Predicting Pathological Tumor Size in Prostate Cancer Based on Multiparametric Prostate Magnetic Resonance Imaging and Preoperative Findings.

PURPOSE: Oncologic efficacy of focal therapies in prostate cancer depends heavily on accurate tumor size estimation. We aim to evaluate the agreement between radiologic tumor size and pathological tumor size, and identify predictors of pathological tumor size. MATERIALS AND METHODS: This single arm study cohort included all consecutive patients with biopsy proven prostate cancer and a corresponding PI-RADS®v2 3 or greater index tumor on multiparametric magnetic resonance imaging who subsequently underwent radical prostatectomy. Radiologic tumor size was defined as maximum tumor diameter on multiparametric magnetic resonance imaging and compared to whole mount histopathology tumor correlates. The difference between radiologic tumor size and pathological tumor size was assessed, and clinical, pathological and radiographic predictors of pathological tumor size were examined. RESULTS: A total of 461 consecutive lesions in 441 men were included for statistical analysis. Mean radiologic tumor size and pathological tumor size was 1.57 and 2.37 cm, respectively (p <0.001). Radiologic tumor size consistently underestimated pathological tumor size regardless of the preoperative covariates, and the degree of underestimation increased with smaller radiologic tumor size and lower PI-RADSv2 scores. Pathological tumor size was significantly larger for biopsy Gleason Grade Group (GG) 5 compared to GG1 (mean change 0.37 cm, p=0.014), PI-RADSv2 5 lesions compared to PI-RADSv2 4 (mean change 0.26, p=0.006) and higher prostate specific antigen density. The correlations between radiologic tumor size vs pathological tumor size according to biopsy GG and radiologic covariates were generally low with correlation coefficients ranging between 0.1 and 0.65. CONCLUSIONS: Multiparametric magnetic resonance imaging frequently underestimates pathological tumor size and the degree of underestimation increases with smaller radiologic tumor size and lower PI-RADSv2 scores. Therefore, a larger ablation margin may be required for smaller tumors and lesions with lower PI-RADSv2 scores. These variables must be considered when estimating treatment margins in focal therapy.

Prostate Microstructure in Prostate Cancer Using 3-T MRI with Diffusion-Relaxation Correlation Spectrum Imaging: Validation with Whole-Mount Digital Histopathology.

Background Microstructural MRI has the potential to improve diagnosis and characterization of prostate cancer (PCa), but validation with histopathology is lacking. Purpose To validate ex vivo diffusion-relaxation correlation spectrum imaging (DR-CSI) in the characterization of microstructural tissue compartments in prostate specimens from men with PCa by using registered whole-mount digital histopathology (WMHP) as the reference standard. Materials and Methods Men with PCa who underwent 3-T MRI and robotic-assisted radical prostatectomy between June 2018 and January 2019 were prospectively studied. After prostatectomy, the fresh whole prostate specimens were imaged in patient-specific three-dimensionally printed molds by using 3-T MRI with DR-CSI and were then sliced to create coregistered WMHP slides. The DR-CSI spectral signal component fractions (fA, fB, fC) were compared with epithelial, stromal, and luminal area fractions (fepithelium, fstroma, flumen) quantified in PCa and benign tissue regions. A linear mixed-effects model assessed the correlations between (fA, fB, fC) and (fepithelium, fstroma, flumen), and the strength of correlations was evaluated by using Spearman correlation coefficients. Differences between PCa and benign tissues in terms of DR-CSI signal components and microscopic tissue compartments were assessed using two-sided t tests. Results Prostate specimens from nine men (mean age, 65 years ± 7 [standard deviation]) were evaluated; 20 regions from 17 PCas, along with 20 benign tissue regions of interest, were analyzed. Three DR-CSI spectral signal components (spectral peaks) were consistently identified. The fA, fB, and fC were correlated with fepithelium, fstroma, and flumen (all P < .001), with Spearman correlation coefficients of 0.74 (95% confidence interval [CI]: 0.62, 0.83), 0.80 (95% CI: 0.66, 0.89), and 0.67 (95% CI: 0.51, 0.81), respectively. PCa exhibited differences compared with benign tissues in terms of increased fA (PCa vs benign, 0.37 ± 0.05 vs 0.27 ± 0.06; P < .001), decreased fC (PCa vs benign, 0.18 ± 0.06 vs 0.31 ± 0.13; P = .01), increased fepithelium (PCa vs benign, 0.44 ± 0.13 vs 0.26 ± 0.16; P < .001), and decreased flumen (PCa vs benign, 0.14 ± 0.08 vs 0.27 ± 0.18; P = .004). Conclusion Diffusion-relaxation correlation spectrum imaging signal components correlate with microscopic tissue compartments in the prostate and differ between cancer and benign tissue. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Lee and Hectors in this issue.

Diagnostic investigations of DKK-1 and PDCD5 expression levels as independent prognostic markers of human chondrosarcoma.

In this study, we investigated the expression levels of Dickkopf-1 (DKK-1) and programmed cell death 5 (PDCD5) by using quantitative real-time PCR and immunohistochemistry in patients with chondrosarcoma. The DKK-1 mRNA levels were significantly higher in chondrosarcoma when compared with the corresponding nontumor tissues (mean ± SD: 4.23 ± 1.54; 1.54 ± 0.87; P = 0.001). PDCD5 mRNA levels were remarkably deceased in tumor tissues when compared with corresponding nontumor tissues (mean ± SD: 1.94 ± 0.73; 5.42 ± 1.73; P = 0.001). The high and moderate DKK-1 expressions were observed for 60% of chondrosarcoma samples in comparison with 27.5% of corresponding nontumor tissues (P  =  0.001). Moreover, low expression of PDCD5 was found in 67.5% of the tumor tissues when compared with the nontumor tissues (32.5%; P = 0.002). The results of this study showed that high DKK-1 expression levels were strongly related to MSTS stage (P = 0.011) and the advancement of histological grade (P < 0.001). Furthermore, the PDCD5 expression levels were correlated with histological grade (P < 0.001), MSTS stage (P = 0.016), and distant metastasis (P = 0.001). Kaplan-Meier survival and log-rank survival showed that patients with high DKK-1 levels and low PDCD5 levels were correlated with shorter overall survival (log-rank test P < 0.001). PDCD5 levels, histological grade, and tumor stage were independent predictors of overall survival. In conclusion, DKK-1 and PDCD5 can be independent predictors of overall survival in patients suffering from chondrosarcoma. © 2016 IUBMB Life, 68(7):597-601, 2016.

Dynamic contrast-enhanced (DCE) MR imaging: the role of qualitative and quantitative parameters for evaluating prostate tumors stratified by Gleason score and PI-RADS v2.

PURPOSE: To investigate the role of qualitative and quantitative DCE-MRI parameters in prostate cancer (PCa) stratified by whole-mount histopathology (WMHP) Gleason score (GS) and PI-RADSv2. METHODS: This retrospective study included 323 PCa tumors in 254 men, who underwent 3T MRI prior to prostatectomy, 7/2009-12/2016. Qualitative DCE curve types included type 1 (progressive), type 2 (plateau) and type 3 (washout). Quantitative DCE-MRI pharmacokinetic (PK) parameters included Ktrans (influx volume transfer coefficient), Kep (efflux reflux rate constant) and iAUC (initial area under the curve). DCE-MRI features of true positive lesions were evaluated for overall, index, transition zone (TZ) and peripheral zone (PZ), based on GS grade (low = 6, high > 6) and PI-RADSv2 score using SPSSv24. RESULTS: There were 57 (17.6%) low-grade and 266 (82.4%) high-grade PCa lesions. PI-RADSv2 3, 4 and 5 included 106, 120 and 97 lesions, respectively. 251 (77.7%) and 72 (22.3%) lesions were located in PZ and TZ, respectively. High-grade lesions had significantly higher proportion of Type 3 curves compared to low-grade lesions in overall (70.3% vs. 54.4%) and TZ (73.5% vs. 43.5%). As PI-RADSv2 increased, the proportion of type 3 curve significantly increased for overall (80.4-51.9%), index (80.4-54.7%) and PZ (78.7-52.1%) lesions. Among PK parameters, Ktrans (0.43 vs 0.32) and iAUC (8.99 vs 6.9) for overall PCa, Ktrans (0.43 vs 0.31) and iAUC (9 vs 6.67) for PZ PCa, and iAUC (8.94 vs 7.42) for index PCa were significantly higher for high-grade versus low-grade lesions. Also, Ktrans (0.51-0.34), Kep (1.75-1.29) and iAUC (9.79-7.6) for overall PCa, Ktrans (0.53-0.32), Kep (1.81-1.26) and iAUC (9.83-7.34) for PZ PCa; and Kep (1.79-1.17) and iAUC (11.3-8.45) for index PCa increased significantly with a higher PI-RADSv2 score. CONCLUSIONS: The results of study show the possible utility of qualitative and quantitative DCE-MRI parameters for assessment of PCa GS and PI-RADSv2 categorization.

The effect of tumor size and location on efficacy and safety of US- and CT- guided percutaneous microwave ablation in renal cell carcinomas.

PURPOSE: To evaluate the effect of size and central location of the tumor on safety and efficacy of percutaneous CEUS- and CT-guided MWA in biopsy-proven renal cell carcinomas (RCCs). MATERIALS AND METHODS: In this IRB-approved retrospective study, 69 biopsy-proven renal tumors in 56 patients, who underwent MWA in our institution from January 2013 to March 2017, were evaluated. Data collection included demographics, tumor characteristics, procedural protocols, and follow-up visits within 6 months post procedure. Primary outcomes were assessed by technical success (TS), local tumor progression (LTP), and complications. The Kaplan-Meier analysis was used for survival rate. RESULTS: Overall technical success was achieved for all 69 lesions (92.8% primary TS, 100% overall). Median nephrometry score was 8 (4-11) and median tumor size was 2.5 cm (0.8-7). Five lesions which required second ablation had significantly higher median tumor size 4 cm (P = 0.039) with the same nephrometry score. Renal function remained stable with no significant change in eGFR before or after ablation. The LTP rate was 5.8%. The most recurrent tumors were clear cell (50%) followed by papillary tumors (25%). The complication rate was 5.8% with minor complications (hematoma and pain) and no major issues. There was no significant association between nephrometry score and technical success, recurrence, or complication rates. Overall and tumor-specific survival rates were 96.7% and 100% at 11.9 months. CONCLUSIONS: Image-guided MWA appears to be a safe and effective treatment regardless of nephrometry score and tumor location with high technical success, low recurrence, and complication rates.

Joint Prostate Cancer Detection and Gleason Score Prediction in mp-MRI via FocalNet.

Multi-parametric MRI (mp-MRI) is considered the best non-invasive imaging modality for diagnosing prostate cancer (PCa). However, mp-MRI for PCa diagnosis is currently limited by the qualitative or semi-quantitative interpretation criteria, leading to inter-reader variability and a suboptimal ability to assess lesion aggressiveness. Convolutional neural networks (CNNs) are a powerful method to automatically learn the discriminative features for various tasks, including cancer detection. We propose a novel multi-class CNN, FocalNet, to jointly detect PCa lesions and predict their aggressiveness using Gleason score (GS). FocalNet characterizes lesion aggressiveness and fully utilizes distinctive knowledge from mp-MRI. We collected a prostate mp-MRI dataset from 417 patients who underwent 3T mp-MRI exams prior to robotic-assisted laparoscopic prostatectomy. FocalNet was trained and evaluated in this large study cohort with fivefold cross validation. In the free-response receiver operating characteristics (FROC) analysis for lesion detection, FocalNet achieved 89.7% and 87.9% sensitivity for index lesions and clinically significant lesions at one false positive per patient, respectively. For the GS classification, evaluated by the receiver operating characteristics (ROC) analysis, FocalNet received the area under the curve of 0.81 and 0.79 for the classifications of clinically significant PCa (GS ≥ 3 + 4) and PCa with GS ≥ 4 + 3, respectively. With the comparison to the prospective performance of radiologists using the current diagnostic guideline, FocalNet demonstrated comparable detection sensitivity for index lesions and clinically significant lesions, only 3.4% and 1.5% lower than highly experienced radiologists without statistical significance.

Characteristics of missed prostate cancer lesions on 3T multiparametric-MRI in 518 patients: based on PI-RADSv2 and using whole-mount histopathology reference.

PURPOSE: To determine the characteristics of missed prostate cancer (PCa) lesions on 3T multiparametric-MRI (mpMRI) based on PI-RADSv2 with whole-mount histopathology (WMHP) correlation. MATERIALS AND METHODS: This IRB-approved, HIPAA-compliant study, included 614 consecutive men with 3T mpMRI prior to prostatectomy at a single tertiary center between 12/2009 and 4/2017. Clinical, mpMRI, and pathologic features were obtained. PI-RADSv2-based MRI detected lesions were matched with previously finalized WMHP by a genitourinary (GU) radiologist and a GU pathologist. Patients with no mpMRI detected PCa lesion, but with at least one lesion ≥ 1 cm on WMHP, were reviewed retrospectively and assigned a PI-RADSv2 score. Tumor characteristics were compared between missed and detected lesions. RESULT: The final cohort included 518 patients with 1085 WMHP lesions. 51.9% (563/1085) of lesions were missed on 3T mpMRI. 71.4% (402/563), 21.7% (122/563), 4.4% (25/563), and 2.5% (14/563) of the missed lesions were Gleason scores (GS) 3 + 3, 3 + 4, 4 + 3, and 8 - 10, respectively. Missed PCa lesions had significantly lower proportion of GS ≥ 7 (p < 0.001) and smaller size for overall (p < 0.001) and index subcohorts (p < 0.001), as compared to detected lesions. 34.5% (194) of overall and 71.2% (79) index missed lesions were larger than 1 cm. In 13.7% (71/518) of patients without MR detected PCa, 149 lesions were detected on WMHP, with 70 (47%) lesions ≥ 1 cm. In retrospective review of these lesions, 42.9% (30), 18.6% (13), 21.5% (15), 10% (7), and 7% (5) were PI-RADSv2 1, 2, 3, 4, and 5, respectively. CONCLUSION: 3T mpMRI has an excellent per patients diagnostic performance for PCa and majority of missed lesions are clinically nonsignificant.

3T multiparametric MR imaging, PIRADSv2-based detection of index prostate cancer lesions in the transition zone and the peripheral zone using whole mount histopathology as reference standard.

PURPOSE: To evaluate 3T mpMRI characteristics of transition zone and peripheral zone index prostate cancer lesions stratified by Gleason Score and PI-RADSv2 with whole mount histopathology correlation. METHODS: An institution review board-approved, HIPAA-compliant single-arm observational study of 425 consecutive men with 3T mpMRI prior to radical prostatectomy from December 2009 to October 2016 was performed. A genitourinary radiologist and a genitourinary pathologist matched all lesions detected on whole mount histopathology with lesions concordant for size and location on 3T mpMRI. Differences in clinical, MRI parameters, and histopathology between transition zone and peripheral zone were determined and analyzed with χ2 and Mann-Whitney U test. AUC was measured. RESULTS: 3T mpMRI detected 248/323 (76.7%) index lesions in peripheral zone and 75/323 (23.2%) in transition zone. Transition zone prostate cancer had higher median prostate-specific antigen (p = 0.001), larger tumor on 3T mpMRI (p = 0.001), lower proportions of PI-RADSv2 category 4 and 5 (p < 0.001), and lower pathological stage (p = 0.055) compared to peripheral zone prostate cancer. No significant differences were detected in prostate-specific antigen density, preoperative biopsy, and pathology Gleason Scores. After adjusting for significant variables from univariate analysis including prostate volume, tumor volume, prostate-specific antigen, PI-RADSv2 category, AUC for predicting clinically significant tumor in transition zone and peripheral zone were 0.80 and 0.72, respectively (p = 0.36). CONCLUSIONS: The diagnostic performance of PI-RADSv2 for clinically significant transition and peripheral zone prostate cancer was similar. However, there was a lower portion of PI-RADSv2 4 and 5 lesions in transition zone compared to peripheral zone.

Head and Neck Cancers in North-East Iran: A 25 year Survey.

INTRODUCTION: Cancers are among the worst noncommunicable diseases around the world. Head and neck cancers are ranked as the fifth most common cancers worldwide. As there are different distributions of risk factors around the world, the incidence of these cancers varies from one place to another. MATERIALS AND METHODS: We conducted a descriptive analytic cross-sectional study, based on census-based records from the private oncology clinic in Mashhad, Iran. Data from 1,075 patients with head and neck cancers were analyzed from 1986 to 2010. We categorized the duration of study into five periods: 1986-1990, 1991-1995, 1996-2000, 2001-2005, and 2006-2010. Head and neck cancers refers to cancers originating from seven sites in the head and neck including the nasal cavity, oral cavity, pharynx, larynx, salivary glands, paranasal sinuses, and thyroid. RESULTS: Data of 1,075 patients were analyzed. 66.2% were male. Mean ± standard deviation (SD) age at the time of diagnosis was 55.37±15.55 years. The most frequent type of head and neck cancer was larynx cancer (36%), followed by pharynx (28.5%), oral (17.5%), thyroid (6.8%), sinus (6.4%), salivary gland (4.10%), and nasal cancer (0.70%). although larynx cancer was the most frequent cancer over the whole study duration, there was a significant (P=0.04) difference in the relative frequency of these cancers across the five time periods. There was a significant difference in mean age between cancer categories (P<0.001). The only cancer with a different mean age at different time periods was pharynx cancer (P=0.02). There was a significant difference between sex and cancer categories (P<0.001). CONCLUSION: Laryngeal cancer was the most common head and neck cancer over the whole duration of this study. The differences in the patterns of other head and neck cancers could be due to geographical differences and also different risk factors and lifestyles all over the world. Further investigations in these fields are suggested in future studies.