The SA Urological Association and the Prostate Cancer Foundation of SA have developed evidence-based recommendations to guide clinicians on screening and early diagnosis of prostate cancer (PCa), the most widespread solid organ malignancy in men and ranking as the fifth leading cause of death globally.
Identifying and treating men with clinically significant disease while avoiding the over-diagnosis and over-treatment of indolent disease remains a significant challenge, write J John, A Adam, L Kaestner, P Spies, S Mutambirwa, and J Lazarus, in the SA Medical Journal.
Recommendations
1. Only offer PCa screening to informed, asymptomatic men, in line with their personal values and preferences, who have a life expectancy of >10 years
PCa screening should only be offered after a detailed, comprehensive explanation of its risks and benefits. The possible benefit of reducing rates of PCa-specific mortality and metastases needs to be weighed against the side effects of screening and increased diagnosis, which lead to over-treatment of mainly clinically insignificant, harmless PCa, and subsequent treatment-related effects
2. Do not offer PCa screening to men who are unlikely to accept therapy even if a significant treatable cancer is subsequently found
3. Do not offer PCa screening to men aged >70 or with a life expectancy of <10 years based on age or comorbidities, because the potential survival benefits from treatment are statistically minimal, and they do not outweigh the significant adverse effects that the patient may experience due to treatment.
Men over 70 have been reported to have the highest incidence of PCa over-diagnosis, with several studies suggesting that screening in this age group is not likely to be beneficial. Data from the European Randomised Study of Screening for Prostate Cancer trial showed that starting screening at age >70 did not result in a reduction in PCa mortality.
Similarly, in patients with a <10-year estimated life expectancy, screening is not likely to provide a benefit in terms of disease-specific or overall mortality. Moreover, evidence from randomised trials that compared surgery, radiation and monitoring has demonstrated that curative treatment becomes less beneficial and more hazardous as age increases.
4. Use the PSA blood test as the first screening test
Although it lacks specificity, PSA is still the recommended screening test for early diagnosis. PSA levels tend to escalate as men age, and the rate of increase is more rapid in elderly men. The accepted threshold for PSA level is typically ≤4 ng/mL. Age-specific ranges have been established to decrease the identification of less-developed cancers in older men and enhance the identification of large yet potentially treatable tumours in the younger age category.
The role of digital rectal examination as part of the initial PCa screening evaluation in asymptomatic patients has recently been reviewed. A comprehensive meta-analysis and systemic review that evaluated eight studies, involving 85 738 participants, found that there was no benefit in terms of the cancer detection rate or the positive predictive value of combined digital rectal examination and PSA testing over PSA testing alone.
Another meta-analysis specifically evaluating the diagnostic accuracy of DRE in the primary healthcare setting came to a similar conclusion, and recommended that routine DRE screening for PCa in the primary care setting could be omitted.
5. Offer early PSA testing to asymptomatic, well-informed men with a life expectancy of >10 years who are at high risk of CaP
Initiate PSA screening in the following patients who are at high risk for CaP:
• From the age of 50 in all men
• From the age of 45 in black men, and in men with a positive family history of prostate and/or breast cancer in a first-degree relative
• In men who have undergone genetic testing and who are carriers of the BRCA2, BRCA1, HOXB13, AT M or CHEK2 genes, screening should be performed at 40 or at 10 years younger than the age of onset of the youngest affected family member if this were before 40.
6. Individualise screening intervals for PSA testing in men who had a normal initial PSA test
The optimal intervals for PSA testing are unknown, and it is therefore recommended to determine further PSA testing on an individual basis based on the initial PSA level. International guidelines suggest that this interval may be extended up to eight years between tests.
However, considering black African men have historically been under-represented in trials and that they have a higher incidence of and mortality from PCa compared with men of other races, more frequent PSA testing is recommended.
7. Discontinue PSA screening in men aged >70 years or with a life expectancy of <10 years, based on age or comorbidities, because the potential survival benefits from treatment are statistically minimal, and they do not outweigh the significant adverse effects that the patient may experience due to treatment
8. Defer PSA screening when factors are present that may transiently elevate PSA enough to affect its performance as a screening test
Apart from age, PCa and benign prostatic hyperplasia, other factors may transiently falsely elevate PSA. It is recommended that screening be deferred in the following situations, for long enough for the PSA elevation to resolve:
• Bacterial prostatitis – defer PSA testing for six to eight weeks after resolution of symptoms
• Acute urinary retention – defer PSA testing for six weeks
• Urethral instrumentation – defer PSA testing for six weeks
• Recent transurethral resection of the prostate – defer PSA testing for six weeks
9. Repeat the PSA test in asymptomatic men in whom the initial PSA level is raised but <10 ng/mL (i.e. the ‘grey zone’) and who have normal findings on DRE
Of men who have recently had an increase in their PSA levels, 25%-40% may expect a return to normal levels upon undergoing a subsequent test.
Sexual activity can minimally elevate the PSA level (usually in the 0.4-0.5 ng/mL range) for ~48-72 hours after ejaculation. Vigorous bicycle riding has also been reported to cause significant elevations in PSA, although studies contradict this.
It is therefore recommended to verify the elevated PSA measurement after abstaining from ejaculation or cycling for at least 48 hours before continuing with additional assessment. It is worth noting that a DRE may cause minor transient elevations that are clinically insignificant.
10. Improve the specificity of cancer detection when total PSA is in the ‘grey zone’ by determining the free/total PSA ratio
We recommend using the free/total PSA ratio to improve the sensitivity of cancer detection when the initial total PSA level is elevated, but still <10 ng/mL in the presence of a normal DRE.
11. Apply a correction factor to obtain a more accurate PSA level in men on 5-alpha-reductase inhibitors (5ARIs): finasteride or dutasteride
12. Do not use antibiotics for asymptomatic men with no clinical features of bacterial infection to reduce the PSA. In the past, it was routine practice to treat asymptomatic men with an elevated PSA with antibiotics to see if a possible infection may be responsible for the PSA increase. This practice may be detrimental and predispose the patient to increased risk of infection after prostate biopsy at a later stage, Clostridium difficile infection and antibiotic resistance, and is therefore not recommended.
13. Do not use alpha-blockers (tamsulosin/doxazosin/alfuzosin) for asymptomatic men to reduce the PSA
14. Refer men with a persistently elevated age-adjusted PSA level or abnormal DRE to the urologist for further work-up
ACS Journals article – Cancer statistics for African Americans, 2019 (Open access)
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Unequal burden of prostate cancer for Africa
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