Early Prostate-specific Antigen Research Articles

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.

Differential treatment effect on overall survival (OS) based on early prostate-specific antigen (PSA) response in metastatic hormone-sensitive prostate cancer (mHSPC): A secondary analysis of TITAN trial.

Differential treatment effect on overall survival (OS) based on early prostate-specific antigen (PSA) response in metastatic hormone-sensitive prostate cancer (mHSPC): A secondary analysis of TITAN trial.

Real-world comparison of prostate-specific antigen (PSA) response in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) or enzalutamide (ENZ).

51 Background: APA and ENZ, two androgen receptor synthesis inhibitors (ARSIs), used in combination with androgen deprivation therapy (ADT) are among the recommended treatments for patients with mCSPC. Deep PSA response, evaluated as ≥90% PSA decline (PSA90), is an important outcome after ARSI initiation, with early, deep response associated with longer survival. The primary objective of this study was to compare PSA90 response in ARSI-naïve patients with mCSPC by 6 months after initiating APA or ENZ in real-world clinical practice. Methods: Linked electronic medical record (EMR) data of US community urology practices in the from PPS Analytics and administrative health data from Komodo Health Solutions Research Database were evaluated. Patients with mCSPC were selected into two cohorts, based on the index date, defined as the first paid pharmacy claim or in-office dispensation for APA or ENZ on or after 16 Dec 2019. Patients were required to have ≥12 months of pre-index EMR clinical activity. Pre-index characteristics (i.e., age, race, geographic region, payer type, index year, time from metastasis, time from first prostate cancer [PC] diagnosis, de novo PC, ADT use, first-generation antiandrogen use, chemotherapy use, metastasis locations, most recent PSA level, testosterone level, and Gleason score) were balanced between cohorts with inverse-probability treatment weighting (IPTW). Patients were followed from index date until the earliest of index ARSI discontinuation or switch, radiopharmaceutical initiation, end of open administrative claim or EMR clinical activity, or end of data availability (30 Sep 2022). PSA90 was defined as the earliest ≥90% decline in PSA relative to most recent pre-index PSA. The proportion of patients achieving PSA90 was compared using a weighted Kaplan-Meier analysis and the time-to-PSA90 response was compared using a weighted Cox proportional hazards model. Results: In total 860 APA and 869 ENZ patients were identified. Patient pre-index characteristics were balanced with IPTW (Table). By 6 months post-index, 80.3% of APA and 75.0% of ENZ patients had ≥1 PSA test result. By 6 months, significantly more APA patients attained a PSA90 response, as compared to ENZ patients (p=0.005; Table). The median time to PSA90 response was 3.5 months for APA and 4.9 months for ENZ. Conclusions: This US real-world study of patients with mCSPC demonstrated that treatment with APA produces a deep, early PSA response by 6 months in a greater percentage of patients than treatment with ENZ. [Table: see text]

Risk of Short-Term Prostate-Specific Antigen Recurrence and Failure in Patients With Prostate Cancer

A shorter time interval to prostate-specific antigen (PSA) failure is associated with worse clinical outcomes; however, specific factors defining this state remain unknown. To evaluate the factors of a short time interval to PSA failure in order to identify patients for treatment escalation randomized clinical trials. This secondary analysis of a randomized clinical trial was a secondary analysis of the Dana-Farber Cancer Institute 05-043 trial and included 350 patients with nonmetastatic unfavorable risk prostate cancer (PC). Patients were randomized 1:1 to receive androgen deprivation therapy (ADT) and radiation therapy (RT) plus docetaxel vs ADT and RT. Cumulative incidence rates curves of PSA failure, defined as PSA nadir plus 2 ng/mL or initiation of salvage therapies, and the Fine and Gray competing risks regression was used to assess the prognostic association between these factors and time to PSA failure. The study included 350 males who primarily had a good performance status (330 [94.3%] with Eastern Cooperative Oncology Group score of 0), median (range) age of 66 (43-86) years, with 167 (46.6%) having Gleason scores of 8 to 10, and 195 (55.2%) presenting with a baseline PSA of more than 10 ng/mL. After a median (IQR) follow-up of 10.2 (8.0-11.4) years, having a PSA level of 10 ng/mL to 20 ng/mL (subdistribution hazard ratio [sHR], 1.98; 95% CI, 1.28-3.07; P = .002) and a Gleason score of 8 to 10 (sHR, 2.55; 95% CI, 1.63-3.99; P < .001) were associated with a shorter time to PSA failure, and older age (sHR, 0.82; 95% CI, 0.72-0.93; P = .002) was associated with reduced risk for PSA failure after adjusting for other baseline clinical factors. The high-risk category, defined by these 3 factors, was associated with a shorter time to PSA failure (sHR, 2.69; 95% CI, 1.84-3.93; P < .001). In this secondary analysis of a randomized clinical trial of males with unfavorable risk PC, young age, PSA of 10 ng/mL or more, and a Gleason score of 8 to 10 estimated a shorter time to PSA failure. A subgroup of males at very high-risk for early PSA failure, as defined by our study, may benefit from treatment escalation with androgen receptor signaling inhibitors or cytotoxic chemotherapy and should be the subject of a prospective randomized clinical trial. NCT00116142.

Prognostic role of early prostate specific antigen changes after [177 Lu]Lu-PSMA radioligand therapy of metastasized prostate cancer: A meta-analysis.

Approximately 10%-20% of prostate cancers progress to metastatic and castration-resistant forms (mCRPC). Radioligand (RLT) therapy with [177 Lu]Lu-prostate-specific membrane antigen (PSMA) is an emerging treatment for metastasized mCRPC and its efficacy is assessed not only but also by prostate specific antigen (PSA) measurement after 12 weeks or more after treatment. Our aim was to evaluate the role of early PSA measurement after RLT in predicting overall survival (OS) of mCRPC patients. A systematic search on PubMed, Web Of Science and Scopus was performed from January to December 2022. PRISMA guidelines for prognostic studies was adopted. Risk of bias was assessed using quality of prognostic studies (QUIPS). Twelve studies at low-intermediate risk of bias, were included in the meta-analysis (1646 patients, mean age 70 years). About 50% of patients showed a PSA decline after 1-2 of [177 Lu]Lu-PSMA, and more than 30% reported a PSA decline ≥50%. The median OS range for patients with any PSA decline was 13-20 months, while for patients with stable or increased PSA, the median OS fell to 6-12 months. The OS rate for a PSA decline after the one-two [177 Lu]Lu-PSMA cycles was 0.39 (95% CI: 0.31-0.50), while OS for a PSA decline ≥50% was 0.69 (95% CI: 0.57-0.83). A PSA decline is observed in almost 50% of mCRPC patients after 1-2 [177 Lu]Lu-PSMA cycles, with a significantly longer OS compared to stable or increased PSA levels, respectively. Accordingly, any PSA decline after 1-2 cycles of therapy should be regarded as a favourable prognostic factor for OS.

Study on Early Prostate Cancer Antigen (EPCA) and existent risk factors of prostate cancer, Sudan: A case-control study

Background: Early prostate cancer antigen (EPCA), a nuclear matrix protein, has recently been recommended as a hopeful biomarker for early prostate carcinogenesis. Objectives: To evaluate the validity of serum early prostate cancer antigen (EPCA) in the early detection of prostate cancer (PCa) and the characteristics of Sudanese patients diagnosed with prostate cancer. Method: In this study, seventy men were considered as a case subject, who were diagnosed as cancer prostate at Gezira Hospital for Renal Disease and Surgery (GHRDS), Sudan during the period February 2018 to July 2019. Randomly selected sixty patients of BPH patients and forty-five apparently healthy men as controls group. EPCA, and PSA estimations were performed from serum samples using the principle of Enzyme Linked Immunosorbent Assay (ELISA). Results: There was significant association between age, family history, residence, unhealthy habits, education, BMI, occupations and prostate cancer, results also revealed a significant elevation between the means of the serum levels of both early prostate cancer antigen and prostate specific antigen of the patients with prostate cancer when compared with the control groups. EPCA biomarker offered the best performance statically (P= 0.00) and highest specificity (81%) and sensitivity (94%) in prostate cancer detection in Sudanese males over PSA biomarker. Conclusions: Cases of studied prostate cancer linked to many risk factors. Serum levels of early prostate cancer antigen and prostate specific antigen were significantly increased in patients with prostate cancer, however, our data proposed that EPCA has higher power statistical value, so could be utilized as a prostate cancer specific and sensitive biomarker for early detection of prostate cancer.

Prostate-specific antigen response after Abiraterone treatment in mCRPC: PSA as a predictor of overall survival

Abiraterone Acetate (AA) is an important agent in the treatment of advanced prostate cancer. It was primarily approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) after failure of androgen deprivation therapy. There is still no available strong data regarding the impact of early decline of prostate-specific antigen (PSA) in the overall survival. The aim of this study was to evaluate the clinical efficacy of an early prostate-specific antigen response as a predictor of overall survival (OS) in metastatic castration-resistant prostate cancer when treated with Abiraterone Acetate. A dual center, retrospective, cohort study on patients diagnosed with mCRPC treated with abiraterone between 2013 and 2020 was performed. Primary end-point was to demonstrate the efficacy of AA, with the analysis of PSA decline, and the correlation with overall survival. The cohort analysis consisted of 84 patients with a median age of 71 ± 9 years. A PSA response of > 30% and > 50% at 60 and 90 days was associated with improved OS. Multivariate analysis revealed that a 60 day PSA decline of > 30% was predictive of overall survival. Median OS of diag-nosed mCRPC patients was 28 months. Docetaxel pre-treatment was not associated with longer OS. The median duration of drug exposure for patients submitted to AA was found to be 14 months. Early PSA response rate can offer clinically meaningful information and can be considered a surrogate of longer OS. A > 30% or > 50% prostate-specific antigen decline at 60 and 90 days provided an important low-cost clinical tool to predict subsequent events in mCRPC patients treated with abiraterone.

Patient outcomes following a response biomarker-guided approach to treatment using 177Lu-PSMA-I&T in men with metastatic castrate-resistant prostate cancer (Re-SPECT).

177LuPSMA is an effective treatment in metastatic castrate-resistant prostate cancer with trials adopting a standardised dose interval. Adjusting treatment intervals utilising early response biomarkers may improve patient outcomes. This study evaluated progression-free survival (PFS) and overall survival (OS) based on treatment interval adjustment utilising 177LuPSMA 24-h SPECT/CT (177Lu-SPECT) and early prostate-specific antigen (PSA) response. Retrospective analysis of a clinical 177Lu-PSMA-I&T treatment programme. In all, 125 men were treated with 6-weekly 177LuPSMA-I&T [median 3 cycles, interquartile range (IQR): 2-4], median dose 8.0 GBq [95% confidence interval (CI): 7.5-8.0]. Imaging screening involved 68GaPSMA-11 PET/diagnostic CT. 177Lu-SPECT/diagnostic CT was acquired following each therapy, and clinical assessments 3-weekly. Following dose 2 (week 6), a composite PSA and 177Lu-SPECT/CT imaging response [partial response (PR), stable disease (SD), and progressive disease (PD)] determined ongoing management. Response group (RG) 1 (marked reduction in PSA/imaging PR) break in treatment until subsequent PSA rise, then re-treatment. RG 2 (stable or reduced PSA and/or imaging SD) 6-weekly treatments until six doses, or no longer clinically benefitting. RG 3 (rise in PSA and/or imaging PD) recommended for an alternative treatment. Overall PSA50% response rate (PSARR) was 60% (75/125), median PSA-PFS 6.1 months (95%CI: 5.5-6.7), and median OS 16.8 months (95%CI: 13.5-20.1). 35% (41/116) were classified as RG 1, 34% (39/116) RG 2, and 31% (36/116) RG 3. PSARRs by RG were 95% (38/41), 74% (29/39), and 8% (3/36); median PSA-PFS rates were 12.1 months (95%CI: 9.3-17.4), 6.1 months (95%CI: 5.8-9.0), and 2.6 months (95%CI: 1.6-3.1); and OS rates were 19.2 months (95%CI: 16.8-20.7), 13.2 months (95%CI: 12.0-18.8), and 11.2 months (95%CI: 8.7-15.6) for RG 1, 2, and 3, respectively. The median months of 'treatment holiday' for RG 1 was 6.1 months (IQR: 3.4-8.7). Nine men had received prior 177LuPSMA-617 and were retreated with 177LuPSMA-I&T, with a PSARR of 56% on re-treatment. Personalising dosing regimens using early response biomarkers with 177LuPSMA has the potential to achieve similar treatment responses to continuous dosing while allowing treatment breaks or intensification. Further evaluation of early response biomarker-guided treatment regimens in prospective trials is warranted. Lutetium-PSMA therapy is a new therapy for metastatic prostate cancer that is well tolerated and effective. However, not all men respond equally, with some responding very well and others progressing early. Personalising treatments require tools that can accurately measure treatment responses, preferably early in the treatment course, so adjustments to treatment can be made. Lutetium-PSMA can measure tumour sites after each therapy by taking whole body 3D images at 24 h using a small radiation wave from the treatment itself. This is called a SPECT scan. Previous work has shown that both prostate-specific antigen (PSA) response and changes in tumour volume on a SPECT scan can predict how patients will respond to treatment as early as dose 2. This study demonstrates that stratifying how men are treated based on the results of the 6-week SPECT scan and PSA response potentially allows a third of men to have break in treatment and that these men have both longer time to disease progression and OS. Men with an increase in tumour volume and increase in PSA early in treatment (6 weeks) had shorter time to disease progression and OS. Men with early biomarker disease progression were offered alternative treatments early in an attempt to allow the opportunity to allow a more effective potential therapy, if one was available. The study is an analysis of a clinical programme, and was not a prospective trial. As such, there are potential biases that could influence results. Hence, while the study is encouraging for the use of early response biomarkers to guide better treatment decisions, this must be validated in a well-designed clinical trial.

Early prostate-specific antigen response among Black and non-Black patients with advanced prostate cancer treated with apalutamide.

Aim: To assess reduction in prostate-specific antigen (PSA) levels among Black and non-Black patients treated with apalutamide for non-metastatic castration-resistant prostate cancer (nmCRPC) or metastatic castration-sensitive prostate cancer (mCSPC). Patients & methods: Patients were identified from electronic medical data. PSA reduction (≥50%, ≥90%or below 0.2 ng/ml) after apalutamide initiation was assessed. Results: A total of 313 patients with nmCRPC and 260 patients with mCSPC were identified. The majority of patients treated with apalutamide achieved a 90% reduction in PSA regardless of indication or race. The proportion of patients achieving a PSA reduction at any level was similar among Black and non-Black patients and was consistent with apalutamide phase III trials. Conclusion: In routine clinical practice, apalutamide consistently produced reduction in PSA levels in Black and non-Black men with nmCRPC or mCSPC.

Immediate Prostate-specific Antigen Decline After Enzalutamide Following Abiraterone Predicts Survival in Castration-resistant Disease.

Although the sequential use of abiraterone and enzalutamide is not recommended because of possible cross-resistance, many patients with metastatic castration-resistant prostate cancer (mCRPC) are receiving sequential abiraterone and enzalutamide in the real world, and a subset of patients can benefit from sequential therapy with these drugs. This study aimed to identify patients who could benefit from the sequential use of enzalutamide after abiraterone use. We included 70 patients with mCRPC who received enzalutamide sequentially following abiraterone treatment. Decline in the prostatespecific antigen (PSA) levels at 4 weeks after enzalutamide initiation and the association between decline in PSA levels and survival were analyzed. Sixteen men (22.9%) achieved a decline of >50% in PSA levels after 4 weeks of enzalutamide administration. Overall survival (OS) after enzalutamide among men with >50% decline at 4 weeks was significantly better than that among men with a PSA decline <50% (not reached vs. 34 months, p=0.008). OS after first-line abiraterone treatment for men with PSA decline >50% and <50% was not reached and 46 months, respectively (p=0.007). A PSA decline of >50% at 4 weeks of enzalutamide administration was an independent predictor of longer OS. A PSA decline of >50% at 4 weeks after the start of sequential enzalutamide treatment following abiraterone treatment predicted long-term survival in patients with mCRPC. Early PSA decline can identify patients who benefit from second-line enzalutamide after abiraterone treatment and can be useful as a decision-making tool regarding treatment.

Stereotactic Radiotherapy for Lesions Detected via 68Ga-Prostate-specific Membrane Antigen and 18F-Fluorodexyglucose Positron Emission Tomography/Computed Tomography in Patients with Nonmetastatic Prostate Cancer with Early Prostate-specific Antigen Progression on Androgen Deprivation Therapy: A Prospective Single-center Study

BackgroundDual-tracer positron emission tomography/computed tomography (PET/CT) with a 68Ga-labelled prostate-specific membrane antigen (PSMA) ligand and 18F-fluorodeoxyglucose (FDG) improves detection of metastatic heterogeneity and burden in patients with nonmetastatic prostate cancer (nmPCa). However, there is limited prospective evidence regarding its impact on the efficacy of stereotactic body radiotherapy (SBRT). ObjectiveTo evaluate metastasis-free survival (MFS) and toxicity after SBRT to dual-tracer PET/CT-detected metastases in patients with nmPCa and early prostate-specific antigen (PSA) progression on androgen deprivation therapy (ADT; PSA ≤2 ng/ml). Design, setting, and participantsPatients were prospectively screened using dual-tracer PET/CT between April 2019 and October 2020. SBRT was recommended for patients with five or fewer nonvisceral metastases (SBRT group). Patients without detectable metastases (N−/M− group) and those who refused SBRT (ADT group) continued to receive ADT. Patients were followed with conventional imaging. InterventionSBRT to each PET/CT-detected metastasis. Outcome measurements and statistical analysisKaplan-Meier methods were used to determine MFS. Toxicity was evaluated using Common Terminology Criteria for Adverse Event v4.0. Results and limitationsSeventy-four consecutive patients were screened. The median PSA and PSA doubling time were 0.59 ng/ml and 4.56 mo, respectively. Overall, 54 patients had metastases and 17 had PSMA-/FDG+ disease. Seven patients were excluded from the MFS analysis, including two with a history of abiraterone treatment and five with more than five metastases. The median follow-up was 21.4 mo. The ADT group had shorter MFS than the SBRT group (11.0 mo vs not reached; hazard ratio [HR] 4.69, 95% confidence interval [CI] 2.92–25.0; p < 0.001) and the N−/M− group (11.0 mo vs not reached; HR 8.78, 95% CI 4.04–40.30; p < 0.001). There was no significant difference in median MFS between the SBRT group and the N−/M− group (p = 0.261). A PSA response >90% was achieved by 86% of patients in the SBRT group. There were no grade ≥3 adverse events after SBRT. The nonrandomized design is the major study limitation. ConclusionsDual-tracer PET/CT-guided SBRT delivered superior local control rates in comparison to ADT alone and had minimal toxicity. Patient summaryWe investigated metastasis-targeted radiotherapy for patients with up to five prostate cancer metastases detected with two different radioisotope scans. Our results show that this approach yields promising metastasis-free survival and low toxicity.

Prediction of early biochemical response after 177Lu-PSMA radioligand therapy with 68Ga-PSMA PET, a different perspective with quantitative parameters.

In this study, our aim was to evaluate the relationship of the quantitative data obtained from pretreatment 68Ga prostate-specific membrane antigen (PSMA) PET-computerized tomography (PET/CT) with treatment response of the patients with the diagnosis of metastatic castrationresistant prostate cancer (mCRPC) who received 177Lu-PSMA radioligand therapy (RLT). The patients who were given three or four cycles of 177Lu-PSMA RLT between January 2016 and June 2018 were evaluated retrospectively. Volumetric data; PSMA tumor volume (TV) and total lesion (TL) PSMA, were obtained from 68Ga-PSMA PET/CT for whole (PSMA-TVT and TL-PSMAT). The distance between the two furthest lesions (Dmax) was calculated. Posttreatment early prostate-specific antigen (PSA) values on the fourteenth day after treatment were obtained. According to the PSA responses, the patients were divided into two groups as progressed and nonprogressed. In univariate analysis, the relationship of PET quantitative data with biochemical response groups was evaluated with Mann-Whitney U test. Logistic regression was used in multivariate analysis. A total of 38 patients were included in the study. In univariate analysis, Dmax, PSMA-TVT and TL-PSMAT values were obtained at lower levels in the progressed group. In multivariate analysis, only Dmax was found to be a prognostic factor in predicting early biochemical response. Dmax is the most prognostic parameter in predicting the early biochemical response in patients with mCRPC; high total tumor volume and burden are also parameters that give us an idea about the response to treatment. The success rate will be higher if 177Lu-PSMA RLT treatment is planned for patients with higher tumor volume and spread.

Early PSA Change after [177Lu]PSMA-617 Radioligand Therapy as a Predicator of Biochemical Response and Overall Survival.

Simple SummaryRadioligand therapy with [177Lu]PSMA-617 (PSMA-RLT) is a promising therapeutic option for metastatic castration-resistant prostate cancers (mCRPC), as its clinical relevance has recently been confirmed in the phase III VISION-trial. As prostate-specific antigen (PSA) plays an important role in the response evaluation of this therapy, and the aim of this study was to prospectively assess the prognostic value of early PSA measurements. We found PSA changes as early as four weeks after the first administration of PSMA-RLT to be predictive of both long-term biochemical and PET imaging response, as well as overall survival. We then evaluated relevant predictive thresholds in PSA change at that time point, as the early detection of long-term (non-)response to PSMA-RLT can be of great benefit in the clinical management of terminally ill mCRPC-patients.Purpose: Radioligand therapy with [177Lu]PSMA-617 (PSMA-RLT) is a promising therapeutic option for metastatic castration-resistant prostate cancer (mCPRP). This study assessed the prognostic value of early PSA measurements during PSMA-RLT. Methods: 27 patients with mCRPC scheduled for PSMA-RLT were prospectively enrolled for a serial short-interval PSA-assessment. Change in PSA (∆%PSA) during two treatment cycles was correlated with biochemical response (BR) and change in tumor volume on PET (TV) after 16 weeks (w16), as well as overall survival (OS). PCWG3 criteria and the recently recommended threshold of ∆%PSA ≤ −30% were assessed for their predictive value. Results: ∆%PSA first correlated with BR, TV and OS after 4 weeks (c1w4). At c1w4, ∆%PSA ≤ −30% was associated with the biochemical response at w16 (p = 0.003) and a longer median OS (p = 0.025), whereas the PCWG3-derived threshold of ∆%PSA ≤ −50% showed no such correlation. In contrast, ∆%PSA ≥ 25% at c1w4 was associated with biochemical progression at w16 (p = 0.003) and a shorter median OS (p < 0.001). Conclusion: PSA changes as early as four weeks after PSMA-RLT allow a significant prediction of later biochemical and PET-based imaging response, as well as OS. At this early time point, a more lenient threshold for a PSA decrease of at least 30% appears better-suited for the prediction of a positive biochemical response and longer OS. In contrast, the PCWG3-derived threshold for PSA increase (+25%) reliably anticipates biochemical progression and shorter OS.

Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN

BackgroundApalutamide plus androgen deprivation therapy (ADT) significantly improved metastasis-free survival (MFS), overall survival (OS), and time to prostate-specific antigen (PSA) progression in the placebo-controlled SPARTAN study of high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC). ObjectiveTo assess the relationships between PSA kinetics, outcomes, and molecular subtypes in SPARTAN. Design, setting, and participantsThe authors conducted a post hoc analysis of nmCRPC patients randomized to receive apalutamide (n = 806) or placebo (n = 401) plus ADT and a subset stratified by molecular classifiers. InterventionApalutamide 240 mg/d. Outcome measurements and statistical analysisThe association between PSA kinetics and MFS, OS, time to PSA progression, and molecular subtypes was evaluated using the landmark analysis and Kaplan-Meier methods. Results and limitationsBy 3 mo, PSA decreased in most apalutamide-treated patients and increased in most placebo-treated patients. After apalutamide, the median time to PSA nadir, confirmed ≥50% PSA reduction, ≥90% PSA reduction, and PSA ≤0.2 ng/ml were 7.4, 1.0, 1.9, and 2.8 mo, respectively. By 6 mo, 90%, 57%, and 32% of apalutamide patients had ≥50% PSA reduction, ≥90% PSA reduction, and PSA ≤0.2 ng/ml, respectively, while only 1.5% of placebo patients experienced ≥50% PSA reduction. PSA reductions were observed within 3 mo and up to 12 mo of apalutamide treatment, and were similar across molecular subtypes. Deep PSA responses (≥90% PSA reduction or PSA ≤0.2 ng/ml) at landmark 6-mo apalutamide treatment were significantly associated with improved time to PSA progression (hazard ratio {HR} [95% confidence interval {CI}] 0.25 [0.18–0.33] or 0.13 [0.08–0.21]), MFS (0.41 [0.29–0.57] or 0.3 [0.19–0.47]), and OS (0.45 [0.35–0.59] or 0.26 [0.18–0.38]; p < 0.001 for all). ConclusionsApalutamide plus ADT produced rapid, deep, and durable PSA responses by 6-mo treatment regardless of assessed molecular prognostic markers. An early PSA response with apalutamide was associated with clinical benefits, supporting prognostic value of PSA monitoring. Patient summaryIn this report, we describe how prostate-specific antigen (PSA) levels relate to outcomes in patients with nonmetastatic castration-resistant prostate cancer treated with apalutamide plus androgen deprivation therapy (ADT). We found that treatment with apalutamide plus ADT resulted in rapid, deep, and durable PSA responses in the majority of patients, including those with high-risk molecular subtypes, which were associated with improved survival.

Prognostic factors, efficacy, and toxicity of involved-node stereotactic body radiation therapy for lymph node oligorecurrent prostate cancer : An investigation of 117 pelvic lymph nodes.

The optimal radiotherapy regimen is not yet defined in the setting of oligorecurrent prostate cancer (oligorPC). There is evidence of high variability in treatment protocols among different centers worldwide, and no international consensus guidelines on treatment volumes, radiation schedules, and techniques. The purpose of the present retrospective study is to evaluate the efficacy and safety of involved-pelvic-node stereotactic body radiotherapy (SBRT) for oligorPC. Patients with pelvic node oligorPC following primary surgery, radical radiotherapy, or salvage radiotherapy for biochemical or local relapse of prostate cancer who underwent involved-node SBRT with biological effective dose (BED) > 100 Gy, with or without concurrent and adjuvant androgen deprivation therapy (ADT), were retrospectively evaluated. Biochemical progression-free survival (bPFS), distant progression-free survival (DPFS), overall survival (OS), possible prognostic factors, and toxicity outcomes were investigated. From November 2012 to December 2019, 74patients fitted the selection criteria. Atotal of 117 lesions were treated. Median follow-up was 31months (range 6-89). Concurrent ADT was administered in 58.1% of patients. The 1‑year, 2‑year, and 3‑year DPFS was 77%, 37%, and 19%, respectively; the 1‑year, 2‑year, and 3‑year OS was 98%, 98%, and 95%, respectively. The presence of asingle target lesion was associated with astatistically significant impact on OS. No in-field recurrence occurred. Patients who reached early prostate-specific antigen (PSA) nadir (< 3months after SBRT) had alower 3‑year survival (p = 0.004). The value of PSA nadir after SBRT and the time between primary treatment and SBRT had an impact on bPFS. Concomitant ADT was associated with improved DPFS. No acute or early late (> 6months) genitourinary and gastrointestinal adverse events of any grade were reported, albeit with relatively short median follow-up. SBRT is asafe and effective treatment for oligorPC, with a100% local control rate in our series. It is not possible to clearly assess the opportunity to postpone ADT prescription in patients with two or more nodal metastases. The number of secondary lesions, time-to-nadir PSA, PSA nadir value, and the time interval between primary treatment and SBRT were identified as prognostic factors. Future prospective randomized studies are desirable to better understand the still open questions regarding the oligorecurrent prostate cancer state.

China county-based prostate specific antigen screening for prostate cancer and a cost-effective analysis.

BackgroundProstate cancer is one of the most common malignant tumors worldwide, and is the third-leading cause of cancer death in men. Nearly 70% of new prostate cancer patients in China are locally advanced or widely metastatic with poor prognosis. Providing active treatment to early stage prostate cancer patients can improve the prognosis of prostate cancer patients. Thus, this study sought to evaluate the economy of early prostate specific antigen (PSA) screening for high-risk prostate cancer.MethodsBased on the data collected from the PSA screening activities of 11 county hospitals from October 2019 to April 2021, this study evaluated a high-risk prostate cancer population who received PSA screening and their quality of life and economy. The screening population comprised males aged over 50 years. All screening patients were tested for PSA. If the PSA value is unnormal, a further diagnosis based on magnetic resonance imagining (MRI) or a transrectal ultrasound-guided prostate biopsy were performed. The decision-tree and Markov model was used to simulate the process of disease development of high-risk prostate cancer patients who underwent screenings and those who did not, and the incremental cost-effectiveness ratio was also evaluated.ResultsA total of 13,726 men received a PSA screening. Of these, 1,062 men had abnormal PSA values, and 73 of these were diagnosed with prostate cancer. Of these 73 patients, 40, 21, and 12 had early stage, mid-stage, and late-stage prostate cancer, respectively. Compared to the patients unscreened, the 1,000 patients who received an early PSA screening increased their quality-adjusted life year (QALY) by 15.69 years; however, each QALY had an additional cost of 38,550 yuan, which was lower than the willingness to pay threshold of 72,447 yuan (per capita gross domestic product in 2020).ConclusionsFor high-risk prostate cancer patients, early screenings have a cost-effective advantage over no screenings. Thus, early screening should be vigorously promoted for high-risk prostate cancer patients.

Early Prostate-Specific Antigen Kinetics for Low- and Intermediate-Risk Prostate Cancer Treated With Definitive Radiation Therapy

PurposeThis study used a patient-specific model to characterize and compare ideal prostate-specific antigen (PSA) kinetics for low- and intermediate-risk prostate cancer after definitive radiation treatment with conventionally fractionated, hypofractionated, stereotactic body radiation therapy, or brachytherapy, both high-dose and low-dose rate. Methods and MaterialsThis retrospective analysis includes low- and intermediate-risk patients with prostate cancer treated between 1998 and 2018 at an National Cancer Institute–designated comprehensive cancer center. Demographics and treatment characteristics were prospectively collected. Patients had at least 2 PSA measurements within 24 months of treatment and were free from biochemical recurrence. The incidence of, time to, and risk factors for PSA nadir (nPSA) and bounce (bPSA) were analyzed at 24 months after radiation therapy. Ideal PSA kinetics were characterized for each modality and compared. ResultsOf 1042 patients, 45% had low-risk cancer, 37% favorable intermediate risk, and 19% unfavorable intermediate risk. nPSAs were higher for ablative modalities, both as absolute nPSA and relative to initial PSA. Median time to nPSA ranged from 14.8 to 17.1 months. Over 50% treated with nonablative therapy (conventionally fractionated, hypofractionated, and low-dose rate) reached an nPSA threshold of ≤0.5 ng/mL compared with 23% of stereotactic body radiation therapy and 33% of high-dose rate cohorts. The incidence of bPSA was 13.3% and not affected by treatment modality, Gleason score, or prostate volume. PSA decay rate was faster for ablative therapies in the 6- to 24-month period. ConclusionsAnalysis of PSA within 24 months after radiation therapy revealed ablative therapies are associated with a latent PSA response and higher nPSA. Multivariable logistics modeling revealed younger age, initial PSA above the median, presence of bPSA, and ablative therapy as predictors for not achieving nPSA ≤0.5 ng/mL. PSA decay rate appears to be faster in ablative therapies after a latent period. Understanding the different PSA kinetic profiles is necessary to assess treatment response and survey for disease recurrence.

Single center retrospective analysis of fifty-two prostate cancer patients with customized MR-guided transurethral ultrasound ablation (TULSA)

ObjectivesMR-guided transurethral ultrasound ablation (TULSA) has primarily been investigated for whole-gland prostate ablation, even though the technology is also well-suited for partial gland treatment. The objectives were to perform a clinical service evaluation of partial to whole-gland TULSA for patients with localized prostate cancer (CaP). TULSA was also evaluated as a combined therapy for a subset of patients presenting with both cancer and concurrent benign prostate hyperplasia (BPH). Subjects and methodsThis retrospective, consecutive clinical service evaluation included men with histopathologically-confirmed CaP who underwent TULSA either as primary or salvage treatment. The planned ablation was dependent on the individual tumor characteristics, concurrent BPH and patient preferences. The Clavien-Dindo classification was used to record complications. Surgeon-assessed functional outcomes were reported. Early treatment success was defined by negative multiparametric MRI (mpMRI) and lack of prostate specific antigen (PSA) recurrence. ResultsFifty-two consecutive patients (47 treatment-naïve and 5 salvage) were included, with median follow-up of sixteen months and a max of thirty-six months. Baseline median (IQR) age and PSA were 67 years (63–76) and 8.0 ng/ml (5.2–13), respectively. Two Grade IIIa adverse events were observed, with no bowel-related complications. For urinary continence outcomes, 1 patient worsened to 1 pad per day. All patients who were previously potent maintained erectile potency. Of the patient subgroup also seeking treatment for BPH, 83% reported symptom improvement. Median (IQR) PSA nadir after primary treatment was 1.1 ng/ml (0.5–2.1). Early treatment success was 88%. Nine patients underwent a single repeat TULSA. ConclusionCustomized prostate ablation with TULSA offers flexible ablation according to patients’ disease characteristics and treatment expectations, providing favorable safety and promising early MRI and PSA results. TULSA is a feasible combination therapy for patients with both cancer and concurrent BPH.

Early Prostate-Specific Antigen (PSA) Change at Four Weeks of the First-Line Treatment Using Abiraterone and Enzalutamide Could Predict Early/Primary Resistance in Metastatic Castration-Resistant Prostate Cancer.

Simple SummarySerum prostate-specific antigen (PSA) level is the most valuable biomarker in prostate cancer. This study investigates the predictive value of achieving >30% PSA decline at four weeks of first-line androgen signaling inhibitors (ASIs) using a multi-institutional cohort dataset of 254 mCRPC patients. The achievement of >30% PSA decline at four weeks is an independent predictor for overall survival (OS). Interestingly, in patients who did not achieve >30% PSA decline at four weeks—an achievement of the >30% PSA decline at 12 weeks is eventually observed in 30.9% of those patients. To identify the variables that discriminate the patient survival in 97 patients without achieving >30% PSA decline at four weeks of the first-line treatment, a multivariate analysis is conducted. The duration of androgen deprivation therapy before CRPC < 12 months and Eastern Cooperative Oncology Group Performance Status ≥ 1 are identified as independent predictors for shorter OS for those patients.The identification of early or primary resistance to androgen signaling inhibitors (ASIs) is of great value for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the predictive value of prostate-specific antigen (PSA) response at dour weeks of first-line ASIs treatment for mCRPC patients. A total of 254 patients treated with ASIs (abiraterone acetate: AA and enzalutamide: Enz) at the first-line treatment are retrospectively analyzed. Patients are stratified according to the achievement of >30% PSA decline at 4 and 12 weeks from the treatment initiation. At four weeks of the treatment, 157 patients (61.8%) achieved >30% PSA decline from the baseline. Thereafter, 177 patients (69.7%) achieved >30% PSA decline at 12 weeks of the treatment. A multivariate analysis exhibits >30% PSA decline at four weeks as an independent predictor for overall survival (OS). We note that 30 of 97 (30.9%) patients who did not achieve >30% PSA decline at four weeks consequently achieved >30% PSA decline at 12 weeks, and had a comparable favorable three years OS rate as the 147 patients achieving >30% PSA decline at both 4 and 12 weeks. To identify the variables that discriminate the patient survival in 97 patients without achieving >30% PSA decline at four weeks, a multivariate analysis is performed. The duration of androgen deprivation therapy before CRPC ≤ 12 months and Eastern Cooperative Oncology Group Performance Status ≥ 1 are identified as independent predictors for shorter OS for those patients. These data offer a concept of early treatment switch after four weeks of first-line ASIs when not observing >30% PSA decline at four weeks—particularly in patients with a modest effect of ADT and poor performance status.

Linear Model Selection and Regularization for Serum Prostate-Specific Antigen Prediction of Patients With Prostate Cancer Using R

Prostate cancer is the commonly diagnosed cancer worldwide, and there were 1,276 thousand new prostate cancer cases and 359 thousand deaths in 2018. Prostate-specific antigen (PSA) blood level is often elevated in men with prostate cancer, so PSA testing can detect prostate tumours when they are small, low-grade, and localized. The PSA testing is hard to apply on the less developed and poor areas without sufficient medical funds, so the early accurate PSA level prediction by statistical machine learning models is significant to avoid later stages of prostate cancer that spread outside the Prostate. In this literature, we compare three linear model selection and regularization methods (shrinkage, subset selection, dimension reduction) and nine candidate models (OLS regression, Ridge regression, Lasso regression, Elastic net, best subset selection, forward subset selection, backward subset selection, PCR, PLS) based on leave-one-out-cross-validation (LOOCV) prediction error. As the selection criteria leave-one-out cross-validation is sensitive to outliers, Mahalanobis distance is used for outlier detection and deletion before running each model. The shrinkage method (only lasso and elastic net models) and subset selection method (based on adjusted <inline-formula> <tex-math notation="LaTeX">$R^{2}$ </tex-math></inline-formula>, BIC, Cp, and cross-validation prediction error) can select the variables out. The feature selection results show that prostate weight, cancer volume, amount of benign prostatic hyperplasia, and whether seminal vesicle invasion is necessary variables must include predicting PSA. Age and capsular penetration are the least important variables. The variables of Gleason score, a percent of Gleason scores 4 or 5 are essential sometimes. All the diagnostic figures and results are coded by R, open access, and published on IEEE Xplore Code Ocean.