A Description and Safety Overview of Irreversible Electroporation for Prostate Tissue Ablation in Intermediate-Risk Prostate Cancer Patients: Preliminary Results from the PRESERVE Trial.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0-72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3-82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.

Cardiovascular/Stroke Risk Assessment in Patients with Erectile Dysfunction-A Role of Carotid Wall Arterial Imaging and Plaque Tissue Characterization Using Artificial Intelligence Paradigm: A Narrative Review.

PURPOSE: The role of erectile dysfunction (ED) has recently shown an association with the risk of stroke and coronary heart disease (CHD) via the atherosclerotic pathway. Cardiovascular disease (CVD)/stroke risk has been widely understood with the help of carotid artery disease (CTAD), a surrogate biomarker for CHD. The proposed study emphasizes artificial intelligence-based frameworks such as machine learning (ML) and deep learning (DL) that can accurately predict the severity of CVD/stroke risk using carotid wall arterial imaging in ED patients. METHODS: Using the PRISMA model, 231 of the best studies were selected. The proposed study mainly consists of two components: (i) the pathophysiology of ED and its link with coronary artery disease (COAD) and CHD in the ED framework and (ii) the ultrasonic-image morphological changes in the carotid arterial walls by quantifying the wall parameters and the characterization of the wall tissue by adapting the ML/DL-based methods, both for the prediction of the severity of CVD risk. The proposed study analyzes the hypothesis that ML/DL can lead to an accurate and early diagnosis of the CVD/stroke risk in ED patients. Our finding suggests that the routine ED patient practice can be amended for ML/DL-based CVD/stroke risk assessment using carotid wall arterial imaging leading to fast, reliable, and accurate CVD/stroke risk stratification. SUMMARY: We conclude that ML and DL methods are very powerful tools for the characterization of CVD/stroke in patients with varying ED conditions. We anticipate a rapid growth of these tools for early and better CVD/stroke risk management in ED patients.

Boosting immune response with GM-CSF optimizes primary cryotherapy outcomes in the treatment of prostate cancer: a prospective randomized clinical trial.

OBJECTIVE: We explored the association of prostate cryotherapy and immunomodulation with granulocyte-macrophage colony-stimulating factor (GMCSF) in the generation of detectable tumor-specific T- and B-cell responses in men with prostate cancer. MATERIALS AND METHODS: A randomized pilot study of patients assigned to either cryotherapy alone (Control group) or in combination with GMCSF (Treatment group). The impact of therapy on the development of T- and B-cell responses against tumor-related antigens was studied using enzyme-linked immune absorbent spot (ELISpot) and protein microarray panels (Sematrix) assays, respectively. Fold changes in response to treatment were calculated by normalization of post-treatment ELISpot values against the mean pre-cryoablation response. Student t tests between treatment and control groups at 4 weeks and 12 weeks across all the antigens were performed. RESULTS: A total of 20 patients were randomized to either control or treatment arm. At 4 weeks after cryotherapy, the treatment group demonstrated an average fold change in cancer antigen-related antibodies of 2.8% above their mean baseline values, whereas controls averaged an 18% change below mean baseline (p < 0.05). At 12 weeks, antibody response in treatment group increased to 25% above baseline, while the average of control group patients remained 9% below baseline (p < 0.05). Patients in treatment group displayed, on average, higher ELISPOT readings for the 4- and 12-week times points (527 vs 481 for PSA and 748 vs 562 for PAP). CONCLUSIONS: GMCSF appeared to broadly elevate antibodies against prostate-specific and nonspecific antigens. Prostate antigen-specific T-cell responses were more enhanced over non-prostate-specific responses, preferentially in the treatment group. Our findings suggest a possible therapeutic effect of adjuvant immunotherapy in association with cryotherapy for the treatment of prostate cancer.

Metastatic renal cell carcinoma to the prostate and seminal vesicle.

Renal cell carcinoma (RCC) a common malignancy with potential to metastasize to visceral organs. However, it uncommonly spreads to the lower genitourinary tract. We present a man with a history of RCC status post radical nephrectomy in April 2012. He presented 8 years later with obstructive lower urinary tract symptoms and an elevated prostate specific antigen (PSA). Further imaging showed a large enhancing mass with internal blood vessels posterior to the left prostate and seminal vesicle. A prostate biopsy was performed and consistent with metastatic RCC. He was ultimately treated with immunotherapy and focal stereotactic radioablation.

The effect of alpha-blocker and 5alpha-reductase inhibitor intake on sexual health in men with lower urinary tract symptoms.

OBJECTIVE: To assess the effect of tamsulosin on the Sexual Health Inventory for Men (SHIM) score in men diagnosed with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Analysis from the national database of a programme of the Prostate Cancer Educational Council identified 7974 men who completed the American Urologic Association Symptom Score (AUA-SS) and SHIM questionnaires. The patients were divided into three groups; group 1, men taking tamsulosin; group 2, men on other prescription medications for treating BPH symptoms; and group 3, men not currently taking any BPH medications. Linear regression was used to assess the association of tamsulosin and other alpha-blocker prescriptions for treating BPH symptoms with the decline in SHIM score. The interaction terms between AUA and the intake of tamsulosin was also adjusted for in the final analysis. RESULTS: The median age of the men was 60 years. In groups 1, 2 and 3, (234, 291 and 7449 men, respectively) the mean (sd) AUA-SS was 13.0 (7.2), 12.1 (7.2) and 6.9 (5.8), and the mean SHIM scores 11.7 (6.8), 12.7 (6.5) and 15.9 (6.0), respectively. Adjusting for the AUA-SS, men in group 1 on tamsulosin had a significantly higher SHIM score with increasing AUA-SS score than men on other medications (P < 0.01), offsetting the negative correlation between the AUA-SS and SHIM (P < 0.01). Moreover, men in group 1 were more likely to have a higher AUA-SS and lower SHIM score than men in the other two groups, suggesting more severe symptoms in these men. CONCLUSIONS: Men taking tamsulosin to treat LUTS appear to be at an advantage over men taking other alpha-blockers when the effect of LUTS on sexual health is considered. Furthermore, this effect was more profound in patients with more severe LUTS than those with mild and moderate symptoms. Future prospective trials are warranted to confirm this effect.

The association of time of day and serum testosterone concentration in a large screening population.

OBJECTIVE: To assess testosterone patterns during clinical hours in a large population of men participating in a national screening programme for prostate cancer, as the effect of time of day on serum testosterone concentration is unclear and largely reported in small studies. SUBJECTS AND METHODS: Testosterone levels were measured in 3006 men attending the national Prostate Cancer Awareness Week screening programme. Blood samples were obtained between 06.00 and 18.00 hours, whenever men presented for screening. All men completed questionnaires on age, comorbidities, height and weight. Testosterone levels were compared based on four periods, i.e. T1, 06.00-10.00 (632 men), T2, 10.00-12.00 (812), T3, 12.00-14.00 (388), and T4, 14.00-18.00 hours (1174). RESULTS: The mean (sd, range) age of the men was 60.3 (9.9, 40-94) years and the mean (sd) testosterone level was 415.2 (190.9) ng/dL. There was no change in mean (sd) testosterone levels over T1, T2 and T3, at 444.9 (206.2), 433.5 (195.8) and 434.4 (181.2) ng/dL, respectively, but levels at T4, at 380.4 (176.4) ng/dL, were lower by approximately 13% (P < 0.05). Advancing age, diabetes and obesity were associated with lower testosterone levels. The percentage of men with biochemical hypogonadism (<300 ng/dL) did not change across all four periods. CONCLUSIONS: Testosterone levels in older men are stable throughout the morning and early afternoon, declining only modestly thereafter. Further case-controlled studies are needed to confirm these findings.

Minimally invasive surgery in prostate cancer: current and future perspectives.

Prostate cancer is a leading cause of death for men. Its prevalence increases substantially with advancing age, which coincides with increased incidence of comorbidities. The mainstay therapy for early prostate cancer remains radical surgery and radiotherapy. In the era of prostate-specific antigen and the newly emerging highly specific screening tests, more men are diagnosed earlier in their life and with confined disease. The application of minimally invasive approaches, such as the laparoscopic/telerobotic approach and focal treatments, is becoming more popular, yielding shorter hospital stays and faster recovery, with minimal complications. In part, this is possible due to groundbreaking advances in laparoscopic equipment, prostate imaging modalities, and gained urologic expertise in minimally invasive treatment. In this review we critically discuss the current knowledge and future perspectives of minimally invasive treatment in prostate cancer.

Observed effect of age and body mass index on total and complexed PSA: analysis from a national screening program.

OBJECTIVES: To assess the effect of aging and body mass index (BMI) on both serum total prostate-specific antigen (tPSA) and complexed PSA (cPSA) from the results of the 2003 Prostate Cancer Awareness Week national screening database. METHODS: A total of 12,943 men were screened for prostate cancer. Of these, 4458 men had simultaneous measurements of tPSA and cPSA. Height and weight were used to calculate the BMI. The subjects were grouped by decade of age and categorized as either obese or nonobese with a cutoff BMI of 30 kg/m2. The rates of increase in mean tPSA and cPSA between consecutive decades were compared. The relationship among BMI, PSA, and cPSA was also analyzed using multivariate regression analysis. RESULTS: The median age of those screened was 60 years. The median PSA and cPSA was 1.10 and 0.69 ng/dL, respectively. Both serum tPSA and cPSA levels showed an exponential increase with advancing age. The ratio of cPSA/tPSA remained relatively constant at 0.6. Compared with the nonobese cohort, men with a BMI of 30 kg/m2 or more had significantly lower tPSA and cPSA levels across all age groups (P <0.01). The overall odds ratio for all age groups was 1.8 (95% confidence interval 1.2 to 2.3). CONCLUSIONS: Both tPSA and cPSA levels increased with age. Across age groups, men with a greater BMI had significantly lower cPSA and tPSA levels. The clinical significance of age-adjusted cutoff levels for PSA in obese men for the diagnosis of prostate cancer should be explored further in future prospective clinical trials.

Combination of low-dose flutamide and finasteride for PSA-only recurrent prostate cancer after primary therapy.

OBJECTIVES: To evaluate the efficacy and tolerability of combined finasteride and low-dose flutamide for prostate-specific antigen (PSA)-only recurrence after definitive therapy and to determine the predictors of recurrence-free survival. METHODS: Seventy-one men with biochemical recurrence after primary therapy for prostate cancer were prospectively enrolled from 1996 to 1998. Forty-two patients had undergone radical retropubic prostatectomy and 29 had undergone external beam radiotherapy. Radionuclide bone scans and computed tomography of the abdomen and pelvis showed no metastasis. The initial treatment with finasteride (5 mg twice daily) and flutamide (125 mg twice daily) was continued unless participants were unable to tolerate the agents or experienced PSA progression. RESULTS: At a mean of 44.4 months (range 12 to 92) of follow-up, 54 (76%) of 71 patients were available for measurement of disease status and response to therapy. Three patients had died of unrelated causes; 5 men withdrew from the study because of side effects and 1 patient for protocol violation. Eight patients were lost to follow-up. Twenty-seven patients (38%) continued receiving therapy with no evidence of PSA progression (PSA level less than 0.4 ng/mL), 6 patients maintained a more than 50% reduction in their baseline PSA level at the time of analysis, and 21 (29%) had PSA progression (ie, elevated PSA level on three consecutive tests more than 4 weeks apart). Major side effects were breast tenderness (90%), gynecomastia (72%), gastrointestinal disturbances (22%), fatigue (10%), and decreased libido (4%). The side effects were mild and well tolerated by most patients. CONCLUSIONS: The combination of finasteride and flutamide showed a moderate efficacy in patients with PSA-only recurrence after definitive therapy. The efficacy appears to be greater in patients who can achieve a PSA nadir of 0.1 ng/mL or less after the start of treatment.