Debra A. Goldman

Magnetic Resonance Imaging for Predicting Prostate Biopsy Findings in Patients Considered for Active Surveillance of Clinically Low Risk Prostate Cancer

PURPOSE A barrier to the acceptance of active surveillance for men with prostate cancer is the risk of underestimating the cancer burden on initial biopsy. We assessed the value of endorectal magnetic resonance imaging in predicting upgrading on confirmatory biopsy in men with low risk prostate cancer. MATERIALS AND METHODS A total of 388 consecutive men (mean age 60.6 years, range 33 to 89) with clinically low risk prostate cancer (initial biopsy Gleason score 6 or less, prostate specific antigen less than 10 ng/ml, clinical stage T2a or less) underwent endorectal magnetic resonance imaging before confirmatory biopsy. Three radiologists independently and retrospectively scored tumor visibility on endorectal magnetic resonance imaging using a 5-point scale (1-definitely no tumor to 5-definitely tumor). Inter-reader agreement was assessed with weighted kappa statistics. Associations between magnetic resonance imaging scores and confirmatory biopsy findings were evaluated using measures of diagnostic performance and multivariate logistic regression. RESULTS On confirmatory biopsy, Gleason score was upgraded in 79 of 388 (20%) patients. Magnetic resonance imaging scores of 2 or less had a high negative predictive value (0.96-1.0) and specificity (0.95-1.0) for upgrading on confirmatory biopsy. A magnetic resonance imaging score of 5 was highly sensitive for upgrading on confirmatory biopsy (0.87-0.98). At multivariate analysis patients with higher magnetic resonance imaging scores were more likely to have disease upgraded on confirmatory biopsy (odds ratio 2.16-3.97). Inter-reader agreement and diagnostic performance were higher for the more experienced readers (kappa 0.41-0.61, AUC 0.76-0.79) than for the least experienced reader (kappa 0.15-0.39, AUC 0.61-0.69). Magnetic resonance imaging performed similarly in predicting low risk and very low risk (Gleason score 6, less than 3 positive cores, less than 50% involvement in all cores) prostate cancer. CONCLUSIONS Adding endorectal magnetic resonance imaging to the initial clinical evaluation of men with clinically low risk prostate cancer helps predict findings on confirmatory biopsy and assess eligibility for active surveillance.

Performance Characteristics of MR Imaging in the Evaluation of Clinically Low-Risk Prostate Cancer: A Prospective Study

PURPOSE To prospectively evaluate diagnostic performance of T2-weighted magnetic resonance (MR) imaging and MR spectroscopic imaging in detecting lesions stratified by pathologic volume and Gleason score in men with clinically determined low-risk prostate cancer. MATERIALS AND METHODS The institutional review board approved this prospective, HIPAA-compliant study. Written informed consent was obtained from 183 men with clinically low-risk prostate cancer (cT1-cT2a, Gleason score≤6 at biopsy, prostate-specific antigen [PSA] level<10 ng/mL [10 μg/L]) undergoing MR imaging before prostatectomy. By using a scale of 1-5 (score 1, definitely no tumor; score 5, definitely tumor), two radiologists independently scored likelihood of tumor per sextant on T2-weighted images. Two spectroscopists jointly recorded locations of lesions with metabolic features consistent with tumor on MR spectroscopic images. Whole-mount step-section histopathologic analysis constituted the reference standard. Diagnostic performance at sextant level (T2-weighted imaging) and detection sensitivities (T2-weighted imaging and MR spectroscopic imaging) for lesions of 0.5 cm3 or larger were calculated. RESULTS For T2-weighted imaging, areas under the receiver operating characteristic curves for sextant-level detection were 0.77 (reader 1) and 0.82 (reader 2). For lesions of ≥0.5 cm3 and, 1<cm3, sensitivities were significantly lower when the lesion Gleason score was ≤6 (0.44 [reader 1] and 0.61 [reader 2]) rather than when the Gleason score was ≥7 (0.73, P=.02 [reader 1]; and 0.84, P=.05 [reader 2]). For lesions of ≥1 cm3, lesion Gleason score did not significantly affect sensitivity (0.83 [reader 1] and 1.00 [reader 2] for Gleason score≤6 vs 0.82 and 0.92 for Gleason score≥7; P≥.07). MR spectroscopic imaging sensitivity was low and was not significantly affected by pathologic lesion volume or Gleason score. CONCLUSION In men with clinically low-risk prostate cancer, detection of lesions of <1 cm3 with T2-weighted imaging is significantly dependent on lesion Gleason score; detection of lesions of ≥1 cm3 is significantly better than detection of smaller lesions and is not affected by lesion Gleason score. The role of MR spectroscopic imaging alone in this population is limited.

Transition Zone Prostate Cancer: Incremental Value of Diffusion-weighted Endorectal MR Imaging in Tumor Detection and Assessment of Aggressiveness

PURPOSE To evaluate the incremental value of using diffusion-weighted magnetic resonance (MR) imaging in addition to T2-weighted imaging for the detection of prostate cancer in the transition zone and the assessment of tumor aggressiveness. MATERIALS AND METHODS This retrospective HIPAA-compliant institutional review board-approved study included 156 consecutive patients (median age, 59.2 years) who underwent MR imaging before radical prostatectomy. Two readers who were blinded to patient data independently recorded their levels of suspicion on a five-point scale of the presence of transition zone tumors on the basis of T2-weighted imaging alone and then, 4 weeks later, diffusion-weighted imaging and T2-weighted imaging together. Apparent diffusion coefficients (ADCs) were measured in transition zone cancers and glandular and stromal benign prostatic hyperplasia. Areas under the receiver operating characteristic curves were used to evaluate detection accuracy, and generalized linear models were used to test ADC differences between benign and malignant prostate regions. Whole-mount step-section histopathologic examination was the reference standard. RESULTS In overall tumor detection, addition of diffusion-weighted imaging to T2-weighted imaging improved the areas under the receiver operating characteristic curves for readers 1 and 2 from 0.60 and 0.60 to 0.75 and 0.71, respectively, at the patient level (P = .004 for reader 1 and P = .027 for reader 2) and from 0.64 and 0.63 to 0.73 and 0.68, respectively, at the sextant level (P = .001 for reader 1 and P = .100 for reader 2). Least squares mean ADCs (× 10(-3) mm(2)/sec) in glandular and stromal benign prostatic hyperplasia were 1.44 and 1.09, respectively. Mean ADCs were inversely associated with tumor Gleason scores (1.10, 0.98, 0.87, and 0.75 for Gleason scores of 3 + 3, 3 + 4, 4 + 3, and ≥ 4 + 4, respectively). CONCLUSION Use of diffusion-weighted imaging in addition to T2-weighted imaging improved detection of prostate cancer in the transition zone, and tumor ADCs were inversely associated with tumor Gleason scores in the transition zone.

Normal Central Zone of the Prostate and Central Zone Involvement by Prostate Cancer: Clinical and MR Imaging Implications

PURPOSE To describe the anatomic features of the central zone of the prostate on T2-weighted and diffusion-weighted (DW) magnetic resonance (MR) images and evaluate the diagnostic performance of MR imaging in detection of central zone involvement by prostate cancer. MATERIALS AND METHODS The institutional review board waived informed consent and approved this retrospective, HIPAA-compliant study of 211 patients who underwent T2-weighted and DW MR imaging of the prostate before radical prostatectomy. Whole-mount step-section pathologic findings were the reference standard. Two radiologists independently recorded the visibility, MR signal intensity, size, and symmetry of the central zone and scored the likelihood of central zone involvement by cancer on T2-weighted MR images and on T2-weighted MR images plus apparent diffusion coefficient (ADC) maps generated from the DW MR images. Descriptive summary statistics were calculated for central zone imaging features. Sensitivity, specificity, and area under the curve were used to evaluate reader performance in detecting central zone involvement. RESULTS For readers 1 and 2, the central zone was visible, at least partially, in 177 (84%) and 170 (81%) of 211 patients, respectively. The most common imaging appearance of the central zone was symmetric, homogeneous low signal intensity. Cancers involving the central zone had higher prostate-specific antigen values, Gleason scores, and rates of extracapsular extension and seminal vesicle invasion compared with cancers not involving the central zone (P < .05). Area under the curve, sensitivity, and specificity in detecting central zone involvement were 0.70, 0.30, and 0.96 for reader 1 and 0.65, 0.35, and 0.93 for reader 2, and these values did not differ significantly between T2-weighted imaging and T2-weighted imaging plus ADC maps. CONCLUSION The central zone was visualized in most patients. Cancers involving the central zone were associated with more aggressive disease than those without central zone involvement.

Value of the Hemorrhage Exclusion Sign on T1-weighted Prostate MR Images for the Detection of Prostate Cancer

PURPOSE To retrospectively determine the prevalence and positive predictive value (PPV) of the hemorrhage exclusion sign on T1-weighted magnetic resonance (MR) images in conjunction with findings on T2-weighted images in the detection of prostate cancer, with use of whole-mount step-section pathologic specimens from prostatectomy as the reference standard. MATERIALS AND METHODS The institutional review board approved this retrospective study, which was compliant with HIPAA, and the requirement to obtain informed consent was waived. Two hundred ninety-two patients with biopsy-proved prostate cancer underwent endorectal MR imaging followed by prostatectomy. The hemorrhage exclusion sign was defined as the presence of a well-defined area of low signal intensity surrounded by areas of high signal intensity on T1-weighted images. Two readers independently assessed the presence and extent of postbiopsy changes and the hemorrhage exclusion sign. The presence of a corresponding area of homogeneous low signal intensity on T2-weighted images was also recorded. The prevalence and PPV of the hemorrhage exclusion sign were calculated. RESULTS Readers 1 and 2 found postbiopsy changes in the peripheral zone in 184 (63%) and 189 (64.7%) of the 292 patients, respectively. In these patients, the hemorrhage exclusion sign was observed in 39 of 184 patients (21.2%) by reader 1 and 36 of 189 patients (19.0%) by reader 2. A corresponding area of homogeneous low signal intensity was seen on T2-weighted images in the same location as the hemorrhage exclusion sign in 23 of 39 patients (59%) by reader 1 and 19 of 36 patients (53%) by reader 2. The PPV of the hemorrhage exclusion sign alone was 56% (22 of 39 patients) for reader 1 and 50% (18 of 36 patients) for reader 2 but increased to 96% (22 of 23 patients) and 95% (18 of 19 patients) when the sign was identified in an area of homogeneous low signal intensity on T2-weighted images. CONCLUSION Postbiopsy change is a known pitfall in the interpretation of T2-weighted images. The authors have shown that a potential benefit of postbiopsy change is the presence of excluded hemorrhage, which, in conjunction with a corresponding area of homogeneous low signal intensity at T2-weighted imaging, is highly accurate for cancer identification.

Bone Metastases in Castration-Resistant Prostate Cancer: Associations between Morphologic CT Patterns, Glycolytic Activity, and Androgen Receptor Expression on PET and Overall Survival

PURPOSE To compare the features of bone metastases at computed tomography (CT) to tracer uptake at fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and fluorine 18 16β-fluoro-5-dihydrotestosterone (FDHT) PET and to determine associations between these imaging features and overall survival in men with castration-resistant prostate cancer. MATERIALS AND METHODS This is a retrospective study of 38 patients with castration-resistant prostate cancer. Two readers independently evaluated CT, FDG PET, and FDHT PET features of bone metastases. Associations between imaging findings and overall survival were determined by using univariate Cox proportional hazards regression. RESULTS In 38 patients, reader 1 detected 881 lesions and reader 2 detected 867 lesions. Attenuation coefficients at CT correlated inversely with FDG (reader 1: r = -0.3007; P < .001; reader 2: r = -0.3147; P < .001) and FDHT (reader 1: r = -0.2680; P = .001; reader 2: r = -0.3656; P < .001) uptake. The number of lesions on CT scans was significantly associated with overall survival (reader 1: hazard ratio [HR], 1.025; P = .05; reader 2: HR, 1.021; P = .04). The numbers of lesions on FDG and FDHT PET scans were significantly associated with overall survival for reader 1 (HR, 1.051-1.109; P < .001) and reader 2 (HR, 1.026-1.082; P ≤ .009). Patients with higher FDHT uptake (lesion with the highest maximum standardized uptake value) had significantly shorter overall survival (reader 1: HR, 1.078; P = .02; reader 2: HR, 1.092; P = .02). FDG uptake intensity was not associated with overall survival (reader 1, P = .65; reader 2, P = .38). CONCLUSION In patients with castration-resistant prostate cancer, numbers of bone lesions on CT, FDG PET, and FDHT PET scans and the intensity of FDHT uptake are significantly associated with overall survival.

Combined pre-treatment MRI and 18F-FDG PET/CT parameters as prognostic biomarkers in patients with cervical cancer

OBJECTIVE To determine the associations of quantitative parameters derived from multiphase contrast-enhanced magnetic resonance imaging (CE-MRI), diffusion-weighted (DW) MRI and 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) with clinico-histopathological prognostic factors, disease-free survival (DFS) and overall survival (OS) in patients with cervical cancer. METHODS AND MATERIALS Our institutional review board approved this retrospective study of 49 patients (median age, 45 years) with histopathologically proven IB-IVB International Federation of Gynecology and Obstetrics (FIGO) cervical cancer who underwent pre-treatment pelvic MRI and whole-body 18F-FDG PET/CT between February 2009 and May 2012. Maximum diameter (maxTD), percentage enhancement (PE) and mean apparent diffusion coefficient (ADCmean) of the primary tumor were measured on MRI. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) were measured on 18F-FDG PET/CT. Correlations between imaging metrics and clinico-histopathological parameters including revised 2009 FIGO stage, tumor histology, grade and lymph node (LN) metastasis at diagnosis were evaluated using the Wilcoxon rank sum test. Cox modeling was used to determine associations with DFS and OS. RESULTS Median follow-up was 17 months. 41 patients (83.6%) were alive. 8 patients (16.3%) died of disease. Progression/recurrence occurred in 17 patients (34.6%). Significant differences were observed in ADCmean, SUVmax, MTV and TLG according to FIGO stage (p<0.001-0.025). There were significant correlations between ADCmean, MTV, TLG and LN metastasis (p=0.017-0.032). SUVmax was not associated with LN metastasis. FIGO stage (p=0.017/0.033), LN metastases (p=0.001/0.020), ADCmean (p=0.007/0.020) and MTV (p=0.014/0.026) were adverse predictors of both DFS/OS. maxTD (p=0.005) and TLG (p=0.024) were adverse predictors of DFS. PE and SUVmax did not correlate with DFS or OS (p=0.18-0.72). CONCLUSIONS Quantitative parameters derived from pre-treatment DW-MRI (ADCmean) and from 18F-FDG PET/CT (MTV and TLG) were associated with high-risk features and may serve as prognostic biomarkers of survival in patients with cervical cancer.

Retrospective Analysis of 18F-FDG PET/CT for Staging Asymptomatic Breast Cancer Patients Younger Than 40 Years

National Comprehensive Cancer Network guidelines consider 18F-FDG PET/CT for only clinical stage III breast cancer patients. However, there is debate whether TNM staging should be the only factor in considering if PET/CT is warranted. Patient age may be an additional consideration, because young breast cancer patients often have more aggressive tumors with potential for earlier metastases. This study assessed PET/CT for staging of asymptomatic breast cancer patients younger than 40 y. Methods: In this Institutional Review Board–approved retrospective study, our hospital information system was screened for breast cancer patients younger than 40 y who underwent staging PET/CT before any treatment. Patients with symptoms or conventional imaging findings suggestive of distant metastases or with prior malignancy were excluded. Initial stage was based on physical examination, mammography, ultrasound, and breast MR imaging. PET/CT was then evaluated to identify unsuspected extraaxillary regional nodal and distant metastases. Results: One hundred thirty-four patients with initial breast cancer stage I to IIIC met inclusion criteria. PET/CT findings led to upstaging to stage III or IV in 28 patients (21%). Unsuspected extraaxillary regional nodes were found in 15 of 134 patients (11%) and distant metastases in 20 of 134 (15%), with 7 of 134 (5%) demonstrating both. PET/CT revealed stage IV disease in 1 of 20 (5%) patients with initial clinical stage I, 2 of 44 (5%) stage IIA, 8 of 47 (17%) stage IIB, 4 of 13 (31%) stage IIIA, 4 of 8 (50%) stage IIIB, and 1 of 2 (50%) stage IIIC. All 20 patients upstaged to stage IV were histologically confirmed. Four synchronous thyroid and 1 rectal malignancies were identified. Conclusion: PET/CT revealed distant metastases in 17% of asymptomatic stage IIB breast cancer patients younger than 40 y. Although guidelines of the National Comprehensive Cancer Network recommend against systemic staging in patients with stage II disease, our data suggest that PET/CT might be valuable in younger patients with stage IIB and III disease. Use of PET/CT in younger patients has the potential to reduce the morbidity and cost of unnecessary therapies in young breast cancer patients.

Stage IB1 Cervical Cancer: Role of Preoperative MR Imaging in Selection of Patients for Fertility-Sparing Radical Trachelectomy

PURPOSE To determine whether magnetic resonance (MR) imaging evaluation of key morphologic tumor characteristics can improve patient selection for radical trachelectomy. MATERIALS AND METHODS The institutional review board approved and waived informed consent for this study of 62 patients (mean age, 32 years; age range, 23-42 years) with International Federation of Gynecology and Obstetrics stage IB1 cervical carcinoma who underwent attempted radical trachelectomy between November 2001 and January 2011 and had preoperative MR imaging. Retrospectively, two radiologists reviewed MR images for tumor presence and size, distance between tumor and internal os, and presence of deep cervical stromal invasion. Associations between MR imaging findings and surgery type were tested. RESULTS Sensitivity and specificity of tumor detection were, respectively, 87% and 100% (reader 1) and 76% and 95% (reader 2). Six of six patients with negative cone biopsy margins and no tumor at postconization MR imaging were without tumor at trachelectomy pathologic analysis. Mean differences between MR imaging and histologic tumor sizes were 0.7 mm (range, -15 to 11 mm) for reader 1 and 2.2 mm (range, -9 to 15 mm) for reader 2. Sensitivities for deep cervical stromal invasion were 75% (reader 1) and 50% (reader 2). For each reader, nine of nine (100%) patients with tumor 5 mm or less from the internal os and three of five (60%) patients with tumor 6-9 mm from the internal os at MR imaging needed radical hysterectomy. For both readers, tumor size of 2 cm or larger (P < .001) and deep cervical stromal invasion (P ≤ .003) at MR imaging were associated with increased chance of radical hysterectomy. CONCLUSION Pretrachelectomy MR imaging can help identify high-risk patients likely to need radical hysterectomy or confirm the absence of residual tumor in the cervix after a cone biopsy with negative margins.

Reducing the influence of b-value selection on diffusion-weighted imaging of the prostate: evaluation of a revised monoexponential model within a clinical setting.

To compare the accuracy of standard and revised monoexponential models of diffusion‐weighted magnetic resonance imaging (DW‐MRI) data for differentiating malignant from benign prostate tissue, using surgical pathology as the reference standard.