Urologic Oncology: Seminars and Original Investigations
Review articlePerformance of multiparametric magnetic resonance imaging in the evaluation and management of clinically low-risk prostate cancer
Introduction
As a consequence of widespread use of prostate-specific antigen (PSA) for prostate cancer screening, high-risk prostate cancers that are amenable to curative therapy are diagnosed earlier. However, at the same time, widespread screening is also associated with false-positive results and detection and overtreatment of low-risk disease. Active surveillance (AS) of prostate cancer is a viable option for the management of low-risk disease. This approach not only reduces the risk of overtreatment of indolent disease, but also appears to provide similar disease-free outcomes when compared with immediate treatment [1]. The most widely used criteria for categorization of low-risk disease are pathologic features described as (1) Gleason ≤ 6 without any Gleason pattern 4 or 5, (2) organ-confined disease, and (3) tumor volume<0.5 cm3 [2], [3].
Although Gleason 6 has been reported to be associated with disease progression after radical prostatectomy, reassessment of prostatectomy specimens revealed undergrading, understaging, and uncertain staging (intraprostatic incision), or grading (presence of tertiary pattern 4) in a setting of disease progression following radical prostatectomy. With precise histologic evaluation, the risk of disease progression after surgery in men with low-risk disease is very low (0.4%) [4].
There are wide variations in pathologic biopsy parameters used for inclusion into AS programs. However, the rate of unfavorable disease is still high and even with strictest criteria and use of 20 plus core biopsy protocol, 20% of patients are misclassified as having a low-risk disease [5].
Few nomograms have been reported to discriminate low-risk disease from clinically significant disease. The most predictive model was suggested by Chun et al. with 90% predictive accuracy of low-risk disease detection [6]. The earliest nomogram was developed by Kattan and colleagues [7]. Recently, they have incorporated imaging findings, from the magnetic resonance imaging and spectroscopy (MRI/MRSI) to the Kattan nomogram and have validated the new models. The area under the curve (AUC) increased from 0.558 to 0.741 in a base model and from 0.707 to 0.762 in another model incorporating percent of positive biopsy cores [8].
MRI has emerged as a promising tool for the evaluation of the prostate because with its high soft tissue contrast, it allows morphologic assessment of the gland, and with its capabilities to evaluate molecular and physiologic parameters of tissues, it aids in detection of metabolic, diffusion, and perfusion abnormalities associated with cancer.
Reclassification of disease in patients undergoing AS mainly occurs 1 to 2 years after the diagnosis, which is primarily owing to undersampling of the more aggressive tumor rather than progression of indolent tumor [9], [10]. These sampling errors result from the lack of access to the more aggressive lesions located anteriorly in the transition zone (TZ) or blind biopsy of lesions even with systematic extended biopsy schemes. Therefore, the introduction of MR-targeted biopsy allowed a more accurate sampling of the most suspicious lesions detected on imaging.
In this article, we review the multiparametric MRI (mMRI) of the prostate and MR-guided prostate biopsy, and their role in the evaluation and management of men with low-risk prostate cancer.
Section snippets
Morphologic MR imaging
The morphologic imaging with T2-weighted imaging (T2WI) gives a picture of the zonal anatomy of the prostate. The peripheral zone (PZ) tumors are typically detected as low signal intensity lesions on the high signal intensity background of normal tissue on T2WI. However, T2WI alone is neither sensitive (47.8%–88.2%) nor specific (44.3%–81%) for prostate cancer detection and should be interpreted in combination with other functional MR parameters [11]. For instance, there are some benign
Tumor localization in low-risk disease
Early studies showed that the addition of functional imaging parameters improves the sensitivity of tumor detection. However, those early studies mostly used low-strength field scanners with a limited specificity [30].
A combination of T2WI, DWI, and DCE-MRI was reported as the best protocol for imaging of unilateral low-risk PZ cancer with sensitivity and specificity of 85% and 83%, respectively. Although the combination of T2WI and DWI is the best imaging protocol for detection of TZ tumors in
Prediction of tumor laterality
Hemiablative focal therapy is a potential treatment method for patients with unilateral clinically significant disease (CSD). Matsuoka et al. assessed the performance of DWI and extended combined transperineal and transrectal ultrasound (TRUS)-guided biopsy to detect unilateral CSD or any indolent disease. They demonstrated that DWI, biopsy, and the combination of the 2 can effectively rule out the presence of any cancer (either indolent or CSD) in 22.1%, 27.8%, and 43.5%, respectively, and
Detection of anterior/TZ prostate cancer
The anterior prostate cancers (APC), comprising approximately 21% of all types of prostate cancer, are anatomically located in anteromedial and inferior portions of TZ or the anterior horns of PZ or both [36].
These tumors are not only nonpalpable with rectal examination but also hard to detect with TRUS biopsy [37]. Moreover, TZ-directed needle biopsy does not detect the dominant TZ lesion in approximately 80% of cases. Thus, screening needle biopsy from TZ is not a reliable method for
Prediction of prognostic outcome
Endorectal MRI has been shown to be useful for prediction of prognosis of intermediate- and high-risk diseases. It appears that radiologic distinction of T3 vs. T2 disease is predictive of a significantly worse biochemical outcome in patients with intermediate- and high-risk prostate cancers [50].
The predictive value of mMRI for prognostic outcome of low-risk patients eligible for AS has not been widely studied. Tumor inapparency at imaging is part of definition of stage T1 disease. Cabrera et
Tumor grading
In a study by Tamada et al. [57], ADC values in PZ tumors are in significant negative correlation with tumor Gleason score (r = 0.497). Similarly, Doo et al. [32] reported that the mean ADC value of tumors with Gleason 7 or higher (779.4×106 mm²/s) is significantly lower than that of low-grade tumors with Gleason 6 (874.6×106 mm2/s). Another study documented a significant negative correlation between the ADC values and cellular density (r = −0.50); cancer tissues with lower ADC values have higher
Targeted prostate biopsy
The accurate and adequate prostate sampling is crucial for determination of both patient eligibility for AS and disease monitoring. The importance of immediate repeat biopsy was evident in a study from Memorial Sloan-Kettering Cancer Center. In this study, repeat targeted biopsy in 3 months of initial biopsy session revealed upstaging and upgrading in 27% of patients eligible for AS. Authors recommended the immediate repeat biopsy for discrimination of best candidates of AS [54].
There is higher
Conclusion
The mMRI, particularly DWI with T2WI, is a useful tool for tumor localization in low-risk prostate cancer and can detect lesions that are more likely missed on extended biopsy schemes. Although the mMRI is not routinely being used for risk stratification and prediction of prognosis in prostate cancer, it may provide valuable information to predict outcome of men with low-risk disease in AS programs. Incorporation of mMRI into the workup and monitoring of patients with low-risk disease can help
References (81)
- et al.
Prostate cancer death of men treated with initial active surveillance: clinical and biochemical characteristics
J Urol
(2010) - et al.
Nonpalpable stage T1c prostate cancer: prediction of insignificant disease using free/total prostate specific antigen levels and needle biopsy findings
J Urol
(1998) - et al.
A pathological reassessment of organ-confined, Gleason score 6 prostatic adenocarcinomas that progress after radical prostatectomy
Hum Pathol
(2009) - et al.
Counseling men with prostate cancer: a nomogram for predicting the presence of small, moderately differentiated, confined tumors
J Urol
(2003) - et al.
Diffusion-weighted MRI of adult male pelvic cancers
Clin Radiol
(2012) - et al.
Dynamic contrast-enhanced MRI and MR diffusion imaging to distinguish between glandular and stromal prostatic tissues
Magn Reson Imaging
(2008) - et al.
Determination of the time for maximal response to neoadjuvant hormone therapy for prostate cancer using magnetic resonance with spectroscopy (MRSI) and dynamic contrast enhancement (DCEMR)
Urol Oncol
(2012) - et al.
MR imaging of the prostate at 3 Tesla: comparison of an external phased-array coil to imaging with an endorectal coil at 1.5 Tesla
Acad Radiol
(2004) - et al.
Prostatic transition zone directed needle biopsies uncommonly sample clinically relevant transition zone tumors
J Urol
(2009) - et al.
Transition zone carcinoma of the prostate gland: a common indolent tumour type that occasionally manifests aggressive behaviour
Pathology
(2003)
Endorectal magnetic resonance imaging as a predictor of biochemical outcome after radical prostatectomy in men with clinically localized prostate cancer
J Urol
Endorectal T2-weighted MRI does not differentiate between favorable and adverse pathologic features in men with prostate cancer who would qualify for active surveillance
Urol Oncol
The contemporary concept of significant versus insignificant prostate cancer
Eur Urol
Magnetic resonance imaging for predicting prostate biopsy findings in patients considered for active surveillance of clinically low risk prostate cancer
J Urol
Impact of multiparametric endorectal coil prostate magnetic resonance imaging on disease reclassification among active surveillance candidates: a prospective cohort study
J Urol
High incidence of prostate cancer detected by saturation biopsy after previous negative biopsy series
Eur Urol
Trans-rectal versus trans-perineal saturation rebiopsy of the prostate: is there a difference in cancer detection rate?
Urology
Three-tesla magnetic resonance-guided prostate biopsy in men with increased prostate-specific antigen and repeated, negative, random, systematic, transrectal ultrasound biopsies: detection of clinically significant prostate cancers
Eur Urol
Prospective assessment of prostate cancer aggressiveness using 3-T diffusion-weighted magnetic resonance imaging-guided biopsies versus a systematic 10-core transrectal ultrasound prostate biopsy cohort
Eur Urol
Transperineal magnetic resonance image targeted prostate biopsy versus transperineal template prostate biopsy in the detection of clinically significant prostate cancer
J Urol
MR-guided biopsy of the prostate: an overview of techniques and a systematic review
Eur Urol
Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves cancer detection following transrectal ultrasound biopsy and correlates with multiparametric magnetic resonance imaging
J Urol
Multiparametric magnetic resonance imaging and ultrasound fusion biopsy detect prostate cancer in patients with prior negative transrectal ultrasound biopsies
J Urol
A novel stereotactic prostate biopsy system integrating pre-interventional magnetic resonance imaging and live ultrasound fusion
J Urol
Image-guided prostate biopsy using magnetic resonance imaging-derived targets: a systematic review
Eur Urol
Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer
J Am Med Assoc
Pathological findings and prostate specific antigen outcomes after radical prostatectomy in men eligible for active surveillance—does the risk of misclassification vary according to biopsy criteria?
J Urol
Critical assessment of tools to predict clinically insignificant prostate cancer at radical prostatectomy in contemporary men
Cancer
Preoperative nomograms incorporating magnetic resonance imaging and spectroscopy for prediction of insignificant prostate cancer
BJU Int
Radical prostatectomy findings in patients in whom active surveillance of prostate cancer fails
J Urol
Changes in prostate cancer grade on serial biopsy in men undergoing active surveillance
J Clin Oncol
Predictive value of MRI in the localization, staging, volume estimation, assessment of aggressiveness, and guidance of radiotherapy and biopsies in prostate cancer
J Magn Reson Imaging
Advancements in MR imaging of the prostate: from diagnosis to interventions
Radiographics
Diffusion-weighted MR imaging for the evaluation of seminal vesicle invasion in prostate cancer: initial results
J Magn Reson Imaging
Differentiation of noncancerous tissue and cancer lesions by apparent diffusion coefficient values in transition and peripheral zones of the prostate
J Magn Reson Imaging
Diffusion-weighted imaging in normal prostate and differential diagnosis of prostate diseases
Abdom Imaging
Overview of dynamic contrast-enhanced MRI in prostate cancer diagnosis and management
Am J Roentgenol
Prognostic value of microvessel density in prostate cancer: a tissue microarray study
World J Urol
Prospective study of prostate tumor angiogenesis and cancer-specific mortality in the health professionals follow-up study
J Clin Oncol
Multi-parametric MR imaging of transition zone prostate cancer: imaging features, detection and staging
World J Radiol
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Who bears the greatest burden of aggressive treatment of indolent prostate cancer?
2015, American Journal of MedicineCitation Excerpt :More accurate identification of precisely which men are appropriate for surveillance may lead to more widespread acceptance of deferred treatment among both patients and physicians. Specifically, methods for selecting those appropriate for surveillance for indolent disease could include more personalized risk stratification as afforded by tools such as the University of California, San Francisco Cancer of the Prostate Risk Assessment score, use of magnetic resonance imaging to rule out potentially higher-grade lesions that could be targeted for biopsy, and novel clinical and molecular markers as they become available.2,5,32-34 Magnetic resonance imaging has a high specificity for low-risk prostate cancer, and currently available imaging techniques hold promise for improving patient selection for surveillance.34