Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors.

The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch technology raise additional issues regarding the biological value of this information. We postulated that a drug-resistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug-resistance profile was correlated with disease-free survival (DFS; patients in adjuvant setting) and time to progression (TTP; metastatic patients) in a 24-months follow-up. Objective response correlation was a secondary end point. Fifty-one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug-resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug-resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.

Prognostic significance of survivin-expressing circulating tumour cells in T1G3 bladder cancer.

OBJECTIVE: To evaluate the prognostic significance of survivin in tumour tissues and that of survivin-expressing circulating tumour cells (CTCs) in T1G3 bladder tumours, as the prognosis of T1G3 bladder cancer is highly variable and unpredictable from clinical and pathological prognostic factors. PATIENTS AND METHODS: The study included 54 patients with T1G3 non-muscle-invasive bladder cancer. Additional inclusion criteria were: tumour size <3 cm, absence of carcinoma in situ and multifocality. The planned follow-up was 24 months. Survivin was evaluated by reverse transcription-polymerase chain reaction in tumour tissues. CTCs were isolated from blood by CELLection Dynabeads (Invitrogen, Carlsbad, CA, USA) coated with the monoclonal antibody towards the human epithelial cell adhesion molecule. Cells were lysed and Dynabeads Oligo(dT) was used to capture poly A + mRNA. cDNA was synthesized and analysed for the expression of CD45, CK8 and survivin. The primary endpoint was disease-free survival (DFS); the favourable group at 24 months was defined as that with no clinical evidence of disease; the unfavourable group was that with evidence of recurrent disease or progressive disease. Tumour survivin expression and presence of CTC were correlated with DFS. Multivariate analysis was used to investigate whether the presence of CTC was an independent indicator of DFS. RESULTS: Survivin was found in half of the tumours; patients with survivin-negative tumours had a longer DFS than those with survivin-positive tumours (chi-square, P = 0.029). CTCs were found in 24/54 patients (44%); 92% of CTC expressed survivin. The difference in DFS between CTC-ve and CTC+ve patients was statistically significant (chi-square, P < 0.001). The presence of CTC was an independent prognostic factor for DFS (P < 0.001). CONCLUSION: The presence of CTC is an independent prognostic factor in patients with T1G3 bladder cancer.

Up-regulation of the inflammatory-reparative phenotype in human prostate carcinoma.

BACKGROUND: Recent studies have underlined the role of tumor cells in the endogenous synthesis of pro-inflammatory molecules. We tested whether malignant progression in prostate cancer was associated with the activation of a phenotype typical of the innate immune system. METHODS: The expression of a set of molecules involved in tissue inflammation and repair was measured by real-time PCR and Western blot analysis in prostate samples in the absence or slight presence of a detectable leukocyte infiltrate. Whole tumor and non-tumor samples were analyzed in addition to laser-capture microdissected tumor and host epithelium. Receptor for advanced glycation end products, purine receptor, inducible enzymes cyclooxygenase-2 and nitric oxide synthase-2, pentraxin-3 and growth-survival factor receptors such as epithelial growth factor and estrogen alpha and beta receptors were all studied. RESULTS: A global survey approach showed an up-regulation in tumor samples of all of the studied genes, with the exception of ERbeta. A laser-capture microdissection approach highlighted over-expression of pro-inflammatory molecules in each tumor sample examined. Nuclear translocation of nuclear factor-kB subunit p65 was observed in tumor tissues. CONCLUSIONS: These data support the evidence that molecules typical of the innate immune system, similar to that of activated leukocytes, are produced by prostate epithelial cells and that their expression is up-regulated in malignant cells. We suggest that the observed pro-inflammatory and repair process activation may represent an important molecular mechanism in the progression of prostate cancer.

Classification of prostatic diseases by means of multivariate analysis on in vivo proton MRSI and DCE-MRI data.

Multivariate analysis has been applied on proton magnetic resonance spectroscopic imaging ((1)H-MRSI) and dynamic contrast enhanced MRI (DCE-MRI) data of patients with different prostatic diseases such as chronic inflammation, fibrosis and adenocarcinoma. Multivariate analysis offers a global view of the entire range of information coming from both the imaging and spectroscopic side of NMR technology, leading to an integrated picture of the system relying upon the entire metabolic and dynamic profile of the studied samples. In this study, we show how this approach, applied to (1)H-MRSI/DCE-MRI results, allows us to differentiate among the various prostatic diseases in a non-invasive way with a 100% accuracy. These findings suggest that multivariate analysis of (1)H-MRSI/DCE-MRI can significantly improve the diagnostic accuracy for these pathological entities. From a more theoretical point of view, the complementation of a single biomarker approach with an integrated picture of the entire metabolic and dynamic profile allows for a more realistic appreciation of pathological entities.

A chemosensitivity test to individualize intravesical treatment for non-muscle-invasive bladder cancer.

OBJECTIVE: To describe the design of a new chemosensitivity assay based on the expression of genes involved in the resistance to standard intravesical regimens, to allow individualization of therapy for high-risk non-muscle-invasive bladder cancer. PATIENTS AND METHODS: To date, 35 patients with high-risk non-muscle-invasive bladder cancer have been enrolled, all candidates for transurethral resection of the bladder (TURB) followed by intravesical treatment. The intravesical regimen was chosen according to the risk profile of each patient. All patients were evaluated by cystoscopy 3 and 6 months after TURB. According to the molecular characterization of each tumour, our team of molecular oncologists determined for each patient a molecular profile of chemosensitivity to BCG, mitomycin c, anthracyclines and gemcitabine. This profile was then correlated to the response to intravesical therapy 6 months after TURB. RESULTS: This chemosensitivity test was able to predict response to treatment in 96% of patients. The assay is easy to perform, inexpensive and quick. CONCLUSION: Our results, although preliminary, are encouraging for the future of an individualized therapeutic approach, with the aim to provide a higher treatment success rate while sparing patients unnecessary toxicity from drugs that are not suited for their tumours.

2D and 3D T2-weighted MR sequences for the assessment of neurovascular bundle changes after nerve-sparing radical retropubic prostatectomy with erectile function correlation.

The aim of this study was to assess the capability of a 3D isotropic MRI T2-weighted sequence (3D T2 ISO) in the depiction of changes of neurovascular bundles (NVBs) after bilateral nerve-sparing radical retropubic prostatectomy (RRP). Furthermore, our aim was also to introduce a new MRI classification score of the NVB alteration patterns using the International Index Erectile Function Five-Item (IIEF-5) score as standard of reference. Fifty-three consecutive patients were postoperatively submitted to two MR examinations, including both 2D TSE T2-weighted (2D T2) and 3D T2 ISO sequences. Image findings were scored using a relative five-point classification and correlated with the postoperative IIEF-5 score. Radiologists attributed 13.2% of patients to class 0, 11.3% to class I, 34% to class II, 24.5% to class III, and 16.9% to class IV. With 3D T2 ISO images, the same radiologists determined 43.3% class 0, 32% class I, 11.4% class II, 7.5% class III, and 5.7% class IV. In all cases, the correlation and regression analysis between the 3D T2 ISO and IIEF-5 score resulted in higher coefficients values. The 3D sequence correlated most closely with patients' grading of erectile function.

Distribution of high chromogranin A serum levels in patients with nonmetastatic and metastatic prostate adenocarcinoma.

OBJECTIVES: We analyzed the incidence of elevated serum levels of chromogranin A (CgA) (as marker of neuroendocrine activity) in nonmetastatic and metastatic prostate cancer populations. MATERIAL AND METHODS: 264 consecutive men with nonmetastatic prostate adenocarcinoma considered for radical prostatectomy (group 1) and 89 consecutive men with metastatic prostate adenocarcinoma (group 2) represented our population. In all 353 cases a blood sample for the determination of serum total PSA and CgA levels was obtained (RIA). Two different cut-off for elevated serum CgA levels were used: >60 and >90 ng/ml. RESULTS: In group 1, 35.0% of cases presented CgA levels >60 ng/ml and 6.4% >90 ng/ml. In group 2, 100% of cases presented CgA levels >60 ng/ml and 69.7% >90 ng/ml. The OR for CgA level >60 and >90 ng/ml significantly increased from nonmetastatic to metastatic cases (p = 0.0001). In group 1 the percentage of cases with CgA >60 ng/ml was 29.6% in Gleason score or=7 (4 + 3) (p = 0.0001). In group 2, the percentage of cases with CgA >90 ng/ml was 51.8% in Gleason score or=7 (4 + 3) (p = 0.0028). CONCLUSIONS: We describe a significant incidence of elevated serum levels of CgA either in nonmetastatic (using 60 ng/ml as cut-off) or in metastatic (using 90 ng/ml as cut-off) prostate adenocarcinoma cases.

p53 gene mutational rate, Gleason score, and BK virus infection in prostate adenocarcinoma: Is there a correlation?

Prostate cancer represents the second leading cause of cancer deaths in Western countries. Viral infections could play a role in prostate carcinogenesis. Human polyomavirus BK (BKV) is a possible candidate because of its transforming properties. In this study, BKV sequences in urine, blood, fresh, and paraffin-embedded prostate cancer samples from 26 patients were searched using Q-PCR analysis. T antigen (TAg) and p53 localization in neoplastic cells were evaluated by immunohistochemical analysis. Also, the presence of mutations in 5-9 exons of p53 gene was analyzed. Results showed that BKV-DNA was found in urine (54%), plasma (31%), and in fresh prostate cancer specimens (85%). The analysis of p53 gene evidenced several mutations in high Gleason patients, according to tumor advanced stage. Immunohistochemical analysis results evidenced the localization of p53 and TAg into cytoplasm, whereas in TAg-negative tumors, p53 was nuclear. This study suggests that BKV acts as cofactor in the pathogenesis of prostate cancer. These observations emphasize previous studies regarding the cellular pathways that may be deregulated by BKV.

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.

Biopsy-derived Gleason artifact and prostate volume: experience using ten samples in larger prostates.

PURPOSE: To verify whether a significant relationship between the risk of Gleason upgrading and the prostate volume remains when the number of biopsies is increased for larger prostate volumes. MATERIALS: A total of 281 biopsy-proven prostate adenocarcinoma cases who underwent radical prostatectomy (RRP) formed the cohort for this study. Change in transrectal ultrasound of the prostate (TRUS) biopsies number based on total gland volume was made simply by increasing the number of biopsies from 6 to 10 when prostate volume was >50 cc. The total number of cancers with Gleason pattern 4 or greater on biopsy and on RRP was tabulated over TRUS volume categories and tests for trend. RESULTS: The proportion of Gleason score (GS) > or =7 at biopsy was 44.5% whereas, at RRP, it was 68.3%. The rate of upgrading from Gleason <7 at biopsy to GS > or =7 at RRP was 46.8%. No significant difference in terms of age, serum PSA, prostate volume and pT stage was found between not upgraded and upgraded cases (p > 0.05). As prostate volume categories increase, the number of cancers upgraded at RRP slightly increases in particular from prostate volume 30-39 to 40-49 cc (where only 6 biopsies were performed). However, either at biopsy or at RRP, the percentage of GS > or =7 tumors does not show a significant trend in changing (p > 0.05). CONCLUSIONS: We verified that the relationship between the risk of Gleason upgrading and prostate volume does not become significant simply by increasing the number of laterally directed biopsies from 6 to 10.

Long-term experience with an anatomical anterograde approach to radical prostatectomy: results in terms of positive margin rate.

PURPOSE: To evaluate the effect of an anterograde approach to radical retropubic prostatectomy (RRP) in terms of positive surgical margins (SM+). METHODS: 323 untreated patients underwent anterograde RRP for clinically localized prostate adenocarcinoma. Spearman coefficients, logistic univariate and multivariate analysis were used. RESULTS: The incidence of SM+ was 14.9% and, in particular, this was 4.5% for apical, 9.0% for lateral, 0.9% for other sites, and 2.8% for multiple SM+. Upon univariate analysis, prostate-specific antigen (PSA; r = 0.2073, p = 0.0002), pathological stage (r = 0.3777, p < 0.0001), and seminal vesicle invasion (r = 0.1453, p = 0.0089) were found to be significantly associated with SM+. Upon multivariate analysis, only PSA (p = 0.0090) and pathological stage (p < 0.0001) were significantly and independently associated with SM+ occurrence. CONCLUSION: In our experience, the anterograde approach to RRP is associated with low SM+ rates.

Neoadjuvant therapy with sorafenib in advanced renal cell carcinoma with vena cava extension submitted to radical nephrectomy.

A 71-year-old man with advanced left renal cell carcinoma (lymph node involvement and vena cava thrombus) was submitted to 6 months of neoadjuvant treatment with sorafenib before open radical nephrectomy. After sorafenib treatment and before surgery a new CT scan confirmed the presence of a 9.0 cm in diameter solid mass in the left kidney but a reduction in thrombus extension, limited to the left renal vein. At histological examination after radical nephrectomy, over 90% of the renal mass was substituted by necrotic tissue.

Comparison of chromogranin A, insulin-like growth factor 1 and prostate-specific antigen serum markers in prostate adenocarcinoma and benign prostatic hyperplasia.

BACKGROUND/AIM: To compare serum chromogranin A (CgA) and insulin-like growth factor 1 (IGF-1) with the classical prostate-specific antigen (PSA) marker in clinically localized prostate adenocarcinomas. MATERIALS AND METHODS: This is a prospective single-center study that included 64 consecutive men with newly diagnosed clinically localized prostate adenocarcinoma and 20 consecutive men with histologically confirmed benign prostatic hyperplasia (BPH). A blood sample for the determination of serum total PSA, CgA and IGF-1 levels (RIA) was obtained from all cases. Analysis of variance was performed to evaluate their variations according to disease and the pathological characteristics of prostate adenocarcinoma. RESULTS: Only serum PSA levels (p < 0.0001) and not IGF-1 (p = 0.5475) or CgA (p = 0.5043) were significantly higher in the prostate cancer (PCa) group as compared to the BPH group. A significant variance between BPH and PCa divided on the basis of pT stage was found for PSA levels (p < 0.0001) but not for CgA (p = 0.0869) and IGF-1 (p = 0.6883) levels. Dividing PCa on the basis of Gleason score, a significant variance was found for CgA (p = 0.0100) and for PSA (p < 0.001), but not for IGF-1 (p = 0.6895) levels. CONCLUSIONS: In our population the quantification of PSA and CgA serum levels and not of IGF-1 provides independent significant information in the diagnosis and aggressiveness of PCa, respectively.

Characterization of circulating blood dendritic cell subsets DC123+ (lymphoid) and DC11C+ (myeloid) in prostate adenocarcinoma patients.

PURPOSE: We verified whether prostate adenocarcinoma produces specific modifications in DC subsets count. METHODS: Twenty-one untreated prostate adenocarcinomas were divided on the basis of clinical stage in localized and metastatic disease. As control we used a population of 18 healthy male subjects. For DCs enumeration, peripheral blood (PB) samples were obtained in all cases. A single-platform flow cytometric assay based on Tru-COUNT was used for the enumeration of the two DCs subsets, myeloid (mDCs) and plasmacytoid (pDCs). RESULTS: We showed a statistically significant reduction in pDCs count in prostate cancer population when compared to healthy controls (P = 0.002). Comparing each clinical stage with healthy controls, significant differences were found between controls and the metastatic group in both pDCs and mDCs (P = 0.005 and P = 0.023 respectively) but not between controls and the localized group (P = 0.055 and P = 0.829 respectively). CONCLUSIONS: We showed that DCs count in PB is significantly affected by prostate adenocarcinoma progression in a metastatic disease.

Quantitative immunohistochemical and in situ hybridization analysis of metalloproteinases in prostate cancer.

The role of matrix metalloproteinases (MMPs) as markers of tumor progression in prostate cancer (CaP) is complex and poorly understood. Using computerized image analysis, the differential expression of interstitial collagenase (MMP-1), gelatinase B (MMP-9), matrilysin-1 (MMP-7) and the membrane-type 1-MMP (MT1-MMP) in the epithelium and stroma of human prostate neoplastic tissues were investigated. Using immunohistochemistry and in situ hybridization techniques, 38 paraffin-embedded prostatic samples were analyzed and CaP was compared with prostate intraepithelial neoplasia (PIN) and its normal adjacent prostate (NAP) counterpart. The association of MMP protein and mRNA expression with Gleason histological tumor grade and TNM clinical stage was also determined. In most prostatectomy specimens examined, detectable amounts of MMP-1, MT1-MMP, MMP-7 and MMP-9 proteins and MT1-MMP and MMP-9 mRNA were found in the epithelial and stromal components of CaP, PIN and NAP. MMP expression was significantly stronger in the epithelium than in the stroma (p < 0.01). In the epithelium of normal and preneoplastic prostate tissue, MMP-1, MMP-9 and MT1-MMP were preferentially expressed in secretory luminal cells; conversely, MMP-7 was concentrated in basal cells. Epithelial and stromal expressions of MMPs differed in normal, preneoplastic and CaP tissues. Whereas MMP-1 was overexpressed in NAP epithelial glands and progressively decreased from PIN to CaP, MMP-7, MMP-9 and MT1-MMP were more strongly expressed in CaP than in PIN and NAP tissue. The MMPs investigated reached their highest levels in prostate tumors with high Gleason scores. The differential MMP expression in epithelial and stromal prostate tissue supports the previous hypothesis that MMPs may be autocrine and paracrine mediators of the stroma-epithelial interaction, an event that plays a critical role in regulating normal and abnormal prostate growth. MMP gene regulation changes during the early stage of prostate cancer. Differential expression of MMP components in CaP may reflect the malignant phenotype and more aggressive tumor behavior.

Can p503s, p504s and p510s gene expression in peripheral-blood be useful as a marker of prostatic cancer?

BACKGROUND: The aim of the study was to investigate whether p503S, p504S and p510S gene expression in peripheral-blood be useful as a diagnostic or prognostic marker of prostatic cancer. METHODS: Circulating cells were identified by reverse transcription-polymerase chain reaction (RT-PCR) to detect p503S, p504S and p510S mRNA in peripheral blood (PB) from 11 patients with treated prostatic carcinoma (CaP), 11 with newly-diagnosed untreated CaP and 20 with benign prostatic hyperplasia (BPH) (controls). RESULTS: RT-PCR amplified P503S in 7 of 11 untreated and 2 of 11 treated patients with CaP and 5 of 20 with BPH; p504S in 7 of 11 untreated and in 9 of 11 treated patients with CaP and 11 of 20 with BPH; whereas it amplified p510S in all subjects with CaP and in 15 of 20 with BPH. CONCLUSION: These findings suggest that the investigated genes are poorly specific and probably of little use as diagnostic or prognostic prostatic markers in peripheral blood for monitoring disease progression and recurrence.

Is DD3 a new prostate-specific gene?

The search for new and more specific molecular markers of prostatic cancers has led, in recent years, to the identification of the DD3 gene. Using reverse transcription (RT)-PCR, we investigated DD3 gene expression in human cell lines, in blood samples from healthy men and women donors and in various neoplastic and non-neoplastic tissues from the prostate and other organs. Whereas RT-PCR analysis using primers that amplified the region spanning exons 1 and 3 yielded DD3 gene expression in all samples examined, a primer downstream to exon 4 detected the expected size DD3 band only in benign and malignant prostatic tissues. These findings indicate that the only prostate specific region of DD3 is exon 4.

Insulin-like growth factor (IGF)-I, IGF-II and IGF type I receptor (IGFR-I) expression in prostatic cancer.

Despite evidence implicating the insulin-like growth factor (IGF) system in the pathogenesis of prostate cancer, its precise role remains unclear. In this study we investigated the differential expression of IGF-I, IGF-II and their type I receptor (IGFR-I) in the epithelium and stroma of prostate neoplastic tissues. Using immunohistochemistry and in situ hybridization techniques, we analyzed 43 paraffin-embedded prostatic samples and compared prostatic cancer (Pca) with prostatic intraepithelial neoplasia (PIN) and its normal adjacent prostate (NAP) counterpart. We then determined a possible correlation of the immunohistochemical and in situ findings with two known prognostic clinical-pathological indices: Gleason score histological tumor grade and TNM clinical stage. In 22 of the 43 frozen prostatectomy specimens, IGF-I, IGF-II and IGFR-I mRNA expression were also evaluated by semiquantitative RT-PCR. Non neoplastic and neoplastic tissues examined contained detectable amounts of epithelial and stromal IGF-I, IGF-II and IGFR-I protein and mRNA; all levels increased significantly from normal tissue to PIN to Pca. In all three areas examined, IGFR-I expression was invariably higher in epithelium than in stroma, whereas expression of IGF ligands differed. In normal prostatic tissue, IGF-I and IGF-II expression was higher in stroma than in epithelium. Conversely, in Pca tissue, both factors were more strongly expressed in epithelial malignant cells. PIN areas showed IGF-I lowest, and IGF-II and IGFR-I levels highest in the epithelium. IGF-II protein and mRNA reached their highest levels in prostate tumors with high Gleason scores. These findings indicate that the IGF system changes as prostate tissue progresses from a normal to a malignant state. Differential expression of certain IGF system components in Pca may be associated with the malignant phenotype and more aggressive tumor behavior. Hence IGFs could serve to predict the outcome of prostatic cancer.

Prostate cancer gene 3 and multiparametric magnetic resonance can reduce unnecessary biopsies: decision curve analysis to evaluate predictive models.

OBJECTIVE: To overcome the well-known prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. METHODS: A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasound-guided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. RESULTS: Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. CONCLUSION: mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies.

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.