For men without a prostate cancer diagnosis or symptoms that might indicate prostate cancer what is the incremental value of performing a digital rectal examination (DRE) in addition to PSA testing in detecting any prostate cancer? (PICOi question 4)
Guidelines developed in partnership with
Prostate Cancer Foundation of Australia and Cancer Council Australia PSA Testing Guidelines Expert Advisory Panel. Clinical practice guidelines PSA Testing and Early Management of Test-Detected Prostate Cancer. Sydney: Cancer Council Australia. [Version URL: http://wiki.cancer.org.au/australiawiki/index.php?oldid=122827, cited 2017 Sep 20]. Available from: http://wiki.cancer.org.au/australia/Guidelines:PSA_Testing/Role_of_digital_rectal_examination.
National Health and Medical Research Council
In approving the guidelines (recommendations), NHMRC considers that they meet the NHMRC standard for clinical practice guidelines. This approval is valid for a period of five years. NHMRC is satisfied that the guidelines (recommendations) are systematically derived, based on the identification and synthesis of the best available scientific evidence, and developed for health professionals practising in an Australian health care setting.This publication reflects the views of the authors and not necessarily the views of the Australian Government.
- 1 Background
- 2 Evidence
- 3 Evidence summary and recommendations
- 4 Footnote
- 5 References
- 6 Discussion
DRE, in combination with measurement of serum prostatic acid phosphatase, was the standard method for establishing the clinical suspicion of prostate cancer prior to the introduction of PSA testing and systematic biopsy of the prostate. However, men were often reluctant to have a DRE and remain so today. Other problems were that a significant volume of cancer needed to be present before a DRE abnormality could be identified, and that there was significant observer variation. Therefore, in an era when PSA testing is increasingly offered to men concerned about the possibility of prostate cancer, with the aim of identifying much smaller foci of cancer, it is important to ask whether DRE still has an important role in the detection of asymptomatic prostate cancer.
Five studies were identified that examined the benefits and harms of using DRE in addition to total PSA levels as initial tests to identify men likely to have prostate cancer. All the studies were assessed to have a moderate risk of bias. The search strategy, inclusion and exclusion criteria, and quality assessment are described in detail in the Technical report.
The most important data were provided by the Prostate Cancer Prevention Trial, a randomised controlled trial comparing finasteride with placebo, in which men underwent testing for 7 years. This was the largest relevant screening study identified, and the only one in which men were biopsied regardless of DRE result or PSA level (i.e. screen-negatives as well as screen-positives were biopsied). Therefore, this study was able to provide reliable estimates of differences in sensitivity and specificity, as well as estimates of increases in cancers detected and unnecessary biopsies. The study was generally well conducted, with potential verification bias investigated and shown not to be an issue. However, the risk of bias was considered to be moderate because the authors did not state whether DRE, PSA tests and pathologist review of biopsy specimens were performed blind. To avoid potential bias due to any possible effects of finasteride, only data from the placebo arm were examined in this review.
The use of DRE in addition to PSA thresholds resulted in a moderate increase in the detection of prostate cancer. However, the incremental gain in cancer detection was at the cost of biopsy referrals for men without prostate cancer (false positives); the rate of false positives increased with decreasing PSA threshold. The rate of false positives was 1.91 for every additional cancer using a PSA threshold of 4.0 ng/mL, 1.99 for every additional cancer using a threshold of 3.0 ng/mL, and 2.44 for every additional cancer using a threshold of 2.0 ng/mL. At a threshold of 3.0 ng/mL, adding DRE resulted in a relative increase in sensitivity of 12 percentage points, accompanied by a specificity decline of 7 percentage points. In absolute terms, this would mean that for every 1000 men repeatedly tested, 26 more cancers would be found, but 52 more false positives would be referred for biopsy. At a PSA threshold of 4.0 ng/mL, there was a 14 percentage-point increase in sensitivity and a 7 percentage-point decline in specificity. In absolute terms, 30 more cancers would be detected but 58 men would undergo unnecessary biopsies per 1000 men tested. Importantly, the same increase in cancer detection rate could have been achieved without DRE by simply using a lower PSA threshold (Figure 2.2).
Figure 2.2. Trade-off between detecting true positives and adding false positives for PSA alone and in combination with DRE
Source: data derived from Thompson et al (2007)
The other four studies examined the addition of DRE to a PSA threshold of 4.0 ng/mL. The results of these studies were roughly in agreement as to the direction and magnitude of accuracy of the incremental gain. The number of false positives for every additional cancer detected was even higher in these studies, despite the use of more extensive biopsies in one study, and the fact that DRE was performed by urologists or urologic residents in three of these studies. However, differences in populations, the frequency of testing, and verification prevent pooling of the data and limit direct comparison.
- Data from the placebo arm of the Prostate Cancer Prevention Trial show that, for every 1000 men tested, adding DRE to a testing protocol with PSA threshold of 4.0 ng/mL would detect three additional cancers with Gleason score > 7 and seven additional cancers with Gleason score > 6. The proportion of higher-grade cancers amongst the additional cancers detected with DRE (23.2% cancers with Gleason score > 6 and 9.0% cancers with Gleason score > 7) was lower than, or similar to, that detected using PSA alone (35.2% cancers with Gleason score > 6 and 10.1% cancers with Gleason score > 7).
- A study conducted among US veterans reported that 34.0% of the additional cancers detected by DRE were Gleason score > 6 and 13.6% were Gleason score > 7.
- In a large US community screening study, 3.3% of additional cancers detected by DRE were Gleason score > 7.
- In a small Mexican screening study the single additional cancer detected by DRE had a Gleason score of 7.
However, based on the data from the Prostate Cancer Prevention Trial, the addition of DRE to PSA increased sensitivity for cancers with Gleason score > 7 by 25.4 percentage points, while specificity was reduced by 8.6 percentage points. For cancers with Gleason score > 6, the addition of DRE to PSA gained a 15.0 percentage-point increase in sensitivity at the cost of a 8.5 percentage-point reduction in specificity.
The findings of the Prostate Cancer Prevention Trial may not be generalisable to the Australian primary care setting because the trial cohort was comprised of men over 55 years old who had undergone previous screening (initial normal DRE and PSA < 3 ng/mL on entry to the study). In comparison, PSA testing in Australia covers a broader range of men. In addition, the trial investigators may have benefited from specific training and have had greater experience in performing DRE, compared with clinicians who perform DRE in Australian primary care. Therefore, the benefits of adding DRE to PSA testing in Australia may be fewer than those reported.
Evidence summary and recommendations
|There is evidence from one large moderate-quality study that the addition of DRE to PSA testing provided an incremental gain in prostate cancers detected, but at a cost of two or more extra false positives per cancer detected. The study also showed that similar gains could be made by lowering the PSA threshold. DRE accuracy is likely to be lower outside the trial setting of this study.||III-2||, , , , |
|The sensitivity for detecting high-grade cancers was increased when DRE was added to PSA testing. However, the gain in detecting higher-grade cancers by adding DRE was generally not greater than that for lower-grade cancers.||III-2||, , , |
|In asymptomatic men interested in undergoing testing for early diagnosis of prostate cancer, digital rectal examination is not recommended as a routine addition to PSA testing in the primary care setting.||C|
Although DRE is not recommended as a routine test for men who, after advice, wish to be tested for the presence of prostate cancer, it will still be an important part of the man's assessment on referral to a urologist or other specialist for further assessment prior to consideration for biopsy.
Health system implications of these recommendations
Current guidelines for preventive care in general practice recommend both DRE and PSA for men who choose to undergo prostate cancer testing after being fully informed of the benefits, harms and uncertainties of testing. Therefore, implementation of this recommendation would alter current practice.
Misuse or new safety concerns from these recommendations are not envisaged. The Evidence-based guideline may reduce litigation alleging malpractice when a diagnosis of prostate cancer is perceived to have been delayed as a consequence of a primary-care practitioner’s non-performance of a DRE.
Implementation of this recommendation would have no significant resource implications. It may slightly reduce the consultation time for men attending primary care.
Barriers to implementation
No barriers to the implementation of this recommendation are foreseen.
i Clinical questions were translated into the PICO framework: population, intervention (or exposure), comparator and outcome (see Appendix 3).
- Carvalhal GF, Smith DS, Mager DE, Ramos C, Catalona WJ. Digital rectal examination for detecting prostate cancer at prostate specific antigen levels of 4 ng./ml. or less. J Urol 1999 Mar;161(3):835-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10022696.
- Fowler JE JR, Bigler SA, Farabaugh PB, Wilson SS. Prostate cancer detection in Black and White men with abnormal digital rectal examination and prostate specific antigen less then 4 ng./ml. J Urol 2000 Dec;164(6):1961-3 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11061891.
- Galic J, Karner I, Cenan L, Tucak A, Hegedus I, Pasini J, et al. Comparison of digital rectal examination and prostate specific antigen in early detection of prostate cancer. Collegium Antropologicum 2003 Jan;27 suppl 1:61-6.
- Gomez-Guerra LS, Martinez-Fierro ML, Alcantara-Aragon V, Ortiz-Lopez R, Martinez-Villarreal RT, Morales-Rodriguez IB, et al. Population based prostate cancer screening in north Mexico reveals a high prevalence of aggressive tumors in detected cases. BMC Cancer 2009 Mar 24;9:91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19317909.
- Thompson IM, Tangen CM, Goodman PJ, Lucia MS, Parnes HL, Lippman SM, et al. Finasteride improves the sensitivity of digital rectal examination for prostate cancer detection. J Urol 2007 May;177(5):1749-52 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17437804.
- Thompson IM, Ankerst DP, Chi C, Lucia MS, Goodman PJ, Crowley JJ, et al. Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. JAMA 2005 Jul 6;294(1):66-70 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15998892.
- Royal Australian College of General Practitioners. Guidelines for preventive activities in general practice. 8th ed. Melbourne: RACGP; 2012.