The latest medical research on Prostate Cancer

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about prostate cancer gathered by our medical AI research bot.

The selection below is filtered by medical specialty. Registered users get access to the Plexa Intelligent Filtering System that personalises your dashboard to display only content that is relevant to you.

Want more personalised results?

Request Access

Impact of Decipher Biopsy testing on clinical outcomes in localized prostate cancer in a prospective statewide collaborative.

Prostate Cancer and Prostatic Diseases

Decipher Biopsy is a commercially available gene expression classifier used in risk stratification of newly diagnosed prostate cancer (PCa). Currently, there are no prospective data evaluating its clinical utility. We seek to assess the clinical utility of Decipher Biopsy in localized PCa patients.

A multi-institutional study of 855 men who underwent Decipher Biopsy testing between February 2015 and October 2019. All patients were tracked through the prospective Michigan Urological Surgery Improvement Collaborative and linked to the Decipher Genomics Resource Information Database (GRID®; NCT02609269). Patient matching was performed by an independent third-party (ArborMetrix Inc.) using two or more unique identifiers. Cumulative incidence curves for time to treatment (TTT) and time to failure (TTF) were constructed using Kaplan-Meier estimates. Multivariable Cox proportional hazard models were used to evaluate the independent association of high-risk Decipher scores with the conversion from AS to radical therapy and treatment failure (biochemical failure or receipt of salvage therapy).

In a prospective statewide registry, high-risk Decipher Biopsy score was strongly and independently associated with conversion from AS to definitive treatment and treatment failure. These real-world data support the clinical utility of Decipher Biopsy. An ongoing phase 3 randomized trial (NCT04396808) will provide level 1 evidence of the clinical impact of Decipher biopsy testing.

Rezūm for retention-retrospective review of water vaporization therapy in the management of urinary retention in men with benign prostatic hyperplasia.

Prostate

Rezūm vapor ablation is a minimally invasive treatment for benign prostatic hyperplasia (BPH) that uses injections of sterile water vapor directly into the prostate for tissue ablation. Although Rezūm is currently indicated for use in men with prostate sizes ≥30 and ≤80 ml, it is unclear how effective Rezūm is for men in urinary retention. We sought to determine whether Rezūm is effective in the treatment of catheter-dependent urinary retention secondary to BPH.

A retrospective chart review was conducted on consecutive patients who presented for urinary retention and subsequently treated with Rezūm. We evaluated procedural details and examined variables pre- and post-Rezūm (at 6 months) including International Prostate Symptom Score (IPSS), IPSS quality of life (IPSS-QOL), maximum flow (Qmax ), post void residual volume (PVR), prostate specific antigen, rate of retention, and use of alpha blockers and 5-alpha reductase inhibitor (5ARI).

Of the 49 patients included in this study, median age of was 73 years, median prostate volume was 73cc (Interquartile range [IQR]: 50, 103) and a median lobe was present in 80% of patients. All patients were in urinary retention before treatment with a median PVR of 900 ml (IQR: 566, 1146). Following Rezum, IPSS (17 pre-Rezūm, 4 post-Rezūm) and IPSS-QOL (4 pre-Rezūm, 1 post-Rezūm) both improved at 6 months (p < 0.01). Qmax increased from 3 to 6 ml/s (p = 0.03) and PVR decreased from 900 to 78 ml (p < 0.01). Only 17/38 patients taking alpha-blockers and 7/15 patients on 5ARIs continued therapy at 6 months following Rezūm (p < 0.01). Of the 49 patients treated, 10 (20.4%) remained in catheter dependent urinary retention following the procedure, and 6 remained in retention at 6 months (12.2%) even after further surgical therapies for BPH (p < 0.01).

Rezūm is a safe and effective therapy for treating catheter dependent urinary retention in patients with BPH, including those with median lobes. As a minimally invasive therapy, it is a promising option in patient, particularly those who are not suitable for prolonged anesthesia.

Natural history of an immediately detectable PSA following radical prostatectomy in a contemporary cohort.

Prostate

A detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) is an unfavorable prognostic factor. However, not all men with a detectable PSA experience recurrence. We describe the natural history and outcomes in men with a detectable PSA following RP in a contemporary cohort.

A retrospective analysis of men who underwent RP for non-metastatic prostate cancer at the University of California, San Francisco from 2000 to 2020 was performed. A detectable PSA was defined as PSA ≥ 0.03 ng/ml within 6 months of RP. Cox regression models tested the effect of detectable PSA on the development of metastasis, prostate cancer-specific mortality, and overall survival.

We identified 2941 men who had RP with 408 (13.9%) with a detectable PSA within the first 6 months. The median follow-up was 4.42 years (interquartile range [IQR], 2.58-8.00). In total, 296 (72.5%) men with a detectable PSA had salvage treatment at a median of 6 months (IQR, 4-11). One hundred sixteen of these men had PSA failure after salvage treatment at a median of 2.0 years (IQR, 0.7-3.8). On multivariable Cox regression, the risk of development of metastasis (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.09; p = .01), prostate cancer-specific mortality (HR, 1.13; 95% CI, 1.05-1.21; p = .0005), and overall mortality (HR, 1.07; 95% CI, 1.03-1.12; p = .002) was associated with PSA velocity after salvage treatment in men with a detectable PSA.

Men with a detectable PSA after RP may have excellent long-term outcomes. PSA velocity after salvage treatment may be an important predictor for the development of metastasis, prostate cancer-specific mortality, and overall mortality.

The prostaglandin pathway is activated in patients who fail medical therapy for benign prostatic hyperplasia with lower urinary tract symptoms.

Prostate

Little is known about how benign prostatic hyperplasia (BPH) develops and why patients respond differently to medical therapy designed to reduce lower urinary tract symptoms (LUTS). The Medical Therapy of Prostatic Symptoms (MTOPS) trial randomized men with symptoms of BPH and followed response to medical therapy for up to 6 years. Treatment with a 5α-reductase inhibitor (5ARI) or an alpha-adrenergic receptor antagonist (α-blocker) reduced the risk of clinical progression, while men treated with combination therapy showed a 66% decrease in risk of progressive disease. However, medical therapies for BPH/LUTS are not effective in many patients. The reasons for nonresponse or loss of therapeutic response in the remaining patients over time are unknown. A better understanding of why patients fail to respond to medical therapy may have a major impact on developing new approaches for the medical treatment of BPH/LUTS. Prostaglandins (PG) act on G-protein-coupled receptors (GPCRs), where PGE2 and PGF2 elicit smooth muscle contraction. Therefore, we measured PG levels in the prostate tissue of BPH/LUTS patients to assess the possibility that this signaling pathway might explain the failure of medical therapy in BPH/LUTS patients.

Surgical BPH (S-BPH) was defined as benign prostatic tissue collected from the transition zone (TZ) of patients who failed medical therapy and underwent surgical intervention to relieve LUTS. Control tissue was termed Incidental BPH (I-BPH). I-BPH was TZ obtained from men undergoing radical prostatectomy for low-volume, low-grade prostatic adenocarcinoma (PCa, Gleason score ≤ 7) confined to the peripheral zone. All TZ tissue was confirmed to be cancer-free. S-BPH patients divided into four subgroups: patients on α-blockers alone, 5ARI alone, combination therapy (α-blockers plus 5ARI), or no medical therapy (none) before surgical resection. I-BPH tissue was subgrouped by prior therapy (either on α-blockers or without prior medical therapy before prostatectomy). We measured prostatic tissue levels of prostaglandins (PGF2α , PGI2 , PGE2 , PGD2 , and TxA2 ), quantitative polymerase chain reaction levels of mRNAs encoding enzymes within the PG synthesis pathway, cellular distribution of COX1 (PTGS1) and COX2 (PTGS2), and tested the ability of PGs to contract bladder smooth muscle in an in vitro assay.

All PGs were significantly elevated in TZ tissues from S-BPH patients (n = 36) compared to I-BPH patients (n = 15), regardless of the treatment subgroups. In S-BPH versus I-BPH, mRNA for PG synthetic enzymes COX1 and COX2 were significantly elevated. In addition, mRNA for enzymes that convert the precursor PGH2 to metabolite PGs were variable: PTGIS (which generates PGI2 ) and PTGDS (PGD2 ) were significantly elevated; nonsignificant increases were observed for PTGES (PGE2 ), AKR1C3 (PGF2α ), and TBxAS1 (TxA2 ). Within the I-BPH group, men responding to α-blockers for symptoms of BPH but requiring prostatectomy for PCa did not show elevated levels of COX1, COX2, or PGs. By immunohistochemistry, COX1 was predominantly observed in the prostatic stroma while COX2 was present in scattered luminal cells of isolated prostatic glands in S-BPH. PGE2 and PGF2α induced contraction of bladder smooth muscle in an in vitro assay. Furthermore, using the smooth muscle assay, we demonstrated that α-blockers that inhibit alpha-adrenergic receptors do not appear to inhibit PG stimulation of GPCRs in bladder muscle. Only patients who required surgery to relieve BPH/LUTS symptoms showed significantly increased tissue levels of PGs and the PG synthetic enzymes.

Treatment of BPH/LUTS by inhibition of alpha-adrenergic receptors with pharmaceutical α-blockers or inhibiting androgenesis with 5ARI may fail because of elevated paracrine signaling by prostatic PGs that can cause smooth muscle contraction. In contrast to patients who fail medical therapy for BPH/LUTS, control I-BPH patients do not show the same evidence of elevated PG pathway signaling. Elevation of the PG pathway may explain, in part, why the risk of clinical progression in the MTOPS study was only reduced by 34% with α-blocker treatment.

Enhancement of prostate cancer diagnosis by machine learning techniques: an algorithm development and validation study.

Prostate Cancer

To investigate the value of machine learning(ML) in enhancing prostate cancer(PCa) diagnosis.

Consecutive systematic prostate biopsies performed from Jan 2003-June 2017 were used as the training cohort, and prospective biopsies performed from July 2017-November 2019 were used as validation cohort. Men were included if PSA was 0.4-50 ng/mL, and information of digital rectal examination (DRE), Transrectal ultrasound(TRUS) prostate volume, TRUS abnormality were known. Clinically significant PCa(csPCa) was defined as Gleason 3 + 4 or above cancers. Area-under-curve (AUC) of receiver-operating characteristics (ROC) was compared between PSA, PSA density, European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (ERSPC-RC), and various ML techniques using PSA, DRE and TRUS information. ML techniques used included XGBoost, LightGBM, Catboost, Support vector machine (SVM), Logistic regression (LR), and Random Forest (RF), where cost sensitive learning was applied.

Training and validation cohorts included 3881 and 778 consecutive men, respectively. RF model performed better than other ML techniques and PSA, PSA density and ERSPC-RC for prediction of PCa or csPCa in the validation cohort. In csPCa prediction, AUC of PSA, PSA density, ERSPC-RC and RF was 0.71, 0.80, 0.83 and 0.88 respectively. At 90-95% sensitivity for csPCa, RF model achieved a negative predictive value (NPV) of 97.5-98.0% and avoided 38.3-52.2% unnecessary biopsies. Decision curve analyses (DCA) showed RF model provided net clinical benefit over PSA, PSA density and ERSPC-RC.

By using the same clinical parameters, ML techniques performed better than ERSPC-RC or PSA density in csPCa predictions, and could avoid up to 50% unnecessary biopsies.

Comprehensive analysis of complications after transperineal prostate biopsy without antibiotic prophylaxis: results of a multicenter trial with 30 days' follow-up.

Prostate Cancer

To investigate infectious and non-infectious complications after transperineal prostate biopsy (TPB) without antibiotic prophylaxis in a multicenter cohort. Secondly, to identify whether increasing the number of cores was predictive for the occurrence of complications. Thirdly, to examine the relation between TPB and erectile dysfunction.

We analyzed a retrospective multicenter cohort of 550 patients from three different urological centers undergoing TPB without antibiotic prophylaxis. The median number of cores was 26. Demographic and clinical data were extracted by reviewing patients' electronic medical records and follow-up data such as postoperative complications obtained by structured phone interviews. To investigate the influence of the number of cores taken on the occurrence of complications, we performed univariate and multivariate mixed effects logistic regression models.

There was no case of sepsis reported. Overall, 6.0% of patients (33/550) presented with any complication besides mild macrohematuria. In all, 46/47 (98%) complications were ≤Grade 2 according to Clavien-Dindo. In multivariate regression analyses, an increased number of cores was associated with overall complications (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.02-1.14, P = 0.01) and specifically bleeding complications (OR 1.28, 95% CI 1.11-1.50, P = 0.01) but not with infectious complications (OR 1.03, 95% CI 0.97-1.10, P = 0.67). A total of 14.4% of patients referred impairment of erectile function after TPB. Of note, 98% of these men were diagnosed with prostate cancer.

This is the first multicenter trial to investigate complications after TPB without antibiotic prophylaxis. In our study, we found no case of sepsis. This underlines the safety advantage of TPB even without antibiotic prophylaxis and supports the ongoing initiative to abandon TRB of the prostate. A higher number of cores were associated with an increase in overall complications specifically bleeding complications, but not with infectious complications. Post-biopsy erectile dysfunction was mainly present in patients diagnosed with PCa.

The microbiome and prostate cancer.

Prostate Cancer

There is growing evidence that the microbiome is involved in development and treatment of many human diseases, including prostate cancer. There are...

Safety and preliminary immunogenicity of JNJ-64041809, a live-attenuated, double-deleted Listeria monocytogenes-based immunotherapy, in metastatic castration-resistant prostate cancer.

Prostate Cancer and Prostatic Diseases

The safety and immunogenicity of JNJ-64041809 (JNJ-809), a live-attenuated, double-deleted Listeria monocytogenes (LADD Lm)-based immunotherapy targeting 4 relevant prostate cancer antigens, was evaluated in a phase 1 study in patients with metastatic castration-resistant prostate cancer (mCRPC).

Men with progressive mCRPC who had received ≥2 prior approved therapies were enrolled. Primary study objectives were to determine the recommended phase 2 dose (RP2D) and to evaluate the safety and immunogenicity of JNJ-809.

A total of 26 patients received JNJ-809 (1 × 108 CFU (n = 6); 1 × 109 CFU (n = 20)). No dose-limiting toxicities were reported, and 1 × 109 CFU was selected as the RP2D. The most common adverse events (AEs) reported were chills (92%), pyrexia (81%), and fatigue (62%). The most frequent grade ≥3 AEs were lymphopenia (27%) and hypertension (23%). Serious AEs were reported in 27% of patients including 1 patient with grade 3 intestinal obstruction. JNJ-809 transiently induced peripheral cytokines, including interferon-γ, interleukin-10, and tumor necrosis factor-α. Of the 7 patients evaluable for T cell responses at the 1 × 109 CFU dose, evidence of post-treatment antigenic responses were observed in 6 to the Listeria antigen listeriolysin O and in 5 to ≥1 of the 4 encoded tumor antigens. Best overall response was stable disease in 13/25 response-evaluable patients. The study was terminated early as data collected were considered sufficient to evaluate safety and immunogenicity.

JNJ-809 has manageable safety consistent with other LADD Lm-based therapies. Limited antigen-specific immune responses were observed, which did not translate into objective clinical responses.

Genetic polymorphisms at 19q13.33 are associated with [-2]proPSA (p2PSA) levels and provide additional predictive value to prostate health index for prostate cancer.

Prostate

Prostate health index (phi), a derivative of [-2]proPSA (p2PSA), has shown better accuracy than prostate-specific antigen (PSA) in prostate cancer (PCa) detection. The present study was to investigate whether previously identified PSA-associated single nucleotide polymorphisms (SNPs) influence p2PSA or phi levels and lead to potential clinical utility.

We conducted an observational prospective study with 2268 consecutive patients who underwent prostate biopsy in three tertiary medical centers from August 2013 to March 2019. Genotyping data of the 46 candidate genes with a ± 100 kb window were tested for association with p2PSA and phi levels using linear regression. Multivariable logistic regression models were performed and internally validated using repeated tenfold cross-validation. We further calculated personalized phi cutoff values based on the significant genotypes. Discriminative performance was assessed using decision curve analysis and net reclassification improvement (NRI) index.

We detected 11 significant variants at 19q13.33 which were p2PSA-associated independent of PCa. The most significant SNP, rs198978 in KLK2 (Pcombined  = 5.73 × 10-9 ), was also associated with phi values (Pcombined  = 3.20 × 10-6 ). Compared to the two commonly used phi cutoffs of 27.0 and 36.0, the personalized phi cutoffs had a significant NRI for PCa ranged from 5.23% to 9.70% among men carrying variant types (all p < .01).

Rs198978, is independently associated with p2PSA values, and can improve the diagnostic ability of phi for PCa using personalized cutoff values.

Development and validation of a predictive model for determining clinically significant prostate cancer in men with negative magnetic resonance imaging after transrectal ultrasound-guided prostate biopsy.

Prostate

The interpretation of negative magnetic resonance imaging (MRI) screening results for clinically significant prostate cancer (csPCa) (International Society of Urological Pathology grade ≥group 2) is debatable and poses a clinical dilemma for urologists. No nomograms have been developed to predict csPCa in such populations. In this study, we aimed to develop and validate a model for predicting the probability of csPCa in men with negative MRI (PI-RADS score 1-2) results after transrectal ultrasound-guided systematic prostate biopsy.

The development cohort consisted of 728 patients with negative MRI results who underwent subsequent prostate biopsy at our center between January 1, 2014 and December 31, 2017. The patients' clinicopathologic data were recorded. The Lasso regression was used for data dimension reduction and feature selection, then multivariable binary logistic regression was used to build a predictive model with regression coefficients. The model was validated in an independent cohort of 334 consecutive patients from January 1, 2018 and June 30, 2020. The performance of the predictive model was assessed with respect to discrimination, calibration, and decision curve analysis.

The predictors incorporated in this model included age, history of previous negative prostate biopsy, prostate specific antigen density (PSAD), and lower urinary tract symptoms, with PSAD being the strongest predictor. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.816-0.933) and good calibration (unreliability test, p = .540). Decision curve analysis demonstrated that the model was clinically useful.

This study presents a good nomogram that can aid pre-biopsy risk stratification for the detection of csPCa, and that may help inform biopsy decisions in patients with negative MRI results.

Chemotherapy with atezolizumab for small cell or neuroendocrine carcinoma of the prostate: A single institution experience.

Prostate

Chemotherapy in combination with immunotherapy has a proven survival benefit compared to chemotherapy alone in extensive stage small cell lung cancer (SCLC) and is the new standard of care. Since extrapulmonary small cell carcinomas (SCCs) are less common, treatment paradigms are reasonably extrapolated from SCLC regimens. We examined our institution's experience utilizing the combination of chemotherapy and immunotherapy (as used in SCLC) for SCC and neuroendocrine carcinoma of the prostate.

Utilizing an institutional database search tool, we queried the electronic medical record to identify patients with SCC or neuroendocrine carcinoma of the prostate who had been treated with atezolizumab and chemotherapy. We recorded patient characteristics, including age, pathology, and disease extent. Treatment characteristics included number of prior treatments, use of concominant androgen deprivation, number of cycles of immunotherapy, and prior systemic therapies (including those for adenocarcinoma of the prostate). Progression free survival (PFS) and overall survival (OS) were the primary outcomes.

We identified seven men who received atezolizumab for metastatic prostate cancer with a small cell or neuroendocrine component. In six of the seven patients, the combination of carboplatin, etoposide, and atezolizumab was the first-line of treatment after diagnosis of small cell or neuroendocrine carcinoma. Two of the seven patients had de novo small cell/neuroendocrine pathology, while the other five had transformation from a preexisting adenocarcinoma. In the patients who received chemotherapy plus immunotherapy in the first-line setting, at a median follow-up of 6.5 months (range: 1.5-15.1) the median PFS was 3.4 months and median OS was 8.4 months.

Small cell or neuroendocrine carcinoma of the prostate was associated with poor survival outcomes despite adding immunotherapy (atezolizumab) to chemotherapy (carboplatin and etoposide). To our knowledge, there has been no demonstrable benefit of adding immunotherapy to chemotherapy in this setting.

Real-world evidence with The Rezūm System: A retrospective study and comparative analysis on the efficacy and safety of 12 month outcomes across a broad range of prostate volumes.

Prostate

To provide 12-month unbiased outcomes with The Rezūm System (Rezūm), a convective water vapor thermal therapy for patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Results from this retrospective, real-world evidence (RWE) study were compared to those of previous studies with the aim to evaluate the device's safety and efficacy in a real-world patient population.

Patients 45 years or older with an International Prostate Symptom Score (IPSS) score ≥8, prostate volume (PV) between 20cc and 120cc, who were 12 months posttreatment, and had at least one follow-up were included. Patients were broken into groups based on baseline PV; 30-80cc, <30cc, and >80cc. IPSS, PV, quality of life (QoL), maximum urinary flow rate (Qmax), adverse events (AE), postvoid residual, prostate-specific antigen, BPH medication usage, and International Index of Erectile Function were collected and analyzed at baseline, 1, 3, 6, and/or 12 months.

A total of 179 patients were included in a retrospective study. IPSS, QoL, and Qmax significantly improved at follow-up time points (p < .05). There were no significant differences at 12 months in IPSS and QoL point reduction or Qmax improvement between the previous studies and any of the RWE groups. BPH medication reduction was seen at 3 months and remained durable up to 12 months. When compared to previous studies, the RWE study had similar rates of urinary retention, urinary tract infection, and dysuria but significantly higher rates of hematuria for the 30-80cc (71.7%), <30cc (58.8%), and >80cc (80.0%) groups (p < .001).

The RWE study shows rapid and durable relief in LUTS, consistent with that observed in literature. Although Rezūm had a reasonably acceptable AEs profile, patients should be counseled preoperatively for AEs. As a first line therapy, Rezūm is an attractive option for men with BPH irrespective of their prostate size.