Risk-adapted prostate cancer screening-update 2021

Purpose18F-DCFPyL prostate-specific membrane antigen (PSMA) PET/CT is commonly applied to locate lesions of prostate cancer (PCa), but its diagnostic function of quantitative parameters is ignored. Our study evaluates the parameters of intraprostatic PSMA uptake in patients newly diagnosed with PCa and explores their predictive value in risk classification, which is similar to D’Amico criteria.Materials and MethodsWe quantified the maximal standardized uptake value (SUVmax), mean SUV (SUVmean), total lesion (TL)-PSMA, prostate/muscle (P/M) ratio of the primary tumor, and PSMA-derived tumor volume (PSMA-TV) from 62 patients with histologically proven PCa. Patients newly diagnosed with PCa were allocated into risk groups (at low, intermediate, and high risk, respectively) in accordance with D’Amico criteria. Afterwards, the five parameters mentioned above among three different risk groups were compared, and their predictive values in the risk classification of PCa were explored.ResultsSignificantly decreased levels of SUVmax, SUVmean, TL-PSMA, and P/M ratio were observed in the risk groups of low or intermediate or both, compared with the high-risk group. However, only the P/M ratio significantly elevated in patients with intermediate risk [mean ± SD (median): 46.58 ± 9.74 (45.27), P = 0.042] or high risk [98.95 ± 38.83 (97.52), P < 0.001], compared with low-risk patients [12.33 ± 5.93 (9.81)]. When P/M ratio was used to distinguish between low-risk and intermediate-risk patients, its c-statistics was 0.660. On the other hand, when distinguishing between intermediate-risk and high-risk groups, the c-statistics of P/M ratio was 0.667. Finally, when P/M ratio was used to distinguish between low-risk and high-risk patients, the c-statistics was 0.969. P/M ratio had a positive correlation with prostate-specific antigen in all enrolled PCa patients.ConclusionThe quantitative parameters of 18F-DCFPyL PET/CT, including SUVmax, SUVmean, and P/M ratio, might assist in distinguishing low-risk or intermediate-risk groups from the high-risk group. Of these parameters, P/M ratio appears to be the better promising parameter for risk classification of prostate cancer than SUVmax.

Objective: To investigate the prognostic value of SYNTAX score on 1 year outcome in coronary heart disease patients underwent percutaneous coronary intervention(PCI). Methods: The present study (PANDA Ⅲ trial) was a perspective, multi-center, randomized controlled trial. Between December 2013 and August 2014, 2 348 patients who underwent PCI from 46 centers were enrolled. SYNTAX score was calculated from all patients. Patients were divided into 3 groups based on SYNTAX score: lower risk group (SYNTAX score≤22, 1 777 patients), intermediate risk group (SYNTAX score 23-32, 412 patients), and higher risk group (SYNTAX score≥33, 159 patients). The patients were followed up after the procedure for one year.Primary endpoint was target lesion failure (TLF), including cardiac death, target vessel myocardial infarction,and ischemia driven target lesion revascularization. Secondary endpoints included stent thrombosis and major adverse cardiac events were defined as a composite of all-cause death, myocardial infarction and any revascularization. Results: (1) A total of 1 766 (99.2%), 411 (99.8%),and 159 (100%) patients in the lower risk group, intermediate risk and higher risk group completed the 1 year follow up. (2) Incidence of TLF were 5.6%(99/1 763) in lower risk group, 8.8%(36/411) in intermediate risk group,and 8.8%(14/159) in higher risk group(P=0.03). The incidence of target vessel myocardial infarction in lower risk group was 3.9%(68/1 763), 6.6%(27/411) in intermediate risk group,and 7.5% (12/159) in higher risk group(P=0.01).Prevalence of cardiac death and ischemia driven target lesion revascularization was similar among the 3 groups(P>0.05).(3) The probable stent thrombosis events rate was 0.1% (1/1 763), 0.7% (3/411), and 0.6% (1/159) in the lower, intermediate,and higher risk groups respectively (P=0.02). The incidence of major adverse cardiac events was 8.1% (142/1 763) in lower-risk group, 11.7% (48/411) in intermediate risk group, and 14.5% (23/159) in higher risk group (P<0.01). The incidence of all-cause death was 1.7%(30/1 763) in lower-risk group, 1.7%(7/411) in intermediate risk group, and 6.3%(10/159)in higher risk group (P<0.01). The incidence of myocardial infarction was 4.2% (74/1 763) in lower-risk group, 6.6% (27/411) in intermediate risk group, and 8.2% (13/159) in higher risk group(P=0.02).Incidence of any revascularization was similar among groups(P=0.59). (4) The multivariable Cox analysis showed that age (HR=1.04, 95%CI 1.02-1.06, P<0.01), total implanted stent length (HR=1.01, 95%CI 1.00-1.02, P=0.03), and baseline SYNTAX score (HR=1.02, 95%CI 1.02-1.04, P=0.02) were independent risk factors of TLF after PCI in this patient cohort. Conclusion: The SYNTAX score is a valuable tool for predicting prognosis on 1 year in coronary heart disease patients underwent PCI. Trial Registration www.clinicaltrials.gov, NCT02017275.

CONTROVERSIES IN PROSTATE CANCER SCREENING

Prostate cancer (PCa) as one of the most prevalent malignancies in men. We introduced a non-invasive quantitative measurement of intraprostatic fat content based on magnetic resonance proton density fat fraction (PDFF) imaging. The study aims to determine the fat fraction (FF) of PCa using proton density magnetic resonance imaging (MRI), gather clinical and routine MRI characteristics, and identify risk factors for high-risk PCa through multifactorial logistic regression. Clinical and imaging data from 191 pathologically confirmed PCa patients were collected. Patients were stratified based on Gleason score (GS), with 63 in the intermediate- and low-risk group (GS =3+3, 3+4) and 128 in the high-risk group (GS ≥4+3). All patients underwent routine prostate MRI and FF imaging. Clinical and imaging data related to PCa were analyzed, including age, body mass index (BMI), prostate volume (PV) measured by MRI, smoking history, alcohol history, diabetes history, serum prostate-specific antigen (PSA) level, apparent diffusion coefficient (ADC) value, T2 signal intensity (T2SI), Prostate Imaging Reporting and Data System 2.1 (PI-RADS 2.1) score, GS, lesion FF, whole gland FF, periprostatic fat thickness (PPFT), and subcutaneous fat thickness (SFT). Independent risk factors for stratifying PCa risk were identified through multivariate logistic regression analysis, and a predictive model was established. Receiver operating characteristic (ROC) curve analysis was conducted for visual analysis. Significant differences were found in BMI, PV, PSA, tumor ADC value, standard T2SI, PI-RADS score, lesion FF, and PPFT between low- and medium-risk and high-risk groups (P<0.05). No significant differences were observed in age, smoking history, drinking history, diabetes history, and SFT between the two groups (P>0.05). GS correlated significantly with FF (ρ=0.6, P<0.001), PSA (ρ=0.432, P<0.001), ADC value (ρ=-0.379, P<0.001), and PI-RADS (ρ=0.366, P<0.001). Multiple logistic regression analysis revealed that an increase in FF, a PI-RADS score increase of 5 points, and a decrease in ADC value and PV were independent predictors of high-risk PCa (P<0.05). The ROC curve showed that the best cut-off value for the model was 0.67, with an area under the curve (AUC) of 0.907, sensitivity of 78.1%, and specificity of 88.9%. The FF of PCa determined by proton density MRI is significantly associated with GS, serving as an independent predictor of high-risk PCa.

The Prostate cancer Intervention Versus Observation Trial:VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): Design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer

At present, increased early detection of prostate cancer appears to be the most feasible way to reduce cancer-related mortality. As a result significant efforts have been made to identify more men with curable cancer. This article reviews the role of serum prostate-specific antigen in an early detection or screening strategy and describes efforts to enhance the specificity of prostate-specific antigen testing.

To evaluate the clinical benefit of tumor contact length as a predictor of pathological extraprostatic extension and biochemical recurrence in patients undergoing prostatectomy. A total of 91 patients who underwent 3T multiparametric magnetic resonance imaging before prostatectomy from April 2014 to July 2019 were included. A total of 94 prostate cancer foci were analyzed retrospectively. We evaluated maximum tumor contact length, which was determined to be the maximum value in the three-dimensional directions, as a predictor of pathological extraprostatic extension and biochemical recurrence. A total of 19 lesions (20.2%) had positive pathological extraprostatic extension. Areas under the curves showed maximum tumor contact length to be a significantly better parameter to predict pathological extraprostatic extension than the Prostate Imaging Reporting and Data System (P=0.002), tumor maximal diameter (P=0.001), prostate-specific antigen (P=0.020), Gleason score (P<0.001), and clinical Tstage (P<0.001). Multivariate analysis showed maximum tumor contact length (P=0.003) to be an independent risk factor for predicting biochemical recurrence. We classified the patients using preoperative factors (prostate-specific antigen >10, Gleason score >3+4 and maximum tumor contact length >10mm) into three groups: (i) high-risk group (patients having all factors); (ii) intermediate-risk group (patients having two of three factors); and (iii) low-risk group (patients having only one or none of the factors). Kaplan-Meier curves showed that the high-risk group had significantly worse biochemical recurrence than the intermediate-risk group (P=0.042) and low-risk group (P<0.001). Our findings suggest that maximum tumor contact length is an independent predictor of pathological extraprostatic extension and biochemical recurrence. A risk stratification system using prostate-specific antigen, Gleason score and maximum tumor contact length might be useful for preoperative assessment of prostate cancer patients.

RE: QUANTITATIVE POLYMERASE CHAIN REACTION DOES NOT IMPROVE PREOPERATIVE PROSTATE CANCER STAGING: A CLINICOPATHOLOGICAL MOLECULAR ANALYSIS OF 121 PATIENTS

A Competing Risks Analysis of Clinical Outcomes of Prostate LDR Brachytherapy at a Single Institution

Background: Prostate cancer is the second most common cause of cancer death in men, being responsible for approximately 13% of all cancer deaths. Due to the high specificity for prostate tissue, prostate-specific antigen (PSA) is the primary serum tumor marker for prostate cancer. To our knowledge, in published data, the highest reported PSA level on initial presentation was 5,666 ng/ml. Case Report: We present a 64-year-old Caucasian man with no specific urologic or pain symptoms and with an initial PSA serum value of 21,380 ng/ml. Initial laboratory studies showed chronic anemia and elevated alkaline phosphatase, most likely from bone marrow infiltration due to metastatic disease. Prostate biopsies diagnosed an adenocarcinoma of the prostate (Gleason score 9). Computed tomography (CT) showed multiple liver metastases with retroperitoneal lymph nodes of up to 1 cm. The prostate was moderately enlarged (estimated weight 35 g). Both kidneys were normal (no hydronephrosis present). A bone scintigraphy demonstrated diffuse osseous metastasis. Treatment was initiated with bilateral subcapsular orchiectomy and bicalutamide therapy in an effort to create total androgen blockade. After 3 months of follow-up, the serum concentration of PSA was 29 ng/ml. Conclusion: This case presents an asymptomatic prostate cancer patient with bone and liver metastasis, enlarged retroperitoneal lymph nodes and the highest PSA level published to date.

Prostate cancer (PCa) is one of the most common cancers in men, and it is the leading cause of cancer deaths in the world today. PCa is detected via a Prostate Specific Antigen (PSA) test. PSA is a protein produced by malignant and noncancerous tissue in the prostate gland. Although PSA levels grow as a result of prostate cancer, a high PSA test result does not always mean a man has prostate cancer. Several studies have corroborated this assertion of the inability of elevated PSA levels to most effectively indicate carcinoma without necessarily following up with histological examination. This study considered men within the 40 – 80 age bracket, who presented at the Urology Clinic of Delta State University Teaching Hospital. Results showed that whereas the mean PSA value for normotensive participants was 8.0 ng/ml (or the 95th percentile of 46.6 ng/ml), the mean PSA of 15.3 ng/ml (or 72.2 ng/ml as the 95th percentile) for those participants with BPH was reported. For study participants with PCa, a mean PSA of 43.2 ng/ml was reported. Although the statutory level for PSA within that age bracket is 4.0 ng/ml, significant increases in the normotensive participants mean that elevated PSA may not have been due to either BPH or carcinoma. Although there was a strong association between PSA levels and PCa based on the Phi and Cramer’s V value of 0.221, sensitivity was 50% and the positive predictive value was less than 20%. With the report of PSA elevations in normotensive individuals, and also with reports of some patients with reported PCa who had low PSA levels, it is suggested PSA levels may not be used in isolation. There is a need therefore to enhance the reliance on PSA or the development of more accurate biomarkers for PCa.

Introduction: African American men have the highest incidence and death rates from prostate cancer in the United States. The insulinlike growth factor (IGF) axis has been implicated in the carcinogenesis of prostate cancer. Several epidemiological studies have shown increased serum concentrations of IGF-1 and alterations of the associated binding proteins-IGFBP-2 and IGFBP-3, as strong risk factors for prostate cancer. This study examined racial differences in risk factors for prostate cancer in a healthy high risk screening population of African American and Caucasian males. The associations between IGF-1, IGFBP-2, IGFBP-3, prostate-specific antigen (PSA), testosterone, body mass index (BMI) and specific dietary macronutrients were examined. Methods: Serum was collected from 461 African American and Caucasian men aged ≥25 years who participated in prostate cancer screening programs located at two university hospitals in Washington, DC. Serum concentrations of IGF-1, IGFBP-2, IGFBP-3, PSA, and testosterone were analyzed using immunoassays from Diagnostic Systems Laboratories (Webster, TX). Height and weight were used to create BMI, which was calculated as weight/height2 (kg/m2). A food-frequency questionnaire was administered over the telephone to 128 study participants who consented. Wilcoxon rank sums test and chi square test examined mean differences and associations with other risk factors. Multiple linear regression analysis was used to examine racial differences in IGF-1, IGFBP-3, IGFBP-2, testosterone, PSA and specific macronutrients, adjusted for covariates such as age and BMI. Results: African American men had significantly lower concentrations of IGFBP-2 (p=0.035), and significantly higher concentrations of IGFBP-3 and testosterone when compared to Caucasian men, p=0.031 and p=0.033 respectively. There were no significant differences found for concentrations of IGF-1 by race. Levels of IGFBP-2 exhibited a significant inverse association with BMI for both races and a positive association with age for Caucasians. African American men had higher mean intakes of total calories, total fat, protein and carbohydrate, but only dietary fat intake was significantly higher when compared to intakes in Caucasian men (p=0.026). Multiple regression analysis revealed no significant relationships between nutrient intake and concentrations of IGF-1, IGFBP-3, IGFBP-2, PSA and testosterone by race. Finally, IGFBP-2 exhibited a significant univariate negative correlation with total calories, protein and total fat, with a somewhat stronger association among Caucasian than African American men. Conclusion: We provide evidence of racial variation in concentrations of IGFBP-2, IGFBP-3 and testosterone, but not for IGF-1. In this sample, African American men had a significantly higher consumption of total dietary fat intake than Caucasians. Further work is needed to determine whether these observations may explain the racial disparity in prostate cancer incidence and mortality in the U.S. Funded by: Department of Defense DAMD17-00-1-0024 Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A78.

Prostate cancer is the second leading cause of cancer death in men in the developed world. A more sensitive and specific detection strategy for lethal prostate cancer beyond serum prostate specific antigen (PSA) population screening is urgently needed. Diagnosis by canine olfaction, using dogs trained to detect cancer by smell, has been shown to be both specific and sensitive. While dogs themselves are impractical as scalable diagnostic sensors, machine olfaction for cancer detection is testable. However, studies bridging the divide between clinical diagnostic techniques, artificial intelligence, and molecular analysis remains difficult due to the significant divide between these disciplines. We tested the clinical feasibility of a cross-disciplinary, integrative approach to early prostate cancer biosensing in urine using trained canine olfaction, volatile organic compound (VOC) analysis by gas chromatography-mass spectroscopy (GC-MS) artificial neural network (ANN)-assisted examination, and microbial profiling in a double-blinded pilot study. Two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. Biopsy-negative controls were used to assess canine specificity as prostate cancer biodetectors. Urine samples were simultaneously analyzed for their VOC content in headspace via GC-MS and urinary microbiota content via 16S rDNA Illumina sequencing. In addition, the dogs’ diagnoses were used to train an ANN to detect significant peaks in the GC-MS data. The canine olfaction system was 71% sensitive and between 70–76% specific at detecting Gleason 9 prostate cancer. We have also confirmed VOC differences by GC-MS and microbiota differences by 16S rDNA sequencing between cancer positive and biopsy-negative controls. Furthermore, the trained ANN identified regions of interest in the GC-MS data, informed by the canine diagnoses. Methodology and feasibility are established to inform larger-scale studies using canine olfaction, urinary VOCs, and urinary microbiota profiling to develop machine olfaction diagnostic tools. Scalable multi-disciplinary tools may then be compared to PSA screening for earlier, non-invasive, more specific and sensitive detection of clinically aggressive prostate cancers in urine samples.

Feasibility of Adenovirus-Mediated hNIS Gene Transfer and 131I Radioiodine Therapy as a Definitive Treatment for Localized Prostate Cancer

Objective: to carry out stratification of patients with locally advanced prostate cancer (PCa) on prognostic groups, depending on the clinical and morphological characteristics for determining the risk of biochemical recurrence after radical prostatectomy (RPE). Materials and methods. During the period from August 2002 to June 2015, 419 patients with PCa were hospitalized on the basis of the Institute of Urology of the Academy of Medical Sciences of Ukraine RPE, of which 106 patients (25.3%) had clinical stage sT 3 N 0 M 0 . The average follow-up period was 55.7 months. Results. Based on the main clinical risk factors, a model of prognostic stratification of locally advanced PCa was developed into three subgroups: low risk – in the absence of data on invasion of seminal vesicles (stage cT 3a ), prostate-specific antigen (PSA) <20 ng / ml, Gleason score with biopsy Ј6; Intermediate risk – in the presence of one of the unfavorable factors of the forecast: stage cT 3v , PSA ≥ 20 ng/ml, Gleason ≥ 7; нigh risk – in the presence of two or more negative prognostic factors. Biochemical relapse in the groups of low, intermediate and high risk was revealed in 14.3%, 37.1% and 70.2% of patients (p<0.05), respectively, and the risk of its development in patients with intermediate risk increased 3.0 times , нigh – 8.5 times. Conclusion. This stratification can be useful for practical specialists and researchers in choosing the optimal treatment tactics for patients with stage III prostate cancer.