Serum PSA Levels Research Articles

Association Between the Aromatase rs2414096 Polymorphism and Prostate Cancer

Abstract Objectives The purpose of this study was to investigate association between the aromatase (CYP19A1) rs2414096 polymorphism and the risk of prostate cancer development, progression and aggressiveness in the Slovak population. Background Aromatase catalyses the final reaction of androgens aromatization to estrogens, irreversible conversion of androstenedione to estrone and testosterone to estradiol. Methods The study population consisted of 721 prostate cancer patients and 660 men in the control group. Genotyping was performed via restriction fragment length polymorphism analysis. The expression levels of CYP19A1 in prostate cancer tissues were compared with those in benign prostatic hyperplasia tissues. Results The CYP19A1 rs2414096 AA genotype and A allele were significantly associated with an increased risk of prostate cancer development. The significant association between this genotype and PSA level ≥ 10 ng/ml, Gleason score ≥ 7 and with the presence of metastases was observed. Significantly decreased relative expression of CYP19A1 was detected in prostate cancer tissues. Patients with the AA genotype presented higher relative CYP19A1 expression than did those with the GG genotype. Significantly lower circulating testosterone levels and higher serum PSA levels were detected in patients with the AA genotype. Conclusion The CYP19A1 rs2414096 polymorphism was significantly associated with prostate cancer development and aggressiveness in Slovak patients.

Exploring the potential of BOLA3-DT as a diagnostic biomarker in prostate cancer.

Exploring the potential of BOLA3-DT as a diagnostic biomarker in prostate cancer. Expression of the lncRNA BOLA3-DT was analyzed between normal and tumor samples in the GDC TCGA PRAD (Genomic Data Commons: The Cancer Genome Atlas Prostate Adenocarcinoma Collection) dataset. Disease progression-related clinicopathological parameters such as serum PSA level (ng/ml) and Gleason score were associated with the expression of BOLA3-DT using the same GDC TCGA PRAD dataset. To validate these findings, the expression of BOLA3-DT was checked in our sample set of 15 PCa (prostate cancer) and 15 BPH (benign hypertrophy of the prostate) patients. In the GDC TCGA PRAD dataset, the expression of the lncRNA BOLA3-DT was significantly downregulated in prostate cancer tissue samples (n = 492) compared to adjacent normal (n = 52; p < 0.0001), and, there was a significant negative correlation between the expression of the lncRNA BOLA3-DT and the serum PSA level (p < 0.01). However, no significant association was found between the lncRNA BOLA3-DT expression and the Gleason score (p > 0.05). In this study, it was found that BOLA3-DT was downregulated in PCa tissue samples compared to BPH samples (p > 0.05). In the GDC TCGA PRAD dataset, it was revealed that BOLA3-DT could serve as an excellent diagnostic marker with a sensitivity of 86.9% and a specificity of 84.6% (AUC-0.916). LncRNA BOLA3-DT, a novel long non-coding RNA, was found to be downregulated in prostate cancer. The expression of the lncRNA BOLA3-DT can serve as a diagnostic marker in prostate cancer.

"Utility of PET/CT with [18F] F-fluorocholine in assessing the response to antiandrogenic therapy in patients with prostate cancer."

To evaluate the correlation between response assessment measured by PET/CT with [18F] F-fluorocholine (Choline PET/CT) and serum levels of PSA in patients with prostate cancer under antiandrogenic treatment. A retrospective study included patients with CRPC and CSPC treated with enzalutamide, abiraterone, or apalutamide between June 2018 and July 2021, who underwent baseline and a follow-up Choline PET/CT. The difference in maximum SUVmax (ΔSUV) between both studies and the PSA value before and at follow-up were recorded. The response to treatment was compared by PSA vs. PET, assessing their association, agreement, and correlation. Thirty patients were included (median age 74 years, range 68-78), 12 with CSPC and 18 with CRPC; 22 had nodal disease, and 15 had active bone disease. The average time between pre-treatment and follow-up PET/CT was 11 months (range 3.5-23). Patients with extra-nodal metastatic disease at the beginning of treatment showed a higher correlation between PSA and ΔSUV (OR 4.375). In patients with bone disease at the start of treatment, 80% were classified as non-responders on PET response assessment, while only 40% were non-responders by PSA. The correlation between PET and PSA was mild (Kendall's tau_b 0.26), and the classification into Responders/Non-responders had only slight agreement (Cohen's kappa 0.30). Choline PET/CT shows low concordance with the PSA values obtained during the follow-up of response to anti-androgen therapy, especially in patients with bone involvement.

Comparing the effectiveness of digital rectal examination, prostate specific antigen, and TRUS guided prostate biopsy, in the detection of prostate cancer

Prostate cancer has been the most common malignancy in men accounting for one fourth of cancers. Use of Trans rectal ultrasonography (TRUS) in men with an abnormal PSA and/or digital rectal examination acting as a guide to direct prostate biopsies will lead to decrease in number of early deaths It is a prospective observational study.All the patients attending the Urology Out patient Department with a suspicion of Ca prostate from clinical signs and symptoms were clinically evaluated using Digital Rectal Examination and screened for serum PSA levels. All the patients in whom abnormality was detected on DRE and/or an elevated serum PSA level were included in the study and TRUS biopsy was done. The statistical analysis was executed by SPSS version 20 continuous variables were analyzed with student t -test. The present study includes 95 men in whom abnormality detected in DRE or in the levels of serum PSA.10 core biopsy was done in 53 patients and 16 core biopsy was done in 42 patients. Among the total number of patients subjected to TRUS guided prostate biopsy either 10 core or 16 core, 31 patients detected with prostatic adenocarcinoma which accounts for 32.6%, 12 patients had High grade PIN accounting for 12.62%, 30 patients (31.57%) detected with fibroadenoleiomyomatous hyper plasia , 5 patients had fibroadenoleiomyomatous hyperplasia with chronic prostatitis which is 5.20% and chronic prostatitis is found in 15 patients attributing to 15.78%.Cancer detection rate with abnormalities in PSA alone was found to be 15% while it was 70% when both DRE and PSA showed abnormal results which is significantly higher. It shows that both DRE and PSA has to be considered while estimating the cancer rate. Detection rate with 16 core TRUS guided biopsy is 54.76% which is significantly (P value 0.0037) higher than that of 10 core biopsy (15.09 %).

Diagnostic Efficacy of grey-zone Serum Prostate Specific Antigen level in patients with Benign Prostatic Hyperplasia and Prostate Carcinoma

Objective: Evaluation of diagnostic role of grey zone serum prostate specific antigen level(4-10ng/ml) in patients with benign prostatic hyperplasia (BPH) and prostate carcinoma keeping histopathology as gold standard. Study design and setting: Cross-sectional study conducted in department of urology and chemical pathology, sheikh Zayed hospital Rahim yar khan. Methodology: Patients with grey zone serum prostate specific antigen level (4-10ng/ml), lower urinary tract symptoms or abnormal DRE (digital rectal examination) were included and diagnosis was confirmed on the basis of histopathology. Chi square test used to see the statistically significant difference between subgroups. P value &lt;0.05 was deemed as significant. Diagnostic role evaluated by ROC curve analysis. Results: Mean age of study subjects was 60.21±10.046 years and 155 (81.2%) subjects were having serum prostate specific antigen level in grey zone (4-10ng/ml). Of the total 191 study subjects, 59(30.9%) were histopathologically confirmed cases of benign prostatic hyperplasia and 34(17.8%) were confirmed cases of prostate carcinoma. 41 (26.45%) cases of benign prostatic hyperplasia were having serum PSA level in grey zone (4-10ng/ml) and 16(10.32%) cases with prostate carcinoma were having PSA level in grey zone (4-10ng /ml). ROC curve analysis shows AUC=0.584 in case of BPH and AUC=0.707 in case of CA prostate. Conclusion: On the basis of our study, it is concluded that grey zone serum PSA level in symptomatic individuals should be used in conjunction with other non-invasive diagnostic and clinical parameters to improve diagnosis and to avoid unnecessary biopsy in every symptomatic individual

Specific immunohistochemical expression of Mmp-26 in prostatic adenocarcinoma

Abstract Matrix metalloproteinases (MMP) have been identified as biomarkers for several diseases, including cancer. The increase in the expression of these enzymes has been related to greater tumor aggressiveness. MMP-26 is expressed constitutively in the endometrium and some cancer cells of epithelial origin. However, there is a lack of studies on its expression on prostatic carcinoma. In this study, the evaluation of MMP-26 reactivity by immunohistochemistry (IHC) was carried out in 150 paraffinized samples representative of benign and malignant prostatic lesions. 70 of the 150 samples showed IHC immunopositivity, being more prevalent in carcinoma cases (44 out of 70 cases) with moderate and strong intensity. The expression and intensity of the MMP-26 reaction showed a significant association with total PSA values. As expected, serum PSA levels were higher in cases of carcinoma than in prostatic hyperplasia or atrophy. Studies have demonstrated the potential of MMP-26 as a tumor marker, and our results have shown that its immunoexpression was useful to differentiate a group of benign and malignant samples in prostate tumors. This characteristic can assist in the predictive assessment and, consequently, in the development of new strategies for the diagnosis, prognosis, and treatment of prostate cancer.

Integration of Genomic Tests in Prostate Cancer Care: Implications for Clinical Practice and Patient Outcomes.

Prostate cancer (PCa) is a common malignancy in men and is among the leading causes of cancer-related death worldwide. Genomic tests assess disease aggressiveness and guide treatment, particularly in low- and intermediate-risk PCa. We reviewed the literature on the use of four genomic tests (Prolaris®, Promark®, Oncotype DX®, and Decipher®) in assessing the prognosis of PCa and their use in treatment decision-making. Most of the studies showed that Prolaris® has a strong correlation with biochemical recurrence, metastasis risk, PCa-specific mortality (PCSM), and pathological features. Similarly, three studies on Promark® indicated a connection between results and pathological features in the subsequent prostatectomy, time to metastasis, and biochemical recurrence. Fourteen studies on Oncotype DX® showed a clear correlation between high scores, death, and PCSM. One study found that routine biopsy pathology reports, combined with serum PSA levels, provide a risk assessment comparable to Oncotype DX® testing. Results from 22 studies on Decipher® were controversial. The test was associated with conservative management, suggesting that patients with a high GC score are more likely to need radiation after surgery. Comparative studies indicated that Oncotype DX® is preferable for assessing PCSM, Decipher® for predicting metastasis, and Prolaris® for predicting recurrence. With the incidence rate of PCa dramatically increasing, genomic tests appear to be useful adjunctive precision medicine tools with significant potential in improving prognostic discrimination, facilitating better risk stratification, and guiding personalized treatment, especially in the intermediate-risk patient group. Large-scale, prospective, multi-sectional studies are required to validate the utility of these tests prior to their integration into clinical practice.

Design of a novel complex 99mTc-Nilutamide as a tracer for prostate cancer disorder detection in mice

Abstract Male prostate cancer (PCa) is considered among the most fatal illnesses. Despite the recent decrease in prostate cancer incidence attributed to advancements in early detection and therapy, these reductions have not effectively mitigated the elevated fatality rate linked to this disease. The drug Nilutamide was effectively radiolabeled with technetium-99m, producing a radiochemical yield of 96 ± 0.14 % under optimal conditions. In our study, two cohorts of mice were utilized, namely the control group and the group with prostate cancer. Various biochemical parameters, including PSA levels in serum, were assessed, revealing a significantly elevated value in the group with prostate cancer, indicating potential tumor development. Furthermore, the activities of antioxidant enzymes (CAT, SOD) were notably lower in the group with prostate cancer compared to the healthy control group, while the oxidative activity reflected by MDA levels, the final product of lipid peroxidation, was higher in the prostate cancer group than in the healthy control group. The biodistribution analysis showed rapid localization of 99mTc-Nilutamide in prostate cancer tissue after 2 h post-injection, with a substantial value of 11.4 ± 1.1 % I. D/g tissue. Consequently, it was deduced that radiolabeled 99mTc-Nilutamide can serve as an effective imaging tool for prostate cancer.

Abstract B062: Transcriptomic analysis of whole blood samples from prostate cancer patients: A comparative study of patients from geographically diverse populations

Abstract Introduction: Prostate cancer is the most frequently diagnosed cancer across 112 countries. Among American men, an estimated 299, 010 new cases and 35,250 deaths are projected for 2024. In this study, the transcriptomic profile of prostate cancer patients from geographically and ethnically diverse cohorts (USA-Caucasian, RSA-Black) were compared to identify gene expression patterns associated with prostate cancer. Methods: Whole blood samples were collected from PCa and controls. Controls had the same age-range as PCa with no clinical indication of prostatic disease and serum PSA levels below 1.5 ng/ml. RNA was isolated, sequencing was carried out on Novaseq 6000, and data analyzed using PartekFlow to identify differential gene expression patterns (RSA-PCa: 6, RSA-Control: 6, USA-PCa: 7, USA-Control: 11). qRT-PCR was undertaken on a cohort of 27 biomarkers (PROSTest) related to PCa in whole blood. Results: Differential expression analysis identified distinct patterns in USA and RSA groups. In the USA PCa cohort, 2,193 genes were differentially expressed compared to the controls with fold change (FC) &amp;gt;1, p-value (p) &amp;lt;0.05, while in the RSA PCa cohort, 1,627 genes were differentially expressed compared to the controls. Pathway analyses identified enrichment for immune responsive genes in the RSA cohorts. We identified that 26 of 27 Wren’s PROSTest genes detectable in both groups. RNAseq and normalized PCR gene expression were well- correlated (r=0.44, p=0.0012, n=30 pairs). Conclusion: Based on this RNAseq study, there may be geographic differences related to ethnicity in overall blood RNA gene expression. We specifically identified alterations in immune function gene expression between the USA and RSA. Importantly, PROSTest genes were detected in both populations and exhibited a significant correlation. Development of gene signatures for biomarker discovery should, however, consider specific ethnicities and geographical regions. Citation Format: Srinivas V Koduru, Mark Kidd, Ané Pieters, S E Nagel, Robert P Millar, Abdel B Halim. Transcriptomic analysis of whole blood samples from prostate cancer patients: A comparative study of patients from geographically diverse populations [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B062.

Experience of rescue therapy with [177Lu]Lu-rhPSMA-10.1 in patients with primary or acquired resistance to [177Lu]Lu-PSMA-I&T

PurposeRadioligand therapy is an increasingly important option for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Radiohybrid ligands targeting prostate-specific membrane antigen (PSMA) are a novel group of theranostic radioligand therapy agents for which higher tumour absorbed radiation doses have been demonstrated compared to established PSMA ligands. Here, we report data from ten patients who were treated within a compassionate use program with the radiohybrid PSMA-ligand [177Lu]Lu-rhPSMA-10.1 after experiencing disease progression under treatment with [177Lu]Lu-PSMA-I&T.MethodsTen patients with advanced PSMA-positive prostate cancer who showed progression under treatment with [177Lu]Lu-PSMA-I&T received up to three cycles of rescue therapy with [177Lu]Lu-rhPSMA-10.1 (7.4–8.1 GBq per cycle). Efficacy (PSA response according to PCWG3 and RECIP) and overall survival were evaluated. Adverse events were recorded from first application.ResultsDespite progression with [177Lu]Lu-PSMA-I&T, after the first cycle of [177Lu]Lu-rhPSMA-10.1 rescue therapy, five patients (50%) showed a decrease in serum PSA level. In imaging, three of the ten patients (30%) showed a partial radiologic response. Four of the five patients with a decrease of serum PSA under [177Lu]Lu-rhPSMA-10.1 had initially responded to treatment with [177Lu]Lu-PSMA-I&T but had become resistant. However, the remaining patient had shown continuous disease progression during [177Lu]Lu-PSMA-I&T therapy but showed an immediate response to [177Lu]Lu-rhPSMA-10.1. The additional treatment with [177Lu]Lu-rhPSMA-10.1 was generally well tolerated by all patients.ConclusionsPatients showing tumour progression while receiving [177Lu]Lu-PSMA-I&T radioligand therapy may benefit from rescue therapy with the novel radiohybrid PSMA ligand, [177Lu]Lu-rhPSMA-10.1. Higher tumour absorbed radiation doses with [177Lu]Lu-rhPSMA-10.1 may overcome primary and acquired radiation resistance.Graphical

Measurement of PDE5 concentration in human serum: proof-of-concept and validation of methodology in control and prostate cancer patients

PurposeWe aimed to investigate if the type 5 phosphodiesterase (PDE5), an enzyme with cardinal biological functions in sexual and cardiovascular health, can be detected and quantited in human serum.MethodsBlood samples were collected from control male and female subjects. PDE5 levels were measured by a specific ELISA kit. ROC curves weighted for age and serum levels of PSA (male subjects), or age (female subjects) were used to identify the predictive ability in the detection of PCa. Sensitivity, specificity, PPV and NPV values were determined for cut-off value determined during ROC curve analysis.Results41 control male subjects, 18 control female subjects, and 55 consecutive subjects, of which 25 were affected by benign prostatic hypertrophy (BPH) and 30 with histologically confirmed prostate cancer (PCa), were studied. PDE5 serum levels were detectable in all subjects (range: 5 to 65 ng/ml). Analysis by MANCOVA identified a significant difference in serum PDE5 between control subjects or hyperplasia patients and PCa patients. Marginal means of serum PDE5 concentrations showed a significant difference (p < 0.001). The ROC curve demonstrated that PDE5 serum levels can predict men with or without PCa, with 0.806 AUC value (p < 0.0001). Using a 12.705 ng/ml PDE5 serum cut-off yielded sensitivity, specificity, PPV, and NPV of 83.3%, 77.27%, 62.5%, and 91.1% in detecting men with histologically proven PCa, respectively.ConclusionsWe demonstrated, for the first time, that PDE5 levels can be detected in human sera and that PCa patients have significantly higher PDE5 concentration compared to BPH patients or male and female controls. While serum PDE5 level measurement may open new research avenues, the clinical relevance of PDE5 levels in PCa patients deserves further investigation.

Clinicopathological Study of Prostate Diseases and Its Correlation with PSA Level, Size of Prostate and Gleason’s Scoring System in Case of Prostatic Carcinoma

Background: Prostate gland diseases significantly impact adult males globally, with an increasing prevalence due to aging populations. The primary conditions affecting the prostate are inflammation, benign prostatic hyperplasia (BPH), and tumors, with BPH being the most common. Prostatic carcinoma is also prevalent, with a high lifetime risk. Prostate cancer incidence increases with age, and early detection relies on digital rectal examination, transrectal ultrasonography, and PSA testing. Aim of the study: The study aims to find out correlation between PSA, Gleasons scoring system and HER-2/NEU gene in prostatic cancer. Methods: This study, conducted from July 2017 to June 2019 at BIRDEM General Hospital, enrolled 110 male patients aged 50-100 with clinical signs of prostatic diseases. Patients provided written informed consent and met specific inclusion criteria. Specimens were obtained via TURP, simple or radical prostatectomy, preserved in 10% neutral buffered formalin and examined for pathological lesions. PSA levels were measured using an immunoassay, and Gleason scoring was used for carcinoma categorization. Data were collected via questionnaires and analyzed using SPSS software. Result: The study analyzed 110 prostatic disease cases, with patients averaging 67.7 years. The most common diagnosis was BPH with inflammation (50.9%), followed by BPH without inflammation (35.5%) and adenocarcinoma (13.6%). Urgency (80%), increased micturition frequency (78.2%), poor stream (78.2%), and urinary retention (77.3%) were the most common symptoms. There was a significant correlation between serum PSA levels and prostate size (p &lt; 0.001), with higher PSA levels indicating larger prostates and a higher likelihood of adenocarcinoma. The most frequent Gleason score was 4+4=8 (40%). HER2/neu overexpression showed a marginal correlation with PSA levels (p=0.053). Conclusion: The study found that the most common age group for prostatic diseases was 61-70 years. Benign prostatic hyperplasia (BPH) was the most frequent lesion. Grade II (31-50g) prostate size was common on ultrasound. Most patients had a PSA level of 0-5 ng/ml, aiding early diagnosis and reducing morbidity

Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels.

PSA screening has led to an over-diagnosis of prostate cancer (PCa) and unnecessary biopsies of benign conditions due to its low cancer specificity. Consequently, more accurate, preferentially non-invasive, tests are needed. We aim to evaluate the potential of semen sEV (small extracellular vesicles) tsRNAs (tRNA-derived small RNAs) as PCa indicators. Initially, following a literature review in the OncotRF database and high-throughput small RNA-sequencing studies in PCa tissue together with the sncRNA profile in semen sEVs, we selected four candidate 5'tRF tsRNAs for validation as PCa biomarkers. RT-qPCR analysis in semen sEVs from men with moderately elevated serum PSA levels successfully shows that the differential expression of the four tRFs between PCa and healthy control groups can be detected in a non-invasive manner. The combined model incorporating PSA and specific tRFs (5'-tRNA-Glu-TTC-9-1_L30 and 5'-tRNA-Val-CAC-3-1_L30) achieved high predictive accuracy in identifying samples with a Gleason score ≥ 7 and staging disease beyond IIA, supporting that the 5'tRF fingerprint in semen sEV can improve the PSA predictive value to discriminate between malignant and indolent prostate conditions. The in silico study allowed us to map target genes for the four 5'tRFs possibly involved in PCa. Our findings highlight the synergistic use of multiple biomarkers as an efficient approach to improve PCa screening and prognosis.

Cryotherapy versus radical prostatectomy as a salvage treatment for radio-recurrent prostate cancer.

The aim of this study is to compare outcomes of SRP (salvage radical prostatectomy) with SCAP (salvage cryoablation of the prostate) in local radio-recurrent PCa (prostate cancer) patients. A retrospective analysis of a multicentric European Society of Uro-technology (ESUT) database was performed. Data on patients with local recurrent PCa after radiotherapy who underwent salvage treatment were collected. Patients and their respective disease characteristics, perioperative complications as well as oncological outcomes were then described. The treatment success rate was defined as PSA nadir < 0,4 ng/ml. Any complications were graded according to the modified Clavien system. A descriptive and comparative analysis was performed using SPSS software. 25 patients underwent SRP and 71 patients received SCAP. The mean follow-up was 24 months. The median PSA level before initial treatment was 8.3 (range 7-127) ng/ml. The success rates of SRP and SCAP were largely comparable (88% (22 patients) vs. 67.7% (48 patients), respectively, p = 0.216). The mean serum PSA levels at 12 months after salvage treatment were 1.2 ± 0.2 ng/mL vs. 0.25 ± 0.5 ng/mL, p > 0.05). During the follow-up period, only 3 (12%) patients in the SRP group had PSA recurrence compared with 21 patients (29.6%) in the SCAP group. The 5-year BRFS was similar (51,6% and 48,2%, p = 0,08) for SRP and SCAP respectively. The 5-year overall survival rate was 91.7%, and 89,7% (p = 0.669) and the 5-year cancer-specific survival was 91.7%, and 97,1% (p = 0.077), after SRP and SCAP respectively. No difference was found regarding the complications. Both SRP and SCAP should be considered as valid treatment options for patients with local recurrence of PCa after radiotherapy. SCAP has a potentially lower risk of morbidity and acceptable intermediate-term oncological efficacy, but a longer follow up and a higher number of patients is ideally needed to draw any long-term conclusions regarding the oncological data.

SEROLOGICAL OUTCOMES OF TREATMENT WITH 3D-CRT AND IMRT IN LOCALIZED PROSTATE CANCER.

Prostate cancer ranks the second most frequent cancer encountered worldwide in men. Radiotherapy has been effectively used to treat localized prostate cancer. Over the years more effective radiation techniques like 3D-Conformal Radiation Therapy (3D-CRT), Proton Therapy, Intensity Modulated Radiation Therapy (IMRT), and Brachytherapy has been evolved and effectively used to deliver radiation therapy. Herein, we compare serological outcomes of two radiation treatment techniques intensity modulated radiation therapy (IMRT) and 3- dimensional conformal radiation therapy (3DCRT) in localized prostate adenocarcinoma. It is a cohort study conducted at Department of Oncology, Dr Ziauddin Hospital, Karachi. Patients with localized prostate adenocarcinoma meeting the inclusion criteria were recruited from July 2016 to June 2022, underwent treatment with a total dose >74 Gy using two different advanced radiotherapy techniques, i.e., IMRT and 3D-CRT. Serum PSA levels were assessed prior to treatment, and 6 weeks and 12 months after treatment. Paired t-Test was applied to identify the difference in PSA levels before, and after the treatment. p-value less than 0.05 was taken as significant at 95% confidence interval. A total of 78 patients with 39 in each group. The mean age of patients in 3D-CRT group was 68±10 years while in IMRT group was 68±07 years. Six weeks after initiation of treatment, we observed that both the treatment methods, i.e., 3D-CRT and IMRT reduced the PSA levels significantly p-value = 0.001 respectively. There was no significant difference in the mean of PSA levels on 06th week and 12th months. Furthermore, the analysis of PSA levels at 12th months when compared with the baseline PSA levels came highly significant in both the groups as depicted in paired-t teat analysis of PSA levels with acceptable toxicity. Radiation therapy modalities 3D-CRT and IMRT both showed a significant serological response with minimal or acceptable gastrointestinal and genitourinary toxicities in the 3D-CRT group in comparison to the IMRT group. Although the sample size is relatively smaller, but the results of this study are encouraging to treat those patients on 3D-CRT, who cannot afford more expansive radiotherapy treatment technique like IMRT.

Impact of definitive radiotherapy on metabolic response measured with 68Ga-PSMA-PET/CT in patients with intermediate-risk prostate cancer.

To assess the early metabolic response of the primary tumor using Gallium-68 (68Ga)-labeled-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET/CT), as well as the relationship between PSMA change in the primary tumor and PSA response after definitive radiotherapy (RT), either alone or in combination with androgen deprivation therapy (ADT) in intermediate risk prostate cancer (IR-PCa) patients. The clinical data of 71 IR-PCa patients treated with RT alone (36 patients, 50.7%) or RT and ADT (35 patients, 49.3%) were retrospectively analyzed. The difference between pre- and Posttreatment primary tumor PSMA expression and serum PSA values measured 4 months after completion of treatment were compared between treatment arms. Correlation between primary tumor metabolic response and serum PSA changes was analyzed. The median duration between pre- and Posttreatment 68Ga-PSMA-PET/CT for the entire patient population was 6.9 months (range, 5.6-8.4 months), and it was similar in both treatment arms. A decrease in primary tumor maximum standardized uptake value (SUVmax) was seen in 66 patients (93.0%), with a median value of 61.2%, which is significantly lower in patients undergoing RT alone than those undergoing RT and ADT (45.1 ± 30.6% vs. 59.1 ± 24.7%; p = 0.004). The complete metabolic response rate was significantly higher in patients undergoing RT and ADT than those treated with RT alone (40% vs. 0%; p < 0.001). Although moderate and positive correlation between pretreatment SUVmax and oosttreatment SUVmax was observed, there was no significant correlation between SUV change and PSA change. For patients treated with RT and ADT, posttreatment SUVmax was significantly lower and SUV change was significantly higher in patients with PSA nadir than in those without. Our preliminary results show that RT, with or without ADT, significantly reduces primary tumor SUVmax and serum PSA levels. Nonetheless, our findings indicate that early treatment response using 68Ga-PSMA-PET/CT is not feasible for those treated with RT alone, and it may only be useful in better distinguishing patients with and without PSA nadir for those who received both RT and ADT.

LX1 Dual Targets AR Variants and AKR1C3 in Advanced Prostate Cancer Therapy.

The development of resistance to current standard-of-care treatments, such as androgen receptor (AR) targeting therapies, remains a major challenge in the management of advanced prostate cancer. There is an urgent need for new therapeutic strategies targeting key resistant drivers, such as AR variants like AR-V7, and steroidogenic enzymes, such as aldo-keto reductase 1C3 (AKR1C3), to overcome drug resistance and improve outcomes for patients with advanced prostate cancer. Here, we have designed, synthesized, and characterized a novel class of LX compounds targeting both the AR/AR variants and AKR1C3 pathways. Molecular docking and in vitro studies demonstrated that LX compounds bind to the AKR1C3 active sites and inhibit AKR1C3 enzymatic activity. LX compounds were also shown to reduce AR/AR-V7 expression and to inhibit their target gene signaling. LX1 inhibited the conversion of androstenedione into testosterone in tumor-based ex vivo enzyme assays. In addition, LX1 inhibited the growth of cells resistant to antiandrogens including enzalutamide (Enza), abiraterone, apalutamide, and darolutamide in vitro. A synergistic effect was observed when LX1 was combined with antiandrogens and taxanes, indicating the potential for this combination in treating resistant prostate cancer. Treatment with LX1 significantly decreased tumor volume, serum PSA levels, as well as reduced intratumoral testosterone levels, without affecting mouse body weight. Furthermore, LX1 was found to overcome resistance to Enza treatment, and its combination with Enza further suppressed tumor growth in both the CWR22Rv1 xenograft and LuCaP35CR patient-derived xenograft models. Collectively, the dual effect of LX1 in reducing AR signaling and intratumoral testosterone, along with its synergy with standard therapies in resistant models, underscores its potential as a valuable treatment option for advanced prostate cancer. Significance: LX1 simultaneously targets androgen receptor variants and the steroidogenic enzyme AKR1C3, offering a promising approach to combat drug resistance and enhancing therapeutic efficacy in conjunction with standard treatments for advanced prostate cancer.

177 Lu-PSMA With Olaparib Radiosensitization Potentiates Response and Toxicity in Extensive Castration-Resistant Metastatic Prostate cancer.

A patient with widespread intensely prostate-specific membrane antigen-expressing, BRCA gene mutation-positive bone metastases at the time of prostate cancer diagnosis had progressed on multiple lines of standard therapy. He received 177 Lu-prostate-specific membrane antigen 8.5 GBq augmented by a short course of olaparib radiosensitization and achieved 90% decrease in serum PSA level after a single treatment. His tumor response was much better than expected by predictive dosimetry. However, his marrow radiotoxicity was worse than anticipated and required hospitalization. This suggests radiosensitizing agents to be a double-edged sword that must be carefully considered and balanced during activity prescription.

A comparative study of 18F-PSMA-1007 PET/CT and pelvic MRI in newly diagnosed prostate cancer

PurposeTo evaluate the difference in the diagnostic efficacy of 18F-PSMA-1007 PET/CT and pelvic MRI in primary prostate cancer, as well as the correlation between the two methods and histopathological parameters and serum PSA levels.MethodsA total of 41 patients with suspected prostate cancer who underwent 18F-PSMA-1007 PET/CT imaging in our department from 2018 to 2023 were retrospectively collected. All patients underwent 18F-PSMA-1007 PET/CT and MRI scans. The sensitivity, PPV and diagnostic accuracy of MRI and 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were calculated after comparing the results of MRI and 18F-PSMA-1007 PET/CT with biopsy. The Spearman test was used to calculate the correlation between 18F-PSMA-1007 PET/CT, MRI parameters, histopathological indicators, and serum PSA levels.ResultsCompared with histopathological results, the sensitivity, PPV and diagnostic accuracy of 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were 95.1%, 100.0% and 95.1%, respectively. The sensitivity, PPV and diagnostic accuracy of MRI in the diagnosis of prostate cancer were 82.9%, 100.0% and 82.9%, respectively. There was a mild to moderately positive correlation between Gleason (Gs) score, Ki-67 index, serum PSA level and 18F-PSMA-1007 PET/CT parameters (p < 0.05). There was a moderately negative correlation between the expression of AMACR (P504S) and 18F-PSMA-1007 PET/CT parameters (p < 0.05). The serum PSA level and the Gs score were moderately positively correlated with the MRI parameters (p < 0.05). There was no correlation between histopathological parameters and MRI parameters (p > 0.05).ConclusionCompared with MRI, 18F-PSMA-1007 PET/CT has higher sensitivity and diagnostic accuracy in the detection of malignant prostate tumors. In addition, the Ki-67 index and AMACR (P504S) expression were only correlated with 18F-PSMA-1007 PET/CT parameters. Gs score and serum PSA level were correlated with 18F-PSMA-1007 PET/CT and MRI parameters. 18F-PSMA-1007 PET/CT examination can provide certain reference values for the clinical diagnosis, evaluation, and treatment of malignant prostate tumors.

Metastatic onset of prostate carcinoma: A clinical and pathological challenge.

Prostate cancer is the second most common cancer, following lung cancer, and the fifth leading cause of cancer death in men worldwide. The onset of the disease, characterized by symptoms or changes caused by distant metastases, is rare and poses a challenge for clinicians and pathologists. We aimed to present a series of prostate carcinoma (PC) with unusual, histologically confirmed distant metastases (pM1) at the time of diagnosis, which raised suspicions of other types or origins of the primary tumor. Patients diagnosed with PC and distant metastases within a five-year timeframe (2017-2022) were extracted from the hospital database. The following data were collected: patient's age, imaging data, serum PSA level, and histopathological evaluation results. Patients with unusual distant metastases were selected and analyzed. We identified 10 patients in whom the diagnosis of PC was established following histopathological examination of tissue taken from distant metastatic sites (pM1). In three patients, the location of distant metastases was unusual: retroperitoneal, cranial/dural/epicranial and supradiaphragmatic lymph nodes which posed diagnostic challenges. Establishing the prostate origin of the tumor relied on immunohistochemical (IHC) investigation guided by clinical-imaging information. A metastasis of PC may rarely present as a cranial/dural tumor, retroperitoneal, or supradiaphragmatic lymphadenopathies in a man over the age of 50, but it should be taken into consideration. In the absence of correlated clinical, imaging, and histopathological/IHC data, diagnosing distant metastasis from PC is difficult, especially considering its potentially confusing IHC profile.