Prostate-specific Antigen Changes Research Articles

A retrospective study of prognostic factors and prostate-specific antigen dynamics in Japanese patients with metastatic hormone-sensitive prostate cancer who received combined androgen blockade therapy with bicalutamide.

This retrospective observational study explored the therapeutic potential of combined androgen blockade (CAB) with bicalutamide (Bic-CAB) as an initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC) in Japan. The electronic health records of 159 patients with mHSPC from three Japanese institutions who received initial treatment with Bic-CAB between 2007 and 2017 were analyzed. The time to prostate-specific antigen (PSA) progression, duration of Bic-CAB treatment, and overall survival (OS), with various definitions for PSA progression, were assessed. A multivariate Cox proportional hazards model was constructed using clinical parameters to predict time to the end of Bic-CAB treatment and OS. The median observation period was 46.4months, and the median age of patients at diagnosis was 71years. A total of 46.5% patients experienced PSA progression with a median survival duration of 29months (according to Prostate Cancer Clinical Trials Working Group 3 criteria), and 49.1% patients achieved a PSA nadir < 0.2ng/mL in a median time of 4.7months. When stratified by PSA nadir and PSA change, patients at low risk for disease progression with a small PSA change due to low initial PSA had a 5-year OS of 100% and a 10-year OS of 75%. The OS during the observation period was 72.9months. These findings highlight the potential effect of Bic-CAB in patients with mHSPC who were at low risk for disease progression. Initial treatment with Bic-CAB and adjusting treatment early based on PSA dynamics may be a reasonable treatment plan for these patients.

Drugs causing prostate-specific antigen changes: the food and drug administration adverse event reporting system combined with Mendelian randomization analysis

ABSTRACT Background Prostate cancer is one of the most common malignancies in men worldwide, and prostate-specific antigen (PSA) screening is widely used for its early detection. Drug use may affect PSA levels, but the effect for most drugs is currently unknown. Methods This study first investigated drugs related to PSA changes through the Food and Drug Administration Adverse Event Reporting System (FAERs) database, and then used a Mendelian randomization (MR) method to explore the causal relationship between specific drugs and PSA changes using a genome-wide association study (GWAS) data. The statistical analysis software SAS and R were used in the study. Results Through analysis of the FAERs database, 22 drugs were found to be associated with an increase in PSA, and 14 drugs were associated with a decrease in PSA. MR analysis showed that the use of tamsulosin may lead to an increase in PSA. Heterogeneity test, horizontal pleiotropy test and leave-one-out Analysis verified the stability of the results. MR analyses for other drugs did not show statistical significance. Conclusion This study provided a basis for better understanding the impact of medications on prostate health, helping to avoid overdiagnosis or underdiagnosis of high-risk patients. However, research still requires larger-scale validation and in-depth exploration.

A multi-center, randomized, open label, two-arm study to evaluate safety & efficacy of nutraceutical tablet as adjuvant when compared with standard of care in patients with benign prostatic hyperplasia

BackgroundBenign Prostrate Hyperplasia (BPH) is a progressive disease of ageing men that may be associated with enlargement of the prostate and lower urinary tract symptoms (LUTS). Herbal/Nutraceutical formulations in addition to standard of care (SOC) could alleviate the symptoms, and thus improve the quality of life of patients. ObjectivesTo evaluate safety & efficacy of nutraceutical tablet as an adjuvant with SOC. Materials and MethodsThis was a prospective, randomized two-arm study aimed to assess the safety and efficacy of Herbal/Nutraceutical Formulation (IP) + SOC versus only SOC, in BPH patients. The primary efficacy endpoint was the change in international prostate symptom score (IPSS) within and between two arms. The safety was evaluated in terms of adverse events and change in prostate specific antigen (PSA) levels. Results140 eligible patients (70 / arm) were evaluated for efficacy and safety endpoints. The baseline characteristics of patients in two arms differed nonsignificantly. The change in IPSS-storage, voiding and QoL scores, from day 1 to 90 were statistically significant in both the arms (p < 0.0001). However, by day 90, the change in these scores in SOC+IP arm were significantly higher than that of SOC arm. Further, the change in International Index of Erectile Function (IIEF) scores was significant in SOC+IP arm (p < 0.05), while non-significant in SOC arm. The adverse events non-significantly differed between two arms. ConclusionThe herbal/nutraceutical formulation combined with SOC are safe and effective for the treatment of BPH. The combination therapy was effective in reducing urine-related symptoms and improving the QoL of BPH patients.

Prostate Specific Antigen and Prostate Cancer in Gender Affirming Hormone Therapy for Transgender or Nonbinary Individuals.

The effects of gender affirming hormone therapy on prostate specific antigen (PSA) and prostate cancer incidence in transgender or non-binary individuals (TGNB) born with prostate glands remains uncharacterized. The cohort included 1,024 self-identified TGNB individuals assigned male at birth who received PSA testing in the VA Healthcare System, matched by birth year to cisgender men. PSA changes were measuring using linear-mixed effects modeling accounting for repeated measured and matching. Non-gonadotrophin releasing hormone agonist or antagonist (GnRH) therapy was associated with 1.30 ng/mL lower PSA (95% confidence interval (CI) 1.14-1.46, p < 0.001) and GnRH therapy was associated with 1.08 ng/mL lower PSA (95% CI 0.60-1.55, p < 0.001) compared with cisgender men. Among 450 TGNB individuals who had PSA testing before and after initiation of hormone therapy, non-GnRH and GnRH therapies resulted in 0.49 ng/mL decrease (95% CI 0.35-0.62, p<0.001) and 0.73 ng/mL decrease (95% CI 0.43-1.02, p<0.001), respectively, from median baseline of 0.70 ng/mL. From time of age 50, TGNB prostate cancer incidence was 1.79 per 1,000 patient-years versus 4.02 per 1,000 patient-years in cisgender men. Gender affirming hormone therapies are associated with significant decreases in PSA, and TGNB individuals assigned male at birth remain at risk for prostate cancer. Future work should establish if a lower threshold for biopsy should be used in these contexts and if the decreased incidence is a result of ascertainment bias or hormone therapy resulting in a true decrease in the incidence of prostate cancer.

Association between 99mTc-PSMA SPECT/CT imaging and prostate-specific antigen (PSA) and alkaline phosphatase (ALP) levels post-endocrine therapy in patients with prostate cancer and bone metastases

AimTo investigate the association between positive lesions detected by 99mTc-PSMA SPECT/CT and blood levels of prostate-specific antigen (PSA) and alkaline phosphatase (ALP) in patients with prostate cancer (PCa) and bone metastasis undergoing endocrine therapy. MethodsA retrospective analysis was performed on 43 patients diagnosed with PCa bone metastasis who underwent endocrine therapy. PSA, ALP, whole body bone imaging and 99mTc-PSMA SPECT/CT imaging were collected from all patients (Among them, 17 cases were re-examined 99mTc-PSMA SPECT/CT imaging). According to the results of the first 99mTc-PSMA SPECT/CT imaging for detecting bone metastasis, all cases were divided into two groups: positive group and negative group. The relationship between 99mTc-PSMA imaging and PSA and ALP was analyzed by ROC curve. Fisher exact probability method was used to examine the changes in imaging radioactivity uptake, PSA, and ALP levels in 17 patients after treatment, and P < 0.05 was statistically significant. ResultsAll 43 patients had different degrees of radioactive concentrations on whole-body bone imaging. The first 99mTc-PSMA SPECT/CT imaging showed positive bone metastases in 31 cases and negative bone metastases in 12 cases. ROC curve analysis of PSA and ALP, AUC were 0.778 and 0.770, respectively. When PSA > 1.13 ng/mL, 99mTc-PSMA SPECT/CT imaging diagnostic sensitivity was 93.55%, and specificity was 66.67%. When ALP was >86U/L, the diagnostic sensitivity of 99mTc-PSMA SPECT/CT imaging was 64.52%, and the specificity was 83.33%. In 17 cases, the PSA level decreased in 7 and increased in 10. There were 10 cases of increased ALP and 7 cases of decreased ALP levels. In the second 99mTc-PSMA imaging lesion, there were 9 cases with decreased or no uptake, and 8 cases with increased uptake or number of lesions. The changes in 99mTc-PSMA uptake by Fisher’s exact probability method were statistically significant (P < 0.05, P = 0.006, and P = 0.006, respectively), and ALP level was not statistically significant (P = 0.563). Conclusion99mTc-PSMA SPECT/CT imaging can detect PCa bone metastases, which are related to PSA levels. When PSA > 1.13 ng/mL, the sensitivity of diagnosis and detection of positive bone metastases is higher, and when ALP is >86U/L, 99mTc-PSMA imaging has higher specificity.

Clinical Factors That Influence Repeat 68Ga-PSMA-11 PET/CT Scan Positivity in Patients with Recurrent Prostate Cancer Under Observation After a Negative 68Ga-PSMA-11 PET/CT Scan: A Single-Center Retrospective Study.

This analysis aimed to identify clinical factors associated with positivity on repeat 68Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 68Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann-Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2-1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9-3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative 68Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat 68Ga-PSMA-11 PET/CT.

Race-Related Differences in Sipuleucel-T Response among Men with Metastatic Castrate-Resistant Prostate Cancer.

Our novel findings of higher expression of co-stimulatory receptor ICOS on CD4+ and CD8+ T cells in African American patients with metastatic castrate-resistant prostate cancer (mCRPC) prior and post-sipuleucel-T suggest activation of CD4+ and CD8+ T cells. The data indicate that racial differences observed in these and other immune correlates before and after sipuleucel-T warrant additional investigation to further our understanding of the immune system in African American men and other men with mCRPC.

Independent association between prostate-specific antigen nadir and PSA progression-free survival in first-line abiraterone acetate treatment in castration-resistant prostate cancer patients: a pilot study.

There is limited evidence regarding the correlation between prostate-specific antigen (PSA) kinetics and clinical outcomes. Therefore, after regulating other covariates, we studied patients with castration-resistant prostate cancer who received abiraterone acetate as the first-line treatment. In this study, we investigated whether time to PSA nadir was independently associated with PSA progression-free survival (PFS). As a retrospective cohort study, this study contained a total of 77 castration-resistant prostate cancer patients who received abiraterone acetate from October 2015 to April 2021 in a Chinese hospital. The dependent variable was PSA-PFS. The objective independent variable was time to PSA nadir (TTPN). Covariates involved in this study included age, duration of androgen deprivation therapy (ADT), PSA level at baseline, time of 50% PSA decline, time of PSA decline to nadir, Gleason score, bone metastasis, previous treatment, PSA decline <50% in 3 months, PSA to nadir in 3 months, PSA decline <90%, PSA decline <0.2 ng/mL, and PSA flare. For the 77 subjects, their mean age was 72.70 ± 8.08 years. Fully calibrated linear regression findings indicated that PSA decline and kinetics were positively associated with PFS (months) after adjusting confounders (β = 0.77, 95% CI: 0.11-1.44). A non-linear relationship was not detected between PSA decline or PSA kinetics and progression-free survival. According to the data of this study, there was a correlation between early PSA changes and patients treated with abiraterone acetate.

MRI-Linac radiation therapy outcomes in patients with prostate, breast and other advanced malignancies.

e13811 Background: MR-guided radiation therapy offers an innovative approach, providing superior soft tissue contrast that enables clinicians to deliver higher doses to the target site with fewer fractions. The objective of the study is to assess objective response rates and adverse effects related to a community-based single-institution experience with the ViewRay MRIdian. Methods: An IRB-approved registrational trial was conducted at the Providence Cancer Institute starting May 2020, with data cutoff of September 2023. All patients treated underwent MR screening, and the target site(s) were treated using hypofractionated radiation therapy in ≤5 fractions. The primary endpoint was to assess adverse effects attributed to radiation therapy. Secondary measures included local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and change in prostate-specific antigen (PSA) for patients treated definitively for prostate cancer. The assessments were performed under the guidance of experienced radiation oncologists. Results: From May 2020 to September 2023, n=257 patients received treatment on the MRIdian with a median follow-up of 430 days [range 4-1221 days]. One and 2-year LRFS was 92% and 87%, and excluding prostate and breast cancer, 83% and 70%. Definitive prostatestereotactic body radiation therapy(SBRT) was delivered to 117 patients and significantly reduced PSA (mean difference -6.27, p&lt;0.0001), with no local failures to date. One and 2-year DMFS was 75% and 67%, though if excluding definitive prostate SBRT and partial breast irradiation, these were 48% and 33%. The OS rate at 1 and 2 years was 86% and 76%. Excluding prostate and breast cancer, the 1 and 2-year OS was 74% and 55%. Grade 3+ adverse events possibly or definitely attributable to radiation therapy were noted in 5% (n=13/257) of patients, including 2 possible treatment-associated deaths (bowel perforation following liver SBRT, and respiratory failure following lung SBRT and trastuzumab-deruxtecan systemic therapy). Conclusions: Our institutional experience with the MRIdian demonstrated high levels of local control, while overall survival was driven by out-of-field failures. Serious adverse events were infrequent, but more common in abdominal targets highlighting the need for careful planning and tight organs at risk (OAR) constraints, particularly if systemic therapy is delivered soon after radiation.

Is the Serum Prostate-Specific Antigen Level Affected by Urethral Catheterization in Patients with Acute Urinary Retention?

Background: The reason for elevated serum prostate-specific antigen (PSA) levels in patients undergoing urethral catheterization due to acute urinary retention (AUR) remains a significant and controversial issue. Objectives: To assess the serum PSA level in men with AUR and its changes after catheterization. Methods: This prospective quasi-experimental study (reviewer 1 - comment 7) was conducted on 43 patients who underwent transurethral catheterization following AUR caused by benign prostatic hyperplasia (BPH). Total PSA levels and free/total PSA ratios were measured before catheterization and one and three days after catheter insertion. Additionally, prostate volume and urine output after catheterization (UOAC) were recorded. Results: The mean age, prostate volume, and UOAC of the patients were 69.05 ± 9.45 years, 60.51 ± 26.35 g, and 844.04 ± 341.66 mL, respectively. The mean and median baseline total PSA levels were 12.59 ± 17.71 ng/mL and 6.30 ng/mL, respectively. These values changed to 13.73 ± 19.83 ng/mL (median = 4.80 ng/mL) and 11.57 ± 17.70 ng/mL (median = 4.40 ng/mL) after 1 and 3 days of catheterization, respectively. The changes in total PSA and free/total PSA levels during the study period were not statistically significant (P &gt; 0.05). Moreover, the PSA levels showed no statistically significant difference before, 1 day, and 3 days after catheterization in groups with total PSA ≤ 4 and total PSA &gt; 4 (P = 0.37; 0.22, respectively). Conclusions: Our results suggest an initial elevation in PSA levels in patients with AUR before urethral catheterization. Both PSA and free/total PSA ratios showed no statistically significant differences before and after urethral catheter insertion, and initial PSA levels did not affect their changes post-catheterization (reviewer 1 - comment 1).

Does enzalutamide related PSMA upregulation affect outcomes of lutetium-177 PSMA radioligand therapy?

Enzalutamide is an antiandrogen drug used prior to lutetium-177 prostate specific membrane antigen (Lu-PSMA) radioligand therapy and has shown promising results for upregulating the PSMA expression on prostate cancer cells. In this study, we aim to compare prostate specific antigen (PSA) level changes in prostate cancer patients who received enzalutamide to those who did not. Prostate cancer patients who underwent Lu-PSMA between 2021 and 2023 were retrospectively included. Patients were grouped based on prior enzalutamide therapy: those who received enzalutamide (EZ+) for at least 14 days and those who did not (EZ-). PSA changes and F-18 DCFPyL SUV (Standardized Uptake Values) were compared. Thirty-seven patients were included, 18 EZ+ and 19 EZ-. The median age, Gleason score, and prior chemo/hormonal therapies were similar for EZ+ and EZ-, except for radium-223. Eleven patients (61%) in EZ+ and 13 patients (68%) in EZ- showed a decrease in PSA after the first cycle (p = 0.64). Four patients (22%) in EZ+ and seven patients (37%) in EZ- had more than 50% decrease in PSA after the first cycle (p = 0.33). The average percent decline at the end of the treatment was 23.3% in EZ+ and 50.4% in EZ- (p = 0.4). There was no difference in terms of lesion with highest SUVmax, mean SUV, total tumor volume or activity on pre-therapy PSMA imaging. Enzalutamide treatment prior to Lu-PSMA does not improve patient outcomes when applied remotely. Larger studies evaluating the combination therapies and the timing of enzalutamide are needed to assess its correlation with Lu-PSMA outcomes.

Prospective Comparison of 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI in Patients with Biochemically Recurrent Prostate Cancer.

Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors are both overexpressed in prostate cancer (PC) but may provide complementary information.68Ga-PSMA-R2 and 68Ga-NeoB (DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-NH-CH[CH2-CH(CH3)2]2) are novel PET radiopharmaceuticals that were developed for theranostic use. In this phase II imaging study, we assessed the feasibility, safety, and diagnostic performance of 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI for detection of biochemically recurrent PC. Methods: We prospectively enrolled 27 men with suspected biochemically recurrent PC after initial treatment but noncontributory conventional imaging results (negative or equivocal findings on MRI, CT, and/or bone scan). Participants underwent 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI within 2 wk in noncontrolled order. The SUVmax of putative PC lesions was measured and compared with a composite reference standard (histopathology, follow-up imaging, prostate-specific antigen change). The SUVmax and SUVmean of background organs were measured. Vital signs were recorded before injection of the radiopharmaceuticals and after the scans. Adverse events were recorded up to 72 h after each scan. Results: The prostate-specific antigen level at enrollment was 3.5 ± 3.9 ng/mL (range, 0.3-13.5 ng/mL). 68Ga-NeoB PET/MRI detected 31 lesions in 18 patients (66.7%), whereas 68Ga-PSMA-R2 identified 20 lesions in 15 participants (55.6%). 68Ga-NeoB PET/MRI showed higher sensitivity (85.7% vs. 71.4%), accuracy (88.9% vs. 77.8%), and negative predictive value (66.7% vs. 50.0%) than 68Ga-PSMA-R2, whereas specificity and positive predictive value were equally high (100.0% for both). In 6 patients, 68Ga-NeoB PET/MRI identified 14 lesions that were false-negative on 68Ga-PSMA-R2 PET/MRI. The mean lesion SUVmax was 6.6 ± 3.2 (range, 2.9-13.2) for 68Ga-NeoB and 4.4 ± 1.5 (range, 2.6-8.8) for 68Ga-PSMA-R2 (P = 0.019). Overall lower uptake was noted in tumors and background organs for 68Ga-PSMA-R2. There were no significant changes in vital signs before and after the scans. No adverse events were reported in the 72-h period after scans. Conclusion: 68Ga-NeoB and 68Ga-PSMA-R2 are safe for diagnostic imaging. 68Ga-NeoB PET/MRI showed better diagnostic performance than 68Ga-PSMA-R2. 68Ga-PSMA-R2 showed overall lower uptake, equally in background organs and tumors, and might therefore not be an ideal theranostic compound. Further evaluation in larger cohorts is needed to confirm our preliminary data.

Quantification of biochemical PSA dynamics after radioligand therapy with [177Lu]Lu-PSMA-I&T using a population pharmacokinetic/pharmacodynamic model

BackgroundThere is an unmet need for prediction of treatment outcome or patient selection for [177Lu]Lu-PSMA therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Quantification of the tumor exposure–response relationship is pivotal for further treatment optimization. Therefore, a population pharmacokinetic (PK) model was developed for [177Lu]Lu-PSMA-I&T using SPECT/CT data and, subsequently, related to prostate-specific antigen (PSA) dynamics after therapy in patients with mCRPC using a pharmacokinetic/pharmacodynamic (PKPD) modelling approach.MethodsA population PK model was developed using quantitative SPECT/CT data (406 scans) of 76 patients who received multiple cycles [177Lu]Lu-PSMA-I&T (± 7.4 GBq with either two- or six-week interval). The PK model consisted of five compartments; central, salivary glands, kidneys, tumors and combined remaining tissues. Covariates (tumor volume, renal function and cycle number) were tested to explain inter-individual variability on uptake into organs and tumors. The final PK model was expanded with a PD compartment (sequential fitting approach) representing PSA dynamics during and after treatment. To explore the presence of a exposure–response relationship, individually estimated [177Lu]Lu-PSMA-I&T tumor concentrations were related to PSA changes over time.ResultsThe population PK model adequately described observed data in all compartments (based on visual inspection of goodness-of-fit plots) with adequate precision of parameters estimates (< 36.1% relative standard error (RSE)). A significant declining uptake in tumors (k14) during later cycles was identified (uptake decreased to 73%, 50% and 44% in cycle 2, 3 and 4–7, respectively, compared to cycle 1). Tumor growth (defined by PSA increase) was described with an exponential growth rate (0.000408 h−1 (14.2% RSE)). Therapy-induced PSA decrease was related to estimated tumor concentrations (MBq/L) using both a direct and delayed drug effect. The final model adequately captured individual PSA concentrations after treatment (based on goodness-of-fit plots). Simulation based on the final PKPD model showed no evident differences in response for the two different dosing regimens currently used.ConclusionsOur population PK model accurately described observed [177Lu]Lu-PSMA-I&T uptake in salivary glands, kidneys and tumors and revealed a clear declining tumor uptake over treatment cycles. The PKPD model adequately captured individual PSA observations and identified population response rates for the two dosing regimens. Hence, a PKPD modelling approach can guide prediction of treatment response and thus identify patients in whom radioligand therapy is likely to fail.

Histopathological and Biochemical Assessment of Annona muricata and Allium sativum Pooled Extract on Testosterone Induced Prostate Hyperplasia in Albino Rats

Aims: To investigate the effect of pooled extract of Annona muricata (A. muricata) and Allium sativum (A. sativum) on testosterone-induced prostate hyperplasia in male albino rats.&#x0D; Experimental Procedure: Male albino rats for the study were divided into seven groups identified as A-G groups. Group A and G were used as negative and positive controls with 12 and 5 rats respectively. Male rats in group B-G were induced with 3mg/kg body weight of testosterone propionate injection subcutaneously for 28 days. Animals in group B and C received 100mg/kg body weight of individual Annona muricata and Allium sativum extract respectively, while animals in group D-F received 100mg/kg, 300mg/kg and 600mg/kg body weight of the pooled extracts. We evaluated relative prostate weight(PI),serum prostate specific antigen(PSA),interleukins-6(IL-6), total protein, and histological changes including KI 67 and BCL2 expressions.&#x0D; Results and Conclusion: The study revealed that pooled extracts of A. muricata and A. sativum significantly inhibited prostatic hyperplasia; decreased PI,serum PSA,IL-6, total protein, and expression of KI 67, far better than the any of the single plant extract in this study. This suggests that pooled extract of A, muricata and A, sativum may be used as a therapeutic agent for prostatic hyperplasia, as a result of the influence of the phytochemical constituents.

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

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

Prognostic Performance of RECIP 1.0 Based on [18F]PSMA-1007 PET in Prostate Cancer Patients Treated with [177Lu]Lu-PSMA I&T.

In metastatic castration-resistant prostate cancer (mCRPC) patients treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), the recently proposed criteria for evaluating response to PSMA PET (RECIP 1.0) based on 68Ga- and 18F-labeled PET agents provided prognostic information in addition to changes in prostate-specific antigen (PSA) levels. Our aim was to evaluate the prognostic performance of this framework for overall survival (OS) in patients undergoing RLT and imaged with [18F]PSMA-1007 PET/CT and compare the prognostic performance with the PSA-based response assessment. Methods: In total, 73 patients with mCRPC who were scanned with [18F]PSMA-1007 PET/CT before and after 2 cycles of RLT were retrospectively analyzed. We calculated the changes in serum PSA levels (ΔPSA) and quantitative PET parameters for the whole-body tumor burden (SUVmean, SUVmax, PSMA tumor volume, and total lesion PSMA). Men were also classified following the Prostate Cancer Working Group 3 (PCWG3) criteria for ΔPSA and RECIP 1.0 for PET imaging response. We performed univariable Cox regression analysis, followed by multivariable and Kaplan-Meier analyses. Results: Median OS was 15 mo with a median follow-up time of 14 mo. Univariable Cox regression analysis provided significant associations with OS for ΔPSA (per percentage, hazard ratio [HR], 1.004; 95% CI, 1.002-1.007; P < 0.001) and PSMA tumor volume (per unit, HR, 1.003; 95% CI, 1.000-1.005; P = 0.03). Multivariable Cox regression analysis confirmed ΔPSA (per percentage, HR, 1.004; 95% CI, 1.001-1.006; P = 0.006) as an independent prognosticator for OS. Kaplan-Meier analyses provided significant segregation between individuals with versus those without any PSA response (19 mo vs. 14 mo; HR, 2.00; 95% CI, 0.95-4.18; P = 0.04). Differentiation between patients with or without progressive disease (PD) was also feasible when applying PSA-based PCWG3 (19 mo vs. 9 mo for non-PD and PD, respectively; HR, 2.29; 95% CI, 1.03-5.09; P = 0.01) but slightly failed when applying RECIP 1.0 (P = 0.08). A combination of both response systems (PCWG3 and RECIP 1.0), however, yielded the best discrimination between individuals without versus those with PD (19 mo vs. 8 mo; HR, 2.78; 95% CI, 1.32-5.86; P = 0.002). Conclusion: In patients with mCRPC treated with RLT and imaged with [18F]PSMA-1007, frameworks integrating both the biochemical (PCWG3) and PET-based response (RECIP 1.0) may best assist in identifying subjects prone to disease progression.

Cardiovascular medications and overall survival in metastatic hormone-sensitive prostate cancer.

75 Background: The assessment of comorbid cardiovascular disease can predict health outcomes and may risk-stratify patients for adverse events and death. Current methods used to estimate patient risk, such as the Charlson Comorbidity Index (CCI), are based on International Classification of Diseases (ICD) codes, which are a poor indicator of severity and complexity of comorbid disease. Alternatively, the number of cardiovascular drugs could be an efficient tool for estimating patient risk. In this study, we examined the relationship between cardiovascular medications and survival in patients being treated for metastatic hormone-sensitive prostate cancer (mHSPC). Methods: A nationwide retrospective observational study of US Veterans with de novo mHSPC in the Veterans Health Administration between 2011-2021 with at least 1 prescription medicine of any class. We determined the number of cardiovascular drugs from Anatomic Therapeutic Chemical (ATC) drug class C prescribed in the year prior up to 14 days before initiation of treatment. Multivariable logistic regression and Cox proportional hazard modeling was used to assess the association between number of drugs with overall survival (OS) while accounting for important covariates including age, body-mass index (BMI), prostate specific antigen (PSA), CCI, race, and weight change. Results: Among 7,875 veterans, a median (IQR) of 2 (1-4) unique cardiovascular medications were filled in the year prior to treatment. The mean age was 74.3 years (SD 10.0) with a median CCI of 3 (3-6). Age was associated with increased number of cardiac medicines with a mean of 1.6 drugs in &lt;60 years, 2.2 drugs in 60-69, 2.5 drugs in 70-80, and 2.5 drugs in 80+ years (p&lt;0.001). Increased number of medications was associated with decreased OS using the Kaplan-Meier method (p&lt;0.001, see table). After adjusting for age, race, BMI, weight change, PSA, and CCI, the number of medications was independently associated with increased mortality with an adjusted hazard ratio (aHR) of 1.05 (1.03-1.06) for each additional cardiac drug. Increased mortality was observed in patients treated with 2 or more cardiac drugs (see table). Conclusions: The number of cardiovascular medications is associated with decreased survival in veterans undergoing treatment for mHSPC, even after accounting for important covariates including age, BMI, PSA, and CCI. The assessment of cardiovascular medications may provide a simple and reliable tool to estimate comorbid disease and survival in patients with cancer. [Table: see text]

Early experience of "En bloc" holmium laser enucleation of the prostate in Saudi Arabia.

Holmium laser enucleation of the prostate (HoLEP) showed higher efficacy than transurethral resection for treating benign prostatic hyperplasia (BPH). The present study aims to report the outcome of BPH treatment by HoLEP in a tertiary center. An observational prospectively collected data for consecutive symptomatic BPH patients undergoing HoLEP between January 2020 and December 2021. Demographic and perioperative data were collected with the International Prostate Symptom Score (IPSS), quality of life, peak flow rate (Qmax), residual urine postvoid residual (PVR), and prostate-specific antigen (PSA) changes, in addition to perioperative and late adverse events. One hundred patients were included with a median age of 73 years (range 65-80). The IPSS improved by 80% postoperatively (25 vs. 5, P < 0.001). Similarly, Qmax significantly improved. Seven patients were found to have incidental prostate cancer. No patient needed a perioperative blood transfusion. Compared to its preoperative values, follow-up PSA has been reduced by 75% (P < 0.001). Urethral stricture and bladder neck contracture were noted in < 2% of the patients. HoLEP is feasible for all prostate sizes and a safe and effective treatment for BPH patients; our results are consistent with the reported data in the literature regarding functional outcomes, complication rates, and urinary incontinence rates.

Patient Satisfaction with Oral Testosterone Undecanoate in Men Who Received Prior Testosterone Therapy: An Open-Label, Single-Center Clinical Trial.

To evaluate patient satisfaction and symptom control in hypogonadal men transitioning from other testosterone therapies to oral testosterone undecanoate (TU). In this open-label clinical trial, men aged 18 to 75 years with hypogonadism were switched to oral TU after a sufficient washout of previous testosterone therapies. Treatment satisfaction and symptom control were primarily measured using the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) and quantitative androgen deficiency in aging males (qADAM) questionnaires, respectively. Secondary outcomes included changes in serum testosterone (T), estradiol (E2), hematocrit (HCT), and prostate-specific antigen (PSA) levels. Forty-one men participated, with significant improvements in all TSQM-9 scores observed over 6 months. Symptom control as measured by qADAM remained consistent. There was a significant increase in serum T and E2 levels, but HCT and PSA levels remained stable. Switching to oral TU from other testosterone therapies is associated with increased patient satisfaction and stable hypogonadal symptom control.

Illustration of association between change in prostate-specific antigen (PSA) values and time to tumor status after treatment for prostate cancer patients: a joint modelling approach

BackgroundProstate cancer (PCa) is the most prevalent tumor in men, and Prostate-Specific Antigen (PSA) serves as the primary marker for diagnosis, recurrence, and disease-free status. PSA levels post-treatment guide physicians in gauging disease progression and tumor status (low or high). Clinical follow-up relies on monitoring PSA over time, forming the basis for dynamic prediction. Our study proposes a joint model of longitudinal PSA and time to tumor shrinkage, incorporating baseline variables. The research aims to assess tumor status post-treatment for dynamic prediction, utilizing joint assessment of PSA measurements and time to tumor status.MethodsWe propose a joint model for longitudinal PSA and time to tumor shrinkage, taking into account baseline BMI and post-treatment factors, including external beam radiation therapy (EBRT), androgen deprivation therapy (ADT), prostatectomy, and various combinations of these interventions. The model employs a mixed-effect sub-model for longitudinal PSA and an event time sub-model for tumor shrinkage.ResultsResults emphasize the significance of baseline factors in understanding the relationship between PSA trajectories and tumor status. Patients with low tumor status consistently exhibit low PSA values, decreasing exponentially within one month post-treatment. The correlation between PSA levels and tumor shrinkage is evident, with the considered factors proving to be significant in both sub-models.ConclusionsCompared to other treatment options, ADT is the most effective in achieving a low tumor status, as evidenced by a decrease in PSA levels after months of treatment. Patients with an increased BMI were more likely to attain a low tumor status. The research enhances dynamic prediction for PCa patients, utilizing joint analysis of PSA and time to tumor shrinkage post-treatment. The developed model facilitates more effective and personalized decision-making in PCa care.