Prostate-specific Antigen Measurements Research Articles

Early Prostate-Specific Antigen Kinetics for Low- and Intermediate-Risk Prostate Cancer Treated With Definitive Radiation Therapy

PurposeThis study used a patient-specific model to characterize and compare ideal prostate-specific antigen (PSA) kinetics for low- and intermediate-risk prostate cancer after definitive radiation treatment with conventionally fractionated, hypofractionated, stereotactic body radiation therapy, or brachytherapy, both high-dose and low-dose rate. Methods and MaterialsThis retrospective analysis includes low- and intermediate-risk patients with prostate cancer treated between 1998 and 2018 at an National Cancer Institute–designated comprehensive cancer center. Demographics and treatment characteristics were prospectively collected. Patients had at least 2 PSA measurements within 24 months of treatment and were free from biochemical recurrence. The incidence of, time to, and risk factors for PSA nadir (nPSA) and bounce (bPSA) were analyzed at 24 months after radiation therapy. Ideal PSA kinetics were characterized for each modality and compared. ResultsOf 1042 patients, 45% had low-risk cancer, 37% favorable intermediate risk, and 19% unfavorable intermediate risk. nPSAs were higher for ablative modalities, both as absolute nPSA and relative to initial PSA. Median time to nPSA ranged from 14.8 to 17.1 months. Over 50% treated with nonablative therapy (conventionally fractionated, hypofractionated, and low-dose rate) reached an nPSA threshold of ≤0.5 ng/mL compared with 23% of stereotactic body radiation therapy and 33% of high-dose rate cohorts. The incidence of bPSA was 13.3% and not affected by treatment modality, Gleason score, or prostate volume. PSA decay rate was faster for ablative therapies in the 6- to 24-month period. ConclusionsAnalysis of PSA within 24 months after radiation therapy revealed ablative therapies are associated with a latent PSA response and higher nPSA. Multivariable logistics modeling revealed younger age, initial PSA above the median, presence of bPSA, and ablative therapy as predictors for not achieving nPSA ≤0.5 ng/mL. PSA decay rate appears to be faster in ablative therapies after a latent period. Understanding the different PSA kinetic profiles is necessary to assess treatment response and survey for disease recurrence.

PREDICTIVE VALUE OF SERUM PROSTATE SPECIFIC ANTIGEN IN DETECTING BONE METASTASIS IN PROSTATE CANCER

Objective: We determine the utility of Prostate Specific Antigen (PSA) for predicting the presence of skeletal metastasis on Bone Scan (BS) in prostate cancer patients. Material & Methods: Retrospective analysis of medical records of 70 consecutive prostate cancer patients subjected to bone scan during the last 2 years was done. 5 cases were excluded due to the following reasons: Serum PSA not available, hormonal or other therapy given prior to serum PSA measurement, and/or Bone Scan, and symptomatic for bone metastasis. In remaining 65 cases, PSA value and bone scan were evaluated. Results: BS was found to be positive in 20/65 (31%) and negative in 45(69%) patients. 24 (37%) had serum PSA > 100 ng/ml, 25 (38.5%) had PSA of 20‐100 ng/ml and only 16 (24.5%) had PSA < 20 ng/ml. Conclusion: Serum PSA < 20 ng/ml have high predictive value in ruling out skeletal metastasis. Our data are in corroboration with results from previous studies that BS should be performed only if PSA > 20 ng/ml. Using this cut‐off, unnecessary investigation can be avoided. Avoiding BS asymptomatic in this group of patients would translate into a significant cost‐saving and reduction in their psychological and physical burden.

Comparison Between Dose-Escalated Intensity Modulated Radiation Therapy and 3-Dimensional Conformal Radiation Therapy for Salvage Radiation Therapy After Prostatectomy

PurposeTo compare long-term outcomes and late toxicity between patients treated with 3-dimensional conformal radiation therapy (3D-CRT) and with dose-escalated intensity modulated radiation therapy (IMRT) as salvage radiation therapy (SRT) after prostatectomy. Methods and MaterialsA total of 110 patients who had been treated at our institution between 2010 and 2018 with SRT for biochemical recurrence after radical prostatectomy were included. The patients were treated either by 3D-CRT with 64 Gy (59 patients) or by IMRT with 70 Gy (51 patients). The irradiation target was the prostate bed only (106 patients) or the prostate bed and pelvic region (4 patients). Twelve patients (11%) received concurrent androgen deprivation therapy. The differences in clinical outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicity between the 3D-CRT and IMRT groups were retrospectively assessed. Toxicities were recorded using the Common Terminology Criteria for Adverse Events, version 5.0. Prostate-specific antigen (PSA) progression after SRT was defined as an increase in the serum PSA level of 0.2 ng/mL from the PSA nadir after SRT and confirmed by a second PSA measurement that was higher than the first. ResultsThe median follow-up time was 7.8 years for 3D-CRT (range:,0.3-9.2 years) and 3.1 years for IMRT (range, 0.4-7.2 years). There was no significant difference in the 4-year biochemical no-evidence-of-disease (bNED) rate between the 3D-CRT and IMRT groups (43.5% vs 52.1%; P = .20). Toxicity analysis showed no significant difference in late GI or GU toxicities of grade 2 or greater between the 3D-CRT and IMRT groups. The respective 4-year cumulative rates of toxicity in the 3D-CRT and IMRT groups were as follows: grade ≥2 GI toxicity, 8.8% and 4.4% (P = .42); grade ≥2 GU toxicity, 19.1% and 20.3% (P = .93); and grade ≥2 hematuria, 5.3% and 8.0% (P = .67). In the 3D-CRT group, the 8-year cumulative rates of GI toxicity, GU toxicity, and hematuria of grade 2 or greater were 8.8%, 28.4%, and 12.6%, respectively. ConclusionsDose-escalated IMRT showed no improvements in bNED or late toxicity compared with 3D-CRT. In addition, the results suggest that GU toxicity can occur after a long period (even after 6 years), whereas GI toxicity is seldom newly observed after 4 years.

Abstract 358: A prospective study of prostate cancer metastases identifies an androgen receptor activity-low, stemness program associated with resistance to androgen receptor axis inhibitors and unveils mechanisms of clonal evolution

Abstract Background: The androgen receptor axis inhibitors (ARi) (e.g, enzalutamide, abiraterone acetate) are administered in daily practice for men with metastatic castration-resistant prostate cancer (mCRPC). However, not all patients respond, and mechanisms of both primary and acquired resistance remain largely unknown. Methods: In a prospective trial MATCH-R (NCT02517892), 55 mCRPC patients underwent whole exome sequencing (WES) (n=45) and RNA-sequencing (RNA-seq) (n=52) of metastatic biopsies before starting ARi. Also, 16 mCRPC patients underwent biopsy at time of resistance (WES=14, RNA-seq = 14). The objectives were to identify genomic alterations associated with resistance to ARi as well as to describe clonal evolution. Primary resistance was determined at 4 months of treatment using composite criteria for progression that included serum prostate specific antigen measurements, bone scan, CT imaging and symptom assessments. Acquired resistance was defined by occurrence of progressive disease after initial response or stable disease. Associations of genomic and transcriptomic alterations with primary resistance were determined using Wilcoxon and Fisher's exact tests. Results: At 4 months, 22/55 patients in the cohort had disease progression (primary resistance). No genomic alterations from WES analysis were significantly associated with primary resistance. Analysis of sequential biopsies suggests that mCRPC follows mainly a parallel evolution model and involve DNA-repair related mutational processes. At time of acquired resistance to ARi, most tumors acquired new drivers affecting AR pathway (e.g, AR, NCOR1/2) or lineage switching (e.g, RB1, PTEN, TP53). Using computational methods, we measured AR transcriptional function and performed gene set enrichment analysis to identify pathways whose activity state correlated with resistance. AR gene alterations and AR expression were similar between responding and non-responding patients. Transcriptional analysis demonstrated that multiple specific gene sets — including those linked to low AR transcriptional activity, stemness program, RB loss and homologous repair deficiency — were activated in both primary and acquired resistance. Conclusion: Resistance to AR axis inhibitors results from multiple transcriptional programs already activated in pre-treatment samples. Clonal evolution analysis along with RNA-seq data indicate the role of genomic instability and lineage switching in driving acquired resistance Citation Format: Naoual Menssouri, Loic Poiraudeau, Carole Helissey, Ludovic Bigot, Jonathan Sabio, Tony Ibrahim, Claudio Nicotra, Maud Ngocamus, Lambros Tselikas, Thierry De Baere, Etienne Rouleau, Ludovic Lacroix, Anne Chaucherau, Luc Friboulet, Ronan Flippot, Giulia Baciarello, Laurence Albiges, Emeline Colomba, Pernelle Lavaud, Stefan Michiels, Aline Maillard, Antoine Italiano, Fabrice Barlesi, Jean-Charles Soria, Jean-Yves Scoazec, christophe Massard, Benjamin Besse, Fabrice André, Karim Fizazi, Daniel Gautheret, Yohann Loriot. A prospective study of prostate cancer metastases identifies an androgen receptor activity-low, stemness program associated with resistance to androgen receptor axis inhibitors and unveils mechanisms of clonal evolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 358.

Risk stratification in men with a negative prostate biopsy: an interim analysis of a prospective cohort study.

To investigate whether a risk score for prostate cancer (PCa) lifetime risk can be used to optimise triaging of patients with a negative prostate biopsy, but under sustained suspicion of PCa. In this prospective clinical study, we included, and risk scored patients who had a PCa-negative transrectal ultrasonography (TRUS)-guided prostate biopsy, but elevated prostate-specific antigen (PSA), a suspicious prostate digital rectal examination and/or a positive family history (FH) of PCa. The risk score estimated individual lifetime risk of PCa, based on a polygenic risk score (33 single nucleotide polymorphisms), age, and FH of PCa. Patients were followed, under urological supervision, for up to 4years with annual controls, always including PSA measurements. Multiparametric magnetic resonance imaging (mpMRI) and/or prostate biopsy was performed at selected annual controls depending on risk score and at the urologist's/patient's discretion, which means that the follow-up differed based on the risk score. We included 429 patients. After risk scoring, 376/429 (88%) patients were allocated to a normal-risk group (<30% PCa lifetime risk) and 53/429 (12%) to a high-risk group (≥30% PCa lifetime risk). The high-risk group had significantly different follow-up, with more biopsy and mpMRI sessions compared to the normal-risk group. PCa was detected in 89/429 (21%) patients, with 67/376 (18%) patients diagnosed in the normal-risk group and 22/53 (42%) in the high-risk group. There was no statistically significant difference in the cumulative incidence of PCa between the normal-risk group and the high-risk group after 4years of follow-up. Currently, 67/429 (16%) patients are still being followed in this ongoing study. In a 4-year perspective, our PCa lifetime risk score did not demonstrate significant prognostic value for triaging patients, with a negative TRUS-guided biopsy and sustained suspicion of PCa.

Multiple Docetaxel Retreatments Without Prednisone for Metastatic Castration-Resistant Prostate Cancer in the Docetaxel-Only Era: Effects on PSA Kinetics and Survival.

IntroductionThis study aimed to assess the effects of multiple docetaxel (DOC) treatments on prostate-specific antigen (PSA) kinetics and survival among patients with metastatic castration-resistant prostate cancer (mCRPC) who were sensitive to first-line DOC and received no other life-prolonging agents. To eliminate the effect of cortisone on serum PSA, only patients who were treated without prednisone were included.MethodsThis IRB-approved retrospective study evaluated 52 patients with mCRPC who were retreated using DOC after first-line DOC (without prednisone in both cases), based on a PSA response of > 50% and no radiographic progression. Twenty-three PSA-based factors, including static and kinetic PSA measures, were evaluate for their ability to predict overall survival (OS)ResultsThe patients received 688 cycles of DOC in 143 series, including 91 courses of retreatments (1 cycle: 28 patients, 2 cycles: 14 patients, 3 cycles: 8 patients, 4 cycles: 1 patient, and 7 cycles: 1 patient). The median overall number of cycles per patient was 12 (range: 7–31). The median durations of the first, second, and third holidays were 18 weeks (6–60 weeks), 16 weeks (3–44 weeks), and 17 weeks (8–51 weeks), respectively. The median OSs were 22 months (10.5–70 months) after the first DOC treatment and 14 months (3–65 months) after the second DOC treatment. The > 50% PSA decline rate was 48% after retreatment. Short treatment holidays (< 3 months) were associated with shortened OS (p = 0.01). In the multivariate analysis, a 25% PSA increase over the nadir was the strongest predictor of survival (HR: 3.20, 95% CI: 1.47–6.99, p = 0.003).ConclusionsDOC retreatment without prednisone had anti-tumor activity in a considerable proportion of mCRPC cases that were initially sensitive to first-line DOC. A 25% PSA increase over the nadir might predict acquired DOC resistance.

Dihydrotestosterone and Free/Total Prostatic Specific Antigen Ratio in Diagnosis and Prognosis of Prostatic Disease

Background: Both benign prostatic hyperplasia (BPH) and prostate cancer (Pca) include prostate enlargement. The second most common cancer among men worldwide is prostate cancer. It has been documented that by the time they reach their 60s, most men will experience benign prostatic hyperplasia. There is a real difficulty differentiating between benign prostatic hyperplasia and prostate cancer, the prostatic specific antigen (PSA) is not used as a reliable marker of prostate cancer. It is a specific biomarker measure specific to prostate tissues and not prostate cancer. Aims In the analysis of the gray zone of tPSA (4-10 ng/ml), add these biochemical markers and differentiate the root cause of prostate tumor in order to minimize painful and intrusive prostate biopsy. Materials and Methods: A cross-sectional and case control study. It included 110 patients ages range (45-81 years) with benign prostatic hyperplasia (n=55) and prostate cancer (n=55). Forty -five apparently healthy subjects were also included as controls. Peripheral blood samples from controls and patients were collected before obtaining a prostatic biopsy from patients. Serum samples were used for measurements of total Prostate Specific Antigen (tPSA), Free Prostate Specific Antigen (fPSA), and Dihydrotestosterone (DHT) by using ELISA technique. Result: Mean (±SD) serum tPSA and fPSA values for Pca were substantially improved compared to both BPH and control (p=0.001 for all), while mean fPSA/tPSA values for PCa were significantly decreased compared to BPH and control values (p=0.001). In PCa, the mean +SD value of the DHT ratios was significantly lower than in each BHP, and controls (P&lt;0.001) were significantly lower in PCa than in each BHP and regulation (P&lt;0.001). The mean DHT values for BPH were significantly higher as compared to control values (p&lt; 0.001). Conclusion: The level of serum tPSA is 4.2 ng/ml for prostate tumor screening, while 10.1 ng/ml for PCa and BPH differentiation.

Non-invasive Prostate Cancer Detection by Measuring Expression Level of miR-21 and miR-214 in Urine

Background: Prostate cancer is the most prevalent cancer among men worldwide. Diagnosis in this cancer is primarily done, using aggressive methods such as biopsy. Laboratory methods, such as the measurement of prostate-specific antigen (PSA) in the blood, do not have high sensitivity and specificity. MicroRNAs (miRNAs), a group of diagnostic biomarkers, can diagnose diseases such as cancer. MicroRNA (miRNA) is a small, non-coding, single-stranded RNA with a length of 21 to 23 nucleotides. Objectives: This study was designed to investigate the changes in the expression level of miR-21 and miR-214 in the urine of patients with prostate cancer compared with healthy controls. Methods: A total of 70 urine samples from prostate cancer patients (32 metastatic and 38 non-metastatic) and 30 from healthy subjects with negative biopsy reports were collected. The expression level of miR-21 and miR-214 in the urine were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: miR-21 showed a significant increase in expression (P = 0.003) and miR-214 showed a significant decrease in expression (P = 0.000) compared with the control group. The specificity, sensitivity, and area under the curve (AUC) were 100, 72.14, and 0.721% for combined panels of miR-21 and miR-214 and 63.33, 61.43, and 0.620%, respectively, for PSA. Conclusions: miR-21 and miR-214 showed significant change in expression in patients with prostate cancer compared with healthy subjects. It is hoped that, with further research, a combined panel of miR-21 and miR-214 can be used as a non-invasive method for detecting prostate cancer with higher sensitivity and specificity than the PSA test.

Whole blood GRHL2 expression as a prognostic biomarker in metastatic hormone-sensitive and castration-resistant prostate cancer.

BackgroundAs potent systemic therapies transition earlier in the prostate cancer disease course, molecular biomarkers are needed to guide optimal treatment selection for metastatic hormone-sensitive prostate cancer (mHSPC). The value of whole blood RNA to detect candidate biomarkers in mHSPC remains largely undefined.MethodsIn this cohort study, we used a previously optimised whole blood reverse transcription polymerase chain reaction assay to assess the prognostic utility [measured by seven-month undetectable prostate-specific antigen (PSA) and time to castration-resistance (TTCR)] of eight prostate cancer-associated gene transcripts in 43 mHSPC patients. Transcripts with statistically significant associations (P<0.05) were further investigated in a metastatic castration-resistant prostate cancer (mCRPC) cohort (n=119) receiving contemporary systemic therapy, exploring associations with PSA >50% response (PSA50), progression-free survival (PFS) and overall survival (OS). Clinical outcomes were prospectively collected in a protected digital database. Kaplan-Meier estimates and multivariable Cox proportional-hazards models assessed associations between gene transcripts and clinical outcomes (mHSPC covariates: disease volume, docetaxel use and haemoglobin level; mCRPC covariates: prior exposure to chemotherapy or ARPIs, haemoglobin, performance status and presence of visceral disease). Follow-up was performed monthly during ARPI treatment, three-weekly during taxane chemotherapy, and three-monthly during androgen deprivation therapy (ADT) monotherapy. Serial PSA measurements were performed before each follow-up visit and repeat imaging was at the discretion of the investigator.ResultsDetection of circulating Grainyhead-like 2 (GRHL2) transcript was associated with poor outcomes in mHSPC and mCRPC patients. Detectable GRHL2 expression in mHSPC was associated with a lower rate of seven-month undetectable PSA levels (25% vs. 65%, P=0.059), and independently associated with shorter TTCR (HR 7.3, 95% CI: 1.5–36, P=0.01). In the mCRPC cohort, GRHL2 expression predicted significantly lower PSA50 response rates (46% vs. 69%, P=0.01), and was independently associated with shorter PFS (HR 3.1, 95% CI: 1.8–5.2, P<0.001) and OS (HR 2.9, 95% CI: 1.6–5.1, P<0.001). Associations were most apparent in patients receiving ARPIs.ConclusionsDetectable circulating GRHL2 was a negative prognostic biomarker in our mHSPC and mCRPC cohorts. These data support further investigation of GRHL2 as a candidate prognostic biomarker in metastatic prostate cancer, in addition to expanding efforts to better understand a putative role in therapeutic resistance to AR targeted therapies.

Verification of Harmonization of Serum Total and Free Prostate-Specific Antigen (PSA) Measurements and Implications for Medical Decisions.

Previous studies have shown that the harmonization of prostate-specific antigen (PSA) assays remained limited even after the introduction of WHO International Standards. This information needs updating for current measuring systems (MS) and reevaluation according to established analytical performance specifications (APS) and the characteristics of antibodies used. Total (tPSA) and free (fPSA) PSA were measured in 135 and 137 native serum samples, respectively, by Abbott Alinity i, Beckman Access Dxl, Roche Cobas e801, and Siemens Atellica IM MSs. Passing-Bablok regression and difference plots were used to compare results from each MS to the all-method median values. Agreement among methods was evaluated against APS for bias derived from biological variation of the 2 measurands. The median interassay CV for tPSA MSs (11.5%; 25-75th percentiles, 9.2-13.4) fulfilled the minimum APS goal for intermethod bias (15.9%), while the interassay CV for fPSA did not [20.4% (25-75th percentiles, 18.4-22.7) vs goal 17.6%]. Considering the all-method median value of each sample as reference, all tPSA MSs exhibited a mean percentage bias within the minimum goal. On the other hand, Alinity (+21.3%) and Access (-24.2%) were out of the minimum bias goal for fPSA, the disagreement explained only in minimal part by the heterogeneity of employed antibodies. The harmonization among tPSA MSs is acceptable only when minimum APS are applied and necessitates further improvement. The marked disagreement among fPSA MSs questions the use of fPSA as a second-level test for biopsy referral.

Potencjalne kliniczne zastosowanie cząsteczek miRNA w diagnostyce raka prostaty

Streszczenie Rak gruczołu krokowego (PCa) jest najczęstszym rodzajem nowotworu wśród mężczyzn w Europie i dotyczy to niemal całego świata. Zalecenia dotyczące badań przesiewowych oraz rozpoznania opierają się na pomiarach antygenu swoistego prostaty (PSA) i badaniu gruczołu krokowego palcem przez odbytnicę (DRE). Obie metody diagnostyczne najczęściej wskazują na konieczność wykonania biopsji prostaty. Ograniczona specyfika testu PSA powoduje jednak potrzebę opracowania nowych i lepszych narzędzi diagnostycznych. W ciągu ostatnich kilku lat, nowe podejście diagnostyczne, zapewniają biomarkery molekularne, które jako alternatywa PSA, zostały wprowadzone do użytku klinicznego. Nowoczesne biomarkery umożliwiają wykorzystywanie ich nie tylko jako nieinwazyjne narzędzia diagnostyczne, ale także zapewniają śledzenie zmian na każdym etapie choroby oraz ocenę agresywności guza i monitorowanie procesu terapeutycznego. Najbardziej obiecującą grupą są markery molekularne, wśród których dużą nadzieję wiąże się z wykorzystaniem pozakomórkowych cząstek mikroRNA (miRNA, miR). miRNA tworzą klasę małych o długości około 22 nukleotydów, niekodujących cząsteczek RNA, które biorą udział w potranskrypcyjnej regulacji ekspresji licznych genów. W artykule przedstawiono aktualną wiedzę dotyczącą roli miRNA w PCa, w tym dane dotyczące szlaku sygnałowego receptora androgenowego (AR signaling), cyklu komórkowego, procesu przejścia nabłonkowo-mezenchymalnego (EMT), rakowych komórek macierzystych (CSC), a nawet rolę miRNA jako narzędzia terapeutycznego PCa. Znalezienie lepszych biomarkerów PCa, na bazie miRNA, zastępujących obecny pomiar PSA, jest bardzo potrzebne w nowoczesnej praktyce onkologicznej.

Evaluation of healthcare for transgender veterans

PurposeTo identify the cohort of veterans diagnosed with gender dysphoria obtaining care through VA Northern California Healthcare System (VANCHCS), and evaluate their care. MethodsUsing ICD-10 criteria, we identified veterans with a diagnosis of gender dysphoria. We stratified these individuals by self-identified gender, and evaluated their medical records for gender affirming-hormone therapy and access to behavioral health, endocrine, speech pathology, and dermatology resources. ResultsOf the 148 Veterans found, 95 identified as transwomen, 43 as transmen, and 10 as non-binary. Non-binary Veterans were excluded from further analysis. Transmen were significantly younger than transwomen (42±13.7 vs 51.5±15.9 yrs., p< 0.001 by t-test). Transwomen were more likely to be Air Force Veterans than transmen (21.1% vs 17.1%), and less likely to be Army Veterans (38.9% vs 43.9%), but were more likely to see a Endocrinologist (83.2% vs 72.1%) and Speech Therapist (44.2% vs. 25.6%). Gender affirming hormone therapy for transwomen included combinations of gonadotropin-releasing hormone analogs, spironolactone, finasteride, estradiol, and progesterone, whereas for transmen, testosterone was the sole therapy. The majority of our Veterans (65 transwomen (68.4%) and 38 transmen (88.4%) had not undergone gender-affirming surgery. Only 59 transwomen (62%) had measurements of prostate-specific antigen (PSA). Both groups were followed comparably in Behavioral Health Clinics (87.4% for transwomen, 90.7% for transmen). Only 35 transwomen (36.8%) were seen in Dermatology clinics for gender specific needs. ConclusionOur patients and their management were diverse. We conclude that care for transgender Veterans could be enhanced by a more consistent, team-based approach to therapy.

A single-center long-term experience of active surveillance for prostate cancer: 15 years of follow-up.

PurposeTo describe a single-center 15-year experience of active surveillance (AS) for prostate cancer (PCa).Materials and MethodsWe retrospectively reviewed patients who underwent AS between 2003 and 2018. One hundred fifty-three patients were selected according to the following criteria: (1) biopsy Gleason pattern ≤3+4 with (2) ≤two positive core(s) and (3) ≤50% core involvement, clinical-stage ≤T2a, and prostate-specific antigen (PSA) ≤20 ng/mL. Follow-up included PSA measurement every six months, prostate biopsies at one year and then every 2–3 years, and MRI every year. Intervention was triggered by (1) Gleason score (GS) upgrading, (2) >two positive cores, or (3) PSA doubling-time in <3 years.ResultsMean (±standard deviation) follow-up was 36.4 (±31.9) months. Ninety-three (60.8%) and 20 (13.1%) patients received second and third biopsies, respectively. Seventy-two patients (47.1%) discontinued AS for various reasons (59, intervention; 13, follow-up loss). Reasons for intervention consisted of GS upgrading (42.4%), >two positive cores (8.5%), abnormal PSA kinetics (11.9%), and patient preference (37.3%). Notably, 12 (25.5%) patients had pathologic GS ≥4+3 (unfavorable disease) and 3 (6.4%) patients had pathologic stage ≥T3a at radical prostatectomy. Median time to treatment-free survival was 19.5 months. Of the 59 patients who switched to intervention, biochemical recurrence was reported in only one (0.7%) patient.ConclusionsAS is an available option for low-risk PCa in carefully selected patients. Further larger prospective studies are needed to determine the optimal criteria for AS, especially in Korean PCa patients.

Diagnostic performance of 18F-DCFPyL positron emission tomography/computed tomography for biochemically recurrent prostate cancer and change-of-management analysis.

Conventional imaging (CI) performs poorly to identify sites of disease in biochemically recurrent prostate cancer. 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) is most studied but has a very short half-life. This study reports the diagnostic performance of the novel prostate-specific membrane antigen (PSMA) radiotracer 18F-DCFPyL using real-life data and tumor board simulation to estimate the impact of 18F-DCFPyL PET on patient management. Ninety-three 18F-DCFPyL PET/CT scans performed for patients previously treated for prostate cancer with a rising prostate-specific antigen (PSA) were retrospectively compared to contemporary CI and clinical imaging and PSA followups. A chart review was performed to document prior imaging, pathology results, serial serum PSA measurements, and other pertinent clinical data. Clinical utility of 18F-DCFPyL PET was measured using a simulated tumor board formed by three physicians with extensive prostate cancer experience deciding on management with and without knowledge of PET/CT results. At median PSA 2.27 (interquartile rage [IQR] 5.27], 82% of 18F-DCFPyL PET/CT demonstrated at least one site of disease: non-regional lymph nodes (37% of scans), regional lymph node metastases (28%), local recurrence (27%), and bone metastases (20%), with higher PET positivity at higher PSA. Compared to 18F-DCFPyL PET/CT, CI showed overall poor performance, with accuracy below 20% for all extent of disease. PET/CT changed management in 44% of cases. The most frequent scenario was a radical change from initiating androgen deprivation therapy (ADT) to stereotactic body radiotherapy (SBRT) of oligo-lesional disease. In univariate and multivariate analysis, no patient characteristic could predict change of management by PET/CT results. 18F-DCFPyL significantly outperforms CI in recurring prostate cancer and is likely to impact management.

The effect of vitamin D supplementation on the progression of benign prostatic hyperplasia: A randomized controlled trial

Inflammation and proliferation are the cause of benign prostatic hyperplasia (BPH) and are the key components of its mechanism of action. In this study we sought to determine the role of 25-hydroxyvitamin D in BPH, because of its anti-inflammatory activities, and its effect on prostate volume and BPH symptoms. This randomized clinical trial (RCT) was conducted on 108 participants >50 years of age who had either asymptomatic or mild BPH symptoms according to the International Prostate Symptom Score (IPSS) questionnaire. Patients were randomly divided into two groups, intervention and control. The intervention group received 50000 units of vitamin D3 and the control group received a placebo every two weeks for six months. Prostate ultrasound, routine clinical examinations, toucher rectal (TR), and laboratory tests were performed for all patients. After six months, the patients underwent another ultrasound evaluation, measurement of prostate-specific antigen (PSA) levels and completed the IPSS. Results of the evaluations before and after the intervention were compared between the groups using the chi-square, t-test, and logistic regression analysis. Repeated measure analysis was used to evaluate the effect of vitamin D intervention on the changes in the IPSS score. The mean age of the participants was 56±9 years. In the control group, the mean prostate volume was higher compared to the intervention group (p<0.001). The control group had a higher mean PSA level than the intervention group (p<0.001). Although the IPSS score decreased over time in both groups, analysis of variance showed that the amount of change or decrease in IPSS score in the intervention group was significantly more than the control group (p<0.001). The results of our study support the effect of vitamin D in reducing prostate volume and PSA levels, and in improving BPH symptoms. Further studies are needed to confirm these findings to verify the use of vitamin D as a treatment for BPH.

Addition of docetaxel or abiraterone to androgen deprivation therapy in metastatic hormone-sensitive prostate cancer in Indian population.

The addition of docetaxel or abiraterone to androgen deprivation therapy (ADT) achieves superior survival outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) in predominantly Western population. We sought to evaluate the treatment outcomes of adding docetaxel or abiraterone to ADT in Indian population. We reviewed the medical records of ninety patients with newly diagnosed mHSPC who received treatment between January 2015 and June 2018. Patients received ADT alone or ADT + docetaxel or ADT + abiraterone as initial treatment. Monthly clinical evaluation and prostate-specific antigen (PSA) measurement were done. Outcome measures analyzed included PSA decline <90%, serological complete response (sCR) (PSA < 0.2 ng/ml), and progression to CRPC. Outcome variable was compared using Fisher's exact test. Patients received ADT alone (n = 37) or ADT + docetaxel (n = 31) or ADT + abiraterone (n = 22). The median age was 67.5 years (range, 41-87 years) and the median PSA was 88.5 ng/ml (range, 1.12-4000). PSA decline <90% was seen in 22 (73%), 24 (86%), and 17 (94%) patients in the ADT alone, ADT + docetaxel, and ADT + abiraterone groups. sCR was achieved in 5 (17%), 10 (36%), and 9 (50%) patients in the ADT alone, ADT + docetaxel, and ADT + abiraterone groups. Progression to CRPC was observed in 18 (60%), 11 (39%), and 2 (11%) patients in the ADT alone, ADT + docetaxel, and ADT + abiraterone groups. The addition of docetaxel or abiraterone to ADT achieves a deeper serological response and reduces progression to CRPC compared to ADT alone in mHSPC patients of Indian origin. Longer follow-up is required to comment on overall survival and also to determine which combination (ADT + docetaxel or ADT + abiraterone) is superior to others, if at all.

Prostate artery embolization has long term efficacy for treatment of severe lower urinary tract symptoms from giant prostatic hyperplasia

BackgroundPatients with severe lower urinary tract symptoms (LUTS) from giant prostatic hyperplasia (GPH): prostate volume greater than 200 mL that do not respond to medical therapy may not be eligible for surgical treatments due to morbidities, technical challenges, and patient preference. This retrospective investigation examined the long-term efficacy and safety of prostatic arterial embolization (PAE) as a treatment option for severe LUTS due to GPH in a large patient cohort.MethodsOf 529 patients who underwent PAE between January 2016 and January 2020, 72 patients had severe LUTS from GPH and were retrospectively evaluated. PAE was performed with two embolic agents in sequence: 100–250 μm particles followed by 2 mm and 3 mm coils. Clinical assessment was performed with international prostate symptoms score (IPSS), quality of life (QoL), peak flow rate (Qmax), post-void residual volume (PVR), and prostate specific antigen (PSA) measurements before and 12 months and 24 months after PAE. Prostate volume (PV) was measured by multiparametric magnetic resonance (MR) imaging before and 12 months and 24 months after PAE.ResultsPatients with severe LUTS from GPH experienced significant clinical improvements in IPSS, QoL, Qmax, PVR, PSA, and PV at 12 months and 24 months after PAE. Mean IPSS decreased from 26.5 to 18.0 (P < 0.01) to 10.5 (P < 0.01). Mean QoL decreased from 6.0 to 4.0 (P < 0.01) to 2.0 (P < 0.01). Mean Qmax increased from 8.0 to 14 mL/s (P < 0.01) to 18 mL/s (P < 0.01). Mean PVR decreased from 198.0 to 152.0 mL (P < 0.01) to 90 mL (P < 0.01). Mean PV decreased from 303.0 mL to 258.0 mL (P < 0.01) to 209.0 mL (P < 0.01). Mean PSA decreased from 11.2 ng/mL to 9.5 ng/mL (P < 0.05) to 7.9 ng/mL (P < 0.05). No major complications occurred.ConclusionsPAE is a safe treatment with long term efficacy for severe LUTS from GPH. PAE may be a viable therapeutic option for patients with severe LUTS from GPH whom fail medical therapy and are not candidates for surgical treatments.

Prostate-Specific Antigen Concentrations in Response to Testosterone Treatment of Severely Hypogonadal Men.

ContextClinical guidelines recommend measurement of the serum prostate-specific antigen (PSA) concentration during testosterone treatment of hypogonadal men to determine whether the increase is sufficiently high to warrant urologic referral. Prior studies of the effect of testosterone treatment on PSA concentrations have been conducted in men who were mildly to moderately hypogonadal.ObjectiveThe objective of this work is to determine the PSA response to testosterone treatment of men who are severely hypogonadal.Design and SettingThis retrospective cohort study was conducted at a single academic medical center.ParticipantsEighty-five men participated who were severely hypogonadal as a result hypothalamic-pituitary or testicular disease.Main Outcome MeasureChanges in serum PSA concentrations were measured during testosterone treatment for up to 18 months.ResultsTestosterone treatment increased the median serum testosterone concentration from 36 ng/dL (interquartile range [IQR], 20-91 ng/dL) at baseline to 395 ng/dL (IQR, 266-542 ng/dL) at 6 to 18 months. This treatment resulted in a median increment in PSA above baseline of 0.70 ng/mL (IQR, 0.10-1.85 ng/mL) at 6 to 18 months. Apropos current Endocrine Society clinical guidelines, 31% of the men experienced a PSA increase above baseline greater than 1.4 ng/mL, and 13% reached an absolute PSA concentration of greater than 4.0 ng/mL. Four men were diagnosed with prostate cancer.ConclusionsThe PSA response to testosterone replacement in men who are severely hypogonadal as a result of pituitary or testicular disease is greater than that previously reported in men with mild to moderate hypogonadism. These results suggest the magnitude of the PSA response to testosterone replacement is related to the degree of hypogonadism.

Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART II.

The summary presented herein represents Part II of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with castration-resistant disease. Please refer to Part I for discussion of the management of patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1[Figure: see text] and detailed herein. The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles. This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.

Texture Analysis of F-18 Fluciclovine PET/CT to Predict Biochemically Recurrent Prostate Cancer: Initial Results.

Predicting biochemical recurrence of prostate cancer is imperative for initiating early treatment, which can improve the outcome of cancer treatment. However, because of inter- and intrareader variability in interpretation of F-18 fluciclovine positron emission tomography/computed tomography (PET/CT), it is difficult to reliably discern between necrotic tissue owing to radiation therapy and tumor tissue. Our goal is to develop a computational methodology using Haralick texture analysis that can be used as an adjunct tool to improve and standardize the interpretation of F-18 fluciclovine PET/CT to identify biochemical recurrence of prostate cancer. Four main textural features were chosen by variable selection procedure using least absolute shrinkage and selection operator logistic regression and bootstrapping, and then included as predictors in subsequent logistic ridge regression model for prediction (n = 28). Age at prostatectomy, prostate-specific antigen (PSA) level before the PET/CT imaging, and number of days between the prostate-specific antigen measurement and PET/CT imaging were also included in the prediction model. The overfitting-corrected area under the curve and Brier score of the proposed model were 0.94 (95% CI: 0.81, 1.00) and 0.12 (95% CI: 0.03, 0.23), respectively. Compared with a model with textural features (TI model) and that with only clinical information (CI model), the proposed model achieved 2% and 32% increase in AUC and 8% and 48% reduction in Brier score, respectively. Combining Haralick textural features based on the PET/CT imaging data with clinical information shows a high potential of enhanced prediction of the biochemical recurrence of prostate cancer.