Prostate-specific Antigen Measurements Research Articles

Multiplexed Opto-Microfluidic Biosensing: Advanced Platform for Prostate Cancer Detection.

Cancer stands as a prominent global cause of mortality, necessitating early detection to augment survival rates and alleviate economic burdens on healthcare systems. In particular, prostate cancer (PCa), impacting 1.41 million men globally in 2020, accentuates the demand for sensitive and cost-effective detection methods beyond traditional prostate-specific antigen (PSA) testing. While clinical techniques exhibit limitations, biosensors emerge as compact, user-friendly alternatives to traditional laboratory approaches. However, existing biosensors predominantly concentrate on PSA detection, prompting the necessity for advancing toward multiplex sensing platforms. This study introduces a compact opto-microfluidic sensor featuring a substrate of gold nanospikes, fabricated via electrodeposition, for enhanced sensitivity. Embedded within a microfluidic chip, this nanomaterial enables the precise and concurrent measurement of PSA, alongside two complementary PCa biomarkers, matrix metalloproteinase-2 (MMP-2) and anti-α-methylacyl-CoA racemase (anti-AMACR) in diluted human plasma, offering a comprehensive approach to PSA analysis. Taking advantage of the localized surface plasmon resonance principle, this biosensor offers robustness and sensitivity in real sample analysis without the need for labeling agents. With the limit of detection at 0.22, 0.37, and 0.18 ng/mL for PSA, MMP-2, and anti-AMACR, respectively, this biosensing platform holds promise for point-of-care analysis, underscoring its potential impact on medical diagnostics.

Increase of prostate-specific antigen doubling time predicts survival in metastatic castration-resistant prostate cancer patients undergoing radium therapy.

Radium-223 (Ra-223) is an important treatment modality for bone-dominant metastatic castration-resistant prostate cancer (mCRPC). However, there is currently a lack of effective markers to monitor treatment response during treatment. We aim to investigate the response in prostate-specific antigen doubling time (PSADT) as a potential marker for assessing Ra-223 treatment in mCRPC patients. We retrospectively collected data from mCRPC patients who underwent radium treatment at our institution between August 2020 and June 2023. Prostate-specific antigen (PSA) measurements prior to treatment and during treatment were collected. Baseline PSADT was calculated from PSA measurements prior to Ra-223 treatment; interim PSADT was calculated from PSA measurements before Ra-223 treatment and prior to the fourth course injection. Overall survival was calculated from the start of treatment to the date of death. Univariable and multivariable analysis using the Cox proportional hazards model were performed to examine the association of factors with overall survival. We included 35 patients from our institution, with a median overall survival of 13.3months. Eighteen (51.4%) completed all six courses of treatment. PSA dynamic response (interim PSADT > baseline PSADT or decreased PSA) was observed in 20 patients. Overall survival was associated with a PSA dynamic response (HR = 0.318, 95% CI 0.133-0.762, p = 0.010) when compared to patients without response. Dynamic changes in PSADT were associated with survival in mCRPC patients receiving radium therapy. Comparing interim and baseline PSADT could serve as a valuable marker for determining treatment benefits.

Association of Pre-Treatment Serum Testosterone Levels with Prostate Cancer: A Prospective Study

Introduction: It has been widely accepted that prostate cancer (PCa) growth is related to serum testosterone (ST). A direct correlation between pre-treatment ST level and PCa growth and progression has been reported. However, recent studies have shown that pre-treatment ST levels have a negative correlation with PCa. Thus, the literature is, at best, conflicting. In this study, we examined the pre-treatment serum total testosterone (ST) levels in PCa. Methods: In this prospective observational study, suspected cases of PCa underwent digital rectal examination, routine blood investigation, Prostate-Specific Antigen (PSA) measurement, and prostate biopsy. Diagnosed cases of PCa without any risk factors affecting testosterone levels were included. Their pre-treatment total ST levels were measured. All patients underwent staging evaluation with either Magnetic Resonance Imaging (MRI) & Bone scan or Ga-68 Prostate Specific Membrane Antigen Positron Emission Tomography (PSMA PET). ST levels were also measured in patients with Benign Prostatic Hyperplasia (BPH) and compared with those in PCa patients. ST levels were also assessed according to Gleason Score (GS) and clinical stage in PCa. Results: 110 cases and 54 patients with BPH were included in the study. The median ST level in PCa patients was significantly lower as compared to BPH patients [352.28 ng/dL (Interquartile Range (IQR) 224.99-563.17) vs. 448.29 ng/dL (IQR 400.97-596.42) (p =0.004)]. The median ST level in metastatic PCa was significantly lower than the localized PCa group [298.20 ng/dL vs. 452.30 ng/dL (p=0.0001)]. Moreover, the median ST level was also significantly lower in patients with Gleason Score ≥ 8 than those with Gleason Score ≤ 7 [285.92 ng/dL (149.97-560.40) vs. 425.13 ng/dL (320.43-571.46) (p=0.002)]. Conclusion: This study shows lower ST levels in patients with PCa compared to patients with BPH, thus supporting a potential association as described in previous studies. ST levels may have prognostic value since a low pre-treatment ST level is associated with a higher clinical stage and aggressive PCa.

Does ejaculation have an effect on urinary flow rates?

The primary objective of this investigation is to explore the impact of ejaculation on urinary flow rates in men experiencing lower urinary tract symptoms. This study involved the enrollment of 55 male patients who presented with lower urinary tract symptoms. An assessment encompassed components, including medical history, questionnaires related to sexual activity and lower urinary tract symptoms, bladder diary, physical examination, urinalysis, urine culture, ultrasound examination and measurements of serum prostate-specific antigen, free flow uroflowmetry, and post-void residual urine volume. All participants were instructed to abstain from ejaculation for 3 days before undergoing uroflowmetry (UF1). Subsequently, they were required to ejaculate. Subsequent uroflowmetry assessments were conducted at 2 to 4 h (UF2) and 48 to 50 h (UF3) after ejaculation. No further ejaculations were permitted during this timeframe. The patients had a mean age of 50.97 ± 1.47 years. Statistically significant differences were observed in the mean values of Qmax and corrected Qmax (cQmax) between UF1 and UF2 measurements (p < 0.05). These differences were only in patients with benign prostatic enlargement (BPE) (p < 0.05). Furthermore, the number of patients with Qmax <15 mL/s showed a statistically significant difference between UF1 and UF2 measurements, specifically in the BPE group (p = 0.016). In this study, we have observed a significant and temporary increase in the Qmax following ejaculation, particularly among patients with BPE. This indicates that ejaculation can potentially complicate the interpretation of uroflowmetry results. Therefore, further research is necessary to gain a more comprehensive understanding of this phenomenon.

Prediction of Prostate Cancer Risk Stratification Based on A Nonlinear Transformation Stacking Learning Strategy.

Prostate cancer (PCa) is an epithelial malignancy that originates in the prostate gland and is generally categorized into low, intermediate, and high-risk groups. The primary diagnostic indicator for PCa is the measurement of serum prostate-specific antigen (PSA) values. However, reliance on PSA levels can result in false positives, leading to unnecessary biopsies and an increased risk of invasive injuries. Therefore, it is imperative to develop an efficient and accurate method for PCa risk stratification. Many recent studies on PCa risk stratification based on clinical data have employed a binary classification, distinguishing between low to intermediate and high risk. In this paper, we propose a novel machine learning (ML) approach utilizing a stacking learning strategy for predicting the tripartite risk stratification of PCa. Clinical records, featuring attributes selected using the lasso method, were utilized with 5 ML classifiers. The outputs of these classifiers underwent transformation by various nonlinear transformers and were then concatenated with the lasso-selected features, resulting in a set of new features. A stacking learning strategy, integrating different ML classifiers, was developed based on these new features. Our proposed approach demonstrated superior performance, achieving an accuracy of 0.83 and an area under the receiver operating characteristic curve value of 0.88 in a dataset comprising 197 PCa patients with 42 clinical characteristics. This study aimed to improve clinicians' ability to rapidly assess PCa risk stratification while reducing the burden on patients. This was achieved by using artificial intelligence-related technologies as an auxiliary method for diagnosing PCa.

Prostate Carcinoma: Urologist's Perspective

AbstractProstate cancer management has undergone radical changes in recent times, due to early diagnosis in localized stage and availability of multiple treatment modalities. But the onus of selecting appropriate treatment rests with the urologist. Radiological investigations are immensely important in these patients. Measurement of prostate-specific antigen and its derivatives is the primary investigation in the diagnosis of prostate carcinoma. Ultrasonogram is of limited utility in prostate carcinoma. Magnetic resonance imaging provides extensive information to the treating physician regarding the approach and the treatment modality to be used in the management of prostate carcinoma. Radiological investigations are the cornerstones for efficient management of prostate carcinoma.

Using joint models for longitudinal and time-to-event data to investigate the causal effect of salvage therapy after prostatectomy.

Prostate cancer patients who undergo prostatectomy are closely monitored for recurrence and metastasis using routine prostate-specific antigen measurements. When prostate-specific antigen levels rise, salvage therapies are recommended in order to decrease the risk of metastasis. However, due to the side effects of these therapies and to avoid over-treatment, it is important to understand which patients and when to initiate these salvage therapies. In this work, we use the University of Michigan Prostatectomy Registry Data to tackle this question. Due to the observational nature of this data, we face the challenge that prostate-specific antigen is simultaneously a time-varying confounder and an intermediate variable for salvage therapy. We define different causal salvage therapy effects defined conditionally on different specifications of the longitudinal prostate-specific antigen history. We then illustrate how these effects can be estimated using the framework of joint models for longitudinal and time-to-event data. All proposed methodology is implemented in the freely-available R package JMbayes2.

Normalised repeat serum prostate-specific antigen: associations with age and magnetic resonance imaging results.

To assess the value of a repeat prostate-specific antigen measurement (PSA2) before magnetic resonance imaging (MRI) in men with a raised PSA (PSA1) <10 µg/L. Medical records of men aged < 75 years referred in 2021 for PSA1 3.0-9.9 µg/L (< 70 years) or 5.0-9.9 µg/L (70-74 years) were reviewed. PSA2 was sampled before MRI within 60 days from PSA1. Odds ratios (ORs) were calculated with logistic regression. Chi-square and trend-test were used for categorical variables. A total of 341 men were included. Median time between PSA1 and PSA2 was 28 days (interquartile range 20-35 days). PSA normalised in 16% (95% confidence interval [CI]: 13-21). Younger men were more likely to have a normal PSA2 (OR: 0.95 per year older, 95% CI: 0.92-0.99). Among men aged < 70 years, those with PSA1 < 5 µg/L were more likely to have normalised PSA2 than those with PSA1 ≥ 5 µg/L (21% vs. 10%, p = 0.01). A greater proportion of men with normalised PSA2 had a Prostate Imaging Data and Reporting System MRI score of 1-3 than men with non-normalised PSA2 (93% vs. 77%, p = 0.01). A clinically significant proportion of men with a moderately raised PSA value have a normal PSA2. Younger men and men with lower PSA1 were more likely to have a normal PSA2. Few men with normalised PSA2 had suspicious MRI findings. Routine repeat PSA-testing may be motivated in men with a moderately raised PSA value to save MRI resources, particularly in younger men.

Prostate-specific antigen (PSA) decline with apalutamide therapy is associated with longer survival and improved outcomes in individuals with metastatic prostate cancer: a plain language summary of the TITAN study.

This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC). A total of 1052 participants with mCSPC were included in the TITAN study. Treatment with apalutamide was compared with treatment with placebo. All participants received androgen deprivation therapy (or ADT), which is a type of hormone therapy that has been part of the main treatment for mCSPC for many years. The results showed that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT. Apalutamide plus ADT also controlled the growth of the cancer for a longer length of time compared with placebo plus ADT. Additionally, participants who received apalutamide plus ADT experienced a greater reduction in the blood levels of prostate-specific antigen (or PSA), called a deep PSA decline, compared with those who received placebo plus ADT. An additional (or post hoc) analysis was carried out to understand whether a decrease in blood PSA levels, in response to treatment, was associated with improved outcomes, including longer survival time. In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes. These results demonstrate that individuals with mCSPC can benefit from treatment with apalutamide plus ADT. The association seen between deep PSA decline and the longer survival time and improved outcomes highlights how PSA measurements can be used to help monitor cancer disease evolution in response to treatment. Monitoring PSA levels will assist doctors and other healthcare professionals to understand how effectively a treatment is working for a patient and to tailor their treatment approach to improve PSA decline.

Exposure to heavy metal elements may significantly increase serum prostate-specific antigen levels with overdosed dietary zinc

BackgroundSerum prostate-specific antigen (PSA) is a primary metric for diagnosis and prognosis of prostate cancer (PCa). Exposure to heavy metals, such as lead, cadmium, mercury, and zinc can impact PSA levels in PCa patients. However, it is unclear whether this effect also occurs in men without PCa, which may lead to the overdiagnosis of PCa. MethodData on a total of 5089 American men who had never been diagnosed with PCa were obtained from the National Health and Nutrition Examination Survey performed from 2003–2010. The relationship between serum PSA levels (dependent variable) and concentrations of lead (μmol/L), cadmium (nmol/L), and mercury (μmol/L) were investigated with dietary zinc intake being used as a potential modifier or covariate in a weighted linear regression model and a generalized additive model. A series of bootstrapping analyses were performed to evaluate sensitivity and specificity using these models. ResultsRegression analyses suggested that, in general, lead, cadmium, or mercury did not show an association with PSA levels, which was consistent with the results of the bootstrapping analyses. However, in a subgroup of participants with a high level of dietary zinc intake (≥14.12 mg/day), a significant positive association between cadmium and serum PSA was identified (1.06, 95% CI, P = 0.0268, P for interaction=0.0249). ConclusionsWith high-level zinc intake, serum PSA levels may rise in PCa-free men as the exposure to cadmium increases, leading to a potential risk of an overdiagnosis of PCa and unnecessary treatment. Therefore, environmental variables should be factored in the current diagnostic model for PCa that is solely based on PSA measurements. Different criteria for PSA screening are necessary based on geographical variables. Further investigations are needed to uncover the biological and biochemical relationship between zinc, cadmium, and serum PSA levels to more precisely diagnose PCa.

Prostate-specific antigen (PSA) response among patients with metastatic castration-sensitive prostate cancer (mCSPC) initiated on apalutamide (APA) or abiraterone acetate (ABI) in real-world urology practices.

53 Background: Recently approved oral therapies APA and ABI (plus prednisone) are effective mCSPC treatments. Prior real-world evidence showed that, relative to ABI, patients who initiated APA had significantly higher rates of PSA decline ≥90% (PSA90), which has been associated with longer overall survival. The objective of this study was to compare PSA90 response among an enhanced cohort of patients with mCSPC initiated on APA or ABI. Methods: Electronic medical records from PPS Analytics including data from US community urology practices were linked with administrative claims from the Komodo Health Solutions Research Database. Androgen receptor signaling inhibitor (ARSI)-naïve patients with mCSPC with ≥12 months of pre-index clinical activity were selected into the APA or ABI cohort based on their first paid claim/dispensation on or after 17 Sep 2019 (index date). Patients were followed to earliest of index ARSI discontinuation or switch, radiopharmaceutical use, end of insurance or clinical activity, or end of data availability (30 Sep 2022). Inverse probability treatment weighting (IPTW) was used to reduce potential pre-index confounding, controlling for age, race, region, insurance payer, index year, time from metastasis to index date, time from first prostate cancer (PC) diagnosis to index date, metastasis locations, de novo PC, use of androgen deprivation therapy, first-generation antiandrogens or chemotherapy, most recent PSA and testosterone levels, and most recent Gleason score. PSA90 was defined as the earliest attainment of ≥90% decline in PSA relative to pre-index (most recent value within 13 weeks). The proportion of patients achieving PSA90 was compared using a weighted Kaplan-Meier analysis and the time-to-PSA90 response was compared using a weighted Cox proportional hazards model. Results: A total of 917 APA and 632 ABI patients were identified. Patient characteristics were balanced with IPTW (Table). By 6 months post-index, 80.9% of APA and 72.8% of ABI patients had a PSA measurement. By 6 months, significantly more APA patients attained a PSA90 response, as compared to ABI patients (P &lt; 0.001; Table). Median time-to-PSA90 was 3.5 months for APA patients and 8.8 months for ABI patients. Conclusions: This real-world study supports previous findings that a greater percentage of patients with mCSPC in the US initiating APA achieved deep PSA response compared to those initiating ABI. [Table: see text]

Illustration of association between change in prostate-specific antigen (PSA) values and time to tumor status after treatment for prostate cancer patients: a joint modelling approach

BackgroundProstate cancer (PCa) is the most prevalent tumor in men, and Prostate-Specific Antigen (PSA) serves as the primary marker for diagnosis, recurrence, and disease-free status. PSA levels post-treatment guide physicians in gauging disease progression and tumor status (low or high). Clinical follow-up relies on monitoring PSA over time, forming the basis for dynamic prediction. Our study proposes a joint model of longitudinal PSA and time to tumor shrinkage, incorporating baseline variables. The research aims to assess tumor status post-treatment for dynamic prediction, utilizing joint assessment of PSA measurements and time to tumor status.MethodsWe propose a joint model for longitudinal PSA and time to tumor shrinkage, taking into account baseline BMI and post-treatment factors, including external beam radiation therapy (EBRT), androgen deprivation therapy (ADT), prostatectomy, and various combinations of these interventions. The model employs a mixed-effect sub-model for longitudinal PSA and an event time sub-model for tumor shrinkage.ResultsResults emphasize the significance of baseline factors in understanding the relationship between PSA trajectories and tumor status. Patients with low tumor status consistently exhibit low PSA values, decreasing exponentially within one month post-treatment. The correlation between PSA levels and tumor shrinkage is evident, with the considered factors proving to be significant in both sub-models.ConclusionsCompared to other treatment options, ADT is the most effective in achieving a low tumor status, as evidenced by a decrease in PSA levels after months of treatment. Patients with an increased BMI were more likely to attain a low tumor status. The research enhances dynamic prediction for PCa patients, utilizing joint analysis of PSA and time to tumor shrinkage post-treatment. The developed model facilitates more effective and personalized decision-making in PCa care.

The Impact of Delayed Radical Prostatectomy on Recurrence Outcomes After Initial Active Surveillance: Results from a Large Institutional Cohort

Background and objectiveActive surveillance (AS) of prostate cancer (PCa) involves regular monitoring for disease progression. The aim is to avoid unnecessary treatment while ensuring appropriate and timely treatment for those whose disease progresses. AS has emerged as the standard of care for low-grade (Gleason grade 1, GG1) PCa. Opponents are concerned that initial undersampling and delay of definitive management for patients with GG2 disease may lead to adverse outcomes. We sought to determine whether the timing for definitive management of GG2 PCa, either upfront or after initial AS, affects recurrence outcomes after radical prostatectomy (RP). MethodsParticipants were diagnosed with cT1–2N0/xM0/x, prostate-specific antigen (PSA) <20 ng/ml, and GG1–2 PCa between 2000 and 2020 and underwent immediate RP for GG2 or AS followed by delayed RP on upgrading to GG2. The outcome was recurrence-free survival (RFS) after surgery, with recurrence defined as either biochemical failure (2 PSA measurements ≥0.2 ng/ml) or a second treatment. Multivariable Cox proportional-hazards regression models were used to calculate associations between the timing for definitive RP and the risk of recurrence, adjusted for age at diagnosis, percentage of positive biopsy cores (PPC), PSA density, PSA before RP, year of diagnosis, surgical margins, genomic risk score, and prostate MRI findings.Key findings: Of the 1259 men who met the inclusion criteria, 979 underwent immediate RP after diagnosis of GG2, 190 underwent RP within 12 mo of upgrading to GG2 on AS, and 90 men underwent RP >12 mo after upgrading to GG2. The 5-yr RFS rates were 81% for the immediate RP group, 80% for the delayed RP ≤12 mo, and 70% for the delayed RP >12 mo group (univariate log-rank p = 0.03). Cox multivariable regression demonstrated no difference in RFS outcomes between immediate RP for GG2 disease and delayed RP after upgrading on AS. PPC (hazard ratio [HR] per 10% increment 1.08, 95% confidence interval [CI] 1.02–1.15; p = 0.01) and PSA before RP (HR 1.06, 95% CI 1.03–1.09; p < 0.01) were significantly associated with the risk of recurrence. Conclusionsand clinical implications: PPC and PSA before RP, but not the timing of definitive surgery after upgrade to GG2, were associated with the risk of PCa recurrence after RP on multivariable analysis. These findings support the safety of AS and delayed definitive therapy for a subset of patients with GG2 disease. Patient summaryIn a large group of 1259 patients with low-grade prostate cancer, we found that delaying surgical treatment after an initial period of active surveillance resulted in no differences in prostate cancer recurrence. Our results support the safety of active surveillance for low-grade prostate cancer.

EMAS position statement: Testosterone replacement therapy in older men.

Late-onset hypogonadism is the clinical entity characterised by low testosterone concentrations associated with clinical symptoms in the absence of organic disease in ageing men. It has been associated with metabolic syndrome, reduced bone mineral density, and increased cardiovascular morbidity and mortality risk. Although testosterone replacement therapy (TRT) reverses most of these conditions in young hypogonadal men, the risk/benefit ratio of TRT in older men is debatable. To update the 2015 EMAS statement on TRT in older men with new research on late-onset hypogonadism and TRT. Literature review and consensus of expert opinion. TRT should be offered only to symptomatic older men with confirmed low testosterone concentrations after explaining the uncertainties regarding the long-term safety of this treatment. TRT may be offered to men with severe hypogonadism and erectile dysfunction to improve sexual desire, erectile, and orgasmic function. It should also be considered in hypogonadal men with severe insulin resistance or pre-diabetes mellitus. TRT may also be considered, in combination with proven treatment strategies, for osteoporosis, or for selected patients with persistent mild depressive symptoms and/or low self-perceived quality of life, combined with standard medical care for each condition. TRT is contraindicated in hypogonadal men actively seeking fertility treatment. Due to a lack of data, TRT should not be routinely used in older men to improve exercise capacity/physical function, improve cognitive function, or prevent cognitive decline. TRT must be avoided in older, frail men with known breast cancer or untreated prostate cancer and all men who have had myocardial infarction or stroke within the last four months, and those with severe or decompensated heart failure. The quality of evidence regarding patients with previous prostate cancer or cardiovascular disease is too low to draw definitive conclusions. Any limits on duration of use are arbitrary, and treatment should continue for as long as the man feels the benefits outweigh the risks for him, and decisions must be made on an individual basis. Withdrawal should be considered when hypogonadism is reversed after the resolution of underlying disorder. Short-acting transdermal preparations should be preferred for TRT initiation in older men, but injectable forms may be considered subsequently. Older men on TRT should be monitored at 3, 6, and 12months after initiation and at least yearly thereafter, or earlier and more frequently if indicated. Evaluation should include assessment of the clinical response, and measurement of total testosterone, haematocrit, and prostate-specific antigen (PSA) concentrations. Bone density and/or quality should also be assessed. Obese and overweight patients should be encouraged to undergo lifestyle modifications, including exercise and weight loss, to increase endogenous testosterone.

Angiotensin II Receptor Blockers Cause Changes in Prostate-specific Antigen Levels: A Retrospective Cohort Study.

We previously reported a decrease in prostate-specific antigen (PSA) levels in patients with castration-resistant prostate cancer treated with angiotensin II receptor blockers (ARBs). However, no studies have reported the effect of ARBs on PSA variability in patients without a history of prostate cancer. Therefore, we conducted a population-based, retrospective study to determine whether ARBs have an inhibitory effect on elevated PSA levels in Japanese patients without a history of prostate cancer. This study was conducted using a large-scale Japanese claim database, including male patients aged ≥60 years who had two or more PSA measurements with an interval between measurements of 3 months to 2 years between April 2008 and June 2019. Patients who had been prescribed ARBs were grouped into the ARB group, and those who were prescribed antihypertensive drugs other than ARBs were grouped into the non-ARB group. We compared the proportions of patients with second PSA levels greater than the first. The numbers of eligible patients in the ARB and non-ARB groups were 777 and 527, respectively. Multivariate logistic regression analysis revealed that the proportion of patients with elevated PSA levels was significantly lower in the ARB group than in the non-ARB group (adjusted odds ratio=0.80, 95% confidence interval=0.64-0.99, p=0.047). ARBs may suppress elevated PSA levels in patients without a history of prostate cancer. This contributes to the prevention of prostate cancer.

Follow-Up of Men Who Have Undergone Focal Therapy for Prostate Cancer with HIFU-A Real-World Experience.

To determine oncological and functional outcomes and side effects after focal therapy of prostate cancer (PCa) with high-intensity focused ultrasound (HIFU). This retrospective single-center study included 57 consecutive patients with localised PCa. Aged 18-80 with ≤2 suspicious lesions on mpMRI (PIRADS ≥ 3), PSA of ≤15 ng/mL, and an ISUP GG of ≤2. HIFU was performed between November 2014 and September 2018. All men had an MRI/US fusion-guided targeted biopsy (TB) combined with a TRUS-guided 10-core systematic biopsy (SB) prior to focal therapy. HIFU treatment was performed as focal, partial, or hemiablative, depending on the prior histopathology. Follow-up included Questionnaires (IIEF-5, ICIQ, and IPSS), prostate-specific antigen (PSA) measurement, follow-up mpMRI, and follow-up biopsies. The median age of the cohort was 72 years (IQR 64-76), and the median PSA value before HIFU was 7.3 ng/mL (IQR 5.75-10.39 ng/mL). The median follow-up was 27.5 (IQR 23-41) months. At the time of the follow-up, the median PSA value was 2.5 ng/mL (IQR 0.94-4.96 ng/mL), which shows a significant decrease (p < 0.001). In 17 (29.8%) men, mpMRI revealed a suspicious lesion, and 19 (33.3%) men had a positive biopsy result. Only IIEF values significantly decreased from 16 (IQR 10.75-20.25) to 11.5 (IQR 4.5-17) (p < 0.001). The rate of post-HIFU complications was low, at 19.3% (11 patients). The limitation of this study is the lack of long-term follow-up. HIFU as a therapy option for nonmetastatic, significant prostate cancer is effective in the short term for carefully selected patients and shows a low risk of adverse events and side effects.

Association between serum 25-hydroxyvitamin D and prostate-specific antigen: a retrospective study in men without prostate pathology.

Recently, vitamin D status has been associated with prostate cancer risk. However, some studies argue that there is no association of vitamin D with prostate cancer risk and serum prostate-specific antigen (PSA) concentrations. No clear conclusions can be drawn from the studies found in the literature. Our aim was to assess the relationship between PSA and 25-hydroxyvitamin D [25(OH)D]. We selected 415 individuals without prostate pathologies and subgroups were generated according to age and 25(OH)D. Statistical analyses were performed using Shapiro-Wilk test, Student's t and ANOVA tests, and Pearson's correlation. Besides, the minimum sample size needed to obtain statistically significant results between groups according to 25(OH)D concentration was calculated and a Student's t-test for paired samples was performed to study individuals with two PSA measurements over time, where 25(OH)D concentration increased or decreased more than 25 %. We observed a slight correlation between age and PSA concentration (r=0.379, p<0.001). However, we found no significant differences when we compared PSA concentrations between groups according to 25(OH)D concentrations (p=0.891): 1.25±1.32 μg/L (group with 25(OH)D<50 nmol/L) and 1.17±0.90 (group with 25(OH)D≥50 nmol/L). Pearson's correlation coefficient was close to 0. The minimum samples size to obtain statistically significant results was 815,346 men, and we observed no differences in PSA concentrations in individuals with two measurements. Our findings show no association in men without prostate pathologies, based on 25(OH)D levels.

Analysis of the learning curve for Retzius-sparing robot-assisted radical prostatectomy for a single surgeon

Background: The learning curve for Retzius-sparing robotic radical prostatectomy is not fully understood. Objective: This study attempts to identify the learning curve across the first 130 cases of a single surgeon. Design, Setting and Participants: All Retzius-sparing robotic radical prostatectomy cases performed by a single surgeon at a high-volume tertiary hospital between April 2019 and July 2022 were included. Outcome Measurements and Statistical Analysis: Outcome measures included positive surgical margin rate, complication rates and unplanned readmission to hospital, postoperative urinary continence, erectile function and prostate-specific antigen (PSA) measurement. Cases were divided chronologically into three groups and differences between groups assessed. Results and Limitation: A total of 130 Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) cases were identified. Differences were found between groups in several areas. Positive surgical margin rate fell between Group 1 (30.2%) and Group 3 (9.1%). Safety, postoperative continence, erectile function and PSA remained stable. Median patient age increased between Group 1 (59 years) and Group 3 (66.5 years) ( p = 0.04). Proportion of patients with stage &gt;T2 increased between Group 1 (27.9%) and Group 2 (41.9%) ( p = 0.036). Median console time increased between Group 1 (120 minutes) and Group 2 (150 minutes) ( p = 0.01). Median gland weight increased between Group 1 (28 g) and Group 3 (35.5 g) ( p &lt; 0.001). Conclusions: The positive surgical margin rate improved over the learning curve, despite the complexity of cases increasing, reflected in older patients, larger prostates and higher stage disease. Safety and functional outcomes are excellent throughout. The learning curve might be facilitated by careful case selection favouring smaller prostates with less advanced disease. Patient Summary: We analysed the learning curve for Retzius-sparing robotic radical prostatectomy. Across the first 130 cases, positive surgical margin rate fell; safety and continence remained excellent. Selection of smaller and less advanced cases may facilitate learning. Level of evidence: III

The Potentiality of Prostate-Specific Antigen as a Prognostic Biomarker in Breast Cancer.

Background Serum prostate-specific antigen (PSA) is a well-established marker that can be measured as an indicator for screening, diagnosing, and managing prostate cancer due to its advanced tissue specificity. Numerous studies have revealed that free PSA is the predominant molecular form of PSA in breast cancer cases. In contrast, total PSA is prevalent in benign breast tumor cases and healthy females. This case-control study aims to measure PSA levels among individuals with breast cancer in order to establish PSA as a prognostic biomarker. Methods The study involved 150 female subjects between the ages of 18 and 70 and was conducted between 2013 and 2014. The subjects were then categorized into three groups: those with malignant breast cancer, those with benign breast tumors, and the control group with no history of malignant or benign breast tumors. Participants were asked to complete a lifestyle questionnaire and interview using hospital medical records to establish past and pertinent patient medical history. These cases were acquired from the 7th of October Hospital's surgery department and Benghazi Central Hospital's oncology clinic in Libya. Sandwich-type ELISA's were used for PSA quantitation, while the Wilcoxon Rank-Sum test was used to identify statistically significant differences between total PSA and free PSA measurements within each patient group. Results This study did not reveal significant statistical differences in total PSA levels between breast cancer cases and control groups (p=0.200), or between breast cancer and fibroadenoma patients (p=0.472). However, there was a significant difference in F-PSA levels between breast cancer and fibroadenoma cases (p=0.0001). Neither total-PSA (p=0.200) nor F-PSA (p=0.262) levels showed significant differences between breast cancer cases and controls. This study paved the way for further investigations into PSA's role in breast cancer. Despite its limitations, it offers an opportunity to delve deeper into understanding PSA's potential role and use in breast cancer. Conclusion A comprehensive statistical analysis revealed a positive correlation between F-PSA levels and breast cancer diagnosis. The findings suggest that PSA may serve as a prognostic biomarker for breast cancer. This may contribute to improved customized treatment approaches, offering precise and accurate risk assessments, understanding breast cancer biology, and improving health outcomes for patients with breast cancer.

Transcriptomic Heterogeneity of Expansile Cribriform and Other Gleason Pattern 4 Prostate Cancer Subtypes

BackgroundProstate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited. ObjectiveTo explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival. Design, setting, and participantsThis was a retrospective cohort study including 165 men with grade group 2–4 prostate cancer who underwent RP at a single academic institution (2016–2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR. Outcomes measurements and statistical analysisPrompted by heterogeneity within pattern 4 subtypes identified via exploratory analyses, we investigated transcriptomic consensus clusters using partitioning around medoids and hallmark gene set scores. The primary clinical outcome was BCR, defined as two consecutive prostate-specific antigen measurements >0.2 ng/ml at least 8 wk after RP, or any additional treatment. Multivariable Cox proportional-hazards models were used to determine factors associated with BCR-free survival. Results and limitationsIn this cohort, 99/165 patients (60%) had EC and 67 experienced BCR. Exploratory analyses and clustering demonstrated transcriptomic heterogeneity within each Gleason pattern 4 subtype. In the multivariable model controlled for pattern 4 subtype, margin status, Cancer of the Prostate Risk Assessment Post-Surgical score, and Decipher score, a newly identified steroid hormone–driven cluster (hazard ratio 2.35 95% confidence interval 1.01–5.47) was associated with worse BCR-free survival. The study is limited by intermediate follow-up, no validation cohort, and lack of accounting for intratumoral and intraprostatic heterogeneity. ConclusionsTranscriptomic heterogeneity was present within and across each Gleason pattern 4 subtype, demonstrating there is additional biologic diversity not captured by histologic subtypes. This heterogeneity can be used to develop novel signatures and to classify transcriptomic subtypes, which may help in refining risk stratification following RP to further guide decision-making on adjuvant and salvage treatments. Patient summaryWe studied prostatectomy specimens and found that tumors with similar microscopic appearance can have genetic differences that may help to predict outcomes after prostatectomy for prostate cancer. Our results demonstrate that further gene expression analysis of prostate cancer subtypes may improve risk stratification after prostatectomy. Future studies are needed to develop novel gene expression signatures and validate these findings in independent sets of patients.