of treatment for prostate cancer. We have tried to further understand the significance of PSA by separating our follow-up PSA values from the original PSA values of patients prior to treatment. Figure 11 describes the percentage of normal PSA values for the follow-up period of three, nine, fifteen, twentyone, and twenty-seven months in the 85

30

FIGURE 11.

UROLOGY

/ JULY 1992 / VOLUME 40, NUMBER 1

Initial Months following Implant

FIGURE 12.

Percentage of normal PSA values post implant (original PSA 11-20 ng/mL).

’ 3

’ 9 ’ 15 ’ 21 Months Following Implant

’ 27



FIGURE 14. Graph shows still slower rate of normal improvement in PSA (original PSA 21-30 ng/ mL).

100

1

t

. . .. .. _

. .... .. .

.

.. .

& LL

...... . .. ..

Months Following Implant Months After Implant

FIGURE 13. Graph shows ongoing but slower improvement in PSA values (original PSA O-20 ng/ mL).

FIGURE 15.

patients whose original PSA values were between O-10 ng/mL. A total of 46 percent of the 61 patients evaluated at three months had normal PSA. Those percentages continue to improve throughout the follow-up periods. Although only 10 patients were available for testing at the twenty-seven-month follow-up, all had normal PSA values. A similar graph shows the percentage of normal PSA values at the follow-up periods when the original PSA values were between 11-20 ng/mL (Fig. 12). Although considerably fewer patients were available for analysis, the trend shows ongoing but slower improvement. When these two cohorts are combined and similarly charted, the tendency of progressive improvement is again apparent (Fig. 13). If the original PSA values were between 2130 ng/mL, a similar trend in normalization of PSA values is again noted, although at a still slower rate (Fig. 14). In spite of the fact that

the numbers are small, 50 percent and 67 percent of those patients at the twenty-one and twenty-seven month follow-up periods had normal PSA values, although 1 patient in the twenty-seven-month group had had an orchiectomy. Of the 2 patients whose original PSA levels were between 31-40 ng/mL, 1 has been followed-up for twenty-one months and his PSA is 6 ng/mL, and in 1 followed up only three months, his PSA dropped to 9 ng/mL. The follow-up PSA of patients whose original values were greater than 40 ng/mL showed some initial improvement, but follow-up has not been long enough for meaningful analysis. The response of the 13 patients presenting with elevated PAP is shown in Figure 15. Nine months after the implant all 6 of the patients tested had normal PAP levels. There was one persistent elevated PAP level starting in the fifteen- and twenty-one-month periods, but that

UROLOGY

/ JULY 1992 / VOLUME 40, NUMBER 1

Percentage of normal PAP values in 13 patients post implant (original PAP abnormal).

31

patient underwent bilateral orchiectomy, and at twenty-seven months his PAP level was again normal. In reviewing the 4 cases that have required bilateral orchiectomy because of rising PSA after seed implantation, case 1 (described in the aforementioned paragraph) originally had PSA of 89 ng/mL and PAP 8 mg/mL but had prostate cancer Stage B3, and Gleason score 5. Case 2 had a PSA of 22 ng/mL, PAP was normal, prostate cancer Stage B3, but the Gleason score was 7. Case 3 had Stage B2 prostate cancer with PSA of 22 ng/mL, but a Gleason score of 9. Case 4 had prostate cancer Stage A2 and Gleason score of 4, but re-biopsy specimen after the PSA began to rise showed a Gleason score of 8. Comment The long-standing controversy between radical surgery and ERT for the treatment of confined prostate cancer as delineated in the urologic and radiologic literature and fought to a draw ifi the 1987 consensus conference6 just became more complicated with recent advancements in the modality of brachytherapy. Transrectal prostatic ultrasound-guided lz51 seed implantation into the prostate combines the best of both worlds. It is a nonsurgical, outpatient procedure which does not have any mortality and is remarkably free of morbidity. It is relatively easy to perform, takes less than one hour, patients go home without a Foley catheter, and more than twice as much radiation is delivered as in conventional ERT. Our results with patients whose original PSA values were between O-20 ng/mL show a marked trend in normalization of PSA at all fol-

32

low-up periods. Even those patients with PSA values in the 21-30 ng/mL range showed the same trend but at a slower pace. These results and the data from the four treatment failures would indicate that patients with PSA values between O-20 ng/mL and/or Gleason scores of 6 or less are the ideal candidates for brachytherapy with lz51. Our treatment failures were considered distant failures, and they may have had metastatic disease at the time of the implantation. The obvious question is whether or not those patients would have failed radical surgery as well. Our answer is, “probably”; and if so, would they rather have had radical surgery or seed implant? The significant point is that a new treatment modality is available with curative intent for patients who are not good candidates for radical surgery or who prefer a nonsurgical approach. 13200 North 103rd Avenue, #35 Sun City, Arizona 85361 References 1. Holm HH, et cl: Transperineal ‘*sIodine seed implantation in prostate cancer guided by transrectal ultrasound, J Urol 103: 283 (1983). 2. Blasko JC, Ragde H, and Schumacher D: Transperineal percutaneous iodine-125 implantation for prostatic carcinoma using transrectal ultrasound and template guidance, Endocuriether Hypertherm Oncol 3: I31 (1987). 3. Stamey TA, McNeal JE, Freiha FS, and Redwine E: Morphometric and clinical studies on 68 consecutive radical prostatectomies, J Urol 139: 1235 (1988). 4. Priestley JB, et aE: Use of Mick Applicator in transperineal ultrasound-guided iesI seed implantation, J Endourol 4: 375 (1990). 5. Priestley JB, and Beyer DC: Balloon dilatation of the prostate after permanent ip51seed implantation, J Endourol 4: 389 (1999). 6. Consensus Conference: The management of clinically localized prostate cancer, JAMA 258: 2727 (1987).

UROLOGY

I

JULY 1992

I

VOLUME 40, NUMBER 1

Guided brachytherapy for treatment of confined prostate cancer.

A total of 133 patients underwent transperineal ultrasound-guided iodine 125 seed implantation for Stages A and B prostate cancer with a twenty-seven-...
1MB Sizes 0 Downloads 0 Views