Prostate-specific Antigen Kinetics Research Articles

Changes in prostate-specific antigen kinetics during androgen-deprivation therapy as a predictor of response to abiraterone in chemonaïve patients with metastatic castration-resistant prostate cancer

PurposeMetastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. Abiraterone acetate (AA), enzalutamide, and chemotherapy are first-line treatments for patients with mCRPC. This study examined prognostic factors for AA response in the form of prostate-specific antigen (PSA) kinetics throughout androgen-deprivation therapy (ADT) in chemonaïve patients with mCRPC.Materials and MethodsWe retrospectively included data from 34 chemonaïve patients with mCRPC who had received AA at some point between January 2017 and December 2018. We separated patients into two study arms according to the decrease in PSA percentages after use of AA for 3 months. We correlated PSA kinetics parameters with response and compared the two study groups with respect to PSA kinetics.ResultsThe patients’ median age was 77 years. In the total group of patients, 64% had a response to AA, whereas 35% did not. The ratio of the PSA level at nadir to the level during ADT was significantly higher in the AA-sensitive group (19.78 vs. 1.03, p=0.019).ConclusionsPatients who experienced a dramatic change in PSA level during ADT were more likely to be resistant to AA after progression to mCRPC. Chemotherapy rather than AA might be more suitable as a first-line treatment for these patients.

PSA and PSA Kinetics as Predictors for 18F-Fluciclovine PET/CT Positivity in Biochemically Recurrent Prostate Cancer

Introduction: ¹⁸F-Fluciclovine PET/CT is one of the imaging techniques currently employed to restage prostate cancer (PCa). Due to the conflicting results reported in the literature, it is not yet known at what PSA threshold ¹⁸F-fluciclovine PET/CT could reliably demonstrate the presence of recurring disease. We explored the association between ¹⁸F-fluciclovine PET/CT positivity and prescan PSA, PSA doubling time, and PSA velocity in patients with biochemical recurrence (BCR) of PCa after curative-intent treatment. Methods: Data from 59 patients who underwent ¹⁸F-fluciclovine PET/CT for BCR after radical prostatectomy or radiotherapy were retrieved from a single institution database. Patients already undergone salvage treatments at the time of PET/CT, with newly diagnosed PCa or with initial diagnosis of metastatic PCa were excluded. A 2-sided independent samples Bayesian t test and Bayesian Mann-Whitney U test were used to assess the association between PET/CT and prescan PSA, PSA doubling time, and PSA velocity. Results: Evidence for no difference between PET/CT-positive and -negative patients for log-transformed PSA was found (BF₀₁ 3.61, % error: 0.01). Robustness check and sequential analysis showed stability across a wide range of prior distribution specifications. The hypothesis of no difference in terms of PSA-dt and for PSA-vel between groups was found to be more likely compared to the alternative hypothesis (BF₀₁ of 3.44 and 3.48, respectively). Conclusion: PSA and PSA kinetics are unlikely to be associated with ¹⁸F-fluciclovine PET/CT positivity in patients with BCR, and none of these serum biomarkers might be used as single predictors of PET/CT detection. Larger studies might be needed to evaluate the role of different predictors.

Advancing Traditional Prostate-specific Antigen Kinetics in the Detection of Prostate Cancer: A Machine Learning Model

BackgroundProstate-specific antigen (PSA) kinetics, defined as the change in PSA over time, may be of use as a predictor of prostate cancer. PSA kinetics can be assessed as the PSA velocity, which is traditionally evaluated dichotomously and classified as abnormal if greater than either 0.35 or 0.75 ng/ml/yr. Machine learning models may provide additional benefit in assessing risk using PSA kinetics instead of PSA velocity. ObjectiveTo improve the utility of PSA kinetics by constructing a generalizable, universal machine learning model. Design, setting, and participantsData were obtained from the PLCO and PCPT trials and from a contemporary Australian cohort. PSA data were interpolated using a modified Gaussian process. A machine learning model based on a two-headed approach was designed, in which the multivariable input was fed into a one-dimensional ResNet18 model. Outcome measures and statistical analysisThe model performance was assessed compared to PSA levels and PSA velocity in terms of area under the receiver operator characteristic curve (AUC). Results and limitationsA total of 10719 patients were included in the analysis. In tests on a validation set of the complete database to diagnose grade group ≥2, the AUC was 0.886 (95% confidence interval [CI] 0.870–0.902) for the machine learning model, compared to 0.807 (95% CI 0.796–0.819) for PSA and 0.627 (95% CI 0.607–0.648) for PSA velocity. ConclusionsMachine learning models can be used to augment the diagnostic utility of PSA kinetics in the diagnosis of prostate cancer. We demonstrated significant improvements in accuracy compared to the traditional approaches of PSA velocity and PSA thresholds. Patient summaryProstate cancer diagnosis is limited by the diagnostic accuracy of the prostate-specific antigen (PSA) blood test. Advances in techniques such as machine learning algorithms can greatly improve the diagnostic accuracy of prostate cancer screening without additional costs or tests.

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.

El índice nutricional pronóstico como factor pronóstico independiente para la respuesta al tratamiento, la supervivencia y la elección del fármaco en el cáncer de próstata metastásico resistente a la castración tratado con acetato de abiraterona o enzalutamida

PurposeWe designed this study to identify the prognostic value of baseline prognostic nutritional index (PNI) in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate or enzalutamide. MethodsOne hundred one mCRPC patients were included. PNI was calculated using formula 10 × serum albumin value (g/dl)+.005 × total lymphocyte count (per mm3). ROC analysis was used for determining prognostic PNI value. ResultsThe statistically significant cut-off value for PNI was 46.62. Initial PSA response and PSA kinetics (early PSA response and 30-50%-90% PSA response at any time) were much better in PNI>46.62 group than the PNI ≤46.62 group (P<.01). In multivariate analysis, baseline PNI level >46.62 was an independent predictor of PSA-PFS (HR: .42; P<.01), radiologic PFS (HR: .53; P<.01), and OS (HR: .42; P<.01). In the PNI≤46.62 group, median OS was 7.4 months (95% CI: 4.1-10.7) for the abiraterone acetate subgroup vs. 17.6 months (95% CI: 10.1-25.1) for enzalutamide subgroups (P<.01). ConclusionPNI is a useful, independent prognostic marker for mCRPC patients treated with either abiraterone acetate or enzalutamide. Using pre-treatment PNI may help clinicians in the prediction of survival and decision making based on abiraterone acetate or enzalutamide.

Incidental prostate cancer after holmium laser enucleation of the prostate-A narrative review.

Prostate cancer can be detected incidentally after surgical therapy for benign prostatic obstruction such as holmium laser enucleation of the prostate (HoLEP), thus called incidental prostate cancer (iPCa). We aimed to review the studies on iPCa detected after HoLEP and investigate its prevalence. A detailed search of original articles was conducted via the PubMed-MEDLINE, Web of Science, Wiley Online Library and Cochrane Library databases in the last 10years up to 1May 2021 with the following search string solely or in combination: "prostate cancer", "prostate carcinoma", "holmium laser enucleation of the prostate" and "HoLEP". We identified 19 articles to include in our analysis and divided them into six main categories: HoLEP versus open prostatectomy and/or transurethral resection of the prostate in terms of iPCa, oncological and functional outcomes, the role of imaging modalities in detecting iPCa, predictive factors of iPCa, the role of prostate-specific antigen kinetics in detecting iPCa and the management of iPCa after HoLEP. We found that the iPCa after HoLEP rate ranges from 5.64% to 23.3%. Functional and oncological outcomes were reported to be encouraging. Oncological treatment options are available in a wide range.

Intermittent Hormone Therapy Models Analysis and Bayesian Model Comparison for Prostate Cancer

The prostate is an exocrine gland of the male reproductive system dependent on androgens (testosterone and dihydrotestosterone) for development and maintenance. First-line therapy for prostate cancer includes androgen deprivation therapy (ADT), depriving both the normal and malignant prostate cells of androgens required for proliferation and survival. A significant problem with continuous ADT at the maximum tolerable dose is the insurgence of cancer cell resistance. In recent years, intermittent ADT has been proposed as an alternative to continuous ADT, limiting toxicities and delaying time-to-progression. Several mathematical models with different biological resistance mechanisms have been considered to simulate intermittent ADT response dynamics. We present a comparison between 13 of these intermittent dynamical models and assess their ability to describe prostate-specific antigen (PSA) dynamics. The models are calibrated to longitudinal PSA data from the Canadian Prospective Phase II Trial of intermittent ADT for locally advanced prostate cancer. We perform Bayesian inference and model analysis over the models’ space of parameters on- and off-treatment to determine each model’s strength and weakness in describing the patient-specific PSA dynamics. Additionally, we carry out a classical Bayesian model comparison on the models’ evidence to determine the models with the highest likelihood to simulate the clinically observed dynamics. Our analysis identifies several models with critical abilities to disentangle between relapsing and not relapsing patients, together with parameter intervals where the critical points’ basin of attraction might be exploited for clinical purposes. Finally, within the Bayesian model comparison framework, we identify the most compelling models in the description of the clinical data.

Single-Center Evaluation of Treatment Success Using Two Different Protocols for MRI-Guided Transurethral Ultrasound Ablation of Localized Prostate Cancer.

ObjectivesTo assess differences in 24-month oncologic and functional outcomes in men with low to intermediate-risk prostate cancer treated with MRI-guided transurethral ultrasound ablation (TULSA) using intentionally conservative versus intensified treatment parameters.Patients and MethodsPatients from a single center involved in two multicenter trials were included in this analysis. This included 14 of 30 patients with Gleason 3 + 3 from a Phase I study using intentionally conservative treatment parameters, and 15 of 115 patients with Gleason ≤ 3 + 4 from a pivotal study using intensified parameters. Follow-up data compared across these cohorts included 12-month biopsy and MRI for all patients, and 24-month PSA, micturition and quality of life (IIEF, IPSS, IPSS-QOL). The prognostic value of baseline parameters and PSA kinetics on 12-month histological recurrence was evaluated by logistic regression.Results12-month biopsy revealed clinically significant residual disease in 4 (29%) and 2 (14%) patients from the Phase I and pivotal studies, respectively. PSA nadir was 0.7 ng/ml for Phase I and 0.5 ng/ml for pivotal study patients. Patient age at diagnosis, use of MRI fusion/systematic prostate biopsy, number of obtained cores at initial biopsy, PSA course, and PSA nadir were identified as prognostic factors for treatment success. All but one patient from each cohort maintained erection firmness sufficient for penetration. No cases of pad use were reported at 24 months. There were no Grade 4 or higher adverse events, and no late toxicity related to the procedure.ConclusionTwo-year follow-up demonstrated the efficacy of TULSA for the treatment of localized prostate cancer, and the durability of PSA and functional outcomes. Intensifying treatment parameters in the pivotal trial had no impact on safety or functional outcomes through 24 months, while reducing the recurrence rate for clinically significant disease. Careful patient selection by MRI fusion/systematic prostate biopsy and adequate follow-up through routine 12-month biopsy are recommended.

Five Year Results of Short Course Complete Androgen Blockade With Abiraterone Acetate and LHRH Agonist for Unfavorable Intermediate and Favorable High Risk Prostate Cancer

Purpose/Objective(s)Androgen deprivation therapy (ADT) and radiotherapy (RT) are synergistic, and the combination results in improved survival outcomes for aggressive prostate cancers. However, long-term ADT carries substantial burden of toxicity and morbidity. We hypothesized that a combination of definitive prostate RT and short-term complete androgen blockade (CAB) in men with unfavorable intermediate or favorable high-risk localized PC would provide excellent biochemical control and allow high rates of testosterone recovery. This combination would allow an escalation of therapy for unfavorable intermediate risk and de-escalation for favorable high-risk patients. We tested this hypothesis in a prospective trial of neoadjuvant/concurrent/adjuvant abiraterone acetate, prednisone, and LHRH agonist given for 6 months in conjunction with definitive prostate external beam RT. We now report the mature results of this trial.Materials/Methods37 men were enrolled in an IRB-approved NCT-registered prospective multi-center single arm investigator-initiated trial between January 2014 and August 2016. Eligibility required unfavorable intermediate risk of low volume high risk (NCCN) prostate cancer. All men were treated with 6 months of abiraterone acetate (1000mg daily), prednisone (5mg daily), and depot LHRH agonist initiated 8 weeks prior to standard fractionation RT to prostate/seminal vesicles +/- pelvis. Endpoints included PSA and testosterone (T) kinetics, biochemical progression-free survival (PFS), metastasis-free survival (MFS), overall survival (OS), and patient-reported quality-of-life.ResultsEnrolled patients were low volume (T1-2 disease and PSAs < 20 ng/ml), with Grade Group 1 (11%), 2 (11%), 3 (35%), 4 (27%), and 5 (16%); 43% were high-risk. The median follow-up time among all 37 surviving patients is 58months (range 24-65). Treatment was well tolerated and has been reported previously. In the entire cohort, 5-year BPFS was 92% (95% CI 72-98%). 32 out of 37 men recovered T to at least 150 ng/dl; the median time to T recovery was 9.2 mo (95% CI: 9.0-12.2). In men with T recovery, the 5-year BPFS was also 92% (95% CI: 71-98%). Hormonal/sexual function declined at six months but had improved by 24 mo and remained stable thereafter.ConclusionFor select men with aggressive prostate cancer, short course CAB with abiraterone acetate plus prednisone in combination with definitive prostate RT allows rapid T recovery and can provide excellent biochemical control up to 5 years. Short-course CAB is feasible for favorable high risk prostate cancer and may support optimization of patient quality of life. Prospective randomized trials should be considered. Androgen deprivation therapy (ADT) and radiotherapy (RT) are synergistic, and the combination results in improved survival outcomes for aggressive prostate cancers. However, long-term ADT carries substantial burden of toxicity and morbidity. We hypothesized that a combination of definitive prostate RT and short-term complete androgen blockade (CAB) in men with unfavorable intermediate or favorable high-risk localized PC would provide excellent biochemical control and allow high rates of testosterone recovery. This combination would allow an escalation of therapy for unfavorable intermediate risk and de-escalation for favorable high-risk patients. We tested this hypothesis in a prospective trial of neoadjuvant/concurrent/adjuvant abiraterone acetate, prednisone, and LHRH agonist given for 6 months in conjunction with definitive prostate external beam RT. We now report the mature results of this trial. 37 men were enrolled in an IRB-approved NCT-registered prospective multi-center single arm investigator-initiated trial between January 2014 and August 2016. Eligibility required unfavorable intermediate risk of low volume high risk (NCCN) prostate cancer. All men were treated with 6 months of abiraterone acetate (1000mg daily), prednisone (5mg daily), and depot LHRH agonist initiated 8 weeks prior to standard fractionation RT to prostate/seminal vesicles +/- pelvis. Endpoints included PSA and testosterone (T) kinetics, biochemical progression-free survival (PFS), metastasis-free survival (MFS), overall survival (OS), and patient-reported quality-of-life. Enrolled patients were low volume (T1-2 disease and PSAs < 20 ng/ml), with Grade Group 1 (11%), 2 (11%), 3 (35%), 4 (27%), and 5 (16%); 43% were high-risk. The median follow-up time among all 37 surviving patients is 58months (range 24-65). Treatment was well tolerated and has been reported previously. In the entire cohort, 5-year BPFS was 92% (95% CI 72-98%). 32 out of 37 men recovered T to at least 150 ng/dl; the median time to T recovery was 9.2 mo (95% CI: 9.0-12.2). In men with T recovery, the 5-year BPFS was also 92% (95% CI: 71-98%). Hormonal/sexual function declined at six months but had improved by 24 mo and remained stable thereafter. For select men with aggressive prostate cancer, short course CAB with abiraterone acetate plus prednisone in combination with definitive prostate RT allows rapid T recovery and can provide excellent biochemical control up to 5 years. Short-course CAB is feasible for favorable high risk prostate cancer and may support optimization of patient quality of life. Prospective randomized trials should be considered.

Working Towards a New Definition of Biochemical Failure in the Era of Stereotactic Body Radiation Therapy for Prostate Cancer

Since the seminal Phoenix definition (nadir PSA+2) of biochemical failure (BCF) was published in 2006, increasingly more patients with low- and intermediate-risk prostate cancer (PCa) are being treated with stereotactic body radiation therapy (SBRT). Since SBRT leads to lower nadir PSA (nPSA) compared to conventionally fractionated RT, we investigated if an earlier nPSA+threshold can be used as an alternative definition of BCF.PSA kinetics from 9 institutions were retrospectively analyzed for patients with localized PCa treated definitively with SBRT alone from 2003 to 2018. Patients received 35 to 40 Gy in 5 fractions, 38 Gy in 4 fractions or 26 Gy in 2 fractions (EQD23 Gy = 70-95 Gy) per institutional standards. Cox multivariable regression model was used to determine the adjusted association of relative change in PSA kinetics with biochemical relapse-free survival (BRFS) and association of BCF with time to nadir+2.A total of 2061 patients were included. Median follow-up was 71.9 months (interquartile range [IQR], 41.2-96.0). BCF occurred in 140 (6.8%) of patients. Median nPSA was 0.16 ng/mL, median time to nPSA was 48 months. Sensitivity of Phoenix definition for BCF was 93%, compared to 96%, 100%, and 100% for nPSA+1.5, nPSA+1.0 and nPSA+0.5, respectively. False positive rate of Phoenix definition was 30%, compared to 41%, 58%, and 71% for nPSA+1.5, nPSA+1.0 and nPSA+0.5, respectively. In patients who developed BCF, lead time gained from an earlier nPSA+threshold definition compared to Phoenix definition was 6 (IQR 0-15.3), 0 (IQR 0-11.3), 0 (IQR 0-0) months for nPSA+0.5, nPSA+1.0 and nPSA+1.5, respectively. Relative change in PSA between 6 months and 18 months after treatment was significantly associated with BRFS (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.28-2.34, P < 0.0004). Among the 30% patients who had a false call of BCF due to PSA bounce, 48 (84.2%) reached nPSA+2 in ≤18 months, and 9 (15.8%) in > 18 months. In patients who had BCF, 27 (19.3%) reached nPSA+2 in ≤18 months, and 113 (80.7%) in > 18 months. Median time to nPSA+2 was significantly longer in patients with BCF (41 vs. 12 months, P < 0.002). BCF is associated with longer time to nPSA+2 (HR 0.13, 95% CI 0.09-0.20, P < 0.002).A lower nadir-based threshold provides minimal increase in sensitivity at the cost of a higher false positive rate and does not provide a clinically relevant lead time benefit for a pending BCF in patients with low- to intermediate-risk PCa undergoing SBRT. A rate-of-change based metric in the first 18 months post-SBRT is significantly associated with BRFS. Patients who have an early PSA bounce after SBRT rarely develop a true BCF and true BCF tends to happen later (> 18 months). Phoenix definition remains a valuable tool in the SBRT era. BCF should not be prematurely called which runs the risk of high rates of false positivity.

Prostate Specific Antigen Dynamics and Features in Prostate Cancer

Abstract Despite the common use of the prostate-specific antigen (PSA) serum level as a tumour marker in diagnosis of prostate cancer, it seems that the PSA doubling time (PSADT) and PSA velocity (PSAV) could be more useful indicators of tumour behaviour and prognosis for patients. The aim of the study was to evaluate the value of PSAV and PSADT in the diagnosis of prostate cancer and their relationship with prostate cancer histopathological characteristics. Eighty-six patients undergoing radical prostatectomy were enrolled in the study. Based on the PSA measurements the PSA dynamic values were calculated: PSADT and PSAV. In addition, clinical and histo-pathological characteristics, including disease stage and prognostic groups were evaluated. The obtained results showed that the first PSA value was 4.29 ng/ml (1.28–13.56), the second PSA value was 7.76 ng/ml (7.60–47.60), and the third PSA value was 9.67 ng/ml (2.56–98.50). The median PSADT was 51.01 months (7.80–311.81) and the median PSAV was 2.66 ng/ml/per year (0.22–4.66). In addition, significant correlations between PSAV and pre- and post-operative Gleason score, and prognostic groups were observed. Significant correlation between PSADT and pre- and pos-toperative Gleason score and prognostic risk groups was demonstrated. This study demonstrated that PSAV and PSADT were significantly correlated with postoperative Gleason score and prognostic risk groups, demonstrating its role in the diagnosis of prostate cancer progression.

PD08-05 DEVELOPMENT AND VALIDATION OF A NOVEL NOMOGRAM PREDICTING LONG-TERM PROGRESSION IN PATIENTS TREATED WITH EARLY SALVAGE RADIATION THERAPY AFTER RADICAL PROSTATECTOMY: THE KEY ROLE OF PSA KINETICS

PD08-05 DEVELOPMENT AND VALIDATION OF A NOVEL NOMOGRAM PREDICTING LONG-TERM PROGRESSION IN PATIENTS TREATED WITH EARLY SALVAGE RADIATION THERAPY AFTER RADICAL PROSTATECTOMY: THE KEY ROLE OF PSA KINETICS

583P Baseline plasma tumour DNA (ptDNA) correlates with PSA kinetics in metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone or enzalutamide

Baseline high ptDNA fraction and androgen receptor (AR) copy number (CN) gain identify mCRPC patients (pts) with worse outcomes on abiraterone (abi) or enzalutamide (enza). This study aimed to assess if plasma DNA analysis associates with PSA kinetics.

PD34-11 PROSTATE-SPECIFIC ANTIGEN KINETICS IN PATIENTS WITH ADVANCED PROSTATE CANCER TREATED WITH APALUTAMIDE: RESULTS FROM THE TITAN AND SPARTAN STUDIES

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) III (PD34)1 Sep 2021PD34-11 PROSTATE-SPECIFIC ANTIGEN KINETICS IN PATIENTS WITH ADVANCED PROSTATE CANCER TREATED WITH APALUTAMIDE: RESULTS FROM THE TITAN AND SPARTAN STUDIES Kim N. Chi, Fred Saad, Simon Chowdhury, Julie N. Graff, Neeraj Agarwal, Stéphane Oudard, Gang Li, Angela Lopez-Gitlitz, Julie S. Larsen, Sharon A. McCarthy, Suneel D. Mundle, Matthew R. Smith, and Eric J. Small Kim N. ChiKim N. Chi More articles by this author , Fred SaadFred Saad More articles by this author , Simon ChowdhurySimon Chowdhury More articles by this author , Julie N. GraffJulie N. Graff More articles by this author , Neeraj AgarwalNeeraj Agarwal More articles by this author , Stéphane OudardStéphane Oudard More articles by this author , Gang LiGang Li More articles by this author , Angela Lopez-GitlitzAngela Lopez-Gitlitz More articles by this author , Julie S. LarsenJulie S. Larsen More articles by this author , Sharon A. McCarthySharon A. McCarthy More articles by this author , Suneel D. MundleSuneel D. Mundle More articles by this author , Matthew R. SmithMatthew R. Smith More articles by this author , and Eric J. SmallEric J. Small More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002038.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The phase 3 TITAN and SPARTAN studies demonstrated improved outcomes with the addition of apalutamide (APA) to androgen deprivation therapy (ADT); outcomes included prolonging overall survival and radiographic progression-free survival (rPFS) in metastatic castration-sensitive prostate cancer (mCSPC) in TITAN, and metastasis-free survival (MFS) in nonmetastatic castration-resistant PC (nmCRPC) in SPARTAN. A post hoc analysis of prostate-specific antigen kinetics (PSA) kinetics in patients (pts) from both studies is reported. METHODS: Baseline PSA at randomization, time to PSA nadir, and proportion of pts achieving a PSA decline of ≥90% (PSA90) and of pts achieving a PSA≤0.2 ng/mL at 3 and 12 months and at any time after treatment in the APA arms of the TITAN and SPARTAN studies were evaluated. Within each study, rPFS/MFS were compared between pts achieving a PSA90 or PSA≤0.2 ng/mL response vs not. RESULTS: 525 TITAN pts and 806 SPARTAN pts treated with APA were included in the analysis. Median baseline PSA, time to PSA nadir, median PSA nadir, and maximum percentage changes from baseline PSA are shown in the table. PSA90 and confirmed PSA≤0.2 ng/mL were evident as early as 3 months in both TITAN and SPARTAN, and percentage of confirmed response continued to increase at 12 months. Pts treated with APA who achieved PSA90 were at lower risk of rPFS events in TITAN and of MFS events in SPARTAN, with a hazard ratio (95% confidence interval) of 0.46 (0.321-0.653) and 0.36 (0.271-0.489) in each respective study (both p<0.0001), compared with APA pts who did not achieve PSA90. Pts with confirmed PSA≤0.2 ng/mL had similar rPFS and MFS benefits. CONCLUSIONS: Pts with advanced PC, whether mCSPC or nmCRPC, treated with APA+ADT demonstrated rapid PSA declines that continued over time. There was a high rate of pts with PSA90 and with PSA≤0.2 ng/mL responses, with a majority of pts reaching PSA90 by 12 months. Pts achieving PSA90 and/or PSA nadir of ≤0.2 ng/mL had a prolonged rPFS and MFS in TITAN and SPARTAN, respectively. Source of Funding: Janssen Research & Development © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e587-e587 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kim N. Chi More articles by this author Fred Saad More articles by this author Simon Chowdhury More articles by this author Julie N. Graff More articles by this author Neeraj Agarwal More articles by this author Stéphane Oudard More articles by this author Gang Li More articles by this author Angela Lopez-Gitlitz More articles by this author Julie S. Larsen More articles by this author Sharon A. McCarthy More articles by this author Suneel D. Mundle More articles by this author Matthew R. Smith More articles by this author Eric J. Small More articles by this author Expand All Advertisement Loading ...

MP62-07 REAL-WORLD VALIDATION AND GENERALIZABILITY OF A PSAK PREDICTION TOOL FOR ACTIVE SURVEILLANCE RECLASSIFICATION

INTRODUCTION AND OBJECTIVE:The utility of prostate-specific antigen kinetics (PSAk) in Active Surveillance (AS) of low-risk prostate cancer remains controversial. The Prostate Active Surveillance S...

MP64-12 SALVAGE PELVIC LYMPH NODE DISSECTION OF LOCALLY RECURRENT PROSTATE CANCER AFTER RADICAL PROSTATECTOMY CAN DELAY THE NEED FOR SYSTEMIC INTERVENTIONS

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy VI (MP64)1 Sep 2021MP64-12 SALVAGE PELVIC LYMPH NODE DISSECTION OF LOCALLY RECURRENT PROSTATE CANCER AFTER RADICAL PROSTATECTOMY CAN DELAY THE NEED FOR SYSTEMIC INTERVENTIONS Erica Huang, Karren Liang, Linda Huynh, Whitney Zhang, and Thomas Ahlering Erica HuangErica Huang More articles by this author , Karren LiangKarren Liang More articles by this author , Linda HuynhLinda Huynh More articles by this author , Whitney ZhangWhitney Zhang More articles by this author , and Thomas AhleringThomas Ahlering More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002104.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: With the advent of the 68-Ga PSMA PET/CT scan, recurrences following radical prostatectomy (RP) can be localized to pelvic lymph nodes, soft pelvic tissue, and/or distant metastases. In our experience, 55% of patients with a biochemical recurrence (BCR) following surgery recur locally in the pelvic lymph nodes (PLN). Standard therapies such as radiation and/or hormonal therapy are known to negatively affect patients’ quality of life (QOL) and, in this regard, the present study introduces salvage pelvic lymph node dissections (sPLND) of local recurrence as a potential treatment for local recurrences. METHODS: Following RP, 87 patients underwent 68 Gallium PSMA/PET CT scan, of which 64 scans were positive, with 35 (40.2%) demonstrating radiographic evidence of localized recurrence in the PLN. Amongst the PLN positive group, 15 patients proceeded with sPLND by a single surgeon. The primary outcome evaluated was PSA kinetics, and secondary outcome evaluated was need for secondary treatment. RESULTS: All surgeries were completed outpatient without complication. Patients were discharged with <24 hours hospitalization with <1 week recovery time. Of the 15 patients who underwent sPLND, 6 (40.0%) patients had a stable rise in PSA with no secondary intervention at mean follow-up time of 2.3 (±0.8) years following sPLND. 4 (26.7%) patients experienced a stable rise in PSA with secondary intervention, and 5 (33.3%) patients experienced BCR immediately, with immediate hormonal therapy as a secondary intervention. In 10/15 (33.33%) of the patients, PSA decreased by an average of 58% following sPLND. 6/15 (40.0%) patients did not require secondary systemic interventions such as radiation and hormonal therapy thus far (Table 1). CONCLUSIONS: This case series explores the utility of PSMA/PET scan imaging and subsequent dissection of pelvic lymph node recurrences, demonstrating its potential to slow PSA progression and delay or eliminate the need for secondary intervention. Future studies with additional patients and greater follow-up are required to evaluate PSA progression and secondary intervention post-sPLND further. Source of Funding: Self-Funded © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1114-e1115 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Erica Huang More articles by this author Karren Liang More articles by this author Linda Huynh More articles by this author Whitney Zhang More articles by this author Thomas Ahlering More articles by this author Expand All Advertisement Loading ...

This Month in Adult Urology

This Month in Adult Urology

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.

Salvage therapy for prostate cancer after radical prostatectomy.

More than 40% of men with intermediate-risk or high-risk prostate cancer will experience a biochemical recurrence after radical prostatectomy. Clinical guidelines for the management of these patients largely focus on the use of salvage radiotherapy with or without systemic therapy. However, not all patients with biochemical recurrence will go on to develop metastases or die from their disease. The optimal pre-salvage therapy investigational workup for patients who experience biochemical recurrence should, therefore, include novel techniques such as PET imaging and genomic analysis of radical prostatectomy specimen tissue, as well as consideration of more traditional clinical variables such as PSA value, PSA kinetics, Gleason score and pathological stage of disease. In patients without metastatic disease, the only known curative intervention is salvage radiotherapy but, given the therapeutic burden of this treatment, importance must be placed on accurate timing of treatment, radiation dose, fractionation and field size. Systemic therapy also has a role in the salvage setting, both concurrently with radiotherapy and as salvage monotherapy.

PO-1357 LDR-Brachytherapy vs SBRT: PSA kinetics and toxicity outcomes in localized prostate carcinoma

PO-1357 LDR-Brachytherapy vs SBRT: PSA kinetics and toxicity outcomes in localized prostate carcinoma