Active surveillance (AS) has emerged as an important management strategy to avoid overtreatment of low-risk indolent prostate cancer and MRI of the prostate has been documented to offer high accuracy for the detection and localization of clinically significant cancer with high negative predictive value. The main role of MRI in AS is in patient selection and monitoring with a potential to minimize the invasiveness of follow-up. Abbreviated prostate MRI protocols offer a diagnostic accuracy and cancer detection rates that are equivalent to those of conventional full multiparametric MRIs.
The over-diagnosis and over-treatment of prostate cancer (PCa) has led to the implementation of active surveillance (AS) as an alternative management strategy for men with favorable-risk disease (low-volume, low-risk prostate cancer) [1]. The premise of AS is that instead of treating PCa at the time of diagnosis, a patient is monitored at frequent intervals for signs of disease progression, at which point the plan is to treat the cancer with definitive curative therapy. Cancer progression is usually monitored with a combination of prostatic specific antigen (PSA), digital rectal exam (DRE), and systematic trans-rectal ultrasound-guided (TRUS) biopsy. Progression on AS is defined as pathologic up-grading (grade-reclassification), or an increase in PCa volume (usually seen as an increase in the number of positive biopsy cores or percentage of a core that is positive for cancer – volume-reclassification) [1]. Progression of disease out of AS eligibility is the trigger for urologists to recommend definitive treatment (radical prostatectomy or radiation therapy for localized disease).
Patient selection for AS and monitoring remains a challenge. For enrollment, most AS programs require National Comprehensive Cancer Network (NCCN) very-low-risk (T1c, Gleason ≤6, PSA <10 ng/mL, <3 positive biopsy cores, ≤50% of each core with cancer, PSA density <0.15 ng/mL/g) or low-risk (T1-2a, Gleason ≤6, PSA <10 ng/mL) disease [2], and a few allow for NCCN low-intermediate-risk disease (low-volume Gleason score 3+4) for men with limited life expectancy [1]. Multiparametric MRI (mpMRI) of the prostate has emerged as an important tool in PCa screening, patient selection for and monitoring in AS. mpMRI has been shown to have good performance for the detection of clinically-significant PCa [3], and has been used to decide on whether or not to biopsy, and to help target MR-visible lesions during prostate biopsy [4].
The PROMIS trial demonstrated the high value of mpMRI and provides compelling evidence for an improved diagnostic performance in the detection of clinically significant PCa (mpMRI more sensitive (93%, 95% CI 88-96%) than TRUS-biopsy (48%, 42-55%; p<0·0001)) and/or a reduction in the need for systematic TRUS biopsies with an MRI-stratified care pathway. Using mp-MRI to triage men might allow 27% of patients avoid a primary biopsy while diagnosing 5% fewer clinically insignificant cancers.
The PRECISION trial of 500 men who underwent randomization into the MRI-based pathway and TRUS-biopsy group showed that clinically significant PCa was detected in 38% of men in the MRI-targeted biopsy group, as compared with 26% in the standard TRUS biopsy group [4]. MRI, with or without targeted biopsy, was superior to standard TRUS biopsy. In the same time, fewer men in the MRI-targeted biopsy group than in the TRUS-biopsy group were diagnosed with clinically insignificant PCa cancer (adjusted difference, −13 %). The application of mpMRI in the diagnosis of clinically significant PCa has been strengthened by recent standardization in image acquisition, interpretation and reporting using the PI-RADS V2 criteria [5]. The PRECISION trial used PI-RADS v2 scoring criteria for prostate lesion classification.
With the robust evidence from the above mentioned trials, the greatest value of mpMRI in men with low volume low risk cancer on AS may be in providing a more accurate initial risk assessment. The negative predictive value for higher grade tumors appears high and mpMRI is especially useful in identifying anterior tumors in the transition zone outside of regions typically sampled with TRUS biopsy. Additional argument in support of MRI in AS is that of the high cost of management of post-biopsy complications including sepsis. As nearly all current AS protocols involve at least one planned repeat prostate biopsy and most programs recommend subsequent serial biopsies over time during the surveillance, this complication is an important consideration. Strategies that can reduce the number of biopsies would have beneficial impact on management of men in AS. The largest gap in clinical and cost knowledge is the value and cost efficacy of serial mpMRI exams in evaluating men in AS. The cost of mpMRI has been associated with several factors which include not only the cost of equipment but also maintenance, operation (personnel, space), utilization, and staff/radiologists training. Shortening of the mpMRI protocol and therefore reducing the scan time holds promise in decreasing the overall cost of the exam.
As demonstrated in the study by Kuhl et al, Radiology 2017 [6], bi-parametric MRI (T2WI and DWI without T1WI and contrast agent injection) in less than 9 minutes allows detection of clinically significant PCa missed by TRUS-guided biopsy and offers a diagnostic accuracy and cancer detection rate that are equivalent to those of conventional full multiparametric contrast-enhanced MRI protocols. Another study by Di Campli et al, Eur J Radiol 2018 [7], showed that the diagnostic accuracy of a bi-parametric MRI protocol is comparable with that of a standard mpMRI protocol for the detection of clinically significant PCa and that the experience of the reader does not significantly modify the diagnostic performance. In a prospective study by Stanzione et al, Eur J Radiol 2016 [8], authors also evaluated the diagnostic accuracy of a bi-parametric protocol and compared results to a multiparametric protocol in a biopsy naïve patient population showing that bi-parametric MRI and mpMRI had a similar overall diagnostic accuracy, with an area under the curve of 0.91 and 0.93 (p = n.s.), respectively.
AS has emerged as an important management strategy to avoid overtreatment of low-risk indolent prostate cancer and recently MRI of the prostate has been documented to offer high accuracy for the detection and localization of clinically significant PCa with high negative predictive value. The use of prostate MRI in both patient selection and follow-up in AS programs is expected to further increase, especially if the cost of MRI can be reduced through efficiency such as abbreviated imaging protocols.