De-escalation strategies in patients with acute coronary syndrome: a step towards precision medicine.

INTRODUCTION: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a cornerstone in the treatment of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Current international guidelines recommend the use of 12 months of DAPT with newer P2Y12 inhibitors (i.e. ticagrelor or prasugrel) as first-line therapy in this setting. However, intense and prolonged DAPT regimens are associated with an increased risk of bleeding, with relevant prognostic implications. Recently, a strategy of de-escalation of P2Y12 inhibitors has been proposed as an alternative to conventional DAPT to mitigate the risk of bleeding while preserving ischemic protection after ACS. AREAS COVERED: In this review, we summarize the available evidence on guided and unguided strategies for P2Y12 inhibitor de-escalation in patients with ACS undergoing PCI. EXPERT OPINION: Among patients with ACS, guided and unguided de-escalation strategies are safe and effective for secondary cardiovascular prevention. Although the implementation of genetic and platelet function tests is of interest for treatment personalization, the routine use of guided de-escalation strategies seems impractical. In this context, unguided de-escalation approaches appear more attractive, convenient, and suitable for contemporary practice.

Use of multiparametric MR with neurovascular bundle evaluation to optimize the oncological and functional management of patients considered for nerve-sparing radical prostatectomy.

INTRODUCTION: To obtain the best results with radical prostatectomy, either from an oncological or a functional point of view, a correct selection of cases and planning of surgery are crucial. Multiparametric magnetic resonance imaging (MRI) promises to make it a successful imaging tool for improving many aspects of prostate cancer management. AIM: The aim of this study is to evaluate whether a modern multiparametric MRI can help either to better select prostate cancer cases for a nerve-sparing radical prostatectomy or to improve the functional evaluation related to neurovascular bundles preservation. MAIN OUTCOME MEASURES: The effect of preoperative MRI on neurovascular bundle management was examined for the frequency and the appropriateness of changes of the surgical plane on the basis of MRI indications. METHODS: In a prospective study, 125 consecutive patients with biopsy proven prostate cancer who were scheduled to undergo bilateral nerve-sparing surgery. All patients included into the study were submitted to a preoperative multiparametric MRI. On the basis of MRI evaluation, patients were divided into two groups. Patients in group A were then submitted to a bilateral nerve-sparing (NS) radical prostatectomy (RP), whereas patients in group B were submitted to unilateral NS or non-NS RP. RESULTS: In group A, the confirmation from the MRI study to perform a bilateral NS procedure was appropriate in 70 of 73 cases (95.9%), whereas in group B, the surgical plan was appropriate in 28 of 32 cases (87.5%). On the contrary, MRI findings suggested a change in the initial surgical plan (group B) for 32 of 105 cases (30.5%). Of these 32 cases in group B, MRI suggested to perform a unilateral NS procedure in 21 of 32 cases (65.6%) and a non-NS procedure in 11 of 32 cases (34.4%). CONCLUSIONS: Multiparametric MRI analysis can significantly improve the standard selection and management of prostate carcinoma cases considered for an NS RP.

Determination of the time for maximal response to neoadjuvant hormone therapy for prostate cancer using magnetic resonance with spectroscopy (MRSI) and dynamic contrast enhancement (DCEMR).

PURPOSE: To determine the time-dependent metabolic and angiogenic changes that occur in prostate cancer (CaP) during neoadjuvant hormone therapy (HT), using a combination of MRSI and DCEMR analysis. MATERIALS AND METHODS: This is a prospective study on a population of non-metastatic CaP submitted to neoadjuvant HT prior to radiation therapy. All cases homogeneously received a 6-month period of neoadjuvant HT using leuprorelin acetate 7.5 mg every 28 days. In all cases, a MRSI/DCEMR study was performed at baseline (pretreatment) and at regular intervals (4, 12, 24 weeks) during HT. Serum PSA was measured at baseline and at the same intervals (4, 12, 24 weeks). All MRI examinations were performed on a commercially available 3 T scanner. RESULTS: There was a significant ( P < 0.01) time-dependent loss of all prostate metabolites during HT. In regions of CaP no significant variation in the absolute value of metabolites was reported at 1-month interval and a higher variation was observed at 24-week compared with 12-week interval. A complete metabolic atrophy was a common feature (30%) at a 24-week interval of HT, but not at short (4-week 0%), and lower at an intermediate interval (12-week 10%). At DCEMR, onset time and time to peak parameters significantly (P < 0.05) increased at 12- and 24-week intervals. CONCLUSIONS: To individualize neoadjuvant HT courses prior to definitive treatment, the combination of MRSI and DCEMR may represent a valid noninvasive method, and the addition to PSA data could be used to better assess the time-dependent efficacy of HT in our patients.

Prostate cancer: 1HMRS-DCEMR at 3T 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).

PCA3 urinary test versus 1H-MRSI and DCEMR in the detection of prostate cancer foci in patients with biochemical alterations.

AIM: To compare the prostate antigen 3 (PCA3) test with (1)H-magnetic resonance spectroscopic imaging ((1)H-MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCEMR) combined examination in the detection of prostate tumor foci in patients with persistently elevated prostate-specific antigen (PSA) levels and prior negative random transrectal ultrasound (TRUS)-guided biopsy. PATIENTS AND METHODS: Forty-three patients with a first random biopsy negative for prostate adenocarcinoma, persistent elevated PSA and negative digital rectal examination were recruited. All the patients were submitted to MRSI examination (MRSI-DCEMR) and were submitted to an attentive prostate massage in order to perform PCA3 assay. Afterwards, 10-core laterally-directed random TRUS-guided prostate biopsy was performed. RESULTS: The overall sensitivity and specificity of a PCA3 score ≥35 for positive biopsy were 76.9% and 66.6%, respectively, with a positive predictive value (PPV) of 80% and a negative predictive value (NPV) of 62.5%; as for MRSI sensitivity and specificity were, respectively, 92.8% and 86.6% with a PPV of 92.8% and a NPV of 86.6%. Receiver operating characteristic (ROC) analysis rates were 0.755 for PCA3 and 0.864 for MRSI. CONCLUSION: Combined MRSI/DCEMR can better improve the cancer detection rate in patients with prior negative TRUS-guided biopsy and altered PSA serum levels than PCA3. Optimization of MRSI will allow more precise diagnosis of local invasion and improved bioptical procedures.

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 >or=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 (1)H-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.

Magnetic resonance spectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced magnetic resonance (DCE-MRI): pattern changes from inflammation to prostate cancer.

PURPOSE: To assess (1)H-magnetic resonance spectroscopic imaging ((1)H-MRSI) and dynamic contrast-enhanced magnetic resonance (DCE-MRI) features in histologically confirmed prostatic chronic inflammation, prostatic intraepithelial neoplasia (PIN), low grade prostate cancer (LGPCa), and high grade prostate cancer (HGPCa). MATERIALS AND METHODS: Ninety-six men were selected, who showed at histology a diagnosis of chronic inflammation (Group B), high grade (HG) PIN (Group C), or prostate cancer (LGPCa = Group D and HGPCa = Group E). RESULTS: ANOVA analysis shows that inflammation (Group B) displays no significantly (p >.05) different choline and citrate levels when compared to HGPIN and LGPCa. CONCLUSION: our results suggest the potential for these MR imaging techniques in the description of inflammatory and proliferative lesions inside the prostate gland.

Use of 3D T2-weighted MR sequences for the assessment of neurovascular bundle changes after nerve-sparing radical retropubic prostatectomy (RRP): a potential diagnostic tool for optimal management of erectile dysfunction after RRP.

INTRODUCTION: Erectile dysfunction (ED) is one of the complications after radical retropubic prostatectomy (RRP), and recovery of erectile function is quantitatively related to the preservation of the neurovascular bundles (NVBs). AIM: The aim of our study was to assess, in patients submitted to a nerve-sparing RRP, the capability of a dedicated 3D isotropic magnetic resonance imaging (MRI) T2-weighted sequence in the depiction of postsurgical changes of NVB formation. METHODS: Fifty-three consecutive patients underwent a bilateral nerve-sparing RRP. Two postoperative magnetic resonance (MR) examinations and International Index of Erectile Function Five-Item (IIEF-5) questionnaire were carried out at 6 and 12 months. Morphological imaging of the postprostatectomy fossa was performed by first acquiring turbo spin echo T2-weighted sequences in the axial and coronal planes and then with 3D T2-weighted isotropic sequence on axial plane. Image findings were scored using a relative 5-point classification (0 = normal; I = mild; II = mild to moderate; III = moderate; IV = severe alterations) and correlated with postoperative IIEF-5 score questionnaire. MAIN OUTCOME MEASURES: The degree of association between the alteration score values obtained by postoperative MR morphologic evaluation for MR sequence and IIEF-5 score. RESULTS: Image interpretation was performed by two radiologists, that scoring MR alterations by the use of axial and multiplanar reconstruction 3D T2 isotropic sequence. The radiologists placed 43.30% of patients in class 0 (23/53 normal or quite normal), 32.00% in class I (17/53 mild), 11.40% in class II (6/53 mild to moderate), 7.50% in class III (4/53 moderate), and 5.70% in class IV (3/53 severe). In all cases, the correlation and regression analyses between the 3D T2 isotropic sequence and IIEF-5 score, resulted in higher coefficient values (rho = 0.45; P = 0.0010). CONCLUSION: The MRI protocol and NVB change classification score proposed in this study would represent an additional tool in the postoperative phase of those patients with ED.

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.

Complete response to the combination therapy with androgen blockade and somatostatin analogue in a patient with advanced prostate cancer: magnetic resonance imaging with 1H-spectroscopy.

A 74-yr-old man with prostatic adenocarcinoma underwent magnetic resonance 1H-spectroscopic imaging (1H-MRSI) of the prostate. Based on the results, he was treated with combination therapy using complete androgen blockade (leuprorelin acetate 3.75 mg every 4 wk plus bicalutamide 50 mg daily) and a somatostatin analogue (lanreotide acetate 60 mg every 4 wk). Serum prostate-specific antigen and chromogranin A levels steadily decreased over a 12-mo follow-up period, at which time the patient is alive without disease progression and with a complete objective and symptomatic response.