Rasmus Bisbjerg

OBJECTIVES: To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. DESIGN: Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa. SETTING: Multiple institutions that were members of international PRACTICAL consortium. PARTICIPANTS: All consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men. MAIN OUTCOME MEASURES: Prediction with hazard score of age of onset of aggressive cancer in validation set. RESULTS: ). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score. CONCLUSIONS: Polygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.

Importance: Multiparametric magnetic resonance imaging (MRI) enhances detection and risk stratification for significant prostate cancer but is time-consuming (approximately 40 minutes) and expensive. Rapid and simpler (approximately 15-minute) biparametric MRI (bpMRI) using fewer scan sequences could be implemented as a prostate MRI triage test on a larger scale before performing biopsies. Objectives: To assess the diagnostic accuracy and negative predictive value (NPV) of a novel bpMRI method in biopsy-naive men in detecting and ruling out significant prostate cancer in confirmatory biopsies. Design, Setting, and Participants: A single-institutional, paired, prospective cohort study of biopsy-naive men with clinical suspicion of prostate cancer from November 1, 2015, to June 15, 2017. Interventions: All patients underwent bpMRI (T2-weighted and diffusion-weighted imaging) followed by standard transrectal ultrasound-guided biopsies (all men) and targeted biopsies of men with suspicious bpMRI findings. Main Outcomes and Measures: Suspicion grades of bpMRI, biopsy results, and NPV of bpMRI were evaluated for detection of or ruling out significant prostate cancer (Gleason score ≥4 + 3 or maximum cancerous core length >50% for Gleason score 3 + 4). We compared the diagnostic performance of standard biopsies in all men vs standard plus targeted (combined) biopsies restricted to men with suspicious bpMRI findings. The reference standard was combined biopsy results from all men. Results: A total of 1020 men were enrolled, with a median age of 67 years (interquartile range, 61-71 years) and a median prostate-specific antigen level of 8.0 ng/mL (interquartile range, 5.7-13.0 ng/mL). Combined biopsies detected any and significant prostate cancer in 655 of 1020 men (64%) and 404 of 1020 men (40%), respectively. Restricting combined biopsies to men with suspicious bpMRI findings meant 305 of 1020 men (30%) with low-suspicious bpMRIs could avoid prostate biopsies (biopsy in 715 men with suspicious bpMRIs vs all 1020 men who required standard biopsies [70%]; P < .001). Significant prostate cancer diagnoses were improved by 11% (396 vs 351 men; P < .001), and insignificant prostate cancer diagnoses were reduced by 40% (173 vs 288 men; P < .001) compared with our current diagnostic standard, standard biopsies alone in all men. The NPV of bpMRI findings in ruling out significant prostate cancer was 97% (95% CI, 95%-99%). Conclusions and Relevance: Low-suspicion bpMRI has a high NPV in ruling out significant prostate cancer in biopsy-naive men. Using a simple and rapid bpMRI method as a triage test seems to improve risk stratification and may be used to exclude aggressive disease and avoid unnecessary biopsies with its inherent risks. Future studies are needed to fully explore its role in clinical prostate cancer management.

INTRODUCTION: Changes in sexual function other than erectile dysfunction are sparsely investigated after radiation therapy for prostate cancer. AIM: To investigate orgasmic dysfunction, urinary incontinence during sexual activity, changes in penile morphology, and sensory disturbances in the penis in patients with prostate cancer treated with external-beam radiation therapy (EBRT). METHODS: In February 2015, men treated with EBRT at our center 3 months to 5 years previously (N = 519) received a study-specific questionnaire. This was developed from purpose-built questions and validated tools including the Erection Hardness Scale. All patients had received a radiation dose of 78 Gy. Androgen deprivation therapy was administered according to disease characteristics. MAIN OUTCOME MEASURES: Outcome measurements were prevalence rates and predictors of these side effects as identified by multivariate logistic regression analyses. RESULTS: One hundred nine patients were eligible (sexually active and had completed androgen deprivation therapy) for inclusion. Twenty-four percent reported anorgasmia, 44% reported a decreased intensity of their orgasms, and 40% reported that the time it took to reach orgasm had increased. Eleven percent reported anejaculation. Fifteen percent reported orgasm-associated pain. Only 4% reported urinary incontinence during sexual activity. Subjective penile length loss in excess of 1 cm was reported by 42%. Twelve percent reported an altered curvature of their penis after EBRT. Six percent reported painful erections. Twenty-seven percent reported decreased sensitivity in the penis after EBRT, 2% reported a cold sensation, and 2% reported paresthesia. Increasing time since final treatment increased the risk of penile sensory disturbances (odds ratio = 1.05; P = .028). CONCLUSION: Orgasmic dysfunction, changes in penile morphology, and sensory disturbances in the penis are common side effects of ERBT. Patients should be properly informed of the occurrence of these side effects before deciding which treatment to pursue. Frey A, Pedersen C, Lindberg H, et al. Prevalence and Predicting Factors for Commonly Neglected Sexual Side Effects to External-Beam Radiation Therapy for Prostate Cancer. J Sex Med 2017;14:558-565.