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   Table of Contents      
ORIGINAL ARTICLE
Year : 2022  |  Volume : 8  |  Issue : 3  |  Page : 252-256

Effect of Chronic Urinary Retention over Serum Prostate-Specific Antigen and Its Role in Histopathological Diagnosis


1 Department of General Surgery, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Jolly Grant, Dehradun, Uttarakhand, India
2 Department of Urology, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Jolly Grant, Dehradun, Uttarakhand, India

Date of Submission17-Oct-2021
Date of Decision07-Nov-2021
Date of Acceptance13-May-2022
Date of Web Publication07-Dec-2022

Correspondence Address:
Sahil Verma
Jaisingh Hospital, Loharu Road, Charkhi Dadri, Haryana, 27306
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mamcjms.mamcjms_114_21

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  Abstract 


Background: Prostate-specific antigen (PSA) rises in all types of retentions and also in carcinoma prostate. The raised levels of PSA levels due to urinary retention may raise a false suspicion of carcinoma prostate in these patients. Unlike chronic urinary retention (CUR), the effect of acute urinary retention (AUR) on serum PSA levels had been studied in detail as evident from the past literature. Objectives: The objectives of the study were first to estimate and interpret serum PSA levels in adult males with CUR due to prostatic pathology, second to assess the need of taking prostatic biopsy based on the studied PSA trends, and finally to assess the prostatic histopathology in cases of persistently high PSA levels after 6 weeks. Materials and Methods: This was an observational follow-up study including 41 patients diagnosed with CUR due to prostatic etiology, matching the inclusion and exclusion criteria. On presentation, serum PSA levels were recorded. Retention was relieved by either per urethral catheterization or suprapubic catheterization. PSA levels were recorded after 24 hours, 1 week, 3 weeks, and 6 weeks and PSA trends were noted. Prostatic biopsy was advised for only those subjects in whom PSA did not attain the baseline value of 4 ng/mL within 6 weeks. The histopathological report of the biopsy was followed in each patient for studying its association with PSA trends. Results: Mean PSA at the time of presentation was 17.92 ng/mL. PSA trends showed that in the majority of the patients “Suspected benign group” (80.49%, n = 33), PSA returned to <4 ng/mL within 6 weeks of catheterization. Six patients, the “Borderline group” (14.63%), showed a downtrend in their PSA trends but could not attain baseline value. PSA trends in only two patients, the “Suspected malignant group” (4.87%), showed a comparative constant or an uptrend. All patients in the “Suspected benign group” and a majority of the “Borderline group” patients (83.33%) had a histopathologically confirmed benign prostatic pathology. Out of the two highly suspected malignant cases, only one patient (50%) had carcinoma prostate on final histopathology. Conclusion: PSA rises mainly in carcinoma prostate, but it falsely rises in all urinary retentions. The relationship between AUR and PSA had been studied in detail as evident from the past literature but needs to be established in patients with CUR. A period of 4 to 6 weeks can be safely employed for waiting for PSA to fall back to normal in CUR. A biopsy is required only for patients in which PSA is constantly high to rule out carcinoma prostate.

Keywords: Benign prostatic hyperplasia, catheterization, prostate-specific antigen, prostate


How to cite this article:
Verma S, Sarpal R, Agarwal S, Kim Mammen J. Effect of Chronic Urinary Retention over Serum Prostate-Specific Antigen and Its Role in Histopathological Diagnosis. MAMC J Med Sci 2022;8:252-6

How to cite this URL:
Verma S, Sarpal R, Agarwal S, Kim Mammen J. Effect of Chronic Urinary Retention over Serum Prostate-Specific Antigen and Its Role in Histopathological Diagnosis. MAMC J Med Sci [serial online] 2022 [cited 2023 Feb 1];8:252-6. Available from: https://www.mamcjms.in/text.asp?2022/8/3/252/362889




  Introduction Top


Urinary retention is the inability to voluntarily void urine. It can be acute urinary retention (AUR), chronic urinary retention (CUR), or acute on chronic urinary retention.

AUR is defined as “painful, palpable, or percussive bladder when the patient is unable to pass any urine.”[1] CUR is defined as a “painless bladder, which remains palpable or percussive after the patient has passed urine.”[1] The definition of CUR had always been controversial in terms of post-void residual volume (PVR). In compliance with the International Continence Society (ICS), American Urological Association has refined the definition as “PVR of more than 300 ml that had persisted for at least six months documented on two or more separate occasions.”[2] Collaborating both, CUR means painless retention where there is a chronic high PVR.

Urinary retention in adult males can be due to various causes, such as obstructive causes, infections, inflammatory conditions, trauma, pharmacological causes, and neurological causes.[3] “As many as 50% of men over 40 years of age may have lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH).”[4]

Serum prostate-specific antigen (PSA) is a gamma semino-protein, which mainly is secreted from prostatic tissue, specifically from the prostatic epithelium. Extra-prostatic PSA is very minor in amount and is contributed by periurethral glands, reflecting that PSA is highly organ specific.[5] PSA helps us to differentiate between benign and malignant prostatic enlargement. Also, it aids in guiding clinicians to suggest prostatic biopsy in suspected patients. The cutoff value of PSA for performing prostatic biopsies varies according to the geographical distribution of the disease and the patient’s age and depends on the trade-off between false positives and false negatives.[6] We have taken serum PSA cutoff of 4.0 ng/mL in our study.

Additionally, PSA may be raised in various other conditions apart from carcinoma prostate including bacterial prostatitis, urinary retentions, prostate biopsy, procedures like transurethral resection of the prostate (TURP), prostatic massage, catheterization, and digital rectal examination (DRE). Physiological processes such as ejaculation also lead to a minimal transient rise in PSA levels.[7],[8] From this knowledge, we infer that PSA is not only specific to carcinoma prostate, but may be falsely raised in many other conditions.

In this study, we will primarily focus on the relationship between PSA and urinary retention. The effect of AUR on serum PSA levels had been studied in detail as evident from the past literature. In contrast, there had been very little literature about the effect of CUR on the PSA kinetics. Based upon the knowledge of PSA trends in AUR, we aim to study the same in CUR.

The raised levels of PSA levels due to urinary retention may raise a false suspicion of carcinoma prostate in these patients. As gathered from previous studies for PSA kinetics in patients of AUR, a period of around 2 weeks is expected for PSA to return to the baseline. Keeping in mind the fact that the pathophysiology is different in CUR, we expect the time duration for PSA to return to baseline in CUR to be comparatively longer, as had been studied for AUR in the past. During this period, we aim at estimating and understanding the kinetics of serum PSA levels in adult male patients above the age of 40 years, with chronic or acute on chronic urinary retention. Since, at the time of presentation, PSA levels are usually high in almost all cases, there is always a clinical dilemma, whether the high PSA is due to the retention of urine or because of the carcinoma prostate.

Therefore, a single high PSA reading on a presentation may misguide the clinician in management. Also, it may cause unnecessary stress to the patient if suspicion of carcinoma prostate is predicted on presentation. On relieving retention by catheterization, PSA due to the retention part will fall down and because of the carcinoma prostate would remain elevated.

Secondly, our aim is to assess the need of taking prostatic biopsies based on the PSA trends. Finally, we aim to assess the histopathology examination findings. In this way, this would help avoid unnecessary prostatic biopsies usually taken at the time of presentation.


  Materials and Methods Top


This observational follow-up study was conducted in the Department of General Surgery, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, over a period of 12 months. A total of 41 subjects were recruited with CUR, matching the inclusion and exclusion criteria. With detailed clinical history and examination, patients for this study were evaluated by USG-KUB with prostate with PVR, serum PSA levels at the presentation by radioimmunoassay, and urine culture/sensitivity test. The patients were subjected to either per urethral catheterization (PUC) or suprapubic catheterization (SPC). PSA levels were again recorded after 24 hours, 1 week, 3 weeks, and 6 weeks, and trends were noted. Transrectal ultrasonography (TRUS) guided core needle prostatic biopsy was advised for only those subjects whose PSA did not attain the baseline value of 4 ng/mL after 6 weeks. The histopathological report of the biopsy was followed in each patient for studying its association with PSA trends.


  Results Top


The mean age of patients was 67.21 years (range 40–84). Most of the cases were in the 60 to 69 years of age group. Duration of symptoms was more than 6 months in all patients, out of which the maximum number of patients (82.9%) had symptoms less than 1 year. Initial PSA, that is, at the time of presentation before catheterization, and DRE was recorded, which showed that a maximum number of subjects (48.78%) had PSA in the range of 10.1 to 20.0 ng/mL with a mean value of 17.92 ng/mL [Table 1].
Table 1 Serum PSA at presentation

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Urinary retention was relieved by PUC in 39 subjects and by SPC in 2 patients. It was noted that a maximum number of subjects (48.78%) had PVR in the range of 300 to 800 mL. PSA trends as noted showed that in 33 out of 41 patients (80.49%), PSA returned to <4 ng/mL after 6 weeks of catheterization [Figure 1].
Figure 1 Attainment of baseline PSA with respect to time after catheterization. PSA, prostate-specific antigen

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Out of these 33 patients, PSA in 23 patients took even less than 6 weeks for returning to its baseline value. Eight patients had persistently raised PSA readings even after waiting for 6 weeks, out of which six patients (14.63%) showed a downtrend in their PSA trends but could not attain baseline value. PSA trends in only two patients (4.87%) showed a comparative constant or an uptrend. Based on the PSA trends and the histopathological nature of pathology suspected, they were categorized into three groups: benign (80.49%, n = 33), borderline (14.63, n = 6), and suspected malignant (4.87%, n = 2) [Table 2].
Table 2 PSA trends during a period of 6 weeks and categorization of subjects into groups based upon the pathology suspected from the PSA trends

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The patients with suspected benign pathology were subjected to TURP, whereas the patients with PSA >4 ng/mL after 6 weeks were all subjected to TRUS guided prostatic biopsy at the end of 6 weeks [Table 3].
Table 3 Assessment of intervention done after 6 weeks of catheterization according to groups and correlating the histopathological findings

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All patients suspected to have a benign pathology based upon PSA trends showed a final HPE confirmed benign prostatic pathology. The borderline group showed a maximum number of patients (83.33%) with a benign prostatic pathology as evident from the biopsy report. Out of the two highly suspected malignant cases, only one patient (50%) showed malignant prostatic pathology [Table 3].


  Discussion Top


Urinary retention is the inability to voluntarily void urine. It can be AUR, CUR, or acute on chronic urinary retention. CUR is painless urinary retention with chronically raised PVR. PSA is an invaluable marker in making the diagnosis of prostate cancer. It helps in differentiating benign from malignant prostatic enlargement. PSA may be falsely raised in other conditions, such as prostatic inflammation, urinary retentions, and per-urethral instrumentation. PSA may be temporarily raised in AUR as reported in the past literature, but very rare data exist in the literature for CUR. It is not uncommon for clinicians to assay PSA at the time a patient presents with CUR. We sought to evaluate whether this practice can be justified based on the past knowledge of PSA kinetics in AUR.

This study dealt with obtaining PSA levels at different time intervals during a period of 4 to 6 weeks and study PSA kinetics in patients with CUR. Based on this, the need of taking prostatic biopsies can be ascertained and also testing of PSA levels in urinary retention can be avoided to minimize false-positive results and implications thereof.

In CUR, we observed that there was a drastic decline in PSA values from the previously measured value till 6 weeks. We excluded patients with established non-prostatic etiology of CUR, established cases of carcinoma prostate and all those patients with UTI, and those with serum PSA measured at the time of presentation <4 ng/mL.

The mean value of initial PSA at the time of presentation was 17.92 ng/mL. Hicks in his case report over AUR in BPH patients and associated PSA elevations noted that it might rise to extremely higher levels in the setting of AUR to the levels as high as 232 ng/ml.[9] In the study conducted on AUR patients by Aliasgiri et al., this value was 9.8 ng/mL.[10] This suggests that the patients with CUR can have a much more rise in serum PSA values as compared to AUR. The possible mechanism of the rise may have a correlation with prostatic micro-infarction, which goes with the conclusions from Spiro et al. in their comparative study of over 200 subjects in which 100 patients with large prostate and AUR were compared with 100 patients posted for elective surgery for BPH. The HPE comparison between the two groups showed that 85% of patients in the first group having HPE confirmed prostatic infarction compared to only 3% in the comparative group.[11]

PSA levels were monitored at regular intervals post de-obstruction in all 41 patients. The need for considering prostatic biopsy was ascertained at each follow-up looking at the PSA levels.

According to Shalini et al., in their study of 4702 patients with LUTS and clinical prostatomegaly, the cutoff for prostatic biopsy in symptomatic men with negative DRE could be safely elevated to 5.4 ng/mL.[12] In this study, cutoff values of PSA of more than 4 ng/mL have been taken as suspicious of malignancy and need confirmation. Using this cutoff, subjects eligible for TRUS guided prostatic biopsy at different phases of study were identified, as shown in [Table 4].
Table 4 Subjects eligible for TRUS guided prostatic biopsy at different phases of study

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In 33 patients, PSA showed a downtrend with a return to <4 value within 6 weeks. This was comparable to the results attained by Aliasgari et al. in their study in 2005 for patients with AUR. According to their study, PSA is raised in AUR by up to twofold and may take up to 2 weeks to return to its baseline value. This in other words suggests that PSA testing at presentation may give a falsely raised value. Therefore, 2 weeks time period can be employed to safely wait to undergo PSA testing in AUR.[10]

Only eight patients, who had persistent elevated PSA at 6 weeks, underwent TRUS guided core needle biopsy, thus fulfilling the second aim of this study. Out of these eight patients, a majority of six patients showed a downtrend in their PSA trends, when initial and the final PSA readings were compared. PSA trends in only two patients showed a comparative constant or an uptrend [Table 2].

Based upon the PSA trends, they were categorized into three groups: suspected benign, suspected borderline, and suspected malignant. The patients with suspected benign pathology were subjected to TURP, whereas the rest were subjected to TRUS guided prostatic biopsy at the end of 6 weeks.

However, the etiology of CUR in terms of HPCR and LPCR was not ascertained in the present study as suggested by Abrams et al. in their study of “urodynamic findings in CUR of urine and their relevance to results of surgery” in 55 patients.[13] This was also found to be one of the limitations of the study.

Looking at the PSA trends, all patients suspected to have a benign pathology showed a final HPE confirmatory of benign prostatic pathology, thus fulfilling the first and third aims of the study. The HPE of the patients in the borderline group showed a maximum number of patients with a benign prostatic pathology (83.33%). Out of the two highly suspected malignant cases, only one patient (50%) showed malignant prostatic pathology [Table 3].

Summarizing the limitations of this study, the study employed PUC in most of the patients as a method to relieve retention, which might cause an alteration in PSA levels. Also, the catheterization for a longer duration as compared to AUR and generally is associated with patient’s discomfort and noncompliance. Also, it may itself lead to UTI and catheter-induced complications. Also, the study did not employ urodynamic studies in the followed up patients before TURP. So, we could not differentiate between HPCR and LPCR. Finally, the short sample size makes it difficult to standardize management guidelines for CUR patients.


  Conclusion Top


From this observational follow-up study done on 41 male patients presenting with features of CUR due to prostatic etiology, we can conclude the following:
  • It is a known fact that PSA rises in carcinoma prostate, but it falsely rises in all urinary retentions.
  • On relieving CUR, the majority of the patients will have PSA back to its baseline within 4 to 6 weeks and do not thereby need a prostatic biopsy or further evaluation/tests.
  • Looking at the PSA trends post de-obstruction, one can estimate or predict the nature of prostatic pathology.
  • Biopsy is required only in patients in whom PSA is constantly high to rule out carcinoma prostate.
  • New recommendations for CUR need to be established and standardized.




 
  References Top

1.
Abrams P, Cardozo L, Fall M et al. The standardization of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology 2003;61:37–49.  Back to cited text no. 1
    
2.
Abrams P, Cardozo L, Fall M et al. Standardisation Sub-Committee of the International Continence Society. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology 2003;61:37–49. doi: 10.1016/s0090-4295(02)02243-4. PMID: 12559262.  Back to cited text no. 2
    
3.
Choong S, Emberton M. Acute urinary retention. BJU Int. 2000;85:186–201.  Back to cited text no. 3
    
4.
Fauci AS, Hauser SL, Jameson JL, Kasper DL, Longo DL, Loscalzo J. Urinary tract obstruction. In: Seifer JL, ed. Harrison’s Principles of Internal Medicine. 19th ed. New York: McGraw-Hill Education; 2015. p. 1872.  Back to cited text no. 4
    
5.
Iwakiri J, Grandbois K, Wehner N, Graves HC, Stamey T. An analysis of urinary prostate specific antigen before and after radical prostatectomy: evidence for secretion of prostate specific antigen by the periurethral glands. J Urol 1993;149:783–6.  Back to cited text no. 5
    
6.
Punglia RS, D’Amico AV, Catalona WJ, Roehl KA, Kuntz KM. Effect of verification bias on screening for prostate cancer by measurement of prostate-specific antigen. N Engl J Med 2003;349:335–42.  Back to cited text no. 6
    
7.
Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987;317:909–16.  Back to cited text no. 7
    
8.
Kawakami J, Siemens DR, Nickel JC. Prostatitis and prostate cancer: implications for prostate cancer screening. Urology 2004;64:1075–80.  Back to cited text no. 8
    
9.
Hicks RJ. Elevated prostate-specific antigen: a case report and analysis. J Fam Prac 1993;37:284–288.  Back to cited text no. 9
    
10.
Aliasgari M, Soleimani M, Hosseini Moghaddam SM The effect of acute urinary retention on serum prostate-specific antigen level. Urol J 2005;2:89–92. PMID: 17629877.  Back to cited text no. 10
    
11.
Spiro LH, Labay G, Orkin LA Role in acute urinary retention.Urology 1974;3:345–347.  Back to cited text no. 11
    
12.
Agnihotri S, Mittal RD, Kapoor R, Mandhani A Raising cut-off value of prostate specific antigen (PSA) for biopsy in symptomatic men in India to reduce unnecessary biopsy. Indian J Med Res 2014;139:851–856. PMID: 25109719; PMCID: PMC4164997.  Back to cited text no. 12
    
13.
Abrams PH, Dunn M, George N. Urodynamic findings in chronic retention of urine and their relevance to results of surgery. BMJ 1978;2:1258–60.  Back to cited text no. 13
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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