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Conventional MRI Capabilities in the Diagnosis of Prostate Cancer in the Transition Zone

¹ Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho chuo-ku, Kobe, Hyogo, Japan 650-0017.
² Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
³ Division of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.

Received May 14, 2004; accepted after revision December 6, 2004.

 
Address correspondence to H. Li.

Abstract

Top Abstract Introduction Materials and Methods Results Discussion References

 
OBJECTIVES. Our objectives were to evaluate the diagnostic capabilities of conventional MRI for the accurate detection of prostate cancer within the transition zone and to compare the results with histopathologic examination results.

MATERIALS AND METHODS. One hundred sixteen prostate specimens with prostate cancer were consecutively obtained. Axial, sagittal, and coronal T2- and T1-weighted MR images with gadopentetate dimeglumine were independently reviewed by two radiologists. The diagnostic base criteria of the MR images were determined for detecting transition zone cancer as follows: lesions with A, uniform low intensity on T2-weighted images; B, homogeneous gadolinium enhancement; and C, irregular margins both on gadolinium-enhanced and T2-weighted images. Wilcoxon's rank sum and chi-square tests and receiver operating characteristic curves were used. Differences of less than 0.05 were considered significant.

RESULTS. Eighty-six lesions in the transition zone were analyzed. Histopathologic analysis showed 53 cancers and 33 benign lesions. The diagnostic sensitivity, specificity, and accuracy for cancer were 50%, 51%, and 51%, respectively with criteria A; 68%, 75%, and 71% with criteria B; and 60%, 72%, and 65% with criteria C. When base criteria were combined into criteria A-B, A-C, and B-C and then further divided into three subgroups, accuracy was found to be highest when the lesion satisfied any two criteria from A, B, and C than those of base criteria, combination criteria, and the other two subgroups.

CONCLUSION. The addition of gadolinium-enhanced MRI to T2-weighted imaging provides better accuracy for detecting cancerous transition zone lesions than the use of T2-weighted imaging alone.

Keywords: cancer • MRI • prostate

Introduction

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MRI has been gaining acceptance as an important tool in the evaluation of prostate cancer [1-5]. Thus far, MRI assessment of prostate cancer has focused on the peripheral zone of the prostate gland [3-5]. Detailed anatomic studies have suggested that 65% of cancers arise in the peripheral zone of the prostate, but up to 30% of prostate cancers occur within the transition zone [6]. Transition zone-originating cancer substantially contributes to morbidity and mortality from prostate cancer [7].

Evaluation of transition zone cancer with imaging, including conventional MRI, gadolinium-enhanced MRI with dynamic data acquisition, and sonography [8-12], is difficult because transition zone cancer is the site of origin of benign prostatic hyperplasia, which can have a heterogeneous appearance [3, 13-19]. Proton MR spectroscopic imaging has been successfully applied to the diagnosis of cancer in the peripheral zone on the basis of the elevation of choline and the reduction of citrate in cancerous tissue [3, 20, 21]. However, the broad range of metabolite ratios observed in transition zone cancer precludes the use of a single ratio to differentiate transition zone cancer from benign transition zone lesions [21-23].

Because a considerable number of cancers originate in the transition zone, research is needed in this part of the prostate. The purpose of this study was to establish the diagnostic criteria for differentiating transition zone cancers from coexisting benign lesions in patients who have undergone radical prostatectomy.

Materials and Methods

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Materials
This retrospective study was conducted between April 1999 and October 2003. One hundred twenty-one consecutive patients with untreated prostate cancer underwent conventional MRI followed by radical prostatectomy. After eliminating patients with unenhanced MRI because of a drug allergy history (n = 3) or serious obstructive voiding symptoms (n = 2), medical records, MRI, and histopathologic data in 116 patients were studied. The patients ranged from 52 to 76 years old (mean, 65 years). One hundred eight of 116 patients were referred for MRI before the sextant biopsy; the remaining eight patients received MRI after the sextant biopsy in a mean interval of 4 weeks (range, 3-6 weeks). For all patients, the period from MRI to radical prostatectomy surgery ranged from 1 to 7 weeks (mean interval, 4 weeks).

View larger version (18K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A —Receiver operating characteristic (ROC) curves from data in Table 5. Graph of three ROC curves was constructed according to base criteria in Table 5. It shows comparison of base criteria of A, B, and C. Base criterion B is preferable to base criteria A and C.

View larger version (19K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B —Receiver operating characteristic (ROC) curves from data in Table 5. Graph of three ROC curves was constructed on combined criteria in Table 5. Line F is preferable to lines D and E in sensitivity but lower in specificity for detection of transition zone cancer.

View larger version (18K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1C —Receiver operating characteristic (ROC) curves from data in Table 5. Graph of three ROC curves was obtained from subgroups G, H, and I according to data in Table 5. Curve G shows higher sensitivity than curves H and I, but for clinically important accuracy subgroup H is better than subgroups G and I.

T1-weighted (TR/TE, 500-685/9-20) and T2-weighted turbo spin-echo (3,500-5,500/100-155; echo-train length, 8-16) sequences were performed in the axial, sagittal, and coronal planes for all patients using a multisection technique. Slice thickness was 4 mm with a 1-mm interslice gap, matrix size was 512 x 512, and field of view was 220 x 220 mm.

After these initial sequences, the enhanced fat-saturated axial T1-weighted imaging was repeated immediately after the bolus injection of IV gadolinium (Magnevist, 0.2 mL/kg, Schering). This set of images was obtained at about 2 min 30 sec. Enhanced images through the prostate from the apex to the base of the prostate were obtained within a time of about 60 sec variable to the number of slices. The mean number in each sequence of MRI slices of the prostate was six slices (range, 4-9 slices).

Histopathologic Examination
One hundred sixteen specimens were coated with India blue or red ink to allow microscopic evaluation of surgical resection margins and fixed in 5% buffered formalin for 24 hr. After dehydration, the prostate glands were serially blocked into 4-mm-thick sections from the apex to the base in transverse planes corresponding to MRI by two doctors. Seven hundred nineteen step-sectioned pathologic specimens were obtained (mean, 6.2 slices for each gland). Each section was copied on paper and then the mounted prostate specimens were embedded in paraffin. A 7-µm-thick slice was obtained from the superior surface of each section and stained with H and E. The contour and size of each lesion were drawn on copying paper and the diagnosis was reported on a separate paper by a pathologist who used the following classification: prostatic adenocarcinoma, benign prostatic hyperplasia subdivided into glandular (> 5% glandular elements), stroma (< 5% glandular elements), mixed glandular and stroma, prostatitis, bleeding, scar, necrosis, and normal stromal and glandular elements.

According to the microscopic examination, 196 discrete prostate cancers were diagnosed by the pathologist, including 53 in the transition zone (27%), 134 in the peripheral zone (68%), and nine (5%) whose origin could not be identified.

MRI Analysis
MR images of each patient were downloaded individually and separately transferred to a computer from the DICOM server in the PACS system of our hospital. The names, ages, and identification numbers recorded on each image were erased by members of this study group.

Two reviewers (with 9 and 15 years' experience, respectively, in reading images of the prostate) blinded to the histopathologic results independently analyzed all images. Both reviewers knew that all patients had prostatectomy-proven prostate cancer.

One reviewer traced each prostate onto paper according to each axial T2-weighted slice for correlation with the pathologic maps. Lesions of the transition zone in which signal intensity was abnormally low compared with the transition zone area or which the reviewer thought were possibly prostatic lesions were drawn on each of the traced prostate images.

Lesions were subsequently recorded and rated by the two reviewers. The two reviewers were restricted to the sites identified by one of the reviewers to ensure they were both rating the same areas. Cancer was considered present on MR image analysis when there was uniform low signal intensity on T2-weighted images, homogeneous gadolinium enhancement, or the interface between the lesion and the inner gland was irregular on gadolinium-enhanced and T2-weighted images (irregular margin was considered according to gadolinium enhancement and T2-weighted images because the interface between cancer and the area of the inner gland sometimes was not easy to identify on T2-weighted images). However, all other nodules showing heterogeneous low intensity with regular margins and heterogeneous gadolinium enhancement were considered benign lesions. The criteria used for MRI analysis have been established in previously reported MRI findings [8-19, 24-28] and were supplemented with the personal experience of the two reviewers.

The criterion for each area was rated by the two reviewers on a five-point scale: 1, definitely cancer; 2, probably cancer; 3, possibly cancer; 4, probably benign; or 5, definitely benign. When a lesion was difficult to rate or when lesions were rated significantly differently, consensus readings were performed until the lesion could be rated.

The reviewers also noted that images did not have large or extensive motion artifacts except in two patients, where artifacts on gadolinium-enhanced imaging arose from hip prostheses. No bleeding was seen within the transition zone areas in any of the MR images except those in one patient who had no history of biopsy before MRI was performed.

Statistical Analysis
In this analysis, the unit of analysis was the cancer and benign diseases in the transition zone. Cancer within the transition zone detected with MRI was considered a true-positive (rated 1-3, cancer present) when cancer was present on the histopathologic copying papers on which each transition zone cancer was drawn within the same region. False-positive results (rated 1-3, cancer absent) were considered if the cancer in the transition zone was diagnosed with MRI but a benign lesion was reported on the histopathologic copying papers. True-negative results (rated 4-5, cancer absent) were considered when benign lesions detected with MRI compared with histopathologic copying papers with benign lesions. If the MRI was considered negative but the histopathologic copying papers showed cancers, then the results were false-negative (rated 4-5, cancer present).

The sensitivity of each criterion was determined by confidence ratings of 1-3. Likewise, specificity was determined by confidence ratings of 4-5 [29]. The sensitivity, specificity, and correct characterization rates were determined by each diagnostic criterion, which was rated on the five-point scale by each reviewer. Statistical differences, receiver operating characteristic curve analysis (Figs. 1A, 1B, and 1C), and 95% confidence intervals were calculated using StatMate III software (ATMS Co. Ltd.). The mean results of the true-positive and false-negative lesions with the mean confidence level from the two reviewers are shown in Tables 4 and 5.

Interobserver agreement was assessed with kappa statistics. Kappa analysis was performed using formulas described by Kundel and Polansky [30]. A kappa value of up to 0.20 stood for slight agreement; a value of 0.21-0.40, fair agreement; 0.41-0.60, moderate agreement; 0.61-0.80, substantial agreement; and 0.81 or greater, almost perfect agreement. In all statistical analyses, a p value of less than 0.05 was considered to indicate a statistically significant difference.

Results

Top Abstract Introduction Materials and Methods Results Discussion References

 
The serum prostate-specific antigen (PSA) level was reduced in 116 patients, ranging from 2.2-71.4 ng/mL before operation (mean, 16.9 ng/mL) (Table 1). All 116 prostatectomy specimens evaluated in this study had a histopathologic diagnosis of cancer and the histologic grades were further defined using the Gleason score (Table 2). Table 3 shows the prostate cancer stages in 116 patients.

Each transition zone lesion recorded on the reviewer's schematic prostate diagram of MRI was aligned as closely as possible to the same histopathologic copying papers on which each transition zone cancer was drawn and compared by reviewers. The correlation between diagnostic criteria of MRI and histopathologic diagnoses is shown in Tables 4 and 5.

A total of 53 transition zone cancers were identified on histopathologic evaluation by a pathologist. In comparison with schematic prostate diagrams of MRI, criterion A of the uniform low intensity on T2-weighted imaging was seen in 27 (51%) of the 53 transition zone cancers (Figs. 2A, 2B, 2C, 2D, 3A, 3B, 3C, 4A, 4B, 4C, and 4D). The remaining 26 (49%) false-negative MRI results were reviewed with histopathologic copying papers as follows: A, mixed with benign prostatic hyperplasia (n = 3) (Figs. 5A, 5B, and 5C); B, hypernephroid pattern (n = 2, of two revealed on histopathologic copying papers) (Figs. 6A, 6B, 6C, and 6D); C, well-differentiated adenocarcinoma (n = 3 of 7); D, ordinary pattern in histopathology (n = 4); E, mixed with the edema fibrosis tissue secondary to prostatitis (n = 1); F, arising within benign prostatic hyperplasia nodules (n = 2); G, arising from residual tissue of the transition zone after a transurethral resection of the prostate (n = 1); H, multiple cancer foci sporadically distributed among the normal gland of the prostate (n = 1); and I, nine cancers that could not be visualized using MRI, including six cancers smaller than 5 mm² in size.

View larger version (157K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A —Prostatic cancer in 68-year-old man with prostate-specific antigen level of 19.3 ng/mL and negative findings on endorectal sonography-guided biopsy. Stage is T2b. No suspicious findings were seen on digital rectal examination or endorectal sonography. Axial and sagittal T2-weighted images (TR/TE, 5,000/155 and 4,700/119; echo-train length, 8) show uniform hypointense area with irregular margin in anterior location of inner gland, which extends toward anterior fibromuscular stroma (arrows). Heterogeneous decreased intensity area is seen in right peripheral zone.

View larger version (152K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B —Prostatic cancer in 68-year-old man with prostate-specific antigen level of 19.3 ng/mL and negative findings on endorectal sonography-guided biopsy. Stage is T2b. No suspicious findings were seen on digital rectal examination or endorectal sonography. Axial and sagittal T2-weighted images (TR/TE, 5,000/155 and 4,700/119; echo-train length, 8) show uniform hypointense area with irregular margin in anterior location of inner gland, which extends toward anterior fibromuscular stroma (arrows). Heterogeneous decreased intensity area is seen in right peripheral zone.

View larger version (163K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C —Prostatic cancer in 68-year-old man with prostate-specific antigen level of 19.3 ng/mL and negative findings on endorectal sonography-guided biopsy. Stage is T2b. No suspicious findings were seen on digital rectal examination or endorectal sonography. Contrast-enhanced T1-weighted image (600/20) with fat suppression shows homogeneous enhancement of lesion at inner gland and enhancement of both peripheral zones.

View larger version (152K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2D —Prostatic cancer in 68-year-old man with prostate-specific antigen level of 19.3 ng/mL and negative findings on endorectal sonography-guided biopsy. Stage is T2b. No suspicious findings were seen on digital rectal examination or endorectal sonography. Histopathologic specimen obtained at corresponding level reveals moderately differentiated adenocarcinoma in anterior position of inner gland (arrow). Tumor size is 35 x 15 mm. Two small tumor foci indicating prostatic intraepithelial neoplasia are seen in background of both peripheral zones (arrowheads) (original magnification, H and E staining).

View larger version (166K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3A —70-year-old man with stage T2b cancer. Prostate-specific antigen is 11.8 ng/mL. Axial T2-weighted image (TR/TE, 5,550/137; echo-train length, 8) illustrates uniform low-intensity abnormality in inner gland at right (arrows).

View larger version (161K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3B —70-year-old man with stage T2b cancer. Prostate-specific antigen is 11.8 ng/mL. Contrast-enhanced T1-weighted image (550/12) with fat suppression shows homogeneous enhancement confined to inner gland.

View larger version (173K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3C —70-year-old man with stage T2b cancer. Prostate-specific antigen is 11.8 ng/mL. Histopathologic specimen at level of tumor shows adenocarcinoma present at inner gland. Tumor size is 24 x 16 mm (original magnification, H and E staining).

View larger version (177K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4A —68-year-old man with stage T2b cancer. Prostate-specific antigen was 17 ng/mL. Axial and sagittal T2-weighted images (TR/TE, 4,500/132 and 4,500/136, respectively; echo-train length, 8) show band-shaped hypointense area in anterior of inner gland (arrows).

View larger version (200K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4B —68-year-old man with stage T2b cancer. Prostate-specific antigen was 17 ng/mL. Axial and sagittal T2-weighted images (TR/TE, 4,500/132 and 4,500/136, respectively; echo-train length, 8) show band-shaped hypointense area in anterior of inner gland (arrows).

View larger version (109K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4C —68-year-old man with stage T2b cancer. Prostate-specific antigen was 17 ng/mL. Hypointense area shows homogeneous enhancement with irregular margin on contrast-enhanced T1-weighted image with fat suppression (517/18).

View larger version (153K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4D —68-year-old man with stage T2b cancer. Prostate-specific antigen was 17 ng/mL. Histopathologic section reveals moderately differentiated adenocarcinoma. Anterior fibromuscular stroma is ruptured (arrow) (original magnification, H and E stain).

View larger version (135K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5A —59-year-old man with stage T2a cancer. Prostate-specific antigen was 71.4 ng/mL. Axial T2-weighted image (TR/TE, 4,617/102; echo-train length, 8) shows large heterogeneous low signal intensity on right side of inner gland (arrows).

View larger version (134K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5B —59-year-old man with stage T2a cancer. Prostate-specific antigen was 71.4 ng/mL. After contrast material administration, homogeneous enhancement is shown in anterior of lesion (arrowheads) and inhomogeneous enhancement in posterior of lesion (arrows) (617/12).

View larger version (176K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5C —59-year-old man with stage T2a cancer. Prostate-specific antigen was 71.4 ng/mL. Histopathologic specimen obtained at corresponding level reveals moderately differentiated adenocarcinoma originating from benign prostatic hyperplasia nodule surrounded by capsule of benign prostatic hyperplasia (arrowheads). Anterior fibromuscular stroma is ruptured. Tumor size is 34 x 28 mm (original magnification, H and E staining).

View larger version (180K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6A —73-year-old man with stage T2b cancer and false-negative interpretation of benign lesion. Prostate-specific antigen is 10 ng/mL. Regular margin of intermediate-signal-intensity nodule (arrows) is shown in inner gland on left on axial T2-weighted image (TR/TE, 4,000/120; echo-train length, 12).

View larger version (129K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6B —73-year-old man with stage T2b cancer and false-negative interpretation of benign lesion. Prostate-specific antigen is 10 ng/mL. Postcontrast T1-weighted image with fat suppression (TR/TE, 672/17) shows no enhancement with regular margin.

View larger version (138K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6C —73-year-old man with stage T2b cancer and false-negative interpretation of benign lesion. Prostate-specific antigen is 10 ng/mL. Histopathologic specimens show hypernephroid pattern of adenocarcinoma. Left of anterior fibromuscular stroma is ruptured (arrowhead, C) (original magnification, x10; H and E stain).

View larger version (177K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6D —73-year-old man with stage T2b cancer and false-negative interpretation of benign lesion. Prostate-specific antigen is 10 ng/mL. Histopathologic specimens show hypernephroid pattern of adenocarcinoma. Left of anterior fibromuscular stroma is ruptured (arrowhead, C) (original magnification, x10; H and E stain).

View larger version (180K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7A —72-year-old man with prostatic cancer located only in peripheral zone, stage T2b. Prostate-specific antigen is 8.8 ng/mL. Nodular whorl area with low signal intensity presents on inner gland on axial T2-weighted image (arrows) (TR/TE, 4,350/100; echo-train length, 12).

View larger version (165K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7B —72-year-old man with prostatic cancer located only in peripheral zone, stage T2b. Prostate-specific antigen is 8.8 ng/mL. Nodule shows homogeneous enhancement with regular edge on contrast-enhanced T1-weighted image (550/11) (arrows).

View larger version (164K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7C —72-year-old man with prostatic cancer located only in peripheral zone, stage T2b. Prostate-specific antigen is 8.8 ng/mL. Transverse section of prostate shows typical nodular benign prostatic hyperplasia (arrowheads) (original magnification, H and E stain).

View larger version (132K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8A —70-year-old man with stage T2b cancer. Prostate-specific antigen is 5.9 ng/mL. Axial T2-weighted image (TR/TE, 4,400/103; echo-train length 8) shows low-intensity area (arrows) in inner gland at right.

View larger version (144K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8B —70-year-old man with stage T2b cancer. Prostate-specific antigen is 5.9 ng/mL. Postcontrast T1-weighted image with fat suppression (550/12) shows no enhancement with clear margin interpreted as benign prostatic hyperplasia nodule (arrows).

View larger version (148K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8C —70-year-old man with stage T2b cancer. Prostate-specific antigen is 5.9 ng/mL. Histopathologic specimen at level of lesion shows pseudohyperplastic adenocarcinoma present at right inner gland (arrowheads) (original magnification, H and E stain).

According to criterion C of the irregular margin analysis, the sensitivity and specificity were 60% and 72%, respectively. Based on histopathologic examination, 21 (39%) false-negative MRI results showed some cancers were globular surrounded by a pseudo-well-circumscribed margin mimicking benign prostatic hyperplasia (Figs. 6A, 6B, 6C, 6D, 8A, 8B, and 8C); others were in contact with the benign prostatic hyperplasia nodule (Figs. 9A, 9B, and 9C) or could not be identified. In the 33 benign lessons, 9 (27%) false-positive MRI results showed benign prostatic hyperplasia (n = 6), prostatitis (n = 2), and periurethral duct inflammation (n = 1).

View larger version (170K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9A —73-year-old man with stage T2b cancer. Prostate-specific antigen is 13 ng/mL. Axial T2-weighted MR image (TR/TE, 4,467/120; echo-train length, 8) shows two hypointense areas in inner gland (arrows and arrowheads).

View larger version (142K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9B —73-year-old man with stage T2b cancer. Prostate-specific antigen is 13 ng/mL. Contrast-enhanced T1-weighted image (TR/TE, 517/13) with fat suppression and anterior lesion shows homogeneous enhancement with irregular margin (arrows). Posterior lesion shows no enhancement with regular margin (arrowheads).

View larger version (145K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9C —73-year-old man with stage T2b cancer. Prostate-specific antigen is 13 ng/mL. Histopathologic section shows well-differentiated adenocarcinoma in anterior (arrows) and nodule benign prostatic hyperplasia surrounded by capsule in posterior (arrowheads) (original magnification, H and E stain).

Then the three subgroups (groups G, H, and I) were further divided according to base criteria A, B, and C. The cancer was considered present if the lesion satisfied any one criterion in first subgroup G, any two criteria in second subgroup H, or all three criteria in third subgroup I among A, B, or C, respectively. The results are shown in Table 5.

To obtain better accuracy, the second subgroup H was considered the best of the three subgroups according to results from Table 5. This was not the case when criteria A, B, and C were analyzed independently or when they were analyzed in combination (A-B, A-C, and B-C).

The 95% confidence interval of each criterion and the kappa statistics performed to measure the agreement between two reviewers are shown in Table 4. There was very good to excellent agreement between the two reviewers for detecting transition zone cancer when using our three criteria.

Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

 
The central prostate gland shows a heterogeneously variable signal intensity appearance in older people with benign prostatic hyperplasia or other coexisting benign diseases. Transition zone cancer tends to have uniform low intensity on T2-weighted imaging [14-19]. However, the uniform low intensities of transition zone cancer are too uncertain to assist with the diagnosis of transition zone cancer in the presence of a coexisting benign disease. After gadopentetate dimeglumine administration in our study, the central gland showed markedly inhomogeneous signal intensity [15], and the configuration and the homogeneous enhancement pattern of the transition zone cancer could be depicted better than on T2-weighted imaging alone.

The importance of recognizing the presence of transition zone cancer was described by Padhani and Nutting [32]. Recently, imaging diagnosis of transition zone cancer has focused on the use of conventional MRI and MR spectroscopy [19, 22]. However, the criteria for the diagnosis of transition zone cancer have not yet been fully established [23]. In this article, we have proposed three diagnostic criteria for detecting transition zone cancer and differentiating it from coexisting benign diseases.

In a previous study aimed at detecting transition zone cancer, Outwater et al. [25] identified none of the 29 central gland tumors in their study. Carter et al. [33] reported 15% sensitivity and Ikonen et al. [19] reported 55% sensitivity. Our data of overall sensitivity, specificity, and accuracy were 68%, 82%, and 73%, respectively, and thus similar to data from Ito et al. [10], who lacked pathologic correlation with radical prostatectomy specimen examinations (invisible cancers smaller than 5 mm² in size were not included). The improved accuracy of identification in our study was probably due to the use of our three criteria for detecting transition zone cancer.

Not all transition zone cancers show uniform low-intensity appearances (so-called T2-isointense prostate cancer [PCa]) [27]. By excluding six nonvisualized transition zone cancers smaller than 5 mm² in size [19, 34], our histopathologic data showed that 20 of 53 transition zone cancers did not show uniform low intensity. False-negative imaging results were obtained: adenocarcinomas with low grade (well-differentiated and pseudohyperplasic pattern) or hypernephroid components [15, 17, 20]; or adenocarcinomas blending with benign prostatic hyperplasia, edema tissue or normal tissue, and so on. However, by using the criteria of homogeneous enhancement and irregular margins, 38% of false-negative cases could be correctly diagnosed as transition zone cancer in our study.

The specificity was low when transition zone cancers were detected only with sequential T2-weighted imaging. T2 hypointense foci in the inner gland can be caused by numerous other conditions such as prostatitis, granulomatous disease, smooth muscle hyperplasia, fibromuscular hyperplasia, atypical adenomatous hyperplasia, scar, infarction, and bleeding that contribute to the poor specificity [3, 17-22]. However, if criteria of homogeneous enhancement and irregular margins were used, the specificity rates could be increased from 51% to 82% in this study.

Inflammation in the anterior fibromuscular stroma (AFS) or periurethral duct may result from false-positive imaging results in our study. Normally, both the anterior fibromuscular stroma and the periurethral duct show low intensity on T2-weighted imaging without enhancement [1]. However, when inflammation occurs, both of them show enhancement similar to transition zone cancer [1, 22].

This study showed the addition of gadolinium-enhanced MRI to T2-weighted imaging provides better accuracy for detecting cancerous transition zone lesions than the use of T2-weighted imaging alone. We also revealed that one third of cancers in the transition zone do not show uniform low intensity on T2-weighted imaging and that when transition zone cancer is suspected, a gadolinium-enhanced imaging study should be used. The most promising clinical application of this technique could be to study patients with a previous negative endorectal sonography-guided biopsy, persistently elevated PSA, and abnormal low intensity on T2-weighted imaging.

References

Top Abstract Introduction Materials and Methods Results Discussion References

 

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