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UNLABELLED: The global uptake of prostate cancer (PCa) active surveillance (AS) is steadily increasing. While prostate-specific antigen density (PSAD) is an important baseline predictor of PCa progression on AS, there is a scarcity of recommendations on its use in follow-up. In particular, the best way of measuring PSAD is unclear. One approach would be to use the baseline gland volume (BGV) as a denominator in all calculations throughout AS (nonadaptive PSAD, PSADNA), while another would be to remeasure gland volume at each new magnetic resonance imaging scan (adaptive PSAD, PSADA). In addition, little is known about the predictive value of serial PSAD in comparison to PSA. We applied a long short-term memory recurrent neural network to an AS cohort of 332 patients and found that serial PSADNA significantly outperformed both PSADA and PSA for follow-up prediction of PCa progression because of its high sensitivity. Importantly, while PSADNA was superior in patients with smaller glands (BGV ≤55 ml), serial PSA was better in men with larger prostates of >55 ml. PATIENT SUMMARY: Repeat measurements of prostate-specific antigen (PSA) and PSA density (PSAD) are the mainstay of active surveillance in prostate cancer. Our study suggests that in patients with a prostate gland of 55 ml or smaller, PSAD measurements are a better predictor of tumour progression, whereas men with a larger gland may benefit more from PSA monitoring.

Low-value testing and treatment contribute to billions of dollars in waste to the United States health care system annually. High frequency, low-cost testing, including prostate-specific antigen (PSA) testing, is a major contributor to this inefficient health care delivery. Despite decreasing mortality of prostate cancer over the last few decades, the reputation of prostate specific antigen (PSA) for prostate cancer screening has fluctuated over the last decade due to lack of clarity of the benefits of screening and high risk for overtreatment. The value of PSA could be improved by efficient implementation of smarter testing strategies that reduce the harms and increase the benefits.

INTRODUCTION: Clinically significant prostate cancer (csCaP) with Gleason ≥3 + 4 is found in 10% negative prebiopsy multiparametric (mp) MRI cases and varies widely for equivocal mpMRI cases. The objective of this study was to investigate long-term outcomes of patients with negative and equivocal mpMRIs and to develop a predictive score for csCaP risk stratification in this group. PATIENTS AND METHODS: Patients who underwent an upfront mpMRI between May 2015 and March 2018 with an MRI score Likert 1 to 3 were included in the study. Patients had either a CaP diagnosis at MRI-targeted biopsy or were not diagnosed and attended follow-up in the community. Outcomes were analysed through the Kaplan-Meier estimator and Cox Model. Regression coefficients of significant variables were used to develop a Risk of significant Cancer of the Prostate score (RosCaP). RESULTS: At first assessment 281/469 patients had mpMRI only and 188/469 mpMRI and biopsy, 26 csCaP were found at biopsy, including 10/26 in Likert 3 patients. 12/371 patients discharged without CaP after first assessment were diagnosed with csCaP during a median of 34.2 months' follow-up, 11/12 diagnosis occurred in patients omitting initial biopsy. csCaP diagnosis-free survival was 95.7% in the MRI group and 99.1% in the biopsy group. From these outcomes, a continuous RosCaP score was developed: RosCaP = 0.083 x Age - 0.202 x (1/PSA Density) + 0.786 (if Likert 3), and 4 risk classes were proposed. Limitations include retrospective design and absence of external validation. CONCLUSION: Age, PSA Density and MRI Likert score were significantly associated to the risk of csCaP and utilised to devise the novel RosCap predictive score focused to support risk assessment in patients with negative or equivocal mpMRI results.

There is a widespread belief that outcomes of cancer patients treated within clinical trials might not be representative of the outcomes obtained within standard clinical settings. We sought to investigate the effect of trial participation on biochemical recurrence (BCR) in localised, D'Amico intermediate- and high-risk prostate cancer patients treated with external beam radiotherapy (EBRT).We relied on a study population treated with EBRT between January 2001 and January 2021 at a single tertiary care centre, stratified according to trial enrolment. Separate Kaplan-Meier and multivariable Cox regression models tested BCR-free survival at 60 months within intermediate- and high-risk EBRT patients, after adjustment for covariables. Additionally, the analyses were refitted after inverse probability treatment weighting was performed separately for both risk subgroups.Of 932 eligible patients, 635 (68%) and 297 (32%) had intermediate- and high-risk prostate cancer, respectively. Overall, 53% of patients were trial participants. BCR rates were 11 versus 5% (P = 0.27) and 12 versus 14% (P = 0.08) in trial participants versus non-participants for intermediate- and high-risk subgroups, respectively. Differences in patient and clinical characteristics were recorded. Trial participation status failed to reach predictor status in multivariable Cox regression models for BCR in both intermediate-risk (hazard ratio 1.34; 95% confidence interval 0.71-2.49; P = 0.4) and high-risk patients (hazard ratio 1.03; 95% confidence interval 0.45-2.34; P = 0.9). Virtually the same results were recorded in inverse probability treatment weighting cohorts.Relying on a large cohort of EBRT-treated intermediate- and high-risk patients, no BCR differences were recorded between trial participants and non-participants after accounting for confounders.

Metastatic castration-resistant prostate cancer; Olaparib; Pembrolizumab Cáncer de próstata metastásico resistente a la castración; Olaparib; Pembrolizumab Càncer de pròstata metastàtic resistent a la castració; Olaparib; Pembrolizumab Background Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC). Objective To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC. Design, setting, and participants Cohort A of the phase 1b/2 KEYNOTE-365 study enrolled patients with molecularly unselected, docetaxel-pretreated mCRPC whose disease progressed within 6 mo of screening. Intervention Pembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily. Outcome measurements and statistical analysis The primary endpoints were safety, confirmed prostate-specific antigen (PSA) response rate, and objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by blinded independent central review. The secondary endpoints included radiographic progression-free survival (rPFS) and overall survival (OS). Results and limitations Of 104 enrolled patients, 102 were treated. The median age was 70 yr (interquartile range [IQR], 65–76), and 59 patients (58%) had measurable disease as per RECIST v1.1. The median time from the first dose to database cutoff was 24 mo (IQR, 22–47). The confirmed PSA response rate was 15%. The confirmed ORR was 8.5% (five partial responses) for patients with measurable disease. The median rPFS was 4.5 mo (95% confidence interval [CI], 4.0–6.5) and median OS was 14 mo (95% CI, 10.4–18.2). Clinical activity was consistent across the programmed death ligand 1 (PD-L1)-positive and homologous recombination repair mutation subgroups. Treatment-related adverse events (TRAEs) occurred in 93 patients (91%). Grade 3–5 TRAEs occurred in 49 patients (48%). Six deaths (5.9%) were due to adverse events; two (myocardial infarction and unknown cause) were attributed to treatment. Limitations of the study include the single-arm design. Conclusions Pembrolizumab plus olaparib had a safety profile consistent with the profiles of the individual agents and demonstrated antitumor activity in previously treated patients with molecularly unselected, docetaxel-pretreated mCRPC.

Approximately 0.4-1.3% of the worldwide population is transgender. Although the exact prevalence is unknown, there is an increase in open identification as transgender. Among transgender women (TW), the prostate is retained even after gender-affirmation surgery, thus necessitating ongoing screening for prostate cancer (CaP). However, little is known about CaP screening in this population.To assess our current understanding of CaP incidence and prostate-specific antigen (PSA) screening in TW.We performed a nonsystematic narrative review of all PubMed publications through June 2022 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Given the limited primary research on this subject, case reports were also included. Studies were reviewed to understand PSA screening practices and reports of CaP in this population, as applicable.There is no consensus regarding PSA screening in TW from any of the major societies, and TW are largely absent from guidelines. Case report data suggest that TW with CaP may have more aggressive disease, and these cancers may have been pre-existing prior to present before gender-affirming hormone therapy (GAHT) or be castrate-resistant.We are in the infancy of our understanding of PSA screening in TW. Important avenues for future research include understanding the risks/benefits of PSA screening in TW, how best to mitigate potential negative psychological effects of PSA screening in TW, establishing baseline PSA values for those on GAHT (and determining what values should be considered "elevated"), establishing when to initiate PSA screening for those on GAHT, and establishing the accuracy of biomarkers for those undergoing GAHT.We examined patterns of prostate cancer screening for transgender women. Little is known about prostate cancer incidence or screening in this population. Additional research is needed to establish guidelines for screening in this population.

To characterize patterns of failure using prostate-specific membrane antigen positron emission tomography (PSMA PET) after radical prostatectomy (RP) and salvage radiotherapy (SRT).Patients with rising PSA post-RP+SRT underwentWe included 133 men who received SRT a median of 20 months post-RP; 56% received SRT to the prostatic fossa alone, while 44% received pelvic SRT. PSMA PET/CT was performed a median of 48 months post-SRT. Overall, 31% of PSMA PET/CT scans were negative, 2% equivocal and 67% had at least 1 positive site. Scan detection was significantly associated with PSA level prior to PSMA PET/CT. Analysis of 89 positive scans demonstrated pelvic nodal (53%) was the most common relapse and fossa relapse was low (9%). Overall, positive scans were pelvic (n = 35, 26%), extra-pelvic nodal (n = 26, 20%) or distant non-nodal failure (n = 28, 21%), and 70% of positive scans were oligorecurrent. We observed similar cumulative incidence for all failure categories and relatively few clinicodemographic associations. Men treated with pelvic SRT had reduced odds of pelvic failure versus exclusive fossa treatment.Pelvic, extra-pelvic nodal, and distant non-nodal failures occur with similar incidence post-SRT. Regional nodal relapse is relatively common, especially with fossa-only SRT. A high oligorecurrence rate suggests a potentially important role for PSMA-guided focal therapies.

Febrile urinary tract infections (fUTI) in men are frequently complicated with subclinical prostatic involvement, measured by a transient increase in serum prostate-specific-antigen (sPSA). The aim of this study was to evaluate recurrence rates in a 6-month follow-up period of 2-week versus 4-week antibiotic treatment in men with fUTI, based on prostatic involvement. Clinical and microbiological cure rates at the end-of-therapy (EoT) were also assessed.Open label, not-controlled, prospective study. Consecutive men diagnosed of fUTI were included. Duration of therapy was 2 weeks for patients with a sPSA level5mg/L (short duration therapy, SDT) or 4 weeks for PSA5 mg/L (long duration therapy, LDT).Ninety-one patients were included; 19 (20%) received SDT. Median age was 56.9 years (range 23-88). Bacteremia was present in 9.8% of patients (Escherichia coli was isolated in 91%). Both groups had similar demographic, clinical characteristics and laboratory findings. Median PSA levels were 2.3 mg/L in the SDT group vs 23.4 mg/L in the LDT group. In the 6-month visit, 26% of patients had achieved complete follow-up. Nonsignificant differences between groups were found neither in recurrence rates after 6 months (9% in SDT vs 10% in LDT) nor in clinical or microbiological cure rates at EoT (100% in SDT vs 95% in LDT and 95% in SDT vs 93% in LDT respectively).One fifth of men with fUTI did not present apparent prostatic involvement. A 2-week regimen seems adequate in terms of clinical, microbiological cure and recurrence rates for those patients without PSA elevation.

To determine the proportion of patients who would have been eligible for focal therapy (FT) in a population of patients who underwent prostatectomies; additionally, to assess the risk of having underestimated disease on the surgical specimen by using consensus selection criteria.We retrospectively analyzed data from 446 patients who underwent radical prostatectomy between 2016 and 2018. Patients suitable for FT had unifocal significant prostate cancer on MRI, as well as on pathological data from targeted and systematic biopsies. Inclusion criteria were defined by the 2014 consensus conference, PSA15ng/mL, tumor stage T1c-T2a and Gleason score 3+3 or 3+4 on biopsies. Disease was considered to be underestimated on postoperative data in the presence of extraprostatic invasion, a high Gleason score (≥4+4) and significant multifocality defined by secondary foci of Gleason 6 (3+3)5mm or Gleason 7 (3+4).In our cohort of 446 patients, 97 patients met the inclusion criteria, and 27 patients (27.8%) were eligible for focal therapy. Among the eligible patients, 4 patients (14.8%) had pT3, and no patient had significant multifocality or a Gleason score of 8 (4+4) on the surgical specimen.In the era of pre-biopsy MRI, there could be a significant proportion of patients who could benefit from focal therapy among patients currently undergoing radical prostatectomy. The 2014 consensus conference eligibility criteria could effectively predict the presence of extraprostatic invasion and safely select patients for FT.

Investigate the intermediate-term oncological outcome after negative multiparametric MRI (mpMRI) of the prostate in patients without biopsy proven prostate cancer (PCa).The retrospective study included 121 patients with negative mpMRI (Prostate Imaging Reporting and Data System version 2.1 category3) performed at our institution between 2012 and 2017 without known biopsy proven PCa. Clinical and pathological data were collated including post-MRI prostatic tissue diagnoses with highest Grade Group and most recent prostate specific antigen (PSA) levels up to any definitive prostate cancer treatment. Mean PSA velocities between patients with and without a subsequent diagnosis of Grade Group 2 or higher (GG2+) PCa were compared, and an optimal threshold value was calculated.Outcome data available included PSA values in 117 patients and prostate tissue sampling in 52 patients. Over a median follow up interval of 49.8 months, only 11 of 121 patients (9.1%) were diagnosed with GG2+ PCa, 10 patients (8.3%) with GG1 PCa, and 31 patients (25.6%) had negative prostate tissue samples. Mean PSA velocity was significantly higher in the patients diagnosed with GG2+ PCa (3.87 ng/mL/year) compared to those not diagnosed with GG2+ PCa (-0.71 ng/mL/year, p 0.001). A threshold PSA velocity of 0.27 ng/mL/year had a 100% sensitivity and 69.8% specificity for GG2+ PCa (AUC: 0.898).10% of patients with negative mpMRI without prior biopsy proven PCa were diagnosed with GG2+ PCa over median follow up of over four years and were associated with PSA velocity of ≥0.27 ng/mL/year. PSA monitoring may be a reasonable management strategy in patients with a negative mpMRI without biopsy proven PCa.

Background Enzalutamide is an important drug in the treatment of prostate cancer. Standard dosing often requires dose reduction because of side effects. There is no information on survival outcomes with lower doses. We investigated the impact of starting enzalutamide at ≤ 50% dose on metastatic prostate cancer outcomes including patients' longevity. Patients and Methods Records of metastatic prostate cancer patients treated with enzalutamide at one center were retrospectively reviewed. Low-dose enzalutamide (≤80 mg/day) was compared with standard-dose (160 mg/day). The primary objective was to compute the restricted mean survival time (RMST - time scale) and restricted mean attained age (RMAA - age scale) using the Irwin method. Secondary objectives included overall survival (OS), progression-free survival (PFS), and PSA progression per PCWG3 criteria (PSA PFS). We used the logrank test and the ∆ difference between RMSTs for comparison. Results Of 111 patients treated, 32 received a low-dose and 79 the standard-dose. Low-dose patients had less prior abiraterone or chemotherapy (28.1% vs. 65.8%, P < .001); more testosterone assessment (65.6% vs. 40.5%, P = .016); poorer ECOG performance status (48.3% score ≥2 vs. 26.6%; P = .040), more comorbidities (75.9% vs. 46.3%; P = .010)) including increased cardiovascular disease (51.7% vs. 21.4%, P = .004). Baseline PSA value and doubling time at start of enzalutamide and distribution of metastases were similar between the groups. OS and PFS did not differ between low-dose and standard-dose. Patients on low-dose had a better longevity with significantly longer RMAA, 89.1 years, versus standard-dose RMAA of 83.8 years (∆ = 5.3 years, P = .003, logrank P = .025). In a subgroup analysis by age at start of enzalutamide

Although multiparametric magnetic resonance imaging (MRI) has high sensitivity, its lower specificity leads to a high prevalence of false-positive lesions requiring biopsy.To develop and externally validate a scoring system for MRI-detected Prostate Imaging Reporting and Data System (PIRADS)/Likert ≥3 lesions containing clinically significant prostate cancer (csPCa).The multicentre Rapid Access to Prostate Imaging and Diagnosis (RAPID) pathway included 1189 patients referred to urology due to elevated age-specific prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE); April 27, 2017 to October 25, 2019.Visual-registration or image-fusion targeted and systematic transperineal biopsies for an MRI score of ≥4 or 3 + PSA density ≥0.12 ng/ml/ml.Fourteen variables were used in multivariable logistic regression for Gleason ≥3 + 4 (primary) and Gleason ≥4 + 3, and PROMIS definition 1 (any ≥4 + 3 or ≥6 mm any grade; secondary). Nomograms were created and a decision curve analysis (DCA) was performed. Models with varying complexity were externally validated in 2374 patients from six international cohorts.The five-item Imperial RAPID risk score used age, PSA density, prior negative biopsy, prostate volume, and highest MRI score (corrected c-index for Gleason ≥3 + 4 of 0.82 and 0.80-0.86 externally). Incorporating family history, DRE, and Black ethnicity within the eight-item Imperial RAPID risk score provided similar outcomes. The DCA showed similar superiority of all models, with net benefit differences increasing in higher threshold probabilities. At 20%, 30%, and 40% of predicted Gleason ≥3 + 4 prostate cancer, the RAPID risk score was able to reduce, respectively, 11%, 21%, and 31% of biopsies against 1.8%, 6.2%, and 14% of missed csPCa (or 9.6%, 17%, and 26% of foregone biopsies, respectively).The Imperial RAPID risk score provides a standardised tool for the prediction of csPCa in patients with an MRI-detected PIRADS/Likert ≥3 lesion and can support the decision for prostate biopsy.In this multinational study, we developed a scoring system incorporating clinical and magnetic resonance imaging characteristics to predict which patients have prostate cancer requiring treatment and which patients can safely forego an invasive prostate biopsy. This model was validated in several other countries.

External beam radiation therapy (EBRT) to oligometastases may improve outcomes in patients with oligometastatic hormone-sensitive prostate cancer (oHSPC). Follow-up on this cohort has been limited to5 years and prospective data on de novo patients with oHSPC are lacking. We reviewed the long-term outcomes of patients with oHSPC treated with EBRT and androgen deprivation therapy on a prospective trial.From 2006 to 2011, patients with oHSPC with 1 to 5 metastases received 36 weeks of androgen deprivation therapy (luteinizing hormone-releasing hormone agonist + bicalutamide) and up to 53 Gy to all visible metastases. When indicated, the primary tumor or prostate bed was treated with EBRT up to 78 or 66 Gy, respectively.Twenty-nine patients were treated: 15 de novo, 14 oligorecurrent, and 21 patients (72.4%) had bone metastases. Median number of metastases per patient was 1 (range, 1-5). EBRT was administered to 52 lesions (38 bone, 12 pelvic lymph nodes [LNs], 2 nonpelvic LNs) up to 53 Gy (range, 47-66). Median follow-up was 9.9 years (years; range, 0.2-14.4). Median overall survival was 9.7 years (95% confidence interval [CI], 5.8-not reached). Median progression-free survival was 1.9 years (95% CI, 1.6-2.2). Patients who presented with prostate cancer-defined de novo metastases had significantly improved (P = .04) median progression-free survival (2.0 years; 95% CI, 1.3-6.0) compared with oligorecurrent patients (1.8 years; 95% CI, 1.0-2.0). Patients who presented with LN-only metastases had numerically improved (P = .13) median PFS (5.8 years; 95% CI, 1.2-not reached) compared with patients with bony metastases (1.8 years; 95% CI, 1.3-2.0). At last follow-up, 17 patients (58.6%) had local control of all EBRT-treated metastases. The metastases that locally progressed had previously been controlled for median 3.5 years (range, 1.7-10.5).Our results compare favorably with other reported studies of patients with oHSPC and provide new insights into their long-term outcomes.

Pretreatment classification tools are used in prostate cancer to inform patient management. The effect of cribriform pattern 4 (CC) and intraductal carcinoma (IDC) on such nomograms is still underexplored. We analyzed the Cancer of Prostate Risk Assessment (CAPRA) and National Comprehensive Cancer Network (NCCN) risk scores in cases with and without CC/IDC to assess impact on biochemical recurrence (BCR) and metastases/death of prostate cancer (event free survival-EFS) after prostatectomy. A matched biopsy- prostatectomy cohort (2010-2017) was reviewed for CC/IDC. CAPRA and NCCN scores were calculated. CAPRA score 0-2 were deemed "low", 3-5 "intermediate" and 6-10 "high". NCCN scores 1-2 "very low/low", 3 "favorable intermediate", 4 "unfavorable intermediate", 5-6 "high/very high". Cases were stratified by presence of CC/IDC. BCR and EFS probabilities were estimated using the Kaplan-Meier method. Prognostic performance was evaluated using log-rank tests and Harrell's concordance index. 612 patients with mean age 63.1 years were included with mean follow up of 5.3 (range 0-10.8) years. CC/IDC was noted in 159/612 (26%) biopsies. There were 101 (17%) BCR and 36 (6%) events. CAPRA discriminated three distinct risk categories for BCR (p 0.001) while only high risk separated significantly for EFS (p 0.001). NCCN distinguished two prognostic groups for BCR (p 0.0001) and three for EFS (p 0.0001). Addition of CC/IDC to CAPRA impacted scores 3-5 for BCR and scores 3-5 and 6-10 for EFS and improved the overall concordance index (BCR: 0.66 vs. 0.71; EFS: 0.74 vs. 0.80). Addition of CC/IDC to NCCN impacted scores 4 and 5-6 and also improved the concordance index for BCR (0.62 vs. 0.68). Regarding EFS, NCCN scores 4 and 5-6 demonstrated markedly different outcomes with the addition of CC/IDC. The CAPRA nomogram allows better outcome stratification than NCCN. Addition of CC/IDC status particularly improves patient stratification for CAPRA scores 3-5, 6-10, and for NCCN scores 4 and 5-6.

European guidelines recommend that well-informed men at elevated risk of having prostate cancer (PCa) should be offered prostate-specific antigen (PSA) testing with risk-stratified follow-up. The Swedish National Board of Health and Welfare recommends against screening for PCa but supports regional implementation of organised prostate cancer testing (OPT).To report the process for designing and implementing OPT programmes.Population-based OPT programmes in two Swedish regions, designed to include men aged between 50 and 74 yr, launched in September 2020 for 50-yr-old men.The number of men invited, the participation rate, and the numbers of magnetic resonance imaging (MRI) scans, urological visits, and biopsies from September 2020 to June 2021 were recorded.Two Swedish regions co-designed an OPT programme with a risk-stratified diagnostic algorithm based on prostate-specific antigen (PSA), PSA density, MRI findings, and age. An automated administrative system was developed on a nationwide web-based platform. Invitation letters and test results are automatically generated and sent out by post. Men with PSA ≥3ng/ml, a suspicious MRI lesion, and/or PSA density ≥0.15 ng/ml/cmWe designed and implemented a framework for OPT with a high grade of automation. The framework and organisational experiences may be of value for others who plan a programme for early detection of PCa.We describe the implementation of an organised testing programme for early detection of prostate cancer in two Swedish regions. This model is the first of its kind and may serve as a template for similar programmes.

Results of this double-blind, phase 2 trial showed patients with metastatic castration-resistant prostate cancer given olaparib plus abiraterone versus placebo plus abiraterone had significantly improved progression-free survival. Here, we present an exploratory analysis of pain and health-related quality of life (HRQOL).This double-blind, randomised, placebo-controlled, phase 2 trial was conducted across 41 urological oncology sites in 11 countries in Europe and North America. Eligible patients were aged 18 years or older, had metastatic castration-resistant prostate cancer, and had previously received docetaxel and up to one additional line of previous chemotherapy. Metastatic castration-resistant prostate cancer was defined as increasing prostate-specific antigen (PSA) concentration or other signs of disease progression despite androgen-deprivation therapy and serum testosterone concentrations at castrate levels (≤50 ng/dL), and with at least one metastatic lesion on bone scan, CT, or MRI. Eligible patients were randomly assigned (1:1) to receive oral olaparib (300 mg twice per day) plus oral abiraterone (1000 mg once a day) and oral prednisone or prednisolone (5 mg twice a day) or placebo plus abiraterone (1000 mg once a day) and prednisone or prednisolone (5 mg twice a day). Randomisation was done without stratification and by use of an interactive voice or web response system. A randomised treatment kit ID number was assigned sequentially to each patient as they became eligible. The primary endpoint (radiographic progression-free survival) has previously been reported. HRQOL was a prespecified exploratory patient-reported outcome. Patients were asked to complete the Brief Pain Inventory-Short Form (BPI-SF), single-item worst bone pain, Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, and EuroQol-5 five-dimension five level (EQ-5D-5L) assessment at baseline, at weeks 4, 8, and 12, then every 12 weeks until treatment discontinuation. Prespecified outcomes were change from baseline in BPI-SF worst pain, single-item worst bone pain and FACT-P Total Outcome Index (TOI) scale scores, time to deterioration in BPI-SF worst pain and worst bone pain, and assessment of the EQ-5D-5L pain and discomfort domain. All analyses were exploratory and done in the full analysis set (all randomly assigned patients, including patients who were randomly assigned but did not subsequently go on to receive study treatment), with the exception of mean baseline and total change from baseline analyses, for which we used the population who had a valid baseline and at least one post-baseline assessment. This trial is registered with Clinicaltrials.gov, NCT01972217, and is no longer recruiting patients.Between Nov 25, 2014, and July 14, 2015, 171 patients were assessed for eligibility. 29 patients were excluded, and 142 were enrolled and randomly assigned to receive olaparib and abiraterone (n=71) or placebo and abiraterone (n=71). Data cutoff was Sept 22, 2017. Median follow-up was 15·9 months (IQR 8·1-25·5) in the olaparib plus abiraterone group and 24·5 months (8·1-27·6) in the placebo plus abiraterone group. Questionnaire compliance was generally high (43-100%). Least-squares mean changes from baseline in BPI-SF worst pain, single-item worst bone pain, and FACT-P TOI remained stable across all visits for patients in both treatment groups. Adjusted mean change in FACT-P TOI from baseline across all visits was -0·10 (95% CI -2·50 to 2·71) in the olaparib plus abiraterone group and -1·20 (-4·15 to 1·74) in the placebo plus abiraterone group (difference 1·30, 95% CI -2·70 to 5·30; p=0·52). Time to deterioration in pain was similar in both groups (BPI-SF worst pain HR 0·90 [95% CI 0·62-1·32], p=0·30; worst bone pain HR 0·85 [0·59-1·22], p=0·18). Improvement rates in the pain and discomfort domain of the EQ-5D-5L were similar in both groups from baseline to week 48, beyond which a higher proportion of patients in the olaparib plus abiraterone arm reported an improvement compared to the placebo plus abiraterone group.In these prespecified exploratory analyses, there was no significant difference in pain or HRQOL when olaparib was added to abiraterone. In this phase 2 trial, a statistically significant radiographic progression-free survival benefit was observed with the olaparib plus abiraterone combination. These results suggest that the improved survival benefits observed when combining olaparib with abiraterone does not result in different HRQOL compared with placebo plus abiraterone. Phase 3 studies are required to validate these results.AstraZeneca and Merck Sharpamp; Dohme, a subsidiary of Merckamp; Co, Rahway, NJ, USA.

18F-Fluciclovine PET is approved for the evaluation of patients with suspected prostate cancer recurrence. 18F-Fluciclovine PET is highly specific for the localization of extraprostatic disease even with negative conventional images and low prostate-specific antigen and has been reported to influence patients' management and improve outcome. With the recent Food and Drug Administration approval of prostate-specific membrane antigen (PSMA) PET, 18F-Fluciclovine is likely to be used as an adjunct modality in patients with suspected occult local recurrence and/or negative PSMA findings.

Background: The widespread use of prostate specific antigen (PSA) caused high rate of overdiagnosis. Overdiagnosis leads to unnecessary definitive treatments of prostate cancer (PCa) with detrimental side effects, such as erectile dysfunction and incontinence. The aim of this study was to evaluate the feasibility of an artificial neural network-based approach to develop a combinatorial model including prostate health index (PHI) and multiparametric magnetic resonance (mpMRI) to recognize clinically significant PCa at initial diagnosis. Methods: To this aim we prospectively enrolled 177 PCa patients who underwent radical prostatectomy and had received PHI tests and mpMRI before surgery. We used artificial neural network to develop models that can identify aggressive PCa efficiently. The model receives as an input PHI plus PI-RADS score. Results: The output of the model is an estimate of the presence of a low or high Gleason score. After training on a dataset of 135 samples and optimization of the variables, the model achieved values of sensitivity as high as 80% and 68% specificity. Conclusions: Our preliminary study suggests that combining mpMRI and PHI may help to better estimate the risk category of PCa at initial diagnosis, allowing a personalized treatment approach. The efficiency of the method can be improved even further by training the model on larger datasets.

Deferred treatment is a growing management strategy for low-risk prostate cancer. However, it is unknown whether this growth is mediated by patient factors. In this study, we sought to evaluate factors associated with deferred treatment in patients with low-risk prostate cancer and shifts in these factors after recent incorporation of active surveillance into national guidelines.We identified 137,915 men diagnosed with low-risk prostate cancer (prostate-specific antigen10 ng/mL, Gleason score ≤6, stage cT1-cT2a) in the National Cancer Database from 2010 to 2017. Multivariate logistic regression models were used to determine factors associated with deferred treatment. Interaction variables were added to determine whether trends in use of deferred treatment over time depend on race, income, education, and insurance status.The use of deferred treatment among men with low-risk prostate cancer increased from 14.7% in 2010-2011 to 46.3% in 2016-2017 (P.001). On multivariate analysis, deferred treatment was associated with older age, more contemporary year of diagnosis, black race, lower income, higher educational attainment, government insurance, being uninsured, treatment at an academic/research facility, and treatment at a facility in New England (each P.05). Incorporation of interaction variables showed that black race, belonging to the two lowest income quartiles, government insurance, and being uninsured became less associated with deferred treatment in recent years.The use of deferred treatment among men with low-risk prostate cancer increased significantly from 2010 to 2017. However, patients who were black, low-income, and not privately insured experienced smaller increases in deferred treatment. Interventions to increase uptake in these groups present opportunities to improve quality of care.

Background The role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging in the initial staging of men with prostate cancer (PCa) has yet to be evaluated adequately. Objective To investigate the concordance of PSMA PET/CT with conventional imaging (CI) with cross-sectional abdominopelvic and/or radionuclide bone imaging in the initial staging of patients with treatment-naive PCa. Design, setting, and participants We performed a post hoc retrospective cohort study of patients enrolled in a prospective single-arm trial ( NCT03368547 ). We included patients with intermediate-risk (IR) and high-risk (HR) PCa who underwent PSMA PET/CT within 6 mo of CI. Patients with any treatment prior to PSMA PET/CT were excluded. Patient- and tumor-specific data, and imaging findings were obtained. Outcome measurements and statistical analysis Our primary outcome measurement was the concordance rate of PSMA PET/CT with CI for the identification of N, M1a, M1b, and M1c disease. Descriptive statistics were used. Results and limitations A total of 168 patients with treatment-naive IR and HR PCa met the inclusion criteria. HR disease accounted for 124/168 (73.8%) patients. The median prostate-specific antigen was 11.4 (6.8–24.6) ng/ml. The rates of nonconcordance between PSMA PET/CT and CI were 34/162 (21.0%), 5/70 (7.1%), 8/92 (8.7%), and 1/71 (1.4%) for N, M1a, M1b, and M1c disease, respectively. PSMA PET/CT assigned a higher stage in 37/168 (22.0%) patients and a lower stage in 12/170 (7.1%) patients. In a subset of 50 patients treated with radical prostatectomy and pelvic lymph node dissection, the prevalence of PSMA PET/CT–positive and that of CI-positive nodal disease were 14% and 4%, and the false negative rates were 30% and 32%, respectively. The principal limitations of this study include the heterogeneity in CI modalities and the 6-mo time frame between CI and PSMA PET. Conclusions PSMA PET/CT imaging may serve as a valuable tool in the initial staging of treatment-naive IR and HR PCa. Patient summary We evaluated how prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) compared with standard imaging (such as computed tomography, bone scan, and prostate magnetic resonance imaging) for initial staging of patients with prostate cancer. Our findings suggest that PSMA PET/CT may detect and rule out more metastatic lesions, which could prove valuable in guiding treatment.

Radium-223 is an alpha-emitting, bone-targeting radiopharmaceutical that confers a survival benefit in patients with confirmed bone-metastatic, castration-resistant prostate cancer with no visceral metastases. We studied real-world use of radium-223 in eligible patients from a tertiary hospital.We retrospectively collected clinical data of patients treated with radium-223 in Tungs' Taichung MetroHarbor Hospital by chart review. Data included biochemical parameters, pain scores, other prostate cancer treatments received and adverse events (AEs).Of 36 patients included in the study, 12 patients received radium-223 as first-line therapy, 11 as second-line treatment and 13 as third-line treatment. Prostate-specific antigen significantly increased from baseline in patients who received radium-223 as third-line treatment and in patients who received radium-223 post-chemotherapy. Pain scores significantly decreased when radium-223 was given as second-line and as third-line treatment. In the patients who were naive to novel anti-hormone (NAH) therapy and chemotherapy, mean alkaline phosphatase level significantly decreased from baseline. The most common AE was anemia, found in 16.7% of patients.Radium-223 had early biochemical benefits, while in the later stages of the disease, it reduced bone pain in this real-world cohort of chemotherapy-naive, NAH-naive patients, and patients with prior therapy, from a tertiary institution in Taiwan.

Disease recurrence is common following prostatectomy in patients with localised prostate cancer with high-risk features. Although androgen deprivation therapy increases the rates of organ-confined disease and negative surgical margins, there is no significant benefit on disease recurrence. Multiple lines of evidence suggest that (Fibroblast Growth Factor/Fibroblast Growth Factor Receptor) FGF/FGFR-signalling is important in supporting prostate epithelial cell survival in hostile conditions, including acute androgen deprivation. Given the recent availability of oral FGFR inhibitors, we investigated whether combination therapy could improve tumour response in the neo-adjuvant setting.We conducted an open label phase II study of the combination of erdafitinib (3 months) and androgen deprivation therapy (4 months) in men with localised prostate cancer with high-risk features prior to prostatectomy using a Simon's 2 stage design. The co-primary endpoints were safety and tolerability and pathological response in the prostatectomy specimen. The effect of treatment on residual tumours was explored by global transcriptional profiling with RNA-sequencing.Nine patients were enrolled in the first stage of the trial. The treatment combination was poorly tolerated. Erdafitinib treatment was discontinued early in six patients, three of whom also required dose interruptions/reductions. Androgen deprivation therapy for 4 months was completed in all patients. The most common adverse events were hyperphosphataemia, taste disturbance, dry mouth and nail changes. No patients achieved a complete pathological response, although patients who tolerated erdafitinib for longer had smaller residual tumours, associated with reduced transcriptional signatures of epithelial cell proliferation.Although there was a possible enhanced anti-tumour effect of androgen deprivation therapy in combination with erdafitnib in treatment naïve prostate cancer, the poor tolerability in this patient population prohibits the use of this combination in this setting.

This study aims to forecast overall and aggressive prostate cancer counts at the local government area (LGA) level over 10 years (2019-2028) in Victoria, Australia, using Victorian Cancer Registry (2001-2018) data.We used the Age-Period-Cohort approach to estimate the annual age-specific incidence in each LGA and used Bayesian spatiotemporal models that account for non-linear temporal trends and area-level risk factors. We evaluated the models' performance by withholding and comparing forecasts with the 2014-2018 data.There were 80,449 prostate cancer cases between 2001 and 2018, with an overall increasing trend. Compared to 2001, prostate cancer incidence increased by 69%, from 3049 to 5167 cases in 2018. Prostate cancer counts are expected to reach 7631 cases in 2028, a further 48% increase. Unexplained area-level spatial variation was substantially reduced after adjusting for the area-level elderly population. Aggressive prostate cancer cases increased by 107% between 2001 and 2018 and are expected to rise by 123% increase in 2028. The proportion of aggressive prostate cancer cases will increase to 31% in 2028 from 20% in 2018. By 2028, overall and aggressive prostate cancer cases are projected to be increasing in 66% and 61% of LGAs.Prostate cancer cases are projected to rise at the state level and most LGAs in the next 10 years, with much steeper increases in aggressive cases. Population growth and an ageing population have primarily contributed to this rise besides prostate-specific antigen testing. These prediction estimates help inform prostate cancer burden and facilitate efficient healthcare delivery.

To assess the association between self-reported alcohol use and prostate cancer (PCa) screening using the U.S.-based Behavioral Risk Factor Surveillance System (BRFSS) survey.A cross-sectional analysis of men aged between 55 and 69 who responded to the PSA screening and alcohol consumption portions of the 2018 BRFSS survey was performed. Alcohol consumption was assessed according with the Centers for Disease Control and Prevention definition of binge and heavy drinking. Rates of PSA screening between binge and non-binge drinkers and among heavy and non-heavy drinkers were compared. A complex weighted multivariable logistic regression model, adjusted for socio-economic covariates and weighted using BRFSS sample weights, was used to test the association between the self-reported alcohol use and the odds of PSA screening.Among 57,774 men eligible for PCa screening, there were 8,276 binge drinkers with an unadjusted PSA screening prevalence of 37% versus 40% in the non-binge drinking group (P = .018). Among 3,836 heavy drinkers, the unadjusted PSA screening prevalence was 34% versus 40% in non-heavy drinkers (P.001). In the multivariable analysis, only heavy drinking status was significantly associated with a lower odds of PSA screening (OR: 0.84, 95% CI: 0.72-0.98, P = .02).Given that alcohol overuse may increase the risk of developing cancer, our finding of lower utilization of PCa screening among heavy drinkers is noteworthy. Efforts to support guideline-concordant cancer screening among heavy drinkers may represent an important strategy to reduce the burden of cancer in these men.

Assess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of Prostate Cancer (PCa) after Radical Prostatectomy (PR) and before Radiation Therapy (RT).A total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into two groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between two groups using T-Student; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables.PCa recurrence (reduction of PSA levels after RT) was 89.8% in the group A and 80.3% in the group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. DWI is the most specific MRI-sequence and DCE the most sensitive. For PSA = 0.5 ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA = 0.9 ng/ml, DCE-AUC increases significantly.mp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of DWI for PSA ≤ 0.5 ng/ml.

Background Focal therapy (FT) for prostate cancer is less invasive than radical treatment but carries a risk of recurrence. Salvage robot-assisted radical prostatectomy (S-RARP) is a possible option after FT failure. Objective To evaluate the impact of FT on functional and oncological outcomes following S-RARP. Design, setting, and participants In a retrospective analysis of data from a prospectively collected institutional database, 53 patients who underwent S-RARP following failure of focal ablation were selected as group I; patients who had whole-gland ablation and external beam therapy were excluded. This group was matched to a control sample (matched at ratios of 1:1, 1:2, 1:3, 1:4) of men who had undergone primary RARP, using age, prostate-specific antigen (PSA), PSA density, body mass index, Sexual Health Inventory for Men score, American Urological Association symptom score, Charlson comorbidity index, prostate weight, preoperative Gleason score (GS), and history of smoking as variables. Surgical procedure S-RARP after FT was performed using a standardized technique developed at our institute with the da Vinci Xi Surgical System. Measurements Oncological and functional outcomes were compared between the S-RARP and primary RARP groups. Results and limitations There was no difference in estimated blood loss (p = 0.8) between the 1:1 matched groups, but operating room time was significantly longer for S-RARP (p = 0.007). The primary RARP group had a higher proportion of patients who underwent a full nerve-sparing procedure. The S-RARP group had higher incidence of positive surgical margins (40% vs 15%; p = 0.008), GS ≥8 (25% vs 15%; p = 0.07), and positive lymph node status (9.4% vs 5.7%; p = 0.02). There was no significant difference in overall complications between the groups. The primary RARP group had a higher incidence of lymphocele drainage after surgery (15% vs 0%; p = 0.006). The main limitation of the study is its retrospective design. Conclusions S-RALP after FT failure is feasible; however, surgery following FT leads to poorer oncological and functional outcomes. Despite the targeted nature of FT, significant nonfocal collateral damage is evident in tissues surrounding the prostate, which in turn translates to poorer functional outcomes after S-RARP. Patient summary We studied the surgical challenges during robot-assisted removal of the prostate after previous focal treatment (FT) for prostate cancer and compared the outcomes to those for robot-assisted prostate removal in patients who had no previous FT. We found that this technique is safe and effective with a limited risk of complications, but poor urinary and sexual functional outcomes.

To investigate specific imaging and patient-related factors associated with a false negative (FN) MRI-targeted prostate fusion biopsies (TBx) of suspicious MRI lesions.Retrospective study of men with PI-RADS 4 or 5 lesions November, 2015-December 2020 with TBx and systematic biopsy (SBx) performed. Only FN and true positive (TP) targeted lesions were included. FN biopsy was defined as a negative TBx with a positive systematic core in the ROI or perilesional sextant. Logistic regression was used to determine the association of patient and imaging-specific factors with the probability of a FN TBx.361 PI-RADS 4 or 5 lesions in 304 patients, including 67 FN (19%) and 294 TP (81%) were included. There was a significant inverse association between lesion size (OR: 0.94, P-value: .02), presence of a suspicious DRE (OR: 0.36, P-value: .02) and PSA density (OR: 0.01, P-value: .004) on the probability of obtaining a FN TBx. There was no association between age, biopsy indication, use of an enema before MRI, prostate size, or discrepant US and MRI segmentation volumes on the probability of a FN TBx.In this cohort, SBx detected 19% of csPCa missed on TBx. Smaller PI-RADS 4/5 lesions, lower PSAD values, and a normal DRE were all associated with an increased probability of a FN TBx.

The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy.A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks.The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores.This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.

Our objective is to assess the long-term results of phytotherapy, focusing on the interval between phytotherapy and pharmacological treatment and the predisposing risk factors to such switch on a 10-year follow-up.The data of patients taking phytotherapy for mild to moderate male lower urinary tract symptoms (LUTS) from January to December 2010 were retrospectively reviewed from a prospectively maintained database. Patients were followed for 10 years through medical visits and telephone consultations.102 patients underwent at least one cycle of phytotherapy for LUTS. Twenty (19.6%) patients resolved their symptoms after one phytotherapy cycle and stopped any treatment, 27 (26.4%) continued phytotherapy, and 52 (51%) switched to alpha-blockers and/or 5a-reductase inhibitors after a median interval of 24 months. The reasons for treatment switch were symptoms (n = 45) or clinical progression (increased residual volume n = 15; urinary retention, n = 5). Patients switching to synthetic drugs had median higher age (60 vs 49), prostate volume (40 vs 26 cc), prostate specific antigen (PSA) (1.9 vs 0.9 ng/ml), residual volume (40 vs 0 cc), and a lower maximum flow rate (Qmax) (12 vs 15 ml/s) at presentation.46% patients with mild to moderate LUTS undergoing phytotherapy will be either free of treatment or still on phytotherapy at 10 years from disease presentation. Older patients with larger prostates, increased residual volume and PSA, should be informed regarding their higher risk of symptomatic or clinical progression: the risk of a treatment switch to alpha-blockers or 5a-reductase inhibitors becomes an actual fact after an average span of 2 years.

To evaluate the outcomes of unfavorable intermediate-risk (UIR) and high-risk (HR) prostate cancer patients treated with combined external beam radiation therapy (EBRT) and low-dose-rate prostate brachytherapy (LDR-PB).A population-based cohort of 568 prostate cancer patients treated with combined EBRT and LDR-PB from 2010 to 2016 was analyzed. All patients received EBRT followed by LDR-PB boost. Outcomes were compared with the results for the brachytherapy arm of the ASCENDE-RT trial.The median followup was 4.5 years. Sixty-nine percent (N = 391) had HR disease. Ninety-four percent of the HR and 57% of UIR were treated with androgen deprivation therapy (ADT) with a median duration of 12 months. The 5-year K-M biochemical progression-free survival (b-PFS), metastasis-free survival (MFS), and overall survival (OS) were 84 ± 2%, 90 ± 2%, and 88 ± 2%, similar to 89 ± 5%, 94 ± 4%, and 92 ± 4% for the ASCENDE-RT LDR-PB arm. The likelihood of achieving a PSA ≤0.2 ng/mL at 4 years was 88%, similar to 86% in the ASCENDE-RT LDR-PB arm. Thirty-three men (5.8%) would have been ineligible for ASCENDE-RT due to high-risk features. The 5-year K-M b-PFS, MFS and OS estimates were 86 ± 2%, 92 ± 1% and 89 ± 2% for the ASCENDE-RT eligible versus 56 ± 10% (p0.001), 73 ± 8% (p0.001), and 77 ± 9% (p = 0.098) for the ineligible patients.In this population-based cohort, combining LDR-PB with pelvic EBRT (+/- ADT) achieves very favorable b-PFS that compares to the LDR-PB arm of the ASCENDE-RT, supporting the generalizability of those results. Men ineligible for ASCENDE-RT, based on prognostic features, have a much higher risk of biochemical recurrence and metastatic relapse.

Magnetic resonance imaging (MRI) misses a proportion of "clinically significant" prostate cancers (csPC) as defined by histopathology criteria. The aim of this study was to analyze whether long-term oncologic outcomes differ between MRI-detectable and MRI-occult csPC.Retrospective analysis of 1449 patients with pre-prostatectomy MRI and csPC on prostatectomy specimens (ie, Grade group ≥2 or extraprostatic spread) between 2001-2006. T2-weighted MRIs were classified according to the Prostate Imaging Reporting and Data System into MRI-occult (categories 1, 2), MRI-equivocal (category 3), and MRI-detectable (categories 4, 5). Cumulative incidence of biochemical recurrence (BCR), metastatic disease, and cancer-specific mortality, estimated with competing risk models. The median follow-up in survivors was 11.0 years (IQR: 8.9-13.1).In 188 (13%) cases, csPC was MRI-occult, 435 (30%) MRIs were equivocal, and 826 (57%) csPC were MRI-detectable. The 15-year cumulative incidence [95% CI] of BCR was 8.3% [2.2, 19.5] for MRI-occult cases, 17.4% [11.1, 24.8] for MRI-equivocal cases, and 43.3% [38.7, 47.8] for MRI-detectable cases (P.001). The cumulative incidences of metastases were 0.61% [0.06, 3.1], 3.5% [1.5, 6.9], and 19.6% [15.4, 24.2] for MRI-occult, MRI-equivocal, and MRI-detectable cases, respectively (P.001). There were no deaths from prostate cancer observed in patients with MRI-occult csPC, compared to an estimated 1.9% [0.54, 4.9], and 7.1 % [4.5, 10.6] for patients with MRI-equivocal and MRI-detectable cancer, respectively (P.001).Oncologic outcomes after prostatectomy for csPC differ between MRI-occult and MRI-detectable lesions. Judging the clinical significance of a negative prostate MRI based on histopathologic surrogates alone might be misleading.Among 1449 patients with pre-prostatectomy MRI and clinically significant prostate cancer on prostatectomy histopathology, MRI-occult cancers (n = 188, 13%) were less likely to recur biochemically (8% vs. 43%, P.001), metastasize (0.6% vs. 20%, P.001), or lead to prostate cancer mortality (0% vs. 7%, P.001) than MRI-detectable cancers (n = 826, 57%). MRI-occult cancers constitute a prognostically distinct subgroup among higher-grade prostate cancers.

Several studies have investigated selection and sequencing of systemic agents to manage recurrent prostate cancer following local definitive treatment.To define the incidence of recurrent prostate cancer in different countries, and systematically review management options and efficacy of first-line systemic therapies for patients with prostate cancer previously treated with definitive radical prostatectomy or radiation therapy.We performed a systematic review of studies published from January 2010 to December 2021 in MEDLINE, EMBASE, or ClinicalTrials.gov according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Quality was assessed using the Grades of Recommendation, Assessment, Development and Evaluation methodology. The potential regional burdens of recurrent prostate cancer were estimated by analyzing various regional registry data.A total of 40 studies met the inclusion criteria and an additional landmark study published after the query was included in this review. Patients with metastatic recurrent disease derive benefit from the addition of androgen receptor signaling inhibitors to androgen deprivation therapy, while docetaxel should be reserved for patients with a high-volume metastatic burden by conventional imaging. Patients with biochemical-only recurrent disease benefit from continuous or intermittent androgen deprivation therapy if they possess high-risk features such as short prostate-specific antigen doubling time or high serum prostate-specific antigen. Current limitations to the published literature include no consideration of contemporary positron emission tomography imaging for evaluating metastatic recurrence or burden and few quality of life assessments.This systematic review summarizes the findings and recommendations for first-line systemic therapy for patients with recurrent prostate cancer following local therapy.We performed a systematic evaluation and summary of all studies published within the past decade on the topic of medications used to treat prostate cancer after it has recurred following radiation therapy or surgery. This review can be used to inform guidelines for prostate cancer management.

Endocrine disruption mechanisms in prostate are an overlooked issue. The anti-androgenic properties of the fungicide vinclozolin (VIN) and its active metabolites - 2-[[(3,5- dichlorophenyl)-carbamoyl]oxy]- 2-methyl-3-butenoic acid (M1) and 3'5'-dichloro-2-hydroxy-2- methylbut-3-enanilide (M2) - were assessed on human prostate-derived cells (LNCaP); the effects were investigated also upon co-treatment with 5α-dihydrotestosterone (DHT), the physiological androgen receptor (AR)-agonist, and compared to the anti-androgenic drugs, 2-hydroxy-flutamide (2OH-FTA) and bicalutamide (BIC). Assessed endpoints were the cellular uptake and subcellular localization of VIN, M1 and M2, DHT-induced PSA gene expression and secretion. VIN, its metabolites, and the reference drugs, significantly reduced DHT-induced PSA secretion and gene expression, M2 showing the strongest downregulation. In absence of DHT, 2OH-FTA and BIC showed a very high (98%) LNCaP uptake with a predominant intranuclear localization (BIC=80%, 2OH-FTA=70%). VIN cellular uptake was 42%: 24.7% made up by M2, mostly localized at nuclear level, differently from VIN and M1. Upon DHT co-treatment, VIN intracellular uptake increased by 28%, especially in the microsomal fraction (MF); M2 also increased mainly in MF but also, to a lower extent, in the intranuclear fraction. Finally, in a 72-hr time-course, the LNCaP uptake of VIN and its metabolites was much faster compared to purified M1 and M2. Overall, M2 resulted the leading compound for VIN endocrine-disrupting effects in LNCaP.

To describe prostate-specific antigen (PSA) response and treatment adherence, overall and stratified by race, for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with apalutamide.Electronic medical records representing 63 urology practices from the United States were used to conduct this study. Patients with ≥2 apalutamide prescription fills and ≥12 months of prior prostate cancer management were identified. Patients were followed from apalutamide initiation until a switch to another antineoplastic treatment, death, or end of data availability (October 4, 2019). PSA response (≥50% decline from baseline PSA) and apalutamide adherence rates are described for the overall nmCRPC population treated and also stratified by race (Black and non-Black cohorts).Overall, 193 patients with nmCRPC were initiated on apalutamide. Thirty-three patients were Black (17.1%), 138 were non-Black (71.5%), and the remaining had an unknown racial background. The mean baseline PSA level for the overall, Black, and non-Black cohorts, was 7.0 ng/mL, 10.5 ng/mL, and 5.6 ng/mL, respectively. At 12 months of follow-up, PSA response was 86.0%, 93.1%, and 85.9% for the overall, Black, and non-Black cohorts, respectively. During a mean follow-up period of 333 days, 352 days, and 326 days, adherence was 93.6%, 90.1%, and 94.5% for the overall, Black and non-Black cohorts, respectively.This real-world study of patients with nmCRPC initiated on apalutamide showed that PSA response was robust and consistent with clinical trial data. Moreover, both Black and non-Black patients demonstrated high treatment adherence.

To assess the correlation between initial tumor apparent diffusion coefficient (ADC) values and clinicopathological parameters in prostate cancer (PCa) patients treated with definitive radiotherapy (RT). Additionally, the prognostic factors for freedom from biochemical failure (FFBF) and progression-free survival (PFS) in this patient cohort were analyzed.The clinical data of 503 patients with biopsy-confirmed PCa were evaluated retrospectively. All patients had clearly evident tumors on diffusion-weighted magnetic resonance imaging (DW-MRI) for ADC values. Univariable and multivariable analyses were used to determine prognostic factors for FFBF and PFS.The median follow-up was 72.9 months. The 5-year FFBF and PFS rates were 93.2% and 86.2%, respectively. Significantly lower ADC values were found in patients with a high PSA level; advanced clinical stage; higher ISUP score, and higher risk group than their counterparts. Receiver operating characteristic (ROC) curve analysis revealed an ADC cut-off value of 0.737 × 10Lower ADC values were found in patients with high-risk characteristics such as a high serum PSA level, stage or grade of tumor, or high-risk disease, implying that ADC values could be used to predict prognosis. Lower ADC values and higher ISUP grades were associated with an increased risk of BF and progression, implying that treatment intensification may be required in these patients.

PURPOSE/OBJECTIVE(S): This study describes the pattern of failure in patients with biochemical (BCR) recurrence after low-dose-rate (LDR) brachytherapy as a component of definitive treatment for prostate cancer. METHODS: Patients with BCR after LDR brachytherapy ± external beam radiation therapy (EBRT) were enrolled on prospective IRB approved advanced imaging protocols. Patients underwent 3T multiparametric MRI (mpMRI); a subset underwent prostate specific membrane antigen (PSMA)-based PET/CT. Pathologic confirmation was obtained unless contraindicated. RESULTS: Between January 2011 and April 2021, 51 patients with BCR after brachytherapy (n = 36) or brachytherapy + EBRT (n = 15) underwent mpMRI and were included in this analysis. Of 38 patients with available dosimetry, only two had D90 < 90%. The prostate and seminal vesicles were a site of failure in 66.7% (n = 34) and 39.2% (n = 20), respectively. PET/CT (n = 32 patients) more often identified lesions pelvic lymph nodes (50%; n = 16) and distant metastases (18.8%; n = 6), than mpMRI. Isolated nodal disease (9.8%; n = 5) and distant metastases (n = 1) without local recurrence were uncommon. Recurrence within the prostate was located in the transition zone in 48.5%, central or midline in 45.5%, and anterior in 36.4% of patients. CONCLUSION: In this cohort of patients with BCR after LDR brachytherapy ± EBRT, the predominant recurrence pattern was local (prostate ± seminal vesicles) with frequent occurrence in the anterior prostate and transition zone. mpMRI and PSMA PET/CT provided complementary information to localize sites of recurrence, with PSMA PET/CT often confirming mpMRI findings and identifying occult nodal or distant metastases. Published by Elsevier Inc. on behalf of American Brachytherapy Society.

To investigate the frequency of prostate-specific antigen (PSA) testing in men receiving testosterone replacement therapy (TT) and with a history of prostate cancer (PCa).We queried the TriNetX network database, a global health research network consisting of 65 million men in 44 large healthcare organizations, to investigate rates of PSA testing in 4 cohorts of men aged 55-69 with a history of PCa diagnosis and/or a prescription for any route or formulation of testosterone. We further stratified each cohort to evaluate PSA testing in men with previously treated (CPT 55,840, 55,866, 77,778, 77,385) or untreated PCa. All cohorts' PSA testing rates were compared against the "no PCa or TT" cohort by Chi-square test.A total of 4,525,259 men, aged 55-69, were included in our study. Following stratification into cohorts based on PCa or TT history, we found that 14.2% (P.0001) of men without PCa or TT underwent PSA testing following an initial ambulatory visit. Among men without PCa who received TT, 33.6% (P.0001) underwent testing. Unfortunately, only 53.2% (P.0001) and 61.0% (P.0001) of men receiving TT with previously untreated and treated PCa, respectively, had PSA testing.In contrast to current guidelines, a large proportion of men receiving TT and with a history of PCa did not undergo PSA testing. Further studies are necessary to better characterize reasons why PSA testing rates are low even in this high-risk cohort.

Aims: We conducted a pooled analysis of four randomised controlled trials and a non-trial retrospective dataset to study the changes in serum prostate-specific antigen (PSA) concentrations during treatment and its impact on survival in men treated with docetaxel for metastatic castration-resistant prostate cancer. We also compared the outcomes and pre-treatment prognostic factors between trial and non-trial patients. Materials and methods: Data were obtained from four randomised controlled trials and a non-trial cohort from a tertiary cancer centre. The PSA kinetics covariates chosen were absolute value (PSAT), best percentage change (BPCH) and tumour growth rate (K). The association between the covariates collected and overall survival was assessed within a Cox proportional hazards model. How well a covariate captured the difference between trial and non-trial patients was assessed by reporting on models with or without trial status as a covariate. Results: We reviewed individual datasets of 2282 patients. The median overall survival for trial patients was 20.4 (95% confidence interval 19.6–22.2) months and for the non-trial cohort was 12.4 (10.7–14.7) months (P < 0.001). Of the pre-treatment factors, we found that only lactate dehydrogenase fully captured the difference in prognosis between the trial and non-trial cohorts. All PSA kinetic metrics appeared to be prognostic in both the trial and non-trial patients. However, the effect size was reduced in non-trial versus trial patients (interaction P < 0.001). Of the time-dependent covariates, we found that BPCH best captured the difference between trial and non-trial patient prognosis. Conclusions: The analysis presented here highlights how data from open-source trial databases can be combined with emerging clinical practice databases to assess differences between trial versus non-trial patients for particular treatments. These results highlight the importance of developing prognostic models using both pre-treatment and time-dependent biomarkers of new treatments.

Context Prostate-specific membrane antigen (PSMA) positron emission tomography/magnetic resonance imaging (PET/MRI) is a novel imaging technique with several potential applications in the prostate cancer (PCa) setting. Objective To perform a systematic review of the current evidence regarding the diagnostic performance of PSMA PET/MRI in patients with primary and recurrent PCa. Evidence acquisition A comprehensive bibliographic search on the MEDLINE and Cochrane Library databases was performed in October 2020. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Studies were deemed eligible if they assessed patients with primary or recurrent PCa (P) undergoing PSMA PET/MRI (I) with or without comparison with other imaging techniques (C) in order to evaluate its diagnostic performance (O). Retrospective and prospective primary clinical studies were included. Results of previous meta-analyses were reported. Evidence synthesis A total of 23 original articles and three meta-analyses were included. Limited evidence on PSMA PET/MRI is available, especially in the setting of partial gland ablation. PET/MRI can be an effective imaging modality for detecting primary PCa, showing higher accuracy than multiparametric MRI alone. It provides accurate local staging of primary PCa; however, there are contradictory results in this context when its performance is compared with other imaging techniques. PET/MRI also shows high performance for restaging and detecting tumor recurrence, even at low prostate-specific antigen levels. Conclusions PSMA PET/MRI could represent a valuable tool in the management of patients with primary and recurrent PCa. No specific recommendations can be provided. Patient summary Encouraging data regarding the benefits of prostate-specific membrane antigen positron emission tomography/magnetic resonance imaging in patients with prostate cancer are emerging from the literature.

Treatment options for men with metastatic castration-resistant prostate cancer are rapidly changing. In addition to novel anti-androgens and taxane-based chemotherapy, radiopharmaceuticals are having an increasing role. Although calcium-mimetic theranostics have been in use for years, newer approaches use molecularly targeted radiation therapy by conjugating isotopes to prostate-specific membrane antigen (PSMA) and in so doing directly target prostate cancer cells

A number of genomic classifiers are available to aid in shared decision-making for men with localized prostate cancer; however, there is no high-level evidence assessing their clinical utility. The two randomized controlled trials in this report prospectively evaluate the use of gene expression classifier testing at the time of cancer diagnosis and after surgical treatment.

The management of local relapse after prostate cancer radiotherapy is frequently based on androgen deprivation therapy. The aim of the study was to report Gustave Roussy's experience with salvage prostate brachytherapy.All cases of localized prostate cancer presenting in an irradiated area who received salvage high dose rate (HDR) brachytherapy from 2013 to 2020 were retrospectively reviewed.A total of 64 patients were included. Median follow up was 30.5 months. Median initial EBRT dose was 70 Gy [Q1-Q3: 70 - 74]. Median PSA at brachytherapy was 6.8 ng/mL [Q1-Q3: 4.4 - 8.7] with a median interval between first and salvage irradiation of 10 years [Q1-Q3: 6.9 - 12.6]. The modality of the first irradiation was an exclusive EBRT in 73% of the cases, mostly with a 3D technique (82%). Dose prescription was two fractions of 12 Gy or 13 Gy associated with androgen deprivation therapy for 63% of the patients. About 23% of the patients were castrate-resistant. Disease free survival at 2 years was 58% in the whole population and 66% in hormone sensitive patients. The only factors associated with disease free survival on multivariate analysis was a high-risk disease at initial diagnosis (HR = 3.59, IC95 [1.75; 7.39], p = 0.0005). Grade 3 urinary and rectal toxicities occurred in 1.5% and 1.5% of the patients, respectively.HDR salvage brachytherapy seems to be a safe option for patients presenting with an isolated local relapse of prostate cancer.

This study compared the currently used swab Prionics ForensiX Evidence Collection Kit with the alternatives Prionics ForensiX Evidence Collection Tube SafeDry and Sarstedt Forensic Swab XL. Volunteers provided intravaginal swabs collected with all swab types at specific time points after unprotected sexual intercourse. Quantifiable DNA, detectability of seminal fluid component (prostate specific antigen, PSA) and spermatozoa were evaluated to find the best-performing swab type. While Sarstedt XL showed significantly higher DNA quantities for sperm cell fractions than ForensiX Kit, the more concise PSA test results clearly favour ForensiX SafeDry. Reassuringly, mostly complete autosomal STR profiles of male components were obtained for sperm cell fractions at all time points and tested swabs. Switching to the higher performing ForensiX SafeDry with improved sampling and processing properties will also benefit victims, medical personnel, and investigators.

Stockholm3 is a risk model that combines the prostate-specific antigen (PSA) test, other plasma protein biomarkers, single nucleotide polymorphisms, and clinical variables. The STHLM3-MRI study (NCT03377881) found that the Stockholm3 test with magnetic resonance imaging (MRI) and combined targeted and systematic biopsies maintained the sensitivity for clinically significant cancers, and reduced the number of benign biopsies and clinically insignificant cancers.To assess the cost-effectiveness of MRI-based screening for prostate cancer using either Stockholm3 as a reflex test or PSA alone.A cost-utility analysis was performed from a lifetime societal perspective using a microsimulation model for men aged 55-69 yr in Sweden. Test characteristics were estimated from the STHLM3-MRI study.No screening and three quadrennial screening strategies, including either PSA ≥3 ng/ml or Stockholm3 with reflex test thresholds of PSA ≥1.5 or 2 ng/ml as criteria for referral to MRI, were performed, and those who were MRI positive had combined targeted and systematic biopsies.Predictions included the number of tests, cancer incidence and mortality, costs, and quality-adjusted life-years. Uncertainties in key parameters were assessed using sensitivity analyses.Compared with no screening, the screening strategies were predicted to reduce prostate cancer deaths by 7-9% across a lifetime. The use of Stockholm3 with PSA ≥2 ng/ml resulted in a 60% reduction in MRI compared with screening using PSA. This Stockholm3 strategy was cost-effective with a probability of 70% at a cost-effectiveness threshold of €47 218 (500 000 Swedish Kronor). As a potential limitation, the economic perspective was specific to Sweden.Screening with the Stockholm3 test at a reflex threshold of PSA ≥2 ng/ml and MRI was predicted to be cost-effective in Sweden.The Stockholm3 test with image-based screening may reduce screening-related harms and costs, while maintaining the health benefits from early detection of prostate cancer.

To present a recent clinical case of Skene's gland carcinoma and review all published literature of Skene's gland malignancy with associated treatment and outcomes.We review a new case of metastatic Skene's gland adenocarcinoma. We then performed a systematic search of PubMed and Ovid-Medline through December 2021 and retrieved English language articles for review. Peer-reviewed articles were deemed eligible if they included patients with Skene's gland malignancy. Reports were reviewed for pathologic accuracy, patient characteristics, clinical presentation, tumor pathology, treatment and outcome.We reviewed 211 articles and included 15 cases from 1974 to 2022. The median patient age was 71 years (range 46-88). The most common presentation was an asymptomatic periurethral or urethral lesion in five cases (33.3%), followed by hematuria or vaginal bleeding in three patients (20.0%). In eight cases, a prostate-specific antigen was measured and found to be elevated, range 0.8-60.8 ng/mL. Treatment approaches varied and included local excision in eight cases, radical surgical resection in two cases, radiation therapy in two cases, and adjunctive androgen deprivation therapy in one case. Pathology was consistent with adenocarcinoma resembling prostate in all cases. In all cases tested, prostate-specific antigen normalized after definitive therapy of any type. Median follow up was 11.5 months, and there were no cases of recurrence or mortality secondary to Skene's gland adenocarcinoma.There are 15 published cases of a Skene's gland malignancy, all adenocarcinoma resembling prostate. Local excision is most often utilized for treatment, with androgen deprivation therapy emerging as a new treatment consideration.

Objectives To investigate the outcome of retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) compared with conventional RARP in the early learning curve. Methods Consecutive patients with prostate cancer who underwent RS-RARP were included to compare against conventional RARP of the same period. Propensity-score matching was performed based on age, prostate size, nerve-sparing approach, and final pathological risk categories. All patients were re-admitted to undergo trial without Foley catheter from post-operative day 7-10. Clinical follow-up was performed with monitoring of continence (day 0, 3 months, and the latest continence during the study period) and surveillance of PSA level. Results Between July 2017 and August 2019, 24 consecutive patients received RS-RARP in our centre. Propensity score matching was performed with the best matched 24 controls receiving conventional RARP. Overall median follow-up duration was 15.5 months. A majority of the patients belonged to the intermediate-risk group, with most of them harbouring pT2 disease (RS-RARP: 87.5%; conventional RARP: 79.2%). More patients in RS-RARP group achieved day-0 continence (33.3% vs 0%, p = 0.002) and 3-month continence (66.7% vs 12.5%, p = 0.001). During the whole study period, more RS-RARP achieved continence with 0 pad (91.7% vs 66.7%, p = 0.033). The mean months to continence is shorter in RS-RARP group (4.0 months vs 13.6 months, p = 0.002). No statistically significant differences between the two groups with respect to surgical margins, post-operative PSA detection, and the use of adjuvant radiotherapy. Conclusions RS-RARP showed better continence rates when compared to conventional RARP even during the learning curve phase.

Background Determining the efficacy, safety, and prognostic factors affecting overall survival (OS) among metastatic prostate cancer patients undergoing PSMA-targeted radioligand therapy (PRLT). Method In this retrospective study, from November 2016 and December 2019, 43 heavily pretreated (90.7% on 1st line androgen deprivation therapy (ADT), 53.5% on 2nd line ADT, 58.1% on docetaxel) metastatic prostate cancer patients with median age of 71 years (range: 51−88 years) were enrolled. Treatment cycles were repeated every 8 weeks (range: 6–12 weeks). To evaluate the biochemical response after each cycle, prostate specific antigen (PSA) levels were measured and analyzed according to the Prostate Cancer Working Group 3 (PCWG3) criteria cutoffs. Possible adverse events after therapy were retrospectively classified according to the Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0. Kaplan-Meier and multivariable Cox proportional hazard regression analyses were used to identify factors associated with OS. Results A total of 112 cycles of PRLT with a median of 3 cycles (range: 1–6) and median administered activity per cycle of 6.29 GBq (range: 4.45–7.7 GBq) were used. PSA decline was observed in 65.1% of patients, and best PSA decline of ≥50% and ≥90% were achieved in 39.5% and 23.3% of patients, respectively. Major (grade III) anemia and thrombocytopenia occurred in 11.6% and 7% of patients, respectively. Median OS and median PSA progression-free survival were 52 and 20 weeks, respectively. In univariate analysis, baseline hemoglobin 2, baseline PSA ≥ 115 ng/mL, cumulative dose of 177Lu-PSMA Conclusion PRLT with 177Lu-PSMA is well-tolerated and effective in metastatic prostate cancer patients who have no other treatment options available. The novel prognostic markers found in this study (high platelet count, superscan pattern) were associated with poor overall survival.

Patients with metastatic castration-resistant prostate cancer (mCRPC) frequently receive docetaxel after they develop resistance to abiraterone or enzalutamide and need more efficacious treatments.To evaluate the efficacy and safety of pembrolizumab plus docetaxel and prednisone in patients with mCRPC.The trial included patients with mCRPC in the phase 1b/2 KEYNOTE-365 cohort B study who were chemotherapy naïve and who experienced failure of or were intolerant to ≥4 wk of abiraterone or enzalutamide for mCRPC with progressive disease within 6 mo of screening.Pembrolizumab 200 mg intravenously (IV) every 3 wk (Q3W), docetaxel 75 mg/mThe primary endpoints were safety, the prostate-specific antigen (PSA) response rate, and the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included time to PSA progression; the disease control rate (DCR) and duration of response (DOR) according to RECIST v1.1 by BICR; ORR, DCR, DOR, and radiographic progression-free survival (rPFS) according to Prostate Cancer Working Group 3-modified RECIST v1.1 by BICR; and overall survival (OS).Among 104 treated patients, 52 had measurable disease. The median time from allocation to data cutoff (July 9, 2020) was 32.4 mo, during which 101 patients discontinued treatment, 81 (78%) for disease progression. The confirmed PSA response rate was 34% and the confirmed ORR (RECIST v1.1) was 23%. Median rPFS and OS were 8.5 mo and 20.2 mo, respectively. Treatment-related adverse events (TRAEs) occurred in 100 patients (96%). Grade 3-5 TRAEs occurred in 46 patients (44%). Seven AE-related deaths (6.7%) occurred (2 due to treatment-related pneumonitis). Limitations of the study include the single-arm design and small sample size.Pembrolizumab plus docetaxel and prednisone demonstrated antitumor activity in chemotherapy-naïve patients with mCRPC treated with abiraterone or enzalutamide for mCRPC. Safety was consistent with profiles for the individual agents. Further investigation is warranted.We evaluated the efficacy and safety of the anti-PD-1 antibody pembrolizumab combined with the chemotherapy drug docetaxel and the steroid prednisone for patients with metastatic prostate cancer resistant to androgen deprivation therapy , and who never received chemotherapy. The combination showed antitumor activity and manageable safety in this patient population. This trial is registered on ClinicalTrials.gov as NCT02861573.

Men with grade group 2 or 3 prostate cancer are often considered ineligible for active surveillance; some patients with grade group 2 prostate cancer who are managed with active surveillance will have early disease progression requiring radical therapy. This study aimed to investigate whether MRI-guided focused ultrasound focal therapy can safely reduce treatment burden for patients with localised grade group 2 or 3 intermediate-risk prostate cancer.In this single-arm, multicentre, phase 2b study conducted at eight health-care centres in the USA, we recruited men aged 50 years and older with unilateral, MRI-visible, primary, intermediate-risk, previously untreated prostate adenocarcinoma (prostate-specific antigen ≤20 ng/mL, grade group 2 or 3; tumour classification ≤T2) confirmed on combined biopsy (combining MRI-targeted and systematic biopsies). MRI-guided focused ultrasound energy, sequentially titrated to temperatures sufficient for tissue ablation (about 60-70°C), was delivered to the index lesion and a planned margin of 5 mm or more of normal tissue, using real-time magnetic resonance thermometry for intraoperative monitoring. Co-primary outcomes were oncological outcomes (absence of grade group 2 and higher cancer in the treated area at 6-month and 24-month combined biopsy; when 24-month biopsy data were not available and grade group 2 or higher cancer had occurred in the treated area at 6 months, the 6-month biopsy results were included in the final analysis) and safety (adverse events up to 24 months) in all patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT01657942, and is no longer recruiting.Between May 4, 2017, and Dec 21, 2018, we assessed 194 patients for eligibility and treated 101 patients with MRI-guided focused ultrasound. Median age was 63 years (IQR 58-67) and median concentration of prostate-specific antigen was 5·7 ng/mL (IQR 4·2-7·5). Most cancers were grade group 2 (79 [78%] of 101). At 24 months, 78 (88% [95% CI 79-94]) of 89 men had no evidence of grade group 2 or higher prostate cancer in the treated area. No grade 4 or grade 5 treatment-related adverse events were reported, and only one grade 3 adverse event (urinary tract infection) was reported. There were no treatment-related deaths.24-month biopsy outcomes show that MRI-guided focused ultrasound focal therapy is safe and effectively treats grade group 2 or 3 prostate cancer. These results support focal therapy for select patients and its use in comparative trials to determine if a tissue-preserving approach is effective in delaying or eliminating the need for radical whole-gland treatment in the long term.Insightec and the National Cancer Institute.

To assess the effectiveness and safety of HYPO-SRT in patients with biochemical recurrence after radical prostatectomy, we performed a cohort study followed by meta-analysis (MA).A cohort study followed by a MA was designed to evaluate the biochemical relapse-free survival (bRFS) and toxicity rates with HYPO-SRT for patients with a biochemical recurrence after radical prostatectomy. Following the PRISMA and MOOSE guidelines, eligible studies were identified on electronic databases through February 2021. A meta-regression analysis was performed. A p-value0.05 was considered significant.A cohort of 43 patients treated by HYPO-SRT was prospectively evaluated. With a median follow-up of 31 months, at 3 years, the bRFS was 93%. In the cohort study, the incidence of late grade 1, 2, and ≥3 GU and GI toxicities were 33% and 20%, 2% and 4%, and 0% and 0%, respectively. Combining our cohort with 5 studies, a total of 412 patients treated with HYPO-SRT were included in the MA. The 3-year bRFS was 73% (95% CI: 63-83%). The estimation of bRFS at 5 years was 61%. The rate of grade ≥2 late GU and GI toxicity was 6 % (95% CI: 1-12), and 3% (95% CI: 1-5), with no toxicities grade 3-5. In the meta-regression, % residual PSA, % positive margins, % ADT and % ≥ Gleason 8 had a significant association with bRFS (all P 0.05). The late GU toxicity was associated with EQD2GyHYPO-SRT produced satisfactory bRFS with reduced acute/ late GU and GI toxicity rates. The MA analysis supports future studies assessing HYPO SRT.