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Role of acid phosphatase measurement in management of prostate cancer
ROLE OF ACID PHOSPHATASE MEASUREMENT IN MANAGEMENT OF PROSTATE CANCER
LESTER PHILIP
A. KLEIN, SHAPIRO,
M.D. M.S.
From the Department of Surgery-Urology, (Longwood Area) and Beth Israel Hospital,
Harvard Medical School Boston, Massachusetts
ABSTRACT - Serum acid phosphatase was measured in 155 people of whom 45 had prostate cancer and 110 were either normal or had other conditions, The assay did not discover early cases of prostate cancer but did reveal accurately patients with metastatic prostate cancer. The assay appears to be valuable for the purposes of staging the disease but not as a method of discovering patients with early fn-ms of prostate cancer. -___ --______---
A radioimmunoassay for the clinical detection of serum prostate acid phosphatase was presented by Foti et al. in 1977. 1 The test was shown to be significantly more sensitive than the enzymatic assay which was, at that time, almost universally applied. The authors proposed that the increased sensitivity would create “the potential for detecting well over half the cases of intracapsular (and thus surgically curable) prostatic carcinoma. ” It was hoped that the assay might become widely used to screen and detect early stage prostatic carcinoma. * The original report by Foti et al. 1 recorded the upper limit of serum acid phosphatase in normal men as 66 ng./ml. When applied to men with benign prostatic hyperplasia (BPH), this limit resulted in a “false” positive rate of 14 per cent. Foti et al. suggested, therefore, that the upper limit of normal be 88 ng./ml., and the “false” positive rate fell to 6 per cent. Since that presentation, assays have appeared with upper limit of normal values of 35,3 1O,4 and 85 ng./ml. It is unclear why successive assays yield lower values, but it has been suggested that better antigen purification methods6 or alternative sources of antigen5 may be responsible. Herein we describe the lowest value for normal serum acid phosphatase yet recorded. While it may be clinically easier, biochemically more accurate, and clinically more useful to
550
measure the immunologic activity rather than the catalytic activity of acid phosphatase, the precise role of the measurement in the management of patients with prostatic carcinoma is undefined and debated.‘B8 Based on the number of false positives reported by Foti et al. it has been estimated that a population of previously unscreened patients with a 5-per cent incidence of prostatic carcinoma would have a false positive rate of 57 per cent, and a population of unscreened men with an incidence of prostatic cancer approaching 1 per cent (which is more likely) would have a false positive rate of 87 per cent.s These projections appear to invalidate the test for widespread screening of previous unscreened, i.e., unexamined men. On the other hand, use of the radioimmunoassay for clinical staging of prostatic carcinoma may be valuable. The current study was designed to establish the parameters of this newer assay and to determine if it might prove advantageous in the clinical staging of prostatic carcinoma. Material
and Methods
Blood samples were obtained from 155 people including 36 volunteers, 13 patients who came to a private physician for nonurologic problems, 45 men with prostatic cancer, 33 men with benign prostatic hypertrophy, 16 men with tissue-proved nonprostatic cancer, and 12
UROLOGY
/
JUNE 1981
i
VOLUME XVII, NUMBER 6
TABLE I.
Clinical data
Acid Phosphatase Values (ng./ml.) No. of Patients
Category -_-______ Normal BPH CaP A B
47 36 7 11 7 14
C D
CaP after treatment Other Ca Women
7 (Z)
--~~____
Mean k SD 1.21 f 0.48 1.50 + 0.77
Range ~----------0.03-2.38 0.22-3.60
1.88 1.69 3.15 6.97 1.53 1.23 1.07
0.87-2.51 0.66-4.95 0.05-53.0 2.88-38.0 0.82-2.14 0.19-2.31 0.45-1.60
k 4 t + t k k
0.56 1.47 2.40 1.70 0.39 0.48 0.33
%> 2.50
#> 2.50 0
0
4
12
0
0
1 5 14 0 0 0
9 71 100 0 0 0
157
TOTAL
women. All the volunteers and patients with urologic problems were examined by a boardcertified urologist. Three patients of the private physician were disqualified from the study because of unverified prostate problems. Five blood samples were obtained after an operative procedure from patients who gave samples preoperatively; thus 157 determinations were made. Patients with prostate cancer were divided into Stages A, B, C, or D on the basis of recognized clinical or surgical procedures (x-ray film, lymphadenectomy, and examination of the tissue by the pathologist). A double antibody precipitation method was used for the radioimmunoassay.* All samples were run in duplicate; samples which showed variance in excess of 10 per cent were restudied. Enzymatic activity of acid phosphatase was done in the clinical laboratory of Beth Israel Hospital by the method of Gutman and Gutmane Results The radioimmunoassay values for acid phosphatase are plotted by diagnostic category in Figure 1 as a scattergram. If 2.5 ng./ml. is taken as an arbitrary cut-off point separating “normal” from “elevated” values, it is clear that none of the normal men, no men with treated prostatic cancer or other cancers, and no women had elevated levels. Three patients with Stage A cancer were on the borderline of normal, and none was elevated. All of the patients with metastatic prostate cancer had elevated values. Two patients -*Gamma-Dab Prostatic Acid Phosphate Radioimmunoassay Kit, provided by Clinical Assays, Cambridge, Massachusetts.
UROLOGY
________
/
JUNE 1961 /
VOLUME XVII, NuMBER 6
Gii -
>E
I(hn
pncrr c I .
,pli .
co
“!lW *
I
e
. :
,-. .
-*._
. . -. . .
??
.I--
I I i f t . -.
.
.
C
-
_-
.
.
. .
k . -
FIGURE 1. Scattergram showing radioimmunoassay value for prostatic acid phosphatase in nanograms per milliliter in all patients studied. Each dot represents one determination, and light horizontal bar is mean value for group. Dashed horizontal line is arbttrary dividing line drawn at 2.5 ng.Iml. It appears to separate most normal from most abnormal results.
with Stage C cancer (29 per cent) had normal values, and 1 patient with Stage B cancer (9 per cent) had an elevated value. Four patients with BPH (12 per cent) had elevated values. These last 7 patients will be described in detail. The mean values of acid phosphatase, the ranges and the percentage of patients with elevated values are shown in Table 1.
551
TABLE II.
determined
Summary of discordant values by radioimmunoassay (RIA) and enzyme assay
Diagnosis Normal BPH CaP A B
Elevated RIA Normal Enzyme
Normal RIA Elevated Enzyme
0
1
2
0
L
D CaP after treatment Other cancer Women
Two patients with clinical Stage C carcinoma had acid phosphatase values below 2.5 ng./ml. The first was a seventy-four-year-old man found to have a nodular prostate proved by needle biopsy to be cancer. Metastatic evaluation including bone scan and pelvic lymphadenectomy was negative. The assignation to Stage C was based primarily on physical examination because the patient underwent radiation therapy and not radical prostatectomy, thereby obviating pathologic staging. The radioimmunoassay value for acid phosphatase was 0.07 ng./ml., and the enzymatic acid phosphatase value was 2.4 units (normal < 3.0). The second patient was assigned Stage C based on the finding of a large prostate proved by biopsy to be cancer. There was no evidence of metastatic disease by either bone scan or x-ray film. The enzymatically determined acid phosphatase was 20.0 units. His age, seventy-six, and the fact that he had had a recent stroke obviated further evaluation, i.e., no lymphadenectomy was performed. The patient with Stage B prostatic carcinoma was a fifty-three-year-old man with mild symptoms of prostatic obstruction and a palpable prostate nodule. Although the radioimmunoassay value for acid phosphatase was elevated, the enzymatically determined value was normal and there were no signs of metastases. Pelvic lymphadenectomy and radical prostatectomy confirmed the diagnosis of Stage B cancer. Two weeks later, the acid phosphatase was 0.8 ng./ml. Four men with BPH had values in excess of 2.5 ng./ml. In one, the value was 2.59 ng./ml. Another had a value of 3.20 ng./ml. His prostate
552
was found to contain areas of fresh infarction and necrosis when examined by the pathologist. The last 2 patients were seventy-three and seventy-four years of age. Both presented with gross hematuria as the major manifestation of benign prostatic hypertrophy. Interestingly, both had histories of bladder neoplasia, but in neither case was there evidence of activity of that neoplasm. The enzymatically determined acid phosphatase was elevated in 1 man and normal in the other. Of the 157 samples studied in this series, 25 values were in excess of 2.5 ng./ml. There was coincident elevation of the enzymatically determined acid phosphatase in 18 of these cases, thus 7 patients had elevated radioimmunoassay values and normal enzymatically determined values. These data are shown in Table II. Also shown in Table II are two samples for which the enzymatically determined value was elevated while the radioimmunoassay value was normal. Comment This study was prompted by the suggestion of Foti et al. ’ that radioimmunoassay of acid phosphatase might be diagnostic of early prostatic carcinoma and therefore of use in screening previously unscreened males for this disease. That suggestion has been controversial, pro-’ ducing optimistic’ and pessimistic* evaluations. The results of our study do not support the contention of Foti et al. Only 1 patient with “curable stage,” i.e., Stage A or B prostatic carcinoma, had an elevated acid phosphatase, an over-all positive rate of 5.6 per cent. (Parenthetically, that 1 case was proved to be a false positive, so that the true positive rate is really 0 per cent). In Foti et al. ’ the positive rate was 50 per cent and 79 per cent for Stages A and B, respectively. Other authors have reported 12 per cent and 26 per cent,5 12 per cent and 32 per cent, lo 15 per cent,” and 0 per cent.” It seems clear that the optimism attending the initial report has to be tempered by the more recent experience. Is the radioimmunoassay superior to the enzymatically-based assay? The radioimmunoassay compares favorably with the enzymatic assay because the stability in serum of the measured product is better; the ease of handling and measuring the material by laboratory personnel is probably equivalent. Biologically, we have shown both false positives and false negatives with both methods, and these are very
UROLOGY
/
JUNE 1981 /
VOLUME XVII, NUMBER 6
well known. On these bases, therefore, the radioimmunoassay is preferable to the enzymatic assay. Every patient with proved metastatic disease in this study had an elevated acid phosphatase. Stage C disease is associated with lymph node metastases 33 to 90 per cent of the time depending on the size of the primary tumor,13 so it is not surprising that 5/7 (71 per cent) of the patients in the current series who were thought to have Stage C disease also had elevated acid phosphatase, It would require lymphadenectomy and biopsy to determine if the elevated acid phosphatase correlated with metastases, but it is worth noting that of the 2 patients with Stage C disease and normal acid phosphatase, one did not have nodal metastases and the other case is unproved. It seems clear that in the presence of metastases, elevated values will be found, and in their absence, values will be normal. Therefore, the proper role of the radioimmunoassay in management of prostatic cancer is to guide the clinician in the correct diagnosis of stage and that is the basis of treatment.r3,r4 Of great concern is the notion that this blood test (sometimes referred to as “the male PAP test”) will detect early prostatic carcinoma. This notion leads to two serious and detrimental consequences. First, the digital rectal examination of the prostate may be ignored. The rectal examination, despite its lack of elegance, remains the most sensitive test available for the detection of prostatic carcinoma.15 Second, the number of false positives may equal or exceed theenumber of early prostate cancers discovered. The morbidity and expense of exposing these false positives have not been calculated, but we are already aware of individual patients who have been harmed in the pursuit of the positive blood test only to find the prostate free
UROLOGY
/
JUNE
1981
/
VOLUME
XVII, NUMBER
6
of malignancy. The radioimmunoassay of acid phosphatase should not be a screening test; it should be ordered once the diagnosis has been made. Boston,
330 Brookline Avenue Massachusetts 02215 (DR. KLEIN)
References 1. Foti AG, Cooper jF, Herschman H, and .Malvaez RR: Detection of prostatic cancer by solid-phase radioimmunoassay of serum prostatic acid phosphatase, N. Engl. J. Med. 297: 1357 (1977). 2. Gittes R: Acid phosphatase reappraised, ibid. 297: 1398 (1977). 3. Rose NR, Choe B, and Pontes JE: Laboratory diagnmis of prostatic cancer, Lab. Manag. 16: 31 (1978). 4. Vihko P, et al: Serum prostate-specific acid phosphatase: development and validation of a specific radioimmunoassay, Clin. Chem. 24: 1915 (1978). 5. Mahan DE, and Doctor BP: A radioimmune assay for human prostatic acid phosphatase-levels in prostatic disease, Clin. Biochem. 12: 10 (1979). 6. Vihko P, Kon Huri M, and Korhonen LK: Purification of human prostatic acid phosphatase by affinity chromatography and isoelectric focusing. Part I. Clin. Chem. 24: 466 (1978). 7. Romas NA, and Tannenbaum M: Immunological detection of prostatic acid phosphatase, Critique I. Human Pathol. 9: 620 (1978). 8. Fink DJ, and Galen RS: Immunologic detection of prostatic acid phosphatase. Critique II. ibid. 9: 621 (1978). 9. Gutman AB, and Gutman EB: An acid phosphatase occurring in the serum of patients with metastasizing carcinoma of the prostate gland, J. Clin. Invest. 17: 473 (1938). 10. Griffiths JC: Prostate-specific acid phosphatase: reevaluation of radioimmunoassay in diagnosing prostatic disease, Clin. Chem. 26: 433 (19%). 11. Quinones G, Rohner TJ, Demers LM, and Drago JR: Will prostatic acid phosphatase determination by radioimmunoassay increase the diagnosis of early prostate cancer? Presented at the 75th meeting of American Urological Association, San Francisco, California, 1980. 12. Choe B, Rose N, Encole C, and Pierce JM: Clinical evaluation of immunological methods for detection of prostatic acid phosphatase, ibid. 13. Klein LA: Prostatic carcinoma, N. Engl. J. Med. 300: 824 (1979). 14. Lindholm GR, Stirton S, Liedtke RJ, and Batjer JD: Prostatic acid phosphatase by radioimmunoassay, JAMA 244: 2071 (1980). 15. Gilbertsen VA: Cancer of the prostate, ibid. 215: 81 (1971).
LESTER PHILIP
A. KLEIN, SHAPIRO,
M.D. M.S.
From the Department of Surgery-Urology, (Longwood Area) and Beth Israel Hospital,
Harvard Medical School Boston, Massachusetts
ABSTRACT - Serum acid phosphatase was measured in 155 people of whom 45 had prostate cancer and 110 were either normal or had other conditions, The assay did not discover early cases of prostate cancer but did reveal accurately patients with metastatic prostate cancer. The assay appears to be valuable for the purposes of staging the disease but not as a method of discovering patients with early fn-ms of prostate cancer. -___ --______---
A radioimmunoassay for the clinical detection of serum prostate acid phosphatase was presented by Foti et al. in 1977. 1 The test was shown to be significantly more sensitive than the enzymatic assay which was, at that time, almost universally applied. The authors proposed that the increased sensitivity would create “the potential for detecting well over half the cases of intracapsular (and thus surgically curable) prostatic carcinoma. ” It was hoped that the assay might become widely used to screen and detect early stage prostatic carcinoma. * The original report by Foti et al. 1 recorded the upper limit of serum acid phosphatase in normal men as 66 ng./ml. When applied to men with benign prostatic hyperplasia (BPH), this limit resulted in a “false” positive rate of 14 per cent. Foti et al. suggested, therefore, that the upper limit of normal be 88 ng./ml., and the “false” positive rate fell to 6 per cent. Since that presentation, assays have appeared with upper limit of normal values of 35,3 1O,4 and 85 ng./ml. It is unclear why successive assays yield lower values, but it has been suggested that better antigen purification methods6 or alternative sources of antigen5 may be responsible. Herein we describe the lowest value for normal serum acid phosphatase yet recorded. While it may be clinically easier, biochemically more accurate, and clinically more useful to
550
measure the immunologic activity rather than the catalytic activity of acid phosphatase, the precise role of the measurement in the management of patients with prostatic carcinoma is undefined and debated.‘B8 Based on the number of false positives reported by Foti et al. it has been estimated that a population of previously unscreened patients with a 5-per cent incidence of prostatic carcinoma would have a false positive rate of 57 per cent, and a population of unscreened men with an incidence of prostatic cancer approaching 1 per cent (which is more likely) would have a false positive rate of 87 per cent.s These projections appear to invalidate the test for widespread screening of previous unscreened, i.e., unexamined men. On the other hand, use of the radioimmunoassay for clinical staging of prostatic carcinoma may be valuable. The current study was designed to establish the parameters of this newer assay and to determine if it might prove advantageous in the clinical staging of prostatic carcinoma. Material
and Methods
Blood samples were obtained from 155 people including 36 volunteers, 13 patients who came to a private physician for nonurologic problems, 45 men with prostatic cancer, 33 men with benign prostatic hypertrophy, 16 men with tissue-proved nonprostatic cancer, and 12
UROLOGY
/
JUNE 1981
i
VOLUME XVII, NUMBER 6
TABLE I.
Clinical data
Acid Phosphatase Values (ng./ml.) No. of Patients
Category -_-______ Normal BPH CaP A B
47 36 7 11 7 14
C D
CaP after treatment Other Ca Women
7 (Z)
--~~____
Mean k SD 1.21 f 0.48 1.50 + 0.77
Range ~----------0.03-2.38 0.22-3.60
1.88 1.69 3.15 6.97 1.53 1.23 1.07
0.87-2.51 0.66-4.95 0.05-53.0 2.88-38.0 0.82-2.14 0.19-2.31 0.45-1.60
k 4 t + t k k
0.56 1.47 2.40 1.70 0.39 0.48 0.33
%> 2.50
#> 2.50 0
0
4
12
0
0
1 5 14 0 0 0
9 71 100 0 0 0
157
TOTAL
women. All the volunteers and patients with urologic problems were examined by a boardcertified urologist. Three patients of the private physician were disqualified from the study because of unverified prostate problems. Five blood samples were obtained after an operative procedure from patients who gave samples preoperatively; thus 157 determinations were made. Patients with prostate cancer were divided into Stages A, B, C, or D on the basis of recognized clinical or surgical procedures (x-ray film, lymphadenectomy, and examination of the tissue by the pathologist). A double antibody precipitation method was used for the radioimmunoassay.* All samples were run in duplicate; samples which showed variance in excess of 10 per cent were restudied. Enzymatic activity of acid phosphatase was done in the clinical laboratory of Beth Israel Hospital by the method of Gutman and Gutmane Results The radioimmunoassay values for acid phosphatase are plotted by diagnostic category in Figure 1 as a scattergram. If 2.5 ng./ml. is taken as an arbitrary cut-off point separating “normal” from “elevated” values, it is clear that none of the normal men, no men with treated prostatic cancer or other cancers, and no women had elevated levels. Three patients with Stage A cancer were on the borderline of normal, and none was elevated. All of the patients with metastatic prostate cancer had elevated values. Two patients -*Gamma-Dab Prostatic Acid Phosphate Radioimmunoassay Kit, provided by Clinical Assays, Cambridge, Massachusetts.
UROLOGY
________
/
JUNE 1961 /
VOLUME XVII, NuMBER 6
Gii -
>E
I(hn
pncrr c I .
,pli .
co
“!lW *
I
e
. :
,-. .
-*._
. . -. . .
??
.I--
I I i f t . -.
.
.
C
-
_-
.
.
. .
k . -
FIGURE 1. Scattergram showing radioimmunoassay value for prostatic acid phosphatase in nanograms per milliliter in all patients studied. Each dot represents one determination, and light horizontal bar is mean value for group. Dashed horizontal line is arbttrary dividing line drawn at 2.5 ng.Iml. It appears to separate most normal from most abnormal results.
with Stage C cancer (29 per cent) had normal values, and 1 patient with Stage B cancer (9 per cent) had an elevated value. Four patients with BPH (12 per cent) had elevated values. These last 7 patients will be described in detail. The mean values of acid phosphatase, the ranges and the percentage of patients with elevated values are shown in Table 1.
551
TABLE II.
determined
Summary of discordant values by radioimmunoassay (RIA) and enzyme assay
Diagnosis Normal BPH CaP A B
Elevated RIA Normal Enzyme
Normal RIA Elevated Enzyme
0
1
2
0
L
D CaP after treatment Other cancer Women
Two patients with clinical Stage C carcinoma had acid phosphatase values below 2.5 ng./ml. The first was a seventy-four-year-old man found to have a nodular prostate proved by needle biopsy to be cancer. Metastatic evaluation including bone scan and pelvic lymphadenectomy was negative. The assignation to Stage C was based primarily on physical examination because the patient underwent radiation therapy and not radical prostatectomy, thereby obviating pathologic staging. The radioimmunoassay value for acid phosphatase was 0.07 ng./ml., and the enzymatic acid phosphatase value was 2.4 units (normal < 3.0). The second patient was assigned Stage C based on the finding of a large prostate proved by biopsy to be cancer. There was no evidence of metastatic disease by either bone scan or x-ray film. The enzymatically determined acid phosphatase was 20.0 units. His age, seventy-six, and the fact that he had had a recent stroke obviated further evaluation, i.e., no lymphadenectomy was performed. The patient with Stage B prostatic carcinoma was a fifty-three-year-old man with mild symptoms of prostatic obstruction and a palpable prostate nodule. Although the radioimmunoassay value for acid phosphatase was elevated, the enzymatically determined value was normal and there were no signs of metastases. Pelvic lymphadenectomy and radical prostatectomy confirmed the diagnosis of Stage B cancer. Two weeks later, the acid phosphatase was 0.8 ng./ml. Four men with BPH had values in excess of 2.5 ng./ml. In one, the value was 2.59 ng./ml. Another had a value of 3.20 ng./ml. His prostate
552
was found to contain areas of fresh infarction and necrosis when examined by the pathologist. The last 2 patients were seventy-three and seventy-four years of age. Both presented with gross hematuria as the major manifestation of benign prostatic hypertrophy. Interestingly, both had histories of bladder neoplasia, but in neither case was there evidence of activity of that neoplasm. The enzymatically determined acid phosphatase was elevated in 1 man and normal in the other. Of the 157 samples studied in this series, 25 values were in excess of 2.5 ng./ml. There was coincident elevation of the enzymatically determined acid phosphatase in 18 of these cases, thus 7 patients had elevated radioimmunoassay values and normal enzymatically determined values. These data are shown in Table II. Also shown in Table II are two samples for which the enzymatically determined value was elevated while the radioimmunoassay value was normal. Comment This study was prompted by the suggestion of Foti et al. ’ that radioimmunoassay of acid phosphatase might be diagnostic of early prostatic carcinoma and therefore of use in screening previously unscreened males for this disease. That suggestion has been controversial, pro-’ ducing optimistic’ and pessimistic* evaluations. The results of our study do not support the contention of Foti et al. Only 1 patient with “curable stage,” i.e., Stage A or B prostatic carcinoma, had an elevated acid phosphatase, an over-all positive rate of 5.6 per cent. (Parenthetically, that 1 case was proved to be a false positive, so that the true positive rate is really 0 per cent). In Foti et al. ’ the positive rate was 50 per cent and 79 per cent for Stages A and B, respectively. Other authors have reported 12 per cent and 26 per cent,5 12 per cent and 32 per cent, lo 15 per cent,” and 0 per cent.” It seems clear that the optimism attending the initial report has to be tempered by the more recent experience. Is the radioimmunoassay superior to the enzymatically-based assay? The radioimmunoassay compares favorably with the enzymatic assay because the stability in serum of the measured product is better; the ease of handling and measuring the material by laboratory personnel is probably equivalent. Biologically, we have shown both false positives and false negatives with both methods, and these are very
UROLOGY
/
JUNE 1981 /
VOLUME XVII, NUMBER 6
well known. On these bases, therefore, the radioimmunoassay is preferable to the enzymatic assay. Every patient with proved metastatic disease in this study had an elevated acid phosphatase. Stage C disease is associated with lymph node metastases 33 to 90 per cent of the time depending on the size of the primary tumor,13 so it is not surprising that 5/7 (71 per cent) of the patients in the current series who were thought to have Stage C disease also had elevated acid phosphatase, It would require lymphadenectomy and biopsy to determine if the elevated acid phosphatase correlated with metastases, but it is worth noting that of the 2 patients with Stage C disease and normal acid phosphatase, one did not have nodal metastases and the other case is unproved. It seems clear that in the presence of metastases, elevated values will be found, and in their absence, values will be normal. Therefore, the proper role of the radioimmunoassay in management of prostatic cancer is to guide the clinician in the correct diagnosis of stage and that is the basis of treatment.r3,r4 Of great concern is the notion that this blood test (sometimes referred to as “the male PAP test”) will detect early prostatic carcinoma. This notion leads to two serious and detrimental consequences. First, the digital rectal examination of the prostate may be ignored. The rectal examination, despite its lack of elegance, remains the most sensitive test available for the detection of prostatic carcinoma.15 Second, the number of false positives may equal or exceed theenumber of early prostate cancers discovered. The morbidity and expense of exposing these false positives have not been calculated, but we are already aware of individual patients who have been harmed in the pursuit of the positive blood test only to find the prostate free
UROLOGY
/
JUNE
1981
/
VOLUME
XVII, NUMBER
6
of malignancy. The radioimmunoassay of acid phosphatase should not be a screening test; it should be ordered once the diagnosis has been made. Boston,
330 Brookline Avenue Massachusetts 02215 (DR. KLEIN)
References 1. Foti AG, Cooper jF, Herschman H, and .Malvaez RR: Detection of prostatic cancer by solid-phase radioimmunoassay of serum prostatic acid phosphatase, N. Engl. J. Med. 297: 1357 (1977). 2. Gittes R: Acid phosphatase reappraised, ibid. 297: 1398 (1977). 3. Rose NR, Choe B, and Pontes JE: Laboratory diagnmis of prostatic cancer, Lab. Manag. 16: 31 (1978). 4. Vihko P, et al: Serum prostate-specific acid phosphatase: development and validation of a specific radioimmunoassay, Clin. Chem. 24: 1915 (1978). 5. Mahan DE, and Doctor BP: A radioimmune assay for human prostatic acid phosphatase-levels in prostatic disease, Clin. Biochem. 12: 10 (1979). 6. Vihko P, Kon Huri M, and Korhonen LK: Purification of human prostatic acid phosphatase by affinity chromatography and isoelectric focusing. Part I. Clin. Chem. 24: 466 (1978). 7. Romas NA, and Tannenbaum M: Immunological detection of prostatic acid phosphatase, Critique I. Human Pathol. 9: 620 (1978). 8. Fink DJ, and Galen RS: Immunologic detection of prostatic acid phosphatase. Critique II. ibid. 9: 621 (1978). 9. Gutman AB, and Gutman EB: An acid phosphatase occurring in the serum of patients with metastasizing carcinoma of the prostate gland, J. Clin. Invest. 17: 473 (1938). 10. Griffiths JC: Prostate-specific acid phosphatase: reevaluation of radioimmunoassay in diagnosing prostatic disease, Clin. Chem. 26: 433 (19%). 11. Quinones G, Rohner TJ, Demers LM, and Drago JR: Will prostatic acid phosphatase determination by radioimmunoassay increase the diagnosis of early prostate cancer? Presented at the 75th meeting of American Urological Association, San Francisco, California, 1980. 12. Choe B, Rose N, Encole C, and Pierce JM: Clinical evaluation of immunological methods for detection of prostatic acid phosphatase, ibid. 13. Klein LA: Prostatic carcinoma, N. Engl. J. Med. 300: 824 (1979). 14. Lindholm GR, Stirton S, Liedtke RJ, and Batjer JD: Prostatic acid phosphatase by radioimmunoassay, JAMA 244: 2071 (1980). 15. Gilbertsen VA: Cancer of the prostate, ibid. 215: 81 (1971).