Effect of Extracorporeal Shock Wave Lithotripsy on Prostate Specific Antigen

00225347/96/1565-1682$03.00/0

VOI. 156,1682-1684, November 1996 Printed in U S A .

THE JOURNAL OF UROLOGY Copyright 0 1996 by AMERICAN UROL~CICAL ASSOCIATION,INC.

EFFECT OF EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY ON PROSTATE SPECIFIC ANTIGEN TH. COLOMBO, R. ZIGEUNER, ST. ALTZIEBLER, K. PUMMER, H. STETTNER

AND

G . HUBMER

From the Universitatsklinik fur Urologic, Karl-Franzens-UniversitatGraz, Graz, and Institute of Mathematics, University of Klagenfurt, Klagenfurt, Austria

ABSTRACT

Purpose: We evaluated the effects of extracorporeal shock wave lithotripsy (ESWL") of distal ureteral calculi on serum prostate specific antigen (PSA). Materials and Methods: A total of 29 consecutive men with distal ureteral calculi a t a maximum of 25 mm. from the ureteral orifice, and without any history of urinary tract infection, benign prostatic hyperplasia or prostate cancer underwent ESWL with the Dornier MPL 9000 X lithotriptor. The therapeutic focus size was 48 x 7 mm. PSA was measured exactly 5 minutes before ESWL, as well as 120 minutes, 24 hours and 7 days after termination of treatment. Results: Fragmentation rate was 100% and all patients were stone-free within 1 week of therapy. There was no statistically significant difference between PSA values before and after treatment. Only 15 patients had a slight increase in PSA a t 120 minutes after treatment (range 0.01 to 0.41 ng./ml., mean 0.07). Conclusions: ESWL can be performed in men at risk for prostate cancer without impairing the predictive value of PSA. KEY WORDS:extracorporeal shockwave lithotripsy, prostate-specific antigen, ureteral calculi

Prostate specific antigen (PSA), a kallikrein-like serine protease that is produced exclusively by the epithelial cells of all prostatic tissues, represents a valuable tool for the clinician, and is clearly the most important tumor marker for adenocarcinoma of the prostate.1.2 However, there are some difficulties in interpreting PSA because this marker is tissue specific rather than cancer specific, and is expressed by benign and malignant tissues. In addition, a variety of diagnostic and/or therapeutic procedures, such as cystoscopy, transrectal sonography, transrectal biopsy, transurethral resection of the prostate or radiation therapy, as well as prostatitis, physical exercise and numerous drugs may increase or decrease PSA, thus influencing accuracy of its measurement.%" Since 1990, extracorporeal shock wave lithotripsy (ESWL) has become the treatment of choice for distal ureteral calculi a t our institution.12 Because the diameter of the therapeutic focus of the ESWL machine used is greater than 45 mm., not only the stone but also adjacent structures, such as the prostate, are within a region of high mechanical energy. Therefore, we studied the effects of ESWL on serum PSA in men undergoing lithotripsy for distal ureteral calculi but without evidence of prostatic disease. MATERIAL AND METHODS

A total of 29 consecutive men 23 to 85 years old (mean age 50.8) with no history of urinary tract infection, benign prostatic hyperplasia or prostate cancer underwent ESWL for distal ureteral calculi on an outpatient basis. Digital rectal examination, performed in all patients older than 40 years, was normal and PSA was within the age specific reference range as proposed by Oesterling' (2 patients with slightly elevated PSA underwent prostate biopsy a t the end of the study to exclude prostate cancer). Only patients with stones within 25 mm. from the ureteral orifice were included in the study. Mean diameter of the calculi was 7 X 4 mm. (range 2 X 2 to 20 x 4, table 1). Accepted for publication April 12, 1996. * Dornier Medical Systems, Inc., Marietta, Georgia.

ESWL was performed with a Dornier MPL 9000 X lithotriptor, which has 2 different ultrasound locating systems (out line and in-line system) as well as a fluoroscopic location device. We exclusively used the in-line system, which also contains the shock wave generation module. During treatment the patient, with a full bladder, is placed prone with the lower abdomen directly on the in line probe. Mean duration of treatment was 35 minutes (range 16 to 521, and 200 to 2,100 shocks (mean 1,528) at 18 to 26 kV. (mean 22) with a maximum pressure of 530 bar in the therapeutic focus were administered to achieve satisfactory stone disintegration. The focus area was 48 X 7 mm. in diameter. PSA was measured using a fully automated PSA immunoassay. Serum samples were drawn exactly 5 minutes before ESWL, and 120 minutes, 24 hours and 7 days after termination of therapy. RESULTS

ESWL was effective in all patients with a fragmentation rate of 100% 1 day after treatment, and all patients were stone-free after 1 week according to abdominal x-ray and ultrasonography. Repeat treatment or auxiliary measures, such as stent placement after ESWL, were not necessary. These excellent results after ESWL are due to the fact that patients were highly selected with respect to ureteral calculi, that is only those with stones 25 mm. or less from the ureteral orifice were included in the study. Within that distance ultrasound guided localization of ureteral calculi is easy and safe. The reason for selection was due to the 48 x 7 mm. therapeutic focus of our lithotriptor, and we wished to guarantee that the calculi and prostate were within the focus. There was no statistically significant difference between PSA values before and after treatment. Only 15 patients had a slight increase in PSA at 120 minutes after treatment (range 0.01 to 0.41 ng./ml., mean 0.07, table 1).However, this difference was not statistically significant. There was no correlation among energy used, duration of treatment and changes in serum PSA concentration. For statistical analysis, Student's t test was used. Mean changes in PSA were

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TABLE1. Patient characteristics PSA (ng./ml.)

Pt ( .YAge d

Stone Size (mm.)

No. Shock Waves

Energy (kV.)

2,000 1,850 1,800 1,805 2,000 1,500 2,000 1,700 482 700 1,200 2,000 1,500 1,377 2,000 2,100 1,500 2,000 611 1,500 2,100 1,500 1,100 2,000 1,586 200 1,600 1,600 1,000

22 22 21 22 19 22 23 22 22 22 22 22 22 22 25 21 26 20 20 22 22 22 20 25 18 21 25 23 20 -

After ESWL

Before ESWL

2 Hrs.

24 Hrs.

7 Days

1.06 0.80 1.84 0.67 0.97 4.17 2.03 1.64 0.66 5.94 1.40 1.64 0.81 1.47 4.48 3.27 2.33 1.83 1.05 1.07 0.53 1.12 1.96 1.41 2.25 0.78 3.99 2.13 1.11

1.10 0.79 1.77 0.68 0.99 2.56 1.96 1.68 0.68 6.06 1.54 1.63 0.86 1.53 4.48 3.09 2.74 1.91 1.10 1.07 0.54 1.14 2.04 1.38 2.25 0.73 3.64 1.94 1.10

1.08 1.59 1.70 0.78 0.81 2.50 1.60 1.40 0.80 5.80 1.54 1.70 0.78 1.45 4.32 3.00 2.05 1.80 1.18 1.05 0.68 1.14 1.75 1.50 2.10 0.52 3.66 1.90 1.00

1.09 0.90 1.10 0.70 0.80 1.90 1.94 1.55 0.40 5.95 1.50 1.60 0.80 1.54 4.40 2.27 2.20 1.66 1.50 1.00 0.60 1.10 2.07 1.80 1.80 0.50 3.73 1.54 1.12

~

15 X 5 8 x 3 4x3 4 x 2 4x2 4 x 3 10 x 4 7 x 6 6 x 3 2 x 2 3 x 5 20 x 4 5 x 4 8 x 5 5 x 4 12 x 5 4 x 4 5 x 5 3 x 3 4 x 4 5 x 5 4 x 4 4 x 5 15 X 5 6 x 4 3 x 3 8 x 6 12 x 7 5 x 5

85 64 25 37 43 65 52 65 25 51 34 54 70 66 47 55 28 54 32 40 61 38 58 78 63 38 63 61 23

+1-1%after 2 hours, -2-7% after 1day and -5-7% after 7 days. Regarding the 95% confidence intervals, these changes were not significant because the observed changes were within the limits of the reported test variance or biological variance (table 21.10 DISCUSSION

Major changes in use of PSA as a tumor marker have occurred during the last decade. Within a short period numerous clinical and basic science observations have greatly Improved our understanding of this tumor marker and increased its clinical usefulness.1.11,13,14Recent data suggest that PSA will have a major role in identifying men with potentially curable cancer. A concept introduced to increase usefulness of PSA for detecting early prostate cancer is to monitor the rate of change in PSA with time, that is PSA velocity. Carter et a1 determined that a PSA velocity of 0.75 W m l . per year or greater indicated prostate cancer and warranted further evaluation.15 However, the usefulness and accuracy of minor PSA changes remain controversial, particularly since a variety of events or conditions may influence serum PSA. Digital rectal examination, transrectal ultrasonography, cystoscopy and prostate biopsy can cause spunOUS elevations in serum PSA, as can bacterial prostatitis and acute urinary retention.5.6.11 In this context, it is believed that rupture of the basement membrane causes diffusion of PSA into the capillary system, thus leading to elevated serum levels. Therefore, it is of utmost importance to learn about all conditions that potentially elevate serum PSA. ESWL for renal or ureteral stones is considered safe, only affecting the focused calculus and not damaging surrounding TABLE2. Mean changes in PSA Mean Change in PSA 95% Confidence Interval (% fmm baseline) (YO from baseline)

T~~~ ARer ESWL 2 Hrs. 1Day - 7 Days

+1(1%) -2 (7%) -5 (4%)

- 1(1%)-+3 (3%)

- 7 ( 8 % t + 2 (5%) -12 ( 9 % t + 2 (0%)

~

~~

tissue, although subcapsular renal hematomas have been reported after ESWL.12.16 In addition, the effects on pelvic structures, such as the ovary, have been controversial.17 We investigated the effects of ESWL on prostatic tissue via serial PSA determinations. Although high focal energy was used, we did not observe significant changes in serum PSA, which underscores the opinion that ESWL does not cause severe damage to the epithelial cells of the prostate. Minor changes in PSA, observed in half of our patients, did not reach statistical significance and may also be attributed to test or biological variances that may reportedly constitute up to 10% of cases.10 In addition, in these patients minor changes in PSA due to recumbancy are unlikely because treatment was performed on an outpatient basis. CONCLUSIONS

Our study suggests that ESWL can be performed in men at risk for prostate cancer without impairing the predictive value of PSA or PSA velocity for the disease. Since the observed changes in serum PSA did not exceed 0.41 ng./ml. 2 hours after therapy and returned to baseline after 1day, we conclude that PSA remains a reliable tool for detection of early prostate cancer even after high energy ESWL. REFERENCES

1. Oesterling, J. E.: Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J. Urol., 1 4 5 907, 1991. 2. Hara, M., Koyanogi, Y., Inoue, T. and Fukuyama, T.: Some physico-chemical characteristics of “gamma-seminoprotein,” an antigenic component specific for human seminal plasma. Forensic immunological study of body fluids and secretion. Jap. J. Legal Med., 2 5 322, 1971. 3. McCarthy, J. F., Catalona, W. J. and Hudson, M. A,: Effect of radiation therapy on detectable serum prostate specific antigen levels following radical prostatectomy: early versus delayed treatment. J. Urol., 151: 1575, 1994. 4. Willett, C. G., Zietman, A. L., Shipley, W. U. and Coen, J. J.: The effect of pelvic radiation therapy on serum levels of prostate specific antigen. J. Urol., 151: 1579, 1994.

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