|Year : 2003 | Volume
| Issue : 2 | Page : 120-124
Effect of urinary retention on the levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in prostatic disease
R Chawla1, Rebecca Abraham1, U Arora1, Kim Mammen2
1 Department of Biochemistry, Christian Medical College, Ludhiana, India
2 Department of Surgery, Christian Medical College, Ludhiana, India
Department of Biochemistry, Christian Medical College & Hospital, Ludhiana - 141 008
Source of Support: None, Conflict of Interest: None
| Abstract|| |
In recent years, prostate specific antigen (PSA) has established itself as the most useful marker for adenocarcinoma of the prostate and has almost replaced the total acid phosphatase and prostatic acid phosphatase (PAP) for screening, diagnosis and monitoring the prostate carcinoma patients. The PSA levels also rise in benign hyperplasia of prostate (BPH) but to a lesser extent and high values are usually diagnostic of malignant disease. The present investigation was conducted to study the relevance of PAP estimation with or without PSA in prostatic disease particularly in the context of hospitalized patients with retention of urine. Levels of the 2 markers were estimated in 132 patients with prostatic disease and results correlated with histological findings. BPH was detected in 112 patients whereas 20 patients were diagnosed with adenocarcinoma (ADCA) of prostate. Majority of the patients in our study were referred from private clinics and 66.1 % of BPH and 50% of ADCA patients presented with acute urinary retention. Mean PSA and PAP levels in adenocarcinoma group were significantly higher (292.7 and 117.35 ng/ml, respectively) than in BPH group (7.05 and 1.92 ng/ml, respectively). It was observed that PSA levels were raised in BPH patients with urinary retention as compared to those with no retention. There was, however, no significant change in PAP levels in these patients. There was a very good correlation between the values of tumor markers (correlation coefficient: 0.86) in all the patients. Therefore, PAP is still a very good tumor marker of prostatic disease with almost comparable efficiency to that of PSA in differentiating the malignant from the benign disease. It appears to be particularly important in hospitalized patients with acute urinary retention as catheterization appears to raise the levels of PSA but not those of PAP.
Keywords: PSA, PAP, BPH, prostate, catheterization.
|How to cite this article:|
Chawla R, Abraham R, Arora U, Mammen K. Effect of urinary retention on the levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in prostatic disease. Indian J Urol 2003;19:120-4
|How to cite this URL:|
Chawla R, Abraham R, Arora U, Mammen K. Effect of urinary retention on the levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in prostatic disease. Indian J Urol [serial online] 2003 [cited 2020 Nov 28];19:120-4. Available from: https://www.indianjurol.com/text.asp?2003/19/2/120/37142
| Introduction|| |
Benign hyperplasia of prostate (BPH) is a common occurrence in all men above 60 years of age, whereas its malignant counterpart, carcinoma of prostate, is the leading cause of mortality amongst all the carcinoma in men. Prostatic acid phosphatase (PAP), a sialoglycoprotein with a molecular weight of 100,000  has been used for early screening and detection of prostate carcinoma in high risk group, , although its role in staging the carcinoma has been doubtful. , Prostate specific antigen (PSA), first identified by the Wang et al,  is a 237-amino acid monomeric serine protease, with a molecular weight of 33-34 kilodaltons.  It has shown considerable promise and has been acclaimed the best marker for prostate malignancy in recent years, although its plasma concentration also increases in BPH, but to a lesser extent. The reduced specificity of the two markers is further complicated by a number of pathological factors like prostatic infarct, acute bacterial prostatitis as well as acute urinary retention or digital rectal examination (DRE). ,
Since a majority of the prostate patients are referred to the hospital after urinary retention and catheterization, the levels of tumor markers may be falsely elevated in these patients. The present study was planned to see the effect of urinary retention on plasma concentration of PSA and PAP.
| Patients and Methods|| |
The serum samples were collected from 132 patients with prostatic disease, who presented at the urology clinic of Christian Medical College Hospital. The sera were stored frozen till analysis for PSA and PAP by radioimmunoassay. The biopsy or the tissue slices collected after transurethral resection of prostate (TURP) were sent to histopathology laboratory for the final diagnosis and the patients were grouped accordingly. A careful clinical examination including DRE was also performed. On the basis of biopsy reports 112 patients were diagnosed to have benign hypertrophy (BPH) and 20 patients adenocarcinoma (ADCA) of prostate. Serum PSA and PAP levels were estimated, in the blood samples drawn before digital rectal examination, by immunoradiometric (IRMA) assays using the commercial kits supplied by Diagnostic Products Corporation (DPC), USA. The PSA kit is based on ligand-coated tubes and three monoclonal anti-PSA (1 125 I-labelled and 2 ligand-labelled) antibodies. PSA in patient's serum is captured between the 2 monoclonals. Separation is achieved by ligand-coated tube/anti-ligand bridge method. The kit is designed to measure the total PSA (free PSA as well as the PSA bound to different proteins) in the patient's serum. The results were analysed with the help of a computer software (Epi-Info ver 6.0) designed specifically for hospital/epidemiological research work.
| Results|| |
The patients in the study ranged from 48 years to 95 years of age with maximum cases belonging to 6th or 7th decades of life. Majority of the patients in both the groups presented with symptoms of urinary obstruction, frequency of micturition, nocturia and hesitancy, whereas in the ADCA group 40% of patients presented with bone pain. About 50% of the ADCA and 67% of BPH patients in our study had urinary retention, signifying the advanced stage of disease in which the patient presented. Since the local stimulation of the prostate is known to influence the levels of the tumor markers, catheterization as well as DRE was performed after the collection of blood samples for PSA and PAP estimation in patients who were not catheterized on admission.
In general, both tumor markers showed significantly (p<0.01) higher concentrations in ADCA patients as compared to those with benign disease. All the ADCA patients, except one, had PSA as well as PAP levels elevated above the corresponding normal ranges. The serum PSA was elevated to greater extent (mean 292.7 ± 65.4 SE ng/ml) than PAP (mean 117.35 ± SE ng/ml) in these patients, whereas the corresponding values for the BPH cases were 7.05 ± 0.77 and 1.92 ± 0.11 ng/ml, respectively [Table - 1]. Within the BPH group, the mean PSA and PAP concentrations in patients with urinary retention were 8.59 ± 1.07SE and 1.97 ± 0.14 SE, respectively. The corresponding values for the no-retention cases were 4.07±0.80 SE and 1.85 ± 0.19 SE. The PAP range for BPH group was 0.0 to 5.6 ng/ml compared to ADCA range of 28.0 to 543.9 ng/ ml (excluding 1 patient mentioned above). 1 patient who had slightly elevated PSA (3.7 ng/ml) and normal PAP (1.5 ng/ml) values presented with abnormal DRE. The transrectal ultrasound (TRUS) showed normal homogenous echotexture and the prostate capsule was intact. The transrectal needle biopsy also proved inconsequential. The histological examination of the prostatic chips resected by TURP revealed the presence of adenocarcinoma of prostate.
Amongst the 74 BPH patients with urinary retention, 42 (56.8%) has elevated PSA [Table - 2],[Figure - 1]; 8 (10.8%) of these patients even showed PSA concentrations above 25 ng/ml. In the no-retention subgroup, only 11 out of 38 (28.9%) had above normal (>3.0 ng/ml) PSA concentrations and in none of these patients the PSA concentration was more than 25 ng/ml. The proportion of the patients with elevated PAP levels, on the other hand, was almost equal in retention (39.2%) and no-retention cases (44.7%). No patient in either of the groups showed PAP more than 10 ng/ml [Table - 3],[Figure - 1].
There was a good correlation in the values of PSA and PAP in the study [Table - 4]. The PSA values were always higher than PAP with significant overall correlation between the two (r=0.86). When the correlation was analyzed separately in the two groups, the two parameters were related closely (r=0.7 1) in the adenocarcinoma group whereas in BPH group the correlation (r=0.20) was not very good. The correlation coefficient in patients with and without urinary retention (ADCA + BPH) was 0.89 and 0.91, respectively. Regression of PSA over PAP [Figure - 2] showed that rise in PSA levels was sharper than that in PAP levels in the urinary retention group.
| Discussion|| |
Since the introduction of PSA into clinical use, investigators have continuously evaluated its performance as compared to PAP. In this study the relative merits of PSA vis a vis PAP in differentiating prostatic carcinoma from hyperplasia have been compared particularly with reference to the patients with acute urinary retention and catheterization.
There was a significant difference (p=0.0002) in the mean serum PSA levels in the adenocarcinoma patients and the BPH group. The mean PSA (7.05 ng/ml) in BPH group was also above the reference normal range and compares well with that reported in literature.  Fifteen (75%) of our patients had PSA levels higher than 100 ng/ml and only one patient with intracapsular disease showed normal PSA levels. Saraswati and Malathi  working with almost similar population of patients reported elevated PSA levels in all the 30 pretherapy adenocarcinoma patients.
The mean PAP concentration in adenocacinoma group was also significantly higher than in BPH group. Normal PAP was observed in 1 patient who also had normal PSA levels. The adenocarcinoma patients showed a wider range of elevations (up to 543.9 ng/ml) compared to BPH group where very mild elevations in PAP were observed. The mean PAP (1.9 ng/ml) in BPH group was also slightly above the upper normal limit, i.e., 1.8 ng/ml.
Most of our patients had moderately differentiated adenocarcinoma which could be another reason for the higher PSA and PAP values in the ADCA patients. The mean PSA and PAP values at various stages of the disease [Table 5] are similar to the findings of Stamey and Kabalin. , They evaluated PSA and PAP against the clinical stage and found that PSA correlated very well with the clinical stage, whereas PAP was much less discriminating even failing to distinguish extracapsular cancer. In the present study also, the patient with intracapsular disease had normal serum PAP levels (1.5 ng/ml) whereas the PSA levels were 3.7 ng/ml.
Urinary retention was one of the major presenting symptoms in our study. To study whether urinary retention was 1 of the confounding factors in raising the PSA and PAP levels, the patients in each group were subdivided into those with and without retention. More significant elevation in PSA were observed in patients with than in those without urinary retention. PSA levels as high as 40.6 ng/ml were observed in BPH patients with urinary retention. The PAP estimation on the other hand has proved to he unaffected by this complication as the increase in PAP levels distributed almost equally between the retention and no-retention cases. The mean PAP levels were also identical in the two. The PSA levels are increased in BPH patients presenting with urinary retention and values as high as l l 8.2 ng/ml have been reported  in such conditions, whereas elevations in the PAP have also been observed by a few workers.  The effect of urinary retention in elevations in PSA was further confirmed by significantly high odds ratio (OR) of 3.22 (95% conf. range 1.29 to 8.15). The corresponding OR for PAP was 0.80 (0.33 - 1.87) meaning the increase in PSA is closely associated with urinary retention in BHP patients, whereas PAP levels remain unaffected. Therefore, it appears that PAP is still a good marker for benign prostatic disease in which case it shows very mild alterations even in the presence of the complications like urinary retention which raise the PSA concentrations to the levels generally representing the cancerous state. This rise in the levels in PSA with urinary retention may be due to the retention pressure and/or physical stimulation by catheterization. Oremak and Seiffert studied 301 healthy volunteers and reported that physical activity increases the PSA levels by threefolds whereas PAP levels showed minimal elevations. Therefore, it appears that the amplitude of elevation of PAP levels in BHP patients is very low compared to PSA which suggested different mechanisms for increase in serum PSA and PAP levels. Further, all of the serum PSA might not be of prostatic origin in these cases, because PSA no longer enjoys the 100% tissue specificity acclaimed earlier.  The immunoreactive PSA might be contributed by periurethral glands  to some extent, particularly in patients with urinary retention.
In the present study, we have observed almost perfect correlation between the values of PSA and PAP [Table - 4]. Surprisingly, a very good correlation between the 2 markers was also found in cases with urinary retention [Figure - 2]. The rest of our data suggested that the PSA is raised in these patients, whereas PAP is unaffected. The high correlation coefficient in these patients, however, signifies that long with PSA, PAP is also raised in this condition but the rise in PSA is much sharper than that in PAP. The slope of PSA levels per unit rise in PAP was 2.8. The rise in PAP values by urinary retention and catheterization is too small to affect the average and cut-offs and hence the performance of the assay.
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[Figure - 1], [Figure - 2]
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]
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