Prostate-Specific Antigen Screening According to Health Professional Counseling and Age in the United States

Background. In 2018, the US Preventive Services Task Force recommended that PSA screening for prostate cancer involve men aged 55–69, based on a personal decision following consultation with a health professional. PSA screening in men aged 70 or older should only occur if symptoms exist. This study identifies the association between having a PSA test in the past two years and whether or not there was consultation with a health professional about the benefits and/or harms of PSA screening. Methods. Analyses were based on data involving men aged 40 years or older, who responded to PSA related questions in the 2018 BRFSS survey. Results. Approximately 32.0% (14.6% for ages 40–54, 41.7% for ages 55–69, and 49.8% for ages 70 years and older) of respondents had a PSA test in the past two years. Approximately 81.7% of these men had talked with a health professional about the benefits and/or harms of PSA screening, with 42.4% having discussed the benefits and harms, 54.6% having discussed the benefits only, and 3.0% having discussed the harms only. The odds of a PSA test in the past two years in men having talked with a health professional about the benefits and harms of the test versus no talk are 10.1 (95% CI 9.3–10.8), in men who talked with a health professional about the benefits only versus no talk are 10.8 (95% CI 10.0–11.6), and in men who talked with a health professional about the harms only versus no talk are 3.9 (95% CI 2.9–5.1). Conclusion. PSA screening is most common in men aged 70 or older, which is counter to the US Preventive Task Force recommendation. Most men having a PSA test have talked with a health professional about the test, but the talks tended to focus on just the benefits of screening and not both potential benefits and harms.

Cosmetic Appeal, HRQoL, and Effectiveness of Simple and Pseudotesticular Techniques of Orchidectomy in Prostate Cancer

Introduction. Orchidectomy is the most cost-effective means of hormonal therapy for locally advanced or metastatic prostate cancer (LAMP). However, cost-effectiveness should not detract from health-related quality of life (HRQoL) considerations. Bilateral simple orchidectomy (BSO) has been linked to negative psychometric deficits from an empty scrotum. This study compared the HRQoL, therapeutic efficacy, and cosmetic appeal of BSO with endogenous pseudotesticular techniques of bilateral subcapsular orchidectomy (BSCO) and bilateral-epididymal-sparing orchidectomy (BESO). Research Design. Nigerian patients with LAMP were randomised into three surgical arms: BSO, BSCO, and BESO. Expanded Prostate Cancer Index Composite-26 HRQoL and sociodemographic questionnaires were administered before and three months after orchidectomy. Serum testosterone and PSA were measured at 0, 1, 2, and 3 hours; 7 days; and 3 months postoperatively. Pseudotesticular volumes and cosmetic appeal were assessed at 3 months. Result. Sixty-three patients were recruited (24 BSO, 21 BSCO, 18 BESO), 73% of whom were low-income earners. There was no significant difference in the procedure cost nor the PSA or testosterone nadirs achieved over the three-month follow-up period (11.3, 12.6, 15.2 ng/ml ( p = 0.667 ) and 0.44, 0.64, 0.79 nmol/l ( p = 0.603 ) respectively). Those with pseudotesticles (BSCO, BESO) felt less emasculated ( p = 0.010 ). BSCO produced the least sexual bother, highest sexual function, and largest pseudotesticular volumes. The cosmetic appeal scores were similar between groups (77.9 ± 22.8, 81 ± 13.9, and 81.9 ± 22.5, respectively, p = 0.858 ). Conclusion. Endogenous pseudotesticular techniques, when compared with BSO, reduce the negative psychological impact experienced by patients without increasing costs. BSCO produced the best pseudotesticular volumes and postoperative sexual function. This study is registered with the ClinicalTrials.gov of the National Institute of Health U.S. National Library of Medicine as TEPSO study, NCT03744494: Comparison of the Therapeutic Efficacy and Patient Satisfaction of Three Techniques of Bilateral Orchidectomy in Prostate Cancer Patients of a Nigerian Sub-population. Registration completed on 16th of November, 2018 (registered retrospectively) NCT03744494.

Management of Patients with Nonmetastatic Castration-Resistant Prostate Cancer: Recommendations of a Multidisciplinary Panel of Experts from South America

Most prostate cancer patients who undergo androgen-deprivation therapy or orchiectomy will eventually develop castration-resistant prostate cancer (CRPC), often preceded by a nonmetastatic CRPC state known as M0CRPC. The recent development of second-generation antiandrogens provides clinicians with efficacious and safe treatments for M0CRPC. However, the complexity of these patients, who typically have to deal with underlying comorbidities and polypharmacy, often challenges therapeutic decisions in this setting. The recent development of novel imaging techniques also provides clinicians with tools for detecting metastases with high sensitivity and specificity. However, the lack of evidence on the early detection of metastases and the corresponding impact on therapeutic decisions makes these techniques a double-edged sword that must be managed appropriately. Here, we present the expert view of the rapidly evolving concept of M0CRPC and provide recommendations for the identification of these patients, the appropriate use of the emerging imaging modalities, and patients’ management, particularly considering their clinical complexity and the recent development of next-generation antiandrogens.

Relevance of Interleukins 6 and 8 Single Nucleotide Polymorphisms in Prostate Cancer: A Multicenter Study

The diverse roles of cytokines as IL-6 and IL-8 have been studied in terms of their SNPs in many diseases but their role in prostate cancer (PCa) is still uncertain. Aim. To determine the relevance of IL-6 rs1800795 SNP and/or IL-8 rs2227306 SNP with prostate cancer’s risk. Subjects and Methods. 40 PCa patients, 40 benign prostate hyperplasia (BPH) patients, and 40-age-matched-control group were enrolled in the study. Genotyping of IL-6 rs1800795 (G/C) SNP and IL-8 rs2227306 (C/T) SNP was determined using real-time PCR. Results. High frequency of IL-6 rs1800795GG and IL-8 rs2227306CC genotypes was noticed among PCa patients with associated OR 10.091 and 8.143, respectively. Comparisons based on allele frequencies revealed that IL-6G and IL-8C alleles are more frequent among PCa patients than other groups. Presence of IL-6 rs1800795G and IL-8 rs2227306C alleles in the same patient increase PCa risk by 16.7 times. Statistical correlations between PSA ratio and both of IL-6 and IL-8 SNP did not show any significant relation among PCa patients. Conclusion. IL-6 rs1800795G and IL-8 rs2227306C alleles could be considered risk factors for PCa development, particularly if presented together. However, no relation was found between both cytokines SNP and severity of prostate cancer.

Optimal PSA Threshold for Obtaining MRI-Fusion Biopsy in Biopsy-Naïve Patients

Objective. The study investigates the prostate-specific antigen threshold for adding targeted, software-based, magnetic resonance imaging-ultrasound fusion biopsy during a standard 12-core biopsy in biopsy-naïve patients. It secondarily explores whether the targeted biopsy is necessary in setting of abnormal digital rectal examination. Methods. 260 patients with suspected localized prostate cancer with no prior biopsy underwent prostate magnetic resonance imaging and were found to have Prostate Imaging Reporting and Data System score ≥ 3 lesion(s). All 260 patients underwent standard 12-core biopsy and targeted biopsy during the same session. Clinically significant cancer was Gleason ≥ 3 + 4. Results. Percentages of patients with prostate-specific antigen 0–1.99, 2–3.99, 4–4.99, 5–5.99, 6–9.99, and ≥ 10 were 3.0%, 4.7%, 20.8%, 16.9%, 37.7%, and 16.9%, respectively. Cumulative frequency of clinically significant prostate cancer increased with the addition of targeted biopsy compared with standard biopsy alone across all prostate-specific antigen ranges. The difference in clinically significant cancer detection between targeted plus standard biopsy compared to standard biopsy alone becomes statistically significant at prostate-specific antigen >4.3 ( p = 0.031 ). At this threshold, combination biopsy detected 20 clinically significant prostate cancers, while standard detected 14 with 88% sensitivity and 20% specificity. Excluding targeted biopsy in setting of a positive digital rectal exam would save 12.3% magnetic resonance imaging and miss 1.8% clinically significant cancers in our cohort. Conclusions. In biopsy-naïve patients, at prostate-specific antigen >4.3, there is a significant increase in clinically significant prostate cancer detection when targeted biopsy is added to standard biopsy. Obtaining standard biopsy alone in patients with abnormal digital rectal examinations would miss 1.8% clinically significant cancers in our cohort.

Implications of Regionalizing Care in the Developing World: Impact of Distance to Referral Center on Compliance to Biopsy Recommendations in a Brazilian Prostate Cancer Screening Cohort

Given growing specialization in medical care, optimal care may require regionalization, which may create access barriers. We tested this within a large prostate cancer (PC) screening program in Brazil. In 2004–2007, Barretos Cancer Hospital prospectively screened men for PC throughout rural Brazil. Men with abnormal screen were referred for follow-up and possible biopsy. We tested the link between distance from screening site to Barretos Cancer Hospital and risk of noncompliance with showing up for biopsy, PC on biopsy and, among those with PC, PC grade using crude and multivariable logistic regression analysis. Among 10,467 men undergoing initial screen, median distance was 257 km (IQR: 135–718 km). On crude and multivariable analyses, farther distance was significantly linked with biopsy noncompliance (OR/100 km: 0.83, P < 0.001 ). Among men who lived within 150 km of Barretos Cancer Hospital, distance was unrelated to compliance (OR/100 km: 1.09, P = 0.87 ). There was no association between distance and PC risk or PC grade (all P > 0.25 ). In Brazil, where distances to referral centers can be large, greater distance was related to reduced biopsy compliance in a PC screening cohort. Among men who lived within 150 km, distance was unrelated to compliance. Care regionalization may reduce access when distances are large.

The Weight of HLA-DPA1 rs3077 Single Nucleotide Polymorphism in Prostate Cancer, a Multicenter Study

Prostate cancer (PCa) has almost the highest genetic transmission that mimics an autosomal dominance hereditary pattern of cancers in some families. Its incidence in Arab countries was reported to be steadily increasing. Aim. To determine the relevance of HLA-DPA1 rs3077 (A/G) SNP with prostate cancer’s risk and/or severity. Subjects and Methods. Forty PCa patients and forty age matched patients with benign prostatic hyperplasia (BPH), as a control group, were enrolled in the study. Serum levels of urea, creatinine, total prostate-specific antigen (PSA), and free PSA were measured. PSA ratio was determined as well. Genotyping of HLA-DPA1 rs3077 (A/G) SNP was done using real-time PCR. Results. The measured lab parameters, except free PSA, were significantly higher among PCa patients in comparison to controls ( P < 0.001 ∗ ). Moreover, PSA ratio was significantly high among PCa patients ( P < 0.001 ∗ ). HLA-DPA1 rs3077 GG genotype was more frequent in PCa patients and the associated OR was 2.546 ( P = 0.059 ), while AA genotype was more frequent in the control group and the associated OR was 0.145 ( P = 0.081 ). Frequency of G allele was higher among PCa patients than the control group while A allele frequency was significantly decreased ( P = 0.034 ∗ ) (protective allele). On multivariate analysis, there is no significant correlation found between HLA-DPA1 rs3077 SNP and PSA ratio (OR = 4.5, 95% CI = 1.2–17.4, P = 0.856 ). Conclusion. HLA-DPA1 rs3077 G allele could be a risk factor for prostate cancer. However, HLA-DPA1 rs3077 SNP has no relation to PCa severity.

High Serum Alkaline Phosphatase Flare after First-Line Androgen Deprivation Therapy Predicts Poor Prognosis in Metastatic Prostate Cancer Patients Treated with Second-Generation Androgen Receptor Targeted Therapy

Objectives. To determine whether an alkaline phosphatase (ALP) flare after androgen deprivation therapy (ADT) is associated with the treatment response in castration-resistant prostate cancer (CRPC) and predicts the prognosis of metastatic prostate cancer (PCa) patients. Methods. One hundred and nineteen patients diagnosed with metastatic PCa between 2008 and 2017 were retrospectively studied. The ALP flare ratio was calculated as the ratio of ALP levels 1 month after beginning ADT to ALP levels at diagnosis. The association of the ALP flare ratio with the prostate-specific antigen (PSA) response to CRPC treatment (second-generation androgen receptor targeted therapy (ART) or docetaxel), time to CRPC, and overall survival (OS) were investigated. Results. The time to CRPC and OS was significantly longer in patients with an ALP flare ratio less than 1.33 compared to a ratio more than 1.33. No difference in PSA response was seen regarding the ALP flare ratio in both ART and docetaxel treatment. Second-generation ART-treated patients with a low ALP flare ratio showed longer OS than those with a higher ALP flare ratio ( p = 0.0367 ). However, no difference was seen between a high and low ALP flare ratio ( p = 0.8054 ) in docetaxel-treated patients. The ALP flare ratio was the most significant prognostic factor for OS ( p < 0.0001 ). Conclusions. A higher ALP flare ratio after first-line ADT was a significant prognostic factor in metastatic PCa, especially in patients treated with second-generation ART for CRPC. Chemotherapy for patients with a higher ALP flare ratio 1 month after induction of ADT may be a clinically relevant decision.

Predictive and Prognostic Role of Lipocalin-2 Expression in Prostate Cancer and Its Association with Gleason Score

Lipocalin-2 has an important role in tumor progression, invasion, and metastasis. However, its role in prostate cancer remains unclear. The objective of this study is to determine the expression level of lipocalin-2 in human prostate cancer tissues and to evaluate the relationship between its expression level and clinicopathologic parameters including response to docetaxel treatment, Gleason score, progression-free survival (PFS), and overall survival (OS). We retrospectively analyzed paraffin-embedded tissue sections from 33 metastatic castrate-resistant prostate cancer (mCRPC) patients whose clinical outcomes had been tracked after docetaxel treatment. The expression status of lipocalin-2 was defined by immunohistochemistry (IHC) using the anti-lipocalin-2 antibody. Lipocalin-2 was highly expressed in 36% of the examined specimens. There was no significant correlation between high lipocalin-2 expression and docetaxel response ( p : 0.09 ). High lipocalin-2 expression was significantly associated with a higher Gleason score ( p = 0.027 ). Kaplan–Meier survival analysis failed to show a significant correlation between expression levels of lipocalin-2 and both OS and PFS although patients with high lipocalin-2 levels had a numerically shorter PFS and OS time compared to patients with low levels. Consequently, it is clear that further studies are needed to evaluate the predictive and prognostic role of lipocalin-2 in prostate cancer patients.

A Multicentric, Retrospective Efficacy and Safety Study of Nanosomal Docetaxel Lipid Suspension in Metastatic Castration-Resistant Prostate Cancer

Purpose. To evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip) in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods. In this multicenter, retrospective study, we analyzed the medical charts of mCRPC patients, who were treated with NDLS administered as 2-weekly (50 mg/m2) or 3-weekly regimens (75 mg/m2). The study endpoints were prostate-specific antigen (PSA) response (>50% PSA decline from baseline), PSA progression (PSA increase from baseline beyond 12 weeks: ≥25% and ≥2 ng/mL), median PSA decline, and time-to-treatment failure (TTF). Overall survival (OS) and safety were also evaluated. Results. Data of 24 patients with mCRPC were analyzed in this study. NDLS was administered as a 2-weekly regimen in 37.5% (9/24; all first-line) patients and as a 3-weekly regimen in 62.5% patients (15/24; first-line: 20% (3/15), second-line: 80% (12/15)). Overall, PSA response was reported in 66.7% (16/24) patients. The PSA response was 77.8% (7/9 patients) in the 2-weekly group and 60% (9/15 patients) in the 3-weekly group. The median decline in PSA was 96.31% in the 2-weekly group and 83.29% in the 3-weekly group; the median TTF was 6.7 and 6.5 months in the 2 weekly group and 3-weekly group, respectively. The median OS was 14.6 months (follow-up: 5.5–25.8 months) in the 2-weekly group whereas it was not reached in the 3-weekly group (follow-up: 7.9–15.6 months). The most common hematological AEs were anemia, lymphopenia, thrombocytopenia, and neutropenia whereas nausea, weakness, constipation, vomiting, and diarrhea were the most common (≥10%) nonhematological AEs. Overall, NDLS treatment was well tolerated without any new safety concerns. Conclusions. Nanosomal docetaxel lipid suspension (2-weekly or 3-weekly) was effective and well tolerated in patients with metastatic castration-resistant prostate cancer.