Low-risk Prostate Cancer Research Articles

Pharmacological targets of SGLT2 inhibition on prostate cancer mediated by circulating metabolites: a drug-target Mendelian randomization study.

The relationship between sodium-glucose cotransporter 2 (SGLT2) inhibitors and prostate cancer is still unknown. Although these inhibitors can influence tumor glycolysis, the underlying mechanism requires further exploration. A two-sample two-step MR was used to determine 1) causal effects of SGLT2 inhibition on prostate cancer; 2) causal effects of 1,400 circulating metabolites or metabolite ratios on prostate cancer; and 3) mediation effects of these circulating metabolites. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene and glycated hemoglobin level (HbA1c). Additionally, positive control analysis on type 2 diabetes mellitus (T2DM) was conducted to test the selection of genetic proxies. Phenome Wide Association Study (PheWAS) and MR-PheWAS analysis were used to explore potential treatable diseases and adverse outcomes of SGLT2 inhibitors. Genetically predicted SGLT2 inhibition (per 1 SD decrement in HbA1c) was associated with reduced risk of T2DM [odds ratio (OR) = 0.66 (95% CI 0.53, 0.82), P = 1.57 × 10-4]; prostate cancer [0.34 (0.23, 0.49), P = 2.21 × 10-8] and prostate-specific antigen [0.26 (0.08, 0.81), P = 2.07 × 10-2]. The effect of SGLT2 inhibition on prostate cancer was mediated by uridine level, with a mediated proportion of 9.34% of the total effect. In MR-PheWAS, 65 traits were found to be associated with SLGT2 inhibitors (P < 1.78 × 10-5), and among them, 13 were related to diabetes. Our study suggested that SGLT2 inhibition could lower prostate cancer risk through uridine mediation. More mechanistic and clinical research is necessary to explore how uridine mediates the link between SGLT2 inhibition and prostate cancer.

The survival outcomes of localized low-risk prostate cancer, a population-based study using NCDB.

The optimal treatment approach for low-risk prostate cancer (LRPC) remains controversial. While active surveillance is an increasingly popular option, definitive local treatments, including radical prostatectomy (RP), external beam radiotherapy (EBRT), and prostate seed implantation (PSI), are also commonly used. This study aimed to evaluate the survival outcomes of patients with LRPC using a large patient population from the National Cancer Database (NCDB). We analyzed data from 195,452 patients diagnosed with LRPC between 2004 and 2015 using the NCDB. Patients were classified based on their treatment modalities, including RP, EBRT, PSI, or no local treatment (NLT). Only patients with Charlson-Deyo comorbidity scores of 0 or 1 were included to ensure comparability. Propensity score analysis was used to balance the treatment groups, and the accelerated failure time model was used to analyze the survival rates of the treatment groups. After a median follow-up of 70.8 months, 24,545 deaths occurred, resulting in an all-cause mortality rate of 13%. RP demonstrated a survival benefit compared with NLT, particularly in patients younger than 74 years of age. In contrast, radiation treatments (EBRT and PSI) did not improve survival in the younger age groups, except for patients older than 70 years for EBRT and older than 65 years for PSI. Notably, EBRT in patients younger than 65 years was associated with inferior outcomes. This study highlights the differences in survival outcomes among LRPC treatment modalities. RP was associated with improved survival compared to NLT, especially in younger patients. In contrast, EBRT and PSI showed survival benefits primarily in the older age groups. NLT is a reasonable choice, particularly in younger patients when RP is not chosen. These findings emphasize the importance of individualized treatment decisions for LRPC management.

The value of synthetic magnetic resonance imaging in the diagnosis and assessment of prostate cancer aggressiveness.

Synthetic magnetic resonance imaging (SyMRI) is a fast, standardized, and robust novel quantitative technique that has the potential to circumvent the subjectivity of interpretation in prostate multiparametric magnetic resonance imaging (mpMRI) and the limitations of existing MRI quantification techniques. Our study aimed to evaluate the potential utility of SyMRI in the diagnosis and aggressiveness assessment of prostate cancer (PCA). We retrospectively analyzed 309 patients with suspected PCA who had undergone mpMRI and SyMRI, and pathologic results were obtained by biopsy or PCA radical prostatectomy (RP). Pathological types were classified as PCA, benign prostatic hyperplasia (BPH), or peripheral zone (PZ) inflammation. According to the Gleason Score (GS), PCA was divided into groups of intermediate-to-high risk (GS ≥4+3) and low-risk (GS ≤3+4). Patients with biopsy-confirmed low-risk PCA were further divided into upgraded and nonupgraded groups based on the GS changes of the RP results. The values of the apparent diffusion coefficient (ADC), T1, T2 and proton density (PD) of these lesions were measured on ADC and SyMRI parameter maps by two physicians; these values were compared between PCA and BPH or inflammation, between the intermediate-to-high-risk and low-risk PCA groups, and between the upgraded and nonupgraded PCA groups. The risk factors affecting GS grades were identified via univariate analysis. The effects of confounding factors were excluded through multivariate logistic regression analysis, and independent predictive factors were calculated. Subsequently, the ADC+Sy(T2+PD) combined models for predicting PCA risk grade or GS upgrade were constructed through data processing analysis. The diagnostic performance of each parameter and the ADC+Sy(T2+PD) model was analyzed. The calibration curve was calculated by the bootstrapping internal validation method (200 bootstrap resamples). The T1, T2, and PD values of PCA were significantly lower than those of BPH or inflammation (P≤0.001) in both the PZ or transitional zone. Among the 178 patients with PCA, intermediate-to-high-risk PCA group had significantly higher T1, T2, and PD values but lower ADC values compared with the low-risk group (P<0.05), and the diagnostic efficacy of each single parameter was similar (P>0.05). The ADC+Sy(T2+PD) model showed the best performance, with an area under the curve (AUC) 0.110 [AUC =0.818; 95% confidence interval (CI): 0.754-0.872] higher than that of ADC alone (AUC =0.708; 95% CI: 0.635-0.774) (P=0.003). Among the 68 patients initially classified as PCA in the low-risk group by biopsy, PCA in the postoperative upgraded GS group had significantly higher T1, T2, and PD values but lower ADC values than did those in the nonupgraded group (P<0.01). In addition, the ADC+Sy(T2+PD) model better predicted the upgrade of GS, with a significant increase in AUC of 0.204 (AUC =0.947; 95% CI: 0.864-0.987) compared with ADC alone (AUC =0.743; 95% CI: 0.622-0.841) (P<0.001). Quantitative parameters (T1, T2, and PD) derived from SyMRI can help differentiate PCA from non-PCA. Combining SyMRI parameters with ADC significantly improved the ability to differentiate between intermediate-to-high risk PCA from low-risk PCA and could predict the upgrade of low-risk PCA as confirmed by biopsy.

The Influence of Disparities on Prostate Cancer at Diagnosis in the Charlotte Metropolitan Area.

Prostate cancer (PCa) is the most diagnosed noncutaneous malignancy and second leading-cause of cancer death in men, yet screening is decreasing. As PCa screening has become controversial, socioeconomic disparities in PCa diagnosis and outcomes widen. This study was designed to determine the current disparities influencing PCa diagnosis in Charlotte, NC. The Levine Cancer Institute database was queried for patients with PCa, living in metropolitan Charlotte. Socioeconomic status (SES) was determined by the Area Deprivation Index (ADI); higher ADI indicated lower SES. Patients were compared by their National Comprehensive Cancer Network risk stratification. Artificial intelligence predictive models were trained and heatmaps were created, demonstrating the geographic and socioeconomic disparities in late-stage PCa. Of the 802 patients assessed, 202 (25.2%) with high-risk PCa at diagnosis were compared with 198 (24.7%) with low-risk PCa. High-risk PCa patients were older (69.8±9.0 vs. 64.0±7.9 years; p<0.001) with lower SES (ADI block: 98.4±20.9 vs. 92.1±19.8; p=0.004) and more commonly African-American (White: 66.2% vs. 78.3%, African-American: 31.3% vs. 20.7%; p=0.009). On regression, ADI block was an independent predictor (odds ratio [OR]=1.013, 95% confidence interval [CI] 1.002-1.024; p=0.024) of high-risk PCa at diagnosis, whereas race was not (OR=1.312, 95% CI 0.782-2.201; p=0.848). A separate regression demonstrated higher ADI (OR=1.016, 95% CI 1.004-1.027; p=0.006) and older age (OR=1.083, 95% CI 1.054-1.114; p<0.001) were independent predictors for high-risk PCa. Findings, depicted in heatmaps, demonstrated the geographic locations where men with PCa were predicted to have high-risk disease based on their age and SES. Socioeconomic status was more closely associated with high-risk PCa at diagnosis than race. Although, of any variable, age was most predictive. The heatmaps identified areas that would benefit from increased awareness, education, and screening to facilitate an earlier PCa diagnosis.

Long-Term Analysis of NRG Oncology RTOG 0415: A Randomized Phase III Noninferiority Study Comparing Two Fractionation Schedules in Patients With Low-Risk Prostate Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.NRG Oncology RTOG 0415 is a randomized phase III noninferiority (NI) clinical trial comparing conventional fractionation (73.8 Gy in 41 fractions) radiotherapy (C-RT) with hypofractionation (H-RT; 70 Gy in 28) in patients with low-risk prostate cancer. The study included 1,092 protocol-eligible patients initially reported in 2016 with a median follow-up of 5.8 years. Updated results with median follow-up of 12.8 years are now presented. The estimated 12-year disease-free survival (DFS) is 56.1% (95% CI, 51.5 to 60.5) for C-RT and 61.8% (95% CI, 57.2 to 66.0) for H-RT. The DFS hazard ratio (H-RT/C-RT) is 0.85 (95% CI, 0.71 to 1.03), confirming NI (P < .001). Twelve-year cumulative incidence of biochemical failure (BF) was 17.0% (95% CI, 13.8 to 20.5) for C-RT and 9.9% (95% CI, 7.5 to 12.6) for H-RT. The HR (H-RT/C-RT) comparing biochemical recurrence between the two arms was 0.55 (95% CI, 0.39 to 0.78). Late grade ≥3 GI adverse event (AE) incidence is 3.2% (C-RT) versus 4.4% (H-RT), with relative risk (RR) for H-RT versus C-RT 1.39 (95% CI, 0.75 to 2.55). Late grade ≥3 genitourinary (GU) AE incidence is 3.4% (C-RT) versus 4.2% (H-RT), RR 1.26 (95% CI, 0.69 to 2.30). Long-term DFS is noninferior with H-RT compared with C-RT. BF is less with H-RT. No significant differences in late grade ≥3 GI/GU AEs were observed between assignments (ClinicalTrials.gov identifier: NCT00331773).

Non-invasively identifying candidates of active surveillance for prostate cancer using magnetic resonance imaging radiomics

Active surveillance (AS) is the primary strategy for managing patients with low or favorable-intermediate risk prostate cancer (PCa). Identifying patients who may benefit from AS relies on unpleasant prostate biopsies, which entail the risk of bleeding and infection. In the current study, we aimed to develop a radiomics model based on prostate magnetic resonance images to identify AS candidates non-invasively. A total of 956 PCa patients with complete biopsy reports from six hospitals were included in the current multicenter retrospective study. The National Comprehensive Cancer Network (NCCN) guidelines were used as reference standards to determine the AS candidacy. To discriminate between AS and non-AS candidates, five radiomics models (i.e., eXtreme Gradient Boosting (XGBoost) AS classifier (XGB-AS), logistic regression (LR) AS classifier, random forest (RF) AS classifier, adaptive boosting (AdaBoost) AS classifier, and decision tree (DT) AS classifier) were developed and externally validated using a three-fold cross-center validation based on five classifiers: XGBoost, LR, RF, AdaBoost, and DT. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE) were calculated to evaluate the performance of these models. XGB-AS exhibited an average of AUC of 0.803, ACC of 0.693, SEN of 0.668, and SPE of 0.841, showing a better comprehensive performance than those of the other included radiomic models. Additionally, the XGB-AS model also presented a promising performance for identifying AS candidates from the intermediate-risk cases and the ambiguous cases with diagnostic discordance between the NCCN guidelines and the Prostate Imaging-Reporting and Data System assessment. These results suggest that the XGB-AS model has the potential to help identify patients who are suitable for AS and allow non-invasive monitoring of patients on AS, thereby reducing the number of annual biopsies and the associated risks of bleeding and infection.

Is MRI ready to replace biopsy during active surveillance?

Active surveillance (AS) is a conservative management option recommended for patients diagnosed with low-risk prostate cancer (PCa) and selected cases with intermediate-risk PCa. The adoption of prostate MRI in the primary diagnostic setting has sparked interest in its application during AS. This review aims to examine the role and performance of multiparametric MRI (mpMRI) across the entire AS pathway, from initial stratification to follow-up, also relative to the utilization of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) criteria. Given the high negative predictive value of mpMRI in detecting clinically significant PCa (csPCa), robust evidence supports its use in patient selection and risk stratification at the time of diagnosis or confirmatory biopsy. However, conflicting results have been observed when using MRI in evaluating disease progression during follow-up. Key areas requiring clarification include addressing the clinical significance of MRI-negative csPCa, optimizing MRI quality, determining the role of biparametric MRI (bpMRI) or mpMRI protocols, and integrating artificial intelligence (AI) for improved performance. CLINICAL RELEVANCE STATEMENT: MRI plays an essential role in the selection, stratification, and follow up of patients in active surveillance (AS) for prostate cancer. However, owing to existing limitations, it cannot fully replace biopsies in the context of AS. KEY POINTS: Multiparametric MRI (mpMRI) has become a crucial tool in active surveillance (AS) for prostate cancer (PCa). Conflicting results have been observed regarding multiparametric MRI efficacy in assessing disease progression. Standardizing MRI-guided protocols will be critical in addressing current limitations in active surveillance for prostate cancer.

Association of Baseline Magnetic Resonance Imaging Prostate Imaging Reporting and Data System Score With Prostate Cancer Active Surveillance Early Biopsy Reclassification: Data From the Michigan Urological Surgery Improvement Collaborative (MUSIC).

The purpose of our study was to evaluate the association of baseline MRI Prostate Imaging Reporting and Data System (PI-RADS) score with biopsy reclassification in a multicenter active surveillance (AS) cohort. We identified men in the Michigan Urological Surgery Improvement Collaborative registry (46 hospital-based/academic/private practice urology groups) with National Comprehensive Cancer Network (NCCN) low-risk and favorable intermediate-risk prostate cancer who underwent MRI within 6 months before or after initial biopsy and enrolled in AS from June 2016 to January 2021. The primary objective was to determine the association of baseline MRI PI-RADS score (≥4 lesion) with reclassification to high-grade prostate cancer (≥grade group 3) on surveillance biopsy. Multivariable Cox proportional hazards regression models were constructed and adjusted for pathologic, MRI, and clinical/biopsy factors, with landmark time of 6 months from diagnostic biopsy. We included an interaction term between PI-RADS score and NCCN group in the Cox model. A total of 1491 men were included with median age 64 years (IQR: 59-69) with median follow-up 11.0 months (IQR: 6.0-23.0) after landmark. Baseline PI-RADS ≥ 4 lesion was associated with an increased hazard of biopsy reclassification (HR: 2.3 [95% CI: 1.6-3.2], P < .001), along with grade group 2 vs 1 (HR: 2.5 [95% CI: 1.7-3.7], P < .001), and increasing age (per 10 years; HR: 1.8 [95% CI: 1.4-2.4], P < .001). The interaction between NCCN risk group with MRI findings was not significant (P = .7). In this multicenter cohort study of real-world data, baseline MRI PI-RADS score was significantly associated with early biopsy reclassification in men undergoing AS with NCCN low- or favorable intermediate-risk prostate cancer.

Understanding Prostate Cancer: Causes, Risks, Diagnosis, and Treatment

Prostate cancer is the most common cancer among men after skin cancer. Most men who get prostate cancer don't die from it. More than 90% of men diagnosed with prostate cancer survive for at least five years. If detected early, while the tumor has not spread outside of the prostate, the survival rate is nearly 100% with treatment. Early-stage prostate cancer rarely causes symptoms, symptoms develop after the disease progresses. Prostate-specific antigen (PSA) blood test and digital rectal exam (DRE) are common screening methods for prostate cancer. However, whether or not to use these screening techniques is still controversial. Active surveillance is a strategy for managing low-risk prostate cancer without immediate treatment. The idea is to avoid unnecessary side effects by carefully watching how the cancer develops over time.

Genetically predicted 91 circulating inflammatory proteins in relation to risk of urological malignancies: a Mendelian randomization study.

Urological malignancies, including kidney, bladder, and prostate cancer, are major health concerns worldwide. Inflammation has been implicated in the pathogenesis of these cancers, and circulating inflammatory proteins may play a role in their development. However, the causal relationship between specific plasma proteins and urological malignancies remains unclear. We performed a two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS). Instrumental variables representing genetic variants associated with circulating inflammatory proteins were used to infer causality on the risk of kidney, bladder, and prostate cancer. Four MR methods were utilized to provide robust effect estimates. Our analysis identified several plasma proteins associated with a lower risk of kidney and bladder cancer, including Eukaryotic translation initiation factor 4E-binding protein 1, Caspase 8, Natural killer cell receptor 2B4, and Tumor necrosis factor ligand superfamily member 12. However, after adjusting for multiple testing, these associations did not remain statistically significant. For prostate cancer, CUB domain-containing protein 1 and Interleukin-10 receptor subunit beta were found to be protective, while Glial cell line-derived neurotrophic factor and SIR2-like protein 2 were identified as risk factors. After FDR adjustment, none of the inflammatory proteins were found to be significantly associated with a lower risk of prostate cancer. Our findings suggest that certain plasma proteins may be involved in the development of urological malignancies. Mendelian randomization provides a useful framework for investigating causal relationships between inflammatory proteins and urological cancers, offering potential insights into their underlying biology and therapeutic targets.

Estimating the Effect of Radical Prostatectomy: Combining Data From the SPCG4 and PIVOT Randomized Trials With Contemporary Cohorts.

Two randomized trials (SPCG4 and PIVOT) have compared surgery to conservative management for localized prostate cancer. The applicability of these trials to contemporary practice remains uncertain. We aimed to develop an individualized prediction model for prostate cancer mortality comparing immediate surgery at a high-volume center to active surveillance. We determined whether the relative risk of prostate cancer mortality with surgery vs observation varied by baseline risk. We then used various estimates of relative risk to estimate 15-year mortality with and without surgery using, as a predictor, risk of biochemical recurrence calculated from a model. We saw no evidence that relative risk varied by baseline risk, supporting the use of a constant relative risk. Compared with observation, surgery was associated with negligible benefit for patients with Grade Group (GG) 1 disease (0.2% mortality reduction at 15 years) and small benefit for patients with GG2 with lower PSA and stage (≤5% mortality reduction). Benefit was greater (6%-9%) for patients with GG3 or GG4 though still modest, but effect estimates varied widely depending on choice of hazard ratio for surgery (6%-36% absolute risk reduction). Surgery should be avoided for men with low-risk (GG1) prostate cancer and for many men with GG2 disease. Surgical benefits are greater in men with higher-risk disease. Integration of findings with a life expectancy model will allow patients to make informed treatment decisions given their oncologic risk, risk of death from other causes, and estimated effects of surgery.

A randomized, double-blind, placebo-controlled trial of metformin in reducing progression among men on expectant management for low-risk prostate cancer: The MAST (Metformin Active Surveillance Trial) study.

LBA5002 Background: Active Surveillance (AS) involves vigilant monitoring of selected prostate cancer (PCa) patients, with radical treatment initiation upon significant disease progression. AS eligibility varies, generally including low-risk PCa men. Metformin, a widely-used oral hypoglycemic agent, is known for its excellent tolerability and efficacy in diabetes management. Extensive preclinical data suggested that metformin may slow PCa progression. The purpose of this study is to examine the effect of metformin on the rates of progression among men with low-risk localized PCa on AS. Methods: A randomized double blind placebo controlled trial was carried out in 14 centres across Canada.Eligible patients had biopsy-proven, low-risk, localized PCa diagnosed within the past 6 months, with a Gleason score of &lt;6 observed in ≤1/3 of the total cores, less than 50% positivity in any one core, a PSA level of ≤10 ng/ml, and a clinical stage between T1c-T2a. Additionally, they chose active surveillance as their primary treatment. Subjects that met eligibility criteria were randomly assigned (1:1) to receive metformin 850 mg BID or placebo for 3 years. All patients underwent repeat prostate biopsy at 18 and 36 months. The primary endpoint indicated was time to progression, defined as the earliest occurrence of primary PCa therapy (e.g., prostatectomy, radiation, hormonal therapy) or pathological progression (&gt;1/3 of total cores involved, at least 50% of any one core involved, or Gleason pattern 4 or higher). Results: In our cohort of 407 patients, 204 were administered metformin, and 203 received a placebo. The median age of the overall cohort was 63 years. Out of the total 407 patients, 141 experienced disease progression. There was no statistically significant difference in progression-free survival (PFS) observed between patients treated with metformin and those receiving placebo (p=0.63). Conclusions: Despite tantalizing preclinical and epidemiological data, metformin consumption does not alter rates of progression among men with low risk PCa on AS. Clinical trial information: NCT01864096 .

Blood metabolites mediate the causal relationship between circulating CX3CL1 levels and prostate cancer: A 2-step Mendelian randomization study.

Chemokines influence the progression of prostate cancer (PCa) through multiple mechanisms. However, the effect of C-X3-C chemokine ligand 1 (CX3CL1) on PCa risk remains controversial. Our study aimed to investigate whether circulating CX3CL1 is causally associated with PCa and to identify metabolites that have mediating effects using the 2-step bidirectional Mendelian randomization (MR) analysis process. Inverse variance weighting (IVW) results were used as the primary observations, while additional sensitivity analyses were conducted. For each standard deviation increase exhibited by the circulating CX3CL1 levels, the risk of PCa was reduced by 0.4% (IVW: OR = 0.996, [95% CI = 0.994-0.998], P < .001), and blood alliin levels increased by 19% (IVW: OR = 1.185, [95% CI = 1.01-1.54], P = .003). For each standard deviation increase in the blood alliin levels, the risk of PCa was reduced by 0.1% (IVW: OR = 0.999, [95% CI = 0.997-0.999], P = .03). Therefore, the protective effect of circulating CX3CL1 on PCa may be mediated by blood alliin levels (mediated proportion = 6.7%). The results supported the notion that high levels of circulating CX3CL1 indicate a lower PCa risk and the idea that the food-derived antioxidant alliin may mediate this association. We emphasize that the use of CX3CL1 as a protective factor against PCa may provide new strategies for PCa prevention and care in the future.

Urinary extracellular vesicle-derived miR-126-3p predicts lymph node invasion in patients with high-risk prostate cancer

To investigate extracellular vesicles (EVs), biomarkers for predicting lymph node invasion (LNI) in patients with high-risk prostate cancer (HRPCa), plasma, and/or urine samples were prospectively collected from 45 patients with prostate cancer (PCa) and five with benign prostatic hyperplasia (BPH). Small RNA sequencing was performed to identify miRNAs in the EVs. All patients with PCa underwent radical prostatectomy and extended pelvic lymph node dissection. Differentially expressed miRNAs were identified in patients with and without pathologically-verified LNI. The candidate miRNAs were validated in low-risk prostate cancer (LRPCa) and BPH. Four miRNA species (e.g., miR-126-3p) and three miRNA species (e.g., miR-27a-3p) were more abundant in urinary and plasma EVs, respectively, of patients with PCa. None of these miRNA species were shared between urinary and plasma EVs. miR-126-3p was significantly more abundant in patients with HR PCa with LNI than in those without (P = 0.018). miR-126-3p was significantly more abundant in the urinary EVs of patients with HRPCa than in those with LRPCa (P = 0.017) and BPH (P = 0.011). In conclusion, urinary EVs-derived miR-126-3p may serve as a good biomarker for predicting LNI in patients with HRPCa.

Natural History of Nonmetastatic Prostate Cancer Managed With Watchful Waiting

It is uncertain to what extent watchful waiting (WW) in men with nonmetastatic prostate cancer (PCa) and a life expectancy of less than 10 years is associated with adverse consequences. To report transitions to androgen deprivation therapy (ADT), castration-resistant prostate cancer (CRPC), death from PCa, or death from other causes in men treated with a WW strategy. This nationwide, population-based cohort study included men with nonmetastatic PCa diagnosed since 2007 and registered in the National Prostate Cancer Register of Sweden with WW as the primary treatment strategy and with life expectancy less than 10 years. Life expectancy was calculated based on age, the Charlson Comorbidity Index (CCI), and a drug comorbidity index. Observed state transition models complemented observed data to extend follow-up to more than 20 years. Analyses were performed between 2022 and 2023. Nonmetastatic PCa. Transitions to ADT, CRPC, death from PCa, and death from other causes were measured using state transition modeling. The sample included 5234 men (median [IQR] age at diagnosis, 81 [79-84] years). After 5 years, 954 men with low-risk PCa (66.2%) and 740 with high-risk PCa (36.1%) were still alive and not receiving ADT. At 10 years, the corresponding proportions were 25.5% (n = 367) and 10.4% (n = 213), respectively. After 10 years, 59 men with low-risk PCa (4.1%) and 221 with high-risk PCa (10.8%) had transitioned to CRPC. Ten years after diagnosis, 1330 deaths in the low-risk group (92.3%) and 1724 in the high-risk group (84.1%) were from causes other than PCa. These findings suggest that the WW management strategy is appropriate for minimizing adverse consequences of PCa in men with a baseline life expectancy of less than 10 years.

Lifetime Health and Economic Outcomes of Biparametric Magnetic Resonance Imaging as First-Line Screening for Prostate Cancer : A Decision Model Analysis.

Contemporary prostate cancer (PCa) screening uses first-line prostate-specific antigen (PSA) testing, possibly followed by multiparametric magnetic resonance imaging (mpMRI) for men with elevated PSA levels. First-line biparametric MRI (bpMRI) screening has been proposed as an alternative. To evaluate the comparative effectiveness and cost-effectiveness of first-line bpMRI versus PSA-based screening. Decision analysis using a microsimulation model. Surveillance, Epidemiology, and End Results database; randomized trials. U.S. men aged 55 years with no prior screening or PCa diagnosis. Lifetime. U.S. health care system. Biennial screening to age 69 years using first-line PSA testing (test-positive threshold, 4 µg/L) with or without second-line mpMRI or first-line bpMRI (test-positive threshold, PI-RADS [Prostate Imaging Reporting and Data System] 3 to 5 or 4 to 5), followed by biopsy guided by MRI or MRI plus transrectal ultrasonography. Screening tests, biopsies, diagnoses, overdiagnoses, treatments, PCa deaths, quality-adjusted and unadjusted life-years saved, and costs. For 1000 men, first-line bpMRI versus first-line PSA testing prevented 2 to 3 PCa deaths and added 10 to 30 life-years (4 to 11 days per person) but increased the number of biopsies by 1506 to 4174 and the number of overdiagnoses by 38 to 124 depending on the biopsy imaging scheme. At conventional cost-effectiveness thresholds, first-line PSA testing with mpMRI followed by either biopsy approach for PI-RADS 4 to 5 produced the greatest net monetary benefits. First-line PSA testing remained more cost-effective even if bpMRI was free, all men with low-risk PCa underwent surveillance, or screening was quadrennial. Performance of first-line bpMRI was based on second-line mpMRI data. Decision analysis suggests that comparative effectiveness and cost-effectiveness of PCa screening are driven by false-positive results and overdiagnoses, favoring first-line PSA testing with mpMRI over first-line bpMRI. National Cancer Institute.

Time-to-first treatment for new cancer diagnoses before and during the COVID-19 pandemic in Manitoba, Canada.

e23103 Background: Disruptions to health care during the COVID-19 pandemic raises the possibility of delays in treatment for individuals diagnosed with cancer. It is critical that we evaluate the association between the COVID-19 pandemic and time-to-first treatment (TTFT) to address public and patient anxiety, inform recovery efforts, and identify strategies to reduce the cancer system’s vulnerability to future disruptions. Objective: To examine the association between the COVID-19 pandemic and time from cancer diagnosis to first treatment in Manitoba, Canada. Methods: A retrospective, population-based, quasi-experimental study that included individuals diagnosed with breast, colon, rectal, hematologic, lung, or prostate cancer between January 2015 and December 2021 was performed. Interrupted time series analyses with competing risk models were used to compare TTFT for those diagnosed before and after the start of the pandemic. Time-to-first treatment was calculated from diagnosis date to first treatment date (i.e., chemotherapy, hormone therapy, immunotherapy, radiotherapy, or surgery). Death without treatment was included as a competing risk. Follow-up time was censored at three months post-diagnosis. Sub-hazard ratios (SHR) and 95% confidence intervals (CI) were reported. Higher SHR indicates earlier treatment. The delta restricted mean time-to-treatment (D_RMTT) at three months was calculated to complement SHR values, where negative times indicate earlier treatment. Since observation is standard of care for low-risk prostate cancer and androgen deprivation therapy was widely used to temporize intermediate and high-risk prostate cancer patients, analyses were restricted to stage IV prostate cancer. Results: Time-to-first treatment was shorter for individuals diagnosed with breast cancer during the COVID-19 pandemic period (SHR: 1.40; 95% CI 1.24-1.57; D_RMTT: -6.6 days). Time-to-first treatment was also shorter for individuals diagnosed with colon cancer from April 2020 to June 2021 (SHR: 1.25; 95% CI 1.09-1.42; D_RMTT: -6.5 days) but not from July 2021 to December 2021 (SHR: 0.96; 95% CI 0.81-1.15; D_RMTT: 1.2 days). All other analyses did not demonstrate a statistically significant change in TTFT: rectal cancer (SHR: 1.00; 95% CI: 0.83-1.21; D_RMTT: 0.0 days), hematological cancers (SHR: 0.87; 95% CI: 0.74-1.01; D_RMTT:3.9 days); lung cancer (SHR: 1.09; 95% CI: 0.97-1.23; D_RMTT: -2.3 days); and stage IV prostate cancer (SHR: 1.15; 95% CI: 0.89-1.49; D_RMTT: -4.1 days). Conclusions: The COVID-19 pandemic has not increased the time from diagnosis date to first treatment date for individuals diagnosed with breast, colon, rectal, hematologic, lung, or stage IV prostate cancer in Manitoba, Canada.

Management outcomes of localized low-risk prostate cancer: A population-based study.

Management outcomes of localized low-risk prostate cancer: A population-based study.

Association between the serum uric acid levels and prostate cancer: evidence from National Health and Nutrition Examination Survey (NHANES) 1999-2010.

Uric acid may play a critical role in protection against cancer by the suppression of inflammation. The association between serum uric acid (SUA) levels and prostate cancer risk is debatable yet has received little attention in the American population. Therefore, we used data from the National Health and Nutrition Examination Survey (NHANES) to determine their correlation. Using information from NHANES 1999-2010, a total of 62,160 individuals from the general population were included in this cross-sectional study. Additionally, a number of covariates were acquired. Prostate cancer was used to divide the participants into two groups: prostate cancer group (n=315) and non-prostate cancer group (n=7,545). A weighted adjusted logistic regression analysis was conducted to examine the potential correlation between SUA and prostate cancer. Our study comprised a total of 7,860 participants. After full adjustment for confounders, SUA was not significantly associated with prostate cancer [odds ratio (OR) 0.91, 95% confidence interval (CI): 0.82-1.00, P=0.058]. In participants aged 60 years and above (≥60 years), a higher SUA was significantly associated with a lower risk of prostate cancer (OR 0.88, 95% CI: 0.80-0.96, P=0.003). However, among those younger than 60 years (<60 years), there was no association between SUA and prostate cancer risk (OR 1.29, 95% CI: 0.69-2.42, P=0.42). In addition, in the subgroup analysis stratified by body mass index, hypertension and diabetes, there was no significant correlation between SUA and prostate cancer. SUA is negatively associated with the risk of prostate cancer in older men, especially for those 60 years of age and beyond.

Targeted microwave ablation for prostate cancer (FOSTINE1b): a prospective 'ablate-and-resect' study.

To assess histopathological outcomes, as well as feasibility and safety of targeted microwave ablation (TMA) via the Trinity® system (KOELIS, La Tronche, France). Prospective, single-institution, interventional Phase IIa study with an 'ablate-and-resect' design. In all, 11 patients diagnosed with localised prostate cancer (PCa) underwent TMA via the Trinity system under conscious sedation in an outpatient setting using a single transrectal TATO® 18-G antenna with different treatment regimens. Magnetic resonance imaging (MRI) and robot-assisted radical prostatectomy (RARP) were conducted at 7 days and 1 month after TMA, respectively. Nine patients received RARP, and two patients chose to withdraw their consent following TMA. These men chose an active surveillance protocol upon confirmation of a low-risk prostate cancer diagnosis. Functional outcomes and adverse events were evaluated at baseline and follow-up visits using validated questionnaires. Prostate volumetry and confirmation of necrosis were carried out through MRI and whole-mount histopathological examination. The TMA was successfully executed, and all patients were discharged on the same day. No severe adverse events (Common Terminology Criteria for Adverse Events Grade ≥3) were reported at the 7-day and 1-month follow-up visits. Additionally, no declines were observed in urinary, sexual and ejaculation functional outcomes. T1-weighted MRI revealed clear and well-defined ablation zones. The RARP was executed without difficulty, particularly during the dissection of the posterior plane. As a result, no intraoperative complications were encountered. Histopathological assessment on surgical specimens confirmed the absence of viable cells, indicating complete necrosis of the ablative zone if a power intensity >10 W was used during TMA. Ablation zone volumetry revealed no notable distinctions between the three-dimensional segmentation of the virtual ablation zone at TMA (median volume: 2 mL) and MRI (median volume: 1.923 mL). Conversely, a significant reduction was noted in the surgical specimen (median volume: 0.221 mL). Targeted microwave ablation via the Trinity system for localised PCa treatment proves to be a secure and feasible procedure, with complete necrosis evidence within the ablation zone on surgical specimens.