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.

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Lifestyle and sociodemographic factors associated with treatment choice of clinically localized prostate cancer in an equal access healthcare system.

Prostate Cancer and Prostatic Diseases

Sociodemographic and lifestyle factors may play a role in determining whether patients with clinically localized prostate cancer (PC) are managed w...

Evaluating post radical prostatectomy mechanisms of early continence.

Prostate

To identify the periprostatic structures associated with early return of urinary continence after radical prostatectomy (RP).

We compared total continence results between four different techniques of robot-assisted radical prostatectomy (RARP). Specifically, we studied 1-week and 1-month zero-pad continence rates of anterior (n = 60), posterior (n = 59), a novel hybrid posterior-anterior (n = 12), and transvesical (n = 12) approaches of RARP. Each technique preserved a unique set of periprostatic anatomic structures, thereby, allowing evaluation of the individual impact of preservation of nerves, bladder neck, and space of Retzius with associated anterior support structures on early continence. Urethral length was preserved in all approaches. The space of Retzius was preserved in posterior and transvesical approaches, while the bladder neck was preserved in posterior and hybrid approaches. Nerve sparing was done per preoperative oncological risk. For all patients, 24-h pad usage rates and 24-h pad weights were noted at 1 week and 1 month after catheter removal. Multivariable logistic regression analysis was performed to identify predictors of early continence. Data were obtained from prospective studies conducted between 2015 and 2021.

At 1 week, 15%, 42%, 45%, and 8% of patients undergoing anterior, posterior, hybrid, and transvesical RARP approaches, respectively, were totally continent (p = 0.003). These rates at 1 month were 35%, 66%, 64%, and 25% (p = 0.002), respectively. The transvesical approach, which preserved the space of Retzius but not the bladder neck, was associated with the poorest continence rates, while the posterior and hybrid approaches in which the bladder neck was preserved with or without space of Retzius preservation were associated with quickest urinary continence recovery. Bladder neck preservation was the only significant predictor of 1-week and 1-month total continence recovery in adjusted analysis, Odds ratios 9.06 (p = 0.001) and 5.18 (p = 0.004), respectively.

The beneficial effect of the Retzius-sparing approach on early continence recovery maybe associated with bladder neck preservation rather than space of Retzius preservation.

An update on the current status and future prospects of erectile dysfunction following radical prostatectomy.

Prostate

Radical prostatectomy (RP) and radiation treatment are standard options for localized prostate cancer. Even though nerve-sparing techniques have been increasingly utilized in RP, erectile dysfunction (ED) due to neuropraxia remains a frequent complication. Erectile function recovery rates after RP remain unsatisfactory, and many men still suffer despite the availability of various therapies.

This systematic review aims to summarize the current treatments for post-RP-ED, assess the underlying pathological mechanisms, and emphasize promising therapeutic strategies based on the evidence from basic research.

Evaluation and review of articles on the relevant topic published between 2010 and 2021, which are indexed and listed in the PubMed database.

Phosphodiesterase type 5 inhibitors, intracavernosal and intraurethral injections, vacuum erection devices, pelvic muscle training, and surgical procedures are utilized for penile rehabilitation. Clinical trials evaluating the efficacy of erectogenic drugs in this setting are conflicting and far from being conclusive. The use of androgen deprivation therapy in certain scenarios after RP further exacerbates the already problematic situation and emphasizes the need for effective treatment strategies.

This article is a detailed overview focusing on the pathophysiology and mechanism of the nerve injury developed during RP and a compilation of various strategies to induce cavernous nerve regeneration to improve erectile function (EF). These strategies include stem cell therapy, gene therapy, growth factors, low-intensity extracorporeal shockwave therapy, immunophilins, and various pharmacological approaches that have induced improvements in EF in experimental models of cavernous nerve injury. Many of the mentioned strategies can improve EF following RP if transformed into clinically applicable safe, and effective techniques with reproducible outcomes.

High intratumoral plasma cells content in primary prostate cancer defines a subset of tumors with potential susceptibility to immune-based treatments.

Prostate Cancer and Prostatic Diseases

Data on advanced prostate cancer (PCa) suggest more prior systemic therapies might reduce tumor immune responsiveness. In treatment-naïve primary PCa, recent work correlated intratumoral plasma cell content with enhanced tumor immune-responsiveness. We sought to identify features of localized PCa at a high risk of recurrence following local treatment with high plasma cell content to help focus future immune-based neoadjuvant trials.

We performed retrospective analyses of molecular profiles from three independent cohorts of over 1300 prostate tumors. We used Wilcoxon Rank Sum to compare molecular pathways between tumors with high and low intratumoral plasma cell content and multivariable Cox proportional hazards regression analyses to assess metastasis-free survival.

We validated an expression-based signature for intratumoral plasma cell content in 113 primary prostate tumors with both RNA-expression data and digital image quantification of CD138+ cells (plasma cell marker) based on immunohistochemisty. The signature showed castration-resistant tumors (n = 101) with more prior systemic therapies contained lower plasma cell content. In high-grade primary PCa, tumors with high plasma cell content were associated with increased predicted response to immunotherapy and decreased response to androgen-deprivation therapy. Master regulator analyses identified upregulated transcription factors implicated in immune (e.g. SKAP1, IL-16, and HCLS1), and B-cell activity (e.g. VAV1, SP140, and FLI-1) in plasma cell-high tumors. Master regulators overactivated in tumors with low plasma cell content were associated with shorter metastasis-free survival following radical prostatectomy.

Markers of plasma cell activity might be leveraged to augment clinical trial targeting and selection and better understand the potential for immune-based treatments in patients with PCa at a high risk of recurrence following local treatment.

Real-world use of MRI for risk stratification prior to prostate biopsy.

Prostate Cancer and Prostatic Diseases

The utilization of MRI to risk stratify elevated PSA prior to prostate biopsy has been inconsistently adopted and varies considerably by practice setting. This study aims to evaluate the usage and performance of MRI as an advanced risk stratification tool of elevated PSA prior to biopsy and identify factors associated with differential utilization of MRI at a large academic setting with ready access to 3T multiparametric MRI of the prostate.

A retrospective single-center study of 2900 men presenting with elevated PSA 2-20 ng/mL from 2018 through 2021 was conducted. We analyzed trends in MRI utilization and outcomes of prostate biopsy by MRI usage. Univariate and multivariate logistic regressions were performed to calculate odds ratios to identify patient- and provider-level predictors of MRI usage.

Rates of prebiopsy MRI utilization increased from 56% in 2018 to 89% in 2021 (p < 0.001). Prebiopsy MRI led to biopsy avoidance in 31% of men. MRI usage enhanced detection of clinically significant prostate cancer by 13% and reduced identification of Gleason Grade Group 1 disease by 3% and negative biopsies by 10% (p < 0.001). Men who received MRI were more likely to be younger than 75 years in age and have private or Medicare insurance, PSA >4 ng/mL, and PHI >27. In both univariate and multivariate analysis, black race and Medicaid insurance were associated with reduced MRI utilization (all p < 0.001). Urologic provider was an independent predictor of MRI usage (p < 0.001).

Use of MRI as a risk stratification tool for elevated PSA rose during this 4-year study period. Men who self-identify as black or men with Medicaid coverage have diminished rates of MRI usage. Considerable provider-level variability in MRI use was observed. Future research aimed at identifying factors affecting implementation of MRI as a routine risk assessment tool is warranted.

Clinical annotations for prostate cancer research: Defining data elements, creating a reproducible analytical pipeline, and assessing data quality.

Prostate

Routine clinical data from clinical charts are indispensable for retrospective and prospective observational studies and clinical trials. Their reproducibility is often not assessed. We developed a prostate cancer-specific database for clinical annotations and evaluated data reproducibility.

For men with prostate cancer who had clinical-grade paired tumor-normal sequencing at a comprehensive cancer center, we performed team-based retrospective data collection from the electronic medical record using a defined source hierarchy. We developed an open-source R package for data processing. With blinded repeat annotation by a reference medical oncologist, we assessed data completeness, reproducibility of team-based annotations, and impact of measurement error on bias in survival analyses.

Data elements on demographics, diagnosis and staging, disease state at the time of procuring a genomically characterized sample, and clinical outcomes were piloted and then abstracted for 2261 patients (with 2631 samples). Completeness of data elements was generally high. Comparing to the repeat annotation by a medical oncologist blinded to the database (100 patients/samples), reproducibility of annotations was high; T stage, metastasis date, and presence and date of castration resistance had lower reproducibility. Impact of measurement error on estimates for strong prognostic factors was modest.

With a prostate cancer-specific data dictionary and quality control measures, manual clinical annotations by a multidisciplinary team can be scalable and reproducible. The data dictionary and the R package for reproducible data processing are freely available to increase data quality and efficiency in clinical prostate cancer research.

Orphan receptors in prostate cancer.

Prostate

The identification of new cellular receptors has been increasing rapidly. A receptor is called "orphan" if an endogenous ligand has not been identified yet.

Here we review receptors that contribute to prostate cancer and are considered orphan or partially orphan. This means that the full spectrum of their endogenous ligands remains unknown.

The orphan receptors are divided into two major families. The first group includes G protein-coupled receptors. Most are orphan olfactory receptors. OR51E1 inhibits cell proliferation and induces senescence in prostate cancer. OR51E2 inhibits prostate cancer growth, but promotes invasiveness and metastasis. GPR158, GPR110, and GPCR-X play significant roles in prostate cancer development and progression. However, GPR160 induces cell cycle arrest and apoptosis. The other major subset of orphan receptors are nuclear receptors. Receptor-related orphan receptor α (RORα) inhibits tumor growth, but RORγ stimulates androgen receptor signaling. PXR contributes to metabolic deactivation of androgens and inhibits cell proliferation. TLX has protumorigenic effects in prostate cancer, while its knockdown triggers cellular senescence and growth arrest. Estrogen-related receptor ERRγ can inhibit tumor growth but ERRα is protumorigenic. Dax1 and short heterodimeric partner are also inhibitory in prostate cancer.

There is a "zoo" of relatively underappreciated orphan receptors that play key roles in prostate cancer.

Association between baseline body mass index and survival in men with metastatic hormone-sensitive prostate cancer: ECOG-ACRIN CHAARTED E3805.

Prostate

E3805 (CHAARTED) is a phase 3 trial demonstrating improved survival for men with metastatic hormone-sensitive prostate cancer (mHSPC) randomized to treatment with docetaxel (D) and androgen-deprivation therapy (ADT) versus ADT alone. We assessed the association of baseline body mass index (BMI) and metformin exposure with quality of life (QOL) and prostate cancer outcomes including survival in patients enrolled in the CHAARTED study.

We performed a posthoc exploratory analysis of the CHAARTED trial of men with mHSPC randomized to treatment with ADT with or without D between 2006 and 2012. Cox proportional hazards models and Kruskal-Wallis test were used to evaluate the association between BMI with QOL and prostate cancer outcomes and between metformin exposure and survival.

In 788 of 790 enrolled patients with prospectively recorded baseline BMI and metformin exposure status, lower BMI was not associated with survival, but was associated with high volume disease (p < 0.0001) and poorer baseline QOL on functional assessment of cancer therapy-prostate (p = 0.008). Only 68 patients had prevalent metformin exposure at baseline in the CHAARTED trial. Four groups were identified: ADT + D + metformin (n = 39); ADT + D (n = 357); ADT + metformin (n = 29); and ADT alone (n = 363). Baseline clinicopathologic characteristics were similar between groups. In this small exploratory multivariable analysis, metformin exposure was not associated with survival (hazard ratio: 1.15; 95% confidence interval: 0.81-1.63, p = 0.44).

There was no link between baseline BMI and survival, but lower baseline BMI was associated with features of greater cancer burden and poorer QOL.

Optimized grade group for reporting prostate cancer grade in systematic and MRI-targeted biopsies.

Prostate

To explore an optimized grade group (oGG) criterion from systematic biopsies (SB) and targeted biopsies (TB) and offer a better prediction of radical prostatectomy (RP) grade group (GG).

Positive needles were collected from 146 patients who underwent SB + TB followed by RP. The grade was assigned for two different kinds of biopsies with five GG criteria: (1) global GG (gGG); (2) most common GG (most common GG from SB + TB, mGG); (3) highest GG (highest numerical GG from SB + TB, hGG); (4) largest volume/linear length cancer GG (defined as GG from the SB + TB with the largest length of cancer in a needle, lGG). These biopsy grades were compared (equivalence, upgrade, or downgrade) with the final grade of the RP lesion, using weighted κ coefficients; (5) Then the best agreement of the (2) (3) (4) grading scores from SB or TB was combined to introduce an oGG.

In this study, gGG showed generally poor agreement (47.2%) with RP GG (weighted κ: 0.43). Using the three criteria (mGG, hGG, and lGG) of SB, mGG had the best agreement (55.5%, weighted κ: 0.46), while hGG and lGG had a lower agreement (48.6% and 48.6%, weighted κ: 0.42 and 0.38). Using the three criteria (mGG, hGG and lGG) of TB: lGG had the best agreement (56.8%, weighted κ: 0.43), while mGG and hGG had lower agreement (50.0% and 49.3%, weighted κ: 0.40 and 0.40); Then oGG was generated (higher GG between mGG of SB and lGG of TB) and the agreement of oGG increased to 59.6% and weighted κ was 0.49. Additionally, oGG had a lower upgrade rate than gGG, while the downgrade rate remained unchanged.

oGG showed better agreement with RP GG than gGG. oGG had a lower upgrade rate than gGG, while downgrade rate remained unchanged.

Does previous prostate surgery affect multiparametric magnetic resonance imaging accuracy in detecting clinically significant prostate cancer? Results from a single institution series.

Prostate

Multiparametric MRI (mpMRI) has demonstrated high diagnostic accuracy for clinically significant PCa (csPCa). However, the accuracy of this test in men that received a previous prostatic surgery is still controversial. We aimed at assessing the effect of previous prostatic surgery on the detection of csPCa in a tertiary referral center.

We relied on a cohort of 311 men with a positive mpMRI (prostate imaging - reporting and data system [PI-RADS] ≥ 3) who underwent a targeted (TBx) plus concomitant systematic random biopsy (SBx) at a single tertiary referral center between 2017 and 2020. The study outcome was to compare the detection of csPCa (Gleason score ≥ 3 + 4) between the two groups (no previous prostate surgery [Group 1] vs. previous prostate surgery [Group 2]). Multivariable logistic regression analysis (MVA) was used to assess the relationship between previous prostate surgery and the detection of csPCa at TBx, after taking into account potential clinical confounders.

Overall, 24 (8%) patients received a previous prostate surgery before undergoing mpMRI. Median prostate-specific antigen density was 0.15 versus 0.08 ng/ml/cc, in Group 1 versus 2, respectively. The most frequent finding at mpMRI was in Group 1 versus 2, PI-RADS 4 (55%) versus PI-RADS 3 and 4 (42% each). The majority of patients were biopsy naïve in both Groups 1 (66%) and 2 (71%). The overall detection of csPCa in Group 1 versus 2 was 83% versus 75%, respectively. Differently, the detection of csPCa at TBx in Groups 1 versus 2 was 76% versus 71%, respectively. At MVA, previous prostate surgery (odds ratio: 0.65; p = 0.02) was significantly associated with lower csPCa detection at TBx, after accounting for potential confounders.

The presence of previous prostate surgery significantly decreases the accuracy of mpMRI in detecting csPCa. These results should be taken into account when assessing patients with a history of prostatic surgery and a suspicious lesion at mpMRI, to better select those who might avoid an unnecessary biopsy.

PSA density is complementary to prostate MP-MRI PI-RADS scoring system for risk stratification of clinically significant prostate cancer.

Prostate Cancer and Prostatic Diseases

While prostate multiparametric-magnetic resonance imaging (MP-MRI) has improved the diagnosis of clinically significant prostate cancer (CSPC), the complementary use of prostate-specific antigen (PSA) levels to risk-stratify for CSPC requires further study. The objective of this project was to determine if prostate MP-MRI and PSA can provide complementary insights into CSPC risk stratification.

In an IRB-approved study, pathologic outcomes from patients who underwent MR/US fusion-targeted prostate biopsy were stratified by various parameters including PSA, PSA density (PSAD), age, race, and PI-RADS v2 score. CSPC was defined as a Gleason score ≥7. Logistic regression was used to determine odds ratios (OR) with 95% confidence intervals (CI). P values were reported as two-sided with p < 0.05 considered statistically significant. ROC curves were generated for assessing the predictive value of tests and sensitivity + specificity optimization was performed to determine optimal testing cutoffs.

A total of 327 patients with 709 lesions total were analyzed. PSAD and PI-RADS scores provided complementary predictive value for diagnosis of CSPC (AUC PSAD: 0.67, PI-RADS: 0.72, combined: 0.78, p < 0.001). When controlling for PI-RADS score, age, and race, multivariate analysis showed that PSAD was independently associated with CSPC (OR 1.03 per 0.01 PSAD increase, 95% CI 1.02-105, p < 0.001). The optimal cutoff of PSAD ≥ 0.1 ng/ml/cc shows that a high versus low PSAD was roughly equivalent to an increase in 1 in PI-RADS score for the presence of CSPC (4% of PI-RADS ≤3 PSAD low, 6% of PI-RADS 3 PSAD high vs. 5% of PI-RADS 4 PSAD low, 22% of PI-RADS 4 PSAD high vs. 29% of PI-RADS 5 PSAD low, 46% of PI-RADS 5 PSAD high were found to have CSPC).

PSAD with a cutoff of 0.1 ng/ml/cc appears to be a useful marker that can stratify the risk of CSPC in a complementary manner to prostate MP-MRI.

Effects of green tea on prostate carcinogenesis in rat models and a human prostate cancer xenograft model.

Prostate

There is evidence to suggest that green tea soy may have protective effects against prostate cancer, but there are several epidemiologic and clinical studies that did not identify such an effect. We tested the notion of protective effects in a rat model of prostate carcinogenesis that has been predictive of the effects of selenium and vitamin E in randomized clinical trials and a human prostate cancer xenograft model in nude mice and rat prostate tumor cells transplanted in immune-competent syngeneic animals.

Prostate cancer was induced in rats with methylnitrosourea and testosterone and tumor incidence was determined. Subcutaneous tumor growth was measured resulting from injected cells isolated from rat prostate cancers grafted in syngeneic animals and from the prostate-specific antigen (PSA)-producing human prostate cancer PC346 xenografted in nude mice. Brewed decaffeinated green tea infusion or caffeinated green tea extract and the same 300 mg/ml concentration of caffeine were provided in drinking water of the rats and nude mice.

Caffeinated green tea extract and caffeine provided in drinking water did not modify the induction of prostate cancer in the rat model compared with control rats. The same drinking water treatments also did not affect the growth and PSA production of PC346 human prostate cancer xenografts in nude mice and the growth of two transplantable rat prostate cancer tumor lines in Wistar Firth rats. Brewed green tea infusion as drinking water did also not affect tumor growth in these xeno- and allograft models.

These animal studies with drinking water exposure to green tea and caffeine do not support the idea that green tea is protective against prostate cancer.