A Study on Correlation of Serum Prostate Specific Antigen with Clinical and Pathological variables in patients of Prostatomegaly

Background: In clinical practice, biopsies are generally performed only when the results ofprostate specific antigen (PSA) test or digital rectal examination (DRE) are abnormal. This leads to misdiagnosis of most small prostatic cancers present in many older men. Patients with lower urinary tract infection (LUTS) who have serum PSA levels higher than 4ng/ml are primarily advised to undergo prostate biopsy to rule out cancer. However, PSA is organ specific not disease specific, so the presence of other prostate diseases such as benign prostatic hyperplasia (BPH) and prostatitis may influence its effectiveness for cancer detection. Hence, the PSA based prostate cancer detection is fraught with high false positive rate. Aim:To evaluate the utility of PSA assay as a method of investigation in diagnosis of prostatic lesion. Objectives: The use of Serum PSA levels for the early detection of prostate cancer and evaluate its role with other modalities for diagnosis of prostate cancer and to diagnose different diseases of prostate, i.e. prostatitis, BPH in prostatomegaly, and its correlation with Serum PSA levels. Materials and Methods: This prospective descriptive study was conducted in Index Medical College, Hospital & Research Centre, Indore, M.P,India in the period of August 2019 to July 2021. The patients were selected from the outdoor Department of General Surgery. Results: A total of 80 male patients presenting with LUTS were included. Their mean age was 68.66 years. The majority i.e. 41 of the study group were in the age group of 61-70 years. 42 of patients had Serum PSA < 4ng/ml. Biopsy proven adenocarcinoma cases 34% of the cases are in the age group of 61-70 years. Out of the biopsy proven adenocarcinoma cases, DRE was suspicious of malignancy in 89%. Conclusion: Serum PSA levels have a significant correlation with the age group, with the increase in age there is rise in Serum PSA levels. Transabdominal ultrasound, DRE and Serum PSA has high sensitivity in diagnosis of prostatomegaly but it was found that none of the screening tool has got much efficacy in differentiating carcinoma prostate from benign hypertrophy, but the combination of DRE and Serum total PSA or DRE, Serum total PSA and ultrasound abdomen showed higher efficacy in diagnosis of carcinoma prostate. Increase in Serum PSA is directly related to carcinoma, but there is no absolute cut-off for Serum PSAfor diagnosis of carcinoma. Key-Words: Prostate specific antigen, Prostatomegaly, Benign Prostatic Hypertrophy, Digital Rectal Examination, International Prostate Severity Score, Carcinoma Prostate.


Introduction
Prostate enlargement encompasses both benign hyperplasia of prostate (BPH) and carcinoma of prostate. Men with lower urinary tract symtoms (LUTS) are screened for prostate cancer with Serum prostate specific antigen (PSA) testing and digital rectal examination (DRE) as a part of routine prostate assessment. There is a general agreement among clinicians that the PSA test has the highest predictive value for prostate cancer as compared to DRE or trans rectal ultrasound. In clinical practice biopsies are generally performed only when results of a PSA test or DRE are abnormal. This leads to misdiagnosis of most small prostatic cancers present in many older men. The patients with LUTS who have Serum PSA levels higher than 4ng/ml are primarily advised to undergo prostate biopsy to rule out cancer. However, PSA is organ specific not cancer specific, so the presence of other prostate diseases like BPH and prostatitis may influence its effectiveness for cancer detection. Hence, the PSA based prostate cancer detection is fraught with high false positive rate.
Among the malignant tumors, the prostate cancer takes a high place worldwide. The incidence and mortality of disease show a big geographical difference. The increase in incidence started from 1980s. This rapid increase is due to extensive spread of determination of PSA. As a cause of death in men who die of malignancy, the prostate cancer is the third one. In general, the prostate cancer is the disease of the old population. The newly diagnosed patients are over 65 years. Thanks to screening programs, the prostate cancer becomes the disease of middle aged as well. On the contrary with decrease in incidence of prostate cancer in the old ages, there is a continuous rise in the 50-59 years population.
As an early detection of the cause of LUTS is necessary to offer selective treatment to the concerned subjects and also selecting patients for radical prostatectomy in organ confined disease, this study is an attempt to have a comparative analysis among the sensitivity, specificity and positive predictive value of DRE, Serum PSA and ultrasound.
This study may enable us to find out an ideal correlation between Serum PSA levels and various clinical parameters as well as biopsy reports so that a specific treatment can be instituted at an early stage.

Study design -
Cases of LUTS with prostatomegaly were selected from OPD who were detected to be having Grade I and above prostatomegaly. All patients were evaluated with DRE, ultrasound abdomen, Serum PSA levels and Biopsies of prostate (where indicated) and findings compared and inference drawn.
Study Technique-i. All patients worked up with detailed history, examination with GRE and investigations such as PSA, ultrasonography and prostatic biopsy where indicated.
ii. All patients off Grade 2 and above of prostatomegaly with other nodularity on DRE and or elevated Serum PSA levels underwent prostatic biopsy.
iii. Subsequent review of patients was done in the follow-up visits and findings noted in the Performa.
iv. In this study transabdominal USG size of prostate was evaluated and recorded as: Grade I-<30 g, Grade II-31-50 g, Grade III-51-80 g and grade IV-> 80 g.
The findings of systemic DRE performed was noted for all patients as subjective examination according to the following true findings: Hard swelling of the prostate, firm swelling, nodular swelling, irregular surface and obligation of middle sulcus attachment to the mucosa of the rectum. As a routine practice, DRE examination was scheduled after collection of blood sample to avoid an increase in Serum PSA that may follow digital manipulation of the gland.
Blood samples were collected in 5 ml sterile container containing ethylene diaminetetraacetic acid. The samples were centrifuged within 20 minutes after collection at 500x for 10 minutes and sera were stored at -20 degree Celsius until assay. The total prostate specific antigen was assessed using ELISA. PSA levels <4ng/ml were considered as normal, those between 4 and 10 ng/ml as diagnostic gray zone and >10 ng/ml as indicative of cancer.
All the patients were subjected to ultrasound examination and followed by biopsy if required. Ultrasound was performed using a real time Biplanar 4.0 MHz ultrasound probe.
Biopsies were done under antibiotic cover. Biopsies were taken with true cut biopsy gun from the base, mid gland and apex of the right and left side and also from any suspicious area. Each of the samples was submitted for pathological examination. The post intervention patients were kept for observation for 6 hours and discharged accordingly with the advice to continue antibiotic for 48 hours and to attend OPD or Emergency Room in case any problem such as hematuria, fever, dysuria or hemospermia arises.
Patients were followed-up firstly at three months interval and after 6 months interval.
Data were analyzed using the graphs and Chi-square testing.

Results
A total of 80 male patients with fresh LUTS were included in the study. Their mean age was 68.66 years (range 50-97 years). The patients were selected from the general surgery OPD of Index Hospital & Research Centre, Indore. <4ng/ml compared to 20(25%) in the range of 4 -10 ng/ml, and only 18(22.5%) with Serum PSA >10 ng/ml.     3 patients had Serum PSA between 4 and 10ng/ml and 9 patients had PSA > 10 ng/ml. 6 patients had Grade-IV Prostatomegaly on USG(>80 g) out of which 2 patients had Serum PSA < 4ng/ml, 2 patients had Serum PSA between 4 and 10 ng/ml and 2 patients had PSA >10ng/ml shown in Table 6.    Table 9 shows correlation of prostate size with IPSS score 31(38.75%) patients had mild score on IPSS and had prostatomegaly grade I, II, III and IV as 12(15%), 14 (17.5%), 5(6.25%) and 0 (0%), respectively. Among the patients having moderate IPSS score prostatomegaly grades were 6(7.5%), 19(23.75%), 12(15%) and 4(5%) respectiveely. Patients having severe IPSS score had 0(0%), 3(3.75%), 3(3.75%) and 2(2.5%), respectively. The majority i.e. 41 of study group was in the age group of 61-70 years. 42 of patients had Serum PSA <4ng/ml in the entire study group compared to 20 in the range of 4-10ng/ml and only 18 with Serum PSA >10 ng/ml. This shows that with the increase in age group the shift is towards increasing Serum PSA levels. The results of our study were comparable with PSA best practice statement 2009 age specific PSA range for Asian population, which also showed increasing Serum PSA levels with the increasing age.
On the other hand a study conducted by Lin et Al, showed that Serum PSA range for the age group of Taiwanese men was 0.8-1.7 ng/ml which was much lower than the mean Serum PSA in our study, this is probably due to the higher average Serum PSA levels in Eastern Indian population.
In our study among the biopsy-proven carcinoma cases, 33% of the cases are in the age group of 71-80 years (table 6).
These results are comparable with study conducted by Anushree and Venkatesh in which maximum incidence of adenocarcinoma was seen in the age group of 70-79 years.

Conclusion
Serum PSA levels correlates with the age group, with the increase in age that is rise in Serum PSA levels.
Transabdominal ultrasound, DRE and Serum PSA has high sensitivity in diagnosis of prostatomegaly but it was found that none of the single screening tool, that is Serum total PSA, DRE, or ultrasound has got much efficacy in differentiating carcinoma prostate from benign hypertrophy, but the combination of the DRE and Serum total PSA or DRE, Serum total PSA and ultrasound abdomen showed higher efficacy in diagnosis of carcinoma prostate. Increase in Serum PSA is directly related to carcinoma prostate, but there is no absolute cutoff for Serum PSA for diagnosis of carcinoma.