Exploration of Serum Prostatic Specific Antigen Level in Enlarged Prostate with its Histopathological Correlation.

Introduction: Prostate lesions are of common occurrence in men, particularly in old age. Digital Rectal Examination (DRE) has remained a primary screening diagnostic aid for these lesions coupled with ultrasound and biopsies. The discovery of Prostate-Specific Antigen (PSA) has led to novel pathways in the detection of these lesions, particularly for malignant types. Hence this study was undertaken to correlate histopathological findings with PSA levels in a health care facility in Ranchi. Material and
Methods: The study was conducted in Rajendra Institute of Medical Sciences, Ranchi. Serum PSA values and histopathological evaluation of prostatic biopsies were conducted and correlated. Raised serum PSA levels were divided into three groups based on set values.
Results: A definite predilection for older ages was noted, with the 5th and 6th decades having the highest numbers of prostatic lesions. The sensitivity of PSA in the detection of carcinoma prostate cases was calculated to be 81.8%. The sensitivity of DRE was found to be 45.45% in the detection of cases of carcinoma of the prostate.
Conclusion: The current study demonstrated serum PSA levels to be a reliable front-line technique in assessing an individual's risk for prostatic lesions. Copyright:

INTRODUCTION

The prostate represents the most inflicted organ in males, particularly with increasing age. Important classes of prostatic disorders are inflammatory conditions (prostatitis), benign prostatic hyperplasia, and carcinoma.[1]

Prostatic Specific Antigen (PSA) secreted by prostatic epithelial cells is a serine protease. PSA levels in the blood increase when the normal glandular structure gets destroyed by inflammation or tumor (benign and malignant). Hence, PSA is considered as a marker for early detection and surveillance for cases of Prostate cancer. Serum PSA is analyzed by Immunoassay.[2] First identified by Wang et al. in 1979, PSA bears a significant impact in managing prostatic pathologies.[3]

Prostate gland enlargement results in retention of urine and dysuria, which directs as prostatectomy. Presently, there is an exponential rise in the prevalence of prostate lesions, of both neoplastic and non-neoplastic types, specifically among the elderly population. PSA is exclusively produced by the prostate gland. PSA is released into the bloodstream in pathological conditions, such as hyperplasia, tumors, or inflammation which may result in elevated serum PSA levels. Differentiation of tumor also plays a significant role in PSA range. Literature evidence documents raised levels of PSA in conditions of ischemia, inflammation, and infarction of the prostate gland.[4]

Presently, prostate cancer in the early stages is identified by PSA acting as a tumor marker.[5] The age of the patient and prostate size influence PSA levels. An increase of 3.2% every year is seen in healthy males without any signs of prostatic cancer. Geographical location can also alter PSA values. Considering this, the present study was undertaken as no studies are reported in this part of the country.

MATERIALS AND METHODS

The study was conducted on 60 cases of prostate enlargement, attending a surgical outdoor clinic, patients presenting to the surgical emergency department, and those admitted in different wards of the Department of Surgery, Rajendra Institute of Medical Sciences, Ranchi. The permission to carry out the study was obtained from the Institutional Ethical Committee of the parent hospital. Informed consent of all patients was obtained by the examiner after explicitly informing them about the study purpose. Cases included were patients aged above 50 years and presenting features of prostatic enlargement. A control group of 10 patients was also recruited for the study, without any presenting features of prostate enlargement.

Case history and DRE

A detailed case proforma of every patient eliciting the patient's demographic data, diet history, clinical history with stress on urine retention, prostatism history including symptoms of obstructive and irritative nature was obtained. This was followed by 3 ml of blood sample withdrawal by venipuncture technique for PSA estimation. Digital rectal evaluation (DRE) was then done to assess size, consistency, nodularity, asymmetry and median groove of prostate, and mobility of rectal mucosa over prostate.

Transabdominal ultrasound

A transabdominal ultrasound was done on all recruited patients, and those suspected of malignancy on DRE were further scanned by transrectal ultrasound.

Assay procedure

A blood sample was centrifuged at low speed and stored at 20°C till the time of analysis. PSA was quantitatively measured using the UBI MAGIWELL TM PSA quantitative test (Microwell ELISA). Reagents were kept at room temperature, concentrated, and then diluted. 20 μl of fresh sample diluent at serum standards of 1.5, 5, 15, 30, 60 ng/ml were dispensed into the appropriate well. 100 μl enzyme conjugate (anti-PSA antibody conjugated to horseradish peroxidase) was then added to each well and incubated for 20 minutes. 50 ml of 1 N H2 SO4 was then added to stop the reaction. A conventional ELISA machine read the optical density of the treated samples. Based on the PSA levels estimated, the cases were categorized into Group 1 – PSA levels <4 ng/ml; Group 2 – PSA levels between 4–10 ng/ml; Group 3 – PSA levels >10 ng/ml.

Transrectal prostate biopsy

It was done in cases detected with abnormal DRE results and PSA levels >4 ng/ml using a trucut prostatic biopsy needle No. 16G and under antibiotic prophylaxis. Laxatives and enema were administered prior to performing the procedure. Biopsy specimens were obtained from 8–10 sites, including the base, mid-portion, and apex of the prostate and were sent for histopathological evaluation. Based on the histopathological assessment, cases were categorized into three groups: Benign prostatic hyperplasia (BPH), Carcinoma of the prostate, and Prostatic Abscess.

Sensitivity analysis

Histopathological diagnosis was compared with PSA levels to determine the sensitivity and specificity of PSA assay.

RESULTS

The current study evaluated the relation of serum PSA levels in 60 cases of prostatic enlargement attending surgical OPD and surgical emergency of R.I.M.S. Ranchi.

The majority of the lesions were noted in the age group of 51–60 years, and most of them had a vegetarian diet [Table 1].

Table 1

Distribution of demographic information

Variables	Categories
Age (in years)	51-60	61-70	71-80
	24	21	15
Diet	Vegetarian	Non-Vegetarian
	48	12
Prostatic enlargement disorders	Carcinoma	BPH	Prostatic abscess
	11	48	2

The patients of prostatic enlargement presented with symptoms such as poor stream, hesitancy, terminal dribbling, the sensation of incomplete voiding, frequency, nocturia, etc. Many patients presented with retention of urine, and two patients had symptoms of bone pain.

Table 2 depicts PSA levels in various prostate lesions. 30% of the cases on DRE had malignancy of prostate, and other 70% of the patients demonstrated findings of benign enlargement of prostate.

Table 2

PSA levels detected in different prostate lesions

PSA (ng/ml)	Carcinoma	BPH	Prostatic Abscess	Total
<4	2	29	-	31
4-10	6	14	1	21
>10	3	4	1	8

The highest sensitivity to detect prostate enlargements (benign and malignant) was noted in the PSA levels with 81.8% as against 60.6% in the case of histopathological sectioning [Table 3]. This demonstrates that PSA levels represent the best screening test to detect prostate enlargements when compared to DRE, Ultrsonography (USG), and histopathological assessment.

Table 3

Sensitivity analysis of prostate lesions to DRE, USG, PSA values, and histopathological evaluation

Assessment	BPH + Prostatic abscess	Carcinoma
DRE examination
Benign enlargement	36	6
Malignant enlargement	13	5
Sensitivity=45.45%; Specificity=73.46%
PSA levels (ng/ml)
<4	29	2
>4	20	9
Sensitivity=81.8%; Specificity=59.18%
USG
Benign enlargement	33	7
Malignant enlargement	16	4
Sensitivity=36.6%; Specificity=67.34%
Histopathological examination
Benign enlargement	4	2
Malignant enlargement	9	3
Sensitivity=60.6%; Specificity=30.76%

DISCUSSION

Prostate lesions are of common occurrence in India, especially prostate cancer, with an increase in life expectancy and improved diagnostic techniques.[6] The present study reported that lesions were most commonly noted in the 5th decade of life (40%) and the 6th decade (35%). Khant SV et al.[7] reported similar findings with benign prostatic lesions occurring in the mean age of 57.7 ± 4.86 years. Shah RS and Pandey DR[8] also gave concordant results with their majority of BPH and Carcinoma Prostate in 61–70 years.

Though various studies have shown that a fatty diet is an important risk factor for carcinoma of prostate,[910] in the present study, no significant relation was observed between the non-vegetarian diet and carcinoma prostate. The probable reason is that none of the patients in the present study had taken animal fat in high amounts. So, no significant relation was observed between non-vegetarian diet and carcinoma prostate in this study, keeping in view the dietary pattern of patients. Among two cases of prostatic abscess, one patient had been taking a non-vegetarian diet and one, vegetarian diet.

Prostate diseases, of both benign and malignant nature, are hormone-dependent, resulting in a significant percentage of mortality and morbidity.[11] DRE and USG are preliminary screening tools with compromised sensitivity.[12] Although DRE does not stand as a reliable parameter for diagnosing prostate cancer, its simplicity makes it a popular diagnostic technique, and on the indication of malignancy, there is a 30–50% probability of carcinoma being detected on prostate biopsy.[13]

PSA is the most commonly employed diagnostic marker for prostate diseases. Only upon the alteration of the normal glandular architecture will the PSA be released to the systemic circulation.

In this study, the patients were grouped into three groups depending upon their serum PSA values. In Group-I, PSA value was less than 4 ng/ml; of 31 patients, two patients had carcinoma of the prostate, whereas 29 patients had benign prostatic hyperplasia-related enlargement of the prostate. In Group-II, patients having PSA value between 4 to 10 ng/ml were put, and of the 21 patients in this group, six patients had carcinoma of the prostate, whereas 14 patients had BPH-related enlargement of the prostate and one patient had enlargement due to Prostatic Abscess. In Group-III, with patients having PSA greater than 10 ng/ml, of eight patients, three patients had carcinoma of the prostate, and four patients had BPH-related prostatic enlargement and one patient had Prostatic Abscess. In the present study, the sensitivity of serum PSA value of greater than 4 ng/ml for detection of carcinoma of the prostate was 81.81%. This was also reported in several studies.[1415]

With the changing demographics of developing nations, it is imperative for males aged 40 years and above to get their PSA levels regularly monitored. This is particularly so in case of prostate disease running in families or manifestation of symptoms. Screening programs must be initiated by the health professionals and the Government to report the disease at the initial stage to ensure its complete cure. A multicentric study incorporating multi-regional and multi-state populations is contemplated to generalize the study findings.

CONCLUSION

There is a physiological increase in serum PSA level with an increase in age in the absence of any prostatic disease and symptom. The sensitivity of PSA in the detection of carcinoma prostate cases was calculated to be 81.8%. The sensitivity of DRE was found to be 45.45% in the detection of cases of carcinoma of the prostate. Thus, PSA has emerged as an important tumor marker for carcinoma of the prostate, and it can be used in the screening of carcinoma prostate cases from patients of prostatic enlargement. Serum PSA value helps in monitoring the response of treatment and disease recurrence or exacerbation after treatment in cases of carcinoma prostate.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.