Diagnosis, staging, and treatment monitoring are still suboptimal for most genitourinary tumours. Diffusion-weighted magnetic resonance imaging (DW-MRI) has already shown promise as a noninvasive imaging modality in the early detection of microstructural and functional changes in several pathologies of various organs.
To assess the potential and limitations of DW-MRI in the management of patients with kidney, prostate, and bladder cancer.
A nonsystematic literature search using the Medline/PubMed and Embase databases for full-length papers reporting on DW-MRI for kidney, prostate, and bladder cancer was performed up to August 1, 2011. Only those articles with complete data reporting on DW-MRI applications with potential implications in solving commonly encountered clinical challenges relating to tumour detection, staging, and treatment monitoring were finally examined.
For kidney tumours DW-MRI is a reasonable alternative to conventional cross-sectional imaging to detect and characterise focal renal lesions, especially in patients with impaired renal function. For prostate cancer, DW-MRI applied in addition to conventional T2-weighted and contrast-enhanced magnetic resonance imaging (MRI) improves tumour detection and localisation. In addition, it has shown promise for the assessment of tumour aggressiveness and for treatment monitoring during active surveillance, radiation therapy, and focal therapy. For bladder cancer, DW-MRI may improve the performance of conventional T2-weighted and contrast-enhanced MRI in the work-up of bladder cancer, helping to differentiate non–muscle-invasive from muscle-invasive tumours. For pelvic lymph nodes, initial results showed the potential to improve nodal staging of prostate and bladder cancer compared with conventional cross-sectional imaging.
DW-MRI holds promise to ameliorate the management of patients with kidney, prostate, and bladder cancer including pelvic lymph node staging. Current limitations include the lack of standardisation of the technique across multiple centres and the still limited expertise.
Keywords: Anatomy, cross-sectional, Diffusion magnetic resonance imaging, Early detection of cancer, Neoplasm staging, Kidney neoplasms, Bladder cancer, Prostate cancer, Lymph nodes.
Contrast-enhanced (CE) computed tomography (CT) and conventional magnetic resonance imaging (MRI) are established imaging techniques for the work-up of genitourinary tumours. Kidney tumours are routinely diagnosed and staged with CE-CT or in selected cases with MRI. Locoregional staging of prostate cancer (PCa) and bladder cancer (BCa) is usually performed with MRI, whereas CE-CT is used to search for metastases. However, the characterisation of focal renal lesions, especially in patients with impaired renal function, and the detection and staging of PCa and BCa as well as pelvic lymph node (LN) staging are issues that often remain unresolved using conventional cross-sectional imaging.
Diffusion-weighted MRI (DW-MRI) is a noninvasive technique measuring the microscopic mobility of water molecules in the tissues without contrast administration. This mobility depends on the integrity of cell membranes and the cellularity of the underlying tissue, thus reflecting biologic abnormalities . DW-MRI was first applied in the brain, where it became the gold standard for the diagnosis of acute stroke because microstructural changes observed on DW-MRI precede morphologic changes detected on conventional cross-sectional imaging  and . Extracranial applications are more challenging, however, because of physiologic motion artefacts (ie, respiration, cardiac, and bowel motion) . Owing to continuous technical improvements including fast sequences, DW-MRI has been increasingly applied in the abdomen and pelvis for functional applications, tumour detection and characterisation, as well as monitoring of treatment response in various organs  and .
This review provides a critical overview of the current literature on DW-MRI for the work-up of kidney tumours, PCa, and BCa, as well as for pelvic LNs, emphasising its potential and limitations in everyday clinical practice.
2. Evidence acquisition
A nonsystematic literature search using the Medline/PubMed and Embase databases for full-length papers and including both medical subject headings and free-text protocols was performed up to August 1, 2011. Entry terms were diffusion-weighted magnetic resonance imaging in conjunction with kidney OR renal, prostat* and bladder tumour OR cancer OR carcinoma OR neoplasm*, and pelvic lymph nodes. Search limitations were title/abstract, humans, all adults, and English language.
Two authors (GG and GP) reviewed the abstracts of the retrieved records and selected only those pertinent to the objectives of the present analysis. Contrasts were eventually solved by the senior author (HCT). All authors then carefully analysed the corresponding full-length articles, and additional referenced papers of interest were identified by hand search and retrieved.
Review articles, case reports, and congress abstracts were excluded. Feasibility studies, papers focusing on technical aspects of DW-MRI, as well as papers published before 2006 were preferentially excluded. Only those articles with complete data reporting on DW-MRI applications with potential implications to solve common challenges encountered in the routine clinical scenario, namely dilemmas in tumour detection, staging, and treatment monitoring for the three most frequent genitourinary tumours including pelvic LN staging of PCa and BCa, were finally analysed.
3. Evidence synthesis
The combined search generated a total of 259 papers. From the retrieved material, 71 papers, 13 for kidney tumours, 44 for PCa, 10 for BCa, and 4 for pelvic LN staging, were selected for final analysis. No study was specifically designed based on the Standards for Reporting of Diagnostic Accuracy guidelines , which are the recommended methodology for reporting studies of diagnostic accuracy.
3.1. Basic principles and technical requirements of diffusion-weighted magnetic resonance imaging
DW-MRI is an MRI technique that visualises molecular diffusion, that is, the Brownian motion of water molecules in biologic tissues , by applying two equally size but opposite diffusion-sensitising gradients, which are characterised by their b-values. The mobility is then quantified by calculating the apparent diffusion coefficient (ADC), which depends mainly on the choice of the underlying b-values. The lower the b-value applied, the higher the resulting ADC value. Image interpretation can be performed qualitatively by visual assessment of the DW images and the corresponding ADC map, and quantitatively by measuring the ADC value of the lesion. This ADC combines the effects of capillary perfusion and water diffusion in the extracellular extravascular space, providing simultaneous information on perfusion and diffusion in any organ . Thus DW-MRI can be used to better differentiate normal and abnormal tissues at an early point in time, and it may improve detection and characterisation of various abnormalities preceding morphologic changes on conventional MRI. When comparing ADC values in the literature for any organ and lesion, attention has to be paid to the choice of the underlying b-values .
Hypercellular tumours lead to impeded movement in the interstitial space and are therefore depicted as hyperintense (bright) lesions on the high b-value images (eg, b
Currently, nearly all available clinical systems (1.5 T and 3 T) have the capability of performing DW-MRI examinations in addition to morphologic/anatomic imaging. For genitourinary tumours, most DW acquisitions are performed in the axial plane either in “free breathing” or with “respiratory triggering” in addition to the conventional MRI sequences, with an extra time of approximately 4
No studies are available so far comparing the diagnostic performance of DW-MRI for prostate and bladder using endorectal versus phased-array body coils. There is some controversy among researchers whether the endorectal coil should be used for prostate imaging. The endorectal coil is recommended when performing MRI at 1.5 T by several radiologists; however, excellent image quality mainly at 3 T, but also at 1.5 T, can be achieved even with phased-array coils, resulting in improved patient comfort and reduced cost. Conversely, there is agreement about the lack of benefit in using the endorectal coil for bladder imaging. Technical details concerning DW-MRI, image parameters, and acquisition techniques can be found in previously published reviews  and .
3.2. Kidney tumours
3.2.1. Detection and characterisation
Although conventional cross-sectional imaging identifies a malignant renal lesion with high accuracy, in specific cases the differentiation between complicated cyst and cystic renal cell carcinoma (RCC), as well as between benign and malignant solid lesions (ie, oncocytoma and RCC) or among different malignant cell types remains difficult or even impossible. In these cases, DW-MRI might be useful thanks to different ADC values observed in benign and malignant lesions as well as in tumour subtypes due to their different cellularity.
The ability of ADC values to characterise focal renal lesions (viable solid tumours, necrotic or cystic tumour areas and cysts) was explored in a study including 25 patients with 26 renal tumours and 11 benign cysts on definitive histology . Renal tumours had significantly lower median ADC values compared with benign cysts, and solid enhancing tumours had significantly lower ADC values compared with necrotic or cystic regions, which in turn had lower ADC values compared with benign cysts. This was likely due to nonviable tissue in necrotic tumours that did not enhance but resulted in impeded diffusion as compared with cystic fluid. There was, however, an overlap of ADC values across the different categories. When renal lesions were stratified by T1 signal characteristics, T1 hyperintense lesions had lower ADC values compared with their hypointense counterparts, and overlap decreased. In another study of 41 patients with 64 non–fat-containing T1 hyperintense renal lesions , mean ADC values for RCC were significantly lower than those for haemorrhagic or proteinaceous cysts. In a further study of 42 patients with 69 focal renal lesions, the ADC values of 7 cystic RCCs were significantly lower (p
DW-MRI has also been investigated in an attempt to differentiate the various RCC subtypes, which is critical for both prognostication and the selection of appropriate systemic therapies for patients with metastatic disease . Contrasting results have been reported in the literature. In a study including 83 patients with 85 tumours , at b-values of 0 and 800
|Study||No. of patients||No. of tumours||Imaging||ADC value (× 10−3 mm2/s) (mean
||Reference standard||Sensitivity, %||Specificity, %||Threshold ADC value,
|Field strength, T||b-values, s/mm2||Papillary RCC||Clear cell RCC||Chromophobic RCC||Nonpapillary RCC||Non–clear cell RCC||Oncocytoma||Solid RCC||Cystic RCC||Benign cysts|
|Yoshikawa et al. ||NR||87||1.5||0, 600||–||–||–||–||–||–||2.49
||H, I, and FU||NR||NR||–|
|Zhang et al. ||25||26||1.5||0, 500, 1000||–||–||–||–||–||–||1.72
|Manenti et al. ||27||27||3||0, 500||1.81
|Kim et al. ||41||64||1.5||0, 400||–||–||–||–||–||–||1.75
||H and FU||71||91||1.88|
|Taouli et al. ||64||109||1.5||0, 400, 800||1.12
||H and FU||82.1*
|Kilickesmez  et al.||52||67||1.5||0, 500, 1000||–||–||–||–||–||–||1.06
|H, I, and FU||NR||NR||–|
|Wang et al. ||83||85||3||0, 500
|Paudyal et al. ||32||32||1.5||0, 300, 1000||–||1.59
|Rosenkrantz et al. ||57||57||1.5||0, 400
|Sandrasegaran et al. ||42||69||1.5||0, 800||–||1.85
||H, I and FU||100*
|Doğanay et al. ||58||67||1.5||100
|H and I||93.7*
|Razek et al. ||52||54||1.5||0, 800||1.65
|Inci et al. ||105||105||1.5||0, 500, 1000||0.90
|H, I and FU||NR||NR||–|
* Diagnosis of RCC (among all lesions).
† Diagnosis of solid RCC (among solid enhancing lesions).
‡ Diagnosis of clear cell RCC versus non–clear cell RCC.§ Diagnosis of high-grade clear cell RCC versus low-grade clear cell RCC.|| Diagnosis of cystic RCC versus benign cysts.¶ Diagnosis of clear cell plus papillary RCC versus other RCC subtypes.
A commonly encountered challenge is the characterisation of focal renal lesions in patients with impaired renal function. In these cases, contrast medium administration should be avoided because of the risk of contrast-induced nephropathy with CT or nephrogenic systemic fibrosis with MRI. DW-MRI could thus be extremely useful in this setting. In the previously mentioned study including 109 focal renal lesions (81 benign lesions and 28 RCCs) , the diagnostic performance of DW-MRI was compared with that of CE-MRI. Sensitivity and specificity for the diagnosis of malignancy were only slightly lower for DW-MRI (86% and 80%, respectively) than for CE-MRI (100% and 89%, respectively). In the other previously mentioned study including 64 complex cystic masses , the diagnostic performance of DW-MRI (71% sensitivity and 91% specificity) was similar to that of the contrast enhancement ratio (65% sensitivity and 96% specificity) in predicting malignancy. Therefore, it may be concluded that DW-MRI is a reasonable alternative to CE-MRI for the characterisation of focal renal lesions in patients with impaired renal function (Fig. 1).
3.2.2. Local staging/treatment monitoring
No publications on the use of DW-MRI in locoregional staging or the prediction and monitoring of treatment response for kidney tumours could be found.
3.3. Prostate cancer
3.3.1. Detection and localisation
The current standard procedure for PCa detection is transrectal ultrasound (TRUS)–guided systematic biopsy . Although TRUS provides a good depiction of the peripheral zone (PZ), evaluation of the transition zone (TZ) and the more anterior region of the prostate remains a major challenge. In addition, free-hand random biopsies are subject to sampling error. In recent years, PCa detection and staging has improved using conventional T2-weighted MRI (T2w-MRI); however, in a high number of cases the differentiation between PCa and normal prostatic tissue can be impossible not only in the TZ but also in the PZ (Fig. 2).
Initial research on the usefulness of DW-MRI in this particular setting has primarily focused on PZ because most prostate tumours are located there. When DW-MRI is combined with T2w-MRI, sensitivity and specificity increase substantially, ranging from 71% to 89% and from 61% to 91%, respectively, compared with from 49% to 88% and from 57% to 84%, respectively, for either modality alone, resulting also in a lower interobserver variability , , , , , , and . In several publications , , , , , , , and , PCa tissue showed significantly lower ADC values than normal PZ tissue with minimal overlap within most single studies. However, due to heterogeneity in technical parameters and postprocessing, the reported sensitivities and specificities varied considerably, ranging from 40% to 95%. Due to the lack of standardisation in DW-MRI protocols, absolute ADC values are influenced by several sources of variability, mainly the choice of the underlying b-values. Therefore, at present, a reliable cut-off ADC value for malignancy that can be used universally in clinical routine and allows comparison between studies is difficult to identify. Table 2 lists recent publications on this topic , , , , , , , , , , , , , , , , , , and .
|Study||No. of patients with PCa||No. of controls||Imaging||ADC value,
||Reference standard||Sensitivity, %||Specificity, %||Threshold ADC value,
|Field strength, T||b-values, s/mm2||Coil||PZ tumour||TZ tumour||PZ patient||TZ patient||PZ control||TZ control|
|Sato et al. ||23||6||1.5||0, 300, 600||PA||1.08
|Pickles et al. ||49||9||3||0, 500||PA||1.38
||Bx and I||NR||NR||–|
|Gibbs et al. ||62||–||3||0, 500||PA||1.19
||–||–||–||Bx and I||82§||78§||1.50|
|Manenti et al. ||19||10||1.5||0, 125, 250, 375, 500||PA||0.96
||Bx and I||NR||NR||–|
|Kumar et al. ||23||7||1.5||0, 250, 500, 750, 1000||PA
||Bx and I||73 §||74 §||1.17|
|deSouza et al. ||30||–||1.5||0, 300, 500, 800||ER||1.30
||–||–||Bx and I||86.7||
|Kim et al. ||35||–||3||0, 1000||PA||1.32
|Reinsberg et al. ||42||–||1.5||0, 300, 500, 800||ER||1.03
||–||–||Bx and I||93.3**
|Tamada et al. ||90||125||1.5||0, 800||PA||1.02
||Bx and I||NR||NR||–|
|Kim et al. ||47||–||1.5||0, 1000||PA
|Kitajima et al. ||26||–||1.5||0, 1000
|–||–||–||Bx and I||NR||NR||–|
|Zelhof et al. ||32||–||3||0, 500||PA||1.45
|Gibbs et al. ||20||–||3||0, 500||PA||1.43
|Wang et al. ||38||33*||1.5||0, 300, 600||PA||0.49
||–||–||RP or Bx||NR||NR||–|
|Woodfield et al. ||57||–||1.5||0, 1000||PA
||–||–||–||Bx and I||NR||NR||–|
|Kim et al. ||48||–||3||0, 1000
|Oto et al. ||49||–||1.5||0, 1000, 1500||PA
|Langer et al. ||24||–||1.5||0, 600||PA
||1.28 (0.85–1.69)†||–||1.56 (1.05 -2.09)†||–||–||–||RP||NR||NR||–|
|Yamamura et al. ||21||–||1.5||50, 400, 800||PA
* Subjects with benign prostatic hyperplasia.
† Median and range.
‡ Subjects with negative Bx.§ Tumour versus no tumour.|| PZ tumour versus PZ patient.¶ PZ tumour versus TZ patient.
** Voxel containing ≥70% tumour.
†† Voxel containing ≥30% tumour.
‡‡ TZ tumour versus TZ patient (for SH).
Detection of PCa in the TZ is more difficult due to the high cellularity observed in both benign prostatic hyperplasia (BPH) and tumour. Although DW-MRI also performs better than T2w-MRI in the TZ, there is a large overlap between PCa and BPH, limiting its usefulness for the individual patient (Table 2). This was recently reconfirmed in a study comparing 38 tumour foci, 38 nodules of stromal hyperplasia, and 38 nodules of glandular hyperplasia in the TZ, where significant ADC differences could be observed between groups but a substantial overlap was evident .
Patients with one or more negative prostate biopsy sets and a high suspicion of PCa would profit most from a noninvasive imaging modality such as DW-MRI. In a study of 43 patients with previously negative TRUS-guided prostate biopsy and persistently elevated prostate-specific antigen (PSA) levels, DW-MRI at 3 T performed before a further TRUS-guided biopsy could detect PCa in 17 (39.5%) patients, whereas T2w-MRI could detect PCa in only 6 of them . The sensitivity rates reported in this study are lower than those reported in previous studies, possibly because of a relatively higher incidence of TZ tumour (76.4%), which is traditionally challenging to detect with any imaging modality. In addition, the suspicious PCa foci detected on the ADC map might have been mistargeted with TRUS guidance. Prostate biopsy under MRI guidance would instead maximise the advantage of improved PCa detection and localisation with DW-MRI. However, there is no current consensus on the optimal technique, and the clinical experience is still limited .
Several studies have consistently demonstrated an inverse correlation between ADC values and Gleason score as well as tumour risk category of commonly accepted criteria, especially for PZ tumours , , , , , and . Lower ADC values seem to be associated with higher Gleason scores, probably due to higher cellular density in poorly differentiated tumours, resulting in more impeded diffusion of water molecules. The main common shortcoming common to all these studies is the substantial overlap between ADC values and different Gleason scores, so that the routine use of DW-MRI to define tumour aggressiveness for the individual patient cannot yet be recommended.
3.3.3. Local staging
Currently, DW-MRI cannot accurately predict extracapsular extension due to frequently encountered image distortion and artefacts, and lower spatial resolution compared with T2w-MRI . However, DW-MRI holds promise to improve the prediction of seminal vesicle invasion, which is still considered a major negative prognostic factor . An initial study including 166 patients conducted on a 3-T scanner reported that DW-MRI used in conjunction with T2w-MRI significantly improved specificity (from 87% to 97%) and accuracy (from 87% to 96%) for the prediction of seminal vesicle invasion compared with T2w-MRI alone . A subsequent study including 283 patients with 39 cases of seminal vesicle invasion confirmed these results using quantitative analysis based on ADC values . Mean ADC values of tumour-bearing seminal vesicles were significantly lower than those of tumour-free seminal vesicles, with an area under the curve (AUC) of T2w-MRI plus DW-MRI (0.897) significantly higher (p
3.3.4. Predicting and monitoring treatment response
22.214.171.124. Active surveillance
Both PSA and its kinetics as well as repeat prostate biopsy strategies due to inherent sampling error and misgrading remain suboptimal in the monitoring of patients on active surveillance . In light of the earlier mentioned ability to predict tumour aggressiveness, DW-MRI might be useful in this setting because it would allow selecting candidates and monitoring changes during follow-up in a noninvasive manner. In a study of 86 patients on active surveillance followed for a median of 29 mo, lower tumour ADC values were significantly associated with both adverse findings on repeat biopsy and shorter time to radical treatment on univariable analysis . These findings were corroborated by the same investigators in two subsequent studies  and .
126.96.36.199. Radical prostatectomy
Two studies demonstrated the potential of DW-MRI to serve as a predictive biomarker for recurrence following radical prostatectomy for clinically localised PCa. In one small study including 12 patients with biochemical recurrence after surgery , the AUC for the Partin tables plus T2w-MRI and qualitative DW-MRI staging (0.79) was significantly greater than the AUC for the Partin tables alone (0.67) in predicting biochemical recurrence. In another study including 30 patients with biochemical recurrence , a multivariable analysis identified tumour ADC as the only independent predictive factor of biochemical recurrence among established preoperative clinical and histologic parameters, with an AUC of 0.755. However, due to the retrospective design, small sample size, and relatively short follow-up, these data should be interpreted with caution. Biochemical recurrence depends on several factors, among which specific tumour biology plays a major role. Therefore, in future studies the information provided by functional imaging should be incorporated into predictive models including numerous variables.
188.8.131.52. Detection of local recurrence after treatment with curative intent
After radiation therapy, prostate biopsy is considered the gold standard to diagnose locally recurrent PCa, but it is associated with substantial false-negative and positive rates . T2w-MRI is often challenging in these patients due to radiation-induced changes in prostatic tissue with a resulting low sensitivity for the detection of recurrent PCa. Despite the additive value of MR spectroscopy in increasing the diagnostic accuracy of endorectal MRI , there is still need for improvement (eg, by faster and more available techniques with easier image interpretation). Two small studies  and  showed that DW-MRI combined with T2w-MRI (in one study) and with delayed contrast-enhanced (DCE) MRI and T2w-MRI (in the other) significantly improved the diagnostic performance of each modality alone in detecting local recurrence after external-beam radiation therapy.
A single study evaluated the role of DW-MRI in detecting local recurrence after high-dose-rate brachytherapy in a multiparametric context including also conventional MRI and DCE-MRI . Sensitivity was highest for multiparametric MRI (77%), followed in decreasing order by DW-MRI (68%), DCE-MRI (50%), and T2w-MRI (27%). Specificity was slightly lower for multiparametric MRI (92%) compared with the individual sequences (range: 95–99%).
Whole-gland ablation with high-intensity focussed ultrasound (HIFU) is an emerging alternative option for the treatment of selected patients with localised PCa, although robust long-term oncologic follow-up data are lacking . A major obstacle to its applicability remains establishing treatment efficacy. Ablation of prostatic tissue leads to coagulation necrosis and cavitation effects, resulting in a diffuse low signal intensity in T2w-MRI sequences, thus hampering the identification of residual/recurrent tumour . In the only available study including 27 PCa patients with biochemical recurrence after HIFU ablation, DW-MRI combined with T2w-MRI had higher specificity but lower sensitivity compared with DCE-MRI in predicting local recurrence . An attractive application of DW-MRI may be the local monitoring of patients undergoing focal therapy of the prostate, which is becoming increasingly popular for the minimally invasive treatment of low-risk PCa .
The literature search did not reveal any publications on the use of DW-MRI to detect local recurrence after radical prostatectomy. Further studies are eagerly awaited to define the optimal imaging technique to evaluate local treatment outcome after various curative approaches.
3.4. Bladder cancer
In patients with gross haematuria or under follow-up after treatment of non–muscle-invasive BCa, the differentiation between benign and malignant lesions of the bladder could avoid the need for invasive procedures, provided that upper tract tumours are excluded. In a prospective study including 130 patients with gross haematuria, DW-MRI had 98.1% specificity and 92.3% sensitivity in discriminating a total of 106 malignant cases from 14 benign conditions . However, the diagnostic performance of T2w-MRI in that study was only slightly lower than that of DW-MRI, likely due to the large mean size of the lesions. A smaller study including 59 patients with gross haematuria or under follow-up after previous BCa showed 97.6% specificity and 96% sensitivity in discriminating 34 malignant lesions from 9 benign conditions . Mean ADC values for malignant lesions were significantly lower than those for benign conditions and normal bladder wall. Details of all published studies on this topic are specified in Table 3, , , , and . In most studies, the exact criteria to define bladder tumour and abnormal but nonmalignant conditions were not reported. Therefore, the value of DW-MRI as a first-line diagnostic test to differentiate tumour from benign disease of the bladder needs further research.
|Study||No. of patients||No. of controls||Imaging||ADC value,
||Reference standard||Sensitivity, %*||Specificity,%*||Threshold ADC value,
|Field strength, T||b-values, s/mm2||Coil||Malignant lesions||Benign lesions||Bladder patient||Bladder control|
|Matsuki et al. ||15||–||1.5||0, 800||PA||1.18
|El-Assmy et al. ||43||–||1.5||0, 800||PA||1.40
|Kiliçkesmez et al. ||14||50||1.5||0, 500, 1000||PA||0.94
||H and I||NR||NR||–|
|Ceylan et al. ||59||–||1.5||NR||PA||1.05
||–||CS and H||97.6||96||NR|
|Avcu et al. ||83||20||1.5||0, 500, 1000||PA||1.07
* Diagnosis of malignant versus benign lesions.
3.4.2. Local staging
Distinguishing non–muscle-invasive from muscle-invasive BCa is crucial for patient management because treatment options differ considerably, ranging from radical surgery to bladder-sparing options . The true advantage of any imaging technique for local staging is debatable because transurethral resection (TUR) cannot be avoided to obtain histologic diagnosis. However, TUR can underestimate the local extent of the disease in a significant proportion of cases . Consequently, the additional information given by preoperative imaging may be helpful.
Currently, BCa staging is usually performed using T2w-MRI and dynamic CE-MRI (DCE-MRI), which are apparently superior to CE-CT. However, upstaging seems to be a major drawback because conventional T2w-MRI cannot accurately differentiate the various bladder wall layers . In addition, this technique requires gadolinium-based contrast agents, which are contraindicated in patients with impaired renal function. To overcome these limitations, several recent studies have investigated the use of DW-MRI in the work-up of BCa (Fig 3 and Fig 4).
In one study including 40 patients with 52 bladder tumours, DW-MRI combined with T2w-MRI was able to differentiate between T1 or lower tumours from T2 or higher tumours with 96% accuracy, and between T2 or lower tumours from T3 to T4 tumours with 92% accuracy based on morphologic findings at high b-values, increasing the performance of T2w-MRI alone. Overall T-stage accuracy increased from 67% using T2w-MRI alone to 88% when DW-MRI was added. This combination was superior to T2w-MRI plus DCE-MRI (79% accuracy) . In another study including 106 BCa patients, an inferior accuracy of 63.6% for differentiating non–muscle-invasive from muscle-invasive tumours and of 69.6% for differentiating organ-confined from non–organ-confined tumours was observed when DW-MRI alone was evaluated, although accuracy for T2w-MRI alone was even worse (6.1% and 15.1%, respectively) . This discrepancy may be due to the better image quality achieved in the former study , where diffusion-sensitising gradients were applied in the three orthogonal directions and 14 signal averages were acquired with a 4-mm-slice thickness, compared with the latter study  in which monodirectional gradients were applied using 7 signal averages and a 5-mm-slice thickness. In a smaller study including 18 patients with histologically confirmed BCa, upstaging decreased from 21% for unenhanced T1w- and T2w-MRI alone to 16% for CE-MRI and to only 5% by using DW-MRI in addition to T1w- and T2w-MRI .
Notably, in all these studies, imaging was performed before TUR. It is well known that post-TUR inflammatory changes negatively affect the staging accuracy of conventional morphologic imaging. However, functional imaging does not apparently overcome this interpretative pitfall.
Histologic grade of BCa is a fundamental prognostic factor. Attempts have been made to define tumour grade noninvasively using DW-MRI. ADC values were found to predict histologic grade in two recent studies. In the previously mentioned study , mean ADC values (b-values: 0 and 1000s/mm2) for G3 tumours (0.81
3.4.4. Treatment monitoring
Predicting the response to induction chemotherapy in patients with muscle-invasive BCa is fundamental to determine whether salvage radical surgery is required. One study explored the role of DW-MRI performed at 1.5 T with b-values of 0, 500, and 1000s/mm2 in assessing the response to induction chemoradiotherapy in 20 patients with muscle-invasive BCa . A significantly higher specificity and accuracy (92% and 80%) compared with T2w-MRI (45% and 44%) and DCE-MRI (18% and 33%) to predict complete response evaluated by histopathology was observed. If confirmed by further experience, these data suggest the potential of DW-MRI to serve as a biomarker of treatment response in the context of neoadjuvant chemotherapy strategies to radical cystectomy, where histopathology is the reference standard, thereby eventually allowing individualised treatment.
3.5. Pelvic lymph node staging
The presence of pelvic LN metastases in patients with PCa and BCa is of major prognostic relevance and decisive for treatment planning  and . LN staging is routinely performed by conventional cross-sectional imaging, and it is only based on dimensional criteria, with a threshold of 8–10
DW-MRI has the potential to discriminate malignant from benign LNs because the former are expected to have an impeded diffusion due to high cellularity, resulting in low ADC values. The specific literature is still limited, however, and with contrasting results. In a study of 29 PCa patients with a total of 118 LNs evaluated by DW-MRI at 1.5 T, highly significantly lower (p
In contrast, disappointing results for DW-MRI at 1.5 T in detecting LN metastases were found in another study including 36 high-risk PCa patients treated with radical prostatectomy and extended pelvic LN dissection, with a sensitivity and a positive predictive value of only 18.8% and 46.2%, respectively, in a LN region-based analysis . These figures increased to 42.9% and 60%, respectively, in a patient-based analysis. However, this poor performance may be due to the 53.1% positive LNs containing only micrometastases or isolated tumour deposits, albeit in some cases macrometastases were also missed. In this study, ADC values were not reported, making it difficult to compare data with previously published research.
A combination of DW-MRI with ultrasmall superparamagnetic particles of iron oxide (USPIO) showed 90% accuracy in detecting metastases even in normal-size LNs of PCa and BCa patients based on visual assessment, thereby facilitating the approach of this challenging diagnostic problem . In this study a meticulous pelvic LN dissection allowed correct assessment of the negative predictive value, which was reported to be 94% per pelvic side. Although these results were encouraging, larger studies are needed to confirm them; unfortunately, USPIO is currently unavailable.
3.6. Future perspectives
The major prerequisite for further advances in DW-MRI is the standardisation of this technique. Image acquisition and sequence parameters of different scanner platforms have to be defined and implemented, thus enabling comparison of imaging studies between different centres. Efforts are strongly required to avoid reading/interpretation bias both in the qualitative and quantitative analysis, thus minimising the interobserver variability. Initial attempts have been made to standardise DW-MRI for various organs and, specifically, multiparametric MRI for PCa detection and localisation  and . The achievement of these goals would enable the conduct of high-quality multicentre clinical trials, which are required for further validation of this promising technique, and also the rapid dissemination of this technique to nonacademic community-based institutions by reducing the individual learning curve. Finally, the applicability of this technique on a large scale may be facilitated by the lack of additional costs compared with conventional cross-sectional imaging. Costs could actually be reduced because contrast medium administration may be avoided in selected cases.
Definition of cut-off values for the noninvasive differentiation between benign and malignant tumours and their LN metastases, and eventually for discrimination of various histologic subtypes and grading, might allow individualised patient management.
In addition, DW-MRI could serve as a biomarker for predicting and monitoring treatment response in patients with genitourinary tumours undergoing targeted therapies. For example, antiangiogenic therapy is an established treatment for metastatic RCC . Because these new agents do not lead to an immediate reduction in tumour size, newer imaging techniques able to detect early changes in tumour metabolism under treatment are warranted. DW-MRI has the potential to show such microstructural changes before dimensional alterations, providing different ADC values at different dose levels and days of therapy and thus acting as a biomarker of early drug activity .
The current trend is toward the use of multiparametric MRI, combining conventional and functional MRI, including DCE-MRI, DW-MRI, MR spectroscopy, arterial spin labelling, and blood oxygen level–dependent MRI, with first studies mainly applied to the prostate . However, the multiparametric approach is time consuming and requires special software, contrast medium, and high expertise. Therefore, future studies ideally will determine which technique or combination of techniques will best answer the clinical questions in daily routine to ultimately optimise patient care.
Although CE-CT and conventional MRI are still standard techniques for the work-up of genitourinary tumours, DW-MRI has shown the potential to address some unresolved clinical needs due to its ability to explore microstructural tissue abnormalities at an early time point. DW-MRI is a reasonable alternative to CE imaging to detect and characterise focal renal lesions especially in patients with impaired renal function. DW-MRI improves the detection and localisation of PCa and may have a role in monitoring patients under active surveillance and after local curative therapy. DW-MRI may improve staging of BCa when used in addition to T2w-MRI. Finally, it has the potential to discriminate malignant from benign pelvic LNs. Standardisation of technical parameters and improvement in image analysis and interpretation will enable the validation of this promising technique.
Study concept and design: Giannarini, Thoeny.
Acquisition of data: Giannarini, Petralia, Thoeny.
Analysis and interpretation of data: Giannarini, Petralia, Thoeny.
Drafting of the manuscript: Giannarini, Petralia, Thoeny.
Critical revision of the manuscript for important intellectual content: Giannarini, Thoeny.
Statistical analysis: None.
Obtaining funding: Thoeny.
Administrative, technical, or material support: Thoeny.
Other (specify): None.
Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.
Funding/Support and role of the sponsor: This work was supported by research grant No. 320000-113512 of the Swiss National Science Foundation and by CARIGEST SA Switzerland, advisor of a generous grantor, which helped design and conduct the study, manage the data, and prepare the manuscript.
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a Department of Urology, University Hospital of Bern, Inselspital, Bern, Switzerland
b Institute of Diagnostic, Interventional, and Paediatric Radiology, University Hospital of Bern, Inselspital, Bern, Switzerland
Corresponding author. Institute of Diagnostic, Interventional, and Paediatric Radiology, University Hospital of Bern, Inselspital, CH-3010 Bern, Switzerland. Tel. +41 31 632 2939; Fax: +41 31 632 4874.
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© 2011 European Association of Urology, Published by Elsevier B.V.