The impact of surgical downgrading on prostate cancer recurrence: systematic review and analysis of a multiethnic population.

OBJECTIVE: To perform a systematic review and a retrospective cohort analysis evaluating the rates of surgical downgrading of prostate cancer (PCa) from biopsy (PBx) to radical prostatectomy (RP), and their association with biochemical recurrence (BCR) in a multiethnic population. METHODS: A systematic review of PubMed and other databases was performed. We included retrospective studies evaluating the relationship between surgical downgrading and BCR-free survival. Data regarding Gleason score (GL) downgrading were abstracted from the articles and categorized as follows: GL8-10 to GL7, GL7 to GL6, and GL 7(4 + 3) to GL7(3 + 4). We also performed a retrospective cohort review of patients who underwent RP at our institution from 2005 through 2020. Kaplan-Meier survival analysis and Cox proportional hazards models were used to compare BCR among downgraded versus non-downgraded men. RESULTS: Systematic review yielded 137 abstracts; of these, 36 full-texts were reviewed, 8 of which were included in our systematic review. Despite substantial variability, all showed that GL at RP is one of the most important factors of BCR-free survival. A total of 1,484 men with PCa were analyzed from our institution. On multivariate analysis, GL7 to GL6 downgrading (HR = 0.50, p = 0.022) and GL8-10 to GL7 downgrading (HR = 0.42, p = 0.011) were associated with reduced risk of BCR when compared to men with GL7 and GL8-10 concordance, respectively. However, GL7(4 + 3) to GL7(3 + 4) downgrading was not significantly associated with reduced BCR (HR = 0.56, p = 0.12), when compared to GL7(4 + 3) concordance, although HR was similar. CONCLUSION: Surgical downgrading at RP was associated with a reduced risk of BCR compared to GL concordant disease, and these findings have been validated within our multiethnic population. Pathologic downgrading at the time of RP may be a more useful predictor of subsequent BCR in comparison to that associated with GL concordant pathology.

Association of Obesity and Diabetes With Prostate Cancer Risk Groups in a Multiethnic Population.

INTRODUCTION: Obesity and diabetes mellitus (DM) have been associated with prostate cancer (PCa) risk, but data examining their combined effects on aggressive PCa are sparse, particularly among non-Hispanic Black and Hispanic men. We investigated the associations of obesity and DM in relation to National Comprehensive Cancer Network (NCCN) PCa risk groups in a racially-diverse patient population. PATIENTS AND METHODS: We abstracted demographic and clinical data from men who underwent radical prostatectomy at our institution between 2005 and 2019. Patients were classified into three NCCN PCa risk-groups: low, intermediate and high-risk. Logistic regression models were used to examine the independent and combined associations of body mass index (BMI)/obesity and DM with risks of intermediate and high-risk PCa, adjusting for age and race/ethnicity. RESULTS: A total of 1303 men with PCa (average age 60 ± 6.9 years) were analyzed. The majority were non-Hispanic Black (N = 493, 38%) or Hispanic (N = 407, 31%). The prevalence of obesity (BMI ≥ 30 kg/m2) and DM was 29.3% (N = 382) and 28.3% (N = 369), respectively. In multivariate analyses, obesity was independently associated with an odds ratio (OR) = 2.21 of high-risk PCa (95% CI: 1.28-3.81), while DM was associated with an OR = 1.49 (95% CI: 1.05-2.11) of intermediate-risk PCa. Compared to non-obese men without diabetes, men with BMI ≥ 30 and DM had increased risks of both intermediate (OR = 1.93; 95% CI 1.12-3.43) and high-risk PCa (OR = 2.40; 95% CI 1.22-4.73). Interestingly, most of the association of high-risk PCa was driven by obesity. CONCLUSION: In this multiethnic population both obesity and DM were independently associated with intermediate- and high-risk PCa; however, most of the association for high-risk cancer was driven by obesity. Our results corroborate findings that obesity increases the risk of aggressive PCa; however, results regarding DM need to be confirmed in other large multiethnic populations.

Dynamic beam filtering for miscentered patients.

PURPOSE: Accurate centering of the patient within the bore of a CT scanner takes time and is often difficult to achieve precisely. Patient miscentering can result in significant dose and image noise penalties with the use of traditional bowtie filters. This work describes a system to dynamically position an x-ray beam filter during image acquisition to enable more consistent image performance and potentially lower dose needed for CT imaging. METHODS: We propose a new approach in which two orthogonal low-dose scout images are used to estimate a parametric model of the object describing its shape, size, and location within the field of view (FOV). This model is then used to compute an optimal filter motion profile by minimizing the variance of the expected detector fluence for each projection. Dynamic filtration was implemented on a cone-beam CT (CBCT) test bench using two different physical filters: 1) an aluminum bowtie and 2) a structured binary filter called a multiple aperture device (MAD). Dynamic filtration performance was compared to a static filter in studies of dose and reconstruction noise as a function of the degree of miscentering of a homogeneous water phantom. RESULTS: Estimated filter trajectories were found to be largely sinusoidal with an amplitude proportional to the amount of miscentering. Dynamic filtration demonstrated an improved ability to keep the spatial distribution of dose and reconstruction noise at baseline levels across varying levels of miscentering, reducing the maximum noise and dose deviation from 53% to 15% and 42% to 14% respectively for the bowtie filter, and 25% to 8% and 24% to 15% respectively for the MAD filter. CONCLUSION: Dynamic positioning of beam filters during acquisition improves dose utilization and image quality over static filters for miscentered patients. Such dynamic filters relax positioning requirements and have the potential to reduce set-up time and lower dose requirements.

Dynamic fluence field modulation for miscentered patients in computed tomography.

Traditional CT image acquisition uses bowtie filters to reduce dose, x-ray scatter, and detector dynamic range requirements. However, accurate patient centering within the bore of the CT scanner takes time and is often difficult to achieve precisely. Patient miscentering combined with a static bowtie filter can result in significant increases in dose, reconstruction noise, and CT number variations, and consequently raise overall exposure requirements. Approaches to estimate the patient position from scout scans and perform dynamic spatial beam filtration during acquisition are developed and applied in physical experiments on a CT test bench using different beam filtration strategies. While various dynamic beam modulation strategies have been developed, we focus on two approaches: (1) a simple approach using attenuation-based beam modulation using a translating bowtie filter and (2) dynamic beam modulation using multiple aperture devices (MADs)-an emerging beam filtration strategy based on binary filtration of the x-ray beam using variable width slits in a high-density beam blocker. Improved dose utilization and more consistent image performance with respect to an unmodulated baseline (static filter) are demonstrated for miscentered objects and dynamic beam filtration in physical experiments. For a homogeneous object miscentered by 4 cm, the dynamic filter reduced the maximum regional noise and dose penalties (compared with a centered object) from 173% to 16% and 42% to 14%, respectively, for a traditional bowtie, 29% to 8% and 24% to 15%, respectively, for a single MAD, and 275% to 11% and 56% to 18%, respectively, for a dual-MAD filter. The proposed methodology has the potential to relax patient centering requirements within the scanner, reduce setup time, and facilitate additional CT dose reduction.