Transdermal oestradiol and exercise in androgen deprivation therapy (ESTRACISE): protocol.

OBJECTIVE: To report the protocol of a study evaluating the efficacy of transdermal oestradiol (E2) gel in reducing the adverse effects of androgen deprivation therapy (ADT), specifically on sexual function, and to assess the utility of E2 in combination with supervised exercise. STUDY DESIGN AND METHODS: The primary endpoint of this open-label Phase IIA randomized controlled trial is the efficacy of transdermal E2 gel. Secondary endpoints include: (i) the occurrence of ADT-induced adverse effects; (ii) the safety and tolerability of E2; (iii) the impact of E2 with or without exercise on physical, physiological, muscle, and systemic biomarkers; and (iv) quality of life. The trial will recruit high-risk PCa patients (n = 310) undergoing external beam radiation therapy with adjuvant subcutaneous ADT. Participants will be stratified and randomized in a 1:1 ratio to either the E2 + ADT arm or the ADT-only control arm. Additionally, a subset of patients (n = 120) will be randomized into a supervised exercise programme. RESULTS: The primary outcome is assessed according to the efficacy of E2 in mitigating the deterioration of Expanded Prostate Cancer Index Composite sexual function domain scores. Secondary outcomes are assessed according to the occurrence of ADT-induced adverse effects, safety and tolerability of E2, impact of E2 with or without exercise on physical performance, body composition, bone mineral density, muscle size, systematic biomarkers, and quality of life. CONCLUSION: The ESTRACISE study's innovative design can offer novel insights about the benefits of E2 gel, and the substudy can reinforce the benefits resistance training and deliver valuable new novel insights into the synergistic benefits of E2 gel and exercise, which are currently unknown. TRIAL REGISTRATION: The protocol has been registered in euclinicaltrials.eu (2023-504704-28-00) and in clinicaltrials.gov (NCT06271551).

Previous inguinal hernia surgery does not limit the likelihood of choosing prostatectomy as primary prostate cancer therapy.

We evaluated whether previous inguinal hernia repair may affect the choice of prostate carcinoma treatment in a population-based cohort. It has been suggested that previous laparoscopic inguinal hernia repair (LIHR) could limit the subsequent possibility of performing a prostatectomy. Several small studies have suggested otherwise. The study cohort included all new prostate cancer cases in Finland 1998-2015 identified through the Finnish cancer registry. Data on the treatment of prostate cancer and surgical inguinal hernia repairs in 1998-2016 was obtained from the HILMO hospital discharge registry. After linkage, the study cohort included 7206 men. Of these, 5500 had no history of inguinal hernia, 1463 had an open hernia repair, and 193 had a minimally invasive repair (LIHR). Compared to men with no history of hernia repair, those with previous hernia repairs were more likely to undergo prostatectomy over radiation therapy as the primary treatment for prostate cancer HR 1.34 (CI 95% 1.19-1.52). The association did not depend on the method of hernia repair, HR 1.58 (CI 95% 1.15-2.18), in men with previous LIHR. The increased likelihood of choosing prostatectomy over radiation therapy concerns all type prostatectomies. Previous hernia repair is not a limiting factor when choosing treatment for prostate cancer.

MiR26a reverses enzalutamide resistance in a bone-tumor targeted system with an enhanced effect on bone metastatic CRPC.

Resistance to androgen receptor (AR) inhibitors, including enzalutamide (Enz), as well as bone metastasis, are major challenges for castration-resistant prostate cancer (CRPC) treatment. In this study, we identified that miR26a can restore Enz sensitivity and inhibit bone metastatic CRPC. To achieve the highest combination effect of miR26a and Enz, we developed a cancer-targeted nano-system (Bm@PT/Enz-miR26a) using bone marrow mesenchymal stem cell (BMSC) membrane and T140 peptide to co-deliver Enz and miR26a. The in vitro/in vivo results demonstrated that miR26a can reverse Enz resistance and synergistically shrink tumor growth, invasion, and metastasis (especially secondary metastasis) in both subcutaneous and bone metastatic CRPC mouse models. We also found that the EZH2/SFRP1/WNT5A axis may be involved in this role. These findings open new avenues for treating bone metastatic and Enz-resistant CRPC.

Protocol of a randomised, controlled trial comparing immediate curative therapy with conservative treatment in men aged ≥75 years with non-metastatic high-risk prostate cancer (SPCG 19/GRand-P).

BACKGROUND: Older men (aged ≥75 years) with high risk, non-metastatic prostate cancer (PCa) are increasingly treated with curative therapy (surgery or radiotherapy). However, it is unclear if curative therapy prolongs life and improves health-related quality of life (HRQoL) in this age group compared to conservative therapy, which has evolved considerably during the last decade. STUDY DESIGN: The Scandinavian Prostate Cancer Group (SPCG) 19/Norwegian Get-Randomized Research Group-Prostate (GRand-P) is a randomised, two-armed, controlled, multicentre, phase III trial carried out at study centres in Norway, Denmark, Finland, and Sweden. ENDPOINTS: The primary endpoints are overall survival and HRQoL (burden of disease scale, European Organisation for the Research and Treatment of Cancer [EORTC] Elderly Cancer patients). Secondary endpoints are PCa-specific survival, metastasis-free survival, role-functioning scale (EORTC quality of life questionnaire 30-item core), urinary irritative/obstructive scale (26-item Expanded Prostate Cancer Index Composite [EPIC-26]), bowel scale (EPIC-26), intervention-free survival, PCa morbidity, use of secondary and tertiary systemic therapies, mean quality-adjusted life-years (QALYs), and mean total healthcare costs. PATIENTS AND METHODS: A total of 980 men (aged ≥75 years) with non-metastatic, high-risk PCa will initially be screened with Geriatric 8 (G8) health status screening tool and Mini-COG© brief cognitive test. Participants identified by G8 as 'fit' or 'frail' will be randomised (ratio 1:1) to either immediate curative therapy (radiotherapy or prostatectomy) or conservative therapy (endocrine therapy or observation). Participants who are unable or unwilling to participate in randomisation will be enrolled in a separate observation group. Randomised patients will be followed for 10 years. TRIAL REGISTRATION: Ethics approval has been granted in Norway (457593), Denmark (H-22051998), Finland (R23043) and Sweden (Dnr 2023-05296-01). The trial is registered on Clinicaltrials.org (NCT05448547).

Prognostic factors of renal cell cancer in elderly patients: a population-based cohort study.

Mortality in renal cell cancer (RCC) is high in the elderly population. Comorbidities have a greater impact on overall prognosis of RCC among elderly patients than in younger patients. All new RCC cases were collected in people over 74 years of age between 1995 and 2018 from the Finnish cancer registry. The comorbidities were identified from the Care Registry for Healthcare. Charlson Comorbidity Index (CCI) was used to evaluate the risk of death based on comorbidities. The overall risk of death was analyzed using the Cox regression model. The risk for RCC death was analyzed using Fine and Gray regression analysis. Individual prognostic role of CCI components was evaluated by adding each component separately into the multivariable Fine and Gray regression model. Using the most prognostic comorbidities we constructed a nomogram to predict RCC mortality. Statistically significant prognostic factors of RCC death were tumor morphology (clear cell, papillary and chromophobe), sex, operative treatment, age, primary tumor extent and CCI. The strongest prognostic factors for overall mortality were tumor extent, tumor morphology and operative treatment. Among the components of CCI, the most important comorbidities predicting mortality were dementia, heart failure and kidney disease. The limitation of this study is that the comorbidities have only been recorded at inpatient and outpatient hospital contacts, which is why the prevalence of comorbidities is probably underestimated. In addition, physical performance status was not available from registry data, but it significantly affects the treatment decisions. RCC mortality is high in the elderly population. Among comorbidities, dementia and heart failure have the greatest impact on the prognosis. Curative treatment in selected elderly patients is efficient and should be considered in patients who can tolerate it and have only limited comorbidities.

Research protocol to identify progression and death amongst patients with metastatic hormone-sensitive prostate cancer treated with available treatments: PIONEER IMI's "big data for better outcomes" program.

Androgen deprivation therapy-based with or without first-generation anti-androgens, was the standard of care for patients with metastatic hormone-sensitive prostate cancer (mHSPC) for decades. However, the development of docetaxel chemotherapy and new androgen receptor-targeted agents, abiraterone acetate and prednisolone, apalutamide , enzalutamide and darolutamide (in combination with docetaxel chemotherapy) has proven that combination of treatments is more effective. Recently, intensification therapy, so-called "triplets", have emerged in the armamentarium of mHSPC treatment. Metastatic disease is a clinical state that remains poorly understood. The optimal diagnostic and management of patients with mHSPC are changing thanks to the development of new imaging techniques and therapies. The primary objective of this study is to develop and validate a predictive model for the occurrence of symptomatic progression, initiation of new treatments and death amongst patients with mHSPC treated with one of the approved treatment plans, on characteristics present at admission.

Testosterone replacement therapy is not associated with increased prostate cancer incidence, prostate cancer-specific, or cardiovascular disease-specific mortality in Finnish men.

BACKGROUND: Concerns have been expressed over the safety of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH). Previous studies have shown controversial results regarding the association of TRT with the risk of cardiovascular events or prostate cancer (PCa) incidence, aggressiveness, and mortality. This study explores the overall risk of PCa and risk by tumor grade and stage, as well as mortality from PCa and cardiovascular disease (CVD), among men treated with TRT compared to men without LOH and TRT use. MATERIALS AND METHODS: The study included 78,615 men of age 55-67 years at baseline from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Follow-up started at randomization and ended at death, emigration, or a common closing date January 1st, 2017. Cox proportional hazards regression model with time-dependent variables and adjustment for age, trial arm, use of other medications, and Charlson comorbidity index was used. Comprehensive information on TRT purchases during 1995-2015 was obtained from the Finnish National Prescription Database. PCa cases were identified from the Finnish Cancer Registry and causes of death obtained from Statistics Finland. RESULTS: Over the course of 18 years of follow-up, 2919 men were on TRT, and 285 PCa cases were diagnosed among them. TRT users did not exhibit a higher incidence or mortality rate of PCa compared to non-users. On the contrary, men using TRT had lower PCa mortality than non-users (HR = 0.52; 95% CI 0.3-0.91). Additionally, TRT users had slightly lower CVD and all-cause mortality compared to non-users (HR = 0.87; 95% CI 0.75-1.01 and HR = 0.93; 95% CI 0.87-1.0, respectively). No time- or dose-dependency of TRT use was evident in any of the analyses. CONCLUSION: Men using TRT were not associated to increased risk for PCa and did not experience increased PCa- or CVD-specific mortality compared to non-users. Further studies considering blood testosterone levels are warranted.

Statin Use, Cholesterol Level, and Mortality Among Females With Breast Cancer.

Importance: Several studies have reported an association between the use of statins and breast cancer (BC) mortality. However, most of these studies did not take into account the underlying cholesterol level. Objective: To investigate the association between serum cholesterol, statin use, and BC mortality. Design, Setting, and Participants: This cohort study included females with invasive BC that was newly diagnosed between January 1, 1995, and December 31, 2013, in Finland. The cohort had available hormone receptor data and at least 1 cholesterol measurement. All data were obtained from Finnish national registries. Statistical analyses were performed from January to May 2022. Exposure: Use of statins; statin dose; and serum cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels measured separately before and after BC diagnosis. Main Outcomes and Measures: Breast cancer mortality and overall mortality between date of BC diagnosis and December 31, 2015. Results: A total of 13 378 female patients with BC (median [IQR] age, 62 [54-69] years) participated in the study. The median (IQR) follow-up was 4.5 (2.4-9.8) years after BC diagnosis, during which 16.4% of patients died and 7.0% died of BC. Prediagnostic statin use was a risk factor for BC death even after adjustment for total cholesterol level (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46; P = .03). Reduced risk for BC death was seen for postdiagnostic statin use (HR, 0.85; 95% CI, 0.73-1.00; P = .05). The risk reduction was robust in participants whose cholesterol level decreased after starting statins (HR, 0.49; 95% CI, 0.32-0.75; P = .001) but was nonsignificant if cholesterol level did not subsequently decrease (HR, 0.69; 95% CI, 0.34-1.40; P = .30). Reduced BC mortality among statin users was also observed in females with estrogen receptor-positive tumors (HR, 0.82; 95% CI, 0.68-0.99; P = .03). Overall mortality was lower among statin users vs nonusers when adjusted for serum cholesterol level (HR, 0.80; 95% CI, 0.72-0.88; P < .001). Conclusions and Relevance: Results of this cohort study showed that postdiagnostic use of statins was associated with reduced BC mortality compared with nonuse, and the risk was associated with subsequent change in serum cholesterol level. This finding suggests that cholesterol-lowering interventions with statins may be beneficial for patients with BC.

Cancer origin tracing and timing in two high-risk prostate cancers using multisample whole genome analysis: prospects for personalized medicine.

BACKGROUND: Prostate cancer (PrCa) genomic heterogeneity causes resistance to therapies such as androgen deprivation. Such heterogeneity can be deciphered in the context of evolutionary principles, but current clinical trials do not include evolution as an essential feature. Whether or not analysis of genomic data in an evolutionary context in primary prostate cancer can provide unique added value in the research and clinical domains remains an open question. METHODS: We used novel processing techniques to obtain whole genome data together with 3D anatomic and histomorphologic analysis in two men (GP5 and GP12) with high-risk PrCa undergoing radical prostatectomy. A total of 22 whole genome-sequenced sites (16 primary cancer foci and 6 lymph node metastatic) were analyzed using evolutionary reconstruction tools and spatio-evolutionary models. Probability models were used to trace spatial and chronological origins of the primary tumor and metastases, chart their genetic drivers, and distinguish metastatic and non-metastatic subclones. RESULTS: In patient GP5, CDK12 inactivation was among the first mutations, leading to a PrCa tandem duplicator phenotype and initiating the cancer around age 50, followed by rapid cancer evolution after age 57, and metastasis around age 59, 5 years prior to prostatectomy. In patient GP12, accelerated cancer progression was detected after age 54, and metastasis occurred around age 56, 3 years prior to prostatectomy. Multiple metastasis-originating events were identified in each patient and tracked anatomically. Metastasis from prostate to lymph nodes occurred strictly ipsilaterally in all 12 detected events. In this pilot, metastatic subclone content analysis appears to substantially enhance the identification of key drivers. Evolutionary analysis' potential impact on therapy selection appears positive in these pilot cases. CONCLUSIONS: PrCa evolutionary analysis allows tracking of anatomic site of origin, timing of cancer origin and spread, and distinction of metastatic-capable from non-metastatic subclones. This enables better identification of actionable targets for therapy. If extended to larger cohorts, it appears likely that similar analyses could add substantial biological insight and clinically relevant value.

Management of functional outcomes after radical prostatectomy in the Nordic countries: A survey of uro-oncological centers.

We aimed to describe the clinical practice regarding erectile dysfunction and urinary incontinence after radical prostatectomy in the Nordic countries. A 37-item survey about pre- and post-prostatectomy evaluation and rehabilitation of sexual and urinary function was sent to 42 uro-oncology centers. Reporting was done according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Twenty-seven centers in Denmark (n = 6), Norway (n = 8), Finland (n = 7), and Sweden (n = 6) responded (64.3%). Post-prostatectomy sexual function was evaluated by 25 centers. The majority used validated questionnaires with significant variations across centers. Post-prostatectomy urinary function was evaluated by 24 centers. Again, the majority used validated questionnaires, while 9 centers used objective measures including uroflowmetry, residual urine volume, and pad usage. Twenty-one centers offered sexual rehabilitation and 12 of these described their protocols. All centers administered phosphodiesterase-5 inhibitors and seven centers offered further treatment options. Two centers offered a consultation with a sexologist. Twenty-three centers provided pelvic floor muscle training and one center used medical support with duloxetine. Our study indicates a need for standardized evaluation and management of erectile dysfunction and urinary incontinence following radical prostatectomy. Especially, there is a need for an increased focus on comprehensive sexual rehabilitation.

Robot-assisted versus three-dimensional laparoscopic radical prostatectomy: 12-month outcomes of a randomised controlled trial.

OBJECTIVES: To compare functional and oncological outcomes of robot-assisted laparoscopic prostatectomy (RALP) to three-dimensional laparoscopic radical prostatectomy (3D-LRP) at 12 months after surgery. PATIENTS AND METHODS: Prospective randomised single-centre study of 145 consecutive men referred to radical prostatectomy in a tertiary referral centre in Finland. Patients were randomised 1:1 to the RALP (N = 75) and 3D-LRP (N = 70) groups. The primary outcome was urinary continence evaluated with the Expanded Prostate Cancer Index Composite 26-item version (EPIC-26) incontinence domain score at 12 months after surgery. Secondary outcomes included the use of protective pads at 12 months after surgery, EPIC-26 domain scores of irritative/obstructive, bowel, sexual and hormonal symptoms, positive surgical margin (PSM) rate, and biochemical recurrence (BCR). Complication frequency within the 3-month period after surgery was evaluated according to Clavien-Dindo classification. Statistical significance between groups was analysed using Mann-Whitney, chi-square and Fisher's exact tests. The trial was terminated after interim analysis based on no statistically significant difference in EPIC-26 urinary incontinence domain scores. Altogether 145 patients of the target accrual of 280 patients were recruited. RESULTS: Postoperative continence at 12 months after surgery according to the EPIC-26 incontinence domain was 79.25 in both groups (P = 0.4). Between group difference was -5.8 (95% confidence interval -15.2 to 3.6). There was no statistically significant difference in the rates of PSM or BCR between the two surgical modality groups. CONCLUSION: We were unable to demonstrate a difference between the RALP and 3D-LRP groups for functional and oncological outcomes at 12 months after surgery.

Nationwide analysis of survival after radical cystectomy for bladder cancer in Finland.

BACKGROUND: Population-based survival results after radical cystectomy (RC) are limited. Our objective was to report short and long-term survival results after RC for bladder cancer from Finland in a population-based setting. MATERIALS AND METHODS: The Finnish National Cystectomy Database containing retrospectively collected essential RC data covering the years 2005-2017 was combined with the survival data from the Finnish Cancer Registry. Kaplan-Meier plots were used to estimate survival and the survival graphs were illustrated according to the final pathological staging. Centers were divided according to operational volume, and the results were then compared using Pearsons's Chi-squared test. RESULTS: A total of 2047 patients were included in the study. 30-, and 90-day mortality was 1.3%, and 3.8%, respectively. The OS of the entire RC population at 5- and 10 years was 66% and 55%, and CSS was 74% and 72%, respectively. Center volume did not significantly associate with surgical mortality or long-term survival. The 5- and 10-year OS according to pT-category was 87% and 74% for pT0, 85% and 69% for pTa-pTis-pT1, 70% and 58% for pT2, 50% and 42% for pT3 and 41% and 30% for pT4. The corresponding 5- and 10-year CSS rates were 96% and 93% for pT0, 91% and 90% for pTa-pTis-pT1, 78% and 75% for pT2, 56% and 55% for pT3 and 47% and 44% for pT4. The 5- and 10-year OS rates in patients with no lymph node metastases (pN-) were 74% and 62%, and CSS 82% and 80%, respectively. If lymph nodes were positive (pN+), the corresponding OS rates were 44% and 34% and CSS 49% and 48%, respectively. CONCLUSION: RC survival results have improved in contemporary series and are associated with the pTNM-status. The nationwide results from Finland demonstrate outcome comparable to high volume single-center series.

Identification of long noncoding RNAs with aberrant expression in prostate cancer metastases.

Prostate cancer (PCa) is the second-most common cause of male cancer-related death in western industrialized countries, and the emergence of metastases is a key challenge in the treatment of PCa. Accumulating studies have shown that long noncoding RNAs (lncRNAs) play an important role in the regulation of diverse cellular and molecular processes during the development and progression of cancer. Here, we utilized a unique cohort of castration-resistant prostate cancer metastases (mCRPC) and corresponding localized tumors and RNA sequencing (RNA-seq). First, we showed that patient-to-patient variability accounted for most of the variance in lncRNA expression between the samples, suggesting that genomic alterations in the samples are the main drivers of lncRNA expression in PCa metastasis. Subsequently, we identified 27 lncRNAs with differential expression (DE-lncRNAs) between metastases and corresponding primary tumors, suggesting that they are mCRPC-specific lncRNAs. Analyses of potential regulation by transcription factors (TFs) revealed that approximately half of the DE-lncRNAs have at least one binding site for the androgen receptor in their regulatory regions. In addition, TF enrichment analysis revealed the enrichment of binding sites for PCa-associated TFs, such as FOXA1 and HOXB13, in the regulatory regions of the DE-lncRNAs. In a cohort of prostatectomy-treated prostate tumors, four of the DE-lncRNAs showed association with progression-free time and two of them (lnc-SCFD2-2 and lnc-R3HCC1L-8) were independent prognostic markers. Our study highlights several mCRPC-specific lncRNAs that might be important in the progression of the disease to the metastatic stage and may also serve as potential biomarkers for aggressive PCa.

Visual Analogue Scale and Expanded Prostate Cancer Index Composite-26 in the Evaluation of Urinary Continence Recovery After Three-Dimensional Laparoscopic Radical Prostatectomy, a Single-Center Prospective Registered Study.

OBJECTIVE: To assess the correlation between the Visual Analogue Scale (VAS) and the Expanded Prostate Cancer Index Composite (EPIC)-26 in the evaluation of urinary continence (UC) recovery after 3-dimensional laparoscopic radical prostatectomy (3D-LRP). METHODS: 105 men underwent 3D-LRP in Seinäjoki Central Hospital Finland between November 2018 and February 2021. VAS forms and EPIC-26 questionnaires were used to assess UC preoperatively and at 6 weeks, 3-, 6-, 9-, 12-, 15-, 18-, 21-, and 24 months postoperatively. On the VAS form, the patient put a mark on the 10 cm long horizontal line in place, which described his experienced degree of UC (0 cm; fully incontinent-10 cm; fully continent). The scores for the urinary incontinence domain of EPIC-26 (UI-EPIC-26) were calculated and transformed to a scale of 0-100. Spearman´s rank correlation coefficient was used to evaluate the correlation between the VAS and UI-EPIC-26. RESULTS: A total of 915 VAS forms and 909 EPIC-26 questionnaires were evaluable. UC improved significantly during the first year but not after that. The medians for UI-EPIC-26 and VAS were 50.8 (0-100) and 7.2 cm (0-10 cm) at 3 months, 76.8 (14.5-100) and 8.7 cm (1.7-10 cm) at 12 months and 79.6 (8.25-100) and 9.0 cm (2.7-10 cm) at 24 months. The correlation coefficient (95% confidence interval) between VAS and UI-EPIC-26 preoperatively, at 12 months and at 24 months was 0.639 (0.505-0.743), 0.807 (0.716-0.871), and 0.831 (0.735-0.894), respectively (P < 0.001). CONCLUSION: The VAS can be utilized as an easy-to-use alternative to the EPIC-26 when evaluating UC recovery after 3D-LRP.

Adaptive and non-adaptive gene expression responses in prostate cancer during androgen deprivation.

Androgen deprivation therapy is the cornerstone treatment of advanced prostate cancer. Eventually prostate cancer cells overcome androgen deprivation therapy, giving rise to castration resistant prostate cancer (CRPC) characterized by increased androgen receptor (AR) activity. Understanding the cellular mechanisms leading to CRPC is needed for development of novel treatments. We used long-term cell cultures to model CRPC; a testosterone-dependent cell line (VCaP-T) and cell line adapted to grow in low testosterone (VCaP-CT). These were used to uncover persistent and adaptive responses to testosterone level. RNA was sequenced to study AR-regulated genes. Expression level changed due to testosterone depletion in 418 genes in VCaP-T (AR-associated genes). To evaluate significance for CRPC growth, we compared which of them were adaptive i.e., restored expression level in VCaP-CT. Adaptive genes were enriched to steroid metabolism, immune response and lipid metabolism. The Cancer Genome Atlas Prostate Adenocarcinoma data were used to assess the association with cancer aggressiveness and progression-free survival. Expressions of 47 AR-associated or association gaining genes were statistically significant markers for progression-free survival. These included genes related to immune response, adhesion and transport. Taken together, we identified and clinically validated multiple genes being linked with progression of prostate cancer and propose several novel risk genes. Possible use as biomarkers or therapeutic targets should be studied further.

Incidence of erectile dysfunction treatment after radical prostatectomy by Statin use in Finnish Nationwide Cohort Study.

BACKGROUND: Erectile dysfunction (ED) is common after radical prostatectomy (RP) due to cavernous nerve damage. Risk of ED is also affected by vascular function. Statins prevent vascular events but their association with post-prostatectomy ED is unclear. We explored the likelihood of starting ED treatment after RP by statin use at the population level. METHODS: The study cohort included 14,295 prostate cancer (PCa) patients with no ED treatment prior to diagnosis of PCa treated with RP in Finland during 1995-2013. Information on use of cholesterol-lowering drugs and ED medication during 1995-2014 and penile prosthesis implantation during 1996-2014 were gathered from national registries. Risk of ED treatment initiation after RP was analyzed by pre-diagnostic and post-diagnostic statin and non-statin cholesterol lowering (NSCL) drug use with Cox regression model. RESULTS: Pre-diagnostic statin use or NSCL drug use overall had no association with risk of ED treatment initiation after RP. Post-diagnostic statin use was associated with a slightly increased risk of initiation of any ED treatment (HR = 1.07; 95% CI = 1.01-1.14). Patients with the longest duration of post-diagnostic statin use had a significantly decreased risk of PDE5 inhibitor initiation compared to non-users (HR = 0.43; 95% CI = 0.20-0.94). Among patients with no cardiovascular comorbidities, pre-diagnostic statin users had a significantly increased risk of initiation of injectable ED drugs (HR = 1.27; 95% CI = 1.04-1.55), however, no association with risk of any other ED treatment was observed. CONCLUSION: Statin users have a slightly increased risk of ED treatment initiation after RP, which probably reflects the effect of the underlying vascular insufficiency.

Visual Analogue Scale (VAS) in the Evaluation of Functional Outcomes After Three-dimensional Laparoscopic Prostatectomy.

OBJECTIVE: To assess suitability of visual analog scale (VAS) in the evaluation of functional outcomes after 3D laparoscopic prostatectomy (3D LRP) METHODS: Two hundred men underwent 3D LRP for localised prostate cancer at Seinäjoki Central Hospital in Finland between December 2013 and September 2018. In October 2019, an EPIC-26 survey along with VAS scales enquiring urinary (VAS-incontinence) and sexual (VAS-sexual) symptoms was mailed to the patients, and the correlations between these 2 methods were evaluated. In the EPIC-26 survey, scores for incontinence-(EPIC-26 UI) and sexual (EPIC-26-sexual) domains were calculated using the University of Michigan scoring system. In the VAS questionnaires, patient put a mark on the 10 cm long horizontal line in place, which described his experience of continence and potency. The Spearman rank correlation coefficient was used to evaluate the correlation between methods. RESULTS: The median scores were as follows: EPIC-26-UI, 79.25 (14.5-100); EPIC-26-sexual, 36.17 (0.0-100); VAS-incontinence, 8.8 cm (1.4-10.0); and VAS-sexual, 3.2 cm (0.0-10). The correlation coefficient between EPIC-26 UI and VAS-incontinence was 0.722 (95% confidence interval [CI], 0.63-0.79; p <.0001) and 0.883 (95% CI, 0.84-0.91; p <.0001) between EPIC-26-sexual and VAS-sexual. CONCLUSION: Our study shows a strong correlation between VAS and EPIC-26 urinary incontinence and sexual domains. In daily clinical practice VAS-scale may serve as a simple tool to evaluate the key functional outcomes of radical prostatectomy.

Antidiabetic drugs, glycemic control and risk of benign prostatic hyperplasia.

BACKGROUND: Diabetes has been associated with an increased risk of benign prostatic hyperplasia (BPH). However, the role of antidiabetic drugs as a BPH risk factor is unclear. The objective of our study was to examine the risk of BPH by antidiabetic drug use and glycemic control in a large population-based cohort of Finnish men. METHODS: A total of 74,754 men in the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) free of BPH at baseline in 1996-1999 were linked to the national medication reimbursement database for information on physician-prescribed antidiabetic drug purchases. Information on recorded BPH procedures and diagnoses was obtained from the National Care Register for Health Care, and for a subgroup of 17,739 men, information on blood glucose levels (BGLs) from the Fimlab Laboratories database. Cox regression with antidiabetic drug use and BGL as time-dependent variables was used to analyze the risks for starting BPH medication, recorded BPH diagnosis, and undergoing BPH surgery. The analysis was adjusted for age, use of statins, antihypertensive medication, and nonsteroidal anti-inflammatory drugs. RESULTS: Of the subjects, 14,012 men (18.7%) used antidiabetic medication. Of the subgroup with fasting blood glucose data available, 7487 (42.2%) had diabetic level. The risks for BPH diagnosis (HR: 1.08, 95% CI: 1.03-1.13) and surgery (HR: 1.16, 95% CI: 1.09-1.24) were slightly elevated among antidiabetic drug users compared to nonusers. The association was strongest for insulin use. Similarly, risk of BPH surgery was increased in men with diabetic blood glucose compared to normoglycemic men. The risk association was attenuated by use of antidiabetic drugs. CONCLUSIONS: Diabetic BGL and antidiabetic medication use, especially insulin, are associated with an elevated risk of BPH surgery compared to nondiabetic men. These findings support the roles of insulin use and untreated hyperglycemia as possible BPH risk factors.

Prostate cancer incidence in men with prostate-specific antigen below 3 ng/mL: The Finnish Randomized Study of Screening for Prostate Cancer.

Prostate-specific antigen (PSA)-based screening for prostate cancer (PCa) can reduce PCa mortality, but also involves overdetection of low-risk disease with potential adverse effects. We evaluated PCa incidence among men with PSA below 3 ng/mL and no PCa diagnosis at the first screening round of the Finnish Randomized Study of Screening for PCa. Follow-up started at the first screening attendance and ended at PCa diagnosis, emigration, death or the common closing date (December 2016), whichever came first. Cox regression analysis was used to estimate hazard ratios and their confidence intervals (CI). Among men with PSA <3 ng/mL, cumulative PCa incidence was 9.1% after 17.6 years median follow-up. Cumulative incidence was 3.6% among men with baseline PSA 0 to 0.99 ng/mL, 11.5% in those with PSA 1.0 to 1.99 ng/mL and 25.7% among men with PSA 2 to 2.99 ng/mL (hazard ratio 9.0, 95% CI: 7.9-10.2 for the latter). The differences by PSA level were most striking for low-risk disease based on Gleason score and EAU risk group. PSA values <1 ng/mL indicate a very low 20-year risk, while at PSA 2 to 2.99 ng/mL risks are materially higher, with 4- to 5-fold risk for aggressive disease. Using risk-stratification and appropriate rescreening intervals will reduce screening intensity and overdetection. Using cumulative incidence of clinically significant PCa (csPCa) as the criterion, rescreening intervals could range from approximately 3 years for men with initial PSA 2 to 2.99 ng/mL, 6 years for men with PSA 1 to 1.99 ng/mL to 10 years for men with PSA <1 ng/mL.

How Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis.

OBJECTIVES: Genome-wide association studies have revealed over 200 genetic susceptibility loci for prostate cancer (PCa). By combining them, polygenic risk scores (PRS) can be generated to predict risk of PCa. We summarize the published evidence and conduct meta-analyses of PRS as a predictor of PCa risk in Caucasian men. PATIENTS AND METHODS: Data were extracted from 59 studies, with 16 studies including 17 separate analyses used in the main meta-analysis with a total of 20,786 cases and 69,106 controls identified through a systematic search of ten databases. Random effects meta-analysis was used to obtain pooled estimates of area under the receiver-operating characteristic curve (AUC). Meta-regression was used to assess the impact of number of single-nucleotide polymorphisms (SNPs) incorporated in PRS on AUC. Heterogeneity is expressed as I2 scores. Publication bias was evaluated using funnel plots and Egger tests. RESULTS: The ability of PRS to identify men with PCa was modest (pooled AUC 0.63, 95% CI 0.62-0.64) with moderate consistency (I2 64%). Combining PRS with clinical variables increased the pooled AUC to 0.74 (0.68-0.81). Meta-regression showed only negligible increase in AUC for adding incremental SNPs. Despite moderate heterogeneity, publication bias was not evident. CONCLUSION: Typically, PRS accuracy is comparable to PSA or family history with a pooled AUC value 0.63 indicating mediocre performance for PRS alone.