His initial review of the status of PSA screening highlighted the flaws with traditional blood-based PSA screening. Specifically, the low reliability of PSA testing (NPV is poor, 25% of men with PSA < 4 ng/dL have clinically significant prostate cancer) combined with the poor PPV (prostate cancer detection rate of 20-45% based on PSA screening) make it clear that better tests are needed. By increasing accuracy, potentially 55-80% biopsies could be avoided; this doesn’t even consider the cost impact of doing too many biopsies and complications from unnecessary biopsies.
Focusing next on traditional transrectal ultrasound biopsy (TRUS Bx), he highlights the fact that systematic TRUS biopsy over-diagnoses insignificant disease (33% of diagnoses), but missed clinically significant cancer ~18% of the time. This ultimately leads to inappropriate risk stratification, which led to inappropriate treatment allocation.
This is where he then reviewed the true substance of the talk – role for multiparametric MRI (mpMRI). He reviewed a few key mpMRI studies that clearly demonstrate the utility of mpMRI in identifying extracapsular extension (ECE) and large anterior lesions that would be missed on standard TRUS Bx.
However, its role in different stages of prostate cancer diagnosis is not yet clear. We first focused on the role of mpMRI in men with clinical concern for prostate cancer and a prior negative systematic TRUS Biopsy. He clarified that this area is no longer controversial – there is general consensus that mpMRI is recommended and appropriate in this patient. The focus was on two specific studies. The first was the study by Siddiqui et al in JAMA,1 in which a TRUS systematic biopsy was compared to a targeted fusion biopsy based on mpMRI. While the use of mpMRI identified 30% more clinically significant prostate cancer and reduced detection of clinically insignificant prostate cancer by 17%, he did not that there were still about a 10% cohort that had higher grade clinically significant prostate diagnosed by systematic biopsy that were missed by targeted biopsy – false negative rate ~10%. In the PMCC smaller single-institution experience of 100 similar patients, 5 of 100 patients had a false negative rate with targeted biopsy. This highlights that even in this sector in which mpMRI is now recommended, it is still not a perfect test.
He next focused the role of mpMRI in active surveillance patients. In a small single-institution series by PMCC,2 of 60 men enrolled, 32% were reclassified while on AS – 10 were reclassified based on a lesion identified by mpMRI, but 2 were reclassified in a group of men with mpMRI without any visible lesions. The JHU experience3 was similar – upgrading was seen in 1 patient (8%) with MR invisible tumor, but in 40.5% (34 patients) in men with MR visible tumor. Ultimately, absence of a visible tumor is a good predictor of prognosis and progression, suggesting that it can be used to reduce the frequency of repeat biopsies on active surveillance.
When assessing the negative predictive value of mpMRI, there have been many studies using different gold standards for comparison (radical prostatectomy, saturation TRU biopsy, transperineal biopsy). The NPV was between 89.6% to 96%. In unpublished data, Dr. Ghai and the group from PMCC have demonstrated a NPV of 86% for all mpMRI guided biopsies, but importantly, it is 96% in men with prior negative biopsy, but 74% in men on active surveillance. As such, in men with prior negative biopsy, mpMRI has a very good NPV.
The most controversial utilization is in biopsy naïve men. However, it is being considered by multiple different groups. In a study by Delongchamps et al,4 of 391 men who underwent systematic TRUS biopsy and targeted biopsy, they found that while the cancer detection rate was similar in both groups (45-47%), the targeted fusion biopsy would have missed only 2 of 63 high grade prostate cancers, while systematic biopsy only identified 17. Finally, no discussion on this topic can be complete without a discussion of the PROMIS study, completed by the UCL group in the UK.5 In that study, 576 men underwent 1.5T mpMRI followed by systematic TRUS bx and transperineal saturation biopsy. Looking for clinically significant prostate cancer, mpMRI had a 51% PPV and 89% NPV, compared to 90% PPV and 74% NPV by systematic TRUS biopsy. Numbers were similar when varying the definition of clinically significant prostate cancer. However, he does point out that they did not specifically assess the value of targeted biopsy alone, they excluded patients > 100 g, used a Likert grading scale rather than PIRADs scoring, and there was significant inter-reader variability. While the UCL group concluded that mpMRI could be used a triage patients, further data is needed.
The false negative rate is not insignificant from mpMRI. It has been known to be somewhat limited by tumor size, especially lesions <= 0.5 cc. Also, numerous studies have noted some inter-reader variability of the PIRADs v2 scoring system. While a permanent tool in the prostate cancer diagnostics armamentarium, further clarification in different states of the diagnostic pathway is needed.
1. Negative test benefit of MRI
- ~25% of men undergo fewer biopsy
- ~75% fewer cores over the population
- Increased detection of clinically significant prostate cancer by 10-15%
- We are missing ~10% of clinically significant prostate cancer (Gleason 4 component)
- We don’t know yet what the trigger biopsy should be in these patients
Presented By: Sangeet Ghai, MD, FRCR, Cancer Clinical Research Unit (CCRU), University of Toronto, Princess Margaret Cancer Centre
Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto Twitter: @tchandra_uromd at the 72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada
1. Siddiqui MM et al. Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. JAMA. 2015 Jan 27;313(4):390-7. doi: 10.1001/jama.2014.17942.
2. Margel D, Yap SA, Lawrentschuk N, Klotz L, Haider M, Hersey K, Finelli A, Zlotta A, Trachtenberg J, Fleshner N. Impact of multiparametric endorectal coil prostate magnetic resonance imaging on disease reclassification among active surveillance candidates: a prospective cohort study. J Urol. 2012 Apr;187(4):1247-52. doi: 10.1016/j.juro.2011.11.112. Epub 2012 Feb 14.
3. Dianat SS et al. Magnetic resonance-invisible versus magnetic resonance-visible prostate cancer in active surveillance: a preliminary report on disease outcomes. Urology. 2015 Jan;85(1):147-53. doi: 10.1016/j.urology.2014.06.085. Epub 2014 Oct 16.
4. Delongchamps NB, Peyromaure M, Schull A, Beuvon F, Bouazza N, Flam T, Zerbib M, Muradyan N, Legman P, Cornud F. Prebiopsy magnetic resonance imaging and prostate cancer detection: comparison of random and targeted biopsies. J Urol. 2013 Feb;189(2):493-9. doi: 10.1016/j.juro.2012.08.195. Epub 2012 Oct 8.
5. Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, Collaco-Moraes Y, Ward K, Hindley RG, Freeman A, Kirkham AP, Oldroyd R, Parker C, Emberton M; PROMIS study group. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017 Feb 25;389(10071):815-822. doi: 10.1016/S0140-6736(16)32401-1. Epub 2017 Jan 20.