Prostate cancer screening among apparently healthy adult males

INTRODUCTION

Despite the underreporting of cancer in our environment, cancer still remains a worrisome disease with psychological, economical, and prognostic burdens.^[1-4] Reports have shown that the incidence of cancer is on the increase in North America, Europe, Asia, and Africa.^[2,5,6] Among the most common cancers globally, prostate cancer remains the most common cancer in adult males with resultant poor prognosis and mortality.^[2,3,5,7-13] In contrast to most literature, prostate cancer was the second and third most common cancer among men in Romania and Singapore.^[4,14]

The increasing mortality associated with prostate cancer underscores the need for timely screening for risk factors for prostate cancer and possibly early detection and treatment of precancerous lesions and prostate cancer.^{[3,4,7,10-12,15]}

Increasing age, red meat enriched diet, white meat enriched diet, smoking, vegetable impoverished diet, family history of prostate cancer, genetic mutations, fruit impoverished diet, prolonged alcohol consumption, dairy product-enriched diets, and decreased sexual activity have been reported as possible risk factors to the development of prostate cancer.^{[2,5-7,9,11-13,16-21]}

Digital rectal examination (DRE) is still a valuable tool in the diagnosis of prostate cancer and shows enlarged nodular, hard-to-craggy prostate with obliterated median groove and sulci as well as fixed rectal mucosa suggestive of suspicious prostate cancer.^{[2,4-6,8,10,14,15,19,20,22-24]}

Serum prostate-specific antigen (PSA) level, a tumor marker, has been used to predict men who are at risk of prostate cancer and determine the choice of medical treatment in benign prostatic hyperplasia (BPH).^{[7,8,10,14,19,20,25-31]} The potential risk of false positivity or negativity of PSA may be associated with over-diagnosis, under-diagnosis, and overtreatment of prostate cancer as well as other prostatic lesions such as urinary tract infections, benign prostatic enlargement (BPE), acute and chronic urinary retention and prostatic trauma from trucut diagnostic biopsy or vigorous DRE may produce raised PSA.^[7,12,14,15] It is pertinent to observe that transrectal ultrasonography (TRUS) of the prostate plays a crucial role in increasing the detection rate of prostate cancer among other mimicking prostatic lesions alongside other complimentary diagnostic tools, including transrectal ultrasound-guided prostate biopsy, PSA, and DRE.^{[4,6,9,13,14,19,26,27]}

Transrectal ultrasound-guided prostate biopsy is the gold standard for diagnosis of prostate cancer, as reported in many studies.^{[2,5,6,8,9,11,14,19,25-27]} Notwithstanding the usefulness of prostate biopsy, it could be limited by inadequate sample size and technical expertise of the medical laboratory scientist, radiologist, and pathologist.^[19,26-28] It is important to scale up screening for prostate cancer among males aged 40 years and above aimed at detecting precancerous lesions such as prostatic intraepithelial neoplasia and atypical small acinar proliferation as well as frank prostate cancer.^{[11,14,29,30]}

Health education of the populace to expose misinformation and strengthen the pursuit of early diagnosis and treatment of diseases, including prostate cancer, should be prioritized by health-care workers, government, and non-governmental organizations.^[4,10,15]

This study is aimed at describing the outcome of tripod-based prostate cancer screening among apparently healthy adult males in tertiary academic and health institutions in Uyo, Akwa Ibom State, Nigeria, with a view to highlighting the need for targeted screening of the disease in the community.

MATERIAL AND METHODS

RESULTS

DISCUSSION

The burden of cancer is still on the increase in Europe, Asia, and Africa, including Nigeria, which may be attributed to the aging and growth of the population as well as the increased prevalence of risk factors associated with the adoption of unhealthy to affluent lifestyle.^[1-6] Although prostate cancer remains the most common cancer in adult males in most countries with resultant poor prognosis and mortality,^[2,3,5,7-13] there are still a few contrasting results of prostate cancer being the second and third leading cancer among men in Romania and Singapore, respectively.^[4,14] Thus, the varying prevalent rates of cancer could be explained by sample size, racial, cultural, and geo-political differences, which further underscore the need for timely screening for risk factors for prostate cancer as well as early detection and treatment of prostate cancer.^{[3,4,7,10-12,15-25]} The index study recorded a mean age of 53.0 ± 2.4 years, which agrees with the preponderant of participants who were above the age of 50 years and fell largely within the age group of 50–59 years (47.8%). These findings compare also with the results of other studies.^[2,5,9,23] Ugwumba et al. in Enugu reported that most participants had a median age of 55.5 years and were ≥50-years-old (73.2%).^[2] Ikuerowo et al. in Lagos, South Western Nigeria, Ogbetere and Irekpita in Benin, South-South Nigeria and Ngwu et al. in Umuahia, South Eastern Nigeria, recorded mean ages of 60.8, 69.8, and 71.3 years, Respectively, which were higher than the values recorded in the index study.^[5,9,19] Similarly, Lauro in Mexico, Walsh et al. in the UK, Lim et al. in the USA, Lee et al. in Singapone and Jia et al. in China reported mean ages of 61.9 years, 63.3 years, 64.2 years, and 68.2 years and 73.5 years respectively.^{[13-15,25,26]} On the other hand, Ukoli et al. in Nigeria reported a mean age of 56.45 + 15.1 years among rural men and preponderance among participants who were ≥50 years of age (61.6%).^[20] In contrast to most studies, Ogbetere and Irekpita reported the peak age range for the participants to be 70–79 years, which is higher than the finding in the index study.^[19] The preference for screening of men aged 40 years and above by aforementioned studies is supported by the fact that prostate cancer is more likely to develop in older men, and the risk of developing the cancer increases gradually from age 40.^[6,7,12] Furthermore, it is obvious that age still remains the strongest risk factor for prostate cancer, and the predominant age group of participants may vary from region to region, and there is a likely possibility that the level of education among participants may have a positive influence on prompt uptake of screening for the prostate cancer.^[6,12,18,19]

Red meat- and white meat-enriched diets were the two leading identifiable risk factors in 30.4% and 15.9% of participants, respectively. Consequently, it is pertinent to highlight the role of variable socioeconomic factors in the process of development of prostate cancer. These risk factors include red meat enriched diet, white meat enriched diet, smoking, vegetable impoverished diet, family history of prostate cancer, genetic mutations, fruit impoverished diet, prolonged alcohol consumption, dairy product enriched diets, and increased sexual activity.^{[2,5-7,9,11-13,16-20,21]} Furthermore, other contributing factors to the development of prostate cancer may include poverty, cultural beliefs, delay in accessing medical care, poor cancer registry quality, difficulty in completing case assessment, estimation of populations at risk, and poor uptake of screening practices.^[2,11] Health education of the populace to strengthen the pursuit of early diagnosis and treatment of diseases, including cancer, should be prioritized by health-care workers, government, and nongovernmental organizations.

In the index study, 28 (13.9%) participants had abnormal DRE findings suspicious of a prostate cancer, whereas the remaining 86.1% of participants had findings suggestive of either benign enlargement or normal-sized features. This compares relatively with a study by AisuodionoeShadrach et al. in Abuja, who reported that six participants had abnormal findings on DRE suggestive of a prostate malignancy.^[7] Akinremi et al. in Abeokuta recorded that 31.4% of the participants showed some DRE abnormalities ranging between various degrees of enlargement and nodularity.^[10] Ukoli et al. also reported that 29.0% of participants had an enlarged prostate, including 2 participants who had nodular prostate.^[20] Walsh et al. reported that DRE abnormalities in referred clients were observed by general practitioners (GPs) and Urologists in the UK in 72% and 58%, respectively.^[15]

Features of abnormal DRE findings suspicious of prostate cancer have been described and are usually characterized by nodular enlargement, hard to craggy consistency, obliterated median groove and sulci, as well as fixed rectal mucosa.^{[2,4-6,8,10,14,15,19,20,22,23]} From the foregoing, although DRE is still a valuable tool in the diagnosis of prostate cancer, expertise is however required to avert mis- or under-diagnosis of prostate lesions.^[3,7] In addition, the importance of DRE in the detection of higher-grade, clinically aggressive prostate cancer has been described.^{[15,19,22,23]}

In the index study, prostatic-specific antigen (PSA values ≤4.0 ng/mL were seen in the majority of participants (82.0%), values >4.0–≤10 ng/mL were seen in 7.5% of the participants, and values >10 ng/mL were seen in 10.5% of the participants. Although the overall mean serum PSA level for all participants was 2.5 ng/mL, which is higher than 2.4 ng/mL recorded in those with benign DRE findings and higher than 33.7 ng/mL reported in those with suspicious DRE findings. These findings compare relatively with a mean serum PSA level of 36.6 ng/mL in those with suspicious DRE findings reported by Ogbetere and Irekpita^[19] and results of PSA values <4 ng/mL were mostly recorded by Okuja et al. and Aisuodionoe-Shadrach et al. in 78.3% and 91.0%, respectively.^[7,8] Similarly, Akinremi et al. and Ukoli et al. reported that 11.2% and 27.0% of all the screened men had PSA ≥4 ng/mL, respectively.^[10,20] Studies have shown that levels of serum prostate-specific antigen (PSA), a tumor marker, could be used to predict men who are at risk of prostate cancer and determine the choice of medical treatment in BPH.^{[7,8,10,14,19,20]} Although reference interval values are a cutoff point for making further diagnostic evaluation and clinical treatment decisions, it is pertinent to establish local reference intervals peculiar to our environment aimed at averting potential risk of false positivity or negativity associated with consequences of over-diagnosis, under-diagnosis, and overtreatment of prostatic carcinoma.^[7,23,32,33] Furthermore, it has been reported that elevated serum PSA levels are not limited to prostatic carcinoma but are also found in benign conditions such as urinary tract infections, BPE, acute and chronic urinary retention, and prostatic trauma from trucut diagnostic biopsy or vigorous DRE.^{[7,12,14,15,19,23,24]} Thus, the patients with elevated serum PSA levels may be subjected to further collaborative diagnostic investigations, including transrectal ultrasound scan of the prostate (TRUS) and transrectal ultrasound scan-guided prostate biopsy to rule out differential diagnoses of elevated PSA levels.^{[4,6,9,13,14,19]}

In our study, most of the participants had TRUS prostate volume between 25 and 50 mLs (44.3%) with features of benign and suspicious nodules in 44.3% and 9.6% of the participants, respectively. These findings compare relatively with a finding of a study conducted by Okuja et al. in Uganda, which recorded prostate volume ranging from 25 mLs to 50 mLs to be the predominant volume (56.0%) and detection of benign and suspicious nodules in 77.0% and 23.0% of participants respectively, though higher than the values recorded in the index study.^[8] We observed that the mean prostatic volume of participants with suspicious for prostate cancer was significantly higher than those with benign prostate lesions, which is in agreement with a study by Ogbetere and Irekpita^[19] It is pertinent to observe that TRUS of the prostate plays a crucial role in increasing the detection rate of prostate cancer among other prostate lesions alongside other important diagnostic tools, including transrectal ultrasound scan-guided prostate biopsy, PSA, and DRE.

Our study showed a significant relationship between variables such as age, DRE, PSA levels, and TRUS findings, thus highlighting their roles in prostate cancer screening as complementary to prostate biopsy.^[9] Furthermore, it has been recommended that screening should commence in adult males from the age of 40 years to stem down morbidity and mortality related to prostate cancer.^[12]

It is pertinent to note that there are controversies surrounding screening for prostate cancer. Criticisms of prostate cancer screening include the financial burden of screening, the morbidity of prostate biopsy, the low positive predictive value of screening, the over-treatment of an indolent disease, and the lack of evidence demonstrating a mortality benefit due to screening.^[34] Nevertheless, there are still some strong points in support of screening for prostate cancer in our environment. They include the assertion that black Africans are at higher risk of developing prostate cancer due to the prevalence of some predisposing genetic or gene mutations such as BRCA, lynch syndrome, and HPC genes 1 and 2. In addition, most screening protocols have adopted a tripod of DRE, PSA, and TRUS as deployed in the index study and disregarded the sole use of PSA for prostate cancer. Furthermore, higher imaging approaches to the diagnosis of prostate cancer, such as multi-parametric magnetic resonance imaging (MRI), which combines anatomic T2-weighted imaging and T1 weighted with magnetic resonance spectroscopic imaging, diffuse-weighted imaging and/or dynamic contrast-enhanced MRI as well as ultrasound fusion techniques and MRI fusion-targeted biopsy have been deployed commonly in developed countries to improve the early detection of prostate cancer.^[35] Unfortunately, these imaging techniques are not available in our center due to cost implications and technicalities as drawbacks. In addition, concerted efforts of all stakeholders should be directed towards early diagnosis of prostatic lesions and prompt treatment as well as provision of funds for a highly subsidized, targeted screening entailing DRE, PSA, TRUS of prostate and transrectal ultrasound-guided prostate biopsy.

CONCLUSION

Tripod of DRE, prostate-specific antigen (PSA) analysis, and transrectal ultrasonography of the prostate are still relevant in a stepwise prostate cancer screening before deployment of confirmatory prostate biopsy. Thus, it is important to scale up screening for prostate cancer among males aged 40 years and above for subjecting subjects with suspicious findings to confirmatory prostate biopsy. In addition, health education of the populace to expose misinformation and strengthen the pursuit of early diagnosis and treatment of prostate diseases, including prostate cancer, should be prioritized by health-care workers, government, and non-governmental organizations.