Abstract
Aim: Magnetic resonance imaging (MRI) accuracy in prostate cancer (PCa) diagnosis in men submitted to saturation prostate biopsy (SPBx) was evaluated. Materials and Methods: From June 2011 to December 2012, 78 patients (median 63 years) underwent repeat SPBx (median 28 cores). Multiparametric MRI using a 3 Tesla pelvic phased-array coil was performed before SPBx and lesions suspicious for PCa were submitted to additional targeted biopsies. Results: A T1c PCa was found in 32 (41%) cases. SPBx vs. MRI-suspicious targeted biopsy diagnosed 28 (87.5%) vs. 26 (81.2%) PCa missing four (12.5%) and six (18.8%) cancers localized in the anterior zone and in the lateral margin of the prostate, respectively; moreover, MRI diameter lesions correlated with PCa diagnosis and Gleason score (p<0.05). Conclusion: Multiparametric MRI improved SPBx accuracy in diagnosing PCa of the anterior zone; moreover, suspicious areas >10 mm resulted as highly predictive of cancer (about 70% of the cases).
Widespread use of the prostate-specific antigen (PSA) test associated with lower PSA threshold and extended biopsy protocols, along with the introduction of mass screening protocols (1) have increased the detection rate of prostate cancer (PCa), currently the most prevalent malignancy in older men. However, extended transrectal-ultrasound (TRUS) guided-biopsy and saturation biopsy (SPBx) performing 12-18 (2) or ≥20 cores (3) have been suggested to improve detection rate for PCa in cases of initial or re-biopsy. Repeat prostate biopsy constitutes about 30% of the entire procedure, with an estimated diagnosis of PCa equal to 20-40%, with an increased risk of over-diagnosis as high as 50% secondary to the detection of cancer, often characterized by small, low-grade tumours that will never threaten the patient's survival (1). In addition, transrectal prostate biopsy has been associated with an increased risk of complications secondary to urinary tract infection and sepsis (1% of the cases), with the necessity for hospital admission in 2% of the cases (4). Therefore, the ideal protocol of diagnosis should perform targeted biopsies to diagnose only significant PCa, reducing the number of unnecessary procedures. In this light, multiparametric magnetic resonance imaging (MRI) using pelvic phased-array coil (pMRI) or endorectal coil (eMRI) has been proposed as a more accurate alternative in comparison with TRUS to increase the detection rate for PCa, especially in repeat biopsy (5-15). In fact, MRI has the benefit of increased resolution, superior imaging of anatomical structures, functional assessment and ability to potentially assign tumor grade (13).
The accuracy of multiparametric pMRI in PCa diagnosis in men with persistent suspicion of cancer submitted to repeat biopsy was evaluated in this prospective study.
Patients and Methods
From June 2011 to December 2012, 78 patients, all of Caucasian origin and between the ages of 49 and 72 years (median=63 years), with primary negative extended biopsy (median 18 cores) underwent SPBx (median 28, range=26-32 cores) for persistent suspicion of PCa. The 78 patients enrolled in a prospective, monocentric and multi-departmental study were selected from a case-finding protocol for PCa detection (16) and had one single previous negative biopsy (normal parenchyma) performed at least six months before (range=6-19 months); the indications for repeat SPBx were: persistently high or increasing PSA value, abnormal digital rectal examination (DRE) and PSA >10 ng/ml or PSA values between 4.1-10 or 2.6-4 ng/ml with free/total PSA ≤25% and ≤20%, respectively.
All patients, provided a written informed consent, underwent multiparametric MRI 3-10 days before undergoing the SPBx. All examinations were performed using a 3.0 Tesla scanner, (ACHIEVA 3T; Philips Healthcare Best, the Netherlands) equipped with surface 16 channels phased-array coil placed around the pelvic area with the patient in supine position; multiplanar turbo spin-echo T2-weighted (T2W), axial diffusion weighted imaging (DWI), axial dynamic contrast enhanced (DCE) and spectroscopy were performed for each patient.
Saturation prostate biopsy scheme: prostate gland regions. Right vs. left lobe (posterior zone: parasagittal cores): 1 vs. 7 (base); 2 vs. 8 (middle); 3 vs. 9 (apex). Right vs. left lobe (posterior zone: lateral margin cores): 4 vs. 10 (base); 5 vs. 11 (middle); 6 vs. 12 (apex). Anterior zone: 13; transition zone: 14.
The criteria (14) for a positive lesion on T2W were the presence of a circumscribed, low signal intensity lesion (hypointense); a positive lesion on DCE was characterized by the presence of foci showing early and intense enhancement and rapid washout after power injection (3.0 ml/s) of gadobutrol 0.1 ml/kg (Gadovist®; Bayer Schering Pharma, Germany) followed by a 15 ml saline flush. A positive lesion on spectroscopy was any area where the choline to citrato ratio was 3 or more standard deviations above the mean healthy value.
Two radiologists (AG, GP) blinded to pre-imaging clinical parameters evaluated the MRI data separately and independently. To ensure that histopatological findings matched with MRI images the assessment of radiological images and SPBx scheme were performed dividing the prostate into 14 regions: apex, middle zone and base of posterior zone for each lobe beginning parasagittally to reach the outer edges of the gland (six regions for each lobe), anterior and transitional zone (Figure 1).
SPBx was performed transperineally using a tru-cut 18 gauge needle (Bard; Covington, GA USA) and a GE Logiq 500 PRO ecograph (General Electric; Milwaukee, WI USA) supplied with a biplanar transrectal probe (5-6.5 MHz) under sedation and antibiotic prophylaxis. The prostate biopsy protocol included a median of 12 cores in the posterior zone of each lobe (apex, middle zone and base of the gland) and 2-3 cores in the transition and anterior zone (17). In the presence of MRI lesions suspicious for cancer, 3-4 (median=3.5 cores) targeted TRUS guided-biopsies in addition to standard SPBx were performed. A probability (p) level of less than 0.05 was considered statistically significant.
Results
All patients had negative DRE and TRUS; median PSA was 11 ng/ml (range=3.7-45 ng/ml): 28 (35.8%) had PSA >10 ng/ml, 46 (59%) between 4-10 ng/ml and 4 (5.2%) between 2.6-4 ng/ml, respectively. MRI was positive in 46 (62.1%) out of 78 patients; in detail 42 (53.8%), 40 (51.2%), 40 (51.2%) and 38 (48.7%) men had a positive T2W, DWI, DCE and spectroscopy, respectively. For the 46 patients submitted to MRI-suspicious targeted biopsy, 160 cores were performed (median=3.5; range=3-4); in 42 (91.3%) out of 46, the lesions were included in the SPBx scheme, on the contrary, in four (8.7%) cases, the suspected areas were localized in the anterior zone near the bladder neck. None had significant complications from SPBx that needed hospital admission; moreover, the MRI procedure was well-tolerated and successfully performed in all cases.
A T1c PCa was found in 32 (41%) out of 78 patients and normal parenchyma in the remaining 46 (59%). Clinical parameters, biopsy quantitative histology, greatest percentage of cancer, Gleason score (GS), number of positive cores and multiparametric pMRI findings in the presence of PCa and normal parenchyma are listed in Table I. SPBx scheme and MRI-suspicious targeted biopsy diagnosed 28 (87.5%) and 26 (81.2%) out of 32 PCa, respectively. In detail SPBx and pMRI missed four (12.5%) and six (18.8%) cases of cancer localized in the anterior zone (Figure 2) and in the lateral margin of the prostate gland (four in the apex and two in the base), respectively. In the presence and absence of PCa the nodular suspicious MRI lesions had a median diameter equal to 14 mm (range=5-32 mm) vs. 7 mm (range=5-13 mm) (p>0.05), respectively; a cut-off of 10 mm detected 18 (69.3%) out of 26 carcinomas with a false-positive rate of 10%. Moreover, median nodular diameter on MRI was correlated to GS (GS 6=9 mm; GS 7=16 mm; GS 8=22 mm) showing a significant statistical difference between GS 6 vs. GS 8 (p <0.05). The detection rate of cancer for each core performing SPBx vs. targeted cores of suspicious MRI lesions was 6.7% vs. 15.7%, respectively (p<0.05).
Clinical parameters, biopsy quantitative histology and pelvic phased-array multiparametric magnetic resonance imaging (MRI) findings for 78 men submitted to repeat saturation prostate biopsy.
Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of multiparametric pMRI vs. each pMRI parameter (T2W, DWI, DCE, spectroscopy) in diagnosing PCa, are listed in Table II.
Discussion
SPBx is the gold standard (3, 4) for PCa diagnosis at repeat prostate biopsy; although TRUS diagnosis was enriched in recent years by the introduction of three-dimensional and computerized images and by the use of contrast media, which allow for better characterization of intraparenchymal microvasculature (18), ultrasound accuracy remains poor in performing targeted-biopsy (19, 20). In recent years, multiparametric MRI has gained growing importance in PCa diagnosis and staging using pMRI or eMRI (5-15); further developments in MRI include greater magnetic field strength (from 1.5 to 3 Tesla), functional imaging with spectroscopy exploiting increased choline and reduced citrate in tumours. Recently, 3-Tesla MRI has been suggested in the reevaluation of patients enrolled in active surveillance protocols (11), and is highly representative of the true GS (13, 21) and predictive of significant PCa (10, 22).
The estimated sensitivity and specificity for PCa detection by MRI varies between 57% and 100% vs. 44% and 96%, respectively (5); therefore, there is increasing interest in using MRI, especially in men with prior negative prostate biopsies and persistent suspicion of PCa. Multiparametric pMRI and eMRI have been introduced in clinical practice to detect for suspicious areas which could be submitted to real-time MRI-guidance targeted-biopsy or translated into real-time MRI/TRUS imaging fusion to perform targeted biopsy (6, 23, 24). Franiel et al. (7) and Hambrock et al. (8) in 54 and 68 patients with previous negative biopsies submitted to MRI-guided biopsy demonstrated a detection rate for PCa of 39% and 59%, respectively. Pinto et al. (6) in 55 out of 101 (54.4%) patients with PCa diagnosed at repeated-biopsy showed a greater detection rate of cancer for each core using MRI imaging/ultrasound fusion-guided biopsy in comparison with standard 12-core transrectal biopsy (20.6% vs. 11.7%, respectively). Kuru et al. (9), performing transperineal stereotactic prostate biopsy after MRI evaluation detected PCa in 54% of 50 patients submitted to prostate biopsy. Although eMRI had the best sensitivity and specificity in diagnosing and staging PCa, recently 3 Tesla pMRI demonstrated good accuracy in detecting areas suspicious for PCa. The use of pMRI provides, in daily practice, more advantages in comparison with eMRI; in fact, its use is widespread in many general hospitals, it is easy to perform and it does not generate discomfort to the patient. In addition, whole-body MRI has been suggested as a one-step procedure for staging men with high-grade PCa (25).
Pelvic phased-array multiparametric magnetic resonance imaging (MRI) accuracy in diagnosing prostate cancer at repeat-biopsy.
A 69-year-old patient with previous negative extended prostate biopsy, negative digital rectal examination and prostate-specific antigen (PSA) of to 8.6 ng/ml. a) Sagittal T2-weighted magnetic resonance imaging (MRI): hypointense area (2 cm) of the anterior zone; b) axial imaging: on gadolinium injection, the suspicious lesion exhibited a greater and clear contrast enhancement (dynamic contrast-enhanced MRI) than the surrounding tissue.
In our series, the SPBx scheme found a greater number of tumours (28 out of 32 cases) localized in the posterior zone of the gland; on the contrary, pMRI detected four (12.5%) significant tumours of the anterior zone, missing six (18.7%) PCa of the posterior zone charaterized by minimal or microfocal biopsy histological disease (1 positive core of GS 6) (18) at risk for the presence of insignificant PCa (cancer volume <0.5 ml and GS ≤6) (22). In addition, a correlation between MRI nodular diameter vs. PCa diagnosis and tumour grade was found.
Finally, multiparametric pMRI demonstrated the best NPV (81.2%) and DWI or DCE alone reported the highest specificity (60.8%) in PCa detection, respectively; spectroscopy alone had poor specificity, on the contrary, it was predictive of cancer aggressiveness when all pMRI parameters (T2W, DWI and DCE) were positive.
Some limitations and considerations of the present study deserve to be mentioned. Firstly, we do not know the true diagnostic accuracy of pMRI in diagnosing PCa because the detection rate for cancer was compared with SPBx results. Secondly, our results should be confirmed in a greater number of patients. Finally, we do not know if the false-positive rate (25.6% of the cases) of MRI was secondary to false-negative SPBx results or was biased because an MRI imaging/ultrasound fusion-guided biopsy, which is theoretically more accurate, was not performed.
In conclusion, multiparametric pMRI improves SPBx accuracy in diagnosing PCa of the anterior zone (12.5% of tumours would be missed) in cases of repeat-biopsy; moreover, suspicious nodular areas ≥10 mm should be submitted to additional guided-biopsy because they are highly predictive of PCa (about 70% of the cases).
- Received January 11, 2013.
- Revision received February 17, 2013.
- Accepted February 18, 2013.
- Copyright© 2013 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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