MRI Reclassification of Prostate Cancer for Active Surveillance
By: Dan Sperling, MD
Originally published 8/5/2015
Sunnybrook Health Sciences Center (Toronto) is home of prostate cancer expert Dr. Laurence Klotz. As we approach 10 years since we posted the blog below, Dr. Klots and an interdisciplinary team published the results of a prospective long-term study on managing Active Surveillance (AS) patients by use of MRI. Specifically, they explored how well negative MRI results during AS showed it was still safe to hold off on biopsy and treatment. Their research included 530 AS patients who were followed for an average of 8.5 years. By “negative MRI” is meant that one or more repeat scans do NOT show an area suspicious for clinically significant PCa (csPCa). Any area that is suspicious for csPCa would trigger a targeted biopsy and a possible move to treatment. Their report shows they were successful in demonstrating that patients can safely stay on AS as long as their imaging is negative for csPCa. They write: “MRI invisible cancers demonstrated dramatically reduced rates of progression and no patient required intervention. Despite the absence of routine biopsies in the MR negative group, none of these patients progressed over time to GG ≥ 3 or metastatic disease.”[i] They concluded that imaging is “sufficient to identify” csPCa, which reinforces our original message over 9 years ago.
With growing interest in multiparametric magnetic resonance imaging (mpMRI) of the prostate, several roles for using this imaging with respect to prostate cancer (PCa) have been identified:
- Detect and identify regions of interest that are suspicious for significant PCa
- Image-based staging of PCa
- Guidance for targeted biopsies
- Guidance for treatment modalities
- Monitor treatment success
- Monitor during active surveillance (AS)
Whether used for either tracking success after treatment or for monitoring during active surveillance, mpMRI is able to combine anatomic imaging and, by applying sequences such as diffusion weighting, dynamic contrast enhancement and spectroscopy, functional differences between healthy and malignant tissues.[ii] Depending on the clinical indication, imaging time can be shortened to 30 minutes by using at least one functional sequence with T2 weighted MRI. Increasingly, mpMRI is recognized as able to differentiate between significant PCa (likely to be aggressive and not amenable to AS) and insignificant PCa (likely to be latent and therefore amenable to AS).
Active surveillance is undergoing a renaissance as more urologists are recommending it to patients who wish to defer radical treatment with its known risks of urinary and sexual side effects. Conventional AS protocols specify not only PSA complex testing at regular intervals, but also repeat biopsy, often as early as one year after diagnosis. The purpose of repeat testing is to avoid missing a trigger for treatment (e.g. rising PSA/PSA doubling time; upgraded Gleason score upon biopsy). However, compliance with repeat biopsy is inconsistent as patients avoid or resist undergoing the TRUS procedure. This is where mpMRI provides a valuable precursor to a possible biopsy, and additionally allows a targeted biopsy if a suspicious change is detected.
How well is mpMRI up to the task? To address this question, a Chinese research team conducted a recent literature review and meta-analysis (aggregate analysis of all reported results) of relevant articles published up to November 2014.[iii] Their goal was to compare mpMRI results with those of confirmatory biopsy among patients on AS, in order to assess the accuracy of MRI in predicting upgrading. They identified seven studies containing necessary diagnostic data, totaling 1028 patients. They calculated sensitivity of 0.69 and specificity of 0.78. The positive predictive value was 0.44, while the negative predictive value was 0.91. In other words, for this series, mpMRI was better at accurately predicting a lack of significant disease than the presence of significant disease. However, based on their analysis, they concluded that “MRI may reveal an unrecognized significant lesion in 33.27% of patients,” and targeted biopsy of those lesions led to a diagnostic reclassification of 14.45% of them as triggering a treatment decision. Just as important, “…when no suspicious disease progression (66.34%) was identified on MRI, the chance of reclassification on repeat biopsy was extremely low at 6.13%.” The authors concluded that this is favorable news for AS patients who are able to be monitored by mpMRI, since the absence of significant disease findings on imaging would support continued observation.
A second article by Quon et al. (2015) likewise points to the high negative predictive value of mpMRI with regard to significant disease.[iv] They refer to mpMRI as a “critical component” of AS. In addition, the authors identify several ways in which those who read/interpret the images may make errors due to ambiguous conditions in certain anatomic areas of the gland:
- The anterior tissue and central zone may produce low signal (dark areas) during T2 weighted imaging, not to be confused with prostate cancer. There are ways to conduct the imaging to distinguish normal tissue from PCa.
- Benign prostate hyperplasia (BPH) may appear similar to PCa so imaging adjustments can help determine the actual condition.
- Acute or chronic prostatitis can also mimic PCa. The authors point out specific ways to analyze diffusion weighted imaging (DWI) to avoid misinterpretation.
The team also points out that suspicious areas detected on imaging “may not be perfectly targeted with TRUS [biopsy] and this must be considered when faced with a suspicious lesion on MP-MRI and a negative targeted TRUS biopsy histopathological result.” Their concern about this challenge underscores the importance of MRI-targeted, in-bore biopsy for accurate diagnosis.
To sum up, patients diagnosed with PCa who choose to go on active surveillance should speak with their doctors about the merits of monitoring their disease through the use of multiparametric MRI. Its ability to rule out clinically significant disease not only helps eliminate an unnecessary repeat biopsy, but offers peace of mind about continuing on AS. On the other hand, image detection of clinically significant disease will trigger a biopsy, but if performed as an MRI-guided targeted biopsy, both patient and physician can have a high degree of confidence in the results if the cancer is reclassified as a higher grade tumor.
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.
References
[i] Klotz L, Loblaw A, Zhang L, Mamedov A, Vesprini D. Prognostic value of MR visibility/invisibility in men on Active Surveillance. Prostate Cancer Prostatic Dis. 2025 Jan 17.
[ii] Vilanova JC, Luna-Alcalá A, Borada M, Barceló. Multiparametric MRI. The role of MRI techniques in the diagnosis, staging and follow up of prostate cancer. Arch Esp Urol. 2015 Apr;68(3):316-33.
[iii] Guo R, Cai L, Fan Y et al. Magnetic resonance imaging on disease reclassification among active surveillance candidates with low-risk prostate cancer: a diagnostic meta-analysis. Prostate Cancer Prostatic Dis. 2015 May 19. doi: 10.1038/pcan.2015.20. [Epub ahead of print]
[iv] Quon JS, Moosavi B, Khanna M et al. False positive and false negative diagnoses of prostate cancer at multi-parametric prostate MRI in active surveillance. Insights Imaging. 2015 Aug;6(4):449-63. doi: 10.1007/s13244-015-0411-3. Epub 2015 May 23.
