Role of MRI in the diagnosis and management of prostate cancer

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1 For reprint orders, please contact: Role of MRI in the diagnosis and management of prostate cancer Andreas G Wibmer*,1, Hebert Alberto Vargas 1 & Hedvig Hricak 1 Multiparametric MRI of the prostate consists of T1- and T2-weighted sequences, which provide anatomical information, and one or more functional sequences, that is, diffusionweighted imaging, dynamic contrast-enhanced sequences and magnetic resonance spectroscopy. Prostate MRI is the most accurate imaging method for local staging of prostate cancer and can also be used for the noninvasive evaluation of tumor aggressiveness. By magnetic resonance-guided prostate biopsy it is possible to target the most cancersuspicious areas of the gland, especially in patients with a negative transrectal biopsy. In patients with biochemical recurrence after radical treatment, MRI is a valuable tool for the detection of local tumor recurrence and whole-body MRI can be used for the diagnosis of distant metastases. Multiparametric MRI of the prostate has evolved into the standard imaging technique for both the local staging of newly diagnosed prostate cancer and the detection of local recurrence. It has also shown the potential to aid pretreatment risk stratification (e.g., the assessment of cancer aggressiveness). MRI-targeted biopsy is increasingly being used to identify and sample suspicious lesions in the prostate, particularly in patients who have negative repeat transrectal ultrasound (TRUS)- guided biopsies despite clinical findings suggestive of cancer. Furthermore, whole-body MRI is emerging as an alternative for the detection and follow-up of distant cancer spread, especially bone marrow metastases. In this manuscript, we first describe the basic principles of multiparametric prostate MRI, followed by a review of essential knowledge for the application of MRI in prostate cancer detection, staging and follow-up. Finally, we discuss the potential of whole-body MRI as an emerging diagnostic technique for patients at risk for distant spread of disease. Keywords cancer detection cancer recurrence cancer staging MRI prostate cancer risk assessment whole-body MRI Basic principles of multiparametric prostate MRI Multiparametric MRI of the prostate consists of T1-weighted and T2-weighted sequences, diffusionweighted imaging (DW-MRI), dynamic contrast-enhanced sequences (DCE-MRI) and magnetic resonance spectroscopic imaging (MRSI). T1-weighted MRI This sequence is primarily used for the evaluation of regional lymph nodes and osseous structures of the pelvis. It is also useful for the detection of postbiopsy changes, which may mimic prostate cancer on other MRI sequences but typically demonstrate high signal intensity compared with the normal prostate on T1-weighted MRI. To lessen the potential for postbiopsy changes to affect MRI interpretation, some centers recommend that prostate MRI be performed 6 8 weeks after biopsy. As 1 Memorial Sloan Kettering Cancer Center, Department of Radiology, 1275 York Avenue, New York City, NY 10065, USA *Author for correspondence: Tel.: ; Fax: ; a.wibmer@gmx.net part of 2015 Future Medicine Ltd Future Oncol. (Epub ahead of print) ISSN

2 Wibmer, Vargas & Hricak both normal prostate tissue and prostate cancer demonstrate homogeneous low signal intensity on T1-weighted imaging, this sequence is not suitable for prostate cancer detection and characterization. T2-weighted MRI Multiplanar T2-weighted images are the backbone of prostate MRI, as they provide high spatial resolution and excellent soft-tissue contrast. The peripheral zone of the prostate, where 70 75% of prostate cancers arise, is normally homogeneously hyperintense on T2-weighted MRI because of its mucin-filled glandular tissue. Prostate cancers, which have a higher cell density and lower fluid content than the normal peripheral zone, typically demonstrate homogeneous low signal intensity on T2-weighted images. The contrast between the normal peripheral zone and cancerous lesions allows for cancer detection and characterization (Figure 1). Noncancerous tissues, such as normal stromal tissue in the transition zone and areas of benign prostate hyperplasia, prostate fibrosis or postradiation changes, may also demonstrate low signal intensity on T2-weighted images. Thus, T2-weighted images alone are limited in their capacity to detect prostate cancer lesions, with sensitivity and specificity of 0.62 and 0.77, respectively, in a recent meta-analysis [1]. Diffusion-weighted MRI The signal intensity on DW-MRI is determined by the rate of Brownian movement of water molecules (i.e., water diffusion) within tissue. Thus, prostate cancer, which typically has high cell density and restricted water diffusion in the intercellular space, can be distinguished on DW-MRI from normal prostate tissue, in which the cell density is lower and water diffusion less restricted. By performing several acquisitions with different degrees of diffusion weighting, it is possible to calculate a measure of the area over which water molecules have diffused over time (mm 2 /s), the apparent diffusion coefficient (ADC). For the interpretation of DW-MRI, it is important to recognize that the signal intensity on ADC maps correlates negatively with cell density and the degree of diffusion restriction: the lower the signal intensity, the higher the cell density (Figure 1). The addition of DW-MRI to the prostate MRI examination protocol improves the detection of prostate cancer. A meta-analysis showed that the use of T2-weighted images in combination with DW-MRI resulted in higher sensitivity (0.72 vs 0.62) and specificity (0.81 vs 0.77) than the use of T2-weighted imaging alone [1]. DW-MRI may also be useful for the detection and characterization of transition zone tumors [2], for which T2-weighted imaging is limited by the heterogeneous appearance of normal transition zone tissue, although stromal hyperplasia and other benign conditions affecting the transition zone may also demonstrate diffusion restriction. Postbiopsy changes and inflammatory Figure 1. T2-weighted and diffusion-weighted MRI of primary prostate cancer. (A) Transverse T2-weighted image, (B) apparent diffusion coefficient map and (C) whole-mount histopathology of a 60-year-old patient with prostate cancer (Gleason score = 7, prostate-specific antigen: 5.41 ng/ml). The dominant lesion in the right lateral peripheral zone of the mid gland (arrows) shows low signal intensity on the T2-weighted image. The low signal intensity on the apparent diffusion coefficient map indicates restricted diffusion of water molecules in this area, which is typical for prostate cancer lesions. Normal peripheral zone prostate tissue (stars) demonstrates homogenously high signal intensity on both sequences. On the histopathology map, areas with a Gleason grade of 3 are circled in green, whereas areas with a Gleason grade >3 are circled in black. For color images please see online at Future Oncol. (Epub ahead of print)

3 Role of MRI in the diagnosis & management of prostate cancer Review Figure 2. T2-weighted and contrast-enhanced MRI of primary prostate cancer. (A) Transverse T2-weighted image, (B) dynamic contrast-enhanced T1-weighted image and (C) whole-mount histopathology of a 62-year-old patient with prostate cancer (Gleason score = 7, prostate-specific antigen: 7.55 ng/ml). The dominant lesion in the right posterolateral peripheral zone of the mid gland (arrows) shows earlier and more intense contrast enhancement than the normal peripheral zone (stars). processes, such as prostatitis, can also cause low signal intensity on ADC maps and must be considered in the differential diagnosis of prostate cancer. Dynamic contrast-enhanced MRI In DCE-MRI, image contrast is based on differences in the velocities and intensities of contrast agent uptake by tumors and normal prostate tissue. After intravenous injection of gadolinium-based contrast agents, sequential, rapid, dynamic MR images of the whole gland are acquired over 5 min. This allows evaluation of both the intensity and the dynamics of contrast enhancement and, indirectly, provides information about the vascularity, vascular permeability, perfusion and intercellular volume of the tissue of interest. Prostate cancers typically show earlier and more intense enhancement and a faster wash-out of contrast media compared with normal prostate tissue (Figure 2). Reported sensitivities and specificities of DCE- MRI alone for the detection of prostate cancer range from 0.46 to 0.96 and 0.71 to 0.96, respectively [3]. The quality of DCE-MRI like that of T2-weighted and DW-MRI can be negatively affected by postbiopsy changes and benign prostate hyperplasia. In addition, partly because of the longer acquisition times compared with standard DW-MRI, this technique is affected by motion artifacts from bowel peristalsis, bladder filling and patient movement. There is an ongoing discussion in the scientific community about the most time- and costeffective imaging protocol for primary prostate cancer. A recent meta-analysis showed that a two-sequence approach including T2-weighted imaging plus DWI or DCE may be sufficient for routine prostate imaging and that the combination of T2-weighted MRI plus DWI may be more favorable [4]. Proton magnetic resonance spectroscopic imaging As the resonance frequency of protons depends on their molecular environment, proton MRSI allows in vivo distinction of metabolites in the prostate (i.e., citrate, choline, polyamines and creatine). Normal prostate tissue is rich in citrate, but this metabolite is typically reduced in prostate cancer. Conversely, the concentration of choline, which is a major compound of cell membranes and a surrogate marker of cell membrane turnover, is low in normal prostate tissue but elevated in cancer. By calculating the ratio between citrate and choline within a voxel, it is possible to distinguish between prostate cancer and normal tissue (Figure 3). In one meta-analysis, pooled mean sensitivities and specificities of combined MRI/MRSI for the detection of prostate cancer were and , respectively, depending on whether prostate cancer was already confirmed or only suspected before the imaging examination [5]. The major limitations of MRSI are its low spatial resolution, the relatively long acquisition time of 15 min and the fact that it is technically more challenging than other MRI techniques. Postbiopsy changes also negatively affect its quality. The role of MRI in the detection of prostate cancer In this section, we discuss the detection of suspected prostate cancer including the limitations encountered with standard TRUS-guided biopsy

4 Wibmer, Vargas & Hricak Cit PA Cho Cr Cho PA Cit Cr ppm ppm Figure 3. MRI and magnetic resonance spectroscopic imaging of primary prostate cancer. (A) Transverse T2-weighted image, (B) apparent diffusion coefficient map and (C) magnetic resonance spectroscopic grid overlaid on the T2-weighted image of a 53-year-old patient with prostate cancer (Gleason score = 7, prostate-specific antigen: 4.28 ng/ml). The white asterisk shows a spectrum suggestive of cancer (D), with elevated Cho and reduced PAs. The black asterisk shows a spectrum indicative of benign tissue (E), with elevated PAs and reduced Cho. Cho: Choline; Cit: Citrate; Cr: Creatine; PA: Polyamine. and give an overview of the role and potential of MRI and MRI-targeted biopsy in this area. Prostate cancer is typically diagnosed by systematic (typically 12-core) TRUS-guided biopsy performed when disease is suspected based on clinical information (elevated serum prostatespecific antigen [PSA] level, abnormal digital rectal examination, strong family history, among others). This method of prostate biopsy has been shown to be superior to sextant biopsy (previously the standard approach) [6]. Nevertheless, a study that analyzed the results of systematic TRUS-guided biopsy by prostate section found false negative rates of up to 49% [7]. TRUSguided biopsy may underestimate not only prostate cancer burden but also prostate cancer aggressiveness, and a recent meta-analysis found that the overall agreement of biopsy-derived and surgical Gleason scores was only fair (weighted kappa: 0.37) [8]. MRI-targeted prostate biopsy is an emerging alternative to the standard 12-core systematic biopsy. There are three main technical approaches: biopsy within the MR magnet ( in bore ); computational fusion of MRI and ultrasound images that allows a lesion seen on MRI to be targeted with ultrasound-guided biopsy; and performing ultrasound-guided biopsy after solely reviewing the MR images ( cognitive fusion ). These techniques allow for targeted biopsy of suspicious lesions and, theoretically, offer greater diagnostic accuracy than the standard TRUS-guided biopsy technique. Two of the most important research questions in this field are whether a lesion suspicious on MRI represents (significant) prostate cancer; and whether it is safe to defer biopsy in patients with a normal or near normal prostate MRI. These questions were addressed by a systematic review and pooled analysis of studies of MRItargeted biopsy conducted in biopsy-naive patients and/or patients with at least one negative prior standard biopsy [9]. Among the cohort of biopsy-naive men (n = 599), 62% had suspicious findings on MRI, of whom 66% had prostate cancer on MRI-targeted biopsy. Of Future Oncol. (Epub ahead of print)

5 Role of MRI in the diagnosis & management of prostate cancer Review the patients with at least one negative standard biopsy (n = 479), 69% had suspicious findings on MRI, of whom 70% had cancer on MRItargeted biopsy. The pooled analysis showed that 23% of patients with an unremarkable MRI had cancer on standard biopsy. Of these patients, one quarter had clinically significant cancer that would have been missed by MRI-targeted biopsy [9]. A recently published prospective study on 1003 men showed that MRI-targeted prostate biopsy detects significantly more high-risk cancers and less low-risk cancers than standard biopsy [10]. The diagnostic accuracy of MRIguided biopsy for the detection of intermediate- or high-risk patients was significantly higher in this study (areas under the receiver operating characteristic curves: 0.73 vs 0.59 for standard extended-sextant biopsy; p = 0.005) [10]. Another important question is whether MRItargeted biopsy can improve the pretreatment assessment of cancer aggressiveness. In one prospective study, 64 patients underwent ten core TRUS-guided biopsies, while 34 patients underwent DW-MRI-targeted biopsies, in which only the lesions with the lowest diffusion values on ADC maps were targeted; in the latter group, the highest Gleason grade found on biopsy matched that found at surgical pathology in 88% of patients, whereas in the former group, the highest biopsy and surgical Gleason grades matched in only 55% of patients [11]. In patients with locally recurrent disease, MRI-targeted biopsy can be used to acquire a tissue specimen from the most suspicious area [12]. The major limitations of MRI-targeted biopsy are its limited availability and relatively high cost. As compared with MRI-targeted biopsy performed within the magnet, targeted biopsy guided by real-time MRI/ultrasound fusion may be more widely accessible and, judging from preliminary studies, may have similar accuracy [13]. A recent analysis showed that the cost effectiveness of MRI-targeted biopsy as an alternative to TRUSguided biopsy depends on the prevalence of cancer in the examined population: the lower the prevalence of cancer, the higher the cost effectiveness of the MRI-targeted approach [14]. Staging of newly diagnosed cancer In this section, we discuss the role and accuracy of prostate MRI in the staging of newly diagnosed prostate cancer in regards to local tumor extent and spread of disease to regional lymph nodes. Of the more than 200,000 patients diagnosed with prostate cancer each year in USA [15], 10% initially present with locally advanced tumors and 12% have regional lymph node metastases [16]. One crucial role of prostate MRI in these patients is to localize the index tumor and identify the presence of extracapsular extension (ECE), seminal vesical invasion (SVI) and/or regional lymph node involvement. The localization of the index tumor allows for targeted biopsy, helps to accurately stage the tumor and is a prerequisite for the application of focal therapies. On the whole, the accuracy of prostate MRI has improved over time. Reported sensitivities and specificities of T2-weighted MRI in tumor localization range from 0.54 to 0.91 and 0.27 to 0.91, respectively [17 19] and it has been shown that prostate MRI is superior to digital rectal examination in regards to correct tumor localization [20]. On prostate MRI, ECE is characterized by the presence of one or more of the following imaging features: broad capsular contact, capsular bulging or an irregular, spiculated or angulated prostatic margin adjacent to the tumor; obliteration of the rectoprostatic angle or asymmetry, traction and/or thickening of the neurovascular bundle (Figure 4). SVI is characterized by the presence of focally or diffusely decreased signal intensity on T2-weighted images within the seminal vesicles or ejaculatory ducts; the loss of natural seminal vesicle architecture; obliteration of the angle between the seminal vesicle, rectum and prostate or by the visibility of direct tumor extension from the prostatic base or through the ejaculatory ducts (Figure 5). Increased size or number of pelvic lymph nodes and asymmetric enlargement of lymph nodes are suggestive of lymph node metastasis. The literature shows wide variability in the accuracy of prostate MRI for the detection of ECE, SVI and lymph node involvement. This variability is attributable to differences not only in magnetic field strengths, but also in the application of endorectal and surface coils, the quality and quantity of sequences applied, the usage of contrast media, patient selection criteria and standards of reference. A meta-analysis of studies published after 2008 that only included patients who had undergone 1.5 T prostate MRI before radical prostatectomy found pooled sensitivity and specificity of 0.49 and 0.82, respectively, for the detection of ECE and 0.45 and 0.96, respectively, for the detection of SVI [21]. For the detection of lymph

6 Wibmer, Vargas & Hricak Figure 4. Extracapsular extension of prostate cancer. (A) Transverse T2-weighted image, (B) apparent diffusion coefficient map and (C) whole-mount histopathology of a 63-year-old patient with prostate cancer (Gleason score = 7, prostate-specific antigen: 10.9 ng/ml). The dominant lesion in the left lateral peripheral zone of the mid gland (arrows) has broad contact with the prostate capsule and causes marked capsular bulging, and the left rectoprostatic angle is obliterated (arrowheads). These findings indicate the presence of extracapsular extension, which was verified on histopathology (blue lines). node metastases with prostate MRI, another meta-analysis reported pooled sensitivity and specificity of 0.39 and 0.82, respectively [22]. Recommendations differ slightly as to when prostate MRI should be used for local staging for prostate cancer that is diagnosed on biopsy; The National Cancer Comprehensive Network recommends MRI to risk stratify men who are considering active surveillance, to characterize large and poorly differentiated prostate cancer (i.e., Gleason score 7) and detect extracapsular extension (T staging) [23]. The American College of Radiology states that its use may be appropriate for patients at low risk for locally advanced disease or metastases and that prostate MRI is usually appropriate if the patient has an intermediate or high risk of locally advanced disease and metastasis or in case of multiple negative prostate biopsies but concern for prostate cancer [24]. Pretreatment risk stratification In this section, we describe the emerging role of multiparametric prostate MRI in the pretreatment assessment of tumor aggressiveness and accurate risk stratification of patients with prostate cancer. The risk stratification of patients with newly diagnosed prostate cancer relies on the PSA level, the clinical tumor stage and data from TRUSguided prostate biopsy, with the Gleason score as the most potent predictive and prognostic biomarker. The major task of these risk-stratification systems is to properly select patients for active surveillance, and the majority of ongoing trials consider patients with tumors of Gleason score 7 or above ineligible for this management approach. Substantial discrepancies between biopsy and prostatectomy Gleason scores are well known. A recent meta-analysis of 16 studies that included more than 14,000 patients showed that for 38% of the patients with a Gleason score of 6 on prostate biopsy, upgrading occurred after radical prostatectomy [8]. Thus, a tool that could more accurately assess tumor aggressiveness before treatment would be helpful to improve treatment selection. MRI has demonstrated the potential to contribute to this task. In a study of 388 patients with low-risk prostate cancer who were considered potential candidates for active surveillance after an initial biopsy session, clear visualization of tumor on T2-weighted MRI alone was predictive of upgrading on a second biopsy performed to confirm the Gleason score [25]. By applying additional MRI techniques, such as DW-MRI, DCE-MRI or MRSI, this prognostic ability may improve. The signal intensity of prostate cancer on DW-MRI has been shown to correlate with its Gleason score on histopathology [26], and DW-MRI-targeted prostate biopsy has been found to significantly improve pretreatment risk stratification [11]. In a study of patients who underwent T2-weighted and DW-MRI before prostatectomy, a strong suspicion of tumor on MRI was a statistically independent predictor of a primary Gleason grade 4 on multivariate analysis, in which the PSA level, biopsy Gleason score, number of positive cores on histopathology and age were covariates [27]. However, ADC values associated with different Gleason scores overlap substantially [28]. DCE-MRI may also Future Oncol. (Epub ahead of print)

7 Role of MRI in the diagnosis & management of prostate cancer Review help optimize pretreatment risk stratification, as a recent study found that DCE-MRI parameters have the potential to discriminate lowfrom intermediate- and high-risk patients who have tumors in the peripheral zone [29]. Finally, adding MRSI to MRI of the prostate has been shown to improve the prediction of clinically insignificant cancer [30]. MRSI findings correlate with the expression of Ki-67, phospho-akt and androgen receptors [31] and both MRSI findings and these molecular markers have been shown to contribute incremental value to standard clinical variables in predicting cancer recurrence after radical prostatectomy [32]. Diagnosis of local recurrence In this section, we focus on the principles and performance of prostate MRI in the detection and characterization of locally recurrent prostate cancer after previous radical prostatectomy or radiotherapy. Detecting local recurrence after radical prostatectomy According to a recent meta-analysis, 20% of patients who undergo radical prostatectomy experience biochemical recurrence within 7 years from surgery [33]. Localizing the site of disease in the setting of biochemical recurrence is essential for treatment planning. The presence of metastatic disease requires systemic treatment, but isolated and accurately localized local recurrence may be amenable to salvage treatment with a curative intent. In patients with biochemical recurrence, MRI can detect and characterize local disease with sensitivities of and specificities of [34,35]. Recurrent tumors are characterized by signal intensities similar to those of muscle on T1-weighted images and slightly higher than those of muscle on T2-weighted images. Typically, recurrent cancer shows earlier and more intense contrast enhancement than noncancerous tissue, and DCE-MRI substantially improves the accuracy of MRI in the diagnosis of local recurrence (Figure 6) [36,37]. The National Comprehensive Cancer Network recommends pelvic MRI after radical prostatectomy when the PSA level fails to become undetectable or when an undetectable PSA becomes detectable, increasing on two or more tests [23]. The American College of Radiology Appropriateness Criteria state that the use of gadolinium injection is promising in detecting local recurrence [24]. Detecting local recurrence after radiation therapy Radiation-induced changes in the prostate gland typically lead to homogeneously low signal intensity of benign prostate and seminal vesicle tissues on T2-weighted images. This decreases the contrast between the noncancerous prostate gland and recurrent tumor. Furthermore, it is challenging to determine if focal T2-hypointense areas in the location of the original tumor represent viable tumor recurrence or nonviable residuum of the primary tumor. A recent study found that in the diagnosis of local recurrence after radiation therapy, the combination of T2-weighted imaging and DW-MRI yielded significantly greater accuracy than T2-weighted imaging alone (areas under receiver operating characteristic curves: versus for reader 1 and versus for reader 2); while the combination of DCE-MRI and T2-weighted Figure 5. Seminal vesicle invasion of prostate cancer. (A) Coronal and (B) transverse T2-weighted images of a 58-year-old patient with prostate cancer (Gleason score = 9; prostate-specific antigen: 13.3 ng/ml). The tumor invades both seminal vesicles, as indicated by signal intensity that is low (white stars) relative to that of the noninvolved parts of the seminal vesicles (black stars).

8 Wibmer, Vargas & Hricak Figure 6. Local recurrence of prostate cancer after radical prostatectomy. (A) Transverse T2-weighted image, (B) contrast-enhanced T1-weighted image and (C) apparent diffusion coefficient map of a 59-year-old patient who had previously undergone radical prostatectomy for prostate cancer. There is a 2 cm, strongly enhancing (B) mass with restricted diffusion (C) in the prostatectomy bed (arrows). These findings are consistent with residual/recurrent prostate cancer, which was histologically proven in this case. MRI performed better than T2-weighted MRI alone, DCE-MRI did not add significant incremental value to the combination of T2-weighted MRI and DW-MRI [38]. Whole-body MRI for the detection of prostate cancer metastases This section describes the technical principals of whole-body (WB) MRI in patients with prostate cancer and presents results from preliminary studies dealing with this emerging diagnostic approach for patients at risk for distant spread of disease. In patients with newly diagnosed prostate cancer and in those with biochemical recurrence after definitive treatment, it is crucial to evaluate the presence of distant metastases before undertaking treatment with a curative intent. Routinely, 99m Tc-bone scintigraphy (bone scan) is used to search for metastases to the bone while CT is applied to screen for the presence of lymph node and solid organ metastases. WB-MRI, which typically incorporates T1-weighted, T2-weighted and DW-MRI sequences, may offer an alternative to both of those methods. On T1-weighted images, bone marrow typically has high signal intensity due to its fat content, while bone marrow metastases, which displace healthy bone marrow, have markedly low signal intensity. In contrast, bone scans do not show bone marrow metastases directly but instead show the reaction of surrounding bone. As the displacement of healthy bone marrow by cancer precedes the reaction of the surrounding bone, WB-MRI may detect bone marrow metastases earlier than bone scans. Furthermore, bone marrow metastases have a higher cell density than the surrounding healthy bone marrow, leading to high contrast on DW-MRI. In clinical studies, WB-MRI was equal to or outperformed bone scans for the detection of prostate cancer bone marrow metastases and performed as well as CT for the evaluation of large lymph nodes in high-risk patients [39,40]. Compared with sodium-fluoride PET/CT, WB-MRI showed higher specificity but lower sensitivity for the detection of bone marrow metastases [41]. Thus, it is possible that WB-MRI may one day replace the multimodality work-up of patients at high risk of distant spread of pr ostate cancer. Conclusion & future perspective MRI of the prostate provides essential information about tumor stage and location in patients with newly diagnosed prostate cancer and is the imaging tool of choice for detecting local recurrence after radical prostatectomy or radiation therapy. The use of multiparametric rather than conventional MRI improves tumor detection and provides an indication of tumor grade. Ongoing research about the predictive and prognostic potential of MRI-derived parameters suggests that they may substantially improve pretreatment risk stratification and thus provide a basis for better treatment selection for patients with prostate cancer. As compared with standard TRUS-guided biopsy, MRI-targeted biopsy may provide more accurate and cost-effective cancer detection in selected populations, as well as more reliable assessment of disease aggressiveness. In addition, research suggests that whole-body MRI could emerge as an alternative to the multimodality evaluation of patients at risk for distant metastasis. Future Oncol. (Epub ahead of print)

9 Role of MRI in the diagnosis & management of prostate cancer Review Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or p ending, or royalties. No writing assistance was utilized in the production of this manuscript. References 1 Wu LM, Xu JR, Ye YQ, Lu Q, Hu JN. The clinical value of diffusion-weighted imaging in combination with T2-weighted imaging in diagnosing prostate carcinoma: a systematic review and meta-analysis. AJR Am. J. Roentgenol. 199(1), (2012). 2 Jung SI, Donati OF, Vargas HA, Goldman D, Hricak H, Akin O. 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