Genitourinary Imaging Original Research

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1 Genitourinary Imaging Original Research Tamada et al. Prostate Imaging After High-Dose-Rate Brachytherapy Genitourinary Imaging Original Research Tsutomu Tamada 1 Teruki Sone 1 Yoshimasa Jo 2 Junichi Hiratsuka 3 Atsushi Higaki 1 Hiroki Higashi 1 Katsuyoshi Ito 1 Tamada T, Sone T, Jo Y, et al. Keywords: brachytherapy, diffusion MRI, local neoplasm recurrence, MRI, prostatic neoplasms DOI: /AJR Received September 13, 2010; accepted after revision January 7, This study was supported by a Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (grant ) and the Kawasaki Medical School Project (grants and ). 1 Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama , Japan. Address correspondence to T. Tamada (ttamada@med.kawasaki-m.ac.jp). 2 Department of Urology, Kawasaki Medical School, Kurashiki City, Okayama, Japan. 3 Department of Radiation Oncology, Kawasaki Medical School, Kurashiki City, Okayama, Japan. AJR 2011; 197: X/11/ American Roentgen Ray Society Locally Recurrent Prostate Cancer After High-Dose-Rate Brachytherapy: The Value of Diffusion-Weighted Imaging, Dynamic Contrast-Enhanced MRI, and T2-Weighted Imaging in Localizing Tumors OBJECTIVE. The purpose of this article is to retrospectively evaluate the utility of prostate MRI for detecting locally recurrent prostate cancer after high-dose-rate (HDR) brachytherapy. MATERIALS AND METHODS. Sixteen men with biochemical failure after HDR brachytherapy for prostate cancer underwent prostate MRI, including T2-weighted imaging, dynamic contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging (DWI), using a 1.5-T MRI unit before 12-core-specimen biopsy. Two radiologists in consensus assessed the presence of tumor on each sequence within eight regions of the prostate (six from the peripheral zone [PZ] and two from the transition zone [TZ]) on the basis of biopsy. RESULTS. Biopsy revealed locally recurrent prostate cancer in 22 (17 in PZ and five in TZ) of 128 regions (17.2%). The sensitivity, specificity, and accuracy of each MRI method in the detection of recurrent tumor were 27%, 99%, and 87%, respectively, for T2-weighted imaging; 50%, 98%, and 90%, respectively, for DCE-MRI; and 68%, 95%, and 91%, respectively, for DWI. The sensitivity of DWI in detecting recurrent tumor was significantly higher than that of T2-weighted imaging (p = 0.004). Multiparametric MRI achieved the highest sensitivity (77%) but with slightly decreased specificity (92%). CONCLUSION. These results indicate that a multiparametric MRI protocol that includes DWI provides a sensitive method to detect local recurrence after HDR brachytherapy. A brachytherapy modality using a high-dose-rate (HDR) 192 Ir afterloading technique has recently been developed to overcome the inhomogeneous dose distribution of interstitial seed brachytherapy and has been proposed as a curative treatment for localized prostate cancer [1 5]. Furthermore, HDR brachytherapy has been expected to improve patient quality of life after therapy [1 5]. On the other hand, recent studies have revealed that clinical failure in the form of local or systematic recurrence occurs in approximately % of patients after treatment with HDR brachytherapy [1 5]. Local recurrence after HDR brachytherapy may be amenable to salvage prostatectomy, brachytherapy, thermal therapy, or cryotherapy, similar to local recurrence after external beam radiation therapy (EBRT) or low-doserate brachytherapy [6 8]. Because increases in prostate-specific antigen (PSA) level do not represent a reliable marker for differentiating local recurrence from distant recurrence [9, 10], the utility of imaging modali- ties such as MRI [11 16], 11 C-acetate PET [17], and 111 In Prosta-Scint SPECT [18] in the detection of local recurrence after EBRT has been reported. In the diagnosis of locally recurrent sites after EBRT using MRI, the utility of T2- weighted MRI [11], dynamic contrast-enhanced MRI (DCE-MRI) [15, 16], MR spectroscopic imaging (MRSI) [12 14], and diffusion-weighted imaging (DWI) [11] has been clarified. Furthermore, the utility of DWI with apparent diffusion coefficient (ADC), not only in the diagnosis of prostate cancer arising in the peripheral zone (PZ) and transition zone (TZ) but also in the evaluation of tumor differentiation of prostate cancer, has been reported in recent years in a number of preliminary studies. This has led to high expectations of clinical applications as an additional method complementing T2- weighted imaging, DCE-MRI, and MRSI [11, 19 27]. Accordingly, these MRI techniques might be expected to show high tumor detectability, even with local recurrence after HDR brachytherapy. However, to our 408 AJR:197, August 2011

2 Prostate Imaging After High-Dose-Rate Brachytherapy knowledge, no studies evaluating the detection of local recurrence after HDR brachytherapy using MRI have been reported. The purpose of this study was thus to retrospectively evaluate T2-weighted MRI, DCE- MRI, and DWI in the detection and localization of locally recurrent prostate cancer after HDR brachytherapy. Materials and Methods Patient Characteristics All study protocols were approved by the institutional review board. The need for obtaining informed consent from patients was waived. To be included in the study, a patient must have been diagnosed with biochemical failure (current PSA level nadir plus 2 ng/ml) after HDR brachytherapy for prostate cancer [28], have shown anticipated general life expectancy longer than 5 years, and have undergone MRI of the prostate before ultrasound-guided systematic prostate biopsy for histopathologic examination of the recurrent prostate cancer. As a result, study subjects included 16 consecutive patients (mean age, 69 years; range, years) who underwent MRI between December 2006 and September The total number of patients who received HDR brachytherapy during the same period (May 2003 to September 2005) as this study population was 206. The mean PSA level at initial diagnosis was ng/ml (range, ng/ml), and the median tumor Gleason score was 7 (range, 6 9). The pretreatment clinical stage of these patients was T1 (n = 3), T2 (n = 8), or T3 (n = 5). None of the patients displayed clinical or pathologic lymph node involvement or distant metastases before radiotherapy. These patients were treated using both EBRT and HDR brachytherapy (n = 11) for patients with intermediate-to-high risk factors (initial PSA level, 10 ng/ml; Gleason score, 7; or stage T2b T3 disease) or HDR brachytherapy alone (n = 5) for patients with low risk factors (initial PSA level, < 10 ng/ml; Gleason score, < 7; and stage T1c T2a disease). Treatment with HDR brachytherapy and EBRT consisted of HDR brachytherapy using an afterloader (microselectron HDR, Nucletron) in four fractions of 6.0 Gy within 30 hours, for a total dose of 24.0 Gy, and EBRT (four ports) to the prostate in 16 fractions of 2.3 Gy, for a total dose of 36.8 Gy. Treatment with HDR brachytherapy alone included HDR brachytherapy using an afterloader in five fractions of 7.5 Gy within 30 hours, for a total dose of 37.5 Gy. Applicator needles remained inserted during the 30-hour irradiation period and then were removed. Seven patients with prostate volume greater than 30 cm 3 underwent neoadjuvant hormonal therapy to reduce prostate size before radiotherapy. No patients received adjuvant hormonal therapy after radiotherapy. The mean interval from radiotherapy to MRI was 30 months (range, months), and that from MRI to subsequent biopsy was 9 days (range, 1 31 days). The mean PSA level before MRI was 7.42 ng/ml (range, ng/ml). MRI MRI was performed using a 1.5-T MRI scanner (Signa Excite, GE Healthcare; maximum gradient amplitude, 33 mt/m; maximum slew rate, 77 mt/m/s). A body coil was used for signal excitation, with a multichannel phased-array coil for signal reception. After intramuscular administration of glucagon to decrease intestinal peristalsis, imaging was performed in all patients under fasting conditions. MRI protocols included T1-weighted fast spinecho (FSE) imaging in the transverse plane, T2- weighted FSE imaging in transverse and coronal planes, T2-weighted echo-planar imaging (EPI) in the transverse plane, DWI in the transverse plane, DCE-MRI in the transverse plane, and contrast-enhanced T1-weighted FSE imaging in the transverse plane. Transverse T1-weighted FSE imaging was performed to evaluate hemorrhage within the prostate gland. Transverse T2-weighted FSE imaging was performed through the prostate gland and seminal vesicles. In addition to T2- weighted sequences, transverse T2-weighted EPI was also performed. Transverse DWI was performed using a multisection spin-echo singleshot EPI sequence. ADC maps were reconstructed by calculating the ADC in each pixel of each slice. Transverse DCE-MRI was performed using an FSE sequence with fat-suppression technique covering the prostate from apex to base, in addition to the seminal vesicles. Data acquisition for DCE-MRI began simultaneously with initiation of IV injection of gadopentetate dimeglumine (Magnevist, Bayer Schering Pharma) at 0.1 mmol/kg of body weight within 10 seconds through a peripheral IV cannula, followed by a 40-mL saline flush. Multiphase DCE images (five phases) were obtained every 30 seconds for 2 minutes 30 seconds without breathholding by patients. The technical parameters of the MRI pulse sequences are listed in Table 1. Image Interpretation and Data Analysis Two radiologists with 8 and 4 years of experience in prostate MRI conducted a consensus review of MRI scans for all 16 patients. The reviewers were aware that patients had been diagnosed with biochemical failure after HDR brachytherapy for prostate cancer but were unaware of all other clinical and histopathologic findings. T1-weighted images were assessed to confirm that none of the subjects showed signs of hemorrhage within the prostate. Hemorrhage was considered as present when an area of signal hyperintensity was identified within the prostate gland on T1-weighted images [22]. Reviewers rated both the degree of postirradiation zonal indistinctness and the degree of diffuse reduction of T2 signal intensity in the gland as TABLE 1: MRI Sequences Used for Prostate Imaging Sequence T1-Weighted FSE T2-Weighted FSE T2-Weighted EPI DWI (Single-Shot EPI) DCE-MRI (FSE) TR/TE (ms) 425/ / / / /9 Echo-train length 2 16 NA NA 3 Matrix size FOV (cm) No. of acquisitions Slices thickness (mm) Interslice gap (mm) Parallel imaging factor NA NA NA 2 NA Scan time 2 min 42 s 4 min 47 s 2 min 43 s 2 min 40 s 2 min 30 s (30 s 5 phases) Note Diffusion-weighted imaging (DWI) was acquired with motion-probing gradient pulses applied sequentially along three orthogonal orientations with two b factors (0 and 800 s/mm 2 ). DCE-MRI = dynamic contrast-enhanced MRI, EPI = echo-planar imaging, FSE = fast spin-echo, NA = not applicable. AJR:197, August

3 Tamada et al. absent, intermediate, or marked, using the methods described by Coakley et al. [12]. Zonal indistinctness was considered as absent if the prostate had zonal differentiation similar to that seen in a nonirradiated prostate gland and was considered as marked if the PZ and TZ were nearly indistinguishable. All other degrees of zonal indistinctness were considered as intermediate. Diffusely reduced T2 signal intensity was considered as absent if the signal intensity of T2-weighted images in the prostate resembled that in a nonirradiated prostate gland and was considered as marked if T2 signal intensity in the prostate was similar to or lower than that in nearby nonirradiated muscle. All other degrees of diffusely reduced T2 signal intensity were considered intermediate. To distinguish PZ and TZ, reviewers used T2- weighted MRI scans, because zonal anatomy of the prostate can be seen on these images only [29]. Landmarks used to distinguish PZ and TZ were the urethra and capsule of the prostate gland. Any surgical pseudocapsule separating the TZ and PZ was also used as a landmark. In the PZ, sections through the bladder neck and proximal prostatic urethra were considered as the base, whereas the prostatic apex was defined by the doughnutshaped appearance of the distal prostatic urethra. The remainder of the PZ was considered as the middle [30]. Eight regions on MRI scans (described later in the article) were individually evaluated with regard to the detectability of prostate cancer. Prostate cancer was localized independently on each MRI study according to standard criteria. Each MRI of the same patient was reviewed with a minimum interval of 3 weeks. On MRI scans, lesions fulfilling the following criteria were regarded as prostate cancer: on T2-weighted imaging (FSE or EPI or both), an area of homogeneous signal hypointensity with mass effect in the PZ, an area of circumscribed round or triangular-shaped localized signal hypointensity in the PZ [31], or an area in the TZ with homogeneous signal hypointensity, ill-defined margins, and lack of capsule, with or without a lenticular shape and invasion of anterior fibromuscular stroma [29]; on DWI and ADC maps, an area with focal signal hyperintensity on DWI and with focal signal hypointensity on the ADC map relative to the background prostatic parenchyma; or on DCE-MRI, an area with focal early enhancement greater than the background prostatic parenchyma until the third phase (60 seconds after contrast media administration) and washout or prolonged enhancement in the delayed phase (fourth and fifth phases). In the interpretation of images from DWI and DCE-MRI, T2- weighted imaging was referred to, so as to confirm anatomic positions after the assessment of each image. In multiparametric MRI, when a positive finding according to the aforementioned criteria was recognized for at least one of the three modalities in each region for each patient, the region was considered to contain prostate cancer. Reference Standard A total of 12 specimens (eight from the PZ and four from the TZ) were taken from each patient during transrectal ultrasound-guided systematic prostate biopsy by a urologist with 13 years of experience in ultrasound-guided prostate biopsy. Biopsy sites included base right, middle right, apex right, far lateral right, base left, middle left, apex left, and far lateral left regions in the PZ, and bilateral ventral and dorsal regions in the TZ. According to the sites of biopsy, the prostate gland was divided into eight regions on MRI scans that is, base right in PZ, middle right and far lateral right in PZ, apex right in PZ, ventral and dorsal right in TZ, base left in PZ, middle left and far lateral left in PZ, apex left in PZ, and ventral and dorsal left in TZ were designated as base right, middle right, apex right, TZ right, base left, middle left, apex left, and TZ left, respectively. A tumor site in each MRI scan was considered to match histologic findings by a radiologist with 8 years of experience in prostate MRI if the tumor was present in the same region of the prostate, as indicated in pathology reports for ultrasound-guided biopsy specimens. Statistical Analysis Diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated for T2-weighted imaging, DWI, DCE-MRI, and the combination of all three MRI techniques (multiparametric MRI). Differences of sensitivity, specificity, PPV, and NPV between any two MRI methods were tested using the McNemar test. The Fisher exact test was used to determine significant differences in sensitivity of multiparametric MRI, to detect tumor recurrence between PZ and TZ. Statistical analyses were performed using SPSS software (version 11.5 J for Windows, SPPS). A p value less than 0.05 was considered indicative of statistically significant differences. Results Location of Recurrent Tumor in Prostate Biopsy Postirradiation biopsy revealed locally recurrent prostate cancer in nine of 16 patients (56%) and in 22 of 128 regions (17.2%), unilaterally in eight patients. The rate of recurrence in the patients who received HDR brachytherapy during the same period as the study population was 4.4% (9/206 patients). The pretreatment risk status of the study population was low risk (n = 3), intermediate risk (n = 2), and high risk (n = 4), indicating that the number of patients with recurrent tumor is evenly distributed among the risk groups of prostate cancer. These recurrent regions were located in the PZ in 17 regions (77%) and in the TZ in five regions (23%). The PZ lesions included seven in the base, seven in the middle, and three in the apex. None of the patients had lymph node or bone metastases after radiotherapy. Consensus Reading In the consensus review of the MRI scans, no disagreement has been observed between two readers. Degree of Hemorrhage No intraglandular hemorrhage was observed in any subjects on T1-weighted imaging. Influence of Radiotherapy on T2-Weighted Imaging of the Prostate Gland Reviewers rated zonal indistinctness as absent in one patient, intermediate in seven patients, and marked in eight patients. Reviewers rated the degree of diffuse T2 signal hypointensity as absent in one patient, intermediate in 13 patients, and marked in two patients (Fig. 1). Detection of Recurrent Prostate Cancer Sensitivity, specificity, accuracy, PPV, and NPV are shown in Table 2. Sensitivity was highest for multiparametric MRI (77%), followed in decreasing order by DWI (68%), DCE-MRI (50%), and T2-weighted imaging (27%). Specificity was slightly lower for mul- Fig year-old man. Transverse T2-weighted fast spin-echo image was obtained 15 months after high-dose-rate brachytherapy for prostate cancer. Degree of zonal indistinctness was considered marked, and degree of diffusely reduced T2 signal intensity was considered intermediate. 410 AJR:197, August 2011

4 Prostate Imaging After High-Dose-Rate Brachytherapy TABLE 2: Differences in Detection of Recurrent Prostate Cancer Using MRI Methods MRI Method Sensitivity Specificity Accuracy PPV NPV Multiparametric MRI a 77 (17/22) 92 (98/106) 90 (115/128) 68 (17/25) 95 (98/103) T2-weighted imaging 27 (6/22) 99 (105/106) 87 (111/128) 86 (6/7) 87 (105/121) Diffusion-weighted imaging 68 (15/22) 95 (101/106) 91 (116/128) 75 (15/20) 94 (101/108) Dynamic contrast-enhanced MRI 50 (11/22) 98 (104/106) 90 (115/128) 85 (11/13) 90 (104/115) Note Data are percentages, with values used to calculate these percentages provided in parentheses. NPV = negative predictive value, PPV = positive predictive value. a Multiparametric MRI refers to the combined use of T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced MRI. A tiparametric MRI (92%) compared with the individual sequences (range, 95 99%). These differences were statistically significant only for the comparisons of sensitivity between T2-weighted imaging and DWI (p = 0.004), between T2-weighted imaging and multiparametric MRI (p = 0.001), and between DCE-MRI and multiparametric MRI (p = 0.031), and for the comparisons of specificity between T2-weighted imaging and multiparametric MRI (p = 0.016) and between DCE-MRI and multiparametric MRI (p = 0.031) (Figs. 2 and 3). None of the remaining pairwise comparisons was statistically significant (p = ). The sensitivity of multiparametric MRI to detect tumor recurrence was substantially lower in the TZ (3/5 patients [60%]) than in the PZ (14/17 patients [82%]), although with no significant difference (p = 0.548). Discussion At a mean of 30 months after HDR brachytherapy (range, months), the influence of radiotherapy on T2-weighted imaging was observed in most patients (15/16 B Fig year-old man with increased prostatespecific antigen level (5.27 ng/ml) at 28 months after high-dose-rate brachytherapy for prostate cancer and positive transrectal biopsy results indicating Gleason score of 7 in middle right region of peripheral zone (PZ). A, No abnormal findings were observed on transverse T2-weighted echo-planar image of prostate. B, Transverse diffusion-weighted image with b factors of 0 and 800 s/mm 2 shows PZ cancer (arrow) revealed as focal signal hyperintensity in right PZ. C E, Transverse dynamic contrast-enhanced MRI of first phase (C), third phase (D), and fifth phase (E) show PZ cancer (arrow, D and E) seen as focal early enhancement and late washout in right PZ. C D E patients [94%]). This finding is consistent with previous studies using endorectal MRI [12]. Coakley et al. [12] reported that because radiation-induced anatomic changes such as diffuse T2 signal hypointensity in the gland and indistinctness of the normal zonal anatomy limit the utility of conventional morphologic evaluations with T2-weighted MRI, MRSI (which provides metabolic, rather than anatomic, information) might be useful in the evaluation of recurrent tumor after EBRT. On the other hand, no patients had intraglandular hemorrhage causing any AJR:197, August

5 Tamada et al. disturbance of accurate tumor detection in functional sequences such as DWI and DCE- MRI. Furthermore, this fact suggests that the diffuse signal hypointensity and the indistinct zonal anatomy on T2-weighted MRI would not be attributed to hemorrhage. All methods of MRI assessed in this study showed good specificity but low sensitivity for the detection of locally recurrent prostate cancer after HDR brachytherapy. In particular, the sensitivity of T2-weighted imaging was lower than that of the other two methods, although a significant difference was observed only with DWI. The low sensitivity of T2-weighted imaging can be attributed to the influence of radiotherapy, as A C Fig year-old man with increased PSA level (4.09 ng/ml) at 43 months after high-dose-rate brachytherapy for prostate cancer and positive transrectal biopsy results indicating Gleason score of 7 in middle right region of peripheral zone (PZ) and right region of transition zone (TZ). A, Transverse T2-weighted fast spin-echo image shows PZ cancer (arrow) as homogeneous signal hypointense lesion with mass effect in right PZ. B, Transverse diffusion-weighted image with b factors of 0 and 800 s/mm 2 shows PZ and TZ cancer (arrows) seen as focal signal hyperintensity in right PZ and right TZ. C and D, No areas of focal early enhancement representing prostate cancer were observed on transverse dynamic contrast-enhanced MRI of first phase (C) or third phase (D). mentioned previously in this article. In other words, with T2-weighted imaging, the low signal intensity with indistinct zonal anatomy of prostate tissue decreases the contrast between the recurrent cancer mass and surrounding benign tissue. In contrast to the low sensitivity of T2- weighted imaging, DCE-MRI has been reported to correlate well with biopsy results from patients with biochemical failure after EBRT [15, 16]. Because contrast enhancement in the fibrotic region after radiotherapy is slow and mild, the recurrent tumor mass, which is usually hypervascular, could show good contrast, resulting in high diagnostic sensitivity for DCE-MRI [32]. However, the B D sensitivity (52%) of DCE-MRI in the current study was not particularly high compared with findings from previous reports (70 74%) and was not significantly different from that of T2-weighted imaging. Sensitivity was probably low in our study because both the PZ and TZ were evaluated in all patients. In fact, our result showed lower detection of recurrent tumor in the TZ than in the PZ, as seen with primary cancer [29]. In addition, for reasons that are unclear, radiotherapy using HDR brachytherapy instead of EBRT may also be associated with low sensitivity of T2-weighted imaging. Compared with these two methods, DWI showed high sensitivity for detecting recurrent prostate cancer after HDR brachytherapy. DWI is based on differences in diffusion of water molecules, mainly attributable to differences in cellular density. Recent studies have found a high degree of differentiation between normal and cancerous prostate tissue, including both primary tumors and locally recurrent tumor after EBRT [11, 19 27]. The high diagnostic performance of DWI for recurrent tumor after EBRT would explain the high sensitivity for recurrent tumor after HDR brachytherapy in the present study. Furthermore, our results suggest that signal intensity of the irradiated prostatic gland with fibrosis is relatively low compared with recurrent cancer, which is depicted as signal hyperintense because of the decreased diffusion of water molecules. A previous report [33] has described increases in the proportion of stromal components (e.g., smooth muscle and connective tissues) to glandular epithelium appearing as increased ADC values, which do not cause increases in signal intensity on DWI. We think that prostatic tissue, after a long period (mean, 30 months; range, months) since radiotherapy such as HDR brachytherapy, has little effect on tumor detection in DWI and that high contrast is maintained between cancerous tissue and the surrounding benign tissue. However, further investigations are necessary to clarify postirradiation effects on various MRI modalities. The current study has some limitations. First, our study was limited by a relatively small number of patients. However, to the best of our knowledge, this represents the only study to date with MRI of locally recurrent prostate cancer after HDR brachytherapy and examination of pathologic correlations. Second, our study included patients who received different treatment protocols, 412 AJR:197, August 2011

6 Prostate Imaging After High-Dose-Rate Brachytherapy such as HDR brachytherapy alone and both EBRT and HDR brachytherapy, with or without neoadjuvant hormonal therapy, before radiation. These differences in treatment may have had some influence on the results of this study. Third, step-section histopathology was not used to determine correlations between MRI and histopathologic findings in this study. MRI results might thus have been underestimated compared with evaluation using histologic specimens of the whole prostate after radical prostatectomy. Fourth, MRI was performed with a phased-array coil only, rather than with a combination of a phased-array coil and an endorectal coil. The use of an endorectal coil yields a substantial increase in the signal-to noise ratio, but it also results in discomfort for the patient and extra cost [26]. Actually, because the poor results of T2-weighted imaging for the detection of locally recurrent prostate cancer after HDR brachytherapy seem to be mainly a result of decreased contrast between recurrent cancer mass and surrounding radiation-induced fibrotic tissue, the use of an endorectal coil might increase the signal-tonoise ratio in T2-weighted imaging with a resultant improvement in tumor detectability. Indeed, a recent prospective study using 3-T MRI comparing a body-array coil and an endorectal coil showed that T2-weighted imaging with an endorectal coil had significantly higher image quality and signal-to-noise ratio as well as tumor detectability in comparison with a body-array coil [34]. Fifth, the image analysis in this study was performed by a consensus reading rather than by a blind reading; therefore, interobserver variability could not be assessed. Sixth, in the statistical analysis, because we assumed that the multiple observations per subject were independent, we did not account for possible intrasubject correlation between the different regions. Finally, consecutive evaluations on MRI before and after HDR brachytherapy have not been performed in studies of the influence of HDR brachytherapy on the prostate gland and the detectability of recurrent prostate cancer. Further prospective studies with larger subject populations, such as multicenter trials, are needed to clarify the clinical utility of prostate MRI for detecting recurrent tumor after HDR brachytherapy. In conclusion, the current study indicates that prostate MRI is a sensitive method to detect local recurrence after HDR brachytherapy and that DWI should be included in the MRI protocol for patients after HDR brachytherapy. 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