Serum Prostate-specific Antigen Levels Research Articles

Clinical Implications of Nadir Serum Prostate-Specific Antigen Levels After Transurethral Enucleation of the Prostate.

ObjectiveProstate-specific antigen levels after transurethral enucleation of the prostate may serve as indicators of residual cancer foci. The objective of this study was to investigate the association between the post-transurethral enucleation of the prostate nadir prostate-specific antigen level and prostate cancer.Materials and MethodsWe retrospectively reviewed the data of 428 men who underwent transurethral enucleation of the prostate between March 2015 and April 2021. Based on the following exclusion criteria, we excluded 106 men from our analysis: men with metastatic prostate cancer, incomplete transurethral enucleation of the prostate, and missing prostate-specific antigen or prostate size data. Three hundred and twenty-two patients were finally enrolled in our study. These patients were classified into four groups according to the surgical pathology: benign, transition zone (cancer only in the adenoma or transition zone), peripheral zone, and transition and peripheral zones. The optimal cutoff post-transurethral enucleation of the prostate nadir prostate-specific antigen level that predicted residual prostate cancer was determined using receiver operating characteristic curve analysis.ResultsIn total, 71 (22.0%) men exhibited prostate cancer (median follow-up, 38.0 months). The benign and combined cancer groups showed similar adenoma removal rates (103.0% and 106.7%, respectively). The median nadir prostate-specific antigen levels after transurethral enucleation of the prostate were 0.76, 0.63, 1.79, and 1.70 ng/ml in the benign, transition zone, peripheral zone, and transition and peripheral zone groups, respectively (p < 0.001), with no difference between the benign and transition zone groups (p = 0.458); this suggested that complete transurethral enucleation of the prostate removed all cancer nests in the adenoma in the transition zone group. Receiver operating characteristic curve analysis showed that nadir prostate-specific antigen ≧1.7 ng/ml predicted residual cancer (area under the curve: 0.787) or cancer with a Gleason score of ≧7 (area under the curve: 0.816) in the remaining prostate. Limitations include the retrospective design and the perioperative peripheral zone biopsy rate.ConclusionsThe post-transurethral enucleation of the prostate nadir prostate-specific antigen ≧1.7 ng/ml after complete transurethral enucleation of the prostate can predict significant residual cancer. Prostate cancer patients with low post-transurethral enucleation of the prostate prostate-specific antigen levels can be conservatively managed.

Construction and Comparison of Different Models in Detecting Prostate Cancer and Clinically Significant Prostate Cancer.

BackgroundWith the widespread adoption of prostatic-specific antigen (PSA) screening, the detection rates of prostate cancer (PCa) have increased. Due to the low specificity and high false-positive rate of serum PSA levels, it was difficult to diagnose PCa accurately. To improve the diagnosis of PCa and clinically significant prostate cancer (CSPCa), we established novel models on the basis of the prostate health index (PHI) and multiparametric magnetic resonance imaging (mpMRI) in the Asian population.MethodsWe retrospectively collected the clinical indicators of patients with TPSA at 4–20 ng/ml. Furthermore, mpMRI was performed using a 3.0-T scanner and reported in the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS). Univariable and multivariable logistic analyses were performed to construct the models. The performance of different models based on PSA derivatives, PHI derivatives, PI-RADS, and a combination of PHI derivatives and PI-RADS was evaluated.ResultsAmong the 128 patients, 47 (36.72%) patients were diagnosed with CSPCa and 81 (63.28%) patients were diagnosed with non-CSPCa. Of the 81 (63.28%) patients, 8 (6.25%) patients were diagnosed with Gleason Grade 1 PCa and 73 (57.03%) patients were diagnosed with non-PCa. In the analysis of the receiver operator characteristic (ROC) curves in TPSA 4–20 ng/ml, the multivariable model for PCa was significantly larger than that for the model based on the PI-RADS (p = 0.004) and that for the model based on the PHI derivatives (p = 0.031) in diagnostic accuracy. The multivariable model for CSPCa was significantly larger than that for the model based on the PI-RADS (p = 0.003) and was non-significantly larger than that for the model based on the PHI derivatives (p = 0.061) in diagnostic accuracy. For PCa in TPSA 4–20 ng/ml, a multivariable model achieved the optimal diagnostic value at four levels of predictive variables. For CSPCa in TPSA 4–20 ng/ml, the multivariable model achieved the optimal diagnostic value at a sensitivity close to 90% and 80%.ConclusionsThe models combining PHI derivatives and PI-RADS performed better in detecting PCa and CSPCa than the models based on either PHI or PI-RADS.

Molecular detection of the COVID-19 genome in prostatic tissue of patients with previous infection

COVID-19 infection has been linked to worsening or de novo lower urinary tract symptoms and transient serum prostate-specific antigen rise in patients with benign prostatic hyperplasia. This pilot study aimed to examine prostatic tissue for evidence for direct involvement with the COVID-19 (SARS-CoV-2) infection. Fourteen patients with previous documented COVID-19 infection who underwent prostate enucleation had their prostate specimens examined for COVID-19 RNA. The specimens were examined using a SARS-CoV-2 test, an in vitro diagnostic test based on reverse transcription polymerase chain reaction technology that analyses the presence of RNA for the SARS-CoV-2 strain. Among the 14 patients, COVID infection was severe in three, mild in seven, and asymptomatic in four patients. The COVID-19 genome was successfully identified in the prostate specimen of a single patient. Although this patient had mild COVID-19 infection, he had positive COVID tests for 40 days after the initial infection. Identification of the COVID-19 genome in prostate tissue is a further step toward better understanding its effect on the genitourinary tract. This study’s findings provide some explanation for the proposed association with lower urinary tract symptoms and rise in serum prostate-specific antigen levels. Larger studies are needed to further investigate this association.

Isolation of Circulating Tumor Cells from Seminal Fluid of Patients with Prostate Cancer Using Inertial Microfluidics.

Simple SummaryProstate cancer (PCa) is notoriously difficult to diagnose owing to the lack of reliable biomarkers and the invasiveness of obtaining a tissue biopsy from the prostate. As an alternative, we developed a liquid biopsy technique, based on isolating tumor cells from semen samples via a microfluidic device. To optimize the device, we first attempted to recover PCa cells from semen samples spiked with PCa cell lines, achieving an average efficiency of >87% cell recovery at the chosen flow rate. We then transitioned to a clinical setting using semen samples from PCa patients. The yield of isolated clinical PCa cells varied between 67 and 307 cells per mL of semen (in 15 cancer patients). These cells were stained and compared to the standard prognostic parameters such as Gleason score and PSA serum level. This study presents a potential liquid biopsy technique to augment the existing diagnosis and prognosis of PCa.Prostate cancer (PCa) diagnosis is primarily based on prostate-specific antigen (PSA) testing and prostate tissue biopsies. However, PSA testing has relatively low specificity, while tissue biopsies are highly invasive and have relatively low sensitivity at early stages of PCa. As an alternative, we developed a technique of liquid biopsy, based on isolation of circulating tumor cells (CTCs) from seminal fluid (SF). The recovery of PCa cells from SF was demonstrated using PCa cell lines, achieving an efficiency and throughput as high as 89% (±3.8%) and 1.7 mL min−1, respectively, while 99% (±0.7%) of sperm cells were disposed of. The introduced approach was further tested in a clinical setting by collecting and processing SF samples of PCa patients. The yield of isolated CTCs measured as high as 613 cells per SF sample in comparison with that of 6 cells from SF of healthy donors, holding significant promise for PCa diagnosis. The correlation analysis of the isolated CTC numbers with the standard prognostic parameters such as Gleason score and PSA serum level showed correlation coefficient values at 0.40 and 0.73, respectively. Taken together, our results show promise in the developed liquid biopsy technique to augment the existing diagnosis and prognosis of PCa.

Assessment of the Utility of Multiparametric Magnetic Resonance Imaging for Initial Detection of Prostate Cancer

BACKGROUND: An accurate diagnosis is essential for the effective treatment of prostate cancer (PCa) and for the patients’ well-being. AIM: Thе main purpose of this study was to assess the utility of multiparametric magnetic resonance imaging (mp-MRI) for initial detection of PCa among the Bulgarian population of men with prostate diseases. MATERIALS AND METHODS: Fifty-three patients, aged 44 to 82 years, were evaluated for clinically significant PCa. Assessment methods included prostate-specific antigen (PSA) serum levels, transrectal ultrasonography (TRUS), GE Discovery 3T MRI, and 12-core TRUS biopsy. RESULTS: mp-MRI showed 83.20% concordance with TRUS biopsy: sensitivity of 91.43% (76.90–98.20), specificity of 75.00% (34.90–96.80), positive predictive values 94.10% (82.80–98.20) and negative predictive values 66.70% (38.70–86.40). Of the patients classified in prostate imaging–reporting and data system (PI-RADS) levels 4 and 5, 94.12% had positive TRUS biopsy, as well as 44.40% of PI-RADS had level 3. Irrespective of the patients’ age and PSA, PI-RADS was found to be a significant predictor of a positive TRUS biopsy (p = 0.009). PSA serum levels showed a low concordance with TRUS biopsy (area under the curve = 0.539; 95% confidence interval [CI]: 0.363–0.712) and a low, although significant, correlation with PI-RADS (rs = 0.416; 95% CI: 0.164–0.617). CONCLUSION: According to our findings, mp-MRI and TRUS biopsy have a high level of concordance for the initial detection of PCa. The incorporation of mp-MRI into the diagnostic pathway for PCa can significantly reduce the number of incorrect diagnoses based on PSA serum levels and/or suspicious physical and digital examinations.

Clinical use of the mRNA urinary biomarker SelectMDx test for prostate cancer

BackgroundMolecular biomarker tests are developed as diagnostic tools for prostate cancer (PCa) diagnosis. The SelectMDx (MDxHealth, Nijmegen, The Netherlands) test is a urinary-based biomarker test intended to be used to predict presence of high-grade PCa upon biopsy in men with elevated serum prostate-specific antigen (PSA) levels. Previous validation of the SelectMDx test revealed that 53% of the unnecessary biopsies (biopsies indicating no- or GG1 PCa) could be avoided using the SelectMDx test as a decision-tool to select men for prostate biopsy. The objective of this study is to examine the use of the commercially available SelectMDx test under routine, real-life practice.MethodsMen that underwent a SelectMDx test between May 2019 and December 2020 and that were originating from countries that perform the SelectMDx test on a regular basis were included in this study, resulting in 5157 cases from 10 European countries. Clinical parameters, urinary RNA scores, and test outcomes were compared between PSA groups, age groups, countries, and the validation cohort (described previously [4]) using the Mann–Whitney U test, Chi-Square test, Benjamini–Hochberg and Kruskal–Wallis tests.Results40.72% of the cases received a negative SelectMDx result. The test is also used in patients outside the intended-use population (PSA < 3 and >10 ng/mL). Clinical parameters (age, PSA density, DRE outcome) varied between patient population from individual countries and the validation cohort, resulting in differences in the potential number of saved biopsies using the test.ConclusionsThe potential number of reduced biopsies in clinical use was 40,72% using the SelectMDx test, assuming a negative SelectMDx test resulted in the decision not to biopsy the patient. This is higher compared to the validation cohort, which is explained by differences in patient population.

Extended Focal Ablation of Localized Prostate Cancer With High-Frequency Irreversible Electroporation

Focal therapy of prostate cancer must balance the oncologic outcome and functional outcome. High-frequency irreversible electroporation (H-FIRE) can destroy cancer cells while selectively preserving surrounding nerves and blood vessels, but no clinical trials have been conducted, to our knowledge. To evaluate the efficacy and safety of H-FIRE in the treatment of localized prostate cancer (PCa). This was a single-group, objective performance criteria, nonrandomized controlled trial. Recruitment began on May 2, 2018, and ended March 27, 2019. The follow-up duration was 6 months. This was a multicenter trial conducted at 4 tertiary teaching hospitals in China. Patients with low or intermediate risk of biochemical recurrence of localized and locally advanced PCa were eligible. Key inclusion criteria were serum prostate-specific antigen (PSA) level less than 20 ng/mL, clinical stage of T2c or less, and Gleason score of 7 or less. Data were analyzed from January 20 to February 20, 2021. H-FIRE ablation of all lesions identified with biopsy. The primary end point was 6-month clinically significant PCa (csPCa), which was defined as any biopsy core with Gleason score of greater than or equal to 7, or Gleason score of 6 plus maximum cancer core length of greater than 3 mm or an increase from the original cancer burden. Secondary outcomes were calculated in patients who actually received H-FIRE treatment. A total of 117 patients (median [IQR] age, 67 [62-73] years) were recruited from 4 centers, and 109 patients (27 [24.8%] low risk and 82 [75.2%] intermediate risk) actually received H-FIRE. Median (IQR) PSA level was 9.0 (6.0-12.7) ng/mL. Among the 100 patients who underwent biopsy at 6 months, the 6-month csPCa rate was 6.0% (95% CI, 2.2%-12.6%; P < .001; 1 in the treatment zone and 5 outside the treatment zone). Superiority criteria vs the historical control of 20% was achieved. PCa was detected in 14 patients, with a Gleason score of 7 in 2 patients and 6 in the remaining 12 patients. At 6 months, median (IQR) PSA level was 1.08 (0.4-3.2) ng/mL, median (IQR) International Prostate Symptom Score was 4.5 (2.0-9.5), and median (IQR) International Index of Erectile Function 5 score was 2.0 (0.5-12.5). Superiority vs the 20% historical control was also met in the subgroup analysis that only included the 57 patients with Gleason score of 7 at baseline (3.5% 6-month csPCa; 95% CI, 0.4%-12.1%). The rate of 6-month csPCa with H-FIRE ablation was lower than the historical control using other energy platforms. ClinicalTrials.gov Identifier: NCT03838432.

Clinical Efficacy and Psychological Impact of Omaha-Based Continuing Care for Prostate Cancer Patients.

Prostate cancer is a common malignancy elderly male urogenital system, because of the special disease position, and postoperative complications such as urinary retention, urinary incontinence, and sexual dysfunction, if not treated, can increase the patients' physical pain, anxiety, and other psychological burden; endocrine therapy after surgery can affect self-image and quality of life of patients. Omaha system was originally used for community health nurses, which contains three main contents: problem classification, nursing intervention, and outcome evaluation. The problem classification dimension includes four dimensions: environment, physiology, social psychology, and health-related behavior. The nursing intervention dimension is composed of 75 intervention objectives and four behavior types. Omaha system is a nursing intervention model based on individual psychological, physiological, educational level, and family and social background. The model has good clinical application effect. This study aimed to explore the continuous nursing intervention effect in the nursing of patients with prostate cancer and its psychological impact. A total of 96 prostate patients with cancer who were admitted to Taizhou First People's Hospital from November 2019 to May 2021 were divided into Omaha system care group and routine care group with 48 cases each by random number table method. The routine care group received routine care and discharge guidance, and the Omaha system care group on the basis of the routine care group; continuation care based on the Omaha system was implemented. The differences in mental state, life quality score, serum prostate specific antigen (PSA) level, average urine flow rate, and self-care ability score were compared between the routine care and Omaha system care group. The results showed that Omaha-based continuation care for prostate cancer is beneficial to reduce bad mood, improve patients' life quality score and self-care ability, and provide certain reference for clinical care of prostate cancer patients.

Does serum prostate specific antigen levels correlate with the prostatic inflammation in elderly patients without clinically proven prostate cancer?

Objectives: To determine the whether histological prostatic inflammation correlates with serum prostate specific antigen (PSA), free PSA (fPSA) and percent of fPSA (%fPSA) levels in elderly patients without clinically proven prostate cancer. Methods: A total of 115 patients without clinically proven prostate cancer with transrectal prostate biopsy were included in this retrospective study. Patients were divided two main groups as patients with and without histologic prostatic inflammation. A grading of the histological prostatic inflammation was performed and patients with prostatic inflammation were divided into three subgroups. The age, prostate volume, serum PSA, fPSA and %fPSA levels were compared between patients with and without prostatic inflammation. Correlation between the parameters and grade of prostatic inflammation was also investigated. Results: Serum PSA and %fPSA levels were significantly higher in men with histologically proven prostatic inflammation (15.47 ± 15.28 ng/mL vs. 11.67 ± 8.12 ng/mL; p = 0.002 and 19.8 ± 0.7 vs. 15.79 ± 0.9; p = 0.01, respectively). The mean serum PSA levels were significantly different among the subgroups (p = 0.02) and prostatic inflammation correlated positively with the PSA levels (r = 0.320, p &amp;lt; 0.001). Conclusions: Our findings suggested that reporting the grade of prostatic inflammation in elderly patients may help avoiding unnecessary repeat biopsies if elevated serum PSA level is the only indication for initial prostate biopsy.

Clinicopathological features and prevalence of prostate cancer in Aseer, Saudi Arabia.

To determine the prevalence and characterize prostate cancer (PC) cases in Aseer, Saudi Arabia. This study involved 883 patients who consulted physicians in Aseer Central Hospital, Abha, Saudi Arabia, for prostate issues between the years 2008-2018. All patients underwent digital rectal examination and measurement of their serum prostate-specific antigen levels. For patients who presented abnormal digital rectal examination findings and elevated prostate-specific antigen levels, prostate biopsies were recommended. Specimens were histopathologically examined to differentiate between malignant and benign tumors. Among the 883 included patients, 132 (15%) underwent a prostate biopsy and were found to have a tumor. Histopathological examination confirmed malignancy (PC) in 77 (8.7%) patients. The absolute majority of the patients diagnosed with PC (96%) were aged >60 years and almost all of them (92%) were found to have a high prostate-specific antigen level of >4 ng/ml. Prostate cancer appears to be a serious disease in Aseer, Saudi Arabia. Further studies aimed at determining the causes of this type of cancer and understanding its mechanisms are warranted.

Large Cell Neuroendocrine Carcinoma of the Prostate Gland: A Review and Update

It has been documented that the 2016 World Health Organization’s histological classification of prostate cancer has included well-differentiated carcinoid tumours and small- or large-cell poorly differentiated tumours within the category of neuroendocrine tumours. Up to May 2021, only 20 cases of large-cell neuroendocrine tumours of the prostate gland (LCNTPs) had been reported within the literature, among which are nine cases of primary tumours. LCNTPs are a rare histological entity whose evolutive profile and therapeutic potential do differ from those of conventional adenocarcinoma of the prostate gland. Primary neuroendocrine tumours of the prostate gland could be pure or associated with an adenocarcinoma component. Mixed forms of large cell neuroendocrine cancers of the prostate gland (LCNECPs) tend to associated with better prognosis when diagnosed early at a localized stage. Nevertheless, most cases of (LCNTPs) at the time of initial diagnosis could tend to be advanced, locally advanced or metastatic. Even though LCNECPs that are diagnosed initially tend to primary prostate cancers that may be pure primary prostate cancers, few large LCNECPs have been found to be metastatic large cell neuroendocrine carcinomas that had metastasised from other sites of the body for example the lung. Primary LCNECP does tend to manifest similarly to primary adenocarcinoma of prostate gland with lower urinary tract symptoms, haematuria, or signs of obstruction of the upper urinary tract or inability to empty the urinary bladder. Cases of primary LCNECP that manifest tend also to be associated with symptoms related to the sites of the metastases. Serum prostate specific antigen levels tend to be slightly elevated with cases of primary LCNECP, but the levels generally tend not to be as high as most cases of advanced, locally advanced or metastatic primary adenocarcinomas of the prostate gland. Diagnosis of LCNECPs tend to be made pursuant to the undertaking of histopathology and immunohistochemistry staining studies of specimens of the prostate that had been obtained from prostate biopsies, trans-urethral reception of prostate specimens or prostatectomy specimens. The microscopy histopathology examination features of LCNECP the prostate gland have been summarized as follows: (a) Microscopy histopathology examination of LCNECP gland does tend to demonstrate large islands or sheets of tumour cells. (b) Large tumour cells with prominent neuroendocrine features such as salt and pepper chromatin and small nucleoli tend to be visualised upon microscopy examination of specimens of the prostate tumour. (c) High grade features such as lack of glandular formation, frequent mitoses and apoptotic bodies and tumour necrosis tend to be frequent findings upon microscopy examination of specimens of LCNECP. Immunohistochemistry staining features of LCNECP include: (a) At least one of the ensuing neuroendocrine tumour markers should be demonstrated upon immunohistochemistry staining including exhibition of positive immunohistochemistry staining for: chromogranin A, synaptophysin, neuron specific enolase, and CD56 may be positive: It has been stated that immunohistochemistry staining studies may exhibit positive staining in cases of LCNECP with utilization of the following: o TTFI tends to be positive in less than 50% of cases of LCNECP. o Positive AMACR immunohistochemistry staining, but this may be focal or weaker than for adenocarcinoma of the prostate gland. o Positive markers including: PSA, PSMA, NKX3.1 prostein (P501S) tend to be negative in majority of cases of LCNECP, but they could be focally positive in a small subset of the tumours. It has been iterated that in cases of LCNECP, immunohistochemistry staining studies tend to demonstrate negative staining for the ensuing markers: • Urothelial markers such as GATA3, p63, and high molecular weight cytokeratins such as CK5 / 6. • CD99. • Carcinoid tumour of the prostate gland. • PNET/Ewing sarcoma of the prostate gland. • Adenocarcinoma of the prostate gland with focal neuroendocrine differentiation. • Urothelial carcinoma with neuroendocrine differentiation. A high index of suspicion is required in order to diagnose early cases of primary large cell neuroendocrine carcinomas by undertaking early biopsies of prostate glands in all patients who have significant lower urinary tract symptoms if their serum prostate specific antigen (PSA) levels are slightly high or high even if they are commenced on Tamsulosin in an attempt to help improve the symptoms of voiding. There is no consensus opinion on the best management of LCNECP, therefore, there is an urgent need for the establishment of a global multi-centre trial related to various management options for the disease in order to ascertain the best options of management for LCNECP. gland.

PROSTATE BIOPSIES AND ITS ASSOCIATION WITH PROSTATE SPECIFIC ANTIGEN IN PATIENT ATTENDING BIRAT MEDICAL COLLEGE TEACHING HOSPITAL

Background: Prostate cancer is the most common malignant tumor in men over the age of 65 years. Most frequently encountered diseases of the prostate are benign prostatic hyperplasia, prostatitis and carcinoma. Prostate specific antigen is a tumour marker and is expressed by both normal and neoplastic prostate tissue. This study was done to determine the association between histopathological diagnosis in prostatic biopsy and serum prostatic specific antigen level. Methods: This was a hospital based cross sectional study carried out in the Department of Pathology, Birat Medical College from February 15, 2020 to October15, 2020. All consecutive patients attending the pathology department with prostate biopsy and serum PSA level were included in the study. Histopathological examination was done and its association with serum prostatic specific antigen level was done. Results: In the biopsy findings, Benign Prostatic Hyperplasia (BPH)was the most common case seen in 41 (48.8%) cases out of 84 cases. Majority of benign cases (BPH and BPH with prostatitis) were seen in the PSA range of 0-7ng/ml. Maximum cases of adenocarcinoma were seen in the range of &gt;20ng/ml. Chi-Square test showed a value of 5.89 while P value was &lt;0.01 indicating that the increasing serum PSA level is associated with higher chance of adenocarcinoma. Conclusions: PSA is a specific marker for prostatic tissue. It can be raised in benign lesions of the prostate due to membrane disruption. However, an increased PSA level above 20 ng/ml increases the chance of detecting malignant lesions.

A Case Report: Application of 68Ga-PSMA-PET/CT for the Diagnosis of Bone Metastases in Patients with Low Prostate-Specific Antigen Levels

Prostate cancer is the second most common type of cancer in men worldwide. It is one of the 5 most common cancer types and contributes to the greatest number of deaths among male patients. It is most common for prostate cancer to metastasize to the vertebrae, ribs, and pelvis. An important determinant of bone metastasis is the level of prostate-specific membrane antigen (PSMA). The risk of metastatic disease is low in patients who have low serum prostate-specific antigen (PSA) levels. This study examined a patient with suspected bone metastasis based on computed tomography (CT), which is considered to be a rare condition, but whose PSA level was abnormally low. 68Ga-PSMA-PET/CT scans were performed on the patient. It was discovered that bone metastases had developed in several regions of the patients’ body. Several sclerotic lesions were observed in the lumbar vertebrae and bilateral iliac wings, suggesting that bone metastases had occurred. An examination of the pelvis revealed a lesion exhibiting Ga-68 PSMA uptake, with a SUVmax of 4.97. Furthermore, laps with Ga-68 PSMA involvement with SUVmax: 8.65 could also be seen in the paracaval and aortokaval regions.

Machine Learning and Clinical-Radiological Characteristics for the Classification of Prostate Cancer in PI-RADS 3 Lesions.

The Prostate Imaging Reporting and Data System (PI-RADS) classification is based on a scale of values from 1 to 5. The value is assigned according to the probability that a finding is a malignant tumor (prostate carcinoma) and is calculated by evaluating the signal behavior in morphological, diffusion, and post-contrastographic sequences. A PI-RADS score of 3 is recognized as the equivocal likelihood of clinically significant prostate cancer, making its diagnosis very challenging. While PI-RADS values of 4 and 5 make biopsy necessary, it is very hard to establish whether to perform a biopsy or not in patients with a PI-RADS score 3. In recent years, machine learning algorithms have been proposed for a wide range of applications in medical fields, thanks to their ability to extract hidden information and to learn from a set of data without previous specific programming. In this paper, we evaluate machine learning approaches in detecting prostate cancer in patients with PI-RADS score 3 lesions via considering clinical-radiological characteristics. A total of 109 patients were included in this study. We collected data on body mass index (BMI), location of suspicious PI-RADS 3 lesions, serum prostate-specific antigen (PSA) level, prostate volume, PSA density, and histopathology results. The implemented classifiers exploit a patient’s clinical and radiological information to generate a probability of malignancy that could help the physicians in diagnostic decisions, including the need for a biopsy.

Simultaneous Determination of Steroids and Glucocorticoids in Human Urine by Ultra-High-Performance Liquid Chromatography – Tandem Mass Spectrometry (UPLC–MS/MS)

Prostate cancer is a hormone-dependent disease and therefore androgens play a critical role in its development. For both research on clinical conditions as well as diagnostic and monitoring purposes, accurate measurement of steroid hormones is essential. This study aimed to develop a sensitive and selective method for simultaneously detecting nine sex steroids and two glucocorticoids in human urine and to evaluate the alterations of urinary endogenous steroid hormones induced by prostate cancer. A total of 97 Chinese subjects were randomly recruited for this study, including 66 patients with prostate cancer and 31 healthy controls. The concentrations of steroid hormones, including dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, dihydrotestosterone (DHT), estrone, estradiol, estriol (E1), progesterone, cortisol (F), and cortisone (E), were simultaneously determined by ultra-high-performance liquid chromatography – tandem mass spectrometry with atmospheric pressure chemical ionization in the positive mode (UPLC–APCI+–MS/MS). The population analysis indicated that prostate cancer patients showed significantly higher DHEAS, DHT, E1, and E than healthy controls. Furthermore, the levels of DHEAS and E1 were significantly positively correlated with serum levels of prostate-specific antigen (PSA), which is considered to be the best conventional prostate cancer marker in the current study. In summary, we validated the use of urine samples for multiple steroid profiling by UPLC–MS/MS. Two steroids were significantly altered and correlated with PSA in the prostate cancer population. These findings open further investigation of the potential role of sex steroids in prostate cancer diagnosis. Studying large samples and determining these steroid hormones in the urine are still necessary.

MpMRI-US Fusion-Guided Targeted Cryotherapy in Patients with Primary Localized Prostate Cancer: A Prospective Analysis of Oncological and Functional Outcomes.

Simple SummaryTargeted cryotherapy is an emerging treatment for prostate cancer (PCa). mpMRI is a powerful tool for image fusion techniques that deliver incremental precision in diagnostic and treatment of PCa. Fusion targeted cryotherapy (FTC) arises from the simultaneous application of both these procedures. Recurrence is a concern after any type of PCa treatment, especially after targeted treatments. In this article we investigate the recurrence rate after FTC and the role of Prostate-Specific Antigen (PSA) as a predictor of recurrences. Our research provides new evidence on the feasibility of FCT by providing new insights on patient management.Targeted therapy (TT) for prostate cancer (PCa) aims to ablate the malignant lesion with an adequate margin of safety in order to obtain similar oncological outcomes, but with less toxicity than radical treatments. The main aim of this study was to evaluate the recurrence rate (RR) in patients with primary localized PCa undergoing mpMRI/US fusion targeted cryotherapy (FTC). A secondary objective was to evaluate prostate-specific antigen (PSA) as a predictor of recurrences. We designed a prospective single-center single-cohort study. Patients with primary localized PCa, mono or multifocal lesions, PSA ≤ 15 ng/mL, and a Gleason score (GS) ≤ 4 + 3 undergoing FTC were enrolled. RR was chosen as the primary outcome. Recurrence was defined as the presence of clinically significant prostate cancer in the treated areas. PSA values measured at different times were tested as predictors of recurrence. Continuous variables were assessed with the Bayesian t-test and categorical assessments with the chix-squared test. Univariate and logistic regression assessment were used for predictions. A total of 75 cases were included in the study. Ten subjects developed a recurrence (RR: 15.2%), while fifty-six (84.8%) patients showed a recurrence-free status. A %PSA drop of 31.5% during the first 12 months after treatment predicted a recurrence with a sensitivity of 53.8% and a specificity of 79.2%. A PSA drop of 55.3% 12 months after treatment predicted a recurrence with a sensitivity of 91.7% and a specificity of 51.9%. FTC for primary localized PCa seems to be associated with a low but not negligible percentage of recurrences. Serum PSA levels may have a role indicating RR.

Prostate-specific antigen age-specific reference ranges and the effect of metabolic syndrome factors in a Thai population Authors

Objectives: An appropriate prostate specific antigen (PSA) cut-off value in Thailand has not been investigated, nor has an age-specific PSA reference range. This study aims to evaluate the correlation between metabolic syndrome, metabolic factors, and age specific PSA level. Materials and Methods: A cross-sectional study in men who underwent medical checkups from September 2019 to December 2019. The 95th percentile PSA value was applied to the normal age-specific reference range. Correlations between PSA levels and a variety of factors were determined using linear regression. Results: A total of 507 men met the criteria to be included in the analysis. Age-specific PSA reference ranges for men aged 40-49, 50-59, and 60-70 years were 0-2.3, 0-3.4, and 0-4.2 ng/ml, respectively. The multivariate adjusted geometric mean PSA model indicated that the factors related to PSA were age, higher body mass index (BMI) and serum fasting blood sugar (FBS) ≥ 100 mg/dl. The age group 50-59 and 60-70 have a 43% and 99% increase in mean PSA compared to the age group 40-49, respectively (p &lt; 0.001). A higher BMI was associated with lower PSA (p &lt; 0.001). And the serum FBS ≥ 100 mg/dl showed a 15% reduction in mean PSA compared to FBS &lt; 100 mg/dl (p = 0.018). Conclusion: The age-specific PSA reference in Thai men was lower than reported in a previous study. Use of the lower PSA cut-off may increase the sensitivity of prostate cancer screening. This study demonstrates that age, BMI, and FBS may all influence the clinical interpretation of serum PSA levels. Screening for prostate cancer using PSA should be carried out with caution in those who have those risk factors.

Enzalutamide Monotherapy vs Active Surveillance in Patients With Low-risk or Intermediate-risk Localized Prostate Cancer

There are few published studies prospectively assessing pharmacological interventions that may delay prostate cancer progression in patients undergoing active surveillance (AS). To compare the efficacy and safety of enzalutamide monotherapy plus AS vs AS alone in patients with low-risk or intermediate-risk prostate cancer. The ENACT study was a phase 2, open-label, randomized clinical trial conducted from June 2016 to August 2020 at 66 US and Canadian sites. Eligible patients were 18 years or older, had received a diagnosis of histologically proven low-risk or intermediate-risk localized prostate cancer within 6 months of screening, and were undergoing AS. Patients were monitored during 1 year of treatment and up to 2 years of follow-up. Data analysis was conducted in February 2021. Randomized 1:1 to enzalutamide, 160 mg, monotherapy for 1 year or continued AS, as stratified by cancer risk and follow-up biopsy type. The primary end point was time to pathological or therapeutic prostate cancer progression (pathological, ≥1 increase in primary or secondary Gleason pattern or ≥15% increased cancer-positive cores; therapeutic, earliest occurrence of primary therapy for prostate cancer). Secondary end points included incidence of a negative biopsy result, percentage of cancer-positive cores, and incidence of a secondary rise in serum prostate-specific antigen (PSA) levels at 1 and 2 years, as well as time to PSA progression. Adverse events were monitored to assess safety. A total of 114 patients were randomized to treatment with enzalutamide plus AS and 113 to AS alone; baseline characteristics were similar between treatment arms (mean [SD] age, 66.1 [7.8] years; 1 Asian individual [0.4%], 21 Black or African American individuals [9.3%], 1 Hispanic individual [0.4%], and 204 White individuals [89.9%]). Enzalutamide significantly reduced the risk of prostate cancer progression by 46% vs AS (hazard ratio, 0.54; 95% CI, 0.33-0.89; P = .02). Compared with AS, odds of a negative biopsy result were 3.5 times higher; there was a significant reduction in the percentage of cancer-positive cores and the odds of a secondary rise in serum PSA levels at 1 year with treatment with enzalutamide; no significant difference was observed at 2 years. Treatment with enzalutamide also significantly delayed PSA progression by 6 months vs AS (hazard ratio, 0.71; 95% CI, 0.53-0.97; P = .03). The most commonly reported adverse events during enzalutamide treatment were fatigue (62 [55.4%]) and gynecomastia (41 [36.6%]). Three patients in the enzalutamide arm died; none were receiving the study drug at the time of death. No deaths were considered treatment-related. The results of this randomized clinical trial suggest that enzalutamide monotherapy was well-tolerated and demonstrated a significant treatment response in patients with low-risk or intermediate-risk localized prostate cancer. Enzalutamide may provide an alternative treatment option for patients undergoing AS. ClinicalTrials.gov Identifier: NCT02799745.

A Combination of Natural Products, BenPros (Green Tea Extract, Soybean Extract and Camellia Japonica Oil), Ameliorates Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men and causes lower urinary tract symptoms due to excessive proliferation of prostate stromal and epithelial cells. The present study investigated the improving effect of BenPros, an edible natural product mixture (green tea extract, soybean extract and camellia japonica oil), against the development of BPH in vitro and in vivo. BenPros treatment showed inhibitory ability on testosterone-induced androgen receptor, prostate-specific antigen (PSA), and 5α-reductase protein expression in LNCap-LN3 cells and anti-inflammatory effects on LPS-induced increases in interleukin-6 and tumor necrosis factor-α in RAW264.7 cells. In a testosterone propionate (TP)-induced BPH rat model, BenPros decreased the up-regulated serum 5α-dihydrotestosterone and PSA levels. Moreover, BenPros also significantly reduced PSA protein expression in prostate tissue. Furthermore, TP-induced increased expression of cyclooxygenase 2 and B-cell lymphoma 2 (Bcl-2) were reduced by BenPros, resulting in an increase in the Bcl-2/BCL2-related X ratio. These regulatory abilities of BenPros on BPH inducing markers also reduced prostate size and epithelial thickness based on histological analysis. These results indicate that BenPros has a protective ability against BPH in vitro and in vivo, and it may be a promising candidate as a functional food in regulating BPH.

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

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