Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.

OBJECTIVE: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). RESULTS: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%]). CONCLUSIONS: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.

Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study.

BACKGROUND: Whether multiparametric MRI improves the detection of clinically significant prostate cancer and avoids the need for systematic biopsy in biopsy-naive patients remains controversial. We aimed to investigate whether using this approach before biopsy would improve detection of clinically significant prostate cancer in biopsy-naive patients. METHODS: In this prospective, multicentre, paired diagnostic study, done at 16 centres in France, we enrolled patients aged 18-75 years with prostate-specific antigen concentrations of 20 ng/mL or less, and with stage T2c or lower prostate cancer. Eligible patients had been referred for prostate multiparametric MRI before a first set of prostate biopsies, with a planned interval of less than 3 months between MRI and biopsies. An operator masked to multiparametric MRI results did a systematic biopsy by obtaining 12 systematic cores and up to two cores targeting hypoechoic lesions. In the same patient, another operator targeted up to two lesions seen on MRI with a Likert score of 3 or higher (three cores per lesion) using targeted biopsy based on multiparametric MRI findings. Patients with negative multiparametric MRI (Likert score ≤2) had systematic biopsy only. The primary outcome was the detection of clinically significant prostate cancer of International Society of Urological Pathology grade group 2 or higher (csPCa-A), analysed in all patients who received both systematic and targeted biopsies and whose results from both were available for pathological central review, including patients who had protocol deviations. This study is registered with ClinicalTrials.gov, number NCT02485379, and is closed to new participants. FINDINGS: Between July 15, 2015, and Aug 11, 2016, we enrolled 275 patients. 24 (9%) were excluded from the analysis. 53 (21%) of 251 analysed patients had negative (Likert ≤2) multiparametric MRI. csPCa-A was detected in 94 (37%) of 251 patients. 13 (14%) of these 94 patients were diagnosed by systematic biopsy only, 19 (20%) by targeted biopsy only, and 62 (66%) by both techniques. Detection of csPCa-A by systematic biopsy (29·9%, 95% CI 24·3-36·0) and targeted biopsy (32·3%, 26·5-38·4) did not differ significantly (p=0·38). csPCa-A would have been missed in 5·2% (95% CI 2·8-8·7) of patients had systematic biopsy not been done, and in 7·6% (4·6-11·6) of patients had targeted biopsy not been done. Four grade 3 post-biopsy adverse events were reported (3 cases of prostatitis, and 1 case of urinary retention with haematuria). INTERPRETATION: There was no difference between systematic biopsy and targeted biopsy in the detection of ISUP grade group 2 or higher prostate cancer; however, this detection was improved by combining both techniques and both techniques showed substantial added value. Thus, obtaining a multiparametric MRI before biopsy in biopsy-naive patients can improve the detection of clinically significant prostate cancer but does not seem to avoid the need for systematic biopsy. FUNDING: French National Cancer Institute.

Characterization of Prostate Cancer with Gleason Score of at Least 7 by Using Quantitative Multiparametric MR Imaging: Validation of a Computer-aided Diagnosis System in Patients Referred for Prostate Biopsy.

Purpose To determine the performance of a computer-aided diagnosis (CAD) system trained at characterizing cancers in the peripheral zone (PZ) with a Gleason score of at least 7 in patients referred for multiparametric magnetic resonance (MR) imaging before prostate biopsy. Materials and Methods Two institutional review board-approved prospective databases of patients who underwent multiparametric MR imaging before prostatectomy (database 1) or systematic and targeted biopsy (database 2) were retrospectively used. All patients gave informed consent for inclusion in the databases. A CAD combining the 10th percentile of the apparent diffusion coefficient and the time to peak of enhancement was trained to detect cancers in the PZ with a Gleason score of at least 7 in 106 patients from database 1. The CAD was tested in 129 different patients from database 2. All targeted lesions were prospectively scored at biopsy by using a five-level Likert score. The CAD scores were retrospectively calculated. Biopsy results were used as the reference standard. Areas under the receiver operating characteristic curves (AUCs) were computed for CAD and Likert scores by using binormal smoothing for per-lesion and per-lobe analyses, and a density function for per-patient analysis. Results The CAD outperformed the Likert score in the overall population and all subgroups, except in the transition zone. The difference was statistically significant for the overall population (AUC, 0.95 [95% confidence interval {CI}: 0.90, 0.98] vs 0.88 [95% CI: 0.68, 0.96]; P = .02) at per-patient analysis, and for less-experienced radiologists (<1 year) at per-lesion (AUC, 0.90 [95% CI: 0.81, 0.95] vs 0.83 [95% CI: 0.73, 0.90]; P = .04) and per-lobe (AUC, 0.92 [95% CI: 0.80, 0.96] vs 0.84 [95% CI: 0.72, 0.91]; P = .04) analysis. Conclusion The CAD outperformed the Likert score prospectively assigned at biopsy in characterizing cancers with a Gleason score of at least 7. © RSNA, 2018 Online supplemental material is available for this article.

Can pre- and postoperative magnetic resonance imaging predict recurrence-free survival after whole-gland high-intensity focused ablation for prostate cancer?

OBJECTIVES: Our aim was to assess whether magnetic resonance imaging (MRI) features predict recurrence-free survival (RFS) after prostate cancer high-intensity focused ultrasound (HIFU) ablation. METHODS: We retrospectively selected 81 patients who underwent (i) whole-gland HIFU ablation between 2007 and 2011 as first-line therapy or salvage treatment after radiotherapy or brachytherapy, and (ii) pre- and postoperative MRI. On preoperative imaging, two senior (R1, R2) and one junior (R3) readers assessed the number of sectors invaded by the lesion with the highest Likert score (dominant lesion) using a 27-sector diagram. On postoperative imaging, readers assessed destruction of the dominant lesion using a three-level score. Multivariate analysis included the number of sectors invaded by the dominant lesion, its Likert and destruction scores, the pre-HIFU prostate-specific antigen (PSA) level, Gleason score, and the clinical setting (primary/salvage). RESULTS: The most significant predictor was the number of prostate sectors invaded by the dominant lesion for R2 and R3 (p≤0.001) and the destruction score of the dominant lesion for R1 (p = 0.011). The pre-HIFU PSA level was an independent predictor for R2 (p = 0.014), but with only marginal significance for R1 (p = 0.059) and R3 (p = 0.053). CONCLUSION: The dominant lesion's size and destruction assessed by MRI provide independent prognostic information compared with usual predictors. KEY POINTS: • The size of the MR-dominant lesion significantly influences post-HIFU recurrence-free survival. • The destruction score of the MR-dominant lesion predicts post-HIFU recurrence-free survival. • Patients with a completely devascularized MR-dominant lesion show better recurrence-free survival • Pre- and post-HIFU MRI provide prognostic information independent of usual predictors.

Stiffness of benign and malignant prostate tissue measured by shear-wave elastography: a preliminary study.

OBJECTIVES: To measure benign and malignant prostate tissue stiffness using shear-wave elastography (SWE). METHODS: Thirty consecutive patients underwent transrectal SWE in the axial and sagittal planes before prostatectomy. After reviewing prostatectomy specimens, two radiologists measured stiffness in regions corresponding to cancers, lateral and median benign peripheral zone (PZ) and benign transition zone (TZ). RESULTS: Cancers were stiffer than benign PZ and TZ. All tissue classes were stiffer on sagittal than on axial imaging, in TZ than in PZ, and in median PZ than in lateral PZ. At multivariate analysis, the nature of tissue (benign or malignant; P < 0.00001), the imaging plane (axial or sagittal; P < 0.00001) and the location within the prostate (TZ, median PZ or lateral PZ; P = 0.0065) significantly and independently influenced tissue stiffness. On axial images, the thresholds maximising the Youden index in TZ, lateral PZ and median PZ were respectively 62 kPa, 33 kPa and 49 kPa. On sagittal images, the thresholds were 76 kPa, 50 kPa and 72 kPa, respectively. CONCLUSIONS: SWE can distinguish prostate malignant and benign tissues. Tissue stiffness is influenced by the imaging plane and the location within the gland. KEY POINTS: • Prostate cancers were stiffer than the benign peripheral zone • All tissue classes were stiffer on sagittal than on axial imaging • All tissue classes were stiffer in the transition zone than in the peripheral zone • All tissue classes were stiffer in the median than in the lateral peripheral zone • Taking into account imaging plane and zonal anatomy can improve cancer detection.

Quantitative Analysis of Prostate Multiparametric MR Images for Detection of Aggressive Prostate Cancer in the Peripheral Zone: A Multiple Imager Study.

Purpose To assess the intermanufacturer variability of quantitative models in discriminating cancers with a Gleason score of at least 7 among peripheral zone (PZ) lesions seen at 3-T multiparametric magnetic resonance (MR) imaging. Materials and Methods An institutional review board-approved prospective database of 257 patients who gave written consent and underwent T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced imaging before prostatectomy was retrospectively reviewed. It contained outlined lesions found to be suspicious for malignancy by two independent radiologists and classified as malignant or benign after correlation with prostatectomy whole-mount specimens. One hundred six patients who underwent imaging with 3-T MR systems from two manufacturers were selected (data set A, n = 72; data set B, n = 34). Eleven parameters were calculated in PZ lesions: normalized T2-weighted signal intensity, skewness and kurtosis of T2-weighted signal intensity, T2 value, wash-in rate, washout rate, time to peak (TTP), mean apparent diffusion coefficient (ADC), 10th percentile of the ADC, and skewness and kurtosis of the histogram of the ADC values. Parameters were selected on the basis of their specificity for a sensitivity of 0.95 in diagnosing cancers with a Gleason score of at least 7, and the area under the receiver operating characteristic curve (AUC) for the models was calculated. Results The model of the 10th percentile of the ADC with TTP yielded the highest AUC in both data sets. In data set A, the AUC was 0.90 (95% confidence interval [CI]: 0.85, 0.95) or 0.89 (95% CI: 0.82, 0.94) when it was trained in data set A or B, respectively. In data set B, the AUC was 0.84 (95% CI: 0.74, 0.94) or 0.86 (95% CI: 0.76, 0.95) when it was trained in data set A or B, respectively. No third variable added significantly independent information in any data set. Conclusion The model of the 10th percentile of the ADC with TTP yielded accurate results in discriminating cancers with a Gleason score of at least 7 among PZ lesions at 3 T in data from two manufacturers. (©) RSNA, 2016 Online supplemental material is available for this article.

How accurate is multiparametric MR imaging in evaluation of prostate cancer volume?

PURPOSE: To assess the factors influencing multiparametric (MP) magnetic resonance (MR) imaging accuracy in estimating prostate cancer histologic volume (Vh). MATERIALS AND METHODS: A prospective database of 202 patients who underwent MP MR imaging before radical prostatectomy was retrospectively used. Institutional review board approval and informed consent were obtained. Two independent radiologists delineated areas suspicious for cancer on images (T2-weighted, diffusion-weighted, dynamic contrast material-enhanced [DCE] pulse sequences) and scored their degree of suspicion of malignancy by using a five-level Likert score. One pathologist delineated cancers on whole-mount prostatectomy sections and calculated their volume by using digitized planimetry. Volumes of MR true-positive lesions were measured on T2-weighted images (VT2), on ADC maps (VADC), and on DCE images [VDCE]). VT2, VADC, VDCE and the greatest volume determined on images from any of the individual MR pulse sequences (Vmax) were compared with Vh (Bland-Altman analysis). Factors influencing MP MR imaging accuracy, or A, calculated as A = Vmax/Vh, were evaluated using generalized linear mixed models. RESULTS: For both readers, Vh was significantly underestimated with VT2 (P < .0001, both), VADC (P < .0001, both), and VDCE (P = .02 and P = .003, readers 1 and 2, respectively), but not with Vmax (P = .13 and P = .21, readers 1 and 2, respectively). Mean, 25th percentile, and 75th percentile, respectively, for Vmax accuracy were 0.92, 0.54, and 1.85 for reader 1 and 0.95, 0.57, and 1.77 for reader 2. At generalized linear mixed (multivariate) analysis, tumor Likert score (P < .0001), Gleason score (P = .009), and Vh (P < .0001) significantly influenced Vmax accuracy (both readers). This accuracy was good in tumors with a Gleason score of 7 or higher or a Likert score of 5, with a tendency toward underestimation of Vh; accuracy was poor in small (<0.5 cc) or low-grade (Gleason score ≤6) tumors, with a tendency toward overestimation of Vh. CONCLUSION: Vh can be estimated by using Vmax in aggressive tumors or in tumors with high Likert scores.

Characterization of prostate lesions as benign or malignant at multiparametric MR imaging: comparison of three scoring systems in patients treated with radical prostatectomy.

PURPOSE: To compare the subjective Likert score to the Prostate Imaging Reporting and Data System (PIRADS) and morphology-location-signal intensity (MLS) scores for categorization of prostate lesions as benign or malignant at multiparametric magnetic resonance (MR) imaging. MATERIALS AND METHODS: Two hundred fifteen patients who underwent T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced multiparametric MR imaging of the prostate before radical prostatectomy were included in a prospective database after they signed the institutional review board-approved forms. Senior readers 1 and 2 prospectively noted the location, shape, and signal intensity of lesions on MR images from individual pulse sequences and scored each for likelihood of malignancy by using a Likert scale (range, 1-5). A junior reader (reader 3) retrospectively reviewed the database and did the same analysis. The MLS score (range, 1-13) was computed by using the readers' descriptions of the lesions. Then, the three readers again scored the lesions they described by using the PIRADS score (range, 3-15). MLS and PIRADS scores were compared with the Likert score by using their areas under the receiver operating characteristic curves. RESULTS: Areas under the receiver operating characteristic curves of the Likert, MLS, and PIRADS scores were 0.81, 0.77 (P = .03), and 0.75 (P = .01) for reader 1; 0.88, 0.74 (P < .0001), and 0.76 (P < .0001) for reader 2; and 0.81, 0.78 (P = .23), and 0.75 (P = .01) for reader 3. For diagnosing cancers with Gleason scores greater than or equal to 7, the Likert score was significantly more accurate than the others, except for the MLS score for reader 3. Weighted κ values were 0.470-0.524, 0.405-0.430, and 0.378-0.441 for the Likert, MLS, and PIRADS scores, respectively. CONCLUSION: The Likert score allowed significantly more accurate categorization of prostate lesions on MR images than did the MLS and PIRADS scores.

Prostate focal peripheral zone lesions: characterization at multiparametric MR imaging--influence of a computer-aided diagnosis system.

PURPOSE: To assess the impact of a computer-aided diagnosis (CAD) system in the characterization of focal prostate lesions at multiparametric magnetic resonance (MR) imaging. MATERIALS AND METHODS: Formal institutional review board approval was not required. Thirty consecutive 1.5-T multiparametric MR imaging studies (with T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced imaging) obtained before radical prostatectomy in patients between September 2008 and February 2010 were reviewed. Twelve readers assessed the likelihood of malignancy of 88 predefined peripheral zone lesions by using a five-level (level, 0-4) subjective score (SS) in reading session 1. This was repeated 5 weeks later in reading session 2. The CAD results were then disclosed, and in reading session 3, the readers could amend the scores assigned during reading session 2. Diagnostic accuracy was assessed by using a receiver operating characteristic (ROC) regression model and was quantified with the area under the ROC curve (AUC). RESULTS: Mean AUCs were significantly lower for less experienced (<1 year) readers (P < .02 for all sessions). Seven readers improved their performance between reading sessions 1 and 2, and 12 readers improved their performance between sessions 2 and 3. The mean AUCs for reading session 1 (83.0%; 95% confidence interval [CI]: 77.9%, 88.0%) and reading session 2 (84.1%; 95% CI: 78.1%, 88.7%) were not significantly different (P = .76). Although the mean AUC for reading session 3 (87.2%; 95% CI: 81.0%, 92.0%) was higher than that for session 2, the difference was not significant (P = .08). For an SS positivity threshold of 3, the specificity of reading session 2 (79.0%; 95% CI: 71.1%, 86.4%) was not significantly different from that of session 1 (78.7%; 95% CI: 70.5%, 86.8%) but was significantly lower than that of session 3 (86.2%; 95% CI: 77.1%, 93.1%; P < .03). The sensitivity of reading session 2 (68.4%; 95% CI: 57.5%, 77.7%) was significantly higher than that of session 1 (64.0%; 95% CI: 52.9%, 73.9%; P = .003) but was not significantly different from that of session 3 (71.4%; 95% CI: 58.3%, 82.7%). CONCLUSION: A CAD system may improve the characterization of prostate lesions at multiparametric MR imaging by increasing reading specificity.

Performance of a Region of Interest-based Algorithm in Diagnosing International Society of Urological Pathology Grade Group ≥2 Prostate Cancer on the MRI-FIRST Database-CAD-FIRST Study.

BACKGROUND AND OBJECTIVE: Prostate multiparametric magnetic resonance imaging (MRI) shows high sensitivity for International Society of Urological Pathology grade group (GG) ≥2 cancers. Many artificial intelligence algorithms have shown promising results in diagnosing clinically significant prostate cancer on MRI. To assess a region-of-interest-based machine-learning algorithm aimed at characterising GG ≥2 prostate cancer on multiparametric MRI. METHODS: The lesions targeted at biopsy in the MRI-FIRST dataset were retrospectively delineated and assessed using a previously developed algorithm. The Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) score assigned prospectively before biopsy and the algorithm score calculated retrospectively in the regions of interest were compared for diagnosing GG ≥2 cancer, using the areas under the curve (AUCs), and sensitivities and specificities calculated with predefined thresholds (PIRADSv2 scores ≥3 and ≥4; algorithm scores yielding 90% sensitivity in the training database). Ten predefined biopsy strategies were assessed retrospectively. KEY FINDINGS AND LIMITATIONS: After excluding 19 patients, we analysed 232 patients imaged on 16 different scanners; 85 had GG ≥2 cancer at biopsy. At patient level, AUCs of the algorithm and PI-RADSv2 were 77% (95% confidence interval [CI]: 70-82) and 80% (CI: 74-85; p = 0.36), respectively. The algorithm's sensitivity and specificity were 86% (CI: 76-93) and 65% (CI: 54-73), respectively. PI-RADSv2 sensitivities and specificities were 95% (CI: 89-100) and 38% (CI: 26-47), and 89% (CI: 79-96) and 47% (CI: 35-57) for thresholds of ≥3 and ≥4, respectively. Using the PI-RADSv2 score to trigger a biopsy would have avoided 26-34% of biopsies while missing 5-11% of GG ≥2 cancers. Combining prostate-specific antigen density, the PI-RADSv2 and algorithm's scores would have avoided 44-47% of biopsies while missing 6-9% of GG ≥2 cancers. Limitations include the retrospective nature of the study and a lack of PI-RADS version 2.1 assessment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The algorithm provided robust results in the multicentre multiscanner MRI-FIRST database and could help select patients for biopsy. PATIENT SUMMARY: An artificial intelligence-based algorithm aimed at diagnosing aggressive cancers on prostate magnetic resonance imaging showed results similar to expert human assessment in a prospectively acquired multicentre test database.

Prostate cancer diagnosis: multiparametric MR-targeted biopsy with cognitive and transrectal US-MR fusion guidance versus systematic biopsy--prospective multicenter study.

PURPOSE: To compare biopsy performance of two approaches for multiparametric magnetic resonance (MR)-targeted biopsy (TB) with that of extended systematic biopsy (SB) in prostate cancer (PCa) detection. MATERIALS AND METHODS: This institutional review board-approved multicenter prospective study (May 2009 to January 2011) included 95 patients with informed consent who were suspected of having PCa, with a suspicious abnormality (target) at prebiopsy MR. Patients underwent 12-core SB and four-core TB with transrectal ultrasonographic (US) guidance, with two cores aimed visually (cognitive TB [TB-COG]) and two cores aimed using transrectal US-MR fusion software (fusion-guided TB [TB-FUS]). SB and TB positivity for cancer and sampling quality (mean longest core cancer length, Gleason score) were compared. Clinically significant PCa was any 3 mm or greater core cancer length or any greater than 3 Gleason pattern for SB or any cancer length for TB. Statistical analysis included t test, paired χ(2) test, and κ statistic. Primary end point (core cancer length) was calculated (paired t test). RESULTS: Among 95 patients (median age, 65 years; mean prostate-specific antigen level, 10.05 ng/mL [10.05 µg/L]), positivity rate for PCa was 59% (n = 56) for SB and 69% (n = 66) for TB (P = .033); rate for clinically significant PCa was 52% (n = 49) for SB and 67% (n = 64) for TB (P = .0011). Cancer was diagnosed through TB in 16 patients (17%) with negative SB results. Mean longest core cancer lengths were 4.6 mm for SB and 7.3 mm for TB (P < .0001). In 12 of 51 (24%) MR imaging targets with positive SB and TB results, TB led to Gleason score upgrading. In 79 MR imaging targets, positivity for cancer was 47% (n = 37) with TB-COG and 53% (n = 42) with TB-FUS (P = .16). Neither technique was superior for Gleason score assessment. CONCLUSION: Prebiopsy MR imaging combined with transrectal US-guided TB increases biopsy performance in detecting PCa, especially clinically significant PCa. No significant difference was observed between TB-FUS and TB-COG for TB guidance.

Influence of imaging and histological factors on prostate cancer detection and localisation on multiparametric MRI: a prospective study.

OBJECTIVES: To assess factors influencing prostate cancer detection on multiparametric (T2-weighted, diffusion-weighted, and dynamic contrast-enhanced) MRI. METHODS: One hundred and seventy-five patients who underwent radical prostatectomy were included. Pre-operative MRI performed at 1.5 T (n = 71) or 3 T (n = 104), with (n = 58) or without (n = 117) an endorectal coil were independently interpreted by two radiologists. A five-point subjective suspicion score (SSS) was assigned to all focal abnormalities (FAs). MR findings were then compared with whole-mount sections. RESULTS: Readers identified 192-214/362 cancers, with 130-155 false positives. Detection rates for tumours of <0.5 cc (cm(3)), 0.5-2 cc and >2 cc were 33-45/155 (21-29 %), 15-19/35 (43-54 %) and 8-9/12 (67-75 %) for Gleason ≤6, 17/27 (63 %), 42-45/51 (82-88 %) and 34/35 (97 %) for Gleason 7 and 4/5 (80 %), 13/14 (93 %) and 28/28 (100 %) for Gleason ≥8 cancers respectively. At multivariate analysis, detection rates were influenced by tumour Gleason score, histological volume, histological architecture and location (P < 0.0001), but neither by field strength nor coils used for imaging. The SSS was a significant predictor of both malignancy of FAs (P < 0.005) and aggressiveness of tumours (P < 0.00001). CONCLUSIONS: Detection rates were significantly influenced by tumour characteristics, but neither by field strength nor coils used for imaging. The SSS significantly stratified the risk of malignancy of FAs and aggressiveness of detected tumours. KEY POINTS: • Prostate cancer volume, Gleason score, architecture and location are MRI predictors of detection. • Field strength and coils used do not influence the tumour detection rate. • Multiparametric MRI is accurate for detecting aggressive tumours. • A subjective suspicion score can stratify the risk of malignancy and tumour aggressiveness.

Increased expression of putative cancer stem cell markers in primary prostate cancer is associated with progression of bone metastases.

BACKGROUND: A number of putative stem cell markers have been associated with aggressiveness of prostate cancer, including alpha 2 and alpha 6 integrin and c-met. The study aimed to test the hypothesis that the development of bone metastasis correlates with the proportion of prostate cancer stem cell-like cells present in the primary tumor. METHODS: Prostate tissue samples were obtained from patients with high-risk prostatic adenocarcinoma. Prostate cancer tumor tissue samples underwent immunohistochemical staining for alpha 2 and alpha 6 integrin and c-met; positive and negative controls were included. Samples were scored as positive if >5% of cells within the sample stained positively. Survival and bone metastasis-free survival curves on the patient cohort were estimated by the actuarial method of Kaplan-Meier. RESULTS: A total of 62 patients were included in the study. Bone metastases progression rate was 46% at 105 months with a median time of 46 months (95% CI: 1-62.5 months); prostate cancer-specific survival was 33% at 122 months with a median survival time of 69.4 months (95% CI: 63.5-109.4 months). Survival curves show that c-met-, alpha 2, and alpha 6 integrin-positive tumors were positively associated with the occurrence of bone metastasis-free survival. There was a higher level of significance when at least c-met and either alpha 2 or alpha 6 integrin was positive. CONCLUSION: It can be concluded that percentage of stem cell-like prostate cancer cells has a prognostic impact especially on the risk of metastatic bone progression.

Is it possible to model the risk of malignancy of focal abnormalities found at prostate multiparametric MRI?

OBJECTIVE: To evaluate whether focal abnormalities (FAs) depicted by prostate MRI could be characterised using simple semiological features. METHODS: 134 patients who underwent T2-weighted, diffusion-weighted and dynamic contrast-enhanced MRI at 1.5 T before prostate biopsy were prospectively included. FAs visible at MRI were characterised by their shape, the degree of signal abnormality (0 = normal to 3 = markedly abnormal) on individual MR sequences, and a subjective score (SS(1) = probably benign to SS(3) = probably malignant). FAs were then biopsied under US guidance. RESULTS: 56/233 FAs were positive at biopsy. The subjective score significantly predicted biopsy results (P < 0.01). As compared to SS(1) FAs, the odds ratios (OR) of malignancy of SS(2) and SS(3) FAs were 9.9 (1.8-55.9) and 163.8 (11.5-2331). Unlike FAs' shape, a simple combination of MR signal abnormalities (into "low-risk", "intermediate" and "high-risk" groups) significantly predicted biopsy results (P < 0.008). As compared to "low risk" FAs, the OR of malignancy of "intermediate" and "high-risk" FAs were 4.5 (1.1-18.4) and 52.7 (6.8-407) in the overall population and 5.4 (1.1-27.2) and 118.2 (6.1-2301) in PZ. CONCLUSIONS: A simple combination of signal abnormalities of individual MR sequences can significantly stratify the risk of malignancy of FAs, holding promise of a more standardised interpretation of MRI by readers with varying experience. KEY POINTS: • Using multiparameter(mp)-MRI, experienced uroradiologists can stratify the malignancy risk of prostatic lesions • The shape of prostatic focal abnormalities in the peripheral zone does not help predicting malignancy. • A simple combination of findings at mp-MRI can help less-experienced radiologists.

Prostate cancer ablation with transrectal high-intensity focused ultrasound: assessment of tissue destruction with contrast-enhanced US.

PURPOSE: To assess contrast material-enhanced ultrasonographic (US) findings seen after high-intensity focused ultrasound (HIFU) ablation of prostate cancer and correlate the US findings with post-HIFU biopsy findings. MATERIALS AND METHODS: The study was ethics committee approved. Written informed consent was obtained from all patients. Twenty-eight patients referred for HIFU prostate cancer ablation underwent contrast-enhanced prostate US before treatment, gadolinium-enhanced magnetic resonance (MR) imaging and repeat contrast-enhanced US 1-3 days after treatment, and contrast-enhanced US-guided biopsy 30-45 days after treatment. The contrast-enhanced US enhancement patterns of the biopsy sites--assigned a score of S0 for no enhancement, S1 for mild and/or patchy enhancement, or S2 for marked enhancement--were compared with corresponding biopsy findings, which were assigned a score of B0 for necrosis and/or fibrosis without viable prostate gland tissue, B1 for vascularized tissue without viable gland tissue, or B2 for viable gland tissue (benign or malignant). Then, six additional patients underwent contrast-enhanced prostate US 15-30 minutes and 1 day after HIFU ablation, and the results of these two US examinations were compared. RESULTS: Contrast-enhanced US performed on days 1-3 and days 30-45 after HIFU ablation depicted a large devascularized zone with peripheral enhancing areas that were localized anteriorly in all 28 patients, posteriorly in nine, laterally in five, and at the apex in 20 patients. MR findings were concordant. At biopsy, viable gland tissue was found at nine (6.2%) of 146 S0 sites, 10 (34%) of 29 S1 sites, and 44 (60%) of 73 S2 sites. The odds ratios for finding viable tissue (score B1 or B2) at S1 and S2 sites as opposed to S0 sites were 21 (95% confidence interval [CI]: 6, 71) and 73 (95% CI: 22, 243), respectively (P < .0001). Contrast-enhanced US performed 15-30 minutes and 1 day after treatment in the six additional patients had similar findings. CONCLUSION: Contrast-enhanced US is a promising tool for distinguishing between ablated (devascularized) and viable (enhancing) tissue immediately after HIFU treatment.

Prognostic Impact of pT3 Subclassification in a Multicentre Cohort of Patients with Urothelial Carcinoma of the Renal Pelvicalyceal System Undergoing Radical Nephroureterectomy: A Propensity Score-weighted Analysis After Central Pathology Review.

BACKGROUND: The current pathological tumour-node-metastasis (pTNM) classification for upper tract urothelial carcinoma (UTUC) does not include any risk stratification of pT3 renal pelvicalyceal tumours. OBJECTIVE: To assess the prognostic impact of pT3 subclassification in a multicentre cohort of patients with UTUC of the renal pelvicalyceal system undergoing radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS: Data from all consecutive patients treated with RNU for pT3 renal pelvicalyceal UTUC at 14 French centres from 1995 to 2013 were reviewed retrospectively. INTERVENTION: A central pathology review (CPR) was used to stratify pT3 patients into those with infiltration of the renal parenchyma on a microscopic level (pT3a) versus those with infiltration of the renal parenchyma visible on gross inspection of the resection specimen and/or invasion of peripelvic fat (pT3b). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Inverse probability weighting (IPW)-adjusted Cox regression analyses were used to compare recurrence-free survival (RFS) and cancer-specific survival (CSS) between pT3a and pT3b patients. RESULTS AND LIMITATIONS: Overall, 202 patients were included and further stratified into pT3a (n = 98; 48.5%) and pT3b (n = 104; 51.5%) subgroups. Median time to follow-up in the weighted population was 68 (interquartile range, 50-95) mo. In IPW-adjusted Cox regression analyses, pT3b versus pT3a substage was associated with a significant adverse effect on RFS (hazard ratio [HR] = 2.02; 95% confidence interval [CI] = [1.36-3.01]; p < 0.001) and CSS (HR = 1.84; 95% CI = [1.20-2.82]; p = 0.005). The study is limited by its retrospective design. CONCLUSIONS: Using IPW-adjusted analyses after the CPR, we observed that RNU patients with pT3b renal pelvicalyceal UTUC had adverse prognosis as compared with those with pT3a disease. As such, this subclassification could help refine the current pTNM system for UTUC. PATIENT SUMMARY: In this report, we looked at the prognostic interest of stratifying patients with pT3 renal pelvicalyceal upper tract urothelial carcinoma based on the extent of local invasion. We found that those with extensive infiltration (pT3b) had adverse prognosis as compared with those with limited infiltration (pT3a). This information could be provided on pathology reports to further guide clinical decision making.

Clonal expansion of mutated mitochondrial DNA is associated with tumor formation and complex I deficiency in the benign renal oncocytoma.

Mutations in mitochondrial DNA (mtDNA) are frequent in cancers but it is not yet clearly established whether they are modifier events involved in cancer progression or whether they are a consequence of tumorigenesis. Here we show a benign tumor type in which mtDNA mutations that lead to complex I (CI) enzyme deficiency are found in all tumors and are the only genetic alteration detected. Actually renal oncocytomas are homogeneous tumors characterized by dense accumulation of mitochondria and we had found that they are deficient in electron transport chain complex I (CI, NADH-ubiquinone oxidoreductase). In this work total sequencing of mtDNA showed that 9/9 tumors harbored point mutations in mtDNA, seven in CI genes, one in complex III, and one in the control region. 7/8 mutations were somatic. All tumors were somatically deficient for CI. The clonal amplification of mutated mtDNA in 8/9 tumors demonstrates that these alterations are selected and therefore favor or trigger growth. No nuclear DNA rearrangement was detected beside mtDNA defects. We hypothesize that functional deficiency of the oxidative phosphorylation CI could create a loop of amplification of mitochondria during cell division, impair substrates oxidation and increase intermediary metabolites availability.

Prostate cancer transrectal HIFU ablation: detection of local recurrences using T2-weighted and dynamic contrast-enhanced MRI.

The objective was to evaluate T2-weighted (T2w) and dynamic contrast-enhanced (DCE) MRI in detecting local cancer recurrences after prostate high-intensity focused ultrasound (HIFU) ablation. Fifty-nine patients with biochemical recurrence after prostate HIFU ablation underwent T2-weighted and DCE MRI before transrectal biopsy. For each patient, biopsies were performed by two operators: operator 1 (blinded to MR results) performed random and colour Doppler-guided biopsies ("routine biopsies"); operator 2 obtained up to three cores per suspicious lesion on MRI ("targeted biopsies"). Seventy-seven suspicious lesions were detected on DCE images (n = 52), T2w images (n = 2) or both (n = 23). Forty patients and 41 MR lesions were positive at biopsy. Of the 36 remaining MR lesions, 20 contained viable benign glands. Targeted biopsy detected more cancers than routine biopsy (36 versus 27 patients, p = 0.0523). The mean percentages of positive cores per patient and of tumour invasion of the cores were significantly higher for targeted biopsies (p < 0.0001). The odds ratios of the probability of finding viable cancer and viable prostate tissue (benign or malignant) at targeted versus routine biopsy were respectively 3.35 (95% CI 3.05-3.64) and 1.38 (95% CI 1.13-1.63). MRI combining T2-weighted and DCE images is a promising method for guiding post-HIFU biopsy towards areas containing recurrent cancer and viable prostate tissue.

Biopsy specimens obtained with small-caliber endoscopes have comparable diagnostic performances than those obtained with conventional endoscopes: a prospective study on 1335 specimens.

BACKGROUND AND STUDY AIMS: Esophagogastroduodenoscopy (EGD) can be routinely performed via a nasal route in adults by using small-caliber endoscopes. The aim of this study was to evaluate the adequacy of biopsy specimens obtained with small forceps for histologic diagnosis. PATIENTS AND METHODS: From January to April 2007, we prospectively compared all biopsy specimens obtained, during conventional EGD (8.8-mm-diameter endoscope), with (CS-EGD) or without sedation (C-EGD), and transnasal or transoral-EGD (4.9-mm-diameter endoscope) without sedation (T-EGD). All biopsy specimens were blindly evaluated by a pathologist. For each specimen, were recorded: site, biopsy size and thickness, type of lesion (focal or diffuse), and in case of focal abnormalities described by the endoscopist, presence of the histologic lesions in the targeted biopsies. RESULTS: One thousand and thirty-five biopsy specimens were obtained from 300 procedures (109 T-EGD, 48 C-EGD, and 143 CS-EGD): 983 biopsy specimens were untargeted (esophagus and cardia in 21%, stomach in 85% and duodenum in 84%) and 352 biopsy specimens were targeted to focal lesions (esophagus and cardia in 79%, stomach in 15%, and duodenum in 16%). The mean size of specimens was 1.8, 2, 2.2 mm diameter, in T-EGD, C-EGD, and CS-EGD groups, respectively (P<0.001). The whole thickness of mucosa was present in 68%, 84%, 71% of the cases among T-EGD, C-EGD, and CS-EGD groups, respectively (P=0.9). There was no significant difference in the rate of definitive histologic diagnosis from targeted or nontargeted biopsies according to the endoscopic procedure. CONCLUSIONS: Biopsy specimens obtained during EGD with small forceps are as effective for diagnosis as those obtained with standard forceps.

Well-differentiated endocrine carcinoma of the renal pelvis: report of a case with sustained objective response to octreotide.

Endocrine tumors of the upper urogenital tract are extremely rare. We report the case of a patient with a primary well-differentiated endocrine carcinoma of the renal pelvis metastatic to the liver, in whom an objective response was obtained under octreotide treatment. A 36-year-old woman without symptoms was admitted for exploration of a solid nodule in the right kidney. A right nephrectomy was performed. The histological examination of the surgical specimen diagnosed a primary well-differentiated endocrine tumor of the renal pelvis. Tumor cells strongly expressed synaptophysin and were focally positive for chromogranin A; they displayed faint reactivity for PSAP. Three months later, multiple liver metastases, proved by biopsy, were diagnosed. After two lines of chemotherapy, octreotide treatment was initiated because of persistent high activity at scintigraphic examination. A marked decrease in tumor volume and in chromogranin A serum levels was obtained. Two years later, there was no further progression. The patient was treated with octreotide. Our report points out the unusual immunophenotypic features which may be encountered in well-differentiated endocrine carcinoma of the upper urogenital tract and the potential interest in somatostatin analogues in the treatment of metastatic cases.