Effect of digital rectal examination on prostate specific antigen levels among patients with lower urinary tract symptoms in Uganda

doi:10.21203/rs.3.rs-2121937/v1

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Effect of digital rectal examination on prostate specific antigen levels among patients with lower urinary tract symptoms in Uganda

https://doi.org/10.21203/rs.3.rs-2121937/v1

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Introduction

Prostatic cancer is a major contributor to mortality among men globally. Prostate-specific antigen (PSA) is a screening investigation for cancer of the prostate. The combination of serum PSA and digital rectal examination (DRE) allows early detection of prostate cancer. Studies have revealed that DRE causes an elevation in serum PSA levels. This rise following DRE may be mistaken for the rise associated with malignancy. Most clients in our setting come to the urology clinic as referrals from primary physicians when DRE has been done. There is a significant knowledge gap regarding whether the PSA change following DRE is significant enough to warrant withholding PSA measurement in these patients that come after having DRE; the reason this study was done.

Methods

This was a single centre prospective longitudinal study done at Ishaka Adventist hospital in which an interviewer administered questionnaire was filled for each patient that consented. After filling the questionnaire, a venous blood sample was drawn, DRE done and 1-hour later, another blood sample drawn. Total PSA was measured for both samples and data analyzed using SPSS version 22.

Results

Data for 102 participants was analyzed, whose mean age was 61.85 ± 12.73 years. The paired samples T test revealed a small mean increase in PSA following DRE (0.40 ng/ml) that was not significant (p = 0.061). The number of patients whose clinical decision would be affected (changed) by the PSA measured after DRE was 3 (2.9%, CI = 0.0%-6.9%) if cutoff was 3 ng/ml and 2 (2.0%, CI = 0.0%-4.9%) at 4 ng/ml cutoff. The confidence intervals in both scenarios included 0.0%, suggesting that there would be no significant effect on the clinical decision if the PSA was done post DRE.

Conclusion. DRE can be used in screening and clinical assessment of prostate cancer without fear of interfering with PSA result interpretation and patient management.

Prostate specific antigen

Digital rectal exam

Prostate cancer

Prostatic malignancy is the second commonest cancer and major contributor to mortality among males in Sub-Saharan Africa, ranking fifth globally (1). Over the last 20 years, in sub-Saharan Africa alone, there has been increase in diagnosis and mortality arising from several malignancies attributed to change in way of life, behaviors and environment (2). In Uganda prostate cancer rate was reported to be 65.0 per 100,000, with a mortality-to-incidence ratio of 71% (3).

Prostate-specific antigen (PSA) is a screening investigation for cancer of the prostate and also gives information about the extent of the malignancy, as well as the disease trajectory during monitoring and therapy (4). Once a year, men at the age of 50 or more should visit a urologist to have a clinical examination of the prostate through the rectum in addition to prostate specific antigen laboratory investigation (5). For those with a family history of prostate cancer or an afro descent, this check should start at the age of 40.(5). Total prostate specific antigen above 4 ng/ml is currently considered pathologic, and values above 10 ng/ml are strongly suggestive of cancer (6). Concepts including age cutoff, PSA velocity and free PSA were created to improve PSA sensitivity (7). PSA is known to be a prostate-specific marker but procedures such as DRE, colonoscopy and prostate biopsy can change PSA levels (8). PSA levels are thought to rise in direct proportion to the procedure's stimulation intensity (9).

The serum PSA test and digital rectal examination (DRE) allow doctors to detect prostate cancer when it is still in its early stages (10). Studies have revealed that DRE causes an elevation in serum PSA levels (11). Following DRE, the PSA starts to raise at 10 munities, reaches its highest level at 1 hour and the effect can last up to 3 weeks (12). This rise following DRE may be mistaken for the rise associated with malignancy of the prostate resulting in miss-diagnosis when PSA is used to screen (10, 13). For this reason, it has been recommended to perform PSA before DRE (14). Currently, both digital rectal examination and prostate specific antigen done at the same time are recommended for prostate cancer screening because this technique offers up to 75% diagnostic sensitivity for prostate carcinoma (14, 15).

PSA testing, digital rectal exam (DRE), and prostate biopsy are the cornerstone of prostate cancer screening (15). Most clients in our setting come to urology clinic as referrals from primary physicians when DRE has been done. This pauses a challenge in interpretation of PSA test values with potential for many falsely positive results resulting in unnecessary invasive procedures, pain, erectile dysfunction, and urinary incontinence, as well as prostate cancer over diagnosis and overtreatment. There has been a significant knowledge gap regarding the extent to which DRE increases PSA levels and whether this change could lead to DRE being withheld before PSA measurement in prostate cancer screening. This study was aimed at assessing the extent of PSA change following DRE among men above 40 years presenting with lower urinary tract symptoms (LUTS).

Study design

The study was a single Centre prospective longitudinal study

Study Setting.

The study was done at Ishaka Adventist Hospital (IAH) which is located in Ishaka municipality Bushenyi district approximately 60 kilometers (39 miles) West of Mbarara district in western Uganda. IAH has two surgeons running the surgical clinic, it treats 50 patients seeking urology care in a month. Patients were reviewed from the outpatient department from Monday to Friday. The hospital has a fully functional laboratory that caters for PSA testing and theater services for prostate biopsy.

Study Population

The study targeted men above 40 years in Bushenyi district, that presented with lower urinary tract symptoms (LUTS) to the outpatient clinic during the period of the study.

Sample Size Determination

Daniel formula (16); n = Z_1−α/2²p(1-p) / d² was used to determine the sample size, where n = estimated minimum sample size required, P = proportion of characteristic in a sample, Z_1−α/2=1.96 (for 95% Confidence interval), e = Margin of error set at 5%. Using findings by (17) who reported the incidence of cancer of the prostate to be 6.4% in Uganda, n= (1.96)² x 0.064 (1-0.064)/ (0.05)², n = 92. To increase the internal validity of study and catering for non-responders, the calculated sample size was increased by 10% giving an estimated sample size of 102.

Sampling Technique

Consecutive recruitment was used until the desired sample size was achieved. Male patients who presented to the surgical outpatient department with LUTS were enrolled following informed consent.

Eligibility Criteria

Inclusion criteria

Men above 40 years with LUTS at surgical outpatient department who consented to participate in the study

Exclusion criteria

Patients with indwelling urethral catheters were excluded in addition to those with a history of prostatectomy, those who had undergone trans-rectal ultrasound scan over the previous one month and those with a history of urogenital trauma.

Data Collection Procedure And Psa Measurement

All patients that were eligible for the study signed a Kampala international university Research and Ethics committee (KIU-REC) format consent form after explaining to them the details of the consent. After consenting, a questionnaire that was pretested and interviewer administered was filled for each patient that consented. After filling the questionnaire, a sample of Venus blood was drawn aseptically for PSA analysis. A digital rectal exam was done and then 1-hour later, another sample for PSA testing was drawn and all samples were analyzed in the hospital laboratory. Patient’s venous blood was collected in a sterile Vacutainer tube without anticoagulant and centrifuged for serum separation and total serum PSA was measured using, i chroma machine (i-CHROMA™). The same machine was used for all samples.

Digital rectal examination

Patient was positioned in the left lateral position with the left leg extended and the right flexed at the knee in the doctor’s examination room with adequate privacy. A double gloved index finger was gently introduced into the rectum via the anal opening after lubricating with K-y jelly. Using the index finger, the prostate was palpated, and assessment made as to whether it is enlarged or not, symmetrical or asymmetrical, nodular or non-nodular, soft, firm or hard, tender or non-tender, palpable groove or obliterated groove, with free mucosa or fixed mucosa. The findings were documented after cleaning the perianal area.

Quality Control

Inclusion and exclusion criteria were strictly adhered to. The research team was instructed on how to administer the questionnaire. The data collection tool was cross checked for completeness. The same equipment was used to measure PSA for all samples. Controls were run regularly.

Data analysis and presentation

Data was coded and entered in excel sheet, and analyzed using SPSS version 22. Frequencies and percentages were used to describe categorical variables while mean and standard deviation were used for continuous variables. To determine the change in PSA following DRE, the PSA values for the patients before and after DRE were entered as continuous variables. Using the paired samples T test procedure, the mean difference between the pre and post DRE PSA level was determined with the corresponding standard deviation and p value. If the corresponding p value was less or equal to 0.05, the difference was considered significant. The values of pre and post DRE PSA were compared for each patient to determine if the post DRE PSA would have affected (changed) the clinical decision in order to assess the clinical significant of the PSA changes.

During the study period, 114 patients presented to the study centre with a history of lower urinary tract symptoms. 10 of the 114, had a urethral catheter inserted before arrival to the study centres. 2 of the remaining had prostatectomy in the previous years. PSA was done for 102 patients as shown in Fig. 1.

Social-demographic characteristics of the study participants

In this study, the mean age of the participants was 61.85 ± 12.73 years and the mean BMI was 24.27 ± 4.17. Majority of the participants were from the rural areas (80.4%), married (92.2%), with maximum level of education as primary (60.8%) and peasants (64.7%) as shown in Table 1.

Table 1

shows the social-demographic characteristics of the study participants.
Characteristic	Statistic
Age	Mean = 61.85, SD = 12.73, Min = 40, Max = 95
Body mass Index (BMI)	Mean = 24.27, SD = 4.17, Min = 14.53, Max = 38.57
	Frequency	Percentage
Age Category
40–50	23	22.5
51–60	26	25.5
61–70	26	25.5
71–80	21	20.6
81–100	6	5.9
BMI Category
14.53–18.50	6	5.9
18.51–29.99	90	88.2
30.00- 38.57	6	5.9
Residence
Rural	82	80.4
Urban	20	19.6
Marital status
Married	94	92.2
Single	3	2.9
Windowed	4	3.9
Divorced	1	1.0
Education Level
Primary	62	60.8
Secondary	22	21.6
Tertiary	16	15.7
No Education	2	2.0
Occupation
Peasant	66	64.7
Business	19	18.6
Formal Employment	14	13.7
Driver	3	2.9
SD = Standard deviation, Min = minimum, Max = Maximum, BMI = Body mass Index.

Effect of Digital rectal examination on PSA levels

In this study, it was noted that in some patients, the PSA after DRE was lower than that done before the rectal exam, yet in others it remained the same or increased as shown in Table 2.

Table 2

Showing the type of PSA change observed
Change type	Frequency	Percentage	Mean Pre DRE PSA	Mean for post DRE PSA	Mean PSA change
Decrease	29	28.5	4.86	4.31	0.55
Same	19	18.6	7.25	7.25	0.00
Increase	54	52.9	4.62	5.70	1.08

On plotting the means of PSA in each age category both the mean pre and post DRE PSA ware seen to increase with age. We observed that the mean Post DRE PSA was lower than the pre-DRE in patients who had a PSA below 6 ng/ml as shown in Fig. 2.

The paired samples T test revealed that there was a small mean increase in PSA following DRE (0.40 ng/ml). This increase was not statistically significant (p = 0.061). Table 3 shows the result of the paired samples T test. The findings of the paired samples T test were supported by a scatter plot which revealed a perfect correlation (R² = 0.975) between the pre and post DRE PSA as shown in Fig. 3.

Table 3

shows the result of the paired samples T test.
Characteristic	Pre DRE PSA	Post DRE PSA
Mean	5.18	5.59
Standard deviation	12.86	13.35
Mean difference	-0.40
Standard error of the mean difference	0.21
Confidence interval of the mean difference	-0.817 to 0.020
P value of mean difference	0.061

DRE = Digital rectal exam, PSA = Prostate specific antigen

R² = Pearson Correlation coefficient, DRE = Digital rectal exam, PSA = Prostate specific antigen

It was also observed that the number of patients whose clinical decision would be affected (changed) by the PSA measured after DRE was 3 (2.9%, CI = 0.0%-6.9%) if cutoff was 3ng/ml and 2 (2.0%, CI = 0.0%-4.9%) at a cutoff of 4ng/ml. The confidence intervals in both scenarios included 0.0%, suggesting that there would be no significant effect on the clinical decision if the PSA was done post DRE as shown in Table 4.

Table 4

shows the impact of change in PSA on Clinical decision
Cutoff	Effect on decision	Frequency	percentage	95% CI
3.00 ng/ml	No change in decision	99	97.1	93.1–100.0
3.00 ng/ml	Change in decision	3	2.9	0.0-6.9
4.00 ng/ml	No change in decision	100	98.0	95.1–100.0
4.00 ng/ml	Change in decision	2	2.0	0.0-4.9

There has been insufficient data about the effect of DRE on PSA in men above 40 years with LUTS in Uganda and sub-Sahara Africa in general. Despite DRE and PSA being the cornerstones of cancer of prostate screening their interplay has not been studied in our setting. Most studies have been performed in white population thus making this the first study to assess the effect of DRE on PSA in Africa.

Our study showed that 29.5% (29 patients) of the study participants had a decrease in PSA with an average decrease of 0.55 ng/ml. In 18.6% (19 patients) there was no change in PSA. 52.9% (54 patients) had increase in PSA with an average increase of 1.08 ng/ml. The above results confirm that DRE affects PSA values, however the decrease in the PSA values after DRE seen in 29.5% of the participants could be explained by the acceptable margin of error of the equipment.

Further analysis revealed that DRE slightly increased the level of PSA with a mean difference of 0.4 ng/ml however this change was statically insignificant with a p value of 0.061. This was similar to a study done in Nigeria by Eshiobo (8) who observed that DRE caused an increase in PSA of 8 to 13% however this was statistically insignificant. In a study that enrolled 199 men in the USA, it was noted that the DRE caused a non-significant increase in PSA (18).

Contrally to our findings, significant changes in PSA were seen by Crawford et al (19) in some males with pre-DRE PSA levels under 4.0 ng/mL, however, the clinical significance of the changes were not reported. Chybowski et al (20) evaluated the effects of DRE in 71 males who had prostatic diseases and 72 controls and noted that some men with initial PSA values up to 4.0 ng/mL presented a statistically significant increase of serum PSA, however the changes were not clinically significant as was seen in this study.

Study Limitations

This study was hospital based, assessing males who already had lower urinary tract symptoms which to a large extent, may have influenced the values of PSA in this study population. There is need for a community based study in these rural areas in preparation for properly regulated screening programs in sub Saharan African countries.

This study revealed that the change in PSA following DRE was not significant both statistically and clinically. Therefore DRE can be used in screening and clinical assessment for cancer of the prostate without fear that it would interfere with PSA value interpretation and patient management.

PSA= Prostate specific antigen, DRE: Digital rectal examination, LUTS= Lower urinary tract symptoms, CI= Confidence interval.

Ethical considerations and consent: All methods were carried out in accordance with relevant guidelines and regulations. The study was approved by the Kampala international university research and ethics committee reference number UG-REC-023/202207. A voluntary and non-coercive recruitment was sought leading to signing of a written informed consent form following thorough explanation to the participant about the study. All the participants provided written informed consent. The Uganda National Guidelines for currying out research during the COVID- 19 pandemic (UNCST, 2020) were also followed.

Consent for publication: The patient data was anonymised, no patient identifying characteristics are submitted for publication.

Availability of data and materials: Data is available upon request. Requests should be sent to BM Via [email protected]

Competing interests: The authors declare that they have no conflict of interest

Sources of funding: This study did not receive any specific grant from funding agencies in public, commercial, or not for profit sectors.

Author contribution: BM was the principle investigator, conceived and designed the study, collected data, analysed data and wrote the draft of the manuscript. JM participated in data analysis, discussion of results and critically revised the manuscript, TH, FKK and MJO participated in discussion of results and critically revised the manuscript, BN and XFO supervised the work, critically revised the manuscript and all authors approved the final paper.

Acknowledgements: We acknowledge all patients that accepted to participate in this study.

Guarantor: BM

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No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Effect of digital rectal examination on prostate specific antigen levels among patients with lower urinary tract symptoms in Uganda

Status:

Version 1

Abstract

Figures

Background

Methods

Study Population

Sample Size Determination

Sampling Technique

Eligibility Criteria

Inclusion criteria

Exclusion criteria

Data Collection Procedure And Psa Measurement

Digital rectal examination

Quality Control

Results

Social-demographic characteristics of the study participants

Effect of Digital rectal examination on PSA levels

DRE = Digital rectal exam, PSA = Prostate specific antigen

R² = Pearson Correlation coefficient, DRE = Digital rectal exam, PSA = Prostate specific antigen

Discussion

Study Limitations

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1

Effect of digital rectal examination on prostate specific antigen levels among patients with lower urinary tract symptoms in Uganda

Status:

Version 1

Abstract

Figures

Background

Methods

Study Population

Sample Size Determination

Sampling Technique

Eligibility Criteria

Inclusion criteria

Exclusion criteria

Data Collection Procedure And Psa Measurement

Digital rectal examination

Quality Control

Results

Social-demographic characteristics of the study participants

Effect of Digital rectal examination on PSA levels

DRE = Digital rectal exam, PSA = Prostate specific antigen

R2 = Pearson Correlation coefficient, DRE = Digital rectal exam, PSA = Prostate specific antigen

Discussion

Study Limitations

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1

R² = Pearson Correlation coefficient, DRE = Digital rectal exam, PSA = Prostate specific antigen