Introduction
Reliable identification of locally advanced prostate cancer (PCa) is regarded crucial for making decisions on treatments [
1]. Traditionally, clinical evaluation of the extent of PCa has been based on prostate-specific antigen (PSA), digital rectal examination (DRE), transrectal ultrasound (TRUS) and biopsy results [
1]. These clinical tools often underestimate tumour extent and are not accurate enough to recognise locally advanced disease [
1‐
4]. For other pelvic malignancies, in particular rectal cancer, magnetic resonance imaging (MRI) is the “gold standard” for detecting locally advanced disease and for treatment stratification [
5]. MRI is increasingly being used and recommended for PCa staging [
6‐
11]. However, a wide range of sensitivities and specificities for staging have been reported [
8,
11]. The use of endorectal phased-array coil has been shown to significantly improve the specificity of extraprostatic extension (EPE) detection, but not the sensitivity when compared with pelvic phased-array coil with equal image resolution [
12]. Furthermore, use of an endorectal coil is associated with increased costs, reduced patient throughput and discomfort to the patient. The performance of MRI is limited by the facts that low-grade tumours are hardly distinguishable from normal prostate tissue [
11], that malignant glandular tissue often is intermixed with benign prostate tissue [
13,
14], and that the typical spatial resolution does not allow for the detection of sub-millimetre disease [
15].
There is currently an ongoing debate regarding the clinical usefulness of PCa staging by MRI [
9,
11,
16,
17]. The main benefit of MRI staging probably lies in the discovery of clinically unrecognised, locally advanced cancer. Being a third-line referral cancer hospital with a significant proportion of patients with locally advanced disease, our study population is in this sense appropriate [
18] for the assessment of the clinical usefulness of MRI staging.
In this study, we explored the performance of clinical routine pelvic MRI using phased-array coil and a widely applicable imaging protocol for the detection of locally advanced PCa. Consecutive and prospectively performed MRI and histopathology interpretations were compared without re-assessments or patient exclusions to ensure that the reported data truly reflected routine clinical practice. We also sought to assess clinical significance by reviewing overstaged and understaged cases and by recording the resection margin status.
Discussion
This report shows that although limited in overall accuracy, the detection of locally advanced disease improved substantially when phased array 1.5-T MRI was added to clinical staging by routine DRE and TRUS. Furthermore, for most patients the misrecognition of EPE did not lead to a compromised surgical outcome.
The accuracy of the detection of locally advanced PCa in our study (65.4 %) was within the range, but at the lower end of previously published studies (59.4–85.9 %) [
12,
27‐
31]. The wide range of reported accuracy levels reflects differences in patient populations, histopathological interpretations, evaluation methods, MR technology and reader experience; thus, comparisons of reported results and assessments of clinical significance are challenging. Even with a MRI protocol representing minimal technical requirements [
9,
16] and a limited overall accuracy, the clinical significance of MRI staging in our study was evident, as EPE leading to a positive margin was overlooked in only 21 cases (15.6 %).
Patient populations influence staging accuracy, as a high rate of organ-confined disease may obscure a poor detection of locally advanced disease, and small study populations may result in higher staging performance [
18]. Our study population was relatively large (
n = 208) and consisted of 64.9 % with stage pT3-disease. Furthermore, we did not exclude examinations with unsatisfactory image qualities; hence, our results reflected routine radiological practice. A limitation to our study is the lack of sector-based comparison between MRI and histopathology. Neither the side nor the level of EPE was consistently reported in the prospectively recorded data.
In 2009 the International Society of Urological Pathology (ISUP) reached consensus that EPE should be stratified into focal (Fig.
4) or minimal, or established (Fig.
5) or extensive [
32]. However, no consensus has been reached regarding the criteria of focal versus established EPE [
1,
32,
33]. ISUP also reported considerable inconsistencies in the interpretation of EPE status in equivocal specimens. This inconsistency inevitably will influence the level of MRI accuracy as histopathological evaluation is considered the “gold standard”. In our study, a striking 64.4 % of the unrecognised T3 cases at MRI had free margins. When considering that extended surgery was not performed due to preoperative interpretation of organ-confined disease, free margins indicate that the extension of EPE was minimal (focal EPE). Consequently, by using established EPE [
32,
33] as the histopathological criterion for clinically significant, locally advanced disease, MRI accuracy may improve.
Image resolution is critical for the visualisation of EPE. According to the Nyquist theorem, anatomical structures must be twice the sampling size (pixel) in order to be detected. The resolution used in our MR sequences does not allow for the reliable depiction of EPE with an extent less than approximately 1 mm. Millimetre resolution is also recommended for MR staging in other pelvic malignancies [
5,
34,
35]. A radial extent of EPE that exceeds 1 mm has recently been reported to predict recurrence [
36,
37]. Improved resolution using endorectal coil [
12] and higher field strengths have been shown to enable the detection of EPE of 0.5 mm [
12,
15]. However, very small voxels does not necessarily translate into improved detection of focal EPE, as minor involuntary movement of the prostate will induce partial volume effects. Furthermore, depicting EPE of less than 1 mm will not necessarily improve surgical outcome. Due to limited spatial resolution, dynamic contrast-enhanced MRI would probably not improve the detection of focal EPE [
28].
In the case of equivocal EPE status at MRI, we agreed to downstage, and thus the overstaging rate was low (9.6 %). However, this practice led to understaging. Tumour admixed with extraprostatic fat or bladder musculature is characteristic of EPE, and microscopic tumour foci and focal EPE (< 1 mm) will not be detectable at MRI (Fig.
4). As a result, understaging is unavoidable. Therefore, if MRI is to be a useful decision-making tool for urologists, overstaging must be minimised. By using clearly visualised EPE as an MRI criterion for T3 disease, a high PPV (85.4 %) was achieved. The risk associated with systematic downstaging is that surgeons may wrongly assume that the nerve-sparing approach is safe.
When attempting to contextualise our MR findings, we realised that concerns related to pathology and surgery had to be considered. As the majority of patients with unrecognised locally advanced disease achieved free resection margin, the clinical significance of MRI is obviously not reflected solely by T-stage accuracy. In the light of recent reports that indicate the prognostic significance of radial EPE quantification [
36,
37] and the limited ability of MRI to detect focal EPE, stratification of EPE as focal or established is of importance when assessing the clinical significance of MRI. If the clinical significance of MRI is assessed in terms of resection margin status, consideration must be given to both the extent of EPE and the surgical plane of dissection (preserving function versus ensuring free margin). Based on the results and limitations of our study, we are currently investigating in a prospective study (ClinicalTrials NCT01464216) the relationship between multiparametric MRI with increased spatial resolution, the radial extent of EPE at pathology, surgical techniques, resection margin status and long-term follow-ups.
In conclusion, although the detection accuracy was limited, MRI substantially improved the detection of locally advanced disease when added to conventional staging by routine DRE and TRUS. Strict MRI criteria for EPE ensured minimal overstaging, but induced understaging. Free resection margins were achieved for the majority of patients were MRI failed to recognise EPE. This indicates that the clinical significance of T-staging by MRI is not fully reflected by the ability to detect EPE per se. By stratifying the extent of EPE into focal or established, the staging accuracy is likely to increase as will the clinical significance of MRI as a tool for treatment planning.