Ljiljana Vlatkovic

Magnetic Resonance Imaging–Transectal Ultrasound Image-fusion Biopsies Accurately Characterize the Index Tumor: Correlation with Step-sectioned Radical Prostatectomy Specimens in 135 Patients

BACKGROUND Prostate biopsies targeted by elastic fusion of magnetic resonance (MR) and three-dimensional (3D) transrectal ultrasound (TRUS) images may allow accurate identification of the index tumor (IT), defined as the lesion with the highest Gleason score or the largest volume or extraprostatic extension. OBJECTIVE To determine the accuracy of MR-TRUS image-fusion biopsy in characterizing ITs, as confirmed by correlation with step-sectioned radical prostatectomy (RP) specimens. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of 135 consecutive patients who sequentially underwent pre-biopsy MR, MR-TRUS image-fusion biopsy, and robotic RP at two centers between January 2010 and September 2013. INTERVENTION Image-guided biopsies of MR-suspected IT lesions were performed with tracking via real-time 3D TRUS. The largest geographically distinct cancer focus (IT lesion) was independently registered on step-sectioned RP specimens. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS A validated schema comprising 27 regions of interest was used to identify the IT center location on MR images and in RP specimens, as well as the location of the midpoint of the biopsy trajectory, and variables were correlated. RESULTS AND LIMITATIONS The concordance between IT location on biopsy and RP specimens was 95% (128/135). The coefficient for correlation between IT volume on MRI and histology was r=0.663 (p<0.001). The maximum cancer core length on biopsy was weakly correlated with RP tumor volume (r=0.466, p<0.001). The concordance of primary Gleason pattern between targeted biopsy and RP specimens was 90% (115/128; κ=0.76). The study limitations include retrospective evaluation of a selected patient population, which limits the generalizability of the results. CONCLUSION Use of MR-TRUS image fusion to guide prostate biopsies reliably identified the location and primary Gleason pattern of the IT lesion in >90% of patients, but showed limited ability to predict cancer volume, as confirmed by step-sectioned RP specimens. PATIENT SUMMARY Biopsies targeted using magnetic resonance images combined with real-time three-dimensional transrectal ultrasound allowed us to reliably identify the spatial location of the most important tumor in prostate cancer and characterize its aggressiveness.

A Randomized Controlled Trial To Assess and Compare the Outcomes of Two-core Prostate Biopsy Guided by Fused Magnetic Resonance and Transrectal Ultrasound Images and Traditional 12-core Systematic Biopsy.

BACKGROUND Prostate biopsy guided by computer-assisted fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) images (MRI group) has not yet been compared with 12-core random biopsy (RB; control group) in a randomized controlled trial (RCT). OBJECTIVE To compare the rate of detection of clinically significant prostate cancer (csPCa) between the two groups. DESIGN, SETTING, AND PARTICIPANTS This RCT included 175 biopsy-naïve patients with suspicion for prostate cancer, randomized to an MRI group (n=86) and a control group (n=89) between September 2011 and June 2013. INTERVENTION In the MRI group, two-core targeted biopsy (TB) guided by computer-assisted fusion of MRI/TRUS images of MRI-suspicious lesions was followed by 12-core RB. In the control group, both two-core TB for abnormal digital rectal examination (DRE) and/or TRUS-suspicious lesions and 12-core RB were performed. In patients with normal MRI or DRE/TRUS, only 12-core RB was performed. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS The detection rates for any cancer and csPCa were compared between the two groups and between TB and RB. RESULTS AND LIMITATIONS Detection rates for any cancer (MRI group 51/86, 59%; control group 48/89, 54%; p=0.4) and csPCa (38/86, 44% vs 44/89, 49%; p=0.5) did not significantly differ between the groups. Detection of csPCa was comparable between two-core MRI/TRUS-TB (33/86, 38%) and 12-core RB in the control group (44/89, 49%; p=0.2). In a subset analysis of patients with normal DRE, csPCa detection was similar between two-core MRI/TRUS-TB (14/66, 21%) and 12-core RB in the control group (15/60, 25%; p=0.7). Among biopsy-proven csPCas in MRI group, 87% (33/38) were detected by MRI/TRUS-TB. The definition of csPCa was only based on biopsy outcomes. CONCLUSION Overall csPCa detection was similar between the MRI and control groups. Two-core MRI/TRUS-TB was comparable to 12-core RB for csPCa detection. PATIENT SUMMARY Our randomized controlled trial revealed a similar rate of prostate cancer detection between targeted biopsy guided by magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) and 12-core random biopsy. The traditional 12-core random biopsy may be replaced by two-core MRI/TRUS targeted biopsy for detection of clinically significant prostate cancer.

Transperineal prostate biopsy detects significant cancer in patients with elevated prostate-specific antigen (PSA) levels and previous negative transrectal biopsies.

Study Type – Diagnostic (exploratory cohort)

Predictive Value of Magnetic Resonance Imaging Determined Tumor Contact Length for Extracapsular Extension of Prostate Cancer

PURPOSE Tumor contact length is defined as the amount of prostate cancer in contact with the prostatic capsule. We evaluated the ability of magnetic resonance imaging determined tumor contact length to predict microscopic extracapsular extension compared to existing predictors of extracapsular extension. MATERIALS AND METHODS We retrospectively analyzed the records of 111 consecutive patients with magnetic resonance imaging/ultrasound fusion targeted, biopsy proven prostate cancer who underwent radical prostatectomy from January 2010 to July 2013. Median patient age was 64 years and median prostate specific antigen was 8.9 ng/ml. Clinical stage was cT1 in 93 cases (84%) and cT2 in 18 (16%). Postoperative pathological analysis confirmed pT2 in 71 patients (64%) and pT3 in 40 (36%). We evaluated 1) in the radical prostatectomy specimen the correlation of microscopic extracapsular extension with pathological cancer volume, pathological tumor contact length and Gleason score, 2) the correlation between microscopic extracapsular extension and magnetic resonance imaging tumor contact length, and 3) the ability of preoperative variables to predict microscopic extracapsular extension. RESULTS Logistic regression analysis revealed that pathological tumor contact length correlated better with microscopic extracapsular extension than the predictive power of pathological cancer volume (0.821 vs 0.685). The Spearman correlation between pathological and magnetic resonance imaging tumor contact length was r = 0.839 (p <0.0001). ROC AUC analysis revealed that magnetic resonance imaging tumor contact length outperformed cancer core involvement on targeted biopsy and the Partin tables to predict microscopic extracapsular extension (0.88 vs 0.70 and 0.63, respectively). At a magnetic resonance imaging tumor contact length threshold of 20 mm the accuracy for diagnosing microscopic extracapsular extension was superior to that of conventional magnetic resonance imaging criteria (82% vs 67%, p = 0.015). We developed a predicted probability plot curve of extracapsular extension according to magnetic resonance imaging tumor contact length. CONCLUSIONS Magnetic resonance imaging determined tumor contact length could be a promising quantitative predictor of microscopic extracapsular extension.

Large scale genomic instability as an additive prognostic marker in early prostate cancer

Background: The clinical outcome for the individual prostate cancer patient is often difficult to predict, due to lack of reliable independent prognostic biomarkers. We tested DNA ploidy as a prognostic factor for clinical outcome in 186 patients treated with radical prostatectomy. Methods: DNA ploidy was measured using an automatic image cytometry system and correlated with preoperative PSA, age at surgery, Mostofi grade, surgical margins and Gleason score. Results: The mean follow up time after operation was 73.3 months (range 2–176 months). Of the 186 prostatectomies, 96 were identified as diploid, 61 as tetraploid and 29 as aneuploid. Twenty-three per cent, 36% and 62% of the diploid, tetraploid and aneuploid cases respectively, suffered from relapse during the observation time. DNA ploidy, Gleason score, Mostofi grading, surgical margins and preoperative PSA were all significant predictors of relapse in a univariate analysis. On multivariate analysis, only Gleason score and DNA ploidy proved to be independently predictors of disease recurrence. Furthermore, among the 68 cases identified with Gleason score 7, DNA ploidy was the only significant predictor of disease recurrence. Conclusion: Our data suggest that DNA ploidy should be included as an important additive prognostic factor for prostate cancer, especially for patients identified with Gleason score 7 tumours.

FAP-α and uPA Show Different Expression Patterns in Premalignant and Malignant Esophageal Lesions

Fibroblast activation protein-α (FAP-α) and urokinase-type plasminogen activator (uPA) are serine proteases involved in cancer invasion and metastasis. The authors examined FAP-α and uPA expression in premalignant and malignant stages of esophageal adenocarcinoma by immunohistochemistry. Additionally, Western blotting was performed on fresh-frozen tissue samples. FAP-α and uPA were detected in metaplastic, dysplastic, and carcinoma cells, as well as in adjacent stroma. Stromal FAP-α expression was associated with depth of tumor invasion, while stromal uPA expression correlated with lymph node metastases in adenocarcinomas. Stromal uPA expression in cells with premalignant changes correlated with histological grading. Immunoblotting showed higher protease expression in carcinoma tissues than in normal esophageal epithelium. These results suggest that FAP-α and uPA expression in metaplastic, dysplastic, and esophageal cancer tissue is associated with neoplastic progression of esophageal lesions.

Impact of a tertiary Gleason pattern 4 or 5 on clinical failure and mortality after radical prostatectomy for clinically localised prostate cancer.

Study Type – Prognosis (case series)

Effect of targeted biopsy guided by elastic image fusion of MRI with 3D-TRUS on diagnosis of anterior prostate cancer

PURPOSE To evaluate the effect of targeted biopsy (TB) with elastic fused magnetic resonance imaging (MRI) and 3-dimensional transrectal ultrasound (3D-TRUS) guidance in the diagnosis of anterior prostate cancer (APCa). MATERIAL AND METHOD A retrospective study was performed on patients who underwent TB with elastic fused MRI/3D-TRUS guidance using a 1.5-T MRI with T2- and diffusion-weighted images. APCa was defined as TB-proven cancer whose MR-imaged center was located anteriorly according to standardized MRI reporting schema. Prostate Imaging Reporting and Data System was used to quantify MRI suspicion. Maximum cancer core length (MCCL), cancer core involvement, primary Gleason grade pattern, and Gleason score (GS) on TB were assessed. A clinically significant cancer on TB was MCCL ≥ 5mm of GS 6 or any cancer with GS ≥ 7. Agreement between TB and radical prostatectomy step sections was assessed for all subjects when possible. RESULTS A total of 211 consecutive subjects were included. APCa was found in 81% (170/211). Median (range) of TB per patient, MCCL, and cancer core involvement were 2 (1-5), 10mm (4-23), and 57% (10%-100%), respectively. According to the level of MRI suspicion, positive rate for any cancer vs. clinically significant cancer was 96% (114/119) vs. 86% (102/119) for highly suspicious, 80% (46/57) vs. 68% (39/57) for likely, and 29% (10/35) vs. 20% (7/35) for equivocal, respectively (P = 0.016 and<0.001). Step-section analysis was possible for 70 patients. Concordance of primary Gleason grade pattern and GS between TB and radical prostatectomy was 90% (κ = 0.7) and 77% (κ = 0.64), respectively. CONCLUSION TB with elastic fused MRI/3D-TRUS guidance significantly enhanced accuracy in diagnosing clinically significant APCa.

Is the clinical malignant phenotype of prostate cancer a result of a highly proliferative immune-evasive B7-H3-expressing cell population?

Objectives:  To assess the expression of the cell surface protein B7‐H3 in prostate cancer, and its association to clinically relevant parameters after radical prostatectomy and to the proliferation marker Ki‐67.

Tumour heterogeneity poses a significant challenge to cancer biomarker research

Background:The high degree of genomic diversity in cancer represents a challenge for identifying objective prognostic markers. We aimed to examine the extent of tumour heterogeneity and its effect on the evaluation of a selected prognostic marker using prostate cancer as a model.Methods:We assessed Gleason Score (GS), DNA ploidy status and phosphatase and tensin homologue (PTEN) expression in radical prostatectomy specimens (RP) from 304 patients followed for a median of 10 years (interquartile range 6–12). GS was assessed for every tumour-containing block and DNA ploidy for a median of four samples for each RP. In a subgroup of 40 patients we assessed DNA ploidy and PTEN status in every tumour-containing block. In 102 patients assigned to active surveillance (AS), GS and DNA ploidy were studied in needle biopsies.Results:Extensive heterogeneity was observed for GS (89% of the patients) and DNA ploidy (40% of the patients) in the cohort, and DNA ploidy (60% of the patients) and PTEN expression (75% of the patients) in the subgroup. DNA ploidy was a significant prognostic marker when heterogeneity was taken into consideration. In the AS cohort we found heterogeneity in GS (24%) and in DNA ploidy (25%) specimens.Conclusions:Multi-sample analysis should be performed to support clinical treatment decisions.