Originally published 7/4/2019
The Prostate MRI Imaging Study (PROMIS) was a landmark event in terms of demonstrating the superiority of multiparametric MRI (mpMRI) for biopsy guidance vs. conventional TRUS (transrectal ultrasound) guidance. Within a few years, more studies began to appear regarding biparametric MRI (bpMRI) as less expensive and less time-consuming than mpMRI. What made bpMRI faster was eliminating the imaging sequence called Dynamic Contrast Enhancement (DCE), which required injection of a contrast agent in order to evaluate tumor blood flow. This raised the question whether the other two MRI parameters (T2 weighted and diffusion weighted) provided enough clinical information about an individual’s prostate cancer (PCa) to guide biopsies and develop treatment plans. Thus, the same authors revisited the extensive data assembled by the original PROMIS study, and recalculated the effect of eliminating the DCE sequence. In fact, the authors found almost no difference in identifying clinically significant PCa when DCE was not included in the scan. They wrote, “Contrast adds little when MP-MRI is used to exclude significant prostate cancer,” and “An intravenous injection of contrast may not be necessary when magnetic resonance imaging is used as a test to rule out significant tumours in the prostate.”[i] While we still prefer to do the full mpMRI scan, it is useful to recognize that where need indicates, using only two parameters will still provide an experienced image reader with sufficient information to rule a biopsy in or out.
In the world of prostate cancer (PCa) diagnosis, the year 2017 began with the January 19 online publication of another brilliant study out of the University College London and other British centers of clinical research.[ii] The study, called PROMIS, was a comparison between multiparametric MRI (mpMRI) vs. TRUS biopsy in terms of diagnostic accuracy. Actually, the basic question at the core of the work was: among men suspected of having PCa and who had never had a biopsy, could mpMRI tell the difference between clinically insignificant and clinically significant PCa? If it could, would that mean that men with apparently insignificant cancer might be able to avoid having a biopsy?
Before describing the study methods and results, I want to explain terms used by the authors:
- Significant or insignificant? Years ago, it was believed by many urologists that ALL PCa, including low grade Gleason 3+3 tumors, were both multifocal and potentially lethal. When it came to making treatment decisions, there were two basic whole-gland choices: radical prostatectomy or whole-gland radiation. Now, however, “…there is an increasing realisation that Gleason 6 lesions do not harbour hallmarks of malignancy and that many Gleason 3+4=7 cancers do well without immediate treatment, whether diagnosed initially or even if missed by a TRUS-biopsy.”[iii] Put another way, Gleason 3+3 and many Gleason 3+4 cancers do not need immediate treatment and can be safely monitored.
- How did the authors define significance? The basic definition of significant PCa used by the authors was the “presence of Gleason ?4 + 3 or more, or a maximum cancer core length (MCCL) involvement of 6mm or more in any location. Other definitions of clinical significance were also assessed secondarily.”
- TPM (transperineal mapping) biopsy as done for the PROMIS study means taking needle samples 5mm apart throughout the gland, accessing the gland through the perineum (skin between the scrotum and anus) rather than through the rectal wall. It was performed under general or spinal anesthesia. NOTE: The purpose of the TPM biopsy was to serve as a reference test because it has the highest biopsy accuracy due to such thorough sampling. Only a prostatectomy specimen can provide more thorough tissue analysis.
- TRUS (transrectal ultrasound) biopsy as done for the PROMIS study means taking 10-12 needle samples in a systematic but random fashion. In this case, it was administered to patients immediately after the TPM biopsy while they were still anesthetized in order to reduce patient visits and minimize dropout between visits.
- Sensitivity and specificity are two statistical terms used in medical diagnosis. Sensitivity means a test correctly identifies those with the disease (true positives). Specificity means the test correctly identifies those without the disease (true negative).
2 purposes of the PROMIS study
The authors wanted to achieve two purposes: a) determine the proportion of men who could safely avoid biopsy altogether, and b) the proportion correctly identified by mpMRI with significant PCa. In short, this study is hypothesizing that mpMRI before biopsy can be used as a triage test for patients. The assumption is that those men suspected of having PCa but who are found by imaging to be truly negative for clinically significant PCa can avoid biopsy. The important word is, of course, significant.
Between May, 2012 and November, 2015, the PROMIS study included 576 participants who met the inclusion criteria and completed the study. Each participant initially had a prostate mpMRI performed on a 1.5 Tesla magnet prior to undergoing TPM and TRUS biopsy. The biopsy results were sent to pathologists who were blinded to (did not know) each patient’s mpMRI results. No patient received an MRI-guided targeted biopsy in order to preserve blinding per the study design.
Since this is such a large, complex and important study on the value of mpMRI before biopsy, I quote the authors’ findings exactly rather than paraphrase them:
On TPM-biopsy, 408 (71%) of 576 men had cancer with 230 (40%) of 576 patients clinically significant. For clinically significant cancer, MP-MRI was more sensitive (93%) than TRUS-biopsy [true positive for clinically significant disease] …Using MP-MRI to triage men might allow 27% of patients avoid a primary biopsy and diagnosis of 5% fewer clinically insignificant cancers. If subsequent TRUS-biopsies were directed by MP-MRI findings, up to 18% more cases of clinically significant cancer might be detected compared with the standard pathway of TRUS-biopsy for all. MP-MRI, used as a triage test before first prostate biopsy, could reduce unnecessary biopsies by a quarter. MP-MRI can also reduce over-diagnosis of clinically insignificant prostate cancer and improve detection of clinically significant cancer.
To sum up, the PROMIS study shows that when both mpMRI and TRUS biopsy are held up against an accurate reference test (TPM biopsy), TRUS performs poorly in detecting clinically significant PCa. On the other hand, the authors calculate that with 93% performance in identifying the presence of clinically significant PCa before biopsy, mpMRI can be spare roughly a quarter of men from biopsy. This is a study that keeps its promise in the world of prostate cancer.NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
[i] Bosaily AE, Frangou E, Ahmed HU, Emberton M et al. Additional Value of Dynamic Contrast-enhanced Sequences in Multiparametric Prostate Magnetic Resonance Imaging: Data from the PROMIS Study. Eur Urol. 2020 Oct;78(4):503-511.
[ii] Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017 Feb 25:389)1007):815-822. https://www.thelancet.com/action/showPdf?pii=S0140-6736%2816%2932401-1
[iii] Ahmed, et al. Diagnostic accuracy of the PROMIS study – Authors’ reply. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31595-7/fulltext