False positive and false negative diagnoses of prostate cancer at multi-parametric prostate MRI in active surveillance
MP-MRI is a critical component in active surveillance (AS) of prostate cancer (PCa) because of a high negative predictive value for clinically significant tumours. This review illustrates pitfalls of MP-MRI and how to recognise and avoid them. The anterior fibromuscular stroma and central zone are low signal on T2W-MRI/apparent diffusion coefficient (ADC), resembling PCa. Location, progressive enhancement and low signal on b ≥1000 mm²/s echo-planar images (EPI) are differentiating features. BPH can mimic PCa. Glandular BPH shows increased T2W/ADC signal, cystic change and progressive enhancement; however, stromal BPH resembles transition zone (TZ) PCa. A rounded morphology, low T2 signal capsule and posterior/superior location favour stromal BPH. Acute/chronic prostatitis mimics PCa at MP-MRI, with differentiation mainly on clinical grounds. Visual analysis of diffusion-weighted MRI must include EPI and appropriate windowing of ADC. Quantitative ADC analysis is limited by lack of standardization; the ADC ratio and ADC histogram analysis are alternatives to mean values. DCE lacks standardisation and has limited utility in the TZ, where T2W/DWI are favoured. Targeted TRUS-guided biopsies of MR-detected lesions are challenging. Lesions detected on MP-MRI may not be perfectly targeted with TRUS and this must be considered when faced with a suspicious lesion on MP-MRI and a negative targeted TRUS biopsy histopathological result.
• Multi-parametric MRI plays a critical role in prostate cancer active surveillance.
• Low T2W signal intensity structures appear dark on ADC, potentially simulating cancer.
• Stromal BPH mimics cancer at DWI and DCE.
• Long b value trace EPI should be reviewed
• Targeted biopsy of MR-detected lesions using TRUS guidance may be challenging.
KeywordsProstate cancer Active surveillance of prostate cancer Multi-parametric MRI Targeted biopsy Diffusion-weighted imaging
Prostate cancer (PCa) is the most common cancer among males in North America [1, 2] and the most common solid neoplasm in Europe . PCa is typically diagnosed with non-targeted systematic trans-rectal ultrasound (TRUS)-guided biopsy in patients with an elevated prostate serum antigen (PSA) level and/or abnormal digital rectal examination (DRE). The management of a particular patient with PCa is multi-factorial and patient specific due to the biological heterogeneity of PCa. Traditional treatment of PCa varies from radical prostatectomy (RP) or radiotherapy (RT) to watchful waiting (delayed symptomatic non-curative treatment of apparently localised PCa in males who are not candidates for aggressive local therapy) [1, 3]. Active surveillance (AS) is defined as the expectant management (deferred immediate therapy) of PCa in carefully selected males with localised disease considered to be at low risk for progression . AS differs from watchful waiting because definitive treatment is used in patients managed with AS when there is evidence that the patient is at an increased risk for disease progression [4, 5]. AS has become the treatment of choice for low-grade, low-volume tumours [6, 7] and is heavily reliant on accurate detection of tumour, accurate estimate of tumour volume and accurate Gleason grading of tumour [6, 7].
Non-targeted TRUS-guided biopsy typically obtains 6–12 core biopsies of the peripheral zone (PZ), which harbours approximately 70 % of cancers [1, 8]. The limitations of non-targeted TRUS-guided biopsy are well known  with an estimated 20 % false-negative rate [9, 10, 11]. Furthermore, non-targeted TRUS-guided biopsy may yield unreliable information regarding the volume, extent and aggressiveness of PCa; it is has been reported that up to 30–45 % of patients are upgraded/upstaged from their initial diagnosis at TRUS-guided needle biopsy after RP . Moreover, certain areas of the prostate gland [i.e., the anterior gland, transition zone (TZ) and apex] are known to be under-sampled or not sampled at all at routine non-targeted TRUS-guided biopsy and are now increasingly being recognised as areas that may contain clinically significant (CS) tumours . These limitations are of critical importance in AS, where treatment decisions are based on risk stratification and dependent on accurate Gleason grading of tumours .
Sequence parameters for multi-parametric MRI of the prostate protocol performed with a pelvic surface coila at 3 Tb
Field of view (mm)
Slice thickness/gap (mm)
Echo train length
Receiver bandwidth (Hz/voxel)
Acquisition time (min)
Number of signals averaged
350 × 350
320 × 320
T1 3D dual-echo GREd
240 × 240
292 × 224
220 × 220
320 × 256
4.0/0 3.0/0 3.0/0
280 × 280
128 × 80
T1 GREf dynamic contrast
220 × 220
128 × 128
A variety of interpretive and technical pitfalls may be encountered at MP-MRI of the prostate. A failure to recognise and correct these errors in AS patients can result in suboptimal care. False-positive diagnoses of areas of potential cancers at MP-MRI create clinical uncertainty and often lead to multiple unnecessary biopsies or in certain cases surgical management of low-grade, low-volume disease. Moreover, a failure to recognise clinically significant cancers in males being considered for or treated with AS could result in suboptimal patient outcomes. The purpose of this review is to illustrate both interpretive and technical pitfalls encountered at MP-MRI in the active surveillance population and how to detect, correct and avoid them.
Normal anatomic structures can mimic anterior and TZ cancers
Post-biopsy haemorrhage can mimic PZ PCa on T2W MRI
Benign prostatic hyperplasia (BPH) resembles TZ PCa
BPH is extremely common in the TZ and its prevalence increases with age. BPH can be nodular and TZ nodules are commonly encountered at MP-MRI , and nodular BPH may mimic TZ PCa . Nodular BPH is categorised into three main subtypes: glandular, stromal and mixed.
At histopathology and MP-MRI, it is more common to identify a TZ BPH nodule with features of both glandular and stromal BPH. Typically one pattern (glandular or stromal) will predominate; however, features of both types of BPH can be seen within the same nodule, which can further complicate the diagnosis. In cases of mixed BPH, a combination of imaging features of glandular and stromal BPH are encountered . Usually, the presence of increased T2W SI and cystic change (from glandular BPH) within a lesion are reassuring findings of BPH (Fig. 7) since these findings are rarely encountered in PCa.
Acute and chronic prostatitis mimics PCa
Ductal variant adenocarcinoma may be occult on T2W MRI
T2W motion correction with radial acquisition obscures some PCa
Visual/quantitative analysis of DWI for tumour detection/grading is complex
DCE lacks standardisation and is limited in the TZ
DCE improves the detection of PCa and DCE parameters correlate with PCa grade [69, 70, 71]. Currently, there is no established interpretation criteria for DCE analysis which varies from simple visual analysis to semi-quantitative analysis to full quantitative pharmacokinetic modelling . A recent study demonstrated that DCE is underutilised in clinical practice compared to DWI and that semi-quantitative and quantitative analyses were not commonly used . In the revised PI-RADS v2.0 guidelines, DCE analysis has been modified from semi-quantitative curve analysis to a simple visual analysis .
Targeted biopsy of MR-detected lesions using TRUS-guidance is challenging
MP-MRI for PCa has transformed practice, but has created new challenges. Obtaining accurate histological correlation from lesions detected at MP-MRI may be challenging. MRI guided biopsy is accurate; however, this technique is limited by cost, availability of and access to MRI, prolonged procedure times and patient discomfort . The use of TRUS guidance for biopsy of MP-MRI-detected lesions is currently a preferred option.
The use of Fusion software (which automatically integrates MP-MRI data with real-time 3D TRUS images) provides an alternative to cognitive registration . Fusion software is not without its own limitations including mainly errors in fusion that relate to the spatial deformation of the prostate at TRUS compared to mp-MRI . Moreover, this technology is expensive and at the moment is available in a few specialised centres, although availability is increasing. Studies comparing cognitively registered targeted TRUS biopsy to software fused targeted TRUS biopsy are lacking and have shown mixed results. While several studies have shown no difference between CR and Fusion software [73, 74], other studies have shown an improvement in the detection rate of cancer using fusion software systems [75, 76].
It is critical to emphasise that when a targeted TRUS-guided biopsy performed for a suspicious lesion detected on MP-MRI (using either cognitive registration or fusion software) is negative, the MP-MRI should be reviewed in the context of the biopsy results and other clinical factors in order to consider the possibility of an erroneous targeted biopsy. In these instances, repeat MRI or targeted biopsies can be contemplated.
In conclusion, MP-MRI has become a critical component for patients being considered for or enrolled in active surveillance protocols for the management of low-grade and low-volume prostate cancers. MP-MRI is a proven imaging modality that can detect clinically significant foci of prostate cancer with high degrees of accuracy; the high negative predictive value of MP-MRI is particularly well suited for the AS of PCa. A number of pitfalls, both interpretive and technical, may be encountered at MP-MRI of the prostate and a failure to recognise these pitfalls in the AS population can result in suboptimal patient care. Targeted biopsies of MP-MR-detected lesions poses a new challenge and opportunity in clinical practice. The limitations of TRUS-guidance for lesion detection during targeted biopsies should be acknowledged in order to improve the diagnostic yield of targeted biopsies. A thorough understanding of these MP-MRI pitfalls is important for the MR practitioner involved in the management of prostate cancer.
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