The debate about prostate-specific antigen (PSA) testing for the diagnosis of prostate cancer continues to rage. The United States Preventive Services Task Force (USPSTF) and the equivalent Canadian body have both advised against PSA screening.1,2 On the other hand, many authoritative bodies, including the American Urological Association,3 the National Comprehensive Cancer Network (US), the American Cancer Society, the European Association of Urology,4 and our own Urological Society of Australia and New Zealand recommend that, instead of population-based screening, decisions about PSA testing of men aged 55–69 years should be shared by doctors and individual patients.
While the USPSTF acknowledged the potential benefit of PSA screening for reducing cancer mortality and morbidity, it decided that the significant potential harms outweighed this benefit. The ongoing impact on the patient's quality of life of the side effects of the various treatments, such as erectile dysfunction and urinary incontinence, are well documented,5 but the diagnostic biopsy itself is also associated with potential morbidity and, if rarely, mortality.6,7
These harms can be summarised as the overdiagnosis and overtreatment of indolent prostate cancer. The root cause of this problem is the troubling inaccuracy of the current diagnostic process that is still considered the standard of care — an elevated PSA level leading to a transrectal ultrasound-guided (TRUS) biopsy.
The poor specificity of PSA for significant prostate cancer is well known.8 What may not be such common knowledge is that about half of all TRUS biopsies are negative for cancer.9 This might seem to imply that a large proportion of men undergoing this invasive procedure do not have prostate cancer. We know, however, that some do, in fact, have significant prostate cancer, but the TRUS biopsy, being a blind random sampling of the gland, has missed it.10
In addition, a large proportion of the prostate cancer currently diagnosed by the combination of an elevated PSA level and a TRUS biopsy is actually low-risk disease.11 The vast majority of such cases require nothing more than active surveillance, but many of the men involved, unfortunately, are subjected to unnecessary treatments.12
Multiparametric magnetic resonance imaging
A diagnostic test, that can detect significant prostate cancer, but can exclude indolent disease, has therefore been desperately needed. Multiparametric magnetic resonance imaging (mpMRI) may turn out to be that test.
Prostate assessment by MRI has been available for many years, but only recently has it shown real promise. This has been achieved by combining multiple parameters, including T2-weighted imaging, diffusion-weighted imaging and dynamic contrast enhancement, and by reporting results in a standardised fashion, such as the framework provided by the Prostate Imaging–Reporting and Data System.13
Recently published mpMRI research by two Australian groups may provide the breakthrough for this approach.
In Brisbane, Pokorny and colleagues undertook a prospective study that compared 12-core TRUS biopsy with mpMRI. Targeted biopsies of suspicious lesions were performed to confirm the mpMRI findings. It was found that mpMRI was considerably more sensitive than TRUS biopsy in detecting significant cancer, with negative predictive values (NPVs) of 97% and 72%, respectively. That is, only 3% of significant cancers were missed by mpMRI, compared with 28% not detected by TRUS biopsy. At the same time, performing only mpMRI-targeted biopsies reduced the diagnosis of indolent disease by as much as 89%, and the need for biopsy by 51%.14
In Sydney, Thompson and colleagues compared mpMRI with 30-core transperineal biopsy, presumed to be a more accurate assessment of the presence of cancer. They also found excellent NPVs of 92%–96% for mpMRI, depending on the definition of “significant cancer”. The overdiagnosis of low-risk cancer by 34% would have been reduced by mpMRI-targeted biopsies, and the need for biopsy by 50%.15
The future role of mpMRI in prostate cancer diagnosis
These landmark reports argue in favour of a significant future role for mpMRI in the diagnosis of prostate cancer. It has already entered prostate cancer guidelines in the United Kingdom, where the National Institute for Health and Care Excellence recently recommended that mpMRI be considered for men with a negative TRUS biopsy, to determine whether a further biopsy is required.16
Although mpMRI might initially seem an expensive addition to the diagnostic algorithm, recent evidence suggests that it may ultimately be cost-effective.17 In Australia, however, the costs of an mpMRI prostate assessment ($400–$1000) are not currently reimbursed by Medicare.
It is important to note that the excellent results obtained in the Australian studies relied heavily on the immense mpMRI experience of the radiologists and urologists involved. Such expertise remains unusual. Further, the results need to be validated by larger multicentre studies before mpMRI be considered for routine use.
In the meantime, a prostate mpMRI should be ordered by urologists only with caution and after discussing it with radiologists with the necessary expertise. At our institution, we conduct a regular multidisciplinary prostate mpMRI meeting, a practice we recommend both as a means of quality control and for accelerating the development of expertise.
It is also imperative that long-term patient outcomes are investigated in settings where MRI has been included in the diagnostic algorithm, so that the value of this exciting advance can be accurately assessed. For this purpose, we have maintained an institutional ethics committee-approved prospective database of all such patients, and look forward to sharing our findings in the future.
The role of mpMRI in prostate cancer detection is rapidly evolving. By enabling targeted biopsies that exclusively detect significant cancer, mpMRI may provide the diagnostic accuracy that has been so sorely lacking. As such, it has the potential to revolutionise both the diagnosis and treatment of prostate cancer.
Provenance: Not commissioned; externally peer reviewed.
- 1. Moyer VA, on behalf of the US Preventive Services Task Force. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med 2012; 157: 120-134.
- 2. Bell N, Gorber SC, Shane A, et al. Recommendations on screening for prostate cancer with the prostate-specific antigen test. CMAJ 2014; 186: 1225-1234.
- 3. Carter HB, Albertsen PC, Barry MJ, et al. Early detection of prostate cancer: AUA Guideline. J Urol 2013; 190: 419-426.
- 4. Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent — update 2013. Eur Urol 2014; 65:124-137.
- 5. Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med 2008; 358: 1250-1261.
- 6. Loeb S, Vellekoop A, Ahmed HU, et al. Systematic review of complications of prostate biopsy. Eur Urol 2013; 64: 876-892.
- 7. Boniol M, Boyle P, Autier P, et al. Critical role of prostate biopsy mortality in the number of years of life gained and lost within a prostate cancer screening programme. BJU Int 2012; 110: 1648-1652.
- 8. Stamey TA, Caldwell M, McNeal JE, et al. The prostate specific antigen era in the United States is over for prostate cancer: what happened in the last 20 years? J Urol 2004; 172: 1297-1301.
- 9. Nam RK, Saskin R, Lee Y, et al. Increasing hospital admission rates for urological complications after transrectal ultrasound guided prostate biopsy. J Urol 2013; 189(1 Suppl): S12-S17.
- 10. Lecornet E, Ahmed HU, Hu Y, et al. The accuracy of different biopsy strategies for the detection of clinically important prostate cancer: a computer simulation. J Urol 2012; 188: 974-980.
- 11. Cooperberg MR, Broering JM, Kantoff PW, Carroll PR. Contemporary trends in low risk prostate cancer: risk assessment and treatment. J Urol 2007; 178: S14-S19.
- 12. Evans SM, Millar JL, Davis ID, et al. Patterns of care for men diagnosed with prostate cancer in Victoria from 2008 to 2011. Med J Aust 2013; 198: 540-545. <MJA full text>
- 13. Barentsz JO, Richenberg J, Clements R, et al. ESUR prostate MR guidelines 2012. Eur Radiol 2012; 22: 746-757.
- 14. Pokorny MR, de Rooij M, Duncan E, et al. Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies. Eur Urol 2014; 66: 22-29.
- 15. Thompson JE, Moses D, Shnier R, et al. Multiparametric magnetic resonance imaging guided diagnostic biopsy detects significant prostate cancer and could reduce unnecessary biopsies and over detection: a prospective study. J Urol 2014; 192: 67-74.
- 16. Graham J, Kirkbride P, Cann K, et al. Prostate cancer: summary of updated NICE guidance. BMJ 2014; 348: f7524.
- 17. de Rooij M, Crienen S, Witjes JA, et al. Cost-effectiveness of magnetic resonance (MR) imaging and MR-guided targeted biopsy versus systematic transrectal ultrasound-guided biopsy in diagnosing prostate cancer: a modelling study from a health care perspective. Eur Urol 2014; 66: 430-436.
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