Living with prostate cancer: a mixed-method evaluation of group therapy intervention to alleviate psychological distress in a Canadian setting.

PURPOSE: To assess the effects of group therapy focused on the experience of living with prostate cancer (PC) on depression and mental well-being among men with the disease and to explore participant experiences of a guided opportunity to 'speak the unspeakable' as it pertains to living with PC. METHODS: We used a mixed-method convergent design. Participants completed four validated self-report questionnaires at baseline, immediately after the final session, and at three, six, and 12 months follow-up. A repeated measures mixed-effect model examined the effects of the program on depression, mental well-being, and masculinity. Seven focus groups (n = 37) and 39 semi-structured individual interviews explored participant reactions at follow-up. RESULTS: Thirty-nine (93%) participants completed the questionnaires at all follow-ups. Responses indicated improved mental well-being up to three months (p < 0.01) and a decrease in depressive symptoms to 12 months (p < 0.05). Qualitative analysis revealed how the cohesive group environment alleviated psychological stress, enabled participants to identify significant issues and concerns in their lives, and improved communication and relationship skills that were of value in the group as well as with family and friends. The facilitation was essential to guiding participants to 'speak the unspeakable.' CONCLUSION: Men with PC who speak of their experience in a group setting with a guided process incorporating features of a life review appear to gain insight into the impact of PC in their lives, experience diminished features of depression and isolation, and enhance their communication skills within the groups as well as with family members and friends.

The "Ins and Outs" of Prostate Specific Membrane Antigen (PSMA) as Specific Target in Prostate Cancer Therapy.

Prostate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate gland and is strongly upregulated in prostatic adenocarcinoma, with elevated expression correlating with metastasis, progression, and androgen independence. Because of its specificity, PSMA is a major target of prostate cancer therapy; however, detectable levels of PSMA are also found in other tissues, especially in salivary glands and kidney, generating bystander damage of these tissues. Antibody target therapy has been used with relative success in reducing tumor growth and prostate specific antigen (PSA) levels. However, since antibodies are highly stable in plasma, they have prolonged time in circulation and accumulate in organs with an affinity for antibodies such as bone marrow. For that reason, a second generation of PSMA targeted therapeutic agents has been developed. Small molecules and minibodies have had promising clinical trial results, but concerns about their specificity had arisen with side effects due to accumulation in salivary glands and kidneys. Herein we study the specificity of small molecules and minibodies that are currently being clinically tested. We observed a high affinity of these molecules for PSMA in prostate, kidney and salivary gland, suggesting that their effect is not prostate specific. The search for specific prostate target agents must continue so as to optimally treat patients with prostate cancer, while minimizing deleterious effects in other PSMA expressing tissues.

Factors Associated with Time to Conversion from Active Surveillance to Treatment for Prostate Cancer in a Multi-Institutional Cohort.

PURPOSE: We examined the demographic and clinicopathological parameters associated with the time to convert from active surveillance to treatment among men with prostate cancer. MATERIALS AND METHODS: A multi-institutional cohort of 7,279 patients managed with active surveillance had data and biospecimens collected for germline genetic analyses. RESULTS: Of 6,775 men included in the analysis, 2,260 (33.4%) converted to treatment at a median followup of 6.7 years. Earlier conversion was associated with higher Gleason grade groups (GG2 vs GG1 adjusted hazard ratio [aHR] 1.57, 95% CI 1.36-1.82; ≥GG3 vs GG1 aHR 1.77, 95% CI 1.29-2.43), serum prostate specific antigen concentrations (aHR per 5 ng/ml increment 1.18, 95% CI 1.11-1.25), tumor stages (cT2 vs cT1 aHR 1.58, 95% CI 1.41-1.77; ≥cT3 vs cT1 aHR 4.36, 95% CI 3.19-5.96) and number of cancerous biopsy cores (3 vs 1-2 cores aHR 1.59, 95% CI 1.37-1.84; ≥4 vs 1-2 cores aHR 3.29, 95% CI 2.94-3.69), and younger age (age continuous per 5-year increase aHR 0.96, 95% CI 0.93-0.99). Patients with high-volume GG1 tumors had a shorter interval to conversion than those with low-volume GG1 tumors and behaved like the higher-risk patients. We found no significant association between the time to conversion and self-reported race or genetic ancestry. CONCLUSIONS: A shorter time to conversion from active surveillance to treatment was associated with higher-risk clinicopathological tumor features. Furthermore, patients with high-volume GG1 tumors behaved similarly to those with intermediate and high-risk tumors. An exploratory analysis of self-reported race and genetic ancestry revealed no association with the time to conversion.

MRI of the Prostate With and Without Endorectal Coil at 3 T: Correlation With Whole-Mount Histopathologic Gleason Score.

OBJECTIVE. The purpose of this article is to prospectively compare image quality and diagnostic accuracy of clinically significant prostate cancer with and without endorectal coil (ERC) at 3 T using a combination of T2-weighted and diffusion-weighted MRI. SUBJECTS AND METHODS. Twenty-three patients with biopsy-proven prostate cancer underwent MRI with and without ERC at the same visit. Patients subsequently underwent radical prostatectomy. Specimens were assessed by whole-mount histopathologic examination. Two radiologists reviewed MR images for image quality (5-point scale) and disease using Prostate Imaging Reporting and Data Systems version 2 (PI-RADSv2). Sensitivity, specificity, and area under the ROC curve (AUC) were calculated with and without ERC. Additionally, apparent diffusion coefficient (ADC) was correlated with Gleason score and ADC values of each lesion were compared with and without ERC. RESULTS. Image quality was comparable with and without ERC (3.8 vs 3.5). Twenty-nine cancer foci larger than 0.5 cm in diameter were found in 23 patients on histopathologic examination; 18 tumors had a Gleason score of 7 or greater. Two radiologists recorded AUC for tumors with a Gleason score of 7 or greater as 0.96 and 0.96 with ERC and 0.88 and 0.91 without ERC. All 13 tumors with a Gleason score of 3 + 4 were detected with ERC, but only 9 were detected without ERC. One of five tumors with Gleason scores less than 3 + 4 was missed with and without ERC. ADC significantly correlated with Gleason score. There was no significant difference in the ADC of a lesion on MRI with and without an ERC. CONCLUSION. MRI with and without ERC was equally accurate at showing prostate cancers with Gleason scores of 4 + 3 or greater. However, MRI with ERC was superior at showing cancer with a Gleason score of 3 + 4. There was no significant difference in ADC values between scores acquired with or without an ERC.

Mapping Canadian Men's Recent and Intended Health Behavior Changes Through the Don't Change Much Electronic Health Program.

BACKGROUND: Although evaluation studies confirm the strong potential of men's electronic health (eHealth) programs, there have been calls to more fully understand acceptability, engagement, and behavior change to guide future work. Relatedly, mapping of behavior changes using health promotion theories including the transtheoretical model (or stages of change) has been recommended to build a translatable empirical base to advance design and evaluation considerations for men's eHealth programs. OBJECTIVE: This study aimed to use a benchmark sample as a reference group to map the recent and intended health behavior changes in Canadian men who use the Don't Change Much (DCM) eHealth program. The hypothesis being tested was that increased exposure to DCM would be positively associated with men's recent and intended health behavior changes. METHODS: DCM users (n=863) were sampled for demographic data and self-reported recent and intended health behavior changes. Respondents also reported their usage (frequency and duration) for each of the 3 DCM components (web, newsletter, and social media) and were allocated to limited exposure (257/863, 29.8%), low exposure (431/863, 49.9%), and high exposure (175/863, 20.3%) subgroups. A benchmark sample (n=2000), comprising respondents who had not accessed DCM provided a reference group. Bivariate analysis of recent and intended health behavior changes and DCM exposure levels were used to compute the strength of association between the independent variables (exposure levels) and the 10 categorical dependent variables (recent and intended health behavior changes). Binary logistic regression models were computed for each of the 10 recent and intended health behavior changes. Linear regression was used to model the association between the number of recent and intended changes and the level of exposure to DCM. RESULTS: Compared with the benchmark reference group, DCM high-exposure respondents had significantly increased odds for 9 of the 10 health behavior changes, with the largest effect size observed for Changed diet or Improved eating habits (odds ratio [OR] 5.628, 95% CI 3.932-8.055). High-exposure respondents also had significantly increased odds for 9 intended health changes, with the largest effect sizes observed for Reduce stress level (OR 4.282, 95% CI 3.086-5.941). Moderate effect size (goodness of fit) was observed for increased total number of recent (F12,2850=25.52; P.001; adjusted R2=.093) and intended health behavior changes (F12,2850=36.30; P.001; adjusted R2=.129) among high-exposure respondents. CONCLUSIONS: DCM respondents contrasted the predominately precontemplative benchmark sample mapping across the contemplative, preparation, and action stages of the transtheoretical health behavior change model. Almost 10% of variation in the recent and 13% of variation in the intended health behavior changes can be explained by DCM exposure and demographic factors, indicating the acceptability of this men's eHealth resource.

Canadian men's health stigma, masculine role norms and lifestyle behaviors.

Men are at high risk for both morbidity and premature mortality from several of the most common serious diseases. Although numerous factors have been identified to explain men's risk, this study focused on the relationship between lifestyle behaviors, health-related self-stigma and masculine role norms. An age and location stratified sample of 2000 Canadian men completed measures assessing five lifestyle behaviors (smoking, alcohol use, sleep, diet and exercise), a screen for depression, and measures of self-stigma and masculine role norms. The results showed that elements of both health-related self-stigma and masculine role norms were associated with increased risk for being above the clinical threshold for four of the lifestyle behaviors and depression. The most frequent and largest relationships were associated with exercise and depression. The total number of lifestyle behaviors for which participants were above the clinical cut-points was also associated with self-stigma and masculine role norms. These findings demonstrate the importance of health-related self-stigma and masculine role norms as potential barriers to men's health and well-being.

Canadian Men's Health Literacy: A Nationally Representative Study.

Though men's health promotion has attracted increased research attention, conspicuously absent have been empirical insights to health literacy levels within and across male subgroups. Recent advancements in the measurement of health literacy have made available avenues for evaluating individual and social determinants of health literacy. Important insights can be drawn to detail patterns and diversity among men as a means to informing the design, implementation, and evaluation of tailored health promotion programs. Drawing on 2000 Canada-based men's responses to the Health Literacy Questionnaire, correlations between demographic variables and six health literacy scales are described. Low income, low education, and living alone were associated with men's low health literacy, with the strongest effect sizes for the "Social support for health" and "Actively engaged with health care professionals" scales. Multiple linear regressions confirmed low income as the strongest predictor of men's low health literacy in all the scales except "Appraisal of health information." Low income, self-identifying as gay, bisexual, or other, and living alone were strongly predictive of low scores on the "Social support for health" scale. The findings affirm the importance of considering men's health literacy and inequities to advance effective men's health promotion programs.

Comparing diagnostic accuracy of luminal water imaging with diffusion-weighted and dynamic contrast-enhanced MRI in prostate cancer: A quantitative MRI study.

Luminal water imaging (LWI) is a new MRI T2 mapping technique that has been developed with the aim of diagnosis of prostate carcinoma (PCa). This technique measures the fractional amount of luminal water in prostate tissue, and has shown promising preliminary results in detection of PCa. To include LWI in clinical settings, further investigation on the accuracy of this technique is required. In this study, we compare the diagnostic accuracy of LWI with those of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI in detection and grading of PCa. Fifteen patients with biopsy-proven PCa consented to participate in this ethics-board-approved prospective study. Patients were examined with LWI, DWI, and DCE sequences at 3 T prior to radical prostatectomy. Maps of MRI parameters were generated and registered to whole-mount histology. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic accuracy of individual and combined MR parameters. Correlation with Gleason score (GS) was evaluated using Spearman's rank correlation test. The results show that area under the ROC curve (AUC) obtained from LWI was equal to or higher than the AUC obtained from DWI, DCE, or their combination, in peripheral zone (0.98 versus 0.90, 0.89, and 0.91 respectively), transition zone (0.99 versus 0.98, n/a, and 0.98), and the entire prostate (0.85 versus 0.81, 0.75, and 0.84). The strongest correlation with GS was achieved from LWI (ρ = -0.81 ± 0.09, P < 0.001). Results of this pilot study show that LWI performs equally well as, or better than, DWI and DCE in detection of PCa. LWI provides significantly higher correlation with GS than DWI and DCE. This technique can potentially be included in clinical MRI protocols to improve characterization of tumors. However, considering the small size of the patient population in this study, a further study with a larger cohort of patients and broader range of GS is required to confirm the findings and draw a firm conclusion on the applicability of LWI in clinical settings.

Assessment of the need for DCE MRI in the detection of dominant lesions in the whole gland: Correlation between histology and MRI of prostate cancer.

The purpose of this study was to evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) in the detection of dominant prostate tumors with multi-parametric MRI of the whole gland. Combined diffusion tensor imaging (DTI) and DCE MRI from 16 patients with biopsy-proven prostate cancer and no previous treatment were acquired with a 3.0-T MRI scanner prior to radical prostatectomy, and used to identify dominant tumors. MRI results were validated by whole-mount histology. Paired t-test and Wilcoxon test, logistic generalized linear mixed effect models and receiver operating characteristic (ROC) analyses were used for the estimation of the statistical significance of the results. In the peripheral zone (PZ), the areas under the ROC curve (ROC-AUC) were 0.98 (sensitivity, 96%; specificity, 98%) for DTI, 0.96 (sensitivity, 92%; specificity, 97%) for DCE and 0.99 (sensitivity, 98%; specificity, 98%) for DTI + DCE. In the entire prostate, the ROC-AUC values were 0.96 (sensitivity, 84%; specificity, 95%) for DTI, 0.87 (sensitivity, 45%; specificity, 94%) for DCE and 0.96 (sensitivity, 88%; specificity, 98%) for DTI + DCE. The increase in ROC-AUC by the addition of DCE was not statistically significant in either PZ or the entire prostate. The results of this study have shown that DTI identified dominant tumors with high accuracy in both PZ and the entire prostate, whereas the inclusion of DCE MRI had no significant impact on the identification of either PZ or entire prostate dominant lesions. Our results suggest that the inclusion of DCE MRI may not increase the accuracy of dominant lesion detection, allowing for faster, better tolerated imaging studies.

Luminal Water Imaging: A New MR Imaging T2 Mapping Technique for Prostate Cancer Diagnosis.

Purpose To assess the feasibility of luminal water imaging, a quantitative T2-based magnetic resonance (MR) imaging technique, for the detection and grading of prostate cancer (PCa). Materials and Methods Eighteen patients with biopsy-proven PCa provided informed consent to be included in this institutional human ethics board-approved prospective study between January 2015 and January 2016. Patients underwent 3.0-T MR imaging shortly before radical prostatectomy. T2 distributions were generated with a regularized non-negative least squares algorithm from multiecho spin-echo MR imaging data. From T2 distributions, maps of seven MR parameters, Ncomp, T2short, T2long, geometric mean T2 (gmT2), luminal water fraction (LWF), Ashort, and Along, were generated and compared with digitized images of hematoxylin-eosin-stained whole-mount histologic slices. A paired t test was used to determine significant differences between MR parameters in malignant and nonmalignant tissue. Correlation with Gleason score (GS) was evaluated with the Spearman rank correlation test. Diagnostic accuracy was evaluated by using logistic generalized linear mixed-effect models and receiver operating characteristic (ROC) analysis. Results The average values of four MR parameters (gmT2, Ashort, Along, and LWF) were significantly different between malignant and nonmalignant tissue. All MR parameters except for T2long showed significant correlation (P < .05) with GS in the peripheral zone. The highest correlation with GS was obtained for LWF (-0.78 ± 0.11, P < .001). ROC analysis demonstrated high accuracy for tumor detection, with the highest area under the ROC curve obtained for LWF (0.97 in the peripheral zone and 0.98 in the transition zone). Conclusion Results of this pilot study demonstrated the feasibility of luminal water imaging in the detection and grading of PCa. A study with a larger cohort of patients and a broader range of GS is required to further evaluate this new technique in clinical settings. © RSNA, 2017.

MR measurement of luminal water in prostate gland: Quantitative correlation between MRI and histology.

PURPOSE: To determine the relationship between parameters measured from luminal water imaging (LWI), a new magnetic resonance imaging (MRI) T2 mapping technique, and the corresponding tissue composition in prostate. MATERIALS AND METHODS: In all, 17 patients with prostate cancer were examined with a 3D multiecho spin echo sequence at 3T prior to undergoing radical prostatectomy. Maps of seven MR parameters, called N, T2-short , T2-long , Ashort , Along , geometric mean T2 time (gmT2 ), and luminal water fraction (LWF), were generated using nonnegative least squares (NNLS) analysis of the T2 decay curves. MR parametric maps were correlated to digitized whole-mount histology sections. Percentage area of tissue components, including luminal space, nuclei, and cytoplasm plus stroma, was measured on the histology sections by using color-based image segmentation. Spearman's rank correlation test was used to evaluate the correlation between MR parameters and the corresponding tissue components, with particular attention paid to the correlation between LWF and percentage area of luminal space. RESULTS: N, T2-short , Along , gmT2 , and LWF showed significant correlation (P < 0.05) with percentage area of luminal space and stroma plus cytoplasm. T2-short and gmT2 also showed significant correlation (P < 0.05) with percentage area of nuclei. Overall, the strongest correlation was observed between LWF and luminal space (Spearman's coefficient of rank correlation = 0.75, P < 0.001). CONCLUSION: Results of this study show that LWF measured with MRI is strongly correlated with the fractional amount of luminal space in prostatic tissue. This result suggests that LWI can potentially be applied for evaluation of prostatic diseases in which the extent of luminal space differs between normal and abnormal tissues. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:861-869.

Erectile Dysfunction Medications and Treatment for Cardiometabolic Risk Factors: A Pharmacoepidemiologic Study.

BACKGROUND: Erectile dysfunction (ED) can be a sentinel marker for future cardiovascular disease and has been described as providing a "window of curability" for men to receive targeted cardiovascular risk assessment. AIM: To determine whether the prescription of phosphodiesterase type 5 inhibitors (PDE5is) for ED leads to the detection and treatment of previously undiagnosed cardiometabolic risk factors. METHODS: We performed a retrospective population-based cohort study of residents of British Columbia, Canada using linked health care databases from 2004 to 2011. An individual-level time series analysis with switching replications was used to determine changes in drug use for hypertension, hypercholesterolemia, and diabetes in men 40 to 59 years old. The observation window for each patient was 720 days before and 360 days after the index date. OUTCOMES: The primary outcome was changes in prescriptions for antihypertensive, statin, and oral antidiabetic drugs, with secondary outcomes being laboratory tests for plasma cholesterol and glucose. RESULTS: 5,858 men 40 to 59 years old newly prescribed a PDE5i were included in the analysis. We found a sudden increase in prescriptions for antihypertensive drugs (40 per 1,000; P < .001), statins (10 per 1,000; P = .001), and antidiabetic drugs (17 per 1,000; P = .002) in the 90 days after a new prescription for a PDE5i. For hypercholesterolemia and diabetes, most of this change was observed in men with relevant screening tests performed in the 30 days after their PDE5i prescription. Only 15% and 17% of men who did not have a screening test for cholesterol and glucose, respectively, in the year before their PDE5i prescription went on to have one in the subsequent 30 days. CLINICAL IMPLICATIONS: The paucity of screening tests observed in our study after PDE5i prescriptions suggests that physicians should be educated on the recommended screening guidelines for men newly diagnosed with ED. STRENGTHS AND LIMITATIONS: The number of men who were ordered a laboratory test or written a prescription but chose not to complete or fill it, respectively, is unknown. CONCLUSION: Treatment for ED with PDE5is can be a trigger or "gateway drug" for the early detection and treatment of cardiometabolic risk factors provided physicians perform the requisite screening investigations. Skeldon SC, Cheng L, Morgan SG, et al. Erectile Dysfunction Medications and Treatment for Cardiometabolic Risk Factors: A Pharmacoepidemiologic Study. J Sex Med 2017;14:1597-1605.

Testosterone Therapy in Patients with Treated and Untreated Prostate Cancer: Impact on Oncologic Outcomes.

PURPOSE: Testosterone deficiency and prostate cancer have an increasing prevalence with age. However, because of the relationship between prostate cancer and androgen receptor activation, testosterone therapy among patients with known prostate cancer has been approached with caution. MATERIALS AND METHODS: We identified a cohort of 82 hypogonadal men with prostate cancer who were treated with testosterone therapy. They included 50 men treated with radiation therapy, 22 treated with radical prostatectomy, 8 on active surveillance, 1 treated with cryotherapy and 1 who underwent high intensity focused ultrasound. We monitored prostate specific antigen, testosterone, hemoglobin, biochemical recurrence and prostate specific antigen velocity. RESULTS: Median patient age was 75.5 years and median followup was 41 months. We found an increase in testosterone (p <0.001) and prostate specific antigen (p = 0.001) in the entire cohort. Prostate specific antigen increased in patients on active surveillance. However, no patients were upgraded to higher Gleason score on subsequent biopsies and none have yet gone on to definitive treatment. We did not note any biochemical recurrence among patients treated with radical prostatectomy but 3 (6%) treated with radiation therapy experienced biochemical recurrence. It is unclear whether these cases were related to testosterone therapy or reflected the natural biology of the disease. We calculated mean prostate specific antigen velocity as 0.001, 0.12 and 1.1 µg/l per year in the radical prostatectomy, radiation therapy and active surveillance groups, respectively. CONCLUSIONS: In the absence of randomized, placebo controlled trials our study supports the hypothesis that testosterone therapy may be oncologically safe in hypogonadal men after definitive treatment or in those on active surveillance for prostate cancer.

Intermittent androgen suppression for rising PSA level after radiotherapy.

BACKGROUND: Intermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial. METHODS: We enrolled patients with a PSA level greater than 3 ng per milliliter more than 1 year after primary or salvage radiotherapy for localized prostate cancer. Intermittent treatment was provided in 8-month cycles, with nontreatment periods determined according to the PSA level. The primary end point was overall survival. Secondary end points included quality of life, time to castration-resistant disease, and duration of nontreatment intervals. RESULTS: Of 1386 enrolled patients, 690 were randomly assigned to intermittent therapy and 696 to continuous therapy. Median follow-up was 6.9 years. There were no significant between-group differences in adverse events. In the intermittent-therapy group, full testosterone recovery occurred in 35% of patients, and testosterone recovery to the trial-entry threshold occurred in 79%. Intermittent therapy provided potential benefits with respect to physical function, fatigue, urinary problems, hot flashes, libido, and erectile function. There were 268 deaths in the intermittent-therapy group and 256 in the continuous-therapy group. Median overall survival was 8.8 years in the intermittent-therapy group versus 9.1 years in the continuous-therapy group (hazard ratio for death, 1.02; 95% confidence interval, 0.86 to 1.21). The estimated 7-year cumulative rates of disease-related death were 18% and 15% in the two groups, respectively (P=0.24). CONCLUSIONS: Intermittent androgen deprivation was noninferior to continuous therapy with respect to overall survival. Some quality-of-life factors improved with intermittent therapy. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00003653.).

MR elastography and diffusion-weighted imaging of ex vivo prostate cancer: quantitative comparison to histopathology.

The purpose of this work was (1) to develop a magnetic resonance elastography (MRE) system for imaging of the ex vivo human prostate and (2) to assess the diagnostic power of mono-frequency and multi-frequency MRE and diffusion weighted imaging (DWI) alone and combined as correlated with histopathology in a patient study. An electromagnetic driver was designed specifically for MRE studies in small-bore MR scanners. Ex vivo prostate specimens (post-fixation) of 14 patients who underwent radical prostatectomy were imaged with MRE at 7 T (nine cases had DWI). In six patients, the MRE examination was performed at three frequencies (600, 800, 1000 Hz) to extract the power-law exponent Gamma. The images were registered to wholemount pathology slides marked with the Gleason score. The areas under the receiver-operator-characteristic curves (AUC) were calculated. The methods were validated in a phantom study and it was demonstrated that (i) the driver does not interfere with the acquisition process and (ii) the driver can generate amplitudes greater than 100 µm for frequencies less than 1 kHz. In the quantitative study, cancerous tissue with Gleason score at least 3 + 3 was distinguished from normal tissue in the peripheral zone (PZ) with an average AUC of 0.75 (Gd ), 0.75 (Gl ), 0.70 (Gamma-Gd ), 0.68 (apparent diffusion coefficient, ADC), and 0.82 (Gd + Gl + ADC). The differentiation between PZ and central gland was modest for Gd (p < 0.07), Gl (p < 0.06) but not significant for Gamma (p < 0.2). A correlation of 0.4 kPa/h was found between the fixation time of the prostate specimen and the stiffness of the tissue, which could affect the diagnostic power results. DWI and MRE may provide complementary information; in fact MRE performed better than ADC in distinguishing normal from cancerous tissue in some cases. Multi-frequency (Gamma) analysis did not appear to improve the results. However, in light of the effect of tissue fixation, the clinical implication of our results may be inconclusive and more experiments are needed.

MR elastography of prostate cancer: quantitative comparison with histopathology and repeatability of methods.

The purpose of this work was to assess trans-perineal prostate magnetic resonance elastography (MRE) for (1) repeatability in phantoms/volunteers and (2) diagnostic power as correlated with histopathology in prostate cancer patients. The three-dimensional (3D) displacement field was obtained using a fractionally encoded gradient echo sequence using a custom-made transducer. The repeatability of the method was assessed based on three repeat studies and by changing the driving frequency by 3% in studies on a phantom and six healthy volunteers. Subsequently, 11 patients were examined with MRE prior to radical prostatectomy. The areas under the receiver operating characteristic curves were calculated using a windowed voxel-to-voxel approach by comparing the 2D registered slides, masked with the Gleason score. For the repeatability study, the average intraclass correlation coefficient for elasticity images was 99% for repeat phantom studies, 98% for ±6 Hz phantom studies, 95% for volunteer repeat studies with 2 min acquisition time, 82% for ±2 Hz volunteer studies with 2 min acquisition time and 73% for repeat volunteer studies with 8 min acquisition time. For the patient study, the average elasticity was 8.2 ± 1.7 kPa in the prostate capsule, 7.5 ± 1.9 kPa in the peripheral zone (PZ), 9.7 ± 3.0 kPa in the central gland (CG) and 9.0 ± 3.4 kPa in the transition zone. In the patient study, cancerous tissue with Gleason score at least 3 + 3 was significantly (p < 0.05) different from normal tissue in 10 out of 11 cases with tumors in the PZ, and 6 out of 9 cases with tumors in the CG. However, the overall case-averaged area under the curve was 0.72 in the PZ and 0.67 in the CG. Cancerous tissue was not always stiffer than normal tissue. The inversion algorithm was sensitive to (i) vibration amplitude and displacement nodes and (ii) misalignment of the 3D wave field due to subject movement.

Erectile Dysfunction and Undiagnosed Diabetes, Hypertension, and Hypercholesterolemia.

PURPOSE: We investigated whether erectile dysfunction, a marker for future cardiovascular disease, is associated with undiagnosed cardiometabolic risk factors among US men. Identifying the presence of these risk factors could lead to earlier initiation of treatment for primary prevention of cardiovascular disease. METHODS: We analyzed cross-sectional data from men aged 20 years and older who participated in the National Health and Nutrition Examination Survey during 2001-2004. Erectile dysfunction was determined by a single, validated survey question. We used logistic regression analyses to investigate the relationship between erectile dysfunction and undiagnosed hypertension, hypercholesterolemia, and diabetes. RESULTS: After multivariate adjustment, men with erectile dysfunction had more than double the odds of having undiagnosed diabetes (odds ratio = 2.20; 95% CI, 1.10-4.37), whereas no association was seen for undiagnosed hypertension or undiagnosed hypercholesterolemia. For the average man aged 40 to 59 years, the predicted probability of having undiagnosed diabetes increased from 1 in 50 in the absence of erectile dysfunction to 1 in 10 in the presence of erectile dysfunction. CONCLUSIONS: Our results underscore the importance of erectile dysfunction as a marker of undiagnosed diabetes. Erectile dysfunction should be a trigger to initiate diabetes screening, particularly among middle-aged men.

Heterosexual couples and prostate cancer support groups: a gender relations analysis.

INTRODUCTION: Men diagnosed with prostate cancer (PCa) can receive supportive care from an array of sources including female partners and prostate cancer support groups (PCSGs). However, little is known about how heterosexual gender relations and supportive care play out among couples who attend PCSGs. Distilling such gender relation patterns is a key to understanding and advancing supportive care for men who experience PCa and their families. PURPOSE: This study describes connections between heterosexual gender relations and PCa supportive care among couples who attend PCSGs. METHOD: In-depth, individual interviews with 30 participants (15 men treated for PCa and their female partners) were analyzed using interpretive descriptive methods. Couples were asked about their relationships, supportive care needs, and attendance at PCSGs. A heterosexual gender relations framework was used to theorize the findings. RESULTS: Findings showed that traditional heterosexual gender relations guided most couples' PCa-related support both in and out of PCSGs. Three themes were inductively derived: "Not pushing too hard"-balancing women's support with men's autonomy, "Confreres"-men supporting men at PCSGs, and "Women are better at reassuring"-support from and for women. CONCLUSIONS: Couples both aligned to and resisted traditional gender roles to accommodate, explain, and rationalize how, as a couple, they approached PCa supportive care needs.

Prostate Cancer Risk Stratification by Digital Histopathology and Deep Learning.

PURPOSE: Prostate cancer (PCa) represents a highly heterogeneous disease that requires tools to assess oncologic risk and guide patient management and treatment planning. Current models are based on various clinical and pathologic parameters including Gleason grading, which suffers from a high interobserver variability. In this study, we determine whether objective machine learning (ML)-driven histopathology image analysis would aid us in better risk stratification of PCa. MATERIALS AND METHODS: We propose a deep learning, histopathology image-based risk stratification model that combines clinicopathologic data along with hematoxylin and eosin- and Ki-67-stained histopathology images. We train and test our model, using a five-fold cross-validation strategy, on a data set from 502 treatment-naïve PCa patients who underwent radical prostatectomy (RP) between 2000 and 2012. RESULTS: We used the concordance index as a measure to evaluate the performance of various risk stratification models. Our risk stratification model on the basis of convolutional neural networks demonstrated superior performance compared with Gleason grading and the Cancer of the Prostate Risk Assessment Post-Surgical risk stratification models. Using our model, 3.9% of the low-risk patients were correctly reclassified to be high-risk and 21.3% of the high-risk patients were correctly reclassified as low-risk. CONCLUSION: These findings highlight the importance of ML as an objective tool for histopathology image assessment and patient risk stratification. With further validation on large cohorts, the digital pathology risk classification we propose may be helpful in guiding administration of adjuvant therapy including radiotherapy after RP.