Baseline Prostate-specific Antigen Values Research Articles

PSA Outcomes and Clinical Surveillance Among Patients With Nonmetastatic Castration-Resistant Prostate Cancer Treated With a Next-Generation Androgen Receptor Inhibitor in Urology Practices With or Without In-Office Dispensing

This retrospective study used electronic medical record data from community-based urology practices in the US (February 1, 2017, to September 17, 2021) to describe prostate-specific antigen (PSA) outcomes and clinical sur­veillance patterns among patients with nonmetastatic castration-resistant pros­tate cancer (nmCRPC) receiving next-generation androgen receptor inhibitors (ARIs) with or without in-office dispensing (IOD) services. Patients who were prescribed apalutamide, darolutamide, or enzalutamide were classified in IOD+ (IOD access + fill), IOD– (IOD access + no fill), or non-IOD cohorts (no IOD ac­cess). Outcomes were described by cohort from 14 days following initial prescrip­tion to the earliest of initiation of a new ARI or advanced prostate cancer medi­cation, end of clinical activity, or end of data availability. In total, 3300 patients were included (IOD+: n = 615; IOD–: n = 2474; non-IOD: n = 211). PSA response defined as a decline ≥50% from the baseline PSA value (PSA50) achieved by 6 and 12 months was observed in 80.0% and 83.8% of patients in the IOD+ cohort, 63.8% and 72.3% in the IOD– cohort, and 62.5% and 69.1% in the non-IOD cohort. Patients in the IOD+ cohort underwent fewer bone scans, computerized tomog­raphy, and next-generation imaging than IOD– and non-IOD cohorts and also had longer time from treatment initiation to first follow-up imaging. IOD services may better support comprehensive disease management for patients with nmCRPC receiving next-generation ARIs and may be associated with better long-term clin­ical outcomes.

Flare phenomenon visualized by 99mTc-bone scintigraphy has prognostic value for patients with metastatic castration-resistant prostate cancer.

This study aimed to determine the prognostic value of the flare phenomenon in patients with metastatic castration-resistant prostate cancer (mCRPC) using the bone scan index (BSI) derived from 99mTc-methylenediphosphonate (MDP) bone scintigraphy images. We categorized 72 patients from the PROSTAT-BSI registry with mCRPC who were followed-up for 2years after starting docetaxel chemotherapy to groups based on pre-chemotherapy BSI values of < 1, 1-4, and > 4. We assessed the effects of the flare phenomenon (defined as a > 10% increase in the BSI within 3months of starting chemotherapy, followed by > 10% improvement within the next 3months) on survival using Kaplan-Meier curves and Cox proportional hazard analyses. The flare phenomenon was found in 26 (36%) of the 72 patients. Prostate-specific antigen (PSA), alkaline phosphatase (ALP), and hemoglobin (Hb) levels steadily increased, then deteriorated in patients with and without flare, respectively. Elevated BSI and PSA values at 3months after starting therapy and the absence of abiraterone or/and enzalutamide therapy led to poor 2-year overall survival (OS) in the group without flare. In contrast, no influence was noticeable in the group with flare. The results of multivariable analyses that included only factors associated with PSA and BSI showed that increased baseline BSI (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.04-1.86; P = 0.023) and PSA (HR, 7.15; 95% CI 2.13-24.04; P = 0.0015) values could be independent risk factors for patients with mCRPC without flare. However, these factors lost significance during flare. The risk for all-cause death was significantly higher among patients with BSI > 4 without, than with flare. The results of univariable analyses indicated that flare positively impacted survival (HR, 0.24; 95% CI 0.06‒0.91; P = 0.035). Multivariable analysis did not identify any factors that could predict outcomes. Favorable prognosis, with fewer disturbances from other factors such as the use of abiraterone or/and enzalutamide, PSA changes, and BSI, was attainable in cases when the mCRPC patient demonstrated flare phenomenon. Follow-up bone scintigraphy at least every 3months could help to determine the prognosis of patients with bone metastasis of mCRPC.

Research of the best screen interval for middle aged and elderly Chinese males with baseline prostate specific antigen levels &lt;2.0 ng/mL in prostate cancer screening

This study aimed to investigate the optimal screening interval of a prostate specific antigen (PSA) screening program for men aged 40–70 with a baseline PSA &lt;2 ng/mL in China. 8-year period clinical data of Chinese males who underwent physical examination annually in our hospital were retrospectively collected. 397 healthy males were included.Total PSA (tPSA) and free PSA (fPSA) were collected, and the free/total PSA ratio (f/t PSA) was calculated. According to the baseline PSA value, study population was divided into 2 groups: 0–0.99 ng/mL and 1–1.99 ng/mL. Prostate biopsy indicates at tPSA &gt;10 ng/mL, or 4–10 ng/mL (gray area) and f/t PSA &lt;0.16. Kaplan-Meier survival analysis was used to calculate the relevant cumulative incidence rate. Over the eight-year screening period, 27 people (6.8%) had abnormal PSA that met prostate biopsy criteria. 7 cases of prostate cancer were detected (detection rate 25.9%) among the 27 patients who performed a biopsy. In the 0–0.99 ng/mL and 1–1.99 ng/mL group, 4.1% (13/317) and 17.5% (14/80) achieved biopsy criteria within 8 years, with a statistically significant difference (p &lt; 0.001). In both groups, abnormal PSA began appearing in the sixth year. According to stratifying the cohort age and PSA, abnormal PSA levels began to appear in all subgroups by the sixth year, except for men aged &lt;50 years plus baseline PSA &lt;1 ng/mL, where they appeared by the seventh year. Furthermore, in the group of baseline 40–49 years and baseline PSA &lt;2 ng/mL, the probability of meeting biopsy indications during eight years was very low (1.4%, 2/143). Chinese men aged 50–70 with baseline PSA &lt;2 ng/mL should undergo for PSA retest in the sixth year, while aged 40–49 with a baseline PSA &lt;2 ng/mL do not need PSA screening within eight years.

Very Long-Term Complete Remission Can Be Achieved in Men With High-Risk Localized Prostate Cancer and a Very High PSA Value: An Analysis of the GETUG 12 Phase 3 Trial.

Serum prostate specific antigen (PSA) is a well-known prognostic parameter in men with prostate cancer. The treatment of men with very high PSA values and apparently no detectable metastases is not fully established. Ancillary analysis from the GETUG 12 phase 3 trial. Patients with non-metastatic high-risk prostate cancer by bone and computerized tomography (CT) scan were randomly assigned to receive androgen deprivation therapy (ADT) and docetaxel plus estramustine or ADT alone. Relapse-free survival (RFS), clinical RFS, metastases-free survival (MFS), overall survival (OS), and prostate cancer-specific survival (PCSS) were estimated using the Kaplan-Meier method for different levels of PSA (50 ng/mL, 75 ng/mL, and 100 ng/mL). The relationship between PSA and outcomes was studied using residual-based approaches and spline functions. The median follow-up was 12 years (range: 0-15.3). Baseline PSA (<50 ng/mL, n=328; ≥50ng/mL, n=85) was associated with improved RFS (P=.0005), cRFS (P=.0024), and MFS (P=.0068). The 12-year RFS rate was 46.33% (CI 40.59-51.86), 33.59% (CI 22.55-44.97), and 11.76% (1.96-31.20) in men with PSA values <50 ng/mL (n=328), 50-100 ng/mL (n=68), and ≥100 ng/mL (n=17), respectively. Exploratory analyses revealed no deviation from the linear relationship assumption between PSA and the log hazard of events. Men with apparently localized prostate cancer and a high baseline PSA value have a reasonable chance of being long-term disease-free when treated with curative intent combining systemic and local therapy.

Outcomes and toxicity of oral Fosfestrol in metastatic castration-resistant prostate cancer-a real-world experience.

Although there are multiple drugs approved for the treatment of metastatic castration-resistant prostate cancer (CRPC), the cost can be a limiting factor in using them in a resource-limited setting. Therefore, less expensive alternatives are the need of the hour. We have been using Fosfestrol which is a cheap and orally administered oestrogen analogue in metastatic CRPC. We carried out a retrospective study to analyse its efficacy and toxicity. A total of 65 patients received Fosfestrol during 2015-2020. The median age was 65 years (range 50-83 years). Thirty-four patients (53%) had other medical comorbidities. Skeletal-only metastasis was the commonest pattern of metastasis (n = 41, 64%) followed by skeletal with nodal metastasis (n = 15, 23%). The majority of the patients had undergone upfront surgical castration (n = 60, 93%). All the patients had adenocarcinoma and 38 patients (58%) had a high Gleason's score. Forty-one patients (63%) had a prostate-specific antigen (PSA) response (decrease of ≥50% in the PSA concentration from the pre-treatment baseline PSA value) and 54 patients (83%) had a symptomatic response. At the end of a median follow-up of 16 months, the median progression-free survival (PFS) was 8.3 months (CI 4.7-11.8) and the median overall survival (OS) was 27.5 months (CI 25.4-29.5). PSA response and prior treatment with abiraterone acetate were found to have a significant association with survival outcomes. Patients with PSA response had better median PFS and OS; while patients who have received prior abiraterone acetate therapy had worse survival outcomes. Twenty-nine patients (45%) received some form of subsequent treatment after stopping Fosfestrol. The most common oxicity observed was thrombosis (n = 9, 13%) followed by gynecomastia (n = 4, 6%). We conclude that oral Fosfestrol is a cheap and effective agent in the armamentarium against metastatic CRPC and warrants further studies in a clinical trial setting.

A multicenter, retrospective observational study investigating baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer treated with primary androgen deprivation therapy.

This multicenter, retrospective, observational study investigated baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer who received primary androgen deprivation therapy, using Japan Study Group of Prostate Cancer registry data. Among patients in the Japan Study Group of Prostate Cancer registry, those who initiated primary androgen deprivation therapy and were aged 20years or older were enrolled in this study. The primary endpoint was time to disease progression, defined as time from primary androgen deprivation therapy initiation to either prostate-specific antigen or clinical progression. Secondary endpoints included prostate-specific antigen progression-free survival, prostate-specific antigen response (90% or greater reduction from baseline) and distribution of second-line treatment. Of the 2494 patients (goserelin, n=564; leuprorelin, n=1148; surgical castration, n=161; degarelix, n=621), those who received degarelix had higher prostate-specific antigen levels and Gleason scores and were at a more advanced clinical stage than those receiving goserelin or leuprorelin. The median time to disease progression (identical to the prostate-specific antigen progression-free survival result) was not reached for goserelin and leuprorelin, 52.7months for surgical castration and 54.0months for degarelix. Although baseline prostate-specific antigen values in the degarelix cohort were higher than those of the leuprorelin or goserelin cohorts, prostate-specific antigen responses were not different among the three cohorts. Regarding second-line treatment, the largest patient group received degarelix followed by leuprorelin (n=195). This study clarified patient characteristics and long-term effectiveness of primary androgen deprivation therapy in real-world clinical practice. Japanese urologists appear to select appropriate primary androgen deprivation therapy based on patient background and tumour characteristics, with degarelix largely reserved for higher risk patients.

Nadir Prostate-specific Antigen as an Independent Predictor of Survival Outcomes: A Post Hoc Analysis of the PROSPER Randomized Clinical Trial.

This post hoc analysis of PROSPER evaluated the relationship between depth of PSA decline and clinical outcomes in enzalutamide-treated men with nonmetastatic castration-resistant prostate cancer. PROSPER was an international, randomized, double-blind, placebo-controlled, phase 3 trial that demonstrated significantly improved metastasis-free survival and overall survival with androgen deprivation therapy plus enzalutamide vs placebo. A total of 905 enzalutamide-treated men were included in this post hoc analysis. Metastasis-free survival (primary endpoint) and overall survival (secondary endpoint) were evaluated for 4 mutually exclusive subgroups defined by PSA decline: <50% (reference); ≥50% to <90%; ≥90%, nadir ≥0.2 ng/mL; and ≥90%, nadir <0.2 ng/mL. Medians and 95% confidence intervals were determined using a 12-month landmark analysis; hazard ratios and P values were based on an unstratified Cox proportional analysis model. In enzalutamide-treated men, PSA declines of <50%, ≥50% to <90%, ≥90% with nadir ≥0.2 ng/mL, and ≥90% with nadir <0.2 ng/mL were associated with median metastasis-free survival in months (95% confidence intervals) of 22.1 (14.8-not reached), 34.2 (29.4-not reached), 36.6 (33.4-not reached), and not reached, respectively, and overall survival in months (95% confidence intervals) of 40.8 (31.7-44.9), 54.4 (49.0-67.0), 64.3 (63.4-not reached), and not reached, respectively. There was a statistically significant correlation between greater depth of PSA decline and improved clinical outcomes, suggesting a previously underappreciated relationship between changes in PSA levels and clinical outcomes in nonmetastatic castration-resistant prostate cancer.

A Personalized Clinical Dynamic Prediction Model to Characterize Prognosis for Patients With Localized Prostate Cancer: Analysis of the CHHiP Phase 3 Trial

The CHHiP trial assessed moderately hypofractionated radiotherapy in localised prostate cancer. We utilised longitudinal prostate-specific antigen (PSA) measurements collected over time to evaluate and characterise patient prognosis. We developed a clinical dynamic prediction joint model to predict the risk of biochemical or clinical recurrence. Modelling included repeated PSA values and adjusted for baseline prognostic risk factors of age, tumour characteristics and treatment received. We included 3,071 trial participants for model development using a mixed-effect submodel for the longitudinal PSAs, and a time-to-event hazard submodel for predicting recurrence of prostate cancer. We evaluated how baseline prognostic factor subgroups impacted on the nonlinear PSA levels over time and quantify the association of PSA on time-to-recurrence. We assessed bootstrapped optimism-adjusted predictive performance on calibration and discrimination. Additionally, we performed comparative dynamic predictions on patients with contrasting prognostic factors and investigated PSA thresholds over landmark times to correlate with prognosis. Patients that developed recurrence had generally higher baseline and overall PSA values during follow-up and had an exponentially rising PSA in the two-years before recurrence. Additionally, most baseline risk factors were significant in the mixed-effect- and relative risk submodels. PSA value- and rate-of-change was predictive of recurrence. Predictive performance of the model was good across different prediction times over an 8-year period, with an overall mean AUC of 0.70, mean Brier score of 0.10, and mean integrated calibration index of 0.048; these were further improved for predictions after 5 years of accrued longitudinal post-treatment PSA assessments. PSA thresholds less than 0.23ng/mL after 3 years were indicative of a minimal risk of recurrence by 8 years. We successfully developed a joint statistical model to predict prostate cancer recurrence, evaluating prognostic factors and longitudinal PSA. We showed dynamically updated PSA information can improve prognostication, which can be used to guide follow-up and treatment management options.

The effect of testosterone therapy on haematocrit and prostate specific antigen in the real-life setting

Testosterone therapy (TT) is commonly prescribed in men with androgen deficiency. TT has several common side effects. Moreover, the effect of TT on serum prostate specific antigen (PSA) levels has been a matter of debate over the last decade. We aimed to investigate the effect of TT on PSA and haematocrit levels in a cohort of men with androgen deficiency. Complete demographic, clinical and laboratory data from 106 consecutive hypogonadal men treated with TT were analysed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Serum hormones, complete blood count and PSA were measured in every patient at baseline and after 3 months of TT. Descriptive statistics and logistic regression models tested the association between clinical parameters and haematocrit and PSA values. Overall, median (IQR) patient's age and BMI were 54 (44-64) years and 26.2 (34.6-29) kg/m2, respectively. Above all, 63 (59.4%), 32 (30.2%) and 11 (10.4%) men were treated with T undecanoate, enanthate and gel formulation, respectively. Out of 106 men, 28 (26.4%) and 12 (11.3%) participants had PSA and haematocrit worsening (any degree), respectively. Patients who had PSA worsening (60.5 vs. 50.1 years, p=0.04) and haematocrit worsening (63 vs. 55 years, p=0.03) were older. At univariable logistic regression analysis, older age (OR 1.1, p<0.01) and lower baseline PSA values (OR 0.6; p=0.04) were associated with PSA worsening after TT. Similarly, older age (OR 1.2, p=0.04) and lower baseline haematocrit values (OR 0.7; p=0.03) were associated with haematocrit worsening after TT. After accounting for clinical and laboratory values no independent predictors of haematocrit rising were found. Approximately 20% and 10% of hypogonadal men treated with TT experienced PSA and haematocrit worsening. The degree of change was not meaningful and we failed to find any independent predictor of PSA and haematocrit rising in the real-life setting. None

Abstract 3318: PSMA-targeted thorium-227 conjugate (PSMA-TTC) inhibits tumor growth and abnormal bone changes in the intratibial LNCaP xenograft model of bone-metastatic prostate cancer

Abstract Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein specifically overexpressed on the cell membrane of prostate cancer cells. PSMA-targeted thorium-227 conjugate (PSMA-TTC, BAY 2315497) consists of a human PSMA-targeting antibody covalently linked to a 3,2-HOPO (hydroxypyridinone) chelator moiety, radiolabeled with alpha-particle emitting thorium-227. Previous studies have demonstrated PSMA-TTC to be an attractive therapy option for patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we investigated the efficacy of PSMA-TTC in the LNCaP intratibial model mimicking prostate cancer metastasized to bone. LNCaP prostate cancer cells were inoculated into the right tibiae of male NOD.scid mice. The mice were randomized to treatment groups (n=12/group) based on serum prostate-specific antigen (PSA) and treated with a single dose of vehicle or PSMA-TTC (300 kBq/kg, 0.75 mg/kg, i.v.). Tumor growth was followed by biweekly serum PSA measurements for 42 days. Tumor-induced abnormal bone growth, PSMA-TTC uptake, bone microarchitecture, bone formation rate and tumor area in tumor-bearing tibiae were determined by radiography, gamma counter, microCT, and dynamic and static histomorphometry, respectively. A single injection of PSMA-TTC efficiently inhibited intratibial tumor growth (p&amp;lt;0.001) as evidenced by a 82.6% decrease from baseline PSA value in the treatment group at the end of the study, whereas the vehicle group increased by 380% from baseline. Furthermore, the tumor-bearing tibiae were heavier (138%) than the non-tumor-bearing tibiae in the vehicle group, whereas in the PSMA-TTC-treated mice no such difference was observed (103%). PSMA-TTC decreased tumor-induced abnormal bone area in the tumor-bearing tibiae (43.5% of the vehicle). PSMA-TTC uptake relative to tibia weight was higher in the tumor-bearing tibiae compared with the non-tumor-bearing tibiae, resulting in higher levels of thorium-227 and its daughter isotype radium-223 both 3 days and 3 weeks post injection. In this preclinical study, PSMA-TTC showed robust antitumor efficacy, for the first time, in a model mimicking prostate cancer metastasized to bone as evidenced by a decrease in serum PSA levels, tumor-induced abnormal bone changes, and tumor-bearing tibia weights in the PSMA-TTC-treated mice. PSMA-TTC binds to PSMA-expressing cancer cells, delivering a cytotoxic dose of alpha radiation. The decay product of thorium-227, radium-223 binds to bone matrix and this could also contribute to the antitumor efficacy in this bone-metastatic model. Taken together, our data indicate activity of PSMA-TTC in bone-metastatic CRPC. PSMA-TTC as a monotherapy as well as in combination with darolutamide is currently being investigated in patients with mCRPC in a phase 1 clinical trial (NCT03724747). Citation Format: Christoph Schatz, Mari I. Suominen, Matias Knuuttila, Sabine Zitzmann-Kolbe, Jukka Rissanen, Sanna-Maria Käkönen, Urs Hagemann, Arne Scholz. PSMA-targeted thorium-227 conjugate (PSMA-TTC) inhibits tumor growth and abnormal bone changes in the intratibial LNCaP xenograft model of bone-metastatic prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3318.

AUTHOR REPLY

The majority of men diagnosed with prostate cancer in the PSA-screening era are eligible for active surveillance and is often the initial therapy in men with low-risk prostate cancer. Active surveillance may reduce unnecessary treatments for patients without increasing risk of prostate cancer mortality.123 However, Black men represented only 7%-13% in these prospective cohort studies. Compared to White men, it has been previously shown that Black men have an increased prostate cancer incidence, higher baseline prostate-specific antigen value, more aggressive prostate cancer features, greater frequency of biochemical recurrence after treatment, and higher overall cancer-specific mortality.

A phase II study of sEphB4-HSA in metastatic castration-resistant prostate cancer.

84 Background: Ephrin receptors and their membrane-localized ligands induce bidirectional signaling and facilitate tumor-stroma interactions. Expression of EphB4 is increased in prostate cancer tissue and cell lines and retained in castration resistant states, and can promote cell migration, invasion, and metastases. Blocking the EphB4-EphrinB2 pathway, which can be accomplished by soluble EphB4 conjugated to human serum albumin (sEphB4-HSA), has efficacy in preclinical models of aggressive prostate cancer. A phase I clinical trial of sEphB4-HSA led to response or stable disease in 56% of patients, with no grade 4 or 5 related adverse events, and combination pembrolizumab sEphB4-HSA led to a 52% response rate in EphrinB2 expressing urothelial cancer. We hypothesized that targeting the EphB4-EphrinB2 pathway may serve as a therapeutic target in the treatment of metastatic castration resistant prostate cancer (mCRPC). Methods: We conducted a single arm, phase II trial in patients with progressive mCRPC and treatment with at least one second generation androgen receptor (AR)-targeted therapy but no more than three prior therapies for mCRPC. On Day 1 of each cycle patients received sEphB4-HSA 1000 mg IV, with cycle length 14 days cycles 1-6 and cycle length 21 days for cycle 7 and beyond. The primary endpoint was confirmed prostate specific antigen (PSA) response rate (confirmed decrease in PSA by &gt; 50%). We employed a Simon two stage Minimax design, requiring two or more responses among the first 15 patients to enroll an additional ten patients. Results: Fourteen eligible patients enrolled in the study. Median age was 73.5 years (range 52-83), patients had a median baseline PSA value of 65.11 ng/mL (range 7.77-2850 ng/mL) and received a median of three prior therapies (range 1-3) for mCRPC. Ten patients received prior taxane for mCRPC or hormone sensitive prostate cancer. The median length of treatment with sEphB4-HSA was 6.5 weeks (range 2-35 weeks). The potentially treatment-related adverse events (AEs) that occurred in more than 25% of patients were hypertension (10 patients) and fatigue (7 patients). Three patients experienced a serious adverse event potentially related to therapy, including one patient with a grade 5 event (cerebral vascular accident) possibly related to study drug. No patient had a confirmed PSA response, and the study was stopped for futility. Thirteen patients had PSA progression ( &gt; 25% increase in PSA), and one patient withdrew due to toxicity prior to having an evaluable PSA response. The median time to PSA progression was 28 days (95% CI 28-64 days), and median time to radiologic progression was 55 days (95% CI 55 days-NR). Of three patients with measurable disease, two had stable disease and one had progressive disease. Conclusions: In patients with mCRPC who progressed on prior second generation AR-targeted therapy, sEphB4-HSA monotherapy had no discernable anti-tumor activity. Clinical trial information: NCT04033432.

OVERALL SURVIVAL EVALUATION OF PROSTATE CANCER PATIENTS TREATED WITH ANDROGEN DEPRIVATION THERAPY BY ESTIMATING FLUCTUANT PATTERNS OF METABOLIC FACTOR SERUM LEVELS

(Background) The effects of fluctuant patterns of serum alkaline phosphatase (ALP) and lactic acid dehydrogenase (LDH) levels on overall survival of patients with prostate cancer (PC) treated with androgen deprivation therapy (ADT) remain unclear. (Methods) We enrolled 236 patients with PC and divided into 3 cohorts by fluctuant patterns of serum levels of ALP and LDH between at baseline and at 1 year later, or at diagnosis of castration-resistant prostate cancer (CRPC): intermediate, within interquartile range (IQR) [I]; lower than IQR [L]; higher than IQR [H]. (Results) In the 1 year later ALP cohort, all parameters except age were significantly different. In the L cohort, 75% of patients had bone metastasis and > 50% developed CRPC or died. In the 1 year later LDH cohort, Eastern Cooperative Oncology Group-performance status (ECOG-PS) and clinical metastasis classification were significantly different among the cohorts. In the CRPC/ALP cohorts, baseline prostate-specific antigen values and clinical metastasis classification were significantly different among the cohorts, and all cases had metastasis in the L cohort. In the CRPC/LDH cohort, the L cohort had higher ECOG-PS and shorter time to CRPC. In the 1 year later ALP cohort, the hazard ratio (HR) for death of the L and H cohort to the I cohort was 3.77 and 2.27, respectively and both were significant. In the CRPC/LDH cohort, the HR for death of L cohort to I cohort was 1.99. (Conclusions) Larger fluctuations in serum ALP and LDH levels were a sign of poorer prognosis, especially for patients in the L cohort.

Myocardial infarction after prostate cancer diagnosis in Norway: a population-wide registry-based study

Abstract Background Survival after prostate cancer (PCa) is high for many patients, and it is now more likely they will die from cardiovascular disease than from PCa specific causes. However, patients with active malignancies have been excluded from trials to evaluate best treatments for myocardial infarction (MI). As people with PCa become a larger subpopulation of those experiencing a MI, clinicians need more comprehensive evidence regarding MI in people with PCa and if they are receiving optimal treatment. Purpose To identify the Norwegian population diagnosed with PCa that have experienced a MI after their cancer diagnosis using routinely collected registry data, and describe relevant patient and treatment characteristics, as well as identify areas of missing data. Methods We used data from Cancer Registry Norway to identify all people diagnosed with PCa between 2004 and 2019. Cancer data was linked with the Norwegian Myocardial Infarction Registry to identify PCa patients that were hospitalised for a MI as well as important features of the MI treatment period. Descriptive statistics were used to describe the number of people with PCa, important cancer specific features and variables related to the MI, as well as to explore missing data within collected variables. Results We identified 70646 people diagnosed with PCa in Norway between 2004 and 2019, of which, 2929 (4.1%) experienced a MI (3465 MIs in total). Most had a single MI (2528, 86.3%), around 10.7% (314) had two MIs, and 3.0% (87) had three or more. Of all the MIs, 20.7% (718 in 700 patients) were classified as ST elevated MIs and 76.2% (2641 in 2218 patients) as non-ST elevated MIs (Table 1). Around 9% of patients were missing a baseline prostate specific antigen value and over 20% did not have an identified cancer stage. Thrombolysis and percutaneous intervention had a high number of records with unknown status of these treatments (58.5% and 36.6%, respectively). Conclusions This population-wide registry-based study has demonstrated that linkage between Cancer Registry Norway and Norwegian Myocardial Infarction Registry provides a comprehensive dataset to further study the relationship between PCa and MI in the Norwegian population. This study benefits from data sourced from registries that have previously been found to be highly comprehensive and accurate. There was evidence of some variables with higher missing data, but we are confident that our planned further linkages with the Norwegian Cardiovascular Disease Registry and Norwegian Patient Registry, as well as using other clinical data, will help to overcome the current missing data issues. It is our plan to carry this research forward to provide a comprehensive, longitudinal analysis of how patients with PCa experience and are treated for an acute MI in Norway including PCa specific risk factors, comparison with current guidelines and if further guidelines should be created for people with PCa. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Norwegian Cancer SocietyNorwegian Institute of Public Health

Prostate-specific antigen response among Black and non-Black patients with advanced prostate cancer treated with apalutamide in a urology setting.

124 Background: Apalutamide (APA) is approved to treat patients with non-metastatic castration-resistant prostate cancer (nmCRPC) or metastatic castration-sensitive prostate cancer (mCSPC) in the United States (US) but low enrollment of Black patients in clinical trials has led to limited clinical data about APA for this population. This study describes prostate-specific antigen (PSA) responses among Black and non-Black patients with nmCRPC or mCSPC treated with APA in a real-world community urology setting. Methods: Clinical data from 2/2018 to 3/2021 collected at 69 US urology practices were used to evaluate nmCRPC or mCSPC patients who received ≥1 APA prescription fill (index date). Baseline PSA was reported based with the most recent baseline PSA value and PSA doubling time (PSADT) in months (mo) was calculated in patients with at least 2 PSA tests before APA initiation. PSA response defined as the proportion of patients achieving either a reduction of 50% (PSA50) or 90% (PSA90) from baseline and was evaluated in patients with a PSA test result 8 weeks or later after initiating APA. Among patients with a response, the time from the index date to the response was also evaluated. Study results for Black and non-Black cohorts were summarized separately. Results: Data from 289 nmCRPC (19% Black) and 237 mCSPC (19% Black) patients were identified. Median baseline PSA, median baseline PSADT and post-index PSA responses are shown in Table. A PSA50 response was attained by numerically similar proportions of Black and non-Black patients with nmCRPC or mCSPC. A PSA90 response was observed in a numerically higher proportion of Black than non-Black nmCRPC patients. Median time to PSA50 and PSA90 was also similar between groups. Conclusions: This real-world study of nmCRPC and mCSPC patients demonstrates that PSA50 and PSA90 responses are achieved by high proportions of both Black and non-Black patients. Moreover, the PSA50 and PSA90 responses observed in this study are highly consistent with those observed in APA’s Phase 3 registrational trials for nmCRPC (SPARTAN)1 and for mCSPC (TITAN)2.

Alkaline Phosphatase And Prostate-Specific Antigen Dynamics And Survival Outcomes In Patients With Metastatic Prostate Cancer Receiving Radium-223

Radium-223 (Ra-223) is a targeted alpha-emitter for metastatic castrate-resistant prostate cancer (mCRPC) patients that demonstrated overall survival (OS) benefit compared to placebo in the ALSYMPCA trial. A secondary analysis of the ALSYMPCA trial demonstrated that decreased alkaline phosphatase (ALP) values at 12 weeks after treatment initiation were associated with improved OS. We further investigate prostate-specific antigen (PSA) and ALP dynamics in a large real-world cohort of patients with mCRPC receiving Radium-223. The Flatiron Health database is a nationwide longitudinal de-identified database derived from electronic health record (EHR) data from 280+ cancer clinics (∼800 sites of care) representing 2.2 million patients in the United States. We included patients with mCRPC treated with Ra-223 between 2013 and 2017 with complete ALP and PSA data. We specified a priori the following factors in a Cox proportional hazards regression for OS: age, performance status, year of treatment, baseline PSA and ALP, occurrence of a PSA or ALP decrease at any point during treatment or within 12 weeks of last administration, timing of response (before cycle 3 versus after cycle 3). Date of first Radium-223 administration was considered the index date for time-dependent analyses. We analyzed data from 586 patients with mCRPC receiving Ra-223 at a median follow-up of 9.8 months, with 252 patients (29.7%) having received prior docetaxel or cabazitaxel. In total, 447 patients (76.3%) achieved any ALP decrease and 250 patients (42.3%) achieved an ALP decrease ≥30%. Of those who achieved an ALP decrease, the response occurred before cycle 3 in 301 patients (67.3%). The median percent change from baseline to ALP nadir was 27.9% (interquartile range [IQR] 10.3% to 46.8%). With respect to PSA, 192 patients (32.7%) achieved any PSA decrease and 124 patients (21.1%) achieved a PSA decrease ≥30%. The median percent change from baseline to PSA nadir was 43.9% (IQR 19.9% to 80.4%). In our survival analysis, we identified age, performance status, ALP value at baseline, PSA value at baseline, presence of an ALP decrease (hazard ratio [HR] 0.61; 95% CI 0.42-0.90; p = 0.012), and presence of a PSA decrease (HR 0.47; 95% CI 0.33-0.65; p = 0.001) as significant predictors of OS. Notably, timing of ALP decrease before or after cycle 3 (HR 0.76; 95% CI 0.57-1.02; p = .066) was not significantly associated with survival. We analyzed PSA and ALP dynamics in the largest reported series of patients receiving Ra-223 based on real-world data. We identified baseline ALP and PSA values, presence of an ALP decrease, and presence of a PSA decrease as predictors of OS. Approximately one-third of patients will have a delayed ALP response after cycle 3; however, timing of ALP response was not significantly associated with OS.

Integration of 68Ga-PSMA-PET/CT in Radiotherapy Planning for Prostate Cancer Patients.

The clinical data of 191 prostate cancer patients treated with definitive intensity-modulated RT were retrospectively analyzed. All patients were initially staged with thoracoabdominal CT and bone scintigraphy, and the second staging was performed using Ga-PSMA-PET/CT. Both stages were evaluated for the decision making of RT and any change in RT target volumes. After staging with Ga-PSMA-PET/CT, 26 patients (13.6%) had risk group changes, 16 patients (8.4%) had an increase in risk group, and 10 patients (5.2%) had a decrease in risk group. Down-staging occurred in 22 patients (11.5%), and upstaging was observed in 30 patients (15.7%). A total of 26 patients (13.6%) had nodal stage changes. After the Ga-PSMA-PET/CT scans, the number of metastatic patient increased to 17 (8.9%), with 4 of them moving from oligo- to polymetastatic disease. An additional irradiation of pelvic lymphatics and metastatic site was performed in 13 patients (6.8%) and 6 patients (3.2%), respectively. The RT was aborted in 4 patients (2.1%) because of parenchymal or distant site metastasis observed in the Ga-PSMA-PET/CT. We found that Ga-PSMA-PET/CT causes considerable migration in stage, risk group, and RT field arrangements, especially in high-risk patients regardless of the GS and baseline prostate-specific antigen values alone. Ga-PSMA-PET/CT seems to have a great influence on RT decision making in prostate cancer patients.

Optimal Timing of Cabazitaxel Introduction for Japanese Patients With Metastatic Castration-resistant Prostate Cancer.

Limited information is available to help physicians decide when to introduce cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC) patients. The objective of this study was to assess the optimal timing of cabazitaxel introduction. The clinical outcomes of 66 mCRPC patients receiving cabazitaxel following failure of docetaxel were retrospectively analyzed. Among the parameters possibly affecting the timing of cabazitaxel introduction, only an increased prostate-specific antigen (PSA) value from the diagnosis of CRPC had a significant impact on overall survival (OS) after the introduction of cabazitaxel. Furthermore, there was a significant correlation between the increased PSA value from the diagnosis of CRPC and the baseline PSA value at cabazitaxel introduction. Multivariate analysis showed that only the baseline PSA value at cabazitaxel introduction is an independent predictor of OS. A comparatively low PSA value could be an alternative index suggesting the optimal timing for cabazitaxel introduction.

Contemporary Trends and Survival Outcomes After Aborted Radical Prostatectomy in Lymph Node Metastatic Prostate Cancer Patients

BackgroundAborted radical prostatectomy (aRP) in lymph node (LN) metastatic (pN1) prostate cancer (PCa) patients showed worse survival in European patients. Contemporary rates of aRP are unknown in North America. ObjectiveTo examine the rate of aRP and its effect on cancer-specific mortality (CSM) in contemporary North American patients. Design, setting, and participantsWithin the Surveillance Epidemiology and End Results database (2004–2014), we identified 3719 pN1 PCa patients. InterventionRP. Outcome measurements and statistical analysisIncidence proportion and median survival of LN metastatic PCa patients who underwent aRP versus completed RP (cRP). Cumulative incidence plots and competing-risks regression (CRR) models tested CSM and other-cause mortality rates according to aRP versus cRP. The effect of selected variables on CSM rate was graphically depicted using LOESS methodology. All analyses were repeated after propensity score matching. Results and limitationsBetween 2004 and 2014, the rate of aRP decreased from 20.4% to 5.6% (p<0.001). Ten-year CSM rates were significantly higher after aRP (38.9% vs 21.6%) versus cRP (p<0.001). In multivariable CRR models, aRP yielded higher CSM (hazard ratio [HR]: 1.99) than cRP. A higher 5-yr CSM rate was recorded after aRP through the entire range of baseline prostate-specific antigen (PSA) values and in patients with up to nine LN metastases. After propensity score matching, aRP resulted in overall higher CSM (HR: 1.72). Higher CSM was recorded after aRP for PSA values up to 50ng/ml and in patients with up to seven LN metastases. Results were limited by a selection bias that applies to aRP patients. ConclusionsOf contemporary North American patients, 5% are affected by aRP. It confers a significant survival disadvantage that applies to patients with baseline PSA values up to 50ng/ml and in those with up to seven LN metastases. Patient summaryRadical prostatectomy should not be aborted in pN1 prostate cancer individuals.

PSA screening - for whom and when?

Reasons for and against screening of prostate cancer have been discussed widely over the last decade. In 2014, the European Randomized Trial for Screening of Prostate Cancer (ERSPC) has reported a relative reduction of the cancer-specific survival of 27% in participants who definitely followed the screening protocol. This relative advantage has proven to be stable from year 7 to year 13 after the beginning of screening. Still, the disadvantages of overdiagnosis and overtreatment are the downsides of a population-based screening approach. But given the overall advantage of screening, a risk-adapted prostate-specific antigen (PSA) screening using a baseline PSA value at ages 45-50 may significantly reduce the number needed to diagnose maintaining the benefits of screening. PROBASE is a randomized risk-adapted screening trial currently ongoing in Germany to answer this important question.