PSA Values Research Articles

Phase II Study of ENZAlutamide Combined With Hypofractionated Radiation Therapy (ENZART) for Localized Intermediate Risk Prostate Cancer.

BackgroundIntermediate-risk prostate cancer (PCa) is usually treated by a combination of external beam radiation therapy (EBRT) and a short course of androgen deprivation therapy (ADT). ADT is associated with multiple side effects, including weight gain, loss of libido, and hot flashes. In contrast, anti-androgen monotherapy is generally better tolerated in spite of higher rates of gynecomastia.ObjectiveThis study assessed the effectiveness of enzalutamide monotherapy combined with hypofractionated EBRT (Hypo-EBRT) for treating intermediate risk prostate cancer.MethodThis trial was a multicenter, open-label phase II study of 6 months of enzalutamide monotherapy combined with Hypo-EBRT for intermediate-risk prostate cancer. Hypo-EBRT was initiated 8–12 weeks after initiating enzalutamide. The primary endpoint was PSA decline >80% measured at the 25th week of enzalutamide administration. Secondary end-points included assessment of toxicity, changes in anthropomorphic body measurements, sexual hormones, and metabolic changes.ResultsSixty-two patients were included in the study from January 2018 to February 2020. A PSA decline of >80% was observed in all evaluable patients at the end of enzalutamide treatment and 92% achieved PSA values under 0.1 ngr/ml. All patients remain in PSA response (<80% reduction of the initial values) 6 months after the end of enzalutamide treatment. The most frequent adverse events were hypertension, asthenia, and gynecomastia. There were no significant changes in bone density, body mass index (BMI), or patient-reported outcomes (PROs).ConclusionEnzalutamide monotherapy is very effective along with hEBRT in reducing PSA levels for patients with intermediate-risk prostate cancer. Longer follow-up is needed to confirm the potential use of this combination in future randomized trials.

The role of Tadalafil in the treatment of benign prostatic hyperplasia and erectile dysfunction

The aim of this study is to investigate the effectiveness of a single 5 mg daily dose of Tadalafil in patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) accompanied by erectile dysfunction (ED). The data of patients who applied to the urology outpatient clinic between 2014 and 2019 and were diagnosed with BPH and ED were retrospectively analysed. Before and after the treatment with 5 mg tadalafil daily for 12 weeks; maximum flow rate (Qmax), average flow rate (Qave), postvoid residual volume (PVR), prostate volume (PV), PSA values, IPSS and IIEF scores of the patients were compared. The mean age of 66 male patients diagnosed with ED and BPH was 48.1±6.9 years. The mean IPSS score of the patients before the treatment was 9.85 which represents moderate LUTS. After the treatment, the mean score decreased to 5.7 which represents mild LUTS. Before the treatment, the mean IIEF score showed mild ED with 18.79. After the treatment, the mean IIEF score increased to 29,9. The treatment statistically significantly decreased ED and increased the IIEF score (p=0.000). While the mean Qmax and Qave were increased statistically significantly (p=0.000). A statistically significant decrease was observed in the mean PVR from 60.1 ml to 37.6 ml (p=0.000). The decrease in PV was not statistically significant (p=0.321). The decrease in PSA values before and after treatment was found to be statistically significant with p=0.046. It has been shown that the daily use of 5 mg Tadalafil alone for 12 weeks can be a preferable treatment option, especially in younger patients with BPH / LUTS and ED.

EDITORIAL COMMENT

The evolution of risk stratifications for prostate cancer reflects advances in anatomic (radiographic), pathologic, and molecular (genomic classifications) understandings. These parameters, combined with traditional “bedside” evaluations of clinical T stage, and PSA values, allow for better sharing of clinical decisions with patients. In this issue of the Gold Journal, investigators MUSIC investigators (Michigan Urological Surgery Improvement Collaborative) sought to improve patient selection criteria for PLND in patients with favorable and unfavorable intermediate risk (F-IR, U-IR) disease by analyzing over 6,800 men who underwent RALP and pelvic lymph node dissection (PLND).

A Retroprospective Clinicopathological Study of Prostatic Lesions in Surgical Specimens

Abstract Background Prostatic diseases such as inflammation, benign prostatic hyperplasia, and tumors are prime causes of mortality and morbidity in males. The prevalence of these lesions increases with advancing age. The second most common cancer among males is prostate cancer, next to lung cancer worldwide. Aim The present study was undertaken with the aim of studying the clinicopathological characteristics of prostate lesions in surgical specimens Methods The present study was a retroprospective study. A total of 212 prostate surgical specimens were included. Information provided in the requisition form regarding age, type of prostatic biopsy and clinical presentation, and histopathological diagnosis was taken into consideration and recorded. All specimens were fixed in 10% neutral buffered formalin and 5μ sections were stained with hematoxylin and eosin stain (H&amp;E stain). Relevant clinical data including age, the presenting complaints, and S.PSA values were recorded. Data were collected and analyzed using simple statistical methods with Microsoft Excel 2016. Results Out of 212 cases analyzed, 161 (76%) were transurethral resection of prostate (TURP) TUPR specimens, 38 (18%) were trucut needle biopsies, and 13 (6%) were open prostatectomy specimens. The youngest patient was 48 years old while the oldest patient was 90 years old with a mean of 71.7 ± 8.2 years. Of the total 212 surgical specimens, 174 (82%) cases were of benign prostatic hyperplasia (BHP), and 38 (18%) were prostatic adenocarcinoma (PAC). Also, 94 (44.3%) of BPH and carcinoma of the prostate cases were most common in the seventh decade of life (61-70 years). Difficulty in micturition was the most common presentation 82 (39%). A maximum number of the BPH cases 81 (46.5%) had the prostate-specific antigen range of 0 to 4 ng/mL. The highest value of serum PSA was noted among the PAC patients in the range of &gt; 80 ng/mL. Out of 38 cases of prostatic adenocarcinoma, moderately differentiated (Gleason scores 7) was the most common core and was seen in 42.1% of the PAC cases. Conclusion The present study showed that the most frequently encountered prostatic lesion was BHP, commonly seen in the age group of 61 to 70 years. The PAC was common among males of more than 60 years. Histopathological examination is the best diagnostic tool for PAC

Baseline Imaging Derived Predictive Factors of Response Following [177Lu]Lu-PSMA-617 Therapy in Salvage Metastatic Castration-Resistant Prostate Cancer: A Lesion- and Patient-Based Analysis.

Earlier studies have mostly identified pre-therapeutic clinical and laboratory parameters for the prediction of treatment response to [177Lu]Lu-PSMA-617 in metastatic castration resistant prostate cancer patients (mCRPC). The current study investigated whether imaging-derived factors on baseline [68Ga]Ga-PSMA-11 PET/CT can potentially predict the response after two cycles of [177Lu]Lu-PSMA-617 treatment, in a lesion- and patient-based analysis in men with mCRPC. Included patients had histologically proven mCRPC and a [68Ga]Ga-PSMA-11 PET/CT before and after two cycles of [177Lu]Lu-PSMA-617 treatment. The imaging-based response was evaluated on lesion-level (standardized uptake value (SUV) reduction) and patient-level (total lesion PSMA (TL-PSMA) reduction). In the lesion-level analysis, a clear relationship was found between SUVpeak/max and the imaging-based response to [68Ga]Ga-PSMA-11 PET/CT (most avid lesion SUVpeak/max ≥ 30% reduction) (p < 0.001), with no significant difference in cut-off values between different sites of metastases (i.e., lymph node, bone or visceral metastasis). In patient-level analysis, baseline PSA and SUVpeak values of most avid metastasis were significantly associated with imaging-based response (TL-PSMA ≥ 30% reduction) (p = 0.019 and p = 0.015). In pre-treatment with [68Ga]Ga-PSMA-11 PET/CT, a clear accumulation-response relationship in lesion-level was found for SUVpeak/max in men with mCRPC receiving two cycles of [177Lu]Lu-PSMA-617 treatment. The SUVpeak of the most avid lesion was the only image-derived factor predictive of the imaging-based response at the patient-level.

The role of multiparametric mri in the diagnosis of local recurrence after radical prostatectomy and before salvage radiotherapy

PurposeAssess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of Prostate Cancer (PCa) after Radical Prostatectomy (PR) and before Radiation Therapy (RT). Materials and methodsA total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into two groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between two groups using T-Student; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables. ResultsPCa recurrence (reduction of PSA levels after RT) was 89.8% in the group A and 80.3% in the group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. DWI is the most specific MRI-sequence and DCE the most sensitive. For PSA = 0.5 ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA = 0.9 ng/ml, DCE-AUC increases significantly. Conclusionmp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of DWI for PSA ≤ 0.5 ng/ml.

Prostate cancer screening - is it time to change approach?

Prostate adenocarcinoma (CaP) is one of the most common malignancies in men in Slovakia and in the world. The disease accounts for more than 22% of all tumors in the male population. Screening studies show an increase in the diagnosis of CaP without improvement in overall or CaP-specific mortality. The main goal of the work is to evaluate the incidence of CaP in the group of patients examined and treated during the period from 2014 to 2019 at the urological outpatient clinic of the Railway Hospital (RH) in Košice, and to evaluate the risks and treatment options. Men aged 40 to 75 years underwent a preventive examination in 2014-2019 at the urology outpatient clinic, RH Košice. The number of screened patients was 3,943. Epidemiological parameter, diagnosis-related examinations (prostate specific antigen - PSA examination, digital rectal examination, and ultrasonography examination) as well as the frequency of examinations were monitored during the specified period on the basis of documentation. The number of prostate biopsies, incidence of prostate cancer and relation to PSA values were also monitored, as well as the classification of prostate cancers according to the degree of risk. Initial treatment in individual patients was also evaluated. PSA values in patients who underwent biopsy ranged from 3.6 ng/mL to 2,000 ng/mL. We observed positive digital rectal examination in 52 patients. Of the number of patients examined, 231 (61.28%) were positive biopsies. There were negative biopsies with the finding of benign prostatic hyperplasia in 92 patients or chronic prostatitis in 54 patients, i.e., 146 (38.72%). According to the criteria for risk assessment based on the PSA value and the result of the histological examination, we diagnosed 109 low-risk patients, 57 medium-risk patients and 24 high-risk patients. CaP is detected by prevention about 10 years before it develops clinically. The main aim of preventive examinations should be to detect, in particular, high-risk forms of early-stage prostate cancer and to improve the quality of life of men. Due to the results of extensive studies, it is necessary to continue the active search for prostate cancer. This reduces the risk of metastatic forms of CaP.

Transvesical versus extraperitoneal single-port robotic radical prostatectomy: a matched-pair analysis.

To compare our initial perioperative and postoperative outcomes of the single-port (SP) transvesical radical prostatectomy (TVRP) approach with the single-port extraperitoneal radical prostatectomy (ERP) approach. Initial consecutive seventy-eight patients underwent SP TVRP between December 2020 and October 2021. Patients with extensive previous abdominal surgeries, or low- to intermediate-risk prostate cancer were selected. Data of consecutive 169 patients treated with SP ERP between February 2019 and November 2020, were used for comparison. Optimal matched-paired analysis of PSA value, biopsy Gleason score, and prostate volume was performed. Preoperative, perioperative, and early functional outcomes were included in the analysis. The median follow-up was 7months and 9months for TVRP and ERP groups respectively. The median total operative time was longer in the TVRP compared to the ERP group (p = .002). There were no differences in intraoperative complications or surgical margin status. TVRP group had less rate of grade 3a Clavien-Dindo complications (p = .026). The Foley catheter duration was 3 (3, 4) days in the TVRP group compared to 7 (7, 8) days in the ERP group (p < .001). There was a consistently improved continence rate in the TVRP group at 6weeks (72% TVRP, 48% ERP, p = .004), 3months (97% TVRP, 81% ERP, p = .008), and 6months postoperatively (100% TVRP, 93% ERP, p = .047). There was no difference in biochemical recurrence at 6months of follow-up. In our initial series, TVRP allows for a faster continence recovery, without other functional or oncological compromises.

Abstract LB112: Liquid biopsy monitoring reveals high molecular weight cfDNA fragments associated with radiotherapy dose-intensity

Abstract Introduction: Radiotherapy aims at delivering a high dose of radiation to a tumor while minimizing the dose absorbed by healthy tissues, minimizing side effects or toxicities. Radiotherapy monitoring currently largely relies on longitudinal imaging with spatial and limited functional information on therapy response. Particularly, discrimination of radiotherapy effect on the tumor versus healthy tissue can be challenging and imaging response may lag behind actual response on the tumor cell level. Liquid biopsy monitoring promises to complement imaging by providing systemic biological information about the effects of radiotherapy. Cell-free DNA (cfDNA) in the blood plasma contains genetic and epigenetic information about cell death processes, and cfDNA monitoring may thus lend itself to observing both tumor response and normal-tissue toxicity during radiotherapy. Methods: Seven polymetastatic patients, seven healthy volunteers, seven oligometastatic patients (OMD) and seven head-and neck cancer patients (H&amp;N) were recruited for the study. OMD patients received stereotactic body radiation therapy in 5 fractions of 5-10 Gy, heterogeneously prescribed, while H&amp;N underwent homogeneously 2 Gy radiation to a total dose of 70 Gy. Blood samples were collected from all patients at baseline and from patients undergoing radiotherapy twice during and twice after treatment, with samples collected up to six months after treatment. cfDNA was isolated and low-pass (7x) whole-genome sequencing was performed to examine fragment-length distribution and copy number alterations. We applied in silico size selection for 90 to 150 bp long fragments to improve copy number variant detection. Clinical measures and imaging findings were compared to cfDNA fragment analysis. Results: Samples showing high circulating tumor DNA content in copy number analysis (tMAD&amp;gt;0.03) also showed a higher proportion of short fragments (80-100 bp) compared to the samples of healthy individuals (ANOVA: p=0.0216, Tukey-pairwise: p=0.0287), whereas samples with low circulating tumor content did not (Tukey-pairwise: p=0.7540). We observed rapidly declining tumor fraction under treatment in a patient with prostate cancer and a high tMAD value at baseline. However, in the follow-up sample, residual tumor was detectable in the cfDNA copy number analysis, which was further confirmed by increasing PSA values. We observed a significant increase in the fraction of fragments between 200 and 250 bp in response to the treatment in oligometastatic patients receiving high-intensity radiotherapy, which returned to baseline in the follow-up measurements (ANOVA: p=0.0252, Tukey-pairwise: p=0.3138). A similar trend was observable (ANOVA: p=0.37) in head-and-neck patients, who received lower fractions of radiotherapy. Conclusions: Applying low-pass whole-genome cfDNA-sequencing, we were able to monitor radiotherapy response in oligometastatic and head-and-neck cancer patients. We have also observed short-term increase in the number fragments between 200 and 250 bp during treatment, which we hypothesize to be a necrotic signal. The minimal invasive nature and the relatively low cost of low-pass cfDNA-sequencing makes it a viable method for frequent monitoring, which may allow prediction of tumor response and patient outcome. Citation Format: Zsolt Balazs, Ivna Ivankovic, Panagiotis Balermpas, Todor Gitchev, Jonas Willmann, Michael Krauthammer, Nicolaus Andratschke. Liquid biopsy monitoring reveals high molecular weight cfDNA fragments associated with radiotherapy dose-intensity [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 LB112.

Alteration of Some Sperm Proteins, Anti-oxidants, and Prostate-specific Antigen in the Seminal Plasma of Bacteriospermic Infertile Males

Aim: To investigate the alteration of some sperm proteins, anti-oxidants, and prostate-specific antigen in the seminal plasma of bacteriospermic infertile males.&#x0D; Study Design: The study is a case-control design to investigate the semen parameters and some sperm proteins in infertile males with bacteriospermia attending urology or fertility clinics in Port Harcourt, Rivers State, Nigeria.&#x0D; Place and Duration of Study: The study was carried out in the Department of Medical Laboratory Science, Rivers State University, Port Harcourt. However, some of the Laboratory investigations were done in the Chemical Pathology Unit and Medical Microbiology Unit of the University of Port Harcourt Teaching Hospital, Port Harcourt. The Study was between the period of September 2019 and Feb. 2022.&#x0D; Methodology: A total 193 subjects were recruited of which 76 were fertile without bacterial infection, 24 were fertile with bacterial infection, 37 infertile without bacterial infection and 56 infertile with bacterial infections. Infertile males were further classified as teratozoospermic, asthenoteratozoospermic, and oligoasthenoteratozoospermic. HSP70, PKA, MDA, TAC, and GPX (in seminal plasma), PSA, and testosterone (in serum) were analyzed using ELISA while TAC was done using spectrophotometric methods. Microbial culture was done to isolate and identify bacteria in semen. Results obtained were analyzed using GraphPad Prism and SPSS.&#x0D; Results: Culture results indicated that 52% of normospermic subjects had no semen infection at the time of the investigation. On the other hand, infertile male subjects without semen infections had 18.7%, while infertile males with semen infections were seen to be 29.2%. Likewise, subjects with bacteriospermia as scanty growth had 12.5%, 9.3% moderate, and 7.3% heavy growth. Significantly higher values of HSP70, PKA, PSA, and MDA were seen in infertile males with bacteriospermia compared with control and infertile males without infection while significantly lower values were seen in TAC, GPX, OPN, and testosterone were observed in the infertile males with bacteriospermia compared with control and infertile males without infection.&#x0D; Conclusion: Bacteriospermia significantly increased lipid peroxidation cum oxidative stress leading to altered physiological sperm proteins in the seminal plasma. These alterations could also be responsible for the poor sperm qualities observed in the infertile subjects.

El papel de la resonancia magnética multiparamétrica en el diagnóstico de la recidiva local tras la prostatectomía radical y antes de la radioterapia de rescate

PurposeAssess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of prostate cancer (PCa) after radical prostatectomy (PR) and before radiation therapy (RT). Materials and methodsA total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into 2 groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between 2 groups using Student-t test; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables. ResultsPCa recurrence (reduction of PSA levels after RT) was 89.8% in group A and 80.3% in group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. Diffusion weighted imaging is the most specific MRI-sequence and dynamic contrast enhanced the most sensitive. For PSA=0.5ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA=0.9ng/ml, dynamic contrast enhanced-AUC increases significantly. Conclusionmp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of diffusion weighted imaging for PSA≤0.5ng/ml.

PSMA PET findings in patients with undetectable PSA more than 3 years after docetaxel for metastatic castration-sensitive prostate cancer (mCSPC).

e17046 Background: Multiple treatment options combined with androgen deprivation therapy (ADT) provide a survival advantage in mCSPC. In this prospective study, mCSPC patients were treated with docetaxel and Prostvac, a therapeutic cancer vaccine. Since initiation of the study, a phase 3 trial of Prostvac did not show independent clinical activity in metastatic castration-resistant prostate cancer. Still, this study offers a chance to evaluate responses to docetaxel-based therapy in mCSPC. More specifically, with FDA approval of prostate-specific membrane antigen (PSMA) PET imaging in just the last year, there is a paucity of data regarding the use of this scan in long-term responders to therapies for mCSPC. Methods: Eligible patients included those with mCSPC and ECOG PS of ≤ 2. As per the CHAARTED regimen, patients started docetaxel within 4 months of initiating ADT with a plan to receive 75mg/m2 for 6 cycles. Patients were randomized to receive Prostvac prior to, concurrent with, or after docetaxel. Restaging was done annually with CT and Tc99 bone scan. The study was powered to evaluate immune responses, which is being reported separately. For this analysis, patients were evaluated as one group. Ten patients are in follow up with continued PSA values of ≤ 0.2 ng/mL and 7/10 were evaluated with 18F-DCFPyL PSMA PET. Results: Seventy-three patients enrolled. Median age was 63 years with a range of 41-86 years. Race distribution was 71.6% White, 20.3% Black, 4.1% other, and 4.1% unknown. Gleason 6, 7, and 8 to 10 was 4.1%, 21.6%, and 68.9% of patients, respectively, with 5.4% being unknown. Median pre-ADT PSA was 34.75 ng/mL. Low-volume disease represented 41.1% of patients and high-volume was 58.9%. After 2 years from the start of ADT, 22% of patients had PSA values of ≤ 0.2 ng/mL. This included 37% of the low-volume group and 12% of the high-volume group. Three years from starting ADT, 14% of patients had PSA values ≤ 0.2 ng/mL (20% of the low-volume group, 9% of the high-volume group). Of the 7 patients who remain in follow-up with PSA values ≤ 0.2 ng/mL and who were evaluated with PSMA PET, median time from start of ADT was 4 years with a range of 3.5-6 years. These patients either had no evidence of disease or minimal residual findings on CT/Tc99 bone scan. Four of the 7 patients still had residual areas of uptake on PSMA PET. Conclusions: Patients treated with docetaxel for mCSPC have the potential for long-term clinical responses. In these long-term responders, despite prolonged PSA response and minimal findings on conventional CT and Tc99 scans, more than half of patients still had findings on PSMA PET imaging. Further studies are required to better understand the clinical implications of these findings and the role of PSMA PET in mCSPC. Clinical trial information: NCT02649855.

Trial in progress: Durvalumab and olaparib for the treatment of prostate cancer in men predicted to have a high neoantigen load.

TPS5099 Background: Approximately 30% of patients (pts) treated with definitive surgical and/or radiation therapy for localized prostate adenocarcinoma develop biochemical recurrence (BCR). The optimal time to initiate androgen deprivation therapy (ADT) for such patients is controversial and depends on patient and provider preference, absolute PSA value, and PSA doubling time (PSADT), which has been associated with time to metastasis. Because the time from BCR to metastasis can be long in many cases, strategies allowing pts to avoid ADT while extending metastasis-free survival are desirable. Prior studies have shown that a high tumor neoantigen load correlates with response to anti-PD(L)1. We hypothesized that PARP inhibitor-induced genomic instability may sensitize tumors to anti-PD(L)1 through: i) increasing mutational burden and subsequent tumor neoantigen formation, and/or ii) through activation of other immunogenic pathways (e.g. the STING pathway). This trial investigates an ADT-sparing approach for men predicted to have high neoantigen load and who have BCR prostate cancer. Methods: This is a phase 2 clinical trial testing durvalumab (1500 mg IV every 4 weeks) and olaparib (300 mg PO twice a day) (one cycle = 4 weeks) in men with BCR (PSADT≤10 months) whose tumors are predicted to have high neoantigen load based on: biallelic CDK12 mutations (Cohort A), mismatch repair deficiency (MMRd)/high microsatellite instability (MSI-H) (Cohort B), or loss of function mutations in homologous recombination repair (HRR) genes (Cohort C). Cohorts A and B will receive 3 cycles of durvalumab followed by 3 cycles of the combination of durvalumab and olaparib. Given the proven efficacy of olaparib in prostate cancer patient whose tumors posses an HRR gene mutation, Cohort C will receive 6 full cycles of the combination. Ten patients will be enrolled in each cohort (total n = 30) at two collaborating sites. This study was designed to provide preliminary efficacy data across eligible cohorts, with a primary objective of estimating the proportion of pts with an undetectable PSA at 12 months within each cohort. Secondary objectives include safety, proportion of patients with ≥50% decline in PSA from baseline and quality of life measures. Correlative studies will assess blood and tissue molecular biomarkers for association with outcomes. The study is open with two patients enrolled at the time of abstract submission. Clinical trial information: NCT04336943.

Profiling of clinically relevant subgroups of asymptomatic or mild-symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients using PSA and testosterone levels and deep learning.

e17032 Background: The optimal time to begin therapy in mCRPC patients who have either no, or minimal symptoms is not defined yet. Estimating prognosis of these patients can avoid undertreatment or overtreatment and guide the follow-up intensity. This study has investigated the ability of a deep learning framework (DLF) to identify asymptomatic or mildly symptomatic mCRPC patients with high risk of disease progression and mortality using PSA and testosterone levels. Methods: Data from the control arm of the NCT00554229 trial was obtained from www.projectdatasphere.org . These mCRPC patients were treated with placebo alone. The dataset consisted of more than 150 clinical variables. We generated synthetic fingerprints (SF) for each patient through the integration of PSA values collected at baseline and during the first 90 days of follow-up and testosterone levels at baseline. These SF were then input into a DLF to identify subgroup of patients based on their similarities. The resultant subgroups were correlated with progression-free survival (PFS) and overall survival (OS). Feature contribution analysis identified the significant predictive clinical variables in each subgroup. Results: After discarding missing data, 189 patients were eligible for this exploratory study. Median PFS and OS for the total population were 8.7 months and 24.5 months, respectively. DLF identified two different subpopulations, SPA (n = 89) and SPB (n = 100), with significantly different survival outcome. Patients in SPA had a lower risk of progression (median PFS 12.2 months vs. 7.2 months; hazard ratio 0.54, 95% CI 0.41-0.71; p &lt; .0001) and death (median OS not reached vs. 20.3 months; hazard ratio 0.33, 95% CI 0.21-0.52; p &lt; .0001) compared to patients in SPB. SPA signature was significantly correlated to leuprolide treatment. These patients also had higher levels of haemoglobin, red blood cells, haematocrit, total bilirubin, Ca, phosphate, and K. Instead, SPB signature was significantly correlated with presence of &gt; 3 bone metastasis, lack of energy or forced time to bed in the FACT-P and moderate problems in selfcare in the EQ-5D, and treatment with goserelin, tamsulosin, opioids and contact laxatives. In addition, these patients had higher levels of platelets, basophils, monocytes, ALP, AST, LDH, PSA, free PSA, Mg, Na, and specific gravity. Conclusions: DLF identifies mCRPC subtypes that correlate with higher risk of progression and death according to PSA and testosterone levels. Model predictions also suggest complex interactions among many clinical features that might be important modulators of key clinical traits and outcome. Further work is required to validate this approach to anticipate the clinical course of asymptomatic or mildly symptomatic mCRPC patients and help to better decide when to start appropriate therapy.

Cohort study of patients with oligorecurrent prostate cancer: Oncological outcomes of patients treated with salvage lymph node dissection via PSMA radioguided surgery.

5009 Background: Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) allows detection of small and/or atypically localized metastatic prostate cancer (PCa) lesions. In a subset of patients with recurrent oligometastatic PCa salvage surgery with PSMA-targeted radioguidance (PSMA-RGS) may be of value. We aimed to evaluate the oncological outcomes of salvage PSMA-RGS for oligo-recurrent PCa and determine predictive preoperative factors of improved outcomes. Methods: In this cohort study within two tertiary care centers, patients with biochemical recurrence (BCR) after radical prostatectomy (RP) and imaging with PSMA PET receiving salvage PSMA-RGS between 2014 and 2020 were analyzed. Kaplan-Meier and multivariable Cox regression models adjusted for various parameters were used to test for BCR-free survival (BFS) and therapy-free survival (TFS) differences. Postoperative complications were classified according to Clavien-Dindo. Results: Overall, 364 patients were assessed. At PSMA-RGS, median (IQR) age and preoperative PSA was 67 (61-71) years and 1.0 (0.5-1.9) ng/ml. Metastatic soft-tissue lesions from PCa metastases could be removed in 343 (94.2%) patients. Within three months from surgery, 24 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. During follow-up, 225 patients experienced BCR and 121 patients received further therapy. Median follow-up for patients who did not experience BCR and who did not receive further therapy was 10.8 months and 10.3 months, respectively. Median (IQR) BFS and TFS was 7.8 (5.4-10.5) and 35.5 months (25.9-45.9 months). At two years of follow-up, BFS rate was 31.9% and TFS rate was 58.0%. In multivariable analyses, higher preoperative PSA (HR: 1.1), higher number of PSMA-avid lesions on preoperative imaging (HR: 1.2) and multiple (pelvic plus retroperitoneal) localizations (HR: 1.9), as well as retroperitoneal localization (HR: 2.0) of lesions in PSMA PET imaging were independent predictors of BCR after PSMA-RGS. Limitations are the retrospective design and lack of a control group. Conclusions: As salvage surgery in oligo-recurrent PCa currently constitutes an experimental treatment approach careful patient selection is mandatory based on life expectancy, low PSA values and low number of PSMA PET avid lesions located in the pelvis. Further studies are needed to confirm our findings and define the oncological value of salvage surgical procedures in oligo-recurrent PCa.

Phase 1b study of bavdegalutamide, an androgen receptor PROTACdegrader, combined with abiraterone in patients with metastatic prostate cancer.

TPS5106 Background: Bavdegalutamide (ARV-110) is a novel, oral PROteolysis TArgeting Chimera (PROTAC) protein degrader that targets wild-type androgen receptor (AR) and clinically relevant mutants. Bavdegalutamide demonstrated tumor growth inhibition in multiple xenograft models (eg, AR gene amplification, AR mutation, enzalutamide resistance, and enzalutamide insensitivity). In a phase 1/2 study (NCT03888612), bavdegalutamide showed clinical activity in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received 1–2 prior novel hormonal agents (eg, abiraterone and/or enzalutamide), including heavily pretreated patients. Abiraterone is approved, in combination with a corticosteroid, to treat patients with mCRPC or with high-risk castration-sensitive prostate cancer (CSPC). Up to a third of patients treated with abiraterone develop primary resistance to this drug and nearly all patients experience disease progression. Here we describe a phase 1b study that will evaluate the combination of bavdegalutamide with abiraterone at the initiation of progression on abiraterone (prostate-specific antigen [PSA] progression without radiographic progression) to test if the addition of bavdegalutamide will overcome resistance to abiraterone and re-establish the AR pathway blockade in patients with prostate cancer. Methods: Eligible patients are men ≥18 years of age with histologically, pathologically, or cytologically confirmed adenocarcinoma of the prostate and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients must be receiving ongoing treatment with stable doses of abiraterone and a concomitant corticosteroid for mCRPC or CSPC and have PSA progression ≥16 weeks after initiation of abiraterone, ≥2 rising PSA values measured ≥1 week apart, and no radiographic evidence of disease progression while receiving abiraterone. Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone analogue or inhibitor or orchiectomy is required. Prior treatment with enzalutamide, apalutamide, darolutamide, or experimental AR-directed therapies is not permitted. Bavdegalutamide, abiraterone, and a corticosteroid will be administered daily in 28-day cycles. Primary objectives are to evaluate the safety and tolerability of bavdegalutamide plus abiraterone and determine the recommended phase 2 dose and schedule of this combination (based on the incidence of first-cycle dose-limiting toxicities and the frequency and severity of adverse events and laboratory abnormalities). Clinical trial information: NCT05177042.

Detection Rate of 68Ga-PSMA PET/CT vs. mpMRI Targeted Biopsy for Clinically Significant Prostate Cancer.

To evaluate the diagnostic accuracy of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) vs. multiparametric magnetic resonance imaging (mpMRI) targeted biopsy (TPBx) in the diagnosis of clinically significant prostate cancer (csPCa: Grade Group ≥2). From January 2021 to January 2022, 45 patients (median age: 67 years) with negative digital rectal examination underwent transperineal prostate biopsy for abnormal PSA values (median 7.3 ng/ml). Before prostate biopsy, all patients underwent mpMRI and 68Ga-PET/CT examinations, which included mpMRI (PI-RADS version 2 ≥3), and 68Ga-PET/CT index lesions suspicious for cancer (SUVmax ≥5 g/ml) underwent cognitive targeted cores (mpMRI-TPBx and PSMA-TPBx: four cores) combined with extended systematic prostate biopsy (eSPBx: median 18 cores). The procedure was performed transperineally using a tru-cut 18-gauge needle under sedation and antibiotic prophylaxis. PCa was found in 29/45 (64.4%) men; in detail, 22/45 (48.9%) were csPCa. 68Ga-PSMA-TPBx vs. mpMRI-TPBx vs. eSPBx missed one (4.5%) vs. four (18.1%) vs. seven (31.8%) csPCa, respectively; mpMRI-TPBx vs. 68Ga-PSMA-TPBx for csPCa showed a diagnostic accuracy of 73.7 vs. 77.5%. 68Ga-PSMA PET/CT TPBx demonstrated good accuracy in the diagnosis of csPCa, which was not inferior to mpMRI-TPBx (77.5 vs. 73.7%), improving the detection rate for cancer in systematic biopsy.

The value of bone scans to predict survival time in patients with diagnosed prostate cancer: single-center retrospective study

Objective: In this study, we investigated the significance of the bone scan results as a prognostic factor to predict survival by comparing age, serum PSA level, and Gleason score. Methods: Medical records of 313 patients were retrospectively examined. 265 patients of 313 were included in the study. Results: 202 (76%) patients of 265 were still alive and 63 (24%) patients of 265 were dead because of prostate cancer. Patients’ mean estimated survival times for those with, without, and suspected bone metastases were 47.4 ± 5.4 months, 159.1 ± 8.6 months, and 71.1 ± 14.4 months, respectively (p = 0.0001). While the mean estimated survival time of &lt; 70 years patients old was 137.1 ± 9.4 months, the mean estimated survival time of ≥ 70 years old patients was 78.2 ± 5.0 (p = 0.031). 243 patients with known PSA values, of those whose PSA levels were &lt; 10 ng/ml, between 10-20 ng/ml, between &gt; 20-50 ng/ml, and &gt; 50 ng/ml, the estimated mean survival time was 106.9 ± 4.2 months, 118.1 ± 14.8 months, 87.6 ± 7.4 months and 51.7 ± 6.2 month, respectively and a significant difference was determined (p = 0.0001). For patients whose Gleason scores were &lt; 7, 7, and &gt;7, the mean estimated survival time was 167.5 ± 10.8 months), 86.8 ± 5.5 months, and 61.0 ± 5.4 months, respectively, and a significant difference was determined (p = 0.0001). Conclusion: We identified that the estimated mean survival time of the patients who had bone metastases, had a high level of PSA, had a high level of Gleason score, and were older than 70 years old was shorter than other groups. We concluded the most important prognostic factor affecting survival time independently was the finding of metastasis detected in bone scintigraphy.

Predictive Effect of EPS Results on Prostate Cancer Detection in Patients with High PSA Values

Predictive Effect of EPS Results on Prostate Cancer Detection in Patients with High PSA Values

Time to castration-resistant prostate cancer and prostate cancer death according to PSA response in men with non-metastatic prostate cancer treated with gonadotropin releasing hormone agonists

Objectives: To predict castration-resistant prostate cancer (CRPC) and prostate cancer (Pca) death by use of clinical variables at Pca diagnosis and PSA levels after start of gonadotropin-releasing hormone agonists (GnRH) in men with non-metastatic castration sensitive prostate cancer (nmCSPC). Materials and Methods: PSA values for 1603 men with nmCSPC in the National Prostate Cancer Register of Sweden who received GnRH as primary treatment were retrieved from Uppsala-Örebro PSA Cohort and Stockholm PSA and Biopsy Register. All men had measured PSA before (pre-GnRH PSA) and 3–6 months after (post-GnRH PSA) date of start of GnRH. Unadjusted and adjusted Cox models were used to predict CRPC by PSA levels. PSA levels and ISUP grade were used to construct a risk score to stratify men by tertiles according to risk of CRPC and Pca death. Results: 788 (49%) men reached CRPC and 456 (28%) died of Pca during follow-up. Post-GnRH PSA predicted CRPC regardless of pre-GnRH PSA. CRPC risk increased with higher post-GnRH PSA, HR 4.7 (95% CI: 3.4–6.7) for PSA > 16 ng/mL vs 0–0.25 ng/mL and with ISUP grade, HR 3.7 (95%: 2.5–5.4) for ISUP 5 vs ISUP 1. Risk of Pca death in men above top vs bellow bottom tertile of post-GnRH PSA and ISUP grade was HR 4.1 (95% CI: 3.0–5.5). Conclusion: A risk score based on post-GnRH PSA and ISUP grade could be used for early identification of a target group for future clinical trials on additional therapy to GnRH.