PCa-related Mortality Research Articles

Long-term oncological outcomes of active surveillance for low-risk prostate cancer diagnosed during the MRI era.

Active surveillance (AS) is the recommended approach for managing Grade-Group1 (GG1) prostate cancer (PCa). Incorporating MRI at entry improve patient selection and outcomes. To evaluate long-term oncological outcomes of patients receiving AS selected with MRI at entry. Retrospective analysis of a single-center cohort of patients selected for AS from 2007 to 2022. Inclusion criteria were GG1 PCa with MRI prior to systematic and targeted biopsies. A per-protocol re-biopsy at one year has not been part of the AS inclusion criteria since 2015. Main outcome was cumulative incidence of: biopsy grade reclassification, AS discontinuation, active treatment, post-active treatment biochemical recurrence, metastasis, and mortality. Secondary outcome was the identification of risk factors for AS discontinuation. Cohort consists of 354 men. Median follow-up is 6.3 years (IQR: 3.2-9.1). Median PSA was 6.3ng/mL (5.0 to 8.5). At 10 years post-diagnosis, the cumulative incidence was 29.6% (95%CI: 23.3-36.2%) for grade reclassification, 40.0% (95%CI: 32.8-47.0%) for AS discontinuation, 36.9% (95% CI: 30.0-43.7) for active treatment, 9.4% (95% CI: 3.7-18.4) for post-active treatment biochemical recurrence and 0.5% for metastatic progression (2 patients). No PCa-related deaths were observed. PI-RADS score, and the number of positive biopsies at inclusion were identified as predictive factors for AS discontinuation. In this cohort of AS patients with MRI at entry, 60% of men remained on AS at 10 years, with less than 1% developing metastatic disease and no PCa-related mortality. These results support AS management with MRI at entry and add to share decision-making with patients. Level 2.

Statin use and mortality risk in Asian patients with prostate cancer receiving androgen deprivation therapy: A population-based cohort study.

This study aimed to examine the associations between the use of statins concurrent with androgen deprivation therapy (ADT) and the risks of mortality in Asian patients diagnosed with prostate cancer (PCa). Adult patients (≥18 years old) diagnosed with PCa who were receiving any form of ADT and were being treated at public hospitals in Hong Kong from December 1999 to March 2021 were retrospectively identified, with follow-up conducted until September 2021. Patients who had received medical castration for <180 days without subsequent bilateral orchidectomy, those who had used statins concurrently with ADT for <180 days, and those with missing baseline total cholesterol levels were excluded. Statin users were defined as individuals who had used statins for ≥180 days concurrent with ADT, while non-users were those who had not used any statins. PCa-related mortality was the primary outcome, while all-cause mortality served as the secondary outcome. Inverse probability treatment weighting was employed to balance the covariates. A total of 4920 patients were included, consisting of 2578 statin users and 2342 non-users (mean age 76.1 ± 8.2 years). Over a mean follow-up period of 4.2 ± 3.3 years, it was observed that statin users had significantly lower risks of both PCa-related mortality (weighted hazard ratio [wHR] 0.56 [95% confidence interval (CI) 0.48, 0.65], p < 0.001) and all-cause mortality (wHR 0.57 [95% CI 0.51, 0.63], p < 0.001), regardless of the type of ADT used. Notably, these associations were more pronounced among patients with less advanced PCa, as indicated by the absence of androgen receptor antagonist or chemotherapy usage (p value for interaction <0.001 for both outcomes). The use of statins concurrent with ADT was associated with reduced mortality risks among Asian patients with PCa. These findings suggest the need for additional research to explore the potential role of statins in the treatment of PCa patients.

Association between serum uric acid and prostate cancer mortality in androgen deprivation therapy: A population-based cohort study.

This population-based study examined the association between baseline uric acid (UA) and prostate cancer (PCa)-related mortality amongst PCa patients receiving androgen deprivation therapy (ADT). Adults with PCa who received ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with missing baseline UA were excluded. Patients were followed up until September 2021. The outcome was PCa-related mortality. Altogether, 4126 patients (median follow-up 3.1[interquartile range 1.4-6.0] years) were included. A J-shaped association was observed between baseline UA level and PCa-related mortality risk, with a direct association in those with mean(0.401 mmol/L) or above-mean baseline UA levels (hazard ratio (HR) per standard deviation-increase 1.35 [95% confidence interval 1.21,1.51], p < 0.001), and an inverse association in those with below-mean baseline UA levels (HR 0.78[0.67,0.92], p = 0.003). The former remained significant on competing risk regression, but not the latter. A J-shaped relationship between baseline UA level and PCa-related mortality risk was identified. This study was mainly limited by potential unmeasured and residual confounders. Further validation studies are warranted.

Clostridium scindens metabolites trigger prostate cancer progression through androgen receptor signaling.

Prostate cancer (PCa) is one of the most common malignancies in men; recently, PCa-related mortality has increased worldwide. Although androgen deprivation therapy (ADT) is the standard treatment for PCa, patients often develop aggressive castration-resistant PCa (CRPC), indicating the presence of an alternative source of androgen. Clostridium scindens is a member of the gut microbiota and can convert cortisol to 11β-hydroxyandrostenedione (11β-OHA), which is a potent androgen precursor. However, the effect of C. scindens on PCa progression has not been determined. In this study, androgen-dependent PCa cells (LNCaP) were employed to investigate whether C. scindens-derived metabolites activate androgen receptor (AR), which is a pivotal step in the development of PCa. Results showed that cortisol metabolites derived from C. scindens-conditioned medium promoted proliferation and enhanced migration of PCa cells. Furthermore, cells treated with these metabolites presented activated AR and stimulated AR-regulated genes. These findings reveal that C. scindens has the potential to promote PCa progression via the activation of AR signaling. Further studies on the gut-prostate axis may help unravel an alternative source of androgen that triggers CRPC exacerbation.

Metformin use and mortality in Asian, diabetic patients with prostate cancer on androgen deprivation therapy: A population-based study.

This study aims to examine the associations between metformin use concurrent with androgen deprivation therapy (ADT) and mortality risks in Asian, diabetic patients with prostate cancer (PCa). This study identified diabetic adults with PCa receiving any ADT attending public hospitals in Hong Kong between December 1999 and March 2021 retrospectively, with follow-up until September 2021. Patients with <6 months of medical castration without subsequent bilateral orchidectomy, <6 months of concurrent metformin use and ADT, or missing baseline HbA1c were excluded. Metformin users had ≥180 days of concurrent metformin use and ADT, while non-users had no concurrent metformin use and ADT or never used metformin. The primary outcome was PCa-related mortality. The secondary outcome was all-cause mortality. The study used inverse probability treatment weighting to balance covariates. The analyzed cohort consisted of 1971 patients (1284 metformin users and 687 non-users; mean age 76.2 ± 7.8 years). Over a mean follow-up of 4.1 ± 3.2 years, metformin users had significantly lower risks of PCa-related mortality (weighted hazard ratio [wHR]: 0.49 [95% confidence interval, CI: 0.39-0.61], p < 0.001) and all-cause mortality (wHR 0.53 [0.46-0.61], p < 0.001), independent of diabetic control or status of chronic kidney disease. Such effects appeared stronger in patients with less advanced PCa, which is reflected by the absence of androgen receptor antagonist or chemotherapy use (p value for interaction: 0.017 for PCa-related mortality; 0.048 for all-cause mortality). Metformin use concurrent with ADT was associated with lower risks of mortality in Asian, diabetic patients with PCa.

1416P Associations between metformin and mortality risks in Asian diabetic patients with prostate cancer undergoing androgen deprivation therapy: A retrospective cohort study

Metformin is associated with lower risks of developing prostate cancer (PCa), but its association with mortality in PCa is unclear. This study examined the associations between metformin use concurrent with androgen deprivation therapy (ADT) and mortality risks in Asian, diabetic patients with PCa. Diabetic adults with PCa receiving any ADT attending public hospitals in Hong Kong between December 1999 and March 2021 were retrospectively identified. Patients with <6 months of medical castration without subsequent bilateral orchidectomy, <6 months of concurrent metformin use and ADT, or missing baseline HbA1c were excluded. Metformin users had ≥6 months of concurrent metformin use and ADT, while non-users had no concurrent metformin use and ADT or never used metformin. Included patients were followed up until September 2021. The primary outcome was PCa-related mortality. The secondary outcome was all-cause mortality. Inverse probability treatment weighting was used to balance covariates. 1971 patients (1284 metformin users and 687 non-users; mean age 76.2±7.8 years) were studied. Over a mean follow-up of 4.1±3.2 years, metformin users had significantly lower risks of PCa-related mortality (weighted hazard ratio (wHR) 0.49 [95% confidence interval 0.39-0.61], p<0.001) and all-cause mortality (wHR 0.53 [0.46-0.61], p<0.001), independent of diabetic control or status of chronic kidney disease. Such associations appeared stronger in patients without androgen receptor antagonist or chemotherapy use (Table).Table: 1416PWeighted comparisons of outcomes by metformin usage with subgroups for androgen receptor antagonist or chemotherapy usage. Weighted hazard ratios (wHR) [95% confidence interval (CI)] were referenced against metformin non-usersAll patientsNever received androgen receptor antagonist or chemotherapy (N=1096)Received androgen receptor antagonist or chemotherapy (N=875)p value for interactionwHR [95% CI]p valuewHR [95% CI]p valuewHR [95% CI]p valueProstate cancer-related mortality0.49 [0.39, 0.61]<0.0010.38 [0.27, 0.52]<0.0010.59 [0.43, 0.81]0.0010.017All-cause mortality0.53 [0.46, 0.61]<0.0010.48 [0.40, 0.57]<0.0010.60 [0.48, 0.75]<0.0010.048 Open table in a new tab Metformin use concurrent with ADT was associated with lower risks of mortality in Asian, diabetic patients with PCa. Its role as adjuvant therapy for PCa warrants further study.

Differences in Prostate Cancer Incidence and Mortality in Lower Saxony (Germany) and Groningen Province (Netherlands): Potential Impact of Prostate-Specific Antigen Testing.

BackgroundProstate cancer (PCa) is the most frequent cancer among men in Europe. Differences in PCa incidence around the world can be partly explained by variations in recommendations for prostate-specific antigen (PSA), particularly for early detection. For example, the PSA testing policy is more conservative in the Netherlands than in Germany. To better understand the relationship between PSA testing recommendations and PCa incidence, stage distribution, and mortality, we compared these variables over time between Lower Saxony in northwestern Germany and the neighboring province of Groningen in the Netherlands.MethodsPopulation data, tumor stage- and age group-specific PCa incidence (ICD-10 C61) and mortality rates for Lower Saxony and Groningen were obtained from the Lower Saxony Epidemiological Cancer Registry, the Netherlands Comprehensive Cancer Organization, and Statistics Netherlands for 2003–2012. Incidence and mortality rates per 100,000 person-years were age-standardized (ASR, old European standard). Trends in age-standardized incidence rates (ASIR) and mortality rates (ASMR) for specific age groups were assessed using joinpoint regression.ResultsThe mean annual PCa ASIR between 2003 and 2012 was on average 19.9% higher in Lower Saxony than in Groningen (120.5 vs. 100.5 per 100,000), while the mean annual ASMR was on average 24.3% lower in Lower Saxony than in Groningen (21.5 vs. 28.4 per 100,000). Between 2003 and 2012, the average annual percentage change (AAPC) in PCa incidence rates did not change significantly in either Lower Saxony (−1.8%, 95% CI −3.5, 0.0) or Groningen (0.2%, 95% CI −5.0, 5.7). In contrast, the AAPC in mortality rate decreased significantly during the same time period in Lower Saxony (−2.5%, 95% CI −3.0, −2.0) but not in Groningen (0.1%, 95% CI −2.4, 2.6).ConclusionsHigher PCa incidence and lower PCa-related mortality was detected in Lower Saxony than in Groningen. Although recommendations on PSA testing may play a role, the assessed data could not offer obvious explanations to the observed differences. Therefore, further investigations including data on the actual use of PSA testing, other influences (e.g., dietary and ethnic factors), and better data quality are needed to explain differences between the regions.

Role of Exosomes in Prostate Cancer Metastasis.

Prostate cancer remains a life-threatening disease among men worldwide. The majority of PCa-related mortality results from metastatic disease that is characterized by metastasis of prostate tumor cells to various distant organs, such as lung, liver, and bone. Bone metastasis is most common in prostate cancer with osteoblastic and osteolytic lesions. The precise mechanisms underlying PCa metastasis are still being delineated. Intercellular communication is a key feature underlying prostate cancer progression and metastasis. There exists local signaling between prostate cancer cells and cells within the primary tumor microenvironment (TME), in addition to long range signaling wherein tumor cells communicate with sites of future metastases to promote the formation of pre-metastatic niches (PMN) to augment the growth of disseminated tumor cells upon metastasis. Over the last decade, exosomes/ extracellular vesicles have been demonstrated to be involved in such signaling. Exosomes are nanosized extracellular vesicles (EVs), between 30 and 150 nm in thickness, that originate and are released from cells after multivesicular bodies (MVB) fuse with the plasma membrane. These vesicles consist of lipid bilayer membrane enclosing a cargo of biomolecules, including proteins, lipids, RNA, and DNA. Exosomes mediate intercellular communication by transferring their cargo to recipient cells to modulate target cellular functions. In this review, we discuss the contribution of exosomes/extracellular vesicles in prostate cancer progression, in pre-metastatic niche establishment, and in organ-specific metastases. In addition, we briefly discuss the clinical significance of exosomes as biomarkers and therapeutic agents.

Long Noncoding RNA PVT1 Promotes Prostate Cancer Metastasis by Increasing NOP2 Expression via Targeting Tumor Suppressor MicroRNAs.

BackgroundMetastatic disease caused by prostate cancer (PCa) is the principal cause of PCa-related mortality. Long non-protein-coding RNAs may possess significant cellular functions. Plasmacytoma variant translocation 1 (PVT1), a long non-coding RNA encoded by the human PVT1 gene, is an oncogene, which can regulate several tumor-related genes. In PCa, the function and mechanism of PVT1 are unclear. NOP2 is being pursued as a prognostic marker for cancer aggressiveness, which promotes mouse fibroblast growth and tumor formation. Essentially, nothing is known about the specific interactions between the PVT1 and NOP2.Methods 190 pairs of PCa tissues and adjacent normal tissues were collected and RNA sequencing was used to identify the differential lncRNAs. Real-time quantitative real-time PCR (RT-qPCR) confirmed these results and gene regulatory relationship. Lentiviral vectors were used to alter PVT1 and genes to analyze their effects on PCa progression. Transwell migration and invasion assays were performed to test the metastasis ability. Biofunction of PVT1 and NOP2 were confirmed in vitro and in vivo.ResultsIn this study, we reported that the long noncoding RNA-PVT1 was upregulated in PCa metastasis tissues and promoted migration of PCa cells in vitro and their metastasis in vivo. High levels of PVT1 significantly downregulated tumor suppressor microRNAs (miRNAs), such as miR-15b-5p, miR-27a-3p, miR-143-3p, and miR-627-5p, whose levels in metastasis tissues were low compared to those in non-metastasis tissues. In vitro and in vivo, PVT1 promotes PCa metastasis via targeting miRNAs. Furthermore, the expression level of PVT1 was positively associated with the expression of NOP2, a cancer metastasis-related protein. We demonstrated that NOP2 promoted invasion and migration of PCa. For specific mechanism, correlation analysis showed that PVT1 promoted metastasis by up-regulating NOP2.ConclusionTaken together, our results show that PVT1 acts as an inducer of PCa metastasis via targeting miRNAs, thereby promoting NOP2. This axis may have diagnostic and therapeutic potential for advanced PCa.

The impact of 5-alpha-reductase inhibitors on mortality in a prostate cancer chemoprevention setting: a meta-analysis.

This study aims to evaluate the impact of 5-alpha-reductase inhibitors (5ARI) for prostate cancer (PCa) primary prevention on specific and overall mortality (primary outcomes), the incidence of PCa diagnosis and disease aggressiveness (secondary outcomes). We searched MEDLINE, EMBASE, Cochrane, ClinicalTrials and BVS through April 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement to identify randomized clinical trials (RCT) and cohort studies (CS). We included articles with data on mortality or PCa incidence for men using 5ARI previously to PCa diagnosis. Regarding the included studies, nine had data on mortality, 16 on PCa incidence and 12 on Gleason scores (GS). We found that the use of 5ARI had no impact on overall mortality (RR 0.93 95% CI 0.78-1.11) and PCa-related mortality (RR 1.35 95% CI 0.50-3.94), nor on high-grade PCa diagnosis (RR 1.06 95% CI 0.72-1.56). We identified a relative risk reduction of 24% in moderate-grade PCa diagnosis (RR 0.76 95% CI 0.59-0.98) and low-grade PCa diagnosis (RR 0.76 95% CI 0.59-0.97) Also, a reduction of 26% in overall PCa diagnosis was observed in the RCT subgroup analysis (RR 0.74 95% CI 0.65-0.84). 5ARI significantly reduced the risk of being diagnosed with PCa, not increasing high-grade disease, overall or cancer-specific mortality. Due to the relatively short mean follow-up of most studies, the mortality analysis is limited.

Robot-assisted radical prostatectomy vs. open radical prostatectomy: latest evidences on perioperative, functional and oncological outcomes.

Despite increasing use of robotic surgery for radical prostatectomy, the benefit of robotic over open approach on different postoperative outcomes is still under debate. The present review aimed to provide a framework on the latest evidences on outcomes of prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP) vs. open radical prostatectomy (ORP). Specifically, we focused on postoperative complications, urinary continence and erectile function recovery, PCa recurrence and PCa-related mortality. Regarding perioperative outcomes, recent studies confirmed lower blood loss, transfusion rates and shorter catheterization time for RARP compared with ORP. Postoperative complications are lower in retrospective analyses, but this trend was not confirmed in prospective studies. Functional outcomes are comparable between RARP and ORP, with a slight nonclinically meaningful benefit in favour of RARP. The mid-term update of a recent randomized trial showed better oncological outcomes at 24 months, but the strength of this finding is limited by methodological flaws. Conversely, contemporary retrospective studies did not demonstrate differences in terms of biochemical recurrence between the two surgical approaches. The recent large uptake of RARP relative to ORP was sustained by evidences showing improved perioperative outcomes but not clear benefit on functional and oncological outcomes.

Lipid quantification by Raman microspectroscopy as a potential biomarker in prostate cancer

Metastatic castration-resistant prostate cancer (mCRPC) remains incurable and is one of the leading causes of cancer-related death among American men. Therefore, detection of prostate cancer (PCa) at early stages may reduce PCa-related mortality in men. We show that lipid quantification by vibrational Raman Microspectroscopy and Biomolecular Component Analysis may serve as a potential biomarker in PCa. Transcript levels of lipogenic genes including sterol regulatory element-binding protein-1 (SREBP-1) and its downstream effector fatty acid synthase (FASN), and rate-limiting enzyme acetyl CoA carboxylase (ACACA) were upregulated corresponding to both Gleason score and pathologic T stage in the PRAD TCGA cohort. Increased lipid accumulation in late-stage transgenic adenocarcinoma of mouse prostate (TRAMP) tumors compared to early-stage TRAMP and normal prostate tissues were observed. FASN along with other lipogenesis enzymes, and SREBP-1 proteins were upregulated in TRAMP tumors compared to wild-type prostatic tissues. Genetic alterations of key lipogenic genes predicted the overall patient survival using TCGA PRAD cohort. Correlation between lipid accumulation and tumor stage provides quantitative marker for PCa diagnosis. Thus, Raman spectroscopy-based lipid quantification could be a sensitive and reliable tool for PCa diagnosis and staging.

Overexpression of the Long Non-coding RNA SChLAP1 Independently Predicts Lethal Prostate Cancer

The long noncoding RNA SChLAP1 is overexpressed in a subset of prostate cancers (PCa), and high SChLAP1 expression by in situ hybridization (ISH) independently predicts biochemical recurrence after radical prostatectomy. Importantly, although biochemical recurrence is a significant clinical outcome, it is not a validated surrogate for PCa-related mortality. Thus, we evaluated the association between SChLAP1 expression and development of lethal PCa in a large cohort of American men with PCa and long-term follow-up. SChLAP1 ISH was performed on tissue microarrays containing representative formalin-fixed, paraffin-embedded PCa tissue from all patients and scored using a semiquantitative method (ISH score range 0–400). Hazard ratios (HRs) for the association between SChLAP1 expression and time to development of lethal PCa were estimated using multivariable Cox regression analysis. Of the 937 patients evaluated, 89 (9.5%) had high SChLAP1 expression (ISH score ≥100), which in patients treated with radical prostatectomy was strongly associated with development of lethal PCa independent of age, Gleason score, pathologic stage, and PTEN status (HR 2.2, 95% confidence interval 1.1–4.1). These results suggest that SChLAP1 may be a useful tissue-based biomarker for identifying PCa patients at higher risk of lethal progression. Patient summaryWe examined expression of the RNA molecule SChLAP1 in a large group of prostate cancer patients with long-term follow-up and found that patients with high SChLAP1 expression had a significantly higher chance of developing lethal disease.

Multigene Methylation Biomarker Analysis in Prostate Cancer

Prostate cancer (PCa) a leading cause of cancer-related death in men. Prostate specific antigen (PSA) screening has reduced PCa-related mortality but at the high price of over-detection of latent disease. Furthermore, PSA is marred by an unacceptably high false-positive rate. Thus, alternative biomarkers are required. Promoter hypermethylation at specific gene loci is known to be a prevalent oncogenic event in PCa. The aim of this study was to carry out an integrative, quantitative analysis of DNA methylation to determine a highly PCa-specific panel that could be used as a molecular correlate of adverse clinicopathologic features as an adjunct to PSA to improve the early detection of PCa. We examined methylation of 9 genes (APC, CDKN2A, DCR2, GSTP1, IGFBP3, IGFBP7, PTGS2, SFRP2 and TMS1) in combination, in PCa and control groups: tumor-adjacent histologically benign tissue (TAB) and benign prostatic hyperplasia (BPH), from men with no evidence of PCa. Using a previously reported analytic method, a methylation (M) score was calculated for each sample to predict the risk of PCa in individual subjects, by summing the log odds ratio for each gene analyzed by multivariate logistic regression analysis of tumor versus benign. Two multi-gene methylation panels (M_score(APC, GSTP1, IGFBP3) and M_score(APC, GSTP1)) were identified, which differentiated between PCa and TAB (sensitivity 91.1%; specificity 80%) or PCa and BPH (sensitivity 91%; specificity 85.9%), respectively. The high tumor-specificity of the M_score warrants further investigations into liquid samples of blood and urine to determine the sensitivity of this test for non-invasive detection of PCa. Keywords: Biomarker, DNA methylation, epigenetics, prostate cancer.

MP4-10 ONE OUT OF THREE INFERTILE MEN YOUNGER THAN 40 YEARS HAVE A TOTAL SERUM PSA VALUE GREATER THAN 1 NG/ML - FINDINGS OF A CROSS-SECTIONAL SURVEY IN WHITE-EUROPEAN MEN PRESENTING FOR COUPLE'S INFERTILITY

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History I1 Apr 2015MP4-10 ONE OUT OF THREE INFERTILE MEN YOUNGER THAN 40 YEARS HAVE A TOTAL SERUM PSA VALUE GREATER THAN 1 NG/ML - FINDINGS OF A CROSS-SECTIONAL SURVEY IN WHITE-EUROPEAN MEN PRESENTING FOR COUPLE'S INFERTILITY Alessandro Serino, Paolo Capogrosso, Luca Boeri, Eugenio Ventimiglia, Giovanni La Croce, Giulia Castagna, Angela Pecoraro, Marco Paciotti, Silvia Ippolito, Roberta Scano, Rocco Damiano, Francesco Montorsi, and Andrea Salonia Alessandro SerinoAlessandro Serino More articles by this author , Paolo CapogrossoPaolo Capogrosso More articles by this author , Luca BoeriLuca Boeri More articles by this author , Eugenio VentimigliaEugenio Ventimiglia More articles by this author , Giovanni La CroceGiovanni La Croce More articles by this author , Giulia CastagnaGiulia Castagna More articles by this author , Angela PecoraroAngela Pecoraro More articles by this author , Marco PaciottiMarco Paciotti More articles by this author , Silvia IppolitoSilvia Ippolito More articles by this author , Roberta ScanoRoberta Scano More articles by this author , Rocco DamianoRocco Damiano More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Andrea SaloniaAndrea Salonia More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.153AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous data have suggested that infertile men have an increased risk of high-grade prostate cancer (PCa). In this context, male infertility may be considered an early and identifiable risk factor for the development of clinically significant PCa. We sought to assess serum PSA levels in men presenting for couples infertility, according to the EAU recommendation that a baseline serum PSA level should be obtained at 40–45 years of age (Heidenreich A, et al. Eur Urol 2013;64:347-54). METHODS Complete data from 403 consecutive men seeking medical help for couple's infertility were analyzed. Primary and secondary infertility were defined according to the World Health Organization (WHO) definition criteria. According to EAU recommendations, patients were stratified as younger (group 1) and older than 40 yrs (group 2). Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI; categorized 0 vs 1 vs ≥2). Testicular volume was assessed with a Prader orchidometer. Semen analysis values were assessed based on 2010 WHO reference criteria. Descriptive statistics and logistic regression models tested the association between potential predictors and total PSA levels. RESULTS Mean (SD; range) age was 36 [3.2 (21–40)] and 46.5 [5 (41–73)] in group 1 [n=198 (49.1%)] and group 2 [n=205 (50.9%)], respectively. Length of couple's infertility at first presentation was 27.7 (23.3; 12–204) and 31.3 (29.5; 12–280) months in group 1 and 2, respectively. Mean PSA levels were 0.93 ng/mL [0.6 (0.01-4.47)] and 0.96 ng/mL [1.2 (0.02-15.3)] in group 1 and group 2, respectively. Of group 1, 68 (34.3%) patients had serum PSA values >1 ng/mL. No differences were found in terms of age, BMI, CCI, testicular volumes, semen parameters, and rates of primary vs secondary infertility between patients of group 1 with PSA levels above vs below 1 ng/mL. At multivariate logistic regression analysis no clinical variables achieved independent predictive value for serum PSA >1 ng/mL in group 1. CONCLUSIONS These cross-sectional data showed that one out of three infertile men younger than 40 years have a total serum PSA value greater than 1 ng/mL. Current findings acquire significant clinical importance according to the EAU recommendations for early detection of PCa, which may reduce PCa-related mortality and reduce the risk of developing advanced and metastatic PCa. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e30 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alessandro Serino More articles by this author Paolo Capogrosso More articles by this author Luca Boeri More articles by this author Eugenio Ventimiglia More articles by this author Giovanni La Croce More articles by this author Giulia Castagna More articles by this author Angela Pecoraro More articles by this author Marco Paciotti More articles by this author Silvia Ippolito More articles by this author Roberta Scano More articles by this author Rocco Damiano More articles by this author Francesco Montorsi More articles by this author Andrea Salonia More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Importance of long chain omega-3 fatty acids in prostate cancer

The benefits of long chain polyunsaturated omega-3 fatty acids (n-3 PUFA) from fish or administered as supplements remain controversial regarding prostate cancer (PCa). Based on the currently available evidence no clear benefit of n-3 PUFA intake to generally reduce PCa incidence has been found. On the other hand n-3 PUFAs have a clear influence on the development of already existing PCa. The intake of n-3-PUFAs considerably reduces the risk of metastasis and PCa-related mortality.

Prostate cancer trends in Latvia during 1990–2012: Incidence, prevalence, mortality, and survival rates

Background and objectiveProstate cancer (PCa) is one of the most common form of cancer in males worldwide. One of the highest PCa-related mortality rates in the world is observed in Latvia. Materials and methodsOur study included male patients diagnosed with PCa between 1990 and 2012. We analyzed incidence, prevalence and mortality trends using joinpoint analysis. Kaplan–Meier analysis was performed for 5-, 10-, 15- and 20-year overall survival and cancer-specific survival rates. ResultsA total of 14,083PCa patients with a mean age of initial PCa diagnosis being 70.1 (SD 8.6) was registered. The standardized incidence rates (per 100,000) increased from 18.9 in 1990 to 74.7 in 2012, while the standardized prevalence rates (per 100,000) increased from 69.9 in 1990 to 437.6 in 2012. Standardized PCa mortality rates (per 100,000) also rose from 13.2 in 1990 to 27.2 in 2006 followed by statistically insignificant decrease continuing up to 2012. The mean 5-year cancer-specific survival rates increased from 43.6% in 1990 to 70.7% in 2007, and the mean 10-year cancer-specific survival rates from 32.9% in 1990 to 40.5% in 2001. ConclusionsThis study revealed that the incidence, prevalence and mortality rates increased between 1990 and 2012, and although the 5- and 10-year overall and cancer-specific survival rates improved over the reviewed period they still needed to get better.

Minireview: The Molecular and Genomic Basis for Prostate Cancer Health Disparities

Despite more aggressive screening across all demographics and gradual declines in mortality related to prostate cancer (PCa) in the United States, race disparities persist. For African American men (AAM), PCa is more often an aggressive disease showing increased metastases and greater PCa-related mortality compared with European American men. The earliest research points to how distinctions are likely the result of a combination of factors, including ancestry genetics and lifestyle variables. More recent research considers that cancer, although influenced by external forces, is ultimately a disease primarily driven by aberrations observed in the molecular genetics of the tumor. Research studying PCa predominantly from European American men shows that indolent and advanced or metastatic prostate tumors have distinguishing molecular genomic make-ups. Early yet increasing evidence suggests that clinically distinct PCa from AAM also display molecular distinctions. It is reasonable to predict that further study will reveal molecular subtypes and various frequencies for PCa subtypes among diverse patient groups, thereby providing insight as to the genomic lesions and gene signatures that are functionally implicated in carcinogenesis or aggressive PCa in AAM. That knowledge will prove useful in developing strategies to predict who will develop advanced PCa among AAM and will provide the rationale to develop effective individualized treatment strategies to overcome disparities.

The effect of prostate cancer screening on stage IV disease in America

Some studies have found that prostate cancer (PCa) screening provides little or no change in PCa-related mortality during the 7-10 years following diagnoses. However, most men are diagnosed with PCa at low-stage disease and die of unrelated causes during this period. Men diagnosed at stage IV are at much higher risk of dying of the disease. Therefore, stage IV rates at first diagnoses may be a surrogate marker of PCa-related mortality over a time span less than 10 years. The study objective is to examine the association between PCa screening and stage IV disease rates in new cases to explore potential benefits for PCa screening. The percent of stages I, II, III, IV and unclassified PCa diagnosed in white males in 2005 was compared to PCa screening rates on a state-by-state basis. To consider access to medical care and socioeconomic status, median family income, degree of urbanization, urologist population density and health insurance status were included in the analysis. PCa stage IV disease correlated inversely with PCa screening rates (r = -0.42, P = 0.006) where r is the correlation coefficient and P is the probability. Stage I PCa correlated with lack of health insurance (r = 0.37, P = 0.02). The results of this study suggest that with PCa screening may be associated with reduced rates of stage IV disease.

Should Pathologists Routinely Report Prostate Tumour Volume? The Prognostic Value of Tumour Volume in Prostate Cancer

BackgroundThe independent prognostic value of tumour volume in radical prostatectomy (RP) specimens is controversial, and it remains a matter of debate whether pathologists should report a measure of tumour volume. In addition, tumour volume might be of value in substaging of pathologic tumour stage (pT2) prostate cancer (PCa). ObjectiveTo assess the prognostic value of PCa tumour volume. Design, setting, and participantsThe cohort consisted of 344 participants in the European Randomised Study of Screening for Prostate Cancer (ERSPC), Rotterdam section, whose PCa was treated with RP. Mean time of follow-up was 96.2 mo. MeasurementsTumour volume was measured in totally embedded RP specimens with a morphometric, computer-assisted method and assessed as a continuous variable, as relative tumour volume (tumour volume divided by prostate volume), and in a binary fashion (≥0.5ml or <0.5ml). These variables were related to prostate-specific antigen (PSA) progression, local recurrence, or distant metastasis and PCa-related mortality using univariate and multivariable Cox proportional hazards analyses. The analyses were repeated in the subgroup with pT2 tumours. Results and limitationsTumour volume was related to tumour stage, Gleason score, seminal vesicle invasion (SVI), and surgical margin status. In univariate analyses, tumour volume and relative tumour volume were predictive for all outcome variables. In multivariable analyses, including age, tumour stage, Gleason score, SVI, and surgical margin status, neither tumour volume nor relative volume were independent predictors of progression or mortality. Tumour volume ≥0.5ml was predictive for PSA recurrence and local and/or distant progression in univariate analyses but not in multivariable analyses. Tumour volume was not predictive for recurrence or mortality in univariate or multivariable analyses in the pT2 subgroup. ConclusionsTumour volume did not add prognostic value to routinely assessed pathologic parameters. Therefore, there seems to be little reason to routinely measure tumour volume in RP specimens.