Short Prostate-specific Antigen Doubling Time Research Articles

Plain language summary: Does the amount of time it takes for prostate-specific antigen to double affect how long men with nonmetastatic castration-resistant prostate cancer live and their healthcare costs?

This is a plain language summary of a research article originally published in Clinical Genitourinary Cancer. The original article described the effect of rapidly rising prostate-specific antigen (PSA) levels on how long men with a type of advanced prostate cancer live and their healthcare costs. The prostate is a part of the male body that helps make semen. PSA is a protein produced by the prostate that can show how advanced prostate cancer has become. One measure of prostate cancer growth is assessing how quickly a patient's PSA level doubles. This is known as the PSA doubling time (PSADT). People with a shorter PSADT usually have faster-growing prostate cancer compared with people who have a longer PSADT of more than 12months (long PSADT). Researchers wanted to know if PSADT can predict cancer spread (known as metastasis) or death for people with a type of advanced prostate cancer called non-metastatic castration-resistant prostate cancer (nmCRPC). Researchers also wanted to know if PSADT can predict healthcare costs. This could help doctors choose the right treatment for their patients with nmCRPC. This was a real-world study, not a clinical trial. This means that researchers looked at what happened when men received the treatments prescribed by their own doctor as part of their usual healthcare treatment. In this study, researchers used insurance claim information. Researchers looked at information for 2800men with nmCRPC. Six out of every 10men (60%) had a long PSADT of more than 12months. Researchers found that it took longer for the cancer to spread to other parts of the body in men with a longer PSADT than men with PSADT of 12months or less. Researchers also found that men with a longer PSADT lived longer than men with PSADT of 12months or less. The long PSADT group had fewer healthcare visits overall than men with PSADT of 10months or less. Over time, it cost less to treat men with a long PSADT than men with PSADT of 10months or less. Generally, if PSADT was shorter, patients tended to do worse. In this real-world study, researchers found that men with nmCRPC lived longer and had lower healthcare costs if they had a long PSADT of more than 12months compared with men who had a shorter PSADT. Men with nmCRPC and a shorter PSADT may benefit from approved treatments that slow cancer spread and help them live longer. However, these treatments may have side effects and cost more than standard treatment. Doctors take all these things into account when choosing treatments for their patients. Most men in this study had a long PSADT of more than 12months. Standard treatment may be the right choice for them because they are more likely to have better outcomes than men with a shorter PSADT.

Survival and Economic Impact of Rapid Prostate-Specific Antigen Doubling Time in Patients With Nonmetastatic Castration-Resistant Prostate Cancer.

In patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), prostate-specific antigen doubling time (PSADT) is associated with risk of metastasis and survival. This study evaluated the association of PSADT with clinical and economic outcomes in a real-world setting among patients with nmCRPC not receiving novel hormonal therapy (NHT), using 2-month PSADT thresholds. We retrospectively identified Veterans Health Administration patients with nonmetastatic prostate cancer and ≥2 PSA increases after medical/surgical castration (2012-2016). The third measurement was the index (CRPC) date. Patients with ≥3 postindex PSA measurements, including index, were followed until death or ≥12 months until disenrollment, study end, or death, and grouped into 2-month cohorts based on postindex PSADT. Cox regression models assessed association between PSADT, time to metastasis, and death. Healthcare resource utilization and costs were evaluated. Among 2800 evaluable patients, median follow-up was 30 months and median PSADT was 17 months. Relative to the reference cohort (PSADT >12 months), all cohorts had significantly higher metastasis risk. PSADT ≤10-month cohorts had significantly greater mortality risk than the reference; hazard ratios (95% confidence intervals) ranged from 12.3 (9.2, 16.4) in the PSADT ≤2-month cohort to 1.3 (0.9, 2.0) in the >10 to ≤12-month cohort. Total costs were significantly higher for cohorts up to and including the PSADT >8 to ≤10-month cohort, than for the reference cohort. Mean per patient per month all-cause medical plus pharmacy costs were $6623, $4768, and $4049 in the PSADT ≤2-month, >2 to ≤4-month cohort, and >4 to ≤6-month cohorts, respectively, versus $1911 in the PSADT >12-month cohort (P <0.05). Most patients with nmCRPC have PSADT >12 months and a long natural history. For those with shorter PSADT, the risk of metastasis, death, and costs increased. These data can help select patients for NHT and conversely those who can safely delay NHT for nmCRPC.

Clinical factors associated with successful liquid tumor biopsy in men with prostate cancer.

e13567 Background: Liquid biopsies using cell-free DNA (cfDNA) can be used in prostate cancer (PrCa) patients when tissue is unavailable and repeat biopsy is not feasible. Given the older age of PrCa patients, liquid biopsy may detect alterations related to clonal hematopoiesis of indeterminate potential (CHIP), generating uncertainty in the clinical utility of the results. We sought to identify clinical predictors of successful cfDNA biopsy, where the reported alterations are more likely to reflect the individual’s prostate cancer cfDNA instead of CHIP in a large cohort of United States Veterans with PrCa. Methods: Next-generation sequencing of cfDNA biopsy specimens was performed through the VA National Precision Oncology Program (NPOP) from February 2019 to November 2022. Successful identification of PrCa cfDNA testing was defined as the identification of an alteration in one or more PrCa-related genes included on the panel ( AR, CDK12, SPOP, MED12, CCND1, BRAF, AKT1, TMPRSS2, ERG, ETV1, and ETV4). Student’s t-tests, univariate, and multivariate logistic regression estimated significant patient and disease-specific factors at the time of cfDNA biopsy and the likelihood of obtaining a successful cfDNA biopsy result. Results: Among 5611 total cfDNA tests performed, 2066 cfDNA tests from 1985 Veterans listed PrCa as the clinical indication, passed quality control measures, and could be linked to patient-level demographics. 814 (39%) tests were deemed successful based upon identification of at least one PrCa related gene alteration. The most frequently encountered PrCa alterations were in AR (76.5%) and TMPRSS2 (22.4%). PSA was significantly higher (IQR 209.1 ng/ml) and PSA doubling time (PSADT) was significantly shorter (IQR 2.4 months) in the cohort of Veterans with successful cfDNA testing (p&lt;0.001). Among 1581 tests that reported tumor fraction, an elevated tumor fraction &gt;10 was also significantly associated with success (46.3% vs 8.1%, p&lt;0.001). On multivariate analysis, PSA elevation above 4.8 ng/ml (p&lt;0.001) and PSADT &lt;6 months (p&lt;0.001) were significantly associated with successful cfDNA testing. Actionable DDR mutations, including ATM (15.2% vs 11.7%, p=0.02), BRCA1 (1.7% vs 0.6%, p=0.03), and BRCA2 (7.4% vs 4.4%, p=0.01) were significantly more likely to be detected in a successful test compared to an unsuccessful test. Conclusions: High PSA and short PSADT are significant predictors of a cfDNA test identifying PrCa-related gene alterations in Veterans with metastatic disease instead of alterations due solely to CHIP. Liquid biopsy in PrCa should be reserved for patients with relatively higher disease burden or more aggressive growth rate, reflected by PSA values &gt; 4.8 and PSADT &lt; 6 months, to increase the likelihood of identifying actionable alterations and improve interpretation of testing.

PD16-12 REAL-WORLD OUTCOMES AMONG MEN WITH NONMETASTATIC CASTRATION-SENSITIVE BIOCHEMICAL RECURRENCE AFTER DEFINITIVE THERAPY WITH SHORT PSA DOUBLING TIME RECEIVING EARLY SECONDARY TREATMENT

You have accessJournal of UrologyCME1 Apr 2023PD16-12 REAL-WORLD OUTCOMES AMONG MEN WITH NONMETASTATIC CASTRATION-SENSITIVE BIOCHEMICAL RECURRENCE AFTER DEFINITIVE THERAPY WITH SHORT PSA DOUBLING TIME RECEIVING EARLY SECONDARY TREATMENT Stephen J Freedland, Wei Gao, Angela Lax, Hongbo Yang, Krishnan Ramaswamy, David Russell, Agnes Hong, and Jasmine Ivanova Stephen J FreedlandStephen J Freedland More articles by this author , Wei GaoWei Gao More articles by this author , Angela LaxAngela Lax More articles by this author , Hongbo YangHongbo Yang More articles by this author , Krishnan RamaswamyKrishnan Ramaswamy More articles by this author , David RussellDavid Russell More articles by this author , Agnes HongAgnes Hong More articles by this author , and Jasmine IvanovaJasmine Ivanova More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003271.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is no consensus on treatment (tx) for men with nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence (BCR) after definitive tx (radical prostatectomy or radiotherapy). We assessed outcomes in men with nmCSPC and short prostate-specific antigen doubling time (PSADT) following BCR after definitive tx. METHODS: We reviewed the Veterans Health Administration (VHA) database between January 1, 2006 and June 22, 2020 for men with nmCSPC and BCR (index date) after definitive tx. Men were required to have PSADT ≤15 months after index date and were categorized into rapid (≤9 months) and less rapid (>9 but ≤15 months) PSADT. Outcomes included time to first antineoplastic tx after BCR and metastasis-free survival (MFS; time to metastasis or death). Cox proportional models compared the rapid and less rapid PSADT cohorts. Adjusted models controlled for baseline demographic and clinical characteristics. RESULTS: 753 men with nmCSPC were included in the analysis (rapid, n=485; less rapid, n=268). The rapid PSADT men were younger, more likely to be White, and had shorter median time from definitive tx to index (Table 1). Versus less rapid PSADT, rapid PSADT men had shorter median time to first antineoplastic tx (11.3 vs. 29.3 months), and MFS (94.1 vs. not reached) after BCR. CONCLUSIONS: Most rapid PSADT men underwent secondary tx within 1 year of BCR compared with less rapid PSADT men (53.2% vs 16.2%), whereas most less rapid PSADT men remained tx free for >2 years. Importantly, median MFS in men with rapid PSADT was 94.1 months, closely approximating the Pound data from Hopkins, wherein median time to metastases after BCR was 96 months (8 years). However, the Pound data included all BCR patients, not just those with rapid PSADT. Also, in the Pound data, no patients received early hormonal tx, whereas most VHA patients received secondary tx within 1 year of BCR. While circumstantial, the fact that rapid PSADT VHA patients heavily treated with secondary tx had similar outcomes to all BCR patients in the Pound series where none received aggressive secondary tx suggests the potential benefit of aggressive early tx of men with rapid PSADT after BCR. Source of Funding: Pfizer © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e493 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stephen J Freedland More articles by this author Wei Gao More articles by this author Angela Lax More articles by this author Hongbo Yang More articles by this author Krishnan Ramaswamy More articles by this author David Russell More articles by this author Agnes Hong More articles by this author Jasmine Ivanova More articles by this author Expand All Advertisement PDF downloadLoading ...

Comparison of Hormone-Sensitive Oligorecurrent Prostate Cancer Patients Based on Routine Use of Choline and/or PSMA PET/CT to Guide Metastasis-Directed Therapy

In hormone-sensitive oligorecurrent prostate cancer (PC), the literature showed [68Ga]Ga-PSMA (PSMA) and [18F]F-choline (FCH) PET/CT can successfully guide metastasis-directed therapies (MDT). This observational retrospective study aimed to explore, in routine use, the impact of FCH or PSMA PET/CT in guiding MDT for hormone-sensitive oligometastatic PC at different recurrences. In 2017-2020, patients initially treated with radical prostatectomy but, in biochemical recurrence (with PSA ≤ 2 ng/mL), diagnosed as oligometastatic based on FCH or PSMA PET/CT, were identified. MDT was stereotactic body radiotherapy (SBRT), elective nodal or prostate bed radiotherapy ± boost and ± androgen deprivation therapy (ADT). The primary endpoint was biochemical relapse-free survival (BR-FS), defined as a PSA increase ≥ 0.2 ng/mL above the nadir and increasing over two successive samples and the secondaries were ADT-free survival (ADT-FS). 123 patients (70 PSMA and 53 FCH) were included. The median follow-up was 42.2 months. The median BR-FS was 24.7 months in the PSMA group versus 13.0 months in the FCH group (p = 0.008). Similarly, ADT-FS (p = 0.001) was longer in patients in the PSMA group. In multivariate analysis, a short PSA doubling time before imaging (p = 0.005) and MDT with SBRT (p = 0.001) were poor prognostic factors for BR-FS. Routine use of FCH or PSMA PET/CT in hormone-sensitive PC showed an advantage for using PSMA PET/CT to guide MDT in terms of BR-FS and ADT-FS in patients with low PSA value. Prospective studies are needed to confirm these hypotheses.

Recurrence characteristics after focal salvage HDR brachytherapy in prostate cancer

Background and purposeRadiorecurrent prostate cancer is often confined to the prostate, predominantly near the index lesion. The purpose of this study was to look at recurrence characteristics in patients treated with focal salvage high dose-rate (HDR) brachytherapy. Materials and methodsPatients treated with MRI-guided HDR brachytherapy, with a single fraction of 19 Gy from July 2013 to October 2021 as focal salvage treatment, were prospectively included in the current study. Imaging data were collected regarding the occurrence of local, regional and distant recurrences, including location of local recurrences (LR) in relation to the HDR radiotherapy field. ResultsOne hundred seventy-five patients were included after focal salvage HDR brachytherapy (median follow-up 36 months (IQR 23–50)). Three-years biochemical recurrence-free survival, LR-free survival, in-field LR-free survival, out-of-field LR-free survival, any-recurrence-free survival and ADT-free survival were 43% (95%CI 34%–52%), 51% (41%–61%), 70% (61%–80%), 92% (88%–97%), 42% (32%–52%) and 86% (80%–92%), respectively. Larger GTV-size and shorter PSA doubling time were associated with in-field LR in multivariable analysis. ConclusionAfter focal salvage HDR brachytherapy with a dose of 1x19 Gy for local prostate cancer recurrence, subsequent recurrences are mostly local and in-field.

LBA63 PRESTO: A phase III, open-label study of androgen annihilation in patients (pts) with high-risk biochemically relapsed prostate cancer (AFT-19)

Pts with biochemically relapsed prostate cancer (BRPC) following radical prostatectomy (RP) and a short PSA doubling time (PSADT) are at risk for distant metastases. Apalutamide (APA), an androgen receptor (AR) antagonist, and abiraterone acetate plus prednisone (AAP), prolong survival in the metastatic setting. We evaluated if intensification of androgen deprivation therapy (ADT) prolongs biochemical progression-free survival (bPFS) in BRPC.

Apalutamide, Darolutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC): A Critical Review.

Simple SummaryApalutamide, darolutamide and enzalutamide are androgen-receptor signaling inhibitors proved to be useful in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). Although computed tomography and bone scans have been used to identify patients with nmCRPC in pivotal trials, currently, novel imaging techniques are widely used to stage patients, and they can detect metastases in many men with nmCRPC who are negative to conventional imaging. This review aims at discussing the role of apalutamide, darolutamide and enzalutamide in nmCRPC and the clinical implications of novel imaging techniques during treatment choice. Nonmetastatic castration-resistant prostate cancer (nmCRPC) represents a condition in which patients with prostate cancer show biochemical progression during treatment with androgen-deprivation therapy (ADT) without signs of radiographic progression according to conventional imaging. The SPARTAN, ARAMIS and PROSPER trials showed that apalutamide, darolutamide and enzalutamide, respectively, prolong metastasis-free survival (MFS) and overall survival (OS) of nmCRPC patients with a short PSA doubling time, and these antiandrogens have been recently introduced in clinical practice as a new standard of care. No direct comparison of these three agents has been conducted to support treatment choice. In addition, a significant proportion of nmCRPC on conventional imaging is classified as metastatic with new imaging modalities such as the prostate-specific membrane antigen positron emission tomography (PSMA-PET). Some experts posit that these “new metastatic” patients should be treated as mCRPC, resizing the impact of nmCRPC trials, whereas other authors suggest that they should be treated as nmCRPC patients, based on the design of pivotal trials. This review discusses the most convincing evidence regarding the use of novel antiandrogens in patients with nmCRPC and the implications of novel imaging techniques for treatment selection.

Third analysis of a randomized trial of finite abiraterone acetate (AA) plus LHRH agonist (LHRHa) versus LHRHa in biochemically recurrent, non-metastatic hormone-naïve prostate cancer (M0HNPC).

135 Background: In pre-operative studies, a short duration of AA + LHRHa produced marked cytoreduction in a subset of men with high-risk prostate cancer (PCa). However, in M0HNPC, androgen signaling inhibition (ASI) is reserved for men with short PSA doubling time. We reasoned that the subset of men who experience cytoreduction with pre-operative AA + LHRHa would also benefit from a short duration of AA + LHRHa at PSA recurrence. This report is a one-year follow-up of our second analysis (ASCO Annual Meeting 2018; PMID 34536949). Methods: FINITE is a phase II trial that randomized (1:1) to two treatment groups, 8 months of LHRHa alone or LHRHa plus AA 1000 mg and prednisone 5 mg daily (NCT01786265). Eligible patients had a rising PSA after definitive therapy and no prior systemic therapy. At disease progression, men were eligible for crossover to 8 months of the alternative therapy. The primary endpoint was PSA-free survival at 12 months (≤ 0.1 ng/dL). Time to PSA progression was calculated from date of initial treatment to date of PSA progression, defined as first occurrence of a rising PSA, if PSA remained detectable after treatment, or when the PSA ≥ 1 ng/dL, if it was undetectable after treatment and confirmed 4 weeks thereafter. The probabilities of PSA progression were defined using the Kaplan-Meier method. Results: 199 men were randomized, and 197 received initial treatment (LHRHa = 99, LHRHa + AA = 98). Median age at enrollment was 65 years, median PSA was 0.95 ng/dL (range 0.1 – 33.3), and median testosterone was 342.5 ng/dL (10-986). At data cut-off (October 1, 2021), men who received LHRHa + AA were more likely to be PSA-free 12 months after completing treatment (34% vs. 19%, p = 0.02). 168 men (85%) had experienced PSA progression, and median time to PSA progression was 24.3 months for entire cohort. Receipt of LHRHa + AA was associated with longer time to PSA progression than LHRHa alone (27.2 vs. 19.9 months, p = 0.003). Conclusions: Our findings support that finite treatment with AA + LHRHa produces more durable disease-free survival than LHRHa. The finite duration of AA + LHRHa is a toxicity-sparing approach that may allow for a transition from a treatment to curative paradigm for a subset of men with M0HNPC. Further analyses will aim to link the subset of men who benefit from finite AA + LHRHa between localized high-risk PCa and M0HNPC. Clinical trial information: NCT01786265.

68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in Recurrent Prostate Cancer: Diagnostic Performance and Association with Clinical and Histopathological Data.

Simple SummaryProstate cancer (PCa) relapse occurs in up to 50% of patients after radical treatment. Once PCa recurrence is detected, a precise identification of the number and sites of recurrence is necessary to tailor the treatment on the patient’s needs. Positron emission tomography (PET) plays a pivotal role in this clinical setting and new radiotracers have been developed to improve its performance. While 68Ga-PSMA is a well-established radiotracer for PCa recurrence detection, 68Ga-DOTA-RM2 is a recently proposed tracer that targets the gastrin-releasing peptide receptors that are overexpressed in prostate cancer. In this work, the performance of 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in identifying recurrent disease were compared on the same cohort, using the same study protocol, as this is the only way to assess whether one outperforms the other and therefore should be preferred in clinical practice. Furthermore, the association between PET findings and clinical and histopathological characteristics was investigated to find potential biomarkers.The aim of the present study is to investigate and compare the performances of 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in identifying recurrent prostate cancer (PCa) after primary treatment and to explore the association of dual-tracer PET findings with clinical and histopathological characteristics. Thirty-five patients with biochemical relapse (BCR) of PCa underwent 68Ga PSMA PET/MRI for restaging purpose, with 31/35 also undergoing 68Ga-DOTA-RM2 PET/MRI scan within 16 days (mean: 3 days, range: 2–16 days). Qualitative and quantitative image analysis has been performed by comparing 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI findings both on a patient and lesion basis. Clinical and instrumental follow-up was used to validate PET findings. Fisher’s exact test and Mann-Whitney U test were used to investigate the association between dual-tracer PET findings, clinical and histopathological data. p-value significance was defined below the 0.05 level. Patients’ mean age was 70 years (range: 49–84) and mean PSA at time of PET/MR scans was 1.88 ng/mL (range: 0.21–14.4). A higher detection rate was observed for 68Ga-PSMA PET/MRI, with more lesions being detected compared to 68Ga-DOTA-RM2 PET/MRI (26/35 patients, 95 lesions vs. 15/31 patients, 41 lesions; p = 0.016 and 0.002). 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI findings were discordant in 11/31 patients; among these, 10 were 68Ga-PSMA positive (9/10 confirmed as true positive and 1/10 as false positive by follow-up examination). Patients with higher levels of PSA and shorter PSA doubling time (DT) presented more lesions on 68Ga-PSMA PET/MRI (p = 0.006 and 0.044), while no association was found between PET findings and Gleason score. 68Ga-PSMA has a higher detection rate than 68Ga-DOTA-RM2 in detecting PCa recurrence. The number of 68Ga-PSMA PET positive lesions is associated with higher levels of PSA and shorter PSA DT, thus representing potential prognostic factors.

Clinical characteristics and outcomes for patients with non\u2011metastatic castration-resistant prostate cancer

This study used linked, routinely-collected datasets to explore incidence, clinical characteristics and outcomes of prostate cancer (PC) patients who experience a rise in prostate-specific antigen (PSA) levels despite androgen deprivation therapy (ADT), without evidence of metastases in their patient record, termed non-metastatic castration-resistant PC (nmCRPC). Routinely collected administrative data in Wales were used to identify patients diagnosed with PC and nmCRPC from 2000–2015. Logrank tests and Cox proportional hazard models were used to compare time-to-events across subgroups defined by PSA doubling time and age. Of 38,021 patients identified with PC, 1,465 met nmCRPC criteria. PC incidence increased over the study period, while nmCRPC categorizations reduced. Median time from PC diagnosis to nmCRPC categorization was 3.07 years (95% confidence interval [CI] 2.91–3.26) and from nmCRPC categorization to metastases/death was 2.86 years (95% CI 2.67–3.09). Shorter PSA doubling time (≤ 10 months, versus > 10 months) was associated with reduced time to metastases or death (2.11 years [95% CI 1.92–2.30] versus 5.22 years [95% CI 4.87–5.51]). Age was not significantly associated with time to metastases/death. Our findings highlight key clinical characteristics and outcomes for patients with nmCRPC prior to the introduction of recently approved treatments.

Prostate-Specific Antigen Kinetics Effects on Outcomes of Low-Volume Metastatic Prostate Cancer Patients Receiving Androgen Deprivation Therapy.

Background The present study aimed to analyse factors influencing the effects of androgen deprivation therapy (ADT) in patients with newly diagnosed metastatic castration-naïve prostate cancer (mCNPC), especially in low-volume disease (LVD), according to subclassification of metastatic prostate cancer established by the CHAARTED trial. Materials and Methods We reviewed 648 patients with newly diagnosed mCNPC receiving ADT at Chang Gung Memorial Hospital from January 2007 to December 2016. Basic characteristics and PSA kinetics profile were subsequently evaluated. Results 48.3% of LVD patients progressed to castration-resistant prostate cancer (mCRPC). Among them, CRPC group had significantly shorter time to PSA nadir (TTN) and faster time from PSA nadir to CRPC (TFNTC) (p < 0.001) compared to non-CRPC group. PSA doubling time (PSADT) < 4 months tended to be associated with faster disease progression and shorter overall survival (OS). Among all patients with metastatic prostate cancer, those with shorter TTN <9 months, higher nadir PSA level ≥1 ng/mL, and shorter PSADT <3 months had increased tendency for biochemical progression. Conclusions PSADT is an effective clinical predictor for disease progression and survival in LVD. Other PSA kinetics including TTN and TFNTC, though not the major predictors for disease progression or OS in LVD, might be the predictors for disease control status.

Current treatment of non-metastatic castration-refractory prostate cancer.

Non-metastatic castration-refractory prostate cancer (nmCRPC) is defined by increasing serum prostate specific antigen (PSA) levels despite androgen deprivation therapy in the absence of metastases on standard imaging methods including CT of the chest, abdomen and pelvis, and bone scan. Patients with nmCRPC and short PSA doubling time (PSAdt) are at high risk of developing early metastatic disease. The objective of this review is to summarize current data on the treatment of nmCRPC. The current data support the efficacy of three novel androgen receptor targeted agents (ARTA), darolutamide, apalutamide and enzalutamide. The design and eligibility criteria of the three key studies with darolutamide, apalutamide and enzalutamide were similar. Patients were required to have aPSAdt.

Efficacy and Safety of [225Ac]Ac-PSMA-617 Augmented [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Highly Advanced mCRPC with Poor Prognosis.

The use of 225Ac in prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), either as monotherapy or in combination with 177Lu, is a promising therapy approach in patients with metastatic castration-resistant prostate carcinoma (mCRPC). In this study, we report the efficacy and safety of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in 177Lu-naive mCRPC patients (n = 15) with poor prognosis (presence of visceral metastases, high total tumor burden with diffuse bone metastases or a short PSA doubling time of <2 months). Biochemical (by PSA serum value) and molecular imaging response (by [68Ga]Ga-PSMA-11 PET/CT) was assessed after two cycles of [177Lu]Lu-PSMA-617 RLT, with at least one [225Ac]Ac-PSMA-617 augmentation. In addition, PSA-based progression-free survival (PSA-PFS), overall survival (OS) and toxicity (according to CTCAE) were analyzed. We observed a biochemical- and molecular imaging-based partial remission in 53.3% (8/15) and 66.7% (10/15) of patients, respectively. The median PSA-PFS and OS was 9.1 and 14.8 months, respectively. No serious acute adverse events were recorded. Two out of fifteen patients experienced grade 3 anemia. No other grade 3/4 toxicities were observed. RLT-related xerostomia (grade 1/2) was recorded in 2/15 patients. Our data showed a high clinical efficacy with a favorable side effects profile of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in this highly challenging patient cohort.

Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART II.

The summary presented herein represents Part II of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with castration-resistant disease. Please refer to Part I for discussion of the management of patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1[Figure: see text] and detailed herein. The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles. This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.

Implementation of repeat biopsy and detection of cancer after a diagnosis of atypical small acinar proliferation of the prostate.

Current guidelines recommend a repeat biopsy within 3-6 months after an initial diagnosis of atypical small acinar proliferation (ASAP) due to the high incidence of cancer detection on repeat biopsy. The current study sought to investigate practice patterns after a diagnosis of ASAP in a real-world setting and examine the clinicopathological outcomes of repeat biopsy. The departmental database of the Hyogo Prefectural Nishinomiya Hospital identified 97 of 1,218 patients with a diagnosis of ASAP on initial biopsy from 2011 to 2016. Clinical and pathological data were retrospectively analyzed. Of the 97 patients, 34 (35.1%) underwent a repeat biopsy. Patients with a repeat biopsy had a significantly higher prostate-specific antigen (PSA) velocity and shorter PSA doubling time than patients without a repeat biopsy (P=0.0002), and of these 34 patients with a repeat biopsy, 16 (47.1%) were diagnosed as having cancer. Multivariate logistic regression analysis revealed that a small prostate (P=0.0250) and advanced age (P=0.0297) were associated with cancer detection on repeat biopsy. Of the 16 cancers identified, 13 (81.6%) were diagnosed with a Gleason score >6. The results indicated that the implementation of a repeat biopsy for patients with ASAP could be affected by clinical characteristics in real-world settings, despite the current recommendation of guidelines endorsing immediate repeat biopsy. Prostate volume and age would aid in the decision-making process to perform repeat biopsy in patients with high PSA velocity and short PSA doubling time after a diagnosis of ASAP.

A Prospective Trial of 68Ga-PSMA and 18F-FDG PET/CT in Nonmetastatic Prostate Cancer Patients with an Early PSA Progression During Castration.

Tumor heterogeneity and burden, which impact treatment outcome in prostate cancer, are rarely evaluated using next-generation imaging. The trial prospectively included 37 patients who had an early PSA progression (≤2 ng/mL) during castration and high-risk (PSA doubling time ≤10 months) nonmetastatic disease by conventional imaging. All patients underwent both 68Ga-PSMA and 18F-FDG PET/CT. Lesions were classified into PSMA+FDG± lesions and PSMA-FDG+ lesions. The primary endpoint was the prevalence of PSMA-FDG+ disease. Tumor burden, predictors for positive imaging, and suitability for oligometastases-directed therapy (OMDT) were also evaluated. All patients were treated with RP and the median duration of castration was 23 months. The median PSA at imaging was 0.57 ng/mL. Overall, 114 lesions were detected in 29 of the 37 patients. A high prevalence (73%) of N+/M+ disease was observed. Of the 114 lesions, 81 were PSMA+FDG± and 33 were PSMA-FDG+. Per patient level, 9 men (24%; 95% confidence interval: 10%-39%) showed at least one new PSMA-FDG+ lesions. A short PSA doubling time (P = 0.009, OR = 8.000) was associated with PSMA+FDG± disease, while a high Gleason grade group (P = 0.022, OR = 13.091) with PSMA-FDG+ disease. Nineteen patients (51%) with 51 lesions, including 10 PSMA-FDG+ lesions, could be enrolled for OMDT. Among different disease stages, PSMA-FDG+ disease was rarely detected in the hormone-sensitive cohort, but frequently found in the castration-resistant cohort. Using 68Ga-PSMA and 18F-FDG PET, we observed a high prevalence of N+/M+ disease and a significant proportion of PSMA-FDG+ disease in patients with an early PSA progression during castration (ChiCTR1900022634).

Clinical indicators for predicting prognosis after radium-223 administration in castration-resistant prostate cancer with bone metastases

Radium-223 (Ra-223) is a targeted alpha therapy that has been shown to prolong overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. However, prognosis after Ra-223 administration varies among patients. The aim of the present study was to assess risk factors associated with the poor prognosis of patients treated with Ra-223. We retrospectively reviewed patients' records of treatment with Ra-223 between October 2016 and December 2019. All patients had mCRPC, bone metastasis, and no known visceral metastases, and received up to six cycles of Ra-223 (55kBq/kg). Prognostic factors for OS were analyzed by Cox proportional hazards model and log-rank test. We identified 42 patients who received at least one cycle of Ra-223 (median six cycles, range 1-6). Approximately two-thirds of patients had received at least two lines of therapy for mCRPC. The median age was 74years, and the median follow-up duration was 13.6months. The median OS time was 16.6months. On multivariate analysis, PSA doubling time (PSADT) (0-3months) at baseline, number of bone metastases (≥ 20), and treatment line of Ra-223 (4th-5th line) remained significantly correlated with the poor OS (HR 4.354, P = 0.003; HR 2.855, P = 0.020; and HR 4.871, P = 0.001, respectively). Our study demonstrated that a shorter PSADT, a heavier volume of bone metastases, and a later treatment line before Ra-223 are poor prognostic factors for mCRPC patients. These newly discovered risk factors may help select patients who potentially have long-term OS after Ra-223 treatment.

Predictors of survival, healthcare resource utilization, and healthcare costs in veterans with non-metastatic castration-resistant prostate cancer

ObjectivesThe objective of this study was to evaluate the association of prostate-specific antigen doubling time (PSADT) with metastasis-free survival (MFS) and overall survival (OS), and to describe healthcare resource utilization (HRU) and costs among patients with non-metastatic castrate-resistant prostate cancer (nmCRPC) in the Veterans Health Administration setting. Methods and MaterialsPatients with nmCRPC were identified from the Veterans Health Administration electronic health record database (1/2007–8/2017). PSADT was categorized as <3 months, 3 to 9 months, 9 to 15 months, ≥15 months, and unknown. MFS and OS were assessed using multivariable Cox proportional hazards regression, including PSADT as a predictor. HRU and costs were described per-patient-per-year (PPPY). ResultsAmong 12,083 patients in the study, shorter PSADT was associated with shorter MFS and OS (PSADT <3 months vs. PSADT ≥15 months hazard ratio [HR] [95% confidence interval (CI)] = 0.307 [0.281, 0.335] and 0.371 [0.335, 0.410], respectively). Patients who developed metastasis had a 3-fold higher risk of death compared to those without metastasis (HR [95% CI] = 2.933 [2.763, 3.113]). Mean HRU increased following the onset of nmCRPC and metastatic castrate-resistant prostate cancer (mCRPC); mean inpatient stays more than doubled (0.2 vs. 0.5 and 0.6 vs. 2.8 PPPY, respectively). Similar increases in healthcare costs were observed; pharmacy costs more than tripled following nmCRPC ($2,074 vs. $6,839 PPPY). From nmCRPC to mCRPC, large increases were observed for inpatient costs ($7,257–$61,691), emergency room costs ($844–$1,958), and pharmacy costs ($4,115–$26,279) PPPY. ConclusionsIn Veterans with nmCRPC, shorter PSADT was significantly associated with shorter MFS and OS. Onset of nmCRPC and mCRPC was associated with substantial HRU and cost increases.

Prospective evaluation of 18F-DCFPyL PET/CT in biochemically recurrent prostate cancer: Analysis of lesion localization and distribution.

5556 Background: 18F-DCFPyL, a promising PET agent targeting prostate specific membrane antigen (PSMA), is prospectively evaluated in a single academic center for detecting recurrent lesions in prostate cancer patients with biochemical recurrence (BCR). Methods: We prospectively enrolled 150 men (51-91 years old, mean ± SD: 70.3±7.5) with biochemical recurrence (PSA median 2.38 ng/mL, range 0.12 to 698.4) after primary definitive treatment with prostatectomy (65%), radiotherapy (35%) or both (19%). The 18F-DCFPyL positive lesions compatible with prostate cancer were evaluated by two independent readers. Impact of 18F-DCFPyL PET/CT on patient management was recorded from clinical chart review. Results: 18F-DCFPyL PET/CT had an overall positivity rate of 83% (125 scans), which increased with higher prostate specific antigen (PSA) levels (ng/mL): 63% (PSA &lt; 0.5), 75% (0.5≤PSA &lt; 1), 91% (1≤PSA &lt; 2), 95% (2≤PSA &lt; 5) and 98% (PSA≥5), respectively. In the cohort who underwent prostatectomy, 18F-DCFPyL PET/CT had higher positivity rate in patients with shorter PSA doubling time (PSAdt) (94% in PSAdt 0-3 months vs. 53% in PSAdt &gt; 12 months, P&lt; 0.01). No difference of 18F-DCFPyL positivity rate was observed in post-radiation patients with different PSAdt, nor were there differences between patients with low grade (Gleason 6) or higher-grade prostate cancer (Gleason 7-10). 20 patients (13%) had lesions in the prostate bed only and 41 patients (27%) had oligometastatic disease (1-3 lesions), making them candidates for locally targeted therapy. We identified a total of 1455 18F-DCFPyL positive lesions, including 51 lesions in the prostate bed, 271 pelvic and 463 extra-pelvic lymph nodes, approximately 585 osseous lesions, including 5 patients with diffuse osseous metastases, and 85 lesions in other organs (most commonly in the lungs). 91 out of 150 patients (61%) had change in treatment after 18F-DCFPyL PET and, most noticeably, 48 of these patients (32% total) had lesions only localized on 18F-DCFPyL PET/CT despite negative conventional imaging. Conclusions: 18F-DCFPyL PET/CT holds great potential to be a “one-stop shop” diagnostic tool in the work-up of BCR prostate cancer, with high (61%) impact on the management of these patients. Clinical trial information: NCT03501940 .