MRI assessment of seminal vesicle involvement by prostate cancer using T2 signal intensity and volume.

BACKGROUND: Seminal vesicle involvement (SVI) in patients with newly diagnosed prostate cancer is associated with high rates of treatment failure and tumor recurrence; correct identification of SVI allows for effective management decisions and surgical planning. METHODS: This single-center retrospective study analyzed MR images of the seminal vesicles from patients undergoing radical prostatectomy with confirmed T3b disease, comparing them to a control group without SVI matched for age and Gleason grade with a final stage of T2 or T3a. Seminal vesicles were segmented by an experienced uroradiologist, "raw" and bladder-normalized T2 signal intensity, as well as SV volume, were obtained. RESULTS: Among the 82 patients with SVI, 34 (41.6%) had unilateral invasion, and 48 (58.4%) had bilateral disease. There was no statistically significant difference in the degree of distension between normal and involved seminal vesicles (P = 0.08). Similarly, no statistically significant difference was identified in the raw SV T2 signal intensity (P = 0.09) between the groups. In the 159 patients analyzed, SVI was prospectively suspected in 10 of 82 patients (specificity, 100%; sensitivity, 12.2%). In all these cases, lesions macroscopically invaded the seminal vesicle, and the raw T2 signal intensity was significantly lower than that in the SVI and control groups (P = 0.02 and 0.01). CONCLUSION: While signal intensity measurements in T2-weighted images may provide insight into T3b disease, our findings suggest that this data alone is insufficient to reliably predict SVI, indicating the need for further investigation and complementary diagnostic approaches.

Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma.

PURPOSE: To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. METHOD: Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT. Changes in imaging parameters before and after sunitinib were assessed with the non-parametric Wilcoxon signed-rank test and the log-rank test was used to assess effects on survival. RESULTS: 12 participants fulfilled the inclusion criteria. After 12 days, the solid and necrotic tumor volumes decreased by 28% and 17%, respectively (p = 0.04). However, tumor-volume reduction did not correlate with progression-free or overall survival (PFS/OS). Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer PFS (p = 0.03) on the log-rank test. An increase in R2* from 19 to 28s-1 (p = 0.001) was observed, paralleled by a decrease in Ktrans from 0.415 to 0.305min-1 (p = 0.01) and a decrease in perfusion fraction from 0.34 to 0.19 (p<0.001). CONCLUSIONS: Physiological imaging confirmed efficacy of the anti-angiogenic agent 12 days after initiating therapy and demonstrated response to treatment. The change in diffusivity shortly after starting pre-surgical sunitinib correlated to PFS in mRCC undergoing nephrectomy, however, no parameter predicted OS. TRIAL REGISTRATION: EudraCtNo: 2005-004502-82.

Diagnostic accuracy of biparametric versus multiparametric prostate MRI: assessment of contrast benefit in clinical practice.

PURPOSE: To assess the added value of dynamic contrast-enhanced (DCE) in prostate MR in clinical practice. METHODS: Two hundred sixty-four patients underwent prostate MRI, with T2 and DWI sequences initially interpreted, prior to full multiparametric magnetic resonance imaging (mpMRI) interpretation using a Likert 1-5 scale. A prospective opinion was given on likely benefit of contrast prior to review of the DCE sequence, and retrospectively following full mpMRI review. The final histology result following targeted and/or systematic biopsy of the prostate was used for outcome purposes. RESULTS: Biparametric magnetic resonance imaging (bpMRI) and mpMRI were assigned the same score in 86% of cases; when dichotomising to a negative or positive MRI (Likert score ≥ 3), concordance increased to 92.8%. At Likert score ≥ 3 bpMRI detected 89.9% of all cancers and 93.5% clinically significant prostate cancers (csPCa) and mpMRI 90.7% and 94.6%, respectively. mpMRI had fewer false positives than bpMRI (11.4% vs 18.9%) and a lower Likert 3 rate (8.3% vs 17%), conferring higher specificity (74% vs 67%), but similar sensitivity (95% versus 94%) and ROC-AUC (90% vs 89%). At a positive MRI threshold of Likert ≥ 4, mpMRI had a higher sensitivity than bpMRI (89% versus 80%) and detected more csPCa (89.2% versus 79.6%). DCE was prospectively considered of potential benefit in 27.3%, but readers would only recall 11% of patients for DCE sequences, mainly to assess score 3 peripheral zone lesions. Following full mpMRI review, DCE was considered helpful in 28.4% of cases; in 23/75 (30.6%) of these cases this only became apparent after reviewing the sequence, reasons included increased confidence, presence of "safety-net" lesions or inflammatory lesions. CONCLUSION: BpMRI has equivalent cancer detection rates to mpMRI; however, mpMRI had fewer Likert 3 call rates and increased specificity and was subjectively considered of benefit by readers in 28.4% of cases. KEY POINTS: • bpMRI has similar cancer detection rates to the full mpMRI protocol at a positive MRI threshold of Likert 3. • mpMRI had fewer intermediate category 3 calls (8.3%) than bpMRI (17%) and fewer false positives than bpMRI (11.4% vs 18.9%), conferring higher specificity (74% vs 67%). • Readers considered DCE beneficial in 28.4% of cases, but in a relatively high number (30.6%) this only became apparent after reviewing the sequence.

Defining the incremental value of 3D T2-weighted imaging in the assessment of prostate cancer extracapsular extension.

OBJECTIVES: To assess the added value of 3D T2-weighted imaging (T2WI) over conventional 2D T2WI in diagnosing extracapsular extension (ECE). METHODS: Seventy-five patients undergoing 3-T MRI before radical prostatectomy were included. PI-RADS ≥ 4 lesions were assessed for ECE on 2D T2W images using a 5-point Likert scale (1 = no ECE, 5 = definite ECE) and the length of tumour prostatic capsular contact. A second read using 3D T2W images and reformats evaluated ECE and the maximal 3D capsular contact length and surface. RESULTS: One hundred six lesions were identified at MRI. ECE was confirmed by histology in 54% (57/106) of lesions and 64% (48/75) of patients. Sensitivity and specificity for 3D T2 reads were 75.4% versus 64.9% (p = 0.058), respectively, and 83.7% versus 85.7% (p = 0.705) for 2D T2 reads, respectively. 3D T2W reads showed significantly higher mean subjective Likert scores of 3.7 ± 1.4 versus 3.3 ± 1.4 (p = 0.001) in ECE-positive lesions and lower mean Likert score of 1.5 ± 1 versus 1.6 ± 0.9 (p = 0.27) in ECE-negative lesions compared with 2D T2W reads. 3D contact significantly increased sensitivity from 59.6 to 73.7% (p = 0.03), whilst maintaining the same specificity of 87.8% (p = 1). High-grade group tumours (≥ Gleason 4 + 3) showed significantly higher ECE prevalence than low-grade tumours (88% versus 44%, p < 0.001) and a positive predictive value (PPV) for ECE of 90.9% with ≥ 5 mm of contact versus PPV of 90.4% at ≥ 12.5 mm for lower grade tumours. CONCLUSIONS: 3D T2WI significantly increases sensitivity and confidence in calling ECE. The capsular contact length threshold differed between low- and high-grade cancers. KEY POINTS: • 3D capsular contact length and 3D surface contact significantly increased sensitivity in diagnosing ECE. • 3D T2W reads significantly increased reader confidence in calling ECE. • Thresholds for capsular contact length differed between low-grade and high-grade cancers.

Comprehensive assessment of estrogen receptor beta antibodies in cancer cell line models and tissue reveals critical limitations in reagent specificity.

Estrogen Receptor-ß (ERß) has been implicated in many cancers. In prostate and breast cancer its function is controversial, but genetic studies implicate a role in cancer progression. Much of the confusion around ERß stems from antibodies that are inadequately validated, yet have become standard tools for deciphering its role. Using an ERß-inducible cell system we assessed commonly utilized ERß antibodies and show that one of the most commonly used antibodies, NCL-ER-BETA, is non-specific for ERß. Other antibodies have limited ERß specificity or are only specific in one experimental modality. ERß is commonly studied in MCF-7 (breast) and LNCaP (prostate) cancer cell lines, but we found no ERß expression in either, using validated antibodies and independent mass spectrometry-based approaches. Our findings question conclusions made about ERß using the NCL-ER-BETA antibody, or LNCaP and MCF-7 cell lines. We describe robust reagents, which detect ERß across multiple experimental approaches and in clinical samples.

Preoperative 3-T diffusion-weighted MRI for the qualitative and quantitative assessment of extracapsular extension in patients with intermediate- or high-risk prostate cancer.

OBJECTIVE: The purpose of this study was to prospectively evaluate the value of diffusion-weighted MRI (DWI) for the assessment of extracapsular extension (ECE) in patients with prostate cancer. SUBJECTS AND METHODS: Between November 2010 and April 2012, 40 patients with intermediate- to high-risk prostate cancer were prospectively recruited. MR images were obtained at 3 T with a phased-array coil. Two independent readers scored the T2-weighted images alone and then in combination with DW images. ROIs were drawn on the apparent diffusion coefficient (ADC) maps, and histogram-derived values were calculated. Whole-mount histopathologic examination was the standard of reference. Reader performance was analyzed, and differences in patient characteristics and histogram-based ADC values, according to ECE status, were evaluated. RESULTS: ECE was present in 23 of 40 (58%) patients and 23 of 43 (53%) tumors. The sensitivity for side-specific ECE detection significantly increased, from 0.22 to 0.44 for reader 1 and 0.33 to 0.82 for reader 2 (both p < 0.05) without a significant change in specificity for either reader with the addition of DWI and ADC mapping. The positive and negative predictive values for both readers also increased. The ADC parameters of median and 10th and 25th centiles showed a statistically significant difference between tumors with and those without ECE (p < 0.05). CONCLUSION: The addition of DWI and ADC mapping to T2-weighted MRI improved the accuracy of preoperative detection of ECE. Median and 10th and 25th centile ADC values were significantly associated with the presence of ECE and may be useful in the pretreatment assessment of patients with prostate cancer.