Prostate Cancer Cases Research Articles

Impact of Dose Perturbations Around Brachytherapy Seeds in External-Beam Radiotherapy Planning: A Fundamental and Clinical Validation Using Treatment Planning System-Based Monte Carlo Simulations.

Background This study evaluates dose perturbations caused by nonradioactive seeds in clinical cases by employing treatment planning system-based Monte Carlo (TPS-MC) simulation. Methodology We investigated dose perturbation using a water-equivalent phantom and 20 clinical cases of prostate cancer (10 cases with seeds and 10 cases without seeds) treated at Fujita Health University Hospital, Japan. First, dose calculations for a simple geometry were performed using the RayStation MC algorithm for a water-equivalent phantom with and without a seed. TPS-independent Monte Carlo (full-MC) simulations and film measurements were conducted to verify the accuracy of TPS-MC simulation. Subsequently, dose calculations using TPS-MC were performed on CT images of clinical cases of prostate cancer with and without seeds, and the dose distributions were compared. Results In clinical cases, dose calculations using MC simulations revealed hotspots around the seeds. However, the size of the hotspot was not correlated with the number of seeds. The maximum difference in dose perturbation between TPS-MC simulations and film measurements was 3.9%, whereas that between TPS-MC simulations and full-MC simulations was 3.7%. The dose error of TPS-MC was negligible for multiple beams or rotational irradiation. Conclusions Hotspots were observed in dose calculations using TPS-MC performed on CT images of clinical cases with seeds. The dose calculation accuracy around the seeds using TPS-MC simulations was comparable to that of film measurements and full-MC simulations, with differences within 3.9%. Although the clinical impact of hotspots occurring around the seeds is minimal, utilizing MC simulations on TPSs can be beneficial to verify their presence.

Etiology and outcome of hematospermia :A prospective study

Background: Although hematospermia is not common but considered an alarming symptom for patient and doctor. The cause of this worry is that it has been described as a dangerous symptom of prostate cancer by the patients and the health workers. Objective: To classify the causes and outcome of hematospermia. Patients and Methods: : This is a prospective study of patients newly diagnosed with hematospermia-diagnosed and treated in private clinic and hospital over a period of 4 years (2018-2022). Data collection and recording done related to demographic, symptomatology, clinical finding, investigations, treatment given and the outcome during 6 months of follow up. Results: One hundred and six patients with hematospermia were seen in the private clinic and hospital. The mean age was 40 years (25-70). Thirty-six (33.9%) patients were diagnosed as prostatitis clinically or by positive seminal fluid culture. Only (4) patients had prostate carcinoma with only one new case and the other three were known cases of prostate cancer already on treatment. With (4) cases had thrombocytopenia and (2) cases with sickle cell anemia and (1) case each prostate cyst and severe hypertension and vesical stone. (2) cases on anticoagulant therapy. And another (2) cases with history of epididymal surgery. There was no identifiable cause in the remaining 53 patients (50%). Conclusion: the majority of patients presented with hematospermia were below 50 years and have benign etiology and most of them were self-limited and less than 1% of cases revealed new prostate cancer. So, we can confidently reassure a patient presented with hematospermia due to benign nature of the disease in the majority of patients, especially in young patients.

Voided Urine Sample in the Diagnosis of Prostate Cancer in Patients with Serum PSA Ranging between 2.6 to 10 ng/mL

Introduction: Prostate cancer (PCa) cells are known to be shed into the prostatic urethra and thus can be collected through a voided urine sample. In this preliminary prospective study, we have assessed the feasibility of detecting cancer of the prostate using a voided urine sample and targeting the genomic VPAC receptors in patients with lower urinary tract symptoms and a serum PSA ranging between 2.6 to 10 ng/mL. Materials & Methods: Patients ≥40 years old, with lower urinary tract symptoms and serum prostate-specific antigen (PSA) ranging between 2.6 - 10 ng/mL formed the study group. The voided urine sample was collected from all these patients for biomarker testing. All patients underwent a standard 12-core prostate biopsy. The results of the histopathological studies were then compared to the results of the urine biomarker. Results: A total of 76 male subjects presented to our hospital with lower urinary tract symptoms and a serum PSA ≥ 2.6 and ≤ 10 ng/mL. The voided urine sample was positive for malignant cells in 24/25 (96%) patients with PCa. There was one case of a false negative in this group. Histopathological examination of the core biopsy specimens was positive for malignancy in 23 (92%) cases of PCa. Conclusions: Voided urine samples can be used to diagnose PCa by targeting the VPAC receptors that are expressed on malignant cells. This test is highly sensitive and serum PSA levels or Gleason’s score have no impact on the sensitivity of this test.

No Association of Trichomonas vaginalis Seropositivity with Advanced Prostate Cancer Risk in the Multiethnic Cohort: A Nested Case-Control Study.

The potential involvement of a sexually transmitted agent has been suggested to contribute to the high number of prostate cancers in the United States and worldwide. We investigated the relationship of Trichomonas vaginalis seropositivity with prostate cancer risk in a nested case-control study within the Multiethnic Cohort in Hawaii and California using blood samples collected prior to cancer diagnoses. Incident cases of advanced prostate cancer (intermediate- to high-grade based on Gleason score ≥ 7 and/or disease spread outside the prostate) were matched to controls by age, ethnicity, and the date of blood collection. T. vaginalis serostatus was measured using an ELISA detecting IgG antibodies against a recombinant T. vaginalis α-actinin protein. Seropositivity to T. vaginalis was observed in 35 of 470 (7.4%) cases and 26 of 470 (5.5%) controls (unadjusted OR = 1.47, 95% CI 0.82-2.64; adjusted OR = 1.31, 95% CI 0.67-2.53). The association was similarly not significant when cases were confined to extraprostatic tumors having regional or distant spread (n = 121) regardless of grade (unadjusted OR = 1.37, 95% CI 0.63-3.01; adjusted OR = 1.20, 95% CI 0.46-3.11). The association of T. vaginalis with prostate cancer risk did not vary by aspirin use. Our findings do not support a role for T. vaginalis in the etiology of advanced prostate cancer.

Modifiable risk factors for subsequent lethal prostate cancer among men with an initially negative prostate biopsy.

Previously suggested modifiable risk factors for prostate cancer could have resulted from detection bias because diagnosis requires a biopsy. We investigated modifiable risk factors for a subsequent cancer diagnosis among men with an initially negative prostate biopsy. In total, 10,396 participants of the Health Professionals Follow-up Study with an initial negative prostate biopsy after 1994 were followed for incident prostate cancer until 2017. Potential risk factors were based on previous studies in the general population. Outcomes included localised, advanced, and lethal prostate cancer. With 1851 prostate cancer cases (168 lethal) diagnosed over 23 years of follow-up, the 20-year risk of any prostate cancer diagnosis was 18.5% (95% CI: 17.7-19.3). Higher BMI and lower alcohol intake tended to be associated with lower rates of localised disease. Coffee, lycopene intake and statin use tended to be associated with lower rates of lethal prostate cancer. Results for other risk factors were less precise but compatible with and of similar direction as for men in the overall cohort. Risk factors for future prostate cancer among men with a negative biopsy were generally consistent with those for the general population, supporting their validity given reduced detection bias, and could be actionable, if confirmed.

Analysis of risk factors for positive surgical margin after laparoscopic radical prostatectomy with and without neoadjuvant hormonal therapy.

Positive surgical margins (PSM) is not only an independent risk factor for recurrence, metastasis, and prognosis, but also an important indicator of adjuvant therapy for prostate cancer (PCa) patients treated with radical prostatectomy (RP). At present, there are few reports analyzing risk factors of PSM in laparoscopic RP (LRP), especially for those PCa cases who accepted neoadjuvant hormonal therapy (NHT). Hence, the aim of the current study was to explore risk factors for PSM after LRP in PCa patients with and without NHT. The clinicopathological data of patients who underwent LRP from January 2012 to July 2020 was retrospectively analyzed. Risk factors for PSM after LRP in NHT and non-NHT groups were respectively explored. The overall PSM rate was 33.3% (90/270), PSM rate was 39.3% (64/163) in patients without NHT and 24.3% (26/107) in those with NHT. The apex was the most common location of PSM in non-NHT group (68.8%, 44/64), while the fundus was the most common location of PSM in NHT group (57.7%, 15/26). Multiple logistic regression revealed that body mass index (BMI), PSA, ISUP grade after LRP, pathological stage T (pT) and pathological lymph node status (pN) were independent factors affecting the PSM for patients without NHT (OR=1.160, 95%CI:1.034-1.301, p=0.011; OR=3.385, 95%CI:1.386-8.268, p=0.007; OR=3.541, 95%CI:1.008-12.444, p=0.049; OR=4.577, 95%CI:2.163-9.686, p<0.001; OR=3.572, 95%CI:1.124-11.347, p=0.031), while pT, pN, and lymphovascular invasion (LVI) were independent risk factors affecting PSM for patients with NHT (OR=18.434, 95%CI:4.976-68.297, p<0.001; OR=7.181, 95%CI:2.089-24.689, p=0.002; OR=3.545, 95%CI:1.109-11.327, p=0.033). The apex was the most common location in NHT group, and BMI, PSA, ISUP after LRP, pT and pN were independent risk factors affecting PSM for NHT patients; while the fundus was the most common location in non-NHT group, and pT, pN, and LVI were independent risk factors affecting PSM for non-NHT patients.

Significant Prostate Cancer in Patients with PI-RADS Category 3 Lesions: A Single-Center, Retrospective Cohort Study.

The Prostate Imaging-Reporting and Data System (PI-RADS) category 3 is the most ambiguous lesion with a variable clinically significant prostate cancer (CsPCa) detection rate. Prostate-specific antigen density (PSAD) has been investigated as an adjunctive factor to improve the diagnostic efficiency of PI-RADS categories. This study aimed to investigate the utility of PSAD as an adjunctive factor in predicting CsPCA risk in patients with PI-RADS 3 lesions. The patients with an initial PI-RADS 3 category lesion (n=142) scheduled for systematic and magnetic resonance imaging-guided prostate biopsy between 2018 and 2022 were retrospectively evaluated. Demographic and clinical variables, including PSAD, were collected. The rate of CsPCa was the primary outcome. The impact of PSAD on the CsPCa detection rate was the secondary outcome. The median age was 62 years. The rate of CsPCa was 8.5% (n=12). The patients with CsPCa have significantly lower prostate volüme and higher PSAD levels than those without CsPCa (p=0.016 and p=0.012). The cut-off values of PSAD in predicting CsPCa in all PI-RADS 3 patients and patients with CsPCa and clinically insignificant prostate cancer (n=26) were ≥0.181 ng/ml2. The sensitivity and specificity values for PSAD ≥0.181 ng/ml2 were of 75% (95% CI: 42.8%-94.5%) and 81.5% (95% CI: 73.4%-88.0%) in predicting CsPCa among PI-RADS 3 category. Conclusion: PSAD values higher than 0.181 ng/ml2 can be used as an adjunctive clinical parameter in predicting CsPCa in patients with PI-RADS 3 lesions and differentiating CsPCa from clinically insignificant prostate cancer cases.

Male-Pattern Vertex Baldness Trajectories, Chest Hair Patterns, and Odds of Overall and Aggressive Prostate Cancer.

The link between hormones and hair growth is well established. Inconsistent associations have been found between hair patterns and cancer of the prostate, a hormone-dependent organ. We assessed vertex baldness trajectories, chest hair amount, and their relationships with the odds of developing prostate cancer in a large case-control study in Montreal, Canada. In-person interviews were conducted with 1,931 incident prostate cancer cases and 1,994 population-based age-matched (±5 years) controls. Participants reported their hair patterns using the validated Hamilton-Norwood scale of baldness for 10-year increments starting at age 30, and their current amount of chest hair. Group-based trajectories were used to identify men sharing similar patterns of vertex baldness severity over adulthood. Multivariable logistic regression assessed associations between indicators of baldness (frontal, vertex, age at onset, severity, and trajectories), chest hair, and odds of prostate cancer. Vertex balding onset at age 30 was associated with increased odds of overall prostate cancer [Odds ratio (OR), 1.30; 95% confidence interval (CI), 1.03-1.64]. Men in the trajectory characterized by early moderate vertex baldness and developing severe baldness had increased odds of overall (OR, 1.42; 95% CI, 1.03-1.96) and especially aggressive prostate cancer (OR, 1.98; 95% CI, 1.21-3.22) compared with men without baldness. Men with little chest hair had higher odds of aggressive tumors than those with a moderate amount/a lot of chest hair. Early-onset moderate vertex baldness that progresses and having little chest hair may be useful biomarkers of aggressive prostate cancer. Integration of early-onset vertex balding patterns into risk prediction models of aggressive prostate cancer should be envisaged.

Relationship between Eccentricity and Volume Determined by Spectral Algorithms Applied to Spatially Registered Bi-Parametric MRI and Prostate Tumor Aggressiveness: A Pilot Study.

(1) Background: Non-invasive prostate cancer assessments using multi-parametric MRI are essential to the reliable detection of lesions and proper management of patients. While current guidelines call for the administration of Gadolinium-containing intravenous contrast injections, eliminating such injections would simplify scanning and reduce patient risk and costs. However, augmented image analysis is necessary to extract important diagnostic information from MRIs. Purpose: This study aims to extend previous work on the signal to clutter ratio and test whether prostate tumor eccentricity and volume are indicators of tumor aggressiveness using bi-parametric (BP)-MRI. (2) Methods: This study retrospectively processed 42 consecutive prostate cancer patients from the PI-CAI data collection. BP-MRIs (apparent diffusion coefficient, high b-value, and T2 images) were resized, translated, cropped, and stitched to form spatially registered BP-MRIs. The International Society of Urological Pathology (ISUP) grade was used to judge cases of prostate cancer as either clinically significant prostate cancer (CsPCa) (ISUP ≥ 2) or clinically insignificant prostate cancer (CiPCa) (ISUP < 2). The Adaptive Cosine Estimator (ACE) algorithm was applied to the BP-MRIs, followed by thresholding, and then eccentricity and volume computations, from the labeled and blobbed detection maps. Then, univariate and multivariate linear regression fittings of eccentricity and volume were applied to the ISUP grade. The fits were quantitatively evaluated by computing correlation coefficients (R) and p-values. Area under the curve (AUC) and receiver operator characteristic (ROC) curve scores were used to assess the logistic fitting to CsPCa/CiPCa. (3) Results: Modest correlation coefficients (R) (>0.35) and AUC scores (0.70) for the linear and/or logistic fits from the processed prostate tumor eccentricity and volume computations for the spatially registered BP-MRIs exceeded fits using the parameters of prostate serum antigen, prostate volume, and patient age (R~0.17). (4) Conclusions: This is the first study that applied spectral approaches to BP-MRIs to generate tumor eccentricity and volume metrics to assess tumor aggressiveness. This study found significant values of R and AUC (albeit below those from multi-parametric MRI) to fit and relate the metrics to the ISUP grade and CsPCA/CiPCA, respectively.

Association of PSA variability with prostate cancer development using large-scale medical information data: a retrospective cohort study

BackgroundProstate cancer is one of the most common cancers among men worldwide and the fourth most common cause of death. The number of prostate cancer cases and deaths is increasing every year because of population aging. This study aimed to clarify the risk of developing prostate cancer due to fluctuations in Prostate Specific Antigen (PSA) levels in patients without a history of prostate cancer using large medical information data.ResultsThis retrospective cohort included 1707 male patients aged 60 years or older who had a PSA level measurement date (2-PSA) within 3 months or more and 2 years from the first PSA level measurement date (1-PSA) in the database between 2008 and 2019. We subtracted 1-PSA from 2-PSA and designated patients with a higher 2-PSA than 1-PSA to the “up” group (n = 967) and patients with a lower 2-PSA than 1-PSA to the “down” group (n = 740). By using Cox proportional hazards model, a significant increase in prostate cancer risk was observed in the up group compared with the down group (adjusted hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.21–2.72; adjusted for patient background factors). Subgroup analysis showed that patients with PSA levels < 4 ng/mL had a significantly increased risk of developing prostate cancer if the next PSA level increases by approximately 20% (adjusted HR = 2.94, 95% CI = 1.14–7.58), and patients with PSA levels of 4 ng/mL or higher if the next PSA level is decreased by approximately 20% had a significantly reduced risk of developing prostate cancer (adjusted HR = 0.36, 95% CI = 0.18–0.74), compared to that with no change.ConclusionsThis is the first study to clarify the association between PSA variability and risk of developing prostate cancer in patients without a history of prostate cancer. These results suggest that the suppression of elevated PSA levels may lead to the prevention of prostate cancer and that it would be better to perform a biopsy because the risk of developing prostate cancer may increase in the future if the PSA value increases above a certain level.

CHRDL1, NEFH, TAGLN and SYNM as novel diagnostic biomarkers of benign prostatic hyperplasia and prostate cancer.

Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are common male diseases whose incidence rates gradually increase with age. They seriously affect men's physical health and quality of life. This study aimed to identify new biomarkers for the diagnosis of BPH and PCa. Two datasets, GSE28204 and GSE134051 (including human PCa and BPH), were downloaded from the GEO database. The batch effect was removed for merging, and then differential gene expression analysis was conducted to identify BPH and PCa cases. The diagnostic biomarkers of BPH and PCa were further screened using machine learning and bioinformatics. ROC curves were drawn to evaluate the diagnostic accuracy of the selected biomarkers. An online website and qPCR were used to preliminarily explore the expression levels of PCa biomarkers. The correlations between the expression of biomarkers and the tumor microenvironment, tumor mutation load and immunotherapy drugs were evaluated. We identified fifteen genes (CHRDL1, DES, FLNC, GSTP1, MYL9, TGFB3, NEFH, TAGLN, SPARCL1, SYNM, TRPM8, HPN, PLA2G7, ENTPD5 and GPR160) as critical diagnostic biomarkers. After reviewing the literature on all selected biomarkers, we found few studies on the four genes CHRDL1, NEFH, TAGLN and SYNM in BPH or PCa. We defined these four genes as new potential diagnostic biomarkers (NPDBs) of BPH and PCa. All NPDBs were downregulated in PCa patients and PCa cell lines and upregulated in BPH patients and cell lines. When the immune landscape and mutation frequencies were analyzed, the results showed that the tumor microenvironment (TME), immune landscape, tumor mutation burden, and drug response were significantly correlated with NPDB expressions. We found four new diagnostic markers of BPH and PCa, which may facilitate the early diagnosis, treatment, and immunotherapeutic responses assessment and may be of major value in guiding clinical practice.

The prevalence of lynch syndrome (DNA mismatch repair protein deficiency) in patients with primary localized prostate cancer using immunohistochemistry screening

BackgroundProstate cancer is one of the most heritable human cancers. Lynch syndrome is an autosomal dominant inheritance caused by germline mutations in DNA mismatch repair (MMR) genes, which are also associated with an increased incidence of prostate cancer. However, prostate cancer has not been defined as a Lynch syndrome-associated cancer. The proportion of Lynch syndrome patients in primary prostate cancers is unclear. In this study, we investigated MMR protein loss using universal immunohistochemical screening to determine the prevalence of Lynch syndrome in patients with localized prostate cancer who underwent radical prostatectomy.MethodsOne hundred twenty-nine surgical specimens from radical prostatectomy performed at Toranomon Hospital between 2012 and 2015 were retrospectively tested using universal screening with immunohistochemistry staining for expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6. For all suspected MMR-deficient patients, germline genetic tests focusing on MMR genes were performed.ResultsMMR protein loss was found in only one patient (0.8%) who showed dual MSH2/MSH6 loss. This patient showed a single nucleotide pathogenic germline mutation from c.1129 C to T (p.Gln377*) at exon 7 in the MSH2 gene. He was diagnosed with a primary prostate cancer at 66 years of age. He had a documented history of Lynch syndrome (Muir–Torre syndrome) with previous colon cancer, sebaceous tumor, and keratoacanthoma as well as subsequent bladder cancer, all of which also showed dual MSH2/MSH6 loss. He also had a strong family history of colorectal and other Lynch syndrome-associated cancers. The pathological stage was pT3aN0M0, and the pathological grade was Gleason 7(4 + 3) with tertiary pattern 5.ConclusionsIn this study, immunohistochemical screening of MMR proteins for Lynch syndrome was performed in a series of prostate cancer cases. The prevalence of Lynch syndrome in localized prostate cancer was 0.8%, which is low compared with other Lynch syndrome-associated cancers.

Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study

PurposeCurrently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk.MethodsUrine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC).ResultsIn Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS.ConclusionThis urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.

Particle Swarm Optimisation Applied to the Direct Aperture Optimisation Problem in Radiation Therapy.

Intensity modulated radiation therapy (IMRT) is one of the most used techniques for cancer treatment. Using a linear accelerator, it delivers radiation directly at the cancerogenic cells in the tumour, reducing the impact of the radiation on the organs surrounding the tumour. The complexity of the IMRT problem forces researchers to subdivide it into three sub-problems that are addressed sequentially. Using this sequential approach, we first need to find a beam angle configuration that will be the set of irradiation points (beam angles) over which the tumour radiation is delivered. This first problem is called the Beam Angle Optimisation (BAO) problem. Then, we must optimise the radiation intensity delivered from each angle to the tumour. This second problem is called the Fluence Map Optimisation (FMO) problem. Finally, we need to generate a set of apertures for each beam angle, making the intensities computed in the previous step deliverable. This third problem is called the Sequencing problem. Solving these three sub-problems sequentially allows clinicians to obtain a treatment plan that can be delivered from a physical point of view. However, the obtained treatment plans generally have too many apertures, resulting in long delivery times. One strategy to avoid this problem is the Direct Aperture Optimisation (DAO) problem. In the DAO problem, the idea is to merge the FMO and the Sequencing problem. Hence, optimising the radiation's intensities considers the physical constraints of the delivery process. The DAO problem is usually modelled as a Mixed-Integer optimisation problem and aims to determine the aperture shapes and their corresponding radiation intensities, considering the physical constraints imposed by the Multi-Leaf Collimator device. In solving the DAO problem, generating clinically acceptable treatments without additional sequencing steps to deliver to the patients is possible. In this work, we propose to solve the DAO problem using the well-known Particle Swarm Optimisation (PSO) algorithm. Our approach integrates the use of mathematical programming to optimise the intensities and utilizes PSO to optimise the aperture shapes. Additionally, we introduce a reparation heuristic to enhance aperture shapes with minimal impact on the treatment plan. We apply our proposed algorithm to prostate cancer cases and compare our results with those obtained in the sequential approach. Results show that the PSO obtains competitive results compared to the sequential approach, receiving less radiation time (beam on time) and using the available apertures with major efficiency.

Digital Rectal Examination Is Not a Useful Screening Test for Prostate Cancer

BackgroundAnnual digital rectal examination (DRE) is recommended as a stand-alone screening test for prostate cancer (PCa) in Germany for 45+ yr olds. DRE diagnostic performance in men as young as 45 yr old has not been proved by a screening trial. ObjectiveTo determine DRE diagnostic performance in a screening trial. Design, setting, and participantsThis analysis was conducted within the multicentric, randomized PROBASE trial, which enrolled >46 000 men at age 45 to test risk-adapted prostate-specific antigen (PSA) screening for PCa. Intervention(1) DRE was analyzed as a one-time, stand-alone screening offer at age 45 in 6537 men in one arm of the trial and (2) PCa detection by DRE was evaluated at the time of PSA-screen–driven biopsies (N = 578). Outcome measurements and statistical analysis(1) True-/false-positive detection rates of DRE as compared with PSA screening and (2) DRE outcome at the time of a prostate biopsy were evaluated. Results and limitations(1) A prospective analysis of 57 men with suspicious DRE at age 45 revealed three PCa. Detection rate by DRE was 0.05% (three of 6537) as compared with a four-fold higher rate by PSA screening (48 of 23 301, 0.21%). The true-positive detection rate by DRE relative to screening by PSA was 0.22 (95% confidence interval [CI] = [0.07–0.72]) and the false-positive detection rate by DRE was 2.2 (95% CI = [1.50–3.17]). (2) Among PSA-screen–detected PCa cases, 86% had unsuspicious DRE (sensitivity relative to PSA was 14%), with the majority of these tumors (86%) located in the potentially accessible zones of the prostate as seen by magnetic resonance imaging. ConclusionsThe performance of stand-alone DRE to screen for PCa is poor. DRE should not be recommended as a PCa screening test in young men. Furthermore, DRE does not improve the detection of PSA-screen–detected PCa. Patient summaryOur report demonstrated the poor diagnostic performance of digital rectal examination in the screening for prostate cancer in young men.

SAT024 Contribution of 11-Ketotestosterone and 11-Ketodihydrotestosterone to Castration-Resistant Prostate Cancer

Abstract Disclosure: H.S. Abu-Lebdeh: None. H.M. Heshmati: None. Background: Prostate cancer is among the most common malignancy in men and represents the second most common cause of cancer-related mortality among men in the US. Androgen-deprivation therapy with surgical or medical castration is widely used to treat hormone-sensitive prostate cancer. Disease progression despite androgen-deprivation therapy is a state defined as castration-resistant prostate cancer that is associated with poor survival rate. This review presents an update on the contribution of two adrenal androgens, 11-ketotestosterone and 11-ketodihydrotestosterone, to the castration-resistant prostate cancer. Methods: A systematic search of literature was conducted using the search terms prostate cancer, testosterone, dihydrotestosterone, adrenal androgens, 11-ketotestosterone, 11-ketodihydrotestosterone, androgen-deprivation therapy, castration, and castration-resistant prostate cancer. Results: In 2022, around 268,490 new cases of prostate cancer were diagnosed in the US with a mortality of 34,500 cases. Although androgen-deprivation therapy with castration is efficient at the beginning, most patients develop a state of castration resistance usually after 2-3 years as a result of the reactivation of androgen-receptor signaling despite low testosterone levels. The adrenal glands produce significant amounts of steroid hormones and metabolites. Among them, 11-ketotestosterone and 11-ketodihydrotestosterone are potent and efficacious androgens with potentially longer activity compared to testosterone and dihydrotestosterone because they are metabolized at a lower rate. Dihydrotestosterone derived from the metabolism of adrenal androgens (e.g., androstenedione and dehydroepiandrosterone) and especially 11-ketotestosterone and 11-ketodihydrotestosterone are important contributors to castration-resistant prostate cancer. In these cases, adrenal suppression with drugs causing a decrease in adrenal androgen production may improve the effectiveness of the androgen-deprivation therapy. Conclusion: In most patients with prostate cancer, androgen-deprivation therapy loses its effectiveness after 2-3 years leading to a state of castration-resistant prostate cancer. Two potent and highly efficacious androgen-receptor agonists of adrenal origin, 11-ketotestosterone and 11-ketodihydrotestosterone, are predominant androgens after castration and play an important role in the development and progression of castration-resistant prostate cancer. Their measurement in blood can be of clinical value during androgen-deprivation therapy. Concomitant treatment aimed to block the production of adrenal androgens is of potential interest in the management of these patients, but more studies are necessary to further investigate the benefits and adverse effects of this approach. Presentation: Saturday, June 17, 2023

THU528 ACTH-dependent Hypercortisolism From Neuroendocrine Prostate Tumor With Negative ACTH Staining Of The Tumor Cells

Abstract Disclosure: M. Fariduddin: None. J. Sanchez Perez: None. U.N. Syed: None. Y. Eisenberg: None. R.M. Sargis: None. Introduction: Ectopic ACTH-dependent Cushing’s syndrome (CS) is a rare entity accounting for 10-20% of hypercortisolism cases. We present a patient with this syndrome. Case Presentation: A 72-year-old man diagnosed with metastatic prostate cancer to the lumbar spine and pelvis was admitted for persistent hypokalemia. Potassium levels were 2.1 mmol/L (ref. range: 3.5-5.2) despite aggressive potassium supplementation. He reported 30-lb weight gain in the previous 2 months, rounding of his face, increased abdominal girth, and proximal muscle weakness. Facial plethora with puffiness was noted on physical exam. Labs were relevant for impaired glucose tolerance with fasting blood glucose of 110 mg/dL and elevated A1c of 6.3% (&amp;lt;5.7%), compared to 5.0% 1 year earlier. 8 AM cortisol was 59 ug/dL (6.7-22.6) and after dexamethasone, cortisol remained elevated at 65.8 ug/dL (&amp;lt;1.8). ACTH level was 312 pg/mL (7.2 - 63.3) and 24-hr urine cortisol was 3586 ug/dL (&amp;lt;= 60.0). Abdominopelvic CT showed new bilateral adrenal thickening without discrete nodularity or mass. Pituitary MRI showed a 1mm microadenoma, inconsistent with the degree of hypercortisolism observed. Patient’s age, known prostate adenocarcinoma with differentiation into neuroendocrine tumor and rapid onset of development of hypercortisolism were all suggestive of ectopic Cushing’s syndrome. Ketoconazole 200 mg BID, Spironolactone 200 mg BID and Amiloride 5 mg daily were started which resolved the hypokalemia. ACTH staining of the prostate tissue biopsy was negative. Patient later died of respiratory failure from Influenza pneumonia. Conclusion: Ectopic ACTH hypercortisolism is a rare but aggressive form of hypercortisolism. Symptoms like proximal muscle weakness, hyperglycemia, hypokalemia, infections, and blood clots develop rapidly, however, these patients rarely have the clinical stigmata of CS. Neuroendocrine tumors of the lung and small cell lung cancer are the most common tumors associated with ectopic ACTH production, but cases of paraneoplastic prostate cancer have been reported. Published case reports demonstrate positive ACTH staining of these tumor cells, but this was not the case in our patient even though his presentation was consistent with ectopic hypercortisolism. The ACTH staining was done on a sample of prostate tissue taken 2 months prior to presentation, at the time of diagnosis of prostate cancer. Neuroendocrine differentiation could have happened within 2 months after the biopsy. This case impresses upon us that ACTH staining can be negative in ectopic ACTH hypercortisolism and patients can still have CS as tumor cells continue to differentiate throughout the course of the malignancy- and this can be especially rapid in neuroendocrine differentiation of tumors. CS increases mortality by 3 times, therefore making it crucial to recognize it early to institute prompt treatment. Presentation: Thursday, June 15, 2023

S2388 Rectal Tropism: A Unique Case of Prostate Cancer With Metastasis to the Rectum

S2388 Rectal Tropism: A Unique Case of Prostate Cancer With Metastasis to the Rectum

Use of Focal Radiotherapy Boost for Prostate Cancer and Perceived Barriers toward its Implementation: A Survey.

In a recent phase III randomized control trial (FLAME), delivering a focal radiotherapy (RT) boost to tumors visible on MRI was shown to improve outcomes for prostate cancer patients without increasing toxicity. The aim of this study was to assess how widely this technique is being applied in current practices worldwide as well as physicians' perceived barriers toward its implementation. An online survey assessing the use of intraprostatic focal boost was conducted in December 2022 and February 2023. The survey link was distributed to radiation oncologists worldwide via email list, group text platform, and social media. Survey questions included how many prostate cancer cases participants treat in a typical month; how often they use focal boost, if at all; the degree to which their practice is genitourinary (GU)-subspecialized; main barriers to implementing focal boost more often in their practice; and demographic information. Subgroup analyses were also conducted for participants from high-income or low-to-middle-income countries, as defined by the World Bank. The survey initially collected 205 responses from various countries over a two-week period in December 2022. The survey was then reopened for one week in February 2023 to allow for more participation, leading to a total of 263 responses. The highest-represented countries were the United States (42%), Mexico (13%), and the United Kingdom (8%). The majority of respondents worked at an academic medical center (52%) and considered their practice to be at least partially GU-subspecialized (74%). 57% of participants overall reported not routinely using intraprostatic focal boost. Even among complete subspecialists, a substantial proportion (39%) do not routinely use focal boost. Less than half of participants in both high-income and low-to-middle-income countries were shown to routinely use focal boost. Perceived barriers to implementation are shown in Table 1. Despite the promising level 1 results of the FLAME trial, many radiation oncologists worldwide are not routinely offering focal RT boost. Adoption of this technique might be accelerated by increased access to high-quality MRI, better registration algorithms of MRI to CT simulation images, physician education on benefit-to-harm ratio, automated planning algorithms, and physician training on contouring prostate lesions on MRI.

Multiparametric Magnetic Resonance Imaging in Prostate Cancer Screening at the Age of 45 Years: Results from the First Screening Round of the PROBASE Trial

BackgroundMagnetic resonance imaging (MRI) has been suggested as a tool for guiding biopsy recommendations in prostate cancer (PC) screening. ObjectiveTo determine the performance of multiparametric MRI (mpMRI) in young men at age 45 yr who participated in a PC screening trial (PROBASE) on the basis of baseline prostate-specific antigen (PSA). Design, setting, and participantsParticipants with confirmed PSA ≥3 ng/ml were offered mpMRI followed by MRI/transrectal ultrasound fusion biopsy (FBx) with targeted and systematic cores. mpMRI scans from the first screening round for men randomised to an immediate PSA test in PROBASE were evaluated by local readers and then by two reference radiologists (experience >10 000 prostate MRI examinations) blinded to the histopathology. The PROBASE trial is registered as ISRCTN37591328 Outcome measurements and statistical analysisThe local and reference Prostate Imaging-Data and Reporting System (PI-RADS) scores were compared, and the sensitivity, negative predictive value (NPV), and accuracy were calculated for both readings for different cutoffs (PI-RADS 3 vs 4). Results and limitationsOf 186 participants, 114 underwent mpMRI and FBx. PC was detected in 47 (41%), of whom 33 (29%) had clinically significant PC (csPC; International Society of Urological Pathology grade group ≥2). Interobserver reliability between local and reference PI-RADS scores was moderate (k = 0.41). At a cutoff of PI-RADS 4, reference reading showed better performance for csPC detection (sensitivity 79%, NPV 91%, accuracy of 85%) than local reading (sensitivity 55%, NPV 80%, accuracy 68%). Reference reading did not miss any PC cases for a cutoff of PI-RADS <3. If PI-RADS ≥4 were to be used as a biopsy cutoff, mpMRI would reduce negative biopsies by 68% and avoid detection of nonsignificant PC in 71% of cases. ConclusionsProstate MRI in a young screening population is difficult to read. The MRI accuracy of for csPC detection is highly dependent on reader experience, and double reading might be advisable. More data are needed before MRI is included in PC screening for men at age 45 yr. Patient summaryMeasurement of prostate specific antigen (PSA) is an effective screening test for early detection of prostate cancer (PC) and can reduce PC-specific deaths, but it can also lead to unnecessary biopsies and treatment. Magnetic resonance imaging (MRI) after a positive PSA test has been proposed as a way to reduce the number of biopsies, with biopsy only recommended for men with suspicious MRI findings. Our results indicate that MRI accuracy is moderate for men aged 45 years but can be increased by a second reading of the images by expert radiologists. For broad application of MRI in routine screening, double reading may be advisable.