|
 
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| ORIGINAL ARTICLE |
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| Year : 2020 | Volume
: 1
| Issue : 2 | Page : 72-78 |
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Role of transrectal ultrasound and prostate-specific antigen density in assessment of clinically suspicious prostate cancer
Muhammad Habeeb Mahe1, Timothy Yakubu Umoru1, Lawan Hassan Adamu2, Suleiman Tanimu Sa'ad1, Philip O Ibinaiye3
1 Department of Radiology, Federal Teaching Hospital, Gombe, Nigeria
2 Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, Bayero University Kano, Kano, Nigeria
3 Department of Radiology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
| Date of Submission | 28-May-2020 |
| Date of Decision | 01-Jun-2020 |
| Date of Acceptance | 15-Jul-2020 |
| Date of Web Publication | 30-Nov-2020 |
Correspondence Address:
Muhammad Habeeb Mahe
Department of Radiology, Federal Teaching Hospital, Gombe
Nigeria
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/JRMT.JRMT_8_20
Background: Prostate cancer (CaP) is a major health concern with rising incidence especially in Black African populations. Digital rectal examination (DRE), transrectal ultrasound scan (TRUS) of the prostate, and prostate-specific antigen density (PSAD) values are useful adjuncts in early diagnosis of CaP. Objective: This study was aimed at evaluating the role of TRUS and PSAD and their correlation with histopathologic findings in patients with DRE features suspicious of CaP. Patients and Methods: This research was a descriptive cross-sectional study of 100 male patients with suspected CaP based on DRE and elevated prostate-specific antigen (PSA) values recruited from the urology clinic and wards of the hospital during 2018–2019. All patients had clinical evaluation, biodata documentation, and grayscale TRUS while PSA values were determined using immunoassay method. PSAD was calculated by dividing the PSA value by the TRUS prostate volume. P ≤ 0.05 at 95% confidence interval was considered significant. Results: The mean age of patients was 66.70 ± 9.60 years with age range of 44–90 years. TRUS features of heterogeneous echotexture (n = 37; 37%), regular outline (n = 73; 73%), and intact capsule (n = 77; 77%) showed the highest frequencies. TRUS alone (P = 0.189, 0.214 and 0.265 for echopattern, outline, and capsular integrity, respectively) was not statistically significant in differentiating between benignity and malignancy. Total mean PSAD was 0.63 ± 0.32 ng/ml/cm3 while the highest mean PSAD was observed in patients with irregular glandular outline (0.74 ± 0.17 ng/ml/cm3) and in those with solitary hypoechoic nodules (0.73 ± 0.61 ng/ml/cm3). There was statistically significant correlation between PSAD values and outcome of prostate biopsy (P = 0.031). Conclusion: PSAD showed a positive correlation with outcome of prostate biopsy as well as greater predictability of CaP than TRUS which was not statistically significant in differentiating between benignity and malignancy.
Keywords: Prostate cancer, prostate-specific antigen density, transrectal ultrasound scan
How to cite this article:
Mahe MH, Umoru TY, Adamu LH, Sa'ad ST, Ibinaiye PO. Role of transrectal ultrasound and prostate-specific antigen density in assessment of clinically suspicious prostate cancer. J Radiat Med Trop 2020;1:72-8 |
How to cite this URL:
Mahe MH, Umoru TY, Adamu LH, Sa'ad ST, Ibinaiye PO. Role of transrectal ultrasound and prostate-specific antigen density in assessment of clinically suspicious prostate cancer. J Radiat Med Trop [serial online] 2020 [cited 2023 Mar 26];1:72-8. Available from: http://www.jrmt.org/text.asp?2020/1/2/72/301902 |
| Introduction | |  |
Prostate cancer (CaP) is the most common cancer in men worldwide, contributing approximately 6.6% to the global cancer burden. Black Africans have up to 74% higher risk of developing CaP compared to other races. Higher mortality rates are also seen in black Africans (19–24 deaths/100,000) and in the Caribbean (29 deaths/100,000).[1],[2],[3] In Port Harcourt and Lagos, respective prevalence rates of 114/100,000 and 127/100,000 were reported while in Zaria, one out of every seven patients with lower urinary tract symptoms had CaP.[4],[5],[6] The prevalence of 9% and 22.4% was reported in a hospital-based study and from a histopathologic review in Kano respectively while a prevalence of 6.15% was reported in a retrospective study in Maiduguri.[7],[8],[9]
Risk factors for CaP include age >50 years, black race, environmental and hereditary factors, loss of p-53 tumor suppressor gene, and trophic effect of androgens. These factors play a significant role in its etiology and prognosis.[10],[11],[12],[13] Ninety-five percent of CaPs are adenocarcinomas, about 4% are transitional cell carcinomas and around 1% are variants with poor prognosis such as signet ring cell, small cell, mucinous, and ductal carcinomas.[12] The gold standard for diagnosis of CaP is histologic examination of biopsy specimen.[14]
High frequency clinical transrectal ultrasound scan (TRUS) was introduced by Watanabe et al.[15] in the late 1960s. It is a safe, reproducible, and affordable imaging modality used mainly for detection of CaP and measuring prostate volume.[16],[17],[18],[19] Zonal anatomy of the prostate is also better demonstrated using TRUS than transabdominal sonography. However, TRUS is operator-dependent, moderately sensitive for assessing capsular integrity in comparison to magnetic resonance imaging (MRI) and poorly differentiates between benign and malignant lesions.[20] Sensitivity of TRUS is further enhanced when used in combination with digital rectal examination (DRE), prostate-specific antigen (PSA), and PSA density (PSAD) thereby improving screening accuracy and reducing mortality.[14],[16],[21]
Most CaPs appear as round or oval hypoechoic nodules typically in the peripheral zones [Figure 1] and [Figure 2] although granulomatous prostatitis, infarction, glandular ectasia, fibrosis, and lymphoma may show similar appearances.[22] Isoechoic lesions (about 39%) are not visible on TRUS while hyperechoic lesions (1%) are thought to result from preexisting calcifications, infiltration into BPH or desmoplastic reaction of glandular cells.[19],[22],[23] Other sonographic features of CaP include gland asymmetry, capsular breach, and irregularity [Figure 2].[23],[24] Hypervascularity due to angiogenesis (71% of malignant lesions versus 3% of benign lesions, P < 0.001) may also be demonstrated on color/power Doppler interrogation and this aids detection of isoechoic cancers.[20],[22] | Figure 1: Longitudinal transrectal ultrasound scan section of the prostate gland in a patient with prostate cancer showing an enlarged gland with heterogeneous echotexture and multiple hypoechoic mass lesions seen in the peripheral zone (white arrows)
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 | Figure 2: Transverse transrectal ultrasound scan section of the prostate gland in a patient with prostate cancer showing heterogeneous echotexture with multiple focal hypoechoic lesions (white arrows) in the peripheral zones bilaterally. The left peripheral and central zones are eccentrically enlarged (+)
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PSAD (PSA index) was developed to improve the screening capability of PSA.[25] PSAD (PSA per unit volume of prostate tissue) differentiates between CaP (which shows elevated PSAD) and BPH, especially in the “grey zone” PSA of 4–10 ng/ml. Biopsies are recommended (in conjunction with clinical and TRUS features) when PSAD is >0.15 ng/ml/cm3.[26],[27],[28],[29] PSAD has also been found to be well correlated to histologic diagnosis, aggressiveness, and poorer outcomes of CaP in patients with PSA >10 ng/ml.[26],[30],[31] Conversely, no significant difference in mean PSAD was observed between BPH and CaP (0.12 and 0.15 ng/ml/cm3, P = 0.258).[28] Furthermore, the reliability of PSAD as a sole indicator of CaP has been questioned and varied PSAD cut off levels with different sensitivities and specificities have been suggested, some values as high as 0.33 ng/ml/cm3 and others in the range of 0.04 ng/ml/cm3.[26],[29],[32]
Although histology is the gold standard for diagnosing CaP, in patients with negative biopsy and rapidly increasing PSA, multiparametric MRI (mpMRI) may be used.[33] Multiparametric TRUS (mpTRUS), additionally utilizing shear wave elastography and contrast-enhanced ultrasound, also showed higher sensitivity and accuracy than mpMRI, suggesting that mpTRUS is a potential alternative to the costly and time-consuming MRI especially in low-resource settings.[33]
The relative wide availability of TRUS and PSA test are useful in assessing patients with suspected CaP. This study aimed to investigate the gray scale sonographic features of CaP and the complementary role PSAD plays in diagnosis of CaP in patients with clinically suspicious disease as correlated with histopathologic analysis.
| Patients and Methods | | |
Ethical approval with registration number NHREC/25/10/2013 was granted for this study by the Research and Ethics Committee on February 21, 2018. One hundred patients were recruited in this descriptive cross-sectional study and all of them had core needle prostate biopsy followed by histological analysis. The study population was made up of patients with clinically suspected CaP on DRE who met the inclusion criteria for the study, namely: age ≥40 years, elevated PSA (≥10 ng/ml), or both. Patients aged <40 years, those with PSA values <10 ng/ml or those who had previous surgical or medical treatment for CaP were excluded from the study. Written informed consent was obtained from all the participants. Age, brief clinical history, DRE findings, and PSA values were obtained from case notes of eligible consenting patients and documented in the data sheet.
Technique of transrectal ultrasound scan
The TRUS procedure was explained to the patients and written informed consent was obtained. Patients were identified by serial numbers for the purpose of confidentiality. TRUS was conducted in both axial and sagittal planes using high-resolution Philips HD-9 ultrasound scanner (Korea, 2010) equipped with a 4–9 MHz broadband curved array rectal transducer among others. PSA value was obtained and recorded before TRUS or biopsy and PSAD was calculated as the quotient of PSA and TRUS prostate volume. Patients were scanned in the left lateral position, arms resting on a pillow with the knees flexed. The transrectal probe was disinfected with chlorhexidine solution before and after each examination. The probe was covered by a latex condom into which enough ultrasound coupling gel was added to cover the tip of the transducer and to expel air and also applied externally over the condom. The probe was then gently introduced into the rectum while encouraging the patient to relax to open the anal sphincter. The probe was inclined slightly posteriorly and then anteriorly to take the rectal contour. During scanning, the probe was positioned in close contact with the anteriorly located prostate gland for efficient ultrasound transmission. First, the entire gland was carefully scanned by moving the probe within the rectum to ensure that all areas of the gland lie within the focal zone of the transducer.
Then, axial plane images were obtained starting at the base with a slightly caudal angulation of the probe to identify the approximate largest transverse diameter of the gland. The capsular margins of the prostate were clearly visible forming a thin hypoechoic rim that merges into the periprostatic tissue. The gland was identified as a triangular or almond-shaped encapsulated structure showing diffuse homogenous echoes located inferior to the neck of the urinary bladder. Transverse and anteroposterior diameters of the gland corresponding to the width and height respectively were then measured in this plane [Figure 3]. The seminal vesicles which have a saccular cystic appearance were imaged at the prostate base and excluded from the measurement of the width or anteroposterior diameter of the prostate. Scanning in the axial plane from base to apex of the prostate was performed by moving the probe caudally and from side to side. | Figure 3: Transverse (left panel) and longitudinal (right panel) transrectal ultrasound scan images showing measurement of the prostate transverse, anteroposterior, and longitudinal diameters (represented by dotted lines). Machine-calculated prostate volume and predicted prostate specific antigen value are also shown
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The probe was then turned 90° for midline sagittal imaging to obtain the longitudinal diameter (length) of the gland and to also assess the seminal vesicles. The prostate contour especially the anterior aspect of the gland and the bladder base were made clearly visible by adjusting the time-gain compensation or focal zones. The longitudinal diameter was measured as the longest distance from the base to the apex in the midline sagittal plane. While scanning in the transverse and longitudinal planes, gland symmetry, size, shape, presence of median groove, and echopattern were evaluated. Any suspicious lesion was further evaluated in an additional view. Lesions noted in lateral aspects of the gland were viewed in the center by manipulating the probe to avoid lateral resolution losses. Prostate volume in milliliters (ml) was calculated electronically by the ultrasound machine based on the prolate ellipsoid formula of length × height × width × 0.5236.
Transrectal digitally guided needle core biopsy was routinely carried out in the theater by the urologists for patients with PSA ≥10 ng/ml, abnormal DRE findings and suspicious findings on TRUS or a combination of these. Image guidance was not utilized. 8–10 cores were obtained while sextant biopsy from base to apex was performed for sonographically homogeneous glands by dividing the prostate into six areas and systematically obtaining core biopsy samples from each area. Tissue samples were processed into paraffin blocks and stained by h and e method in the histopathology laboratory. Total serum PSA was quantified at the chemical pathology laboratory using the fluorescence enzyme immunoassay method with Tosoh AIA-360 automated immunoassay analyzer (Tosoh Bioscience Inc., San Francisco, USA). PSA values, DRE, TRUS findings, and prostate volume were recorded for each patient and then PSAD was determined from the prostate volume and the PSA values obtained using the formula PSAD = PSA/TRUS prostate volume.
Data from the structured data sheet were entered into the computer to generate a data base for analysis and processing using Statistical Package for Social Sciences (SPSS) for Windows version 20.0 package (IBM SPSS Inc., Chicago IL, USA, 2016). Data were expressed as mean ± standard deviation, frequency, and percentages. Independent sample t-test was employed to determine difference in mean values of PSA, prostate volume and PSAD based on histological outcome of biopsy. Chi-square test of independency was used to assess the association of DRE and TRUS parameters with histopathologic finding. Relationship between age and prostatic parameters with prostate carcinoma was evaluated using simple linear regression analysis. P ≤ 0.05 at 95% confidence interval was considered statistically significant. The results were presented in the form of tables, graphs, and charts as appropriate.
| Results | | |
A total of 100 subjects participated in the study. The age range of the participants was 44–90 years with a mean age of 66.70 ± 9.60. About a third of the patients, 35/100 (i.e., 35%) were in the age group of 60–69 years while there was only one patient in the age group 90 years and above, as summarized in [Figure 4].
The frequency distribution of prostate gland echopattern is shown in [Figure 5]. Heterogeneous echopattern had the highest frequency (37%) while patients with a solitary hypoechoic nodule showed the lowest frequency (12%). In 73% of patients (73/100), the prostate outline was regular whereas 27% (27/100) showed irregularity of the glandular outline. The proportions of patients with intact prostatic capsule and those who showed TRUS features of capsular breach was 77% (77/100) and 23% (23/100), respectively. | Figure 5: Frequency distribution of prostate gland echopattern as seen on transrectal ultrasound scan
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The total mean PSAD was 0.63 ± 0.32 ng/ml/cm3 with a range of 0.14-2.5 ng/ml/cm3. The highest mean PSAD value was in the 60–69 years of age group (0.69 ± 0.28) although one patient in the ≥90 years of age group had PSAD of 0.84 as shown on [Table 1]. [Figure 6] shows a summary of comparison between mean PSAD and prostate echopattern on TRUS showing the highest mean PSAD of 0.73 ng/ml/cm3 in the group with solitary hypoechoic nodules. Mean PSAD of patients with irregular glandular outline was 0.74 ng/ml/cm3 while those with capsular breach had a slightly higher mean PSAD of 0.7813 ng/ml/cm3. There was statistically significant difference in PSAD values between the groups with irregular and regular glandular outline (P = 0.037) as well as between those with breached and intact capsule (P = 0.011) [Figure 7]. | Table 1: Mean prostate-specific antigen density values according to age groups
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 | Figure 6: Comparison between mean prostate-specific antigen density and prostate echopattern on transrectal ultrasound scan (similar superscript letters indicate significant differences at P < 0.05)
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 | Figure 7: Comparison between mean prostate specific antigen density with prostate gland outline and capsular integrity on transrectal ultrasound scan (asterisks indicate significant difference between the groups atP < 0.05)
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[Table 2] shows how age, PSA, prostate volume, and PSAD may predict prostate carcinoma. The coefficient of regression (β values) represents unit increase in the parameter that increases the chances of prostatic carcinoma with their corresponding P values. Only PSAD was found to be statistically significant as a predictor of prostate carcinoma (P = 0.031). | Table 2: Relationship between age and prostatic parameters with prostate carcinoma
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[Table 3] shows the result of Chi-square tests performed to determine correlation between TRUS features and DRE findings with the outcome of prostate biopsy and their respective frequencies and P values. Both DRE and TRUS were not statistically significant in differentiating between benignity and malignancy in the study population. However, there was statistically significant association between PSAD and outcome of biopsy (P = 0.031) [Table 4]. | Table 3: Chi-square test associating digital rectal examination and transrectal ultrasound scan parameters with histopathologic finding
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 | Table 4: Difference in mean values of prostate-specific antigen, prostate volume, and prostate-specific antigen density based on histological outcome of biopsy
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[Figure 8] presents a summary of the relationship between mean PSAD, DRE findings, TRUS features, and outcome of prostate biopsy in the study population. | Figure 8: Summary of comparison between mean prostate-specific antigen density, digital rectal examination features (green bars), transrectal ultrasound scan findings (blue bars), and outcome of prostate biopsy (red bars)
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| Discussion | | |
This study showed that TRUS features, namely prostatic echopattern, glandular outline, and capsular integrity alone may not discriminate between CaP and benign prostate in suspected cases of CaP (P = 0.189, 0.214, and 0.265, respectively). This finding is in agreement with earlier reports by Sheth et al.[34] in the United States who found that TRUS was nonspecific in diagnosing CaP with a specificity of only 37% and therefore unsuitable for early detection of carcinoma. This study also found a 37% prevalence (37/100) of prostates with heterogeneous echotexture, similar to 39.7% reported by Ahmed et al.[35] in Zaria, Northwest Nigeria. Heterogeneous echopattern, especially when found in benign prostatic lesions, invariably make detection of discrete isolated hypoechoic foci usually associated with malignancy more difficult which may account for the low sensitivity of TRUS in our study. Another possible reason for the lack of significance of TRUS features in predicting CaP in this study may be due to the nonapplication of Doppler ultrasound (which was not part of the methodology of this study), contrast enhancement, and elastography in addition to gray scale imaging. These additional techniques, as part of mpTRUS, performed better than only gray scale TRUS in recognizing CaP.[36],[37],[38]
Despite this study showing that TRUS may not discriminate between benignity and malignancy, all of the hypoechoic nodules observed in the peripheral zone (46% of patients in this study) were found to be malignant. Consistent with this finding, hypoechoic nodules observed on TRUS have been noted to have a high predictive value in identifying CaP.[14],[18],[19]
Furthermore, the prevalence of 27% (27/100) irregular prostate outline (all of which were malignant) and 73% (73/100) regular outline (94% of which were malignant) on TRUS was observed in this study in contrast with the findings of Lee et al.[24] in Korea who reported irregular prostatic outline in 81% of CaP patients compared with 43% in benign prostatic lesions (P ≤ 0.001). This much higher prevalence of capsular irregularity in benign prostatic lesions may be due to racial differences and may indicate lack of sensitivity of capsular outline in predicting malignancy. All patients with capsular breach had CaP, similar to the findings of Ahmed et al.[35] Although this study found that TRUS is less sensitive as a predictor of early CaP, it is nonetheless useful as an adjunctive modality in assessing focal lesions in advanced disease especially when combined with PSA and clinical assessment as reported by other researchers.[35]
This study also found that PSAD is sensitive in predicting CaP in patients with clinically suspicious cancer on DRE. Mean PSAD of 0.63 ± 0.32 ng/ml/cm3 was more significant than PSA alone in distinguishing between CaP and BPH (P = 0.031). This is similar to the findings of Udeh et al.[29] in Enugu, Southeast Nigeria, who reported a mean PSAD value of 0.77 ± 0.98 ng/ml/cm3 which was significant in predicting CaP (P = 0.000) despite the fact that their study population comprised only patients with normal DRE and lower PSA limit of 4 ng/ml. Similarly, Tsang et al.[33] revealed better performance of PSAD than PSA (P = 0.004) in predicting CaP in Asians.
A slightly higher mean PSAD of 0.73 ng/ml/cm3 was observed in patients with solitary hypoechoic nodules than in patients with multiple hypoechoic nodules (0.71 ng/ml/cm3) or heterogeneous echotexture (0.64 ng/ml/cm3), all of which had irregular capsule and evidence of capsular breach on TRUS. These showed statistically significant difference when compared with prostate echopattern in patients with intact and regular capsule which may suggest a correlation between PSAD and periprostatic cancer infiltration. Similar observation was reported by Sertkaya et al.[39] in Turkey who recorded an elevated PSAD value of 0.23 ± 0.07 ng/ml/cm3 in patients with extra-capsular tumor extension as against 0.17 ± 0.04 ng/ml/cm3 in patients with tumor confined to the prostate (P = 0.03).
| Conclusion | | |
PSAD was comparably most significant in differentiating between benign and malignant prostate than most clinically employed variables including PSA. Although TRUS is less sensitive as a predictor of CaP, it is still useful in characterizing lesions in advanced disease and relevant in guiding systematic prostate biopsy of focal or multiple hypoechoic lesions. This is the most prevalent echopattern noted by this study which is also associated with positive predictive value of being malignant. Therefore, it would be suggested that PSAD, in conjunction with clinical and other TRUS features, be routinely used for screening of candidates for prostate biopsy instead of PSA alone.
Acknowledgments
Our gratitude goes to Dr. Aminu U. Usman (HOD Radiology, FTH Gombe) for his general support and unfettered access to the ultrasound suite. We acknowledge the support of Dr. Mustapha Kura, Dr. A. Arogundade, Dr. Khalifa Abdussalam and nursing staff of urology unit FTH Gombe. Dr. Musa Ali-Gombe, Dr. Abdullahi Gombe, Dr. Aliyu Lawan and laboratory staff of Chemical Pathology and Histopathology departments have been most generous with their technical support.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1], [Table 2], [Table 3], [Table 4]
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