Prostate-specific Antigen Kinetics Research Articles

The Dominant Source Mechanism of Infrasound Generation in Powder Snow Avalanches

AbstractPowder snow avalanches (PSAs) radiate infrasound energy, yet the source mechanism remains unclear, limiting hazard monitoring and mitigation with infrasound‐based technologies. Here, we analyze a unique data set from a large PSA to improve the understanding of the source mechanism. Through comparison of cluster activity within the airborne layers of the PSA and the recorded infrasound signal in the frequency domain, we demonstrate that infrasound is mainly generated from particle clusters suspended by turbulent eddies or ejected from the denser basal layer. Further correlating infrasound amplitudes with radar‐derived spatial distributions of these clusters, we reveal a distributed source extending hundreds of meters behind the avalanche front. Additionally, we establish a relationship between infrasound and kinetic energy of suspended particles. These findings deepen our understanding of the complex dynamics of infrasound generation, offering valuable insights for avalanche detection and early warning strategies, and fundamental comprehension of PSA dynamics.

Rapid and Deep Prostate-Specific Antigen Decline is a Prognostic Marker in Metastatic Hormone-Sensitive Prostate Cancer: A Real-World Multi-Intuitional Analysis.

Prostate-specific antigen (PSA) kinetics has been investigated as a prognostic marker in post hoc analyses of clinical trials. This study validated the prognostic value of rapid and deep PSA decline in metastatic hormone-sensitive prostate cancer (mHSPC) using real-world data. In total, 1296 patients with mHSPC were retrospectively reviewed. We assessed the prognostic value of a PSA decline to ≤ 0.2 ng/mL after 12 weeks of treatment and investigated several potential risk factors for a poor PSA response. Of 1296 patients, 714 (cohort 1: 55.1%) were treated with conventional hormonal therapy, while 582 (cohort 2: 44.9%) received androgen signaling inhibitors. There were significant differences in progression-free survival and overall survival between patients with PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment and others (p < 0.001 for each). In addition, patients with an initial PSA ≥ 200 ng/mL, Clinical T4 and Grade Group 5 were less likely to achieve PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment, with odds ratios of 0.31 (p < 0.001), 0.67 (p = 0.039) and 0.70 (p = 0.043), respectively. Our findings suggested that PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment may be a useful prognostic biomarker for mHSPC in the real-world setting. The prognostic value of this should be further investigated in a prospective cohort, and identification of an optimal cutoff value is necessary for its application in clinical trial design or clinical practice.

Characterization of PSA dynamics and oncological outcomes in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors.

This study investigated the characteristics of prostate-specific antigen (PSA) dynamics when androgen receptor signaling inhibitor (ARSI), or vintage agent (bicalutamide) was used for patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 213 mHSPC patients from each of the ARSI and bicalutamide groups treated between 2015 and 2022 were selected from multiple institutions using propensity score-matched analysis to align backgrounds. PSA progression-free survival (PFS) and overall survival (OS) were assessed. PSA level at 3months, PSA nadir level, and time to PSA nadir were examined to analyze of PSA kinetics. ARSI treatment significantly improved PSA PFS compared to bicalutamide (P = 0.0063), although no significant difference in OS was seen (P = 0.3134). No significant differences were observed between treatment groups in median PSA levels at 3months (1.47 vs 0.52ng/ml, P = 0.3042) or PSA nadir levels (0.263 vs 0.1345ng/ml, P = 0.1228). Bicalutamide treatment demonstrated longer time to nadir than ARSI in progression-free cases (median: 243 vs 213.5days, P = 0.0003). Survival tree analysis found that PSA nadir ≤ 1.5ng/ml and time to nadir ≥ 145days were the optimal cut-offs for best stratifying OS with bicalutamide, while PSA nadir ≤ 0.45ng/ml and time to nadir ≥ 70days were optimal with ARSI. No significant differences in PSA response was seen between groups; however, distinct optimal cut-offs were demonstrated for PSA nadir and time to nadir. The present findings will be useful for optimal PSA monitoring for mHSPC patients and for early identification of poor-prognosis populations.

Prostate-specific antigen kinetics in Asian patients with metastatic castration-sensitive prostate cancer treated with apalutamide in the TITAN trial: A post hoc analysis.

In the TITAN trial of patients with metastatic castration-sensitive prostate cancer (mCSPC), deep and rapid prostate-specific antigen (PSA) decline with apalutamide plus androgen deprivation therapy (ADT) was associated with longer overall survival (OS), radiographic progression-free survival (rPFS), time to PSA progression (TTPP), and time to castration resistance (TTCR) compared with no decline (all p < 0.0001). This post hoc analysis evaluated PSA kinetics in the Asian subpopulation. Data were analyzed for patients enrolled in China, Japan, and Korea and treated with apalutamide (n = 111) or placebo (n = 110) plus ADT. Examined were depth of PSA response, rates of PSA decline, and associations between a deep PSA response and clinical outcomes in apalutamide-treated patients. Confirmed PSA response rates were higher with apalutamide than placebo: 73.9% versus 33.6% for PSA ≤0.2 ng/mL, 90.1% versus 58.2% for PSA reduction ≥50% [PSA50], and 74.8% versus 25.5% for PSA reduction ≥90% [PSA90]. Median (Q1; Q3) time to PSA ≤0.2 ng/mL, PSA50 and PSA90 response in the apalutamide group was 1.9 (1.0; 3.7), 1.0 (1.0; 1.0), and 1.8 (1.0; 1.9) months, respectively. PSA responses with apalutamide or placebo were consistent irrespective of high- or low-volume disease. Achievement of confirmed PSA ≤0.2 ng/mL or PSA90 response with apalutamide at landmark 3 months was associated with significantly (nominal p-values) longer OS (hazard ratio: 0.23; p = 0.0009), TTPP (0.16; p = 0.0001), TTCR (0.20; p < 0.0001), and time to progression on first subsequent therapy or death (0.19; p < 0.0001) compared with no decline. PSA kinetics have applications for early prognostic evaluation in Asian patients with mCSPC.

Is prostate-specific antigen density superior than prostate-specific antigen kinetics and prostate volume in predicting clinically insignificant prostate cancer?

Objectives: In this study, we aimed to evaluate the parameters that could predict clinically insignificant prostate cancer (ciPCa) in men who underwent transrectal ultrasound (TRUS)-guided prostate biopsy. Methods: Data of patients who underwent transrectal prostate biopsy between January 2015 and November 2019 were examined retrospectively. Free/total PSA ratio (fPSA%), serum total and free prostate-specific antigen (PSA) levels, prostate volumes (PV) measured by ultrasonography, and PSA density (PSAD) values of the patients before biopsy were recorded. ciPCa patients were defined as patients with Gleason scores ≤6 and clinical stage ≤T2a (Group 1). The remaining patients (Gleason score &amp;gt;6 and clinical stage &amp;gt;T2a) were included in Group 2 (clinical significant prostate cancer (csPCa). The parameters examined before biopsy were compared between groups. Results: After performing the exclusion criteria, the study counts in 168 patients with the current data of total/free PSA levels, age, PV calculated by TRUS, rectal examination findings, and pathology reports. Group 1 consisted of 115 patients and Group 2 consisted of 53 patients. In the univariate analysis, PV, total PSA and PSAD were found significantly different between groups, while age, free PSA, and fPSA% showed no significant difference between the two groups. According to the results of the multivariate analysis, the independent predictor of ciPCa was determined to be PSAD while total PSA and PV were not independent predictors. Conclusion: PSAD was found to be superior to other PSA kinetics in predicting ciPCa.

The TROG 15.01 stereotactic prostate adaptive radiotherapy utilizing kilovoltage intrafraction monitoring (SPARK) clinical trial database.

The US National Institutes of Health state that Sharing of clinical trial data has great potential to accelerate scientific progress and ultimately improve public health by generating better evidence on the safety and effectiveness of therapies for patients (https://www.ncbi.nlm.nih.gov/books/NBK285999/ accessed 2024-01-24.). Aligned with this initiative, the Trial Management Committee of the Trans-Tasman Radiation Oncology Group (TROG) 15.01 Stereotactic Prostate Adaptive Radiotherapy utilizing Kilovoltage intrafraction monitoring (KIM) (SPARK) clinical trial supported the public sharing of the clinical trial data. The data originate from the TROG 15.01 SPARK clinical trial. The SPARK trial was a phase II prospective multi-institutional clinical trial (NCT02397317). The aim of the SPARK clinical trial was to measure the geometric and dosimetric cancer targeting accuracy achieved with a real-time image-guided radiotherapy technology named KIM for 48 prostate cancer patients treated in 5 treatment sessions. During treatment, real-time tumor translational and rotational motion were determined from x-ray images using the KIM technology. A dose reconstruction method was used to evaluate the dose delivered to the target and organs-at-risk. Patient-reported outcomes and toxicity data were monitored up to 2 years after the completion of the treatment. The dataset contains planning CT images, treatment plans, structure sets, planned and motion-included dose-volume histograms, intrafraction kilovoltage, and megavoltage projection images, tumor translational and rotational motion determined by KIM, tumor motion ground truth data, the linear accelerator trajectory traces, and patient treatment outcomes. The dataset is publicly hosted by the University of Sydney eScholarship Repository at https://doi.org/10.25910/qg5d-6058. The 3.6Tb dataset, with approximately 1 million patient images, could be used for a variety of applications, including the development of real-time image-guided methods, adaptation strategies, tumor, and normal tissue control modeling, and prostate-specific antigen kinetics.

Prognostic role of prostate specific antigen kinetics in primary high volume metastatic hormonal sensitive prostate cancer treated with novel hormonal therapy agents

The prognostic value of prostate-specific antigen (PSA) kinetics in primary high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with novel hormonal therapy agents is still unclear. Here, we retrospectively reviewed the data of 102 patients with primary high-volume mHSPC who received novel hormonal therapy agents. The median follow-up was 32.25 ± 14.51 months and the median nadir PSA (nPSA) was 0.20 (0.06, 11.71) ng/mL after treatment. The mean time to nPSA was 10.82 ± 7.27 months and 55 patients (53.9%) had a PSA-density (PSA-D) ≤ 0.08 at 3-months. Univariate and multivariate Cox regression analyses showed that the absence of visceral metastases, nPSA ≤ 0.2 and PSA-D ≤ 0.08 were independent prognostic factors for better PFS and OS (all P < 0.05). Moreover, patients with nPSA ≤ 0.2 and PSA-D ≤ 0.08 had the best PFS and OS, and the combination of the nPSA and PSA-D had a better predictive accuracy for PFS and OS than nPSA and PSA-D alone. Thus, Visceral metastases, nPSA and PSA-D were independent prognostic factors for primary high-volume mHSPC patients treated with novel hormonal therapy agents. Patients with lower nPSA and PSA-D had a best survival outcome, and the combination of nPSA and PSA-D had a better effect on prognosis predicting.

PSA Kinetics Affect Prognosis in Patients With Castration-resistant Prostate Cancer Treated With Enzalutamide.

There is little evidence regarding the predictive value of prostate-specific antigen (PSA) kinetics in patients with castration-resistant prostate cancer treated with an androgen receptor signaling inhibitor. This study investigated the correlation between PSA kinetics and prognosis in patients with castration-resistant prostate cancer treated with enzalutamide. We analyzed data from 103 patients who received enzalutamide as primary treatment for castration-resistant prostate cancer at our hospital, focusing on the associations between overall survival and PSA kinetics variables, such as maximal PSA response, PSA nadir, and time to PSA nadir. The median PSA level at the initiation of enzalutamide was 18.1 ng/ml (interquartile range=7.9-61.2 ng/ml). The median maximal PSA response rate was 88% (interquartile range 55-98), and the median PSA nadir was 1.84 (interquartile range (IQR)=0.38-14.7) ng/ml. The median time to PSA nadir was 19 (IQR=6-28.5) weeks. Maximal PSA response rate <90% [hazard ratio (HR)=2.28, 95% confidence interval (CI)=1.03-5.03, p=0.0413], PSA nadir >2 ng/ml (HR=2.30, 95%CI=1.05-5.07, p=0.0379), time to nadir <19 weeks (HR=2.48, 95%CI=1.15-5.35, p=0.0204) were all independently predictive of shortened overall survival even after adjusting for pre-treatment factors. Maximal PSA response, PSA nadir, and time to PSA nadir correlated with survival in patients with castration-resistant prostate cancer receiving enzalutamide as a first-line therapy.

Patient-specific prostate tumour growth simulation: a first step towards the digital twin.

Prostate cancer (PCa) is a major world-wide health concern. Current diagnostic methods involve Prostate-Specific Antigen (PSA) blood tests, biopsies, and Magnetic Resonance Imaging (MRI) to assess cancer aggressiveness and guide treatment decisions. MRI aligns with in silico medicine, as patient-specific image biomarkers can be obtained, contributing towards the development of digital twins for clinical practice. This work presents a novel framework to create a personalized PCa model by integrating clinical MRI data, such as the prostate and tumour geometry, the initial distribution of cells and the vasculature, so a full representation of the whole prostate is obtained. On top of the personalized model construction, our approach simulates and predicts temporal tumour growth in the prostate through the Finite Element Method, coupling the dynamics of tumour growth and the transport of oxygen, and incorporating cellular processes such as proliferation, differentiation, and apoptosis. In addition, our approach includes the simulation of the PSA dynamics, which allows to evaluate tumour growth through the PSA patient's levels. To obtain the model parameters, a multi-objective optimization process is performed to adjust the best parameters for two patients simultaneously. This framework is validated by means of data from four patients with several MRI follow-ups. The diagnosis MRI allows the model creation and initialization, while subsequent MRI-based data provide additional information to validate computational predictions. The model predicts prostate and tumour volumes growth, along with serum PSA levels. This work represents a preliminary step towards the creation of digital twins for PCa patients, providing personalized insights into tumour growth.

Patterns of failure with 18F-DCFPyL PSMA-PET/CT in the post-prostatectomy setting: A regional cohort analysis.

This study aimed to assess the detection rate of prostate cancer recurrence by prostate-specific member antigen positron emission tomography/computed tomography (PSMA PET/CT) with 18F-DCFPyL in patients with residual disease or biochemical recurrence (BCR), and its association with surgical pathology and prostate-specific antigen (PSA) kinetics. Men from South Central Ontario enrolled in the PSMA Registry for Recurrent Prostate cancer (PREP) between April 2019 and December 2021 after radical prostatectomy (RP) and who had 1) pathologic stage N1 or persistent elevated PSA; or 2) BCR (PSA >0.10 ng/mL) where initial postoperative PSA was undetectable were included. A total of 169 men (median age 68 years; interquartile range [IQR] 62-71) with complete data met the above criteria. The median PSA was 0.27 ng/mL (IQR 0.16-0.85) prior to PSMA-PET. Overall positivity rate 59%; when PSA was <0.40 ng/mL, overall positivity rate 42% vs. 85% with PSA ≥0.40 ng/mL (p<0.001). Higher pathologic tumor stage increased detection of regional lymph nodes (LN) (pT2-3a: 32% vs. pT3b: 69%, p<0.001) but not distant metastases (pT2-3a: 12% vs. pT3b: 24%, p=0.15). PSMA-PET detected 18% with prostate bed, 42% with regional LN disease, and 44% with pelvic-only disease. The three most involved LN chains were the internal (21%) and external (20%) iliac, and obturator chains (16%). This prospective study of patients with residual disease or BCR after RP illustrates patterns of failure that could impact diagnosis and postoperative management. Such patients have significant risk of regional LN positivity on PSMA-PET highlighting a need to include pelvic LN within salvage radiotherapy volumes.

Correlation of PSA and survival in metastatic hormone-sensitive prostate cancer treated with rezvilutamide plus ADT in the CHART trial.

This exploratory analysis of the CHART trial (ClinicalTrials.gov: NCT03520478) investigated prostate-specific antigen (PSA) kinetics and the correlation between PSA and survival outcomes in high-volume, metastatic, hormone-sensitive prostate cancer (mHSPC). A total of 654 patients were randomized 1:1 to receive either rezvilutamide plus androgen deprivation therapy (ADT; n= 326) or bicalutamide plus ADT (n= 328). PSA kinetics were evaluated, and the correlation between survival and the achievement of undetectable PSA (≤0.2ng/mL) or ≥90% PSA reduction (PSA90) was assessed. The rezvilutamide group exhibited higher proportions of ≥50% PSA reduction (PSA50; 98.2% vs. 87.5%), PSA90 (88.7% vs. 63.1%), and undetectable PSA (38.3% vs. 17.7%) responses compared to the bicalutamide group by 3months. The rezvilutamide group demonstrated superior efficacy in delaying PSA progression compared to the bicalutamide group (hazard ratio [HR] 0.21, 95% confidence interval 0.16-0.27). The achievement of undetectable PSA and PSA90 by 6months in the rezvilutamide group was associated with prolonged overall survival (undetectable PSA, HR= 0.34; PSA90, HR= 0.22), radiographic progression-free survival (HR= 0.36, HR= 0.26), time to PSA progression (HR= 0.25, HR= 0.17), and time to castration resistance (HR= 0.34, HR= 0.23) compared to those who did not achieve these PSA milestones. Stratification by baseline PSA level revealed consistent survival improvements with rezvilutamide plus ADT across quartiles. PSA kinetics is a valuable prognostic factor in mHSPC treated with rezvilutamide plus ADT, and the achievement of undetectable PSA and PSA90 is associated with improved survival. These findings highlight the importance of monitoring PSA kinetics in the management of mHSPC. This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Importance of PSA Kinetics as a Prognostic Factor in Locally Advanced/Metastatic Prostate Cancer Patients with Prior Androgen Deprivation Therapy

Abstract Background Prostatic cancer ranks 2nd amongst men in worldwide while 4th in Egypt. Many factors are used to predict patients’ survival. PSA kinetics are one of the main prognostic factors used for treatment response in advanced or relapsed cases. However, its application as prognostic marker is lacking in Egyptian clinical settings and research. Aim of Study In this retrospective study, we aimed to assess correlation between PSA kinetics among locally advanced and metastatic prostatic cancer patients and their survival status for prognostic aspects. Methods We conducted a retrospective cohort study at Clinical Oncology department, Ain Shams University hospitals from January 2013 till December 2022 (10 years). All prostate cancer patients who were initially hormonal sensitive locally advanced or metastatic that later developed biochemical failure during follow up period were included in our study. Results Our study included 77 patients with a mean age of 66.4±7.4 years. Three cases were locally advanced while 74 cases were metastatic. The most frequent mode of ADT monotherapy prior biochemical failure was GnRH analogue in 55 cases. Upon disease progression, most of the cases were shifted to abiraterone acetate. The initial median PSA value was 100 (49.1-193.9) ng/ml. It took about 9 (6-14) months (median TTN) with a median declining rate of 10.5 (3.75-35.1) % for their PSA values to reach nadir level of median 1.2 (0.21-5.27) ng/dl. When ADT failed, PSA levels increased again reaching a median value of 8.9 (3.75-35.2) ng/ml. The median PSA velocity after progression was 35.2 (2.8-208) ng/dl/yr while median PSA DT was 3.6 (1.3-7.25) months. Univariate analysis revealed PSA nadir &amp;lt;0.76 ng/dl level (P value= 0.003) and TTN &amp;gt;11 m (p value = 0) significantly associated with longer PFS and improved survival. However, PSA DT &amp;lt; 3.1 (p value=0.017) predicts higher mortality. Meanwhile, multivariate results showed that PSA declining rate (P value= 0.047) and age &amp;gt; 67 years (P value 0.016) were statistically significant as independent factors when associated to PFS. Conclusion TTN &amp;gt; 11 months and PSA nadir &amp;lt;0.76 during initial treatment was associated with prolonged PFS and OS. They were associated with better clinical response to treatment in castration resistant prostate cancer patients. Thus, it could be helpful for decision making of early treatment strategy in castration resistant cases.

A retrospective study of prognostic factors and prostate-specific antigen dynamics in Japanese patients with metastatic hormone-sensitive prostate cancer who received combined androgen blockade therapy with bicalutamide.

This retrospective observational study explored the therapeutic potential of combined androgen blockade (CAB) with bicalutamide (Bic-CAB) as an initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC) in Japan. The electronic health records of 159 patients with mHSPC from three Japanese institutions who received initial treatment with Bic-CAB between 2007 and 2017 were analyzed. The time to prostate-specific antigen (PSA) progression, duration of Bic-CAB treatment, and overall survival (OS), with various definitions for PSA progression, were assessed. A multivariate Cox proportional hazards model was constructed using clinical parameters to predict time to the end of Bic-CAB treatment and OS. The median observation period was 46.4months, and the median age of patients at diagnosis was 71years. A total of 46.5% patients experienced PSA progression with a median survival duration of 29months (according to Prostate Cancer Clinical Trials Working Group 3 criteria), and 49.1% patients achieved a PSA nadir < 0.2ng/mL in a median time of 4.7months. When stratified by PSA nadir and PSA change, patients at low risk for disease progression with a small PSA change due to low initial PSA had a 5-year OS of 100% and a 10-year OS of 75%. The OS during the observation period was 72.9months. These findings highlight the potential effect of Bic-CAB in patients with mHSPC who were at low risk for disease progression. Initial treatment with Bic-CAB and adjusting treatment early based on PSA dynamics may be a reasonable treatment plan for these patients.

Deep PSA response and extended time-to-nadir as robust predictors of survival in Asian patients with de novo metastatic hormone-sensitive prostate cancer receiving upfront intensified treatment.

In de novo metastatic hormone-sensitive prostate cancer (mHSPC) treated with upfront intensification using androgen receptor signaling inhibitor or chemotherapy (Docetaxel), achieving a PSA nadir less than 0.2 ng/mL, indicative of superior survival in trials, may often be unattainable in real-world settings. We explored the predictive value of the degree of PSA decline and time to PSA nadir (TTPN) on oncological outcomes. A prospectively maintained database of consecutive prostate cancer cases in Hong Kong was accessed. Patients diagnosed with de novo mHSPC from 2016 to 2022 and treated with upfront intensification were included in this analysis. Landmark analysis on PSA kinetics at 6-months following treatment intensification was performed. They were classified based on 1) TTPN (≥6 months vs. <6 months), and 2) a combined response (deep responders achieving both ≥95% PSA decline and TTPN ≥ 6 months vs. shallow responders). Multivariable regression analysis was employed to identify the effects of confounders. A total of 131 patients were included in this analysis. Classifying patients by combined response best predicted survival outcomes. Deep responders had better progression-free survival (HR = 0.56; 95%CI = 0.34-0.91; p = 0.019), overall survival (HR = 0.50; 95%CI = 0.26-0.97; p = 0.036), and cancer-specific survival (HR = 0.43; 95%CI = 0.19-0.99; p = 0.042). Difference in overall survival remained significant after adjustment in multivariable regression analysis. Our analysis demonstrates that alternative PSA targets can predict treatment response and survival outcomes in de novo mHSPC patients in a real-world setting, providing valuable information for patient counselling and potentially guiding future trial design.

MRI and active surveillance: thoughts from across the pond.

In the United States (US), urological guidelines recommend active surveillance (AS) for patients with low-risk prostate cancer (PCa) and endorse it as an option for those with favorable intermediate-risk PCa with a > 10-year life expectancy. Multiparametric magnetic resonance imaging (mpMRI) is being increasingly used in the screening, monitoring, and staging of PCa and involves the combination of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced T1-weighted imaging. The American Urological Association (AUA) guidelines provide recommendations about the use of mpMRI in the confirmatory setting for AS patients but do not discuss the timing of follow-up mpMRI in AS. The National Comprehensive Cancer Network (NCCN) discourages using it more frequently than every 12 months. Finally, guidelines state that mpMRI can be used to augment risk stratification but should not replace periodic surveillance biopsy. In this review, we discuss the current literature regarding the use of mpMRI for patients with AS, with a particular focus on the approach in the US. Although AS shows a benefit to the addition of mpMRI to diagnostic, confirmatory, and follow-up biopsy, there is no strong evidence to suggest that mpMRI can safely replace biopsy for most patients and thus it must be incorporated into a multimodal approach. CLINICAL RELEVANCE STATEMENT: According to the US guidelines, regular follow-ups are important for men with prostate cancer on active surveillance, and prostate MRI is a valuable tool that should be utilized, in combination with PSA kinetics and biopsies, for monitoring prostate cancer. KEY POINTS: According to the US guidelines, the addition of MRI improves the detection of clinically significant prostate cancer. Timing interval imaging of patients on active surveillance remains unclear and has not been specifically addressed. MRI should trigger further work-ups, but not replace periodic follow-up biopsies, in men on active surveillance.

(218) PHYSICIAN AWARENESS AND INDICATIONS OF 5-ALPHA REDUCTASE INHIBITOR USE FOR BENIGN PROSTATIC HYPERPLASIA IN THE PRIMARY CARE SETTING

Abstract Introduction Primary care physicians (PCPs) commonly prescribe 5-alpha-reductase inhibitors (5-ARIs) for benign prostatic hyperplasia (BPH). 5-ARIs can affect prostate-specific antigen (PSA) kinetics by decreasing PSA levels by approximately half, and therefore delay early detection of prostate cancer (PCa). Our team previously presented preliminary findings revealing a general low level of knowledge regarding the effects of 5-ARIs on PSA kinetics. Objective Thus, the objective of this study is to now present further, expanded data investigating PCPs’ level of awareness and indications of 5 ARI use for BPH in the primary care setting. Methods An anonymous 14-question survey was emailed to PCPs in the specialties of Family Medicine or Internal Medicine at a diverse, urban academic institution. Questions focused on residency graduation year, patient volume, medical practice characteristics, knowledge of 5-ARIs and their effects on PSA kinetics, role of 5-ARIs in PCa prevention, and indications for prostate biopsy referral. Results 221 PCPs were emailed. Overall, 85 PCPs responded, yielding a response rate of 38.5%. All PCPs reported to see men &amp;gt;40 years of age and the majority (78.8%) reported to have prescribed 5-ARIs in practice. Approximately 39% of PCPs were not aware of the suppressive effects of 5-ARIs on PSA and 63.5% were not sure or incorrectly answered when asked about calculating the corrected PSA of a patient who is taking 5-ARIs. Furthermore, nearly 80% were not sure or would not refer a patient who is taking 5-ARIs and has an elevated corrected PSA for a prostate biopsy. 63.5% were not sure or believed that 5-ARIs may decrease the risk of high-grade PCa and 49.4% were not sure or believed that 5-ARIs are approved for the prevention of PCa. Conclusions Overall, our expanded culmination of data within an academic, urban institution reveals a low level of knowledge amongst PCPs as it relates to the effect of 5 ARIs on PSA kinetics and subsequently the indications for biopsy referral in these patients. Thus, this gap in knowledge may represent an important initiative to work with our primary care colleagues in caring for patients taking 5 ARIs for BPH. Disclosure No.

Prostate-specific Antigen Nadir and Cancer-Control Outcomes in Real-world Apalutamide-treated Metastatic Hormone-Sensitive Prostate Cancer Patients: A Single-Center Analysis

Background and objectiveCurrently available post hoc phase 3 trial–derived data suggest better cancer-control outcomes in apalutamide-treated metastatic hormone-sensitive prostate cancer (mHSPC) patients achieving an (ultra)low prostate-specific antigen (PSA) nadir. This study aims to validate ultralow PSA nadir cutoffs. MethodsRelying on an institutional prostate cancer database, 107 eligible patients were yielded. The currently available PSA nadir cutoffs (SWOG trial: <0.2 ng/ml; ultralow TITAN trial: ≤0.02 vs 0.02–0.2 vs >0.2 ng/ml) and PSA responses (≥99%) were tested for time to castration-resistant prostate cancer (ttCRPC) and overall survival (OS) in mHSPC patients treated with apalutamide. Finally, comparisons were made against abiraterone mHSPC treatment. Key findings and limitationsOverall, 107 mHSPC patients treated with apalutamide at a median age of 68 yr and baseline PSA of 29 ng/ml were included. The highest proportion of included patients (40.2%) achieved an ultralow PSA nadir of ≤0.02 ng/ml. Patients reaching the SWOG 9346–defined PSA nadir of <0.2 ng/ml and ultralow PSA nadir of ≤0.02 ng/ml harbored the longest time to metastatic castration-resistant prostate cancer (mCRPC) and OS (all p < 0.05). Moreover, 80% of mHSPC patients treated with apalutamide achieved a PSA response of ≥99%. These patients also harbored better time to mCRPC and OS outcomes, relative to patients with a <99% PSA response (both p < 0.05). In the second step of analyses, a comparison against abiraterone patients showed a significantly higher rate of achieving an ultralow PSA nadir of ≤0.02 ng/ml: 40.2% versus 8.8% for apalutamide versus abiraterone, resulting in a significantly longer ttCRPC for the apalutamide-treated (37 mo) than for the abiraterone-treated (22 mo) group (p = 0.001), even after multivariable adjustment and in sensitivity analyses for high-risk mHSPC patients only. The study is limited by its retrospective design. Conclusions and clinical implicationsIn the real-world setting, most mHSPC patients treated with apalutamide achieve an ultralow PSA nadir, which is associated with better cancer-control outcomes. Moreover, a PSA response of ≥99% predicts better outcomes. In head-to-head comparisons, apalutamide achieves better PSA kinetics and ttCRPC outcomes than abiraterone. Patient summaryA prostate-specific antigen (PSA) nadir of <0.02 ng/ml and PSA responses ≥99% are associated with better cancer-control outcomes in metastatic hormone-sensitive prostate cancer patients treated with apalutamide.

Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) study: ultralow prostate-specific antigen decline with apalutamide plus androgen-deprivation therapy.

To assess the association between achievement of prostate-specific antigen (PSA) levels ≤0.2 ng/mL (henceforth 'ultralow') and clinical outcomes in patients in the 'Targeted Investigational Treatment Analysis of Novel Anti-androgen' (TITAN) study (ClinicalTrials.gov Identifier NCT02489318) with metastatic castration-sensitive prostate cancer (mCSPC). Patients in the TITAN study with mCSPC were randomised to 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy. This post hoc analysis assessed the achievement of a PSA level of 0.2->0.02 ng/mL ('ultralow one' [UL1]) and ≤0.02 ng/mL ('ultralow two' [UL2]) vs >0.2 ng/mL with apalutamide treatment and its association with radiographic progression-free survival (rPFS), overall survival (OS), time to castration-resistant PC (TTCRPC), and time to PSA progression (TTPP). The landmark analysis and Kaplan-Meier methods were used. By 3 months, more patients achieved UL1 and UL2 with apalutamide (38% and 23%) vs placebo (15% and 5%). In the apalutamide-treated patients, UL2 vs PSA >0.2 ng/mL at landmark 3 months was associated with significantly longer rPFS (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.14-0.54), OS (HR 0.24, 95% CI 0.13-0.43), TTCRPC (HR 0.2, 95% CI 0.11-0.38), and TTPP (HR 0.11, 95% CI 0.04-0.27; nominal P values all <0.001); this association was also observed but less pronounced for UL1. Similar findings were observed at 6 months. Early onset of decline to UL2 by 3 months was associated with improved survival vs PSA >0.2 ng/mL anytime (HR 0.12, 95% CI 0.06-0.22; P < 0.001) in apalutamide-treated patients. In this post hoc analysis of TITAN, patients with the deepest PSA decline derived the greatest benefit. These results extend our findings of apalutamide efficacy in the overall TITAN population, underscoring the clinical value of PSA kinetics as a marker for treatment efficacy. Patients with metastatic prostate cancer that is sensitive to ongoing hormonal treatment benefited significantly from the addition of apalutamide compared with placebo. Those who achieved rapid and deep PSA reduction had the greatest survival benefit.

Independent association between prostate-specific antigen nadir and PSA progression-free survival in first-line abiraterone acetate treatment in castration-resistant prostate cancer patients: a pilot study.

There is limited evidence regarding the correlation between prostate-specific antigen (PSA) kinetics and clinical outcomes. Therefore, after regulating other covariates, we studied patients with castration-resistant prostate cancer who received abiraterone acetate as the first-line treatment. In this study, we investigated whether time to PSA nadir was independently associated with PSA progression-free survival (PFS). As a retrospective cohort study, this study contained a total of 77 castration-resistant prostate cancer patients who received abiraterone acetate from October 2015 to April 2021 in a Chinese hospital. The dependent variable was PSA-PFS. The objective independent variable was time to PSA nadir (TTPN). Covariates involved in this study included age, duration of androgen deprivation therapy (ADT), PSA level at baseline, time of 50% PSA decline, time of PSA decline to nadir, Gleason score, bone metastasis, previous treatment, PSA decline <50% in 3 months, PSA to nadir in 3 months, PSA decline <90%, PSA decline <0.2 ng/mL, and PSA flare. For the 77 subjects, their mean age was 72.70 ± 8.08 years. Fully calibrated linear regression findings indicated that PSA decline and kinetics were positively associated with PFS (months) after adjusting confounders (β = 0.77, 95% CI: 0.11-1.44). A non-linear relationship was not detected between PSA decline or PSA kinetics and progression-free survival. According to the data of this study, there was a correlation between early PSA changes and patients treated with abiraterone acetate.

Prostate cancer patients with lymphatic node involvement detected by immunohistochemistry. Is the effort worthwhile?

IntroductionLymph node (LN) status is one of the main prognostic factors in localized prostate cancer (CaP) patients after surgery. Examining palpable lymph nodes with hematoxylin and eosin (HE) is the most common approach in clinical practice; however, immunohistochemistry (IHC) has been reported to increase the LN detection rate. We reviewed the oncological results of patients with LN metastasis detected by IHC. MethodsRetrospective study of CaP patients who underwent lymphadenectomy at the time of the prostatectomy. Extended lymphadenectomy was performed with complementary indocyanine green (ICG) guidance. Three groups were considered according to LN status. Definition of the pN+ group was made if LNs were detected by HE, occulted lymph node-positive (OLN+) was considered when ≥ 1 LN was identified with IHC and occulted lymph node-negative (OLN-) if no metastatic nodes were found. Oncological outcomes were reported regarding PSA kinetics, biochemical recurrence (BCR), need for secondary treatments and metastasis-free survival (MFS). ResultsA total of 283 patients with a median follow-up of 69 months were included in the study. Immunohistochemical assessment revealed metastatic LNs in 8.9% of patients. The rate of locally advanced disease and positive surgical margins was higher in the OLN + and pN + groups vs the OLN – group (P < 0.05). At the end of follow-up, 19%, 44% and 52% of patients from the OLN -, OLN + and pN + groups experienced BCR (P < 0.001), respectively. Additionally, 2.6%, 17% and 22% of patients developed metastatic progression from the OLN -, OLN + and pN+ group (P < 0.001), respectively. In the multivariate analysis, the OLN + group had a higher risk HR: 12 (95% CI, 2.4-56; P = 0.002) of metastatic progression in comparison with OLN – patients. This difference was not observed in the risk of biochemical recurrence HR 1.8 (95% CI, 0.9-3.8; P = 0.09). ConclusionConventional HE histological analysis underdiagnosed nearly 10% of patients. IHC-detected patients were at higher risk of metastasis development than OLN - patients. This report highlights the importance of optimizing the anatomopathological analysis properly.