Alessandro Sciarra

Advances in Magnetic Resonance Imaging: How They Are Changing the Management of Prostate Cancer

CONTEXT Although magnetic resonance imaging (MRI) is emerging as the most commonly used imaging modality for prostate cancer (PCa) detection, treatment planning, and follow-up, its acceptance has not been uniform. Recently, great interest has been shown in multiparametric MRI, which combines anatomic T2-weighted (T2W) imaging with MR spectroscopic imaging (MRSI), dynamic contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging (DWI). OBJECTIVE The aim of this article is to review the current roles of these MR techniques in different aspects of PCa management: initial diagnosis, biopsy strategies, planning of radical prostatectomy (RP) and external radiation therapy (RT), and implementation of alternative focal therapies. EVIDENCE ACQUISITION The authors searched the Medline and Cochrane Library databases (primary fields: prostatic neoplasm, magnetic resonance). The search was performed without language restriction from January 2008 to November 2010. EVIDENCE SYNTHESIS Initial diagnosis: The data suggest that the combination of T2W MRI and DWI or MRSI with DCE-MRI has the potential to guide biopsy to the most aggressive cancer foci in patients with previously negative biopsies, increasing the accuracy of the procedure. Transrectal MR-guided prostate biopsy can improve PCa detection, but its availability is still limited and the examination time is rather long. Planning of RP: It appears that adding MRSI, DWI, and/or DCE-MRI to T2W MRI can facilitate better preoperative characterization of cancer with regard to location, size, and relationship to prostatic and extraprostatic structures, and it may also facilitate early detection of local recurrence. Thus, use of these MR techniques may improve surgical, oncologic, and functional management. Planning of external RT and focal therapies: MR techniques have similar potential in these areas, but the published data remain very limited. CONCLUSIONS MRI technology is continuously evolving, and more extensive use of MRI technology in clinical trials and practice will help to improve PCa diagnosis and treatment planning.

Distribution of inflammation, pre-malignant lesions, incidental carcinoma in histologically confirmed benign prostatic hyperplasia: A retrospective analysis

OBJECTIVES We analyze our experience on BPH through 20 years of histopathological examinations performed by the same pathologist. METHODS We retrospectively reviewed all histopathological examinations performed from January 1979 to December 1998 in patients undergoing surgery in our urological clinic who were diagnosed with BPH. We limited our evaluation to the following variables in each BPH case analyzed: inflammatory aspects associated with BPH, presence of focal acinar atrophy, atypical adenomatous hyperplasia (AAH), prostatic intraepithelial neoplasia (PIN), incidental prostate carcinoma (IC). These histological variables were analyzed according to some clinical parameters such as age, prostate volume and serum PSA. RESULTS The study population was comprised of 3942 cases with histological diagnosis of BPH. The mean patient age was 68.85+/-7.67 years. In particular, inflammatory aspects were associated with BPH in a high percentage of cases (43.1% =1700 cases), predominantly as chronic inflammation. Observation of focal acinar atrophy significantly increased according to patient decade of age (p=0.027). There was a significant trend to increase with age decades (p=0.036) for high grade PIN. A significant difference was found in IC (T1a, T1b) distribution in the different decades of age and especially in regards to both T1a and T1b tumors, there was a trend to increase with patient age (p=0.020 and p=0.025, respectively). On the contrary, the distribution of inflammatory aspects (p<0.001) and AAH (p=0.003) significantly varied according to prostate volume, and particularly in regards to chronic inflammation, there was a trend to increase depending on the prostate volume (p=0.002). Only the presence of T1b tumor but not of the other histological parameters associated to BPH, was able to significantly influence serum PSA. CONCLUSION In our analysis different histological variables associated to BPH are differently influenced by the age of patients and prostate volume, and they differently influence serum PSA levels.

Role of Dynamic Contrast-Enhanced Magnetic Resonance (MR) Imaging and Proton MR Spectroscopic Imaging in the Detection of Local Recurrence after Radical Prostatectomy for Prostate Cancer

OBJECTIVES To assess the accuracy of magnetic resonance (MR) spectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced MR (DCEMR) in the depiction of local prostate cancer recurrence in patients with biochemical progression after radical prostatectomy (RP). MATERIALS AND METHODS 1H-MRSI and DCEMR were performed in 70 patients at high risk of local recurrence after RP. The population was divided on the basis of the clinical validation of MR results with the use of a transrectal ultrasound biopsy examination in a group of 50 patients (group A) and the prostate-specific antigen (PSA) serum level restitution after external beam radiotherapy, in a group of 20 patients (group B). RESULTS In group A, 1H-MRSI analysis alone showed a sensitivity of 84% and a specificity of 88%; the DCEMR analysis alone, a sensitivity of 71% and a specificity of 94%; combined 1HMRSI-DCEMR, a sensitivity of 87% and specificity of 94%. Areas under the receiver operating characteristic (ROC) curve for 1HMRSI, DCEMR, and combined 1HMRSI /DCEMR were 0.942, 0.93,1 and 0.964, respectively. In group B, 1HMRSI alone showed a sensitivity of 71% and a specificity of 83%; DCEMR, a sensitivity of 79% and a specificity of 100%; combined 1HMRSI and DCEMR, a sensitivity of 86% and a specificity of 100%. Areas under the ROC curve for each of these groups were 0.81, 0.923, and 0.94, respectively. CONCLUSION Our results show that combined 1H-MRSI and DCMRE is an accurate method to identify local prostate cancer recurrence in patients with biochemical progression after RP.

Value of magnetic resonance spectroscopy imaging and dynamic contrast-enhanced imaging for detecting prostate cancer foci in men with prior negative biopsy

Purpose: This study aimed to prospectively analyze the role of magnetic resonance spectroscopy imaging (MRSI) and dynamic-contrast enhancement magnetic resonance (DCEMR) in the detection of prostate tumor foci in patients with persistently elevated prostate-specific antigen levels (in the range of ≥4 ng/mL to <10 ng/mL) and prior negative random trans-rectal ultrasound (TRUS)-guided biopsy. Experimental Design: This was a prospective randomized single-center study. One hundred and eighty eligible cases were included in the study. Patients in group A were submitted to a second random prostate biopsy, whereas patients in group B were submitted to a 1H-MRSI-DCEMR examination and samples targeted on suspicious areas were associated to the random biopsy. Results: At the second biopsy, a prostate adenocarcinoma histologic diagnosis was found in 22 of 90 cases (24.4%) in group A and in 41 of 90 cases (45.5%) in group B (P = 0.01). On a patient-by-patient basis, MRSI had 92.3% sensitivity, 88.2% specificity, 85.7% positive predictive value (PPV), 93.7% negative predictive value (NPV), and 90% accuracy; DCEMR had 84.6 % sensitivity, 82.3% specificity, 78.5% PPV, 87.5% NPV, and 83.3% accuracy; and the association MRSI plus DCEMR had 92.6% sensitivity, 88.8% specificity, 88.7% PPV, 92.7% NPV, and 90.7% accuracy, for predicting prostate cancer detection. Conclusions: The combination of MRSI and DCEMR showed the potential to guide biopsy to cancer foci in patients with previously negative TRUS biopsy. To avoid a potential bias, represented from having taken more samples in group B (mean of cores, 12.17) than in group A (10 cores), in the future a MRSI/DCEMR directed biopsy could be prospectively compared with a saturation biopsy procedure. Clin Cancer Res; 16(6); 1875–83

Multiparametric magnetic resonance imaging vs. standard care in men being evaluated for prostate cancer: A randomized study

OBJECTIVES To assess whether the proportion of men with clinically significant prostate cancer (PCa) is higher among men randomized to multiparametric magnetic resonance imaging (mp-MRI)/biopsy vs. those randomized to transrectal ultrasound (TRUS)-guided biopsy. METHODS In total, 1,140 patients with symptoms highly suggestive of PCa were enrolled and divided in 2 groups of 570 patients to follow 2 different diagnostic algorithms. Group A underwent a TRUS-guided random biopsy. Group B underwent an mp-MRI and a TRUS-guided targeted+random biopsy. The accuracy of mp-MRI in the diagnosis of PCa was calculated using prostatectomy as the standard of reference. RESULTS In group A, PCa was detected in 215 patients. The remaining 355 patients underwent an mp-MRI: the findings were positive in 208 and unremarkable in 147 patients. After the second random+targeted biopsy, PCa was detected in 186 of the 208 patients. In group B, 440 patients had positive findings on mp-MRI, and PCa was detected in 417 at first biopsy; 130 group B patients had unremarkable findings on both mp-MRI and biopsy. In the 130 group B patients with unremarkable findings on mp-MRI and biopsy, a PCa Gleason score of 6 or precancerous lesions were detected after saturation biopsy. mp-MRI showed an accuracy of 97% for the diagnosis of PCa. CONCLUSIONS The proportion of men with clinically significant PCa is higher among those randomized to mp-MRI/biopsy vs. those randomized to TRUS-guided biopsy; moreover, mp-MRI is a very reliable tool to identify patients to schedule in active surveillance.

Functional Magnetic Resonance Imaging in Prostate Cancer

CONTEXT Magnetic resonance imaging (MRI) combined with magnetic resonance spectroscopy imaging (MRSI), dynamic contrast-enhanced MRI, and diffusion-weighted MRI emerged as promising tests in the diagnosis of prostate cancer, and they show encouraging results. OBJECTIVE This review emphasizes different functional MRI techniques in the diagnosis of prostate cancer and includes information about their clinical value and usefulness. EVIDENCE ACQUISITION The authors searched the Medline, Embase, and Cochrane Library databases. There were no language restrictions. The last search was performed in October 2008. EVIDENCE SYNTHESIS The combination of conventional MRI with functional MRI techniques is more reliable for differentiating benign and malignant prostate tissues than any other diagnostic procedure. At present, no guideline is available that outlines which technique is best in a specific clinical situation. It also remains uncertain whether improved spatial resolution and signal-to-noise ratio of 3-T MRI will improve diagnostic performance. CONCLUSIONS A limited number of small studies suggest that functional MRI may improve the diagnosis and staging of prostate cancer. This finding needs further confirmation in larger studies, and cost-effectiveness needs to be established.

Prostate growth and inflammation.

INTRODUCTION There is emerging evidence that prostatic inflammation may contribute to prostate growth either in terms of hyperplastic (BPH) or neoplastic (PC) changes. Inflammation is thought to incite carcinogenesis by causing cell and genome damage, promoting cellular turnover. METHODS We reviewed our personal experience and the international recent literature on the clinical data supporting a role of inflammation on BPH and PC growth and progression. RESULTS BPH: Among those patients with self-reported prostatitis, 57% had a history of BPH. MTOPS study showed that men with inflammation had a significantly higher risk of BPH progression and acute urinary retention. We showed that the use of a COX-2 inhibitor in combination with a 5 alpha reductase inhibitor could increase the apoptotic index in BPH tissue. Prostate cancer: A PCR-based analysis of bacterial colonization in PC specimens and normal prostate tissue showed highly suggestive correlation of bacterial colonization and chronic inflammation with a diagnosis of PC. Evidence from genetic studies support the hypothesis that prostate inflammation may be a cause of prostate cancer. De Marzo proposed that proliferative inflammatory atrophy (PIA) is a precursor to PIN and cancer. CONCLUSION The concept that inflammation can promote prostate growth either in terms of BPH and PC risk remains highly suggestive.

Prostate cancer: 1HMRS-DCEMR at 3 T versus [(18)F]choline PET/CT in the detection of local prostate cancer recurrence in men with biochemical progression after radical retropubic prostatectomy (RRP)

OBJECTIVES This study compares proton magnetic resonancespectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined techniques at 3T magnet versus [(18)F]choline PET/computed tomography (CT) in the detection of local prostate cancer recurrence in patients with biochemical progression after radical retropubic prostatectomy (RRP). MATERIALS AND METHODS 84 consecutive patients at high risk of local recurrence underwent combined 1HMRSI-DCEMR and 18-Fcholine- PET/CT. MR scan protocol included turbo spin echo (TSE) T2-weighted sequences in the axial, sagittal and coronal planes; three-dimensional (3D) chemical shift imaging (CSI) sequences with spectral/spatial pulses optimized for quantitative detection of choline and citrate; dynamic contrast enhanced gradient-echo (GRE) T1-weighted sequence. The population was divided into two groups. Group A included 28 patients with a lesion size ranging between 5.00mm and 7.2mm and PSA reduction following radiation therapy. Group B included 56 patients with a lesion size between 7.6mm and 19.4mm. Sensitivity, specificity, positive predictive value (PPV) and accuracy were evaluated and receiver operating characteristic (ROC) curves were performed. RESULTS In Group A combined 1H-MRSI and DCE-MRI showed a sensitivity of 92%, a specificity of 75% (PPV 96%) while PET-CT examination showed a sensitivity of 62% and a specificity of 50% (PPV 88%) in identifying local recurrence. The accuracy of MRI was 89% while PET-CT showed an accuracy of 60%. Areas under the ROC curve (AUC) values for MR and PET-CT were 0.833 and 0.562, respectively. In Group B combined 1H-MRSI and DCEMR showed a sensitivity of 94% and a specificity of 100% (PPV 100%) with accuracy of 94%. PET-CT had a sensitivity of 92% and a specificity of 33% (PPV 98%) with accuracy of 91%. The AUCs for MR and PET-CT values were 0.971 and 0.837, respectively. CONCLUSION The diagnostic accuracy of combined 1HMRSI-DCEMR was higher than PET/CT to identify local prostate cancer recurrence, mostly in patients with low biochemical progression after RRP (0.2-2ng/mL).

Effects of long‐term treatment with Serenoa repens (Permixon®) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia

The n‐hexane lipido‐sterol extract of Serenoa repens (LSESr, Permixon®, Pierre Fabre Médicament, Castres, France), a phytotherapeutic agent used in the treatment of benign prostatic hyperplasia (BPH), has a multisite mechanism of action including inhibition of types 1 and 2 5α‐reductase and competitive binding to androgen receptors in prostatic cells. Here, the response of testosterone (T), dihydrotestosterone (DHT), and epidermal growth factor (EGF) in BPH tissue of patients treated with LSESr (320 mg/day for 3 months) is analyzed.

The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH)

Several different stimuli may induce chronic prostatic inflammation, which in turn would lead to tissue damage and continuous wound healing, thus contributing to prostatic enlargement. Patients with chronic inflammation and benign prostatic hyperplasia (BPH) have been shown to have larger prostate volumes, more severe lower urinary tract symptoms (LUTS) and a higher probability of acute urinary retention than their counterparts without inflammation. Chronic inflammation could be a predictor of poor response to BPH medical treatment. Thus, the ability to identify patients with chronic inflammation would be crucial to prevent BPH progression and develop target therapies. Although the histological examination of prostatic tissue remains the only available method to diagnose chronic inflammation, different parameters, such as prostatic calcifications, prostate volume, LUTS severity, storage and prostatitis‐like symptoms, poor response to medical therapies and urinary biomarkers, have been shown to be correlated with chronic inflammation. The identification of patients with BPH and chronic inflammation might be crucial in order to develop target therapies to prevent BPH progression. In this context, clinical, imaging and laboratory parameters might be used alone or in combination to identify patients that harbour chronic prostatic inflammation.