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).

Prevalence of prostate cancer in men with haematuria: a systematic review and meta-analysis.

OBJECTIVES: To investigate the prevalence of prostate cancer in men attending evaluation for haematuria, as this could help healthcare providers to determine whether men with haematuria should have prostate examinations performed. METHODS: The study was performed according to a pre-specified protocol uploaded to the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022299383). A systematic search of MEDLINE, Ovid and Google Scholar was performed in December 2021. Two independent researchers evaluated all titles, available abstracts, and full texts. We included studies on adult men (aged ≥18 years) describing haematuria and prostate cancer. RESULTS: We screened 4252 titles and abstracts when available and assessed 350 studies in full text. In total, 65 studies were included and 42 was summarised in a meta-analysis. In total, 18 752 men with haematuria were included, and the pooled prevalence (95% confidence interval [CI]) of prostate cancer was 3.0% (2.0-4.1%). In men with macroscopic haematuria, the pooled prevalence (95% CI) of prostate cancer was 5.9% (2.9-9.9%; n = 265/5373). In men with microscopic haematuria, the pooled prevalence (95% CI) of prostate cancer was 1.4% (0.8-2.2%; n = 71/6642). CONCLUSION: Our findings indicate that the prevalence of prostate cancer is considerable in men attending evaluation for haematuria. Therefore, digital rectal examination and prostate-specific antigen measurement should become a standard procedure for all men with haematuria, especially for men with macroscopic haematuria.

Community-based football in men with prostate cancer: 1-year follow-up on a pragmatic, multicentre randomised controlled trial.

BACKGROUND: Physical exercise has been shown to be effective in relation to fatigue, aerobic fitness, and lower body strength in men with prostate cancer. However, research into the clinically relevant effects of interventions conducted in heterogeneous patient populations and in real-life clinical practice settings is warranted. METHODS AND FINDINGS: We conducted a pragmatic, multicentre, parallel randomised controlled trial in 5 Danish urological departments. Recruitment began in May 2015, the first participant was randomised in June 2015, and the last participant was included in February 2017. In total, 214 men with prostate cancer were randomly assigned to either 6 months of free-of-charge football training twice weekly at a local club (football group [FG]) (n = 109) or usual care (usual care group [UG]) (n = 105), including brief information on physical activity recommendations at randomisation. Participants were on average 68.4 (SD 6.2) years old, 157 (73%) were retired, 87 (41%) were on castration-based treatment, 19 (9%) had received chemotherapy, and 41 (19%) had skeletal metastases at baseline. In this 1-year follow-up study, we evaluated the effects of community-based football training on the following outcomes: primary outcome, quality of life; secondary outcomes: continuation of football after 6 months, hip and lumbar spine bone mineral density (BMD), mental health score, fat and lean body mass, and safety outcomes, i.e., fractures, falls, and hospital admissions. Intention to treat (ITT) and per protocol (PP) analyses were conducted. No statistically significant between-group difference was observed in change in prostate-cancer-specific quality of life (ITT: 1.9 points [95% CI -1.9 to 5.8], p = 0.325; PP: 3.6 points [95% CI -0.9 to 8.2], p = 0.119). A statistically significant between-group difference was observed in change in total hip BMD, in favour of FG (0.007 g/cm2 [95% CI 0.004 to 0.013], p = 0.037). No differences were observed in change in lumbar spine BMD or lean body mass. Among patients allocated to football, 59% chose to continue playing football after the end of the 6-month intervention period. At 1-year follow-up in the PP population, FG participants had more improvement on the Mental Component Summary (2.9 [95% CI 0.0 to 5.7], p = 0.048 points higher) than UG participants, as well as a greater loss of fat mass (-0.9 kg [95% CI -1.7 to -0.1], p = 0.029). There were no differences between groups in relation to fractures or falls. Hospital admissions were more frequent in UG compared to FG (33 versus 20; the odds ratio based on PP analysis was 0.34 for FG compared to UG). There were 3 deaths in FG and 4 in UG. Main limitations of the study were the physically active control group and assessment of physical activity by means of self-report. CONCLUSIONS: In this trial, participants allocated to football appeared to have improved hip BMD and fewer hospital admissions. Men who played football more than once a week for 1 year lost fat mass and reported improved mental health. Community-based football proved to be acceptable, even when club membership was not subsidised. TRIAL REGISTRATION: ClinicalTrials.gov NCT02430792.

Trends in prostate cancer in elderly in Denmark, 1980-2012.

BACKGOUND: The purpose of the study is to elucidate the epidemiology of elderly patients with prostate cancer in Denmark and identify the differences between younger (<70 years) and elderly (≥70 years) patients. MATERIAL AND METHODS: Prostate cancer was defined as ICD-10 code C61. Data were derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data are delivered from the Danish Cancer Registry and the Danish Cause of Death Registry. RESULTS: The average annual number of newly diagnosed prostate cancers in Denmark has risen from 1297 patients in 1980 to 4315 patients in 2012. The prevalence increased consistently in all age groups more than seven-fold in the period, from 3987 patients in 1980 to 28 951 patients in 2012. The cancer-specific mortality in Denmark has slightly increased over the observed period, in coherence with the growth of the population, resulting in unchanged mortality rates, with the exception of the patients above 80 years, where the mortality rates are increased. The one- and five-year relative survival for prostate cancer improved significantly for all age groups over the time period from 1980 to 2012. CONCLUSION: The incidence, prevalence, and survival of elderly prostate cancer patients has increased over the observed period but with unchanged mortality rates, except in patients above 80 years, where the mortality rates were increasing.

Evaluation of Botox treatment in patients with chronic scrotal pain: Protocol for a randomized double-blinded control trial.

Background: Chronic scrotal pain is a common condition with a prevalence of 2.5-4.8% in male outpatients. Up to 40% of these patients report depressive symptoms and many feel isolated. Minimal invasive treatment is lacking, while spermatic cord injections of Botox® (BTX) have been proposed to offer long-term pain relief. Study Design: This research protocol comprises a prospective multicentre, randomized, double-blinded clinical trial drawing patients from other urological departments in the region of Southern Denmark. End Points: The primary end point will be reduction in pain evaluated by visual analogue score for pain at 3 months. Secondary end point will be length of effect of BTX injections along with changes in quality of life. Patients and Methods: The study will include 50 patients for randomization to either spermatic cord block with 100 IE BTX or sterile saline. All patients will prior to randomization undergo physical examination and will be asked to fulfil multiple questionnaires regarding pain and impact in daily life, that is, (1) visual analogue score for pain, (2) quality of life (EQ-5D-5L), (3) Chronic Prostatitis Symptom Index (NIH-CPSI), (4) ICD-10 depression questionnaire (MDI), (5) Likert global assessment scale, and (6) International Index of Erectile Function questionnaire. Physical examination and fulfilment of the questionnaires will be repeated multiple times throughout the study period of 12 weeks. After this time point, patients will be unblinded, and the control arm will be given the opportunity of cross-over.

Prostate cancer.

This review investigates prostate cancer which with approx. 4,500 new cases annually is the most frequent male cancer, and the incidence is expected to increase due to demographic developments. Prostate cancer can have a natural history without progression to symptomatic or fatal disease, which is why overdiagnosis is one of the disease's biggest challenges. In contrast to potential curable localized clinically significant disease, this is not the case after metastasis. Fortunately, new treatments, and not least combinations thereof, have increased both lifespan and quality of life in these patients significantly.

Danish Prostate Cancer Consortium Study 1 (DPCC-1) protocol: Multicentre prospective validation of the urine-based three-microRNA biomarker model uCaP.

INTRODUCTION: The primary objective of the Danish Prostate Cancer Consortium Study 1 (DPCC-1) is to provide validation for a novel urine-based microRNA biomarker, called uCaP, for a diagnosis of prostate cancer. METHODS AND ANALYSIS: Eligible participants are biopsy naïve men aged ≥18 years with prostate-specific antigen (PSA) levels ≥3 ng/mL, who are referred to prostate MRI due to suspicion of PC at one of the following three major urology/uroradiology centers: Aarhus University Hospital, Herlev & Gentofte University Hospital, or Odense University Hospital, where MRI and targeted biopsy are implemented in clinical use. Exclusion criteria include previous diagnosis of urogenital cancer, contraindication to MRI, gender reassignment treatment or PSA level >20 ng/mL. The participants will be asked to donate a urine sample in connection with their MRI. The study is observational, uses a diagnostic accuracy testing setup and will integrate into the current diagnostic pathway.We will measure the levels of the three microRNAs in the uCaP model (miR-222-3 p, miR-24-3 p and miR-30c-5p) in extracellular vesicle-enriched cell-free urine samples, to assess if uCaP can improve specificity and retain sensitivity for International Society of Urological Pathology Grade Group ≥2 PC, when used as a reflex test to PSA ≥3 ng/mL. We hypothesise that uCaP can improve selection for prostate MRI and reduce the number of unnecessary scans and biopsies. ETHICS AND DISSEMINATION: This study is approved by the Central Denmark Region Committee on Health Research Ethics (reference number: 1-10-72-85-22). All participants will provide written informed consent. Study results will be published in peer-reviewed journals and presented in scientific meetings. TRIAL REGISTRATION NUMBER: NCT05767307 at clinicaltrials.gov.

A randomised trial of [18F]PSMA-1007-PET/CT versus NaF-PET/CT for staging primary prostate cancer: A trial protocol.

Background: Prostate-specific membrane antigen (PSMA)-positron emission tomography/contrast-enhanced computed tomography (PET/CT) is a sensitive imaging modality for prostate cancer (PCa). Due to lack of knowledge of the patient benefit, PSMA-PET/CT is not yet recommended in the European guidelines for staging and treatment planning of patients with newly diagnosed PCa. We will investigate the potential difference in progression-free survival (PFS) and quality of life (QoL) of using PSMA-PET/CT versus sodium fluoride (NaF)-PET/CT for staging and treatment planning in patients with newly diagnosed PCa. Study Design: This is a prospective randomised controlled multicentre trial carried out at three centres in the Region of Southern Denmark. Endpoints: The primary endpoint is PFS. Secondary endpoints are residual disease, stage migration, impact on treatment strategies, stage distribution, QoL and diagnostic accuracy measures. Patients and Methods: Patients eligible for the study have newly diagnosed unfavourable intermediate- or high-risk PCa. A total of 448 patients will be randomised 1:1 into two groups: (A) a control group staged with Na[18F]F-PET/CT and (B) an intervention group staged with [18F]PSMA-1007-PET/CT. A subgroup in the intervention group will have a supplementary blinded Na[18F]F-PET/CT performed for the purpose of performing accuracy analyses. QoL will be assessed at baseline and with regular intervals (3-12 months) during the study period. Treatment decisions are achieved at multidisciplinary team conferences based on the results of the respective scans and according to current Danish guidelines. Trial Registration: The Regional Committees on Health Research Ethics for Southern Denmark (S-20190161) and the Danish Medicines Agency (EudraCT Number 2021-000123-12) approved the study, and it has been registered on clinicaltrials.gov (Record 2020110469).

Transperineal biopsy of the prostate.

Prostate needle biopsies are an essential step in the diagnostic evaluation of prostate cancer. The conventional ultrasound-guided transrectal needle biopsy entails a significant risk of infection, which with increasing antibiotic resistance is thought to increase in the future. This has sparked a renewed interest in transperineal prostate biopsies, as this approach avoids the multiple passages of the rectal mucosa, thus reducing the risk of infection significantly. This review describes the devolvement, technical aspects, and current recommendations of transperineal biopsies.

Introduction of free-hand MRI-guided transperineal prostate biopsies as an outpatient procedure.

INTRODUCTION: Direct biopsy of the prostate is used for diagnosing prostate cancer and most prostate biopsies are performed transrectally with ultrasonic guidance (TRUS-BX). The transrectal approach carries a risk of sepsis as bacteria may transfer directly into the prostate from the rectum. Approximately 6% of the patients will be hospitalised within seven days after TRUX-BX. Increasing antibiotic resistance has spurred a renewed interest in the transperineal approach (TP-BX). Aseptic TP-BX may be performed, significantly reducing the risk of infection. We described the first Danish experience with multiparametric MRI-guided freehand TP-BX. METHODS: Men scheduled for TP-BX were included. Patient age, prostate-specific antigen level, previous biopsy history, weight and height were recorded. We employed a visual analogue scale (VAS) for the various procedure parts and the patients rated their satisfaction. Complications and International Society of Urological Pathology scores were recorded and cancer detection rates calculated. RESULTS: A total of 143 men had TP-BX performed in a consecutive series. The cancer detection rate was 81.8% (95% confidence interval: 74.5-87.8%). The procedure was well tolerated with a median VAS of 2 (range: 0-7), and patients expressed a high degree of satisfaction with the procedure. One patient was hospitalised due to infection. CONCLUSION: TP-BX is well tolerated and feasible as an outpatient procedure performed in local anaesthesia. Transperineal biopsies have a low risk of infection. FUNDING: none. TRIAL REGISTRATION: not relevant.

Introduction of salvage prostatectomy in Denmark: the initial experience.

OBJECTIVE: To introduce salvage prostatectomy in Denmark. Prior to this, no national curative treatment for recurrent prostate cancer following radiation therapy existed in Denmark. This pilot study represent our initial experiences and the feasibility of performing salvage robot-assisted radical prostatectomy for true local, high-risk recurrence after initial therapy with external beam radiation for high-risk prostate cancer. RESULTS: Five patients underwent sRARP between April 2020 and July 2021. All patients were discharged within 48 h and no major complications were observed within 3 months. All patients had unmeasurable PSA (< 0.1 ng/ml) at follow-up 6 months after surgery. One patient with longer follow-up than 6 months experienced biochemical recurrence. At 3-months follow-up all patients reported considerable incontinence, at 6-month follow-up, pad usage decreased to 1 or 2 pads daily. Based on our initial results, the idea to introduce sRARP as a nationwide option remains and further patients will be included to establish the true role of sRARP in patients with recurrence after primary radiotherapy for PCa.

Implementation of sacral neuromodulation for urinary indications. A Danish prospective study during the initial 15 months of a new service in a tertiary referral hospital.

OBJECTIVE: Sacral neuromodulation (SNM) is a well-established treatment modality for idiopathic overactive bladder and urgency incontinence, idiopathic fecal incontinence and non-obstructive urinary retention. This study describes the start-up phase of establishing the SNM service. Primary objective: To investigate the patient-reported outcome measures of SNM on lower urinary tract dysfunction symptoms. Secondary objectives: To investigate bowel function, sexual satisfaction and to monitor SNM safety. MATERIALS AND METHODS: Twenty-two patients with refractory idiopathic and neurogenic lower urinary tract dysfunction were offered a two-stage test-phase procedure and SNM device implantation. On completing the study, the patients rated their satisfaction with the treatment using a five-point Likert scale and a bother score of urinary, bowel and sexual symptoms on a scale of 1-10 (the worst). Their complications were assessed. RESULTS: Nineteen patients (86%) were responders during the test phase and had the pulse generator implanted. Seventeen patients were very satisfied/satisfied. A statistically significant change in urinary symptoms bother score was observed in the idiopathic and neurogenic patients, a reduction from 10 to 4 (p = .0057) and 10 to 3 (p = .014), respectively. Eleven patients (58%) had symptoms from two or three pelvic compartments. Nine patients (47%) had complications. All but one event was resolved. CONCLUSIONS: SNM is safe in this heterogeneous group of patients with refractory lower urinary tract dysfunction of various etiologies. A substantial improvement was observed in the pelvic organ dysfunction, demanding a multidisciplinary approach. More studies are required to standardize the evaluation of the subjective and objective outcomes of SNM.

Tissue distribution of ethanol after intraprostatic injection using a porous needle.

Purpose: To develop a safe and precise method for intraprostatic injection, and to establish correlation between the volume of ethanol injectate and the volume of subsequent infiltrated prostate tissue. Materials and methods: We performed intraprostatic injection of 96% ethanol using a needle which has a segment of its wall made of capillary membrane with hundreds of pores in an acute and chronic canine experiment, in heart-beating cadaveric organ donors, and in a xenograft model of human prostate cancer. Whole mount tissue sections were used for three-dimensional reconstruction of the necrotic lesions and calculation of their volumes. Results: The ethanol injection resulted in oval shaped lesions of well-delineated coagulative necrosis. In both healthy human and canine prostates, the prostatic pseudocapsule and neurovascular bundle remained intact without evidence of disruption. There was a linear correlation between administered volume of ethanol and the volume of necrotic lesion. Regression analysis showed strong correlation in the acute canine experiments and in experiments performed on xenografts of human prostate cancer. A formula was calculated for each experiment to estimate the relationship between the injected volume and the volume of infiltrated prostate tissue area. Conclusions: Intraprostatic injection using a porous needle allows for effective and predictable tissue distribution of the injectate in the prostate. Through varying the volume of the agent injected and use of needles with a different length of the porous segment, the volume of infiltrated tissue could be adjusted allowing for targeted focal treatment.

Safety and Effects of Football in Skeletal Metastatic Prostate Cancer: a Subgroup Analysis of the FC Prostate Community Randomised Controlled Trial.

BACKGROUND: Skeletal metastatic disease excludes many cancer patients from participating in exercise and physical activity due to safety concerns. Empirical evidence from high-quality trials is warranted to guide clinicians and patients. OBJECTIVE: To evaluate the safety and potential benefits of high-impact aerobic exercise in patients with prostate cancer with skeletal metastases. DESIGN: Exploratory subgroup analysis of a pragmatic, multicentre, parallel randomised controlled trial. SETTING: The trial recruited 214 patients from five hospital urological departments in Denmark. PARTICIPANTS: Patients with prostate cancer with skeletal metastases (n = 41). INTERVENTION: Six months of football training twice weekly at a local club or usual care. Both groups received brief information on physical activity recommendations at the time of randomisation. MAIN OUTCOME(S) AND MEASURE(S): Safety, defined as falls, fractures and hospital admissions. Effects were evaluated on the primary outcome (prostate cancer-specific quality of life) and secondary outcomes (lean body mass, fat mass, hip and spine bone mineral density, and general physical and mental health). RESULTS: The original trial comprised 214 participants, 41 of whom had skeletal metastases at enrolment. Of these, 22 were allocated to football and 19 to usual care. The trial retention rate was 95% at 12 weeks and 88% at 6 months. Football participants attended 13 sessions on average at 12 weeks and 23 at 6 months. There were two falls, one in each group after 6 months, and no fractures. There were four unplanned hospital admissions in the study period, all four in the usual care group. Statistically significant between-group difference was observed in the primary outcome change in prostate cancer-specific quality of life at 12 weeks (7.6 points [95% CI 0.5 to 15.0]; P = 0.038). No statistical changes were found in the secondary outcomes. CONCLUSION: The analysis showed that football training was safe in patients with skeletal metastatic prostate cancer and significantly improved quality of life. Larger analyses and/or trials are warranted to confirm the safety of exercise more broadly in cancer patients with skeletal metastatic disease. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02430792 . Date of registration 30 April 2015.

Artificial intelligence-based detection of lymph node metastases by PET/CT predicts prostate cancer-specific survival.

INTRODUCTION: Lymph node metastases are a key prognostic factor in prostate cancer (PCa), but detecting lymph node lesions from PET/CT images is a subjective process resulting in inter-reader variability. Artificial intelligence (AI)-based methods can provide an objective image analysis. We aimed at developing and validating an AI-based tool for detection of lymph node lesions. METHODS: A group of 399 patients with biopsy-proven PCa who had undergone 18 F-choline PET/CT for staging prior to treatment were used to train (n = 319) and test (n = 80) the AI-based tool. The tool consisted of convolutional neural networks using complete PET/CT scans as inputs. In the test set, the AI-based lymph node detections were compared to those of two independent readers. The association with PCa-specific survival was investigated. RESULTS: The AI-based tool detected more lymph node lesions than Reader B (98 vs. 87/117; p = .045) using Reader A as reference. AI-based tool and Reader A showed similar performance (90 vs. 87/111; p = .63) using Reader B as reference. The number of lymph node lesions detected by the AI-based tool, PSA, and curative treatment was significantly associated with PCa-specific survival. CONCLUSION: This study shows the feasibility of using an AI-based tool for automated and objective interpretation of PET/CT images that can provide assessments of lymph node lesions comparable with that of experienced readers and prognostic information in PCa patients.

A prospective study of a urine and plasma biomarker test for the prediction of gleason ≥3 + 4 prostate cancer in a mixed cohort.

Purpose: Definitive diagnosis of prostate cancer is based on biopsies, a procedure associated with side-effects. The use of biomarkers in blood and urine could potentially help clinicians select patients for whom biopsies are needed. The aim of the study was to test a new urine and plasma biomarker test in detecting medium and high grade prostate cancer.Materials and methods: Blood and urine samples were prospectively collected from 41 patients prior to prostate biopsy or TUR-P and again after 3 months. The cohort included patients with suspicion of prostate cancer and patients with prior prostate cancer diagnosis. The mRNA expression of ten selected genes measured by PCR were used together with clinical data in multiple algorithms for prediction of medium-high grade prostate cancer in prostate biopsies. The testing was originally developed and validated in the USA. The method was transferred to a local Danish laboratory. Medium and high grade cancer was defined as Gleason score ≥ 3 + 4.Results: Using the biomarker test, prior to any prostate procedures, the sensitivity for detecting medium-high grade prostate cancer was 100% and the specificity was 56% and 63%, depending on the cut-off point used. When using the biomarker test, following biopsy or TUR-P, the sensitivity and specificity were reduced to 89% and 28-34% respectively. When comparing results, there was a significant difference (p < 0.05), favoring the test performed prior to the procedures.Conclusions: We were able to predict the presence of medium-high grade prostate cancer, thereby confirming earlier findings of the biomarker test.

Impact of Abiraterone Acetate plus Prednisone or Enzalutamide on Patient-reported Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer: Final 12-mo Analysis from the Observational AQUARiUS Study.

BACKGROUND: Few studies have examined patient-reported outcomes (PROs) with abiraterone acetate plus prednisone (abiraterone) versus enzalutamide in metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: To determine the impact of abiraterone and enzalutamide on PROs. DESIGN, SETTING, AND PARTICIPANTS: AQUARiUS (NCT02813408) was a prospective, 12-mo, observational study in patients with mCRPC from Denmark, France, and the UK. INTERVENTION: Abiraterone or enzalutamide treatment according to routine practise. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PROs were collected over 12 mo using Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), Brief Fatigue Inventory-Short Form (BFI-SF), Brief Pain Inventory-Short Form, and European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (QLQ-C30) at baseline and routine visits. Outcomes included mean change in PROs, patients with clinically meaningful worsening (CMW) in PROs, and safety. Data were analysed using repeated measures linear and logistic models adjusted for baseline characteristics. RESULTS AND LIMITATIONS: Abiraterone-treated (N = 105) and enzalutamide-treated (N = 106) patients were included. Key PRO items (cognitive impairments and fatigue) were significantly (p < 0.05) in favour of abiraterone versus enzalutamide during the study. "Perceived cognitive impairment" and "comments from others" (FACT-Cog); "fatigue right now", "usual level of fatigue", and "worst level of fatigue" (BFI-SF); and "cognitive functioning" and "fatigue" (QLQ-C30) were significantly in favour of abiraterone over enzalutamide for three or more consecutive periods up to month 12. From study initiation, significantly fewer patients receiving abiraterone experienced one or more CMW episode in cognition and fatigue. Fatigue and asthenia (adverse events) were lower with abiraterone than with enzalutamide (5% vs 15% and 10% vs 11%, respectively). There were no treatment-related deaths. Limitations included lack of randomisation. CONCLUSIONS: In a real-world setting, this 12-mo analysis suggests an advantage of abiraterone acetate plus prednisone over enzalutamide on fatigue and cognitive function; this finding occurred early after treatment initiation. This difference should be considered when choosing treatment. PATIENT SUMMARY: This study looked at the effect of two treatments (abiraterone acetate plus prednisone and enzalutamide) for metastatic castration-resistant prostate cancer on patient quality of life over 12 mo. Using established questionnaires, patients reported that they experienced less fatigue and cognitive impairments (including memory loss and reduced thinking abilities) with abiraterone acetate plus prednisone than with enzalutamide.

Osteoporosis and prostate cancer; a 24-month prospective observational study during androgen deprivation therapy.

Objective: To analyze the prevalence of osteoporosis during androgen deprivation therapy (A.D.T.). Background: Treatment and prognosis of prostate cancer necessitate management of long-term consequences of A.D.T., including accelerated bone loss resulting in osteoporosis; osteoporotic fractures are associated with excess morbidity and mortality. Patients and methods: Patients with prostate cancer awaiting initiation of A.D.T. were consecutively included from the daily clinic. They were followed every 6 months for 2 years. The study consisted of questionnaires, blood and urine samples and a D.X.A. scan every 6 months and yearly bone scintigraphy. A.D.T. was given as L.H.R.H. agonists, L.H.R.H. antagonists or orchiectomy. None of the patients had received prior A.D.T. or osteoporosis treatment. Results: A total of 105 individuals were included. The mean age was 70 years, median PSA level was 30.5 µg/L and median Gleason score was 7. During the study, the prevalence of osteoporosis rose from 10% at inclusion to 22% after the 2 years of follow-up and the prevalence of normal bone mineral density (B.M.D.) decreased from 32% to 8%. Osteoporotic fractures were prevalent; six patients had a clinical vertebral fracture and two patients had a hip fracture. One patient died after his hip fracture. Conclusion: After 2 years of A.D.T. the vast majority of prostate cancer patients will have osteoporosis or osteopenia. A rigorous observation strategy did not appear to prevent osteoporotic fractures. A new strategy to reduce A.D.T. induced osteoporotic fractures is mandatory.

Does therapy of the primary tumor matter in oligometastatic prostate cancer? A prospective 10-year follow-up study.

Objective: The effect of curative treatment for oligometastatic prostate cancer patients is unsolved, both with regard to morbidity and mortality. With this study, we provide some of the first long-term follow-up data on progression and mortality in oligometastatic prostate cancer patients after curative treatment of their primary tumor. Methods: A cohort of 210 patients with diagnosed prostate cancer was established between 2008 and 2010. All patients were scheduled for intended curative treatment, and all underwent blinded 18F-choline positron-emission tomography/computed tomography at inclusion prior to curative treatment. Upon unblinding, 12 patients (6%) were recategorized as being oligometastatic. They had a mean age of 64 years, median prostate-specific antigen of 18 ng/mL, and median Gleason score of 7. Six patients were staged as T3, one T2, and five T1. The patients had a median of one bone metastasis (range 1-2). All underwent intended curative radiotherapy or prostatectomy. Mean follow-up was 10.1 (8.9-11.0) years. Results: During follow-up of the 12 patients, three (25%) had biochemical recurrence, two developed castration-resistant disease, and one died due to prostate cancer. Conclusion: Our results suggest that intended curative treatment of the primary tumor in oligometastatic prostate cancer may have a role in highly selected patients.

18F-Fluoromethylcholine-positron emission tomography/computed tomography for diagnosing bone and lymph node metastases in patients with intermediate- or high-risk prostate cancer.

BACKGROUND: The use of molecular imaging in staging of prostate cancer (PC) is debated. In patients with newly diagnosed PC we investigated the diagnostic value of 18F-flouromethylcholine positron emission tomography/computed tomography (18F-FCH-PET/CT) for the detection of bone and lymph node metastases compared to whole-body bone scintigraphy (WBS) with technetium-99-methylene diphosphonate (99mTc-MDP) and results of extended pelvic lymph node dissection, respectively. MATERIALS AND METHODS: Between January 2013 and April 2016, 143 patients, aged 49-83, mean 69, years with newly diagnosed PC and disease characteristics necessitating WBS underwent both WBS and 18F-FCH-PET/CT using magnetic resonance imaging as standard. Eighty of these patients underwent pelvic lymph node dissection as part of radical prostatectomy or prior to external beam radiation and in these results of 18F-FCH-PET/CT were compared to histologic findings. RESULTS: Bone metastases were detected in 8/143 patients and sensitivity and specificity of WBS were 37.5% and 85.2% versus 100.0% and 96.3% with 18F-FCH-PET/CT, P=0.63 and 0.002, respectively. Histologically confirmed metastases to regional lymph nodes were found in 25/80 patients. Suspicious choline uptake on PET/CT in pelvic lymph nodes was found in 35 patients. Sensitivity, specificity, PPV, NPV and accuracy of 18F-FCH-PET/CT in detection of lymph node metastases were 62.5%, 69.6%, 46.9%, 81.3% and 67.5%, respectively. CONCLUSIONS: Findings in this study suggested that 18F-FCH-PET/CT is a more sensitive and specific method for detection of bone metastases from PC than WBS and could potentially reduce the need for confirmatory imaging if used instead of WBS. However, 18F-FCH-PET/CT performs sub-optimally in pre-operative staging of lymph node metastases in patients undergoing extended pelvic lymph node dissection.