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To investigate prevalence, course, and predictors of longitudinal decision regret in long-term prostate cancer (PC) survivors treated by radical prostatectomy (RP).1003 PC survivors from the multicentre German Familial PC Database completed questionnaires on average seven years after RP in 2007 and at follow-up 13 years later in 2020. Patients completed standardized patient-reported outcome measures on decision regret, decision-making, HRQoL, and psychosocial factors. Hierarchical multivariable logistic regression was used to assess predictors of longitudinal decision regret.Decision regret increased significantly over time (9.0% after 6.9 years in 2007 and 12% after 19 years in 2020; p=0.009). Favourable localized PC (OR 1.97, 95% CI 1.05-3.68), decision regret in 2007 (OR: 6.38, 95% CI 3.55-11.47), and a higher depression score (OR 1.37 95% CI 1.03-1.83) were associated with decision regret in 2020. Shared decision-making (OR: 0.55, 95% CI 0.33-0.93) was associated with less decision regret.Findings of the present study underline the perseverance of decision regret in long-term PC survivors and the definitive need for involving patients in the decision-making process to mitigate regret over the long term.

Purpose The objective of the current study was to assess whether and how preoperative risk group distribution and pathological outcomes have changed in men treated with radical prostatectomy (RP) over the past 25 years. Methods 11,071 patients from a large contemporary registry-based nationwide cohort with RP as primary treatment between 1995 and 2019 were included. Preoperative risk stratification, postoperative outcomes, and 10 years other-cause mortality (OCM) were analyzed. Results After 2005, the proportion of low-risk prostate cancer (PCa) decreased from 39.6% to 25.5% in 2010 and decreased further to 15.5% in 2015, and 9.4% in 2019 (p p p Conclusion The current analysis documents a clear shift in utilization of RP toward higher-risk PCa in men with long life expectancy. Patients with low-risk PCa or favorable localized PCa are rarely operated. This suggests a shift in applying surgery only to patients who may really benefit from RP and the long-standing discussion of overtreatment might become outdated.

Supplementary Grant Support

Supplementary Figure S1. LocusZoom regional association plots for the seven new cross-cancer loci that were > 1 Mb from known index SNPs. Supplementary Figure S2A-B. Box plots showing eQTL associations between (A) rs9375701 and L3MBTL3 in normal breast and prostate tissues and (B) rs8037137 and RCCD1 in normal breast and ovarian tissues. Supplementary Figure S3. Interactions between BCL2L11 and the 32 Biocarta "Death Pathway" genes. Interactions were identified using the GeneMania server. Circles contain gene names, lines represent interactions, and the color of the line indicates a specific type of interaction as listed in the legend.

Supplementary Table S1. Known risk loci for each cancer. Supplementary Table S2. Regions where known index SNPs for at least two of the three cancers lie within 1 Mb of each other. Supplementary Table S3. Full results from the meta-analysis of breast, ovarian, and prostate cancer showing the 18 independent loci associated at P < 10-8 with the same direction of effect across all three cancers. Supplementary Table S4. Conditional analysis of the rs1469713 (breast-ovarian-prostate cancer) signal, conditioning on the rs4808801 (breast cancer-specific) signal that was < 1 Mb away using GCTA software. Supplementary Table S5. Most significantly-associated genotyped SNP at new loci where index SNPs were imputed. Supplementary Table S6. Expression QTL analysis results from the GTEx Portal for the new cross-cancer risk loci listed in main Table 2. Supplementary Table S7. SNPs with P < 10-8 at the new cross-cancer risk loci listed in main Table 2 that overlap predicted enhancers in at least two cell types. Supplementary Table S8. HaploReg and non-coding RNA annotation of variants with P < 10-8 at the new cross-cancer risk loci listed in main Table 2. Supplementary Table S9. Eight of the 32 genes involved in induction of apoptosis through DR3 and DR4/5 Death Receptors (MSigDB: Biocarta "Death Pathway") a that were < 1 Mb away from an independent P < 10-5 index SNP in the 3-cancer meta-analysis. Supplementary Table S10. INRICH pathway analysis results for pathways with empirical P < 0.05. Apoptosis-related pathways containing BCL2L11 are shaded.

Supplementary Figure 3. Absolute Risk (A model with only family history of prostate cancer)

Supplementary acknowledgments.

Supplemental Table 1: A) Multivariable analysis for the association with biochemical recurrence comparing histopathologic and molecular lymph node status as categorical variables excluding 7 patients receiving adjuvant treatment for pN1-disease B) Multivariable analysis for the association with biochemical recurrence comparing histopathologic lymph node status and molecular maximum KLK3 expression in lymph nodes per patient as continuous variable excluding 7 patients receiving adjuvant treatment for pN1-disease Supplemental Figure 1: Distribution of the maximum KLK3 expression in lymph nodes per patient stratifying the study cohort in patients without lymph node metastases (pN0/molN0), patients with lymph node metastases detected exclusively by molecular analysis (pN0/molN1) or detected by both histopathologic and molecular analysis (pN1/molN1). Supplemental Figure 2: Biochemical recurrence-free survival according to lymph node status by (A) histopathology and (B) molecular analysis in a subgroup of 104 patients, who did not receive adjuvant treatment for pN1-status. Median biochemical recurrence-free survival was 3 months (95%CI 1.0-5.0) in 21 pN1-patients vs. not reached in 83 pN0-patients (p

Supplementary Notes. This document includes description of studies that they have been used for the analysis.

Purpose: Molecular lymph node (LN) analysis using quantitative polymerase chain reaction (qPCR) detects LN metastases with higher sensitivity than histopathology. However, the prognostic role of molecular LN status in prostate cancer patients treated with radical prostatectomy (RP) and extended pelvic LN dissection (ePLND) is unclear. To investigate the association of molecular compared with histopathologic LN status with biochemical recurrence.Experimental Design: Patients with intermediate and high-risk prostate cancer were prospectively enrolled and underwent RP with ePLND, including the obturator, internal, external, and the common iliac region. LNs ≥3 mm were bisected and examined by standard histopathology and qPCR for Kallikrein3 (KLK3) expression. Biochemical recurrence was defined by confirmed postoperative PSA > 0.2 ng/mL.Results: In 111 patients, 2,411 of 3,173 removed LNs were examined by both methods. Histopathology detected 68 LN metastases in 28 (25%) patients. Molecular analysis confirmed elevated KLK3 expression in 65 histopathologic LN metastases of all 28 pN1 patients (pN1/molN1) and additionally reclassified 224 histopathologic negative LNs and 32 (29%) pN0 patients as LN-positive (pN0/molN1).At a median follow-up of 48 months, 52 (47%) patients developed biochemical recurrence. Median biochemical recurrence-free survival was 9 months [95% confidence interval (CI), 0.0–20.1] in pN1/molN1 patients, 24 months (95% CI, 1.7–46.3) in pN0/molN1 patients and was not reached in pN0/molN0 patients (P < 0.001). On multivariable Cox regression analysis, molecular LN status [HR 4.1 (95% CI, 1.9–8.8), P < 0.001] but not histopathologic LN status [HR 1.5 (95% CI, 0.8–3.0), P = 0.198] was confirmed as independent predictor of biochemical recurrence.Conclusions: Molecular LN analysis identified pN0 patients with a high risk of biochemical recurrence and provided superior prognostic information in comparison with histopathology alone. Clin Cancer Res; 24(10); 2342–9. ©2018 AACR.

Supplementary Figure 1. Absolute Risk (With family history of prostate cancer)

Background: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer.Methods: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history.Results: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4–57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2–5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09).Conclusions: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles.Impact: We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. Cancer Epidemiol Biomarkers Prev; 24(7); 1121–9. ©2015 AACR.

Supplementary Tables 1-8. Supplementary table 1: Total number of cases and controls in PRACTICAL III and GWAS stage 3 by population and study. Supplementary Table 2: Data information for family history and age at diagnosis/observation. Supplementary Table 3: Grade-specific and family history-specific odds ratios. Supplementary Table 4: PSA levels by genotype in controls. Supplementary Table 5: Age-specific odds ratios. Supplementary Table 6: The results of 29 pair wise interaction of 25 SNPs significant at P

Background: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical.Methods: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR).Results: We observed no significant association between genetic variants and prostate cancer survival.Conclusions: Common genetic variants with large impact on prostate cancer survival were not observed in this study.Impact: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes. Cancer Epidemiol Biomarkers Prev; 24(11); 1796–800. ©2015 AACR.

Fusion of the 5′-untranslated region of androgen-regulated TMPRSS2 promoter with ETS transcription factor family members is found frequently in prostate cancers, and recent work suggests that the most common TMPRSS2-ERG fusion is associated with an aggressive clinical phenotype compared with fusion-negative prostate cancer. Thus far, analysis of the fusion has been limited to sporadic cases of prostate cancer. In the current study, we explore for an enrichment of TMPRSS2-ERG fusion in familial prostate cancer. TMPRSS2-ERG fusion was identified using a break-apart fluorescence in situ hybridization assay on tissue microarrays. Presence of TMPRSS2-ERG fusion was associated with higher Gleason scores (P = 0.027). Of 75 patients with established history of prostate cancer, we detected the TMPRSS2-ERG fusion in 44 (59%) patients. Almost three quarters (73%) of fusion-positive patients accumulated within 16 specific families whereas only 27% were single fusion-positive cases within one family. Based on reported prevalence rates, we calculated a sibling recurrence risk ratio of up to 18.9. A subset (63%) of families with uniformly TMPRSS2-ERG–positive prostate cancer underwent a genome-wide linkage scan at 500 markers. This revealed several loci located on chromosomes #9, #18, and X that were suggestive of linkage to the TMPRSS2-ERG fusion-positive prostate cancer phenotype with linkage-of-disease scores up to 2.16 and nonparametric linkage scores up to 2.77. This suggests the presence of an inherited susceptibility to developing the TMPRSS2-ERG fusion. Given the association of TMPRSS2-ERG fusion and aggressive prostate cancer, close surveillance of relatives of patients with established fusion-positive prostate cancer or a family history of prostate cancer in general would be warranted. [Cancer Res 2009;69(4):640–6]

Supplementary Table 1 from Genome-Wide Linkage Analysis of TMPRSS2-ERG Fusion in Familial Prostate Cancer

Purpose To identify factors associated with cancer-related self-perception after being affected by prostate cancer (PCa) and radical prostatectomy. Subjects and methods Men affected by PCa and radical prostatectomy were asked to choose one of 5 cancer-related identities (“patient,” “victim,” “someone who has had cancer,” “cancer survivor,” and “cancer conqueror”). Associations with clinical data, functional outcome (continence and sexual activity), and psychological factors were assessed. Results One thousand seven hundred seventy-two men were included. Most men perceived themselves as “someone who has had cancer” (46.8%) which was associated with no cancer recurrence (OR: 0.54 [0.36–0.81]) and low cancer-related distress (OR: 0.69 [0.53–0.89]) or “patient” (35.4%) which was associated with ongoing therapy (OR: 2.59 [1.59–4.22]) and biochemical disease recurrence (OR: 1.91 [1.28–2.85]). Self-perception, as “cancer survivor” (7.8%), “cancer conqueror” (8.2%), or “victim” (1.8%), was less common. “Cancer survivor” was associated with high perceived disease severity (OR: 2.07 [1.33–3.24]) and incontinence (1.99 [1.27–3.12]). “Cancer survivor” and “cancer conqueror” were related to high benefit finding (OR: 2.05 [1.30–3.23], OR: 1.89 [1.27–2.81], respectively); only “cancer conqueror” was associated with higher quality of life (OR: 1.38 [1.21–1.58]). Conclusions Self-perception in men affected by PCa can vary widely and is associated with distinct characteristics that reflect the experienced severity of the disease, therapy side effects, and psychological well-being. Implications for Cancer Survivors The assessment of cancer-related self-perception can give important insights when evaluating men affected by PCa who need assistance in coping with their disease.

Prostate cancer (PC)-related anxiety is associated with clinically significant declines in health-related quality of life (HRQoL) and psychological well-being. This longitudinal study investigates course and predictors of PC-related anxiety in long-term PC survivors treated by radical prostatectomy (RP).Two thousand nine hundred and three survivors from the multicenter German Familial PC Database completed the Memorial Anxiety Scale for PC on average 11 years after RP at the initial assessment in 2015 and then 5 years later. Hierarchical multiple linear regression was used to assess predictors of PC-related anxiety at follow-up.PC-related anxiety remained stable over the 5 years. In hierarchical multiple linear regression, longitudinal predictors of PC-related anxiety 5 years later included a lower level of education (beta: -0.035, p = 0.019), biochemical recurrence (BCR; beta: 0.054, p = 0.002), late BCR (beta: 0.054, p 0.001), PC anxiety at initial assessment (beta: 0.556, p 0.001), HRQoL (beta: -0.076, p 0.001), depression and anxiety symptoms (beta: 0.072, p = 0.001; beta: 0.165, p 0.001). Predictors of prostate-specific antigen (PSA) anxiety 5 years later included late BCR (beta: 0.044, p = 0.019), PSA anxiety at initial assessment (beta: 0.339, p 0.001), depression and anxiety symptoms (beta: 0.074, p = 0.008; beta: 0.191, p 0.001), and treatment decision regret (beta: 0.052, p = 0.006).PC-related anxiety remains a burden to survivors many years after diagnosis and treatment. The respective disease-specific anxiety was the strongest predictor of this anxiety 5 years later, which emphasizes the need of screening and monitoring in a timely manner for PC-related anxiety. Treating urologists should screen, identify, and monitor patients at risk for targeted referrals to psychosocial services.

PROBASE is a population-based, randomized trial of 46 495 German men recruited at age 45 to compare effects of risk-adapted prostate cancer (PCa) screening starting either immediately at age 45, or at a deferred age of 50 years. Based on prostate-specific antigen (PSA) levels, men are classified into risk groups with different screening intervals: low-risk (3 ng/ml, recommendation for immediate biopsy). Over the first 6 years of study participation, attendance rates to scheduled screening visits varied from 70.5% to 79.4%, depending on the study arm and risk group allocation, in addition 11.2% to 25.4% of men reported self-initiated PSA tests outside the PROBASE protocol. 38.5% of participants had a history of digital rectal examination or PSA testing prior to recruitment to PROBASE, frequently associated with family history of PCa. These men showed higher rates (33% to 57%, depending on subgroups) of self-initiated PSA testing in-between PROBASE screening rounds. In the high-risk groups (both arms), the biopsy acceptance rate was 64% overall, but was higher among men with screening PSA ≥4 ng/ml (>71%) and with PIRADS ≥3 findings upon multiparameter magnetic resonance imaging (mpMRI) (>72%), compared with men with PSA ≥3 to 4 ng/ml (57%) or PIRADS score ≤ 2 (59%). Overall, PROBASE shows good acceptance of a risk-adapted PCa screening strategy in Germany. Implementation of such a strategy should be accompanied by a well-structured communication, to explain not only the benefits but also the harms of PSA screening. in press

Background: Missing risk factors, whether random or not measured at all, across different hospitals and patients provide challenges, both for the developers of online clinical risk tools and the patients trying to use such tools. This paper provides a development and end-user solution to the commonly encountered limitations of clinical risk tool based decision making due to missing information.Methods: Six state-of-the-art logistic regression approaches accommodating missing data were compared using prostate cancer data from ten North American and European cohorts from the Prostate Biopsy Collaborative Group (PBCG). An additional large European PBCG cohort was withheld for external validation, where calibration-in-the-large (CIL), calibration curves, and area-underneath-the-receiver-operating characteristic curve (AUC) were evaluated. Ten-fold leave-one-cohort-internal validation further validated the optimal missing data approach.Results: Among 12,703 biopsies from 10 training cohorts, 3,597 (28%) had clinically significant prostate cancer, compared to 1,757 of 5,540 (32%) in the external validation cohort. In external validation, the available cases method that pooled individual patient data containing all risk factors input by an end-user had best CIL, under-predicting risks as percentages by 2.9% on average, and obtained an AUC of 75.7%. Imputation had the worst CIL (-13.3%). The available cases method was further validated as optimal in internal cross-validation and thus used for development of an online risk tool. For end-users of the risk tool, two risk factors were mandatory: serum prostate-specific antigen (PSA) and age, and ten were optional: digital rectal exam, prostate volume, prior negative biopsy, 5-alpha-reductase-inhibitor use, prior PSA screen, African ancestry, Hispanic ethnicity, first-degree prostate-, breast-, and second-degree prostate-cancer family history.Conclusion: Developers of clinical risk prediction tools should optimize use of available data and sources even in the presence of high amounts of missing data and offer options for users with missing risk factors.

Eine positive Familienanamnese (mindestens ein erstgradig betroffener Verwandter) haben 20 % aller Prostatakarzinompatienten und bei einem Teil dieser Patienten wird eine genetische Ursache angenommen. Eine Literaturrecherche und Analyse der Studien mittels PubMed und Embase zur Inzidenz, Diagnose und klinischem Verlauf des familiaren im Vergleich zum sporadischen Prostatakarzinom (PCa) sowie mogliche genetische Ursachen wurden durchgefuhrt. Das Risiko einer Prostatakrebserkrankung hangt u. a. von der Anzahl, dem Verwandtschaftsgrad und dem Erkrankungsalter der Manner in der Familie ab. Davon abhangig ist die Inzidenz erhoht und das Diagnosealter fruher im Vergleich zum sporadischen PCa. Der Verlauf des familiaren ist meist dem des sporadischen PCa vergleichbar, jedoch bei Vorliegen einer Keimbahnmutation ist es aggressiver und bedarf einer intensivierten Therapie. Zur Risikoeinschatzung ist das Erheben einer detaillierten Familienanamnese essentiell, ggf. auch die Erstellung eines Stammbaums inklusive der Karzinomanamnese der Familie. Bei Verdacht auf eine Hoch-Risiko-Familie sollte eine genetische Beratung durchgefuhrt werden und die PSA-Screeningintervalle (prostataspezifisches Antigen) jahrlich und bereits ab dem 40. Lebensjahr durchgefuhrt werden. Bei Nachweis einer Keimbahnmutation kann eine intensivierte PCa-Therapie aufgrund eines aggressiveren Verlaufs notig sein.

PurposeBenefit finding (BF) represents possible positive changes that people may experience after cancer diagnosis and treatment and has proven to be valuable to the psychological outcome. Knowledge of such beneficial consequences of prostate cancer (PCa) is limited in long-term survivors (> 5 years). Thus, the present study investigated the occurrence of benefit finding (BF) and its determinants in a large sample of (very-) long-term PCa survivors.MethodsBF was assessed in 4252 PCa survivors from the German database “Familial Prostate Cancer” using the German version of the Benefit Finding Scale (BFS). Associations between BF and sociodemographic, clinical, and psychosocial (e.g., depressive and anxiety symptoms and perceived severity of the disease experience) variables were analyzed using hierarchical multiple linear regression analysis.ResultsMean age at survey was 77.4 years (SD = 6.2) after a mean follow-up of 14.8 years (SD = 3.8). Mean BFS score was 3.14 (SD = 1.0); the prevalence of moderate-to-high BF (score ≥ 3) was 59.7%. Younger age at diagnosis, lower educational level, and higher perceived severity of the disease experience were predictive of BF. Objective disease severity or family history of PCa was not uniquely associated with BF.ConclusionsBF occurs in older, (very-) long-term PCa survivors. Our findings suggest that the self-asserted severity of the disease experience in a patient’s biography is linked to BF in the survivorship course above all tangible sociodemographic and clinical factors.Implications for cancer survivorsPCa survivors may express BF regardless of clinical disease severity. Treating urologists should consider inquiring BF to enrich a patient’s cancer narrative.

Purpose To determine whether fatal family history (FFH) or mode of inheritance in prostate cancer (PCa) has an impact on long-term outcomes following radical prostatectomy (RP). Methods 1076 PCa patients after RP with at least one deceased first-degree relative with PCa were included and stratified by FFH (four subgroups: fraternal, paternal, multiple, and none) and by mode of inheritance (two subgroups: male to male, non-male to male). We compared clinicopathological characteristics between subgroups with Fisher’s exact or Chi-square tests. Biochemical recurrence-free survival (BRFS) and cancer-specific survival (CSS) were analyzed using the method of Kaplan and Meier. Simple and multiple Cox regression with backward elimination were performed to select prognostic factors for BRFS and CSS. Results Median age at surgery was 63.3 (range 35.9–79.4) years. The overall Kaplan–Meier estimated BRFS rate at 10 and 15 years was 65.6% and 57.0%, respectively. The overall Kaplan–Meier estimated CSS rate at 10 and 15 years was 98.1% and 95.7%, respectively. Neither FFH nor mode of inheritance were factors associated with worse BRFS. However, in multiple Cox regression, paternal FFH was an important prognostic factor for a better CSS (HR 0.19, CI 0.05–0.71, p = 0.014) compared to non-FFH. Conclusion FFH and mode of inheritance do not seem to be prognostic factors of worse long-term outcomes following RP. Rather, a paternal FFH was associated with a better CSS; however, the reasons remain unclear. Nevertheless, patients after RP and FFH could be reassured that their own PCa diagnosis is not associated with a worse long-term outcome.

OBJECTIVES Psychosocial distress is common in cancer patients and survivors and encompasses a broad range of concerns and psychological symptoms. The aim of the current study was to identify subgroups of respondents who experience a specific constellation of distress symptoms. METHODS This study uses data from a large data base (n = 21 680) of cancer patients from diverse settings who provided data in the Questionnaire on Distress in Cancer Patients-Short Form (QSC-R10). Cluster analysis was applied to identify subgroups with a distinct constellation of distress symptoms. RESULTS The results showed five distinct clusters: minimally distressed patients (46.6% of the sample), highly distressed patients (12.7%), mainly physically distressed patients (15.2%), mainly psychologically distressed patients (15.6%), and mainly socially distressed patients (9.9%). These groups differed with regard to age, sex, cancer site, treatment setting, and disease progression. CONCLUSION The results revealed large heterogeneity in the experience of distress. Distress clusters were associated with socio-demographic and clinical variables. These associations might aid a clinician to tailor interventions and to address specific types of distress.

Introduction: In the last century, there have been major changes within the population structure in Germany. The aim of this study was to determine the impact of a changing population structure on identification of familial prostate cancer (PCa), and to investigate how many and which types of other cancers have occurred in patients and their first-degree relatives. Materials and Methods: A total of 19,540 patients were evaluated in a prospectively collected PCa family database and divided into four birth cohorts: 1925–1934 (cohort A), 1935–1944 (cohort B), 1945–1954 (cohort C), and 1955–1964 (cohort D). Other primary cancers and cancers of first-degree relatives were evaluated. Results: The percentage of PCa patients with ≥2 sons declined (A: 28.9% to D: 21.6%). The percentage of patients whose fathers lived for ≥65 years increased (B: 64.2% to D: 73.0%). Malignancies of the skin, the urinary tract, and the lymphoid/hematopoietic tissue were more common in patients with a positive first-degree PCa family history and their first-degree relatives. Additionally, first-degree relatives reported more often neoplasms of respiratory/intrathoracic organs and the female breast. Conclusions: A small family size, an early deceased father, and a high number of sporadic cases complicate the identification of familial PCa patients. Thus, a detailed family history should also include unaffected first-degree relatives to avoid any misclassification. Findings of other primary cancers in patients and their relatives warrant further investigation.

Zusammenfassung Hintergrund Die durch ein Prostatakarzinom (PCa) verursachte psychosoziale Belastung kann bei Patienten noch Jahre nach erfolgter Therapie persistieren. Ein möglicher Faktor ist dabei die subjektiv wahrgenommene Krankheitsursache, die das Belastungserleben, die Therapie und das weitere Präventivverhalten maßgeblich beeinflussen kann. Ziel der Studie war deswegen, von Patienten geäußerte subjektive Gründe für das PCa zu erfassen und assoziierte Faktoren zu untersuchen. Material und Methoden Eingeschlossen wurden an PCa erkrankte Patienten aus dem nationalen Forschungsprojekt „Familiäres Prostatakarzinom“. Im Rahmen der jährlichen Nachbefragung, die postalisch erfolgt, wurde den Patienten eine Frage zu den subjektiv wahrgenommenen Krankheitsursachen für ihr Prostatakarzinom gestellt. Die Antworten wurden 18 möglichen Kategorien zugeordnet. Zudem wurde der Zusammenhang der subjektiv wahrgenommenen Krankheitsursache mit Zweittumoren, einer positiven Familienanamnese für Tumorerkrankungen und soziodemografischen Faktoren untersucht. Ergebnisse Von den 9 047 befragten Männern machten 4 054 (44,8 %) Angaben zu den subjektiv wahrgenommenen Ursachen für ihr PCa. Die mittlere Zeit seit Diagnose lag bei 10,1 Jahren bei einem mittleren Alter bei Diagnose von 63,1 Jahren. Die häufigsten Antworten waren „Weiß nicht.“ (31,8 %), Genetik (30,1 %) und Stress (18,5 %). Mit 2,5 % wurde das Alter, der wichtigste Risikofaktor für PCa, nur selten genannt. Neben diesen Antworten wurden auch ungewöhnliche nicht evidenzbasierte Gründe angegeben. Männer mit einer positiven Familienanamnese für PCa nannten gegenüber sporadischen Fällen etwa 4-mal häufiger Genetik als Ursache für ihre Erkrankung. Dieser Anteil nahm mit steigender Anzahl an von PCa betroffenen Familienmitgliedern weiter zu. Männer, die bei Diagnose 65 Jahre oder jünger waren, gaben etwa doppelt so häufig Stress als den Auslöser ihres PCa an als Männer, die bei Diagnose älter als 65 Jahre waren. Schlussfolgerung Die meisten befragten Männer gaben nicht evidenzbasierte Gründe als ursächlich für ihr Prostatakarzinom an. Hier mangelt es offensichtlich noch an Aufklärung, sodass Vorsorgeprogramme gezielt und öffentlichkeitswirksam auf die evidenzbasierten Ursachen eingehen sollten. Aufgrund der Bedeutung der subjektiven Krankheitstheorie für das Belastungserleben und die weitere Behandlung sollte die subjektive Krankheitsursache des Patienten vom behandelnden Urologen erhoben und berücksichtigt werden.

Das Internet bietet zahlreiche Informationen uber das Prostatakarzinom (PCa). Inwieweit PCa-Langzeituberlebende das Internet nutzen, den gefundenen Informationen vertrauen und von welchen Parametern dies abhangig ist, wurde in vorliegender Studie untersucht. Auf Basis der nationalen Datenbank „Familiares Prostatakarzinom“ wurden Langzeituberlebende 2017 hinsichtlich ihrer Internetnutzung befragt und die Assoziation zu soziodemographischen (Befragungsalter, Kinder, Partnerschaft, Schulbildung) und krankheitsbezogenen Parametern (Zeit seit Diagnose, PCa-Familienanamnese, Progress) mittels multipler logistischer Regression analysiert. In die Analyse gingen 4636 PCa-Langzeituberlebende (Alter: M = 76,9 ± 6,6 Jahre) mit einem durchschnittlichen Follow-up von 14,0 Jahren ein. 62,1 % der PCa-Langzeituberlebenden nutzten das Internet. Unter den Nichtnutzern hatten 23,5 % starke Bedenken, bei den Nutzern nur 2,8 %. 47,2 % der Nutzer suchten nach PCa-Informationen, davon gaben 18,0 % Schwierigkeiten an. Mehr als die Halfte fand die Informationen zum PCa unpassend. Niedrigeres Alter, kurzere Zeit seit Diagnose, Progress und haufigere Internetnutzung waren mit PCa-bezogener Informationssuche assoziiert. Nur ein Drittel vertraute den Informationen voll. Dieses Vertrauen war mit einem hohen Alter, hoherer Schulbildung und haufiger Informationssuche assoziiert. Viele gaben an, v. a. ihrem Urologen zu vertrauen. Zwei Drittel der PCa-Langzeituberlebenden nutzt das Internet. Bei der PCa-Informationssuche bestehen Schwierigkeiten, passende und vertrauenswurdige Informationen zu finden. Urologen sollten daher mit Internetangeboten vertraut sein, um Patienten beraten und internetbezogene Informationen empfehlen zu konnen.

The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.

Objectives: We developed the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up of germ cell tumours (GCT) of the testes in adult patients. We present the guideline content in 2 separate publications. The present second part summarizes therecommendations for the treatment of advanced disease stages and for the management of follow-up and late effects. Materials and Methods: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search in March 2018), were provided. Thirty-one experts, who were entitled to vote, rated the final clinical recommendations and statements. Results: Here we present the treatment recommendations separately for patients with metastatic seminoma and non-seminomatous GCT (stages IIA/B and IIC/III), for restaging and treatment of residual masses, and for relapsed and refractory disease stages. The recommendations also cover extragonadal and sex cord/stromal tumours, the management of follow-up and toxicity, quality-of-life aspects, palliative care, and supportive therapy. Conclusion: Physicians and other medical service providers who are involved in the diagnostics, treatment, and follow-up of GCT (all stages, outpatient and inpatient care as well as rehabilitation) are the users of the present guideline. The guideline also comprises quality indicators for measuring the implementation of the guideline recommendations in routine clinical care; these data will be presented in a future publication.

Regular self-examination can facilitate early detection of testicular cancer and malignancies of the breast and may ensure a curative treatment. In this analysis we explored the tendencies of medical students to perform self-examination and associated factors.As part of their urology rotation, medical students of the Technical University of Munich were surveyed via questionnaires regarding their health and sexual behavior. In all, 98.8% of the students participated and data from 473 of 477 students were included in this analysis. Data were analyzed using univariate and multivariate regression analysis.In all, 64.2% (n = 177) of the male students and 72.3% (n = 296) of the female students performed regular self-examination of the testis and breast, respectively. Students who did not communicate with their partners or friends about their sex lives were less likely to preform regular self-examination (p 0.05). Male students without sexual intercourse in the 4 weeks prior to the survey and female students who did not masturbate in the 4 weeks prior to the survey were also less likely to preform regular self-examination (p 0.05).The rate of regular self-examination is high in medical students compared to previous studies on young adults and non-medical students. This shows that knowledge about the significance of testicular cancer and breast cancer are fundamental for promoting self-examination in teenagers and young adults. A distressed sex life might hinder young adults in preforming regular self-examination. Therefore, improved education about the significance of testicular cancer and routine urological consultations for male teenagers and young men are ways to promote testicular self-examination within this age group.HINTERGRUND: Durch eine regelmäßige Selbstuntersuchung kann ein Malignom der Hoden oder Brust gegebenenfalls frühzeitig erkannt und kurativ behandelt werden. Ziel dieser Arbeit war es, das Selbstuntersuchungsverhalten von Medizinstudierenden zu untersuchen und Faktoren, die eine regelmäßige Selbstuntersuchung beeinflussen, zu identifizieren.Medizinstudierende wurden mittels Fragebogen bezüglich ihres Gesundheits- und Sexualverhaltens befragt. 98,8 % der Studierenden nahmen teil (n = 473). Die erhobenen Daten wurden mittels univariater und multivariater logistischer Regression analysiert.Es gaben 64,2 % der männlichen Studierenden (n = 177) an, regelmäßig ihre Hoden zu untersuchen und 72,2 % der weiblichen Studierenden (n = 296) gaben an, regelmäßig ihre Brust abzutasten. Studierende, die nicht mit ihrer/ihrem PartnerIn bzw. mit ihren FreundInnen über ihre Sexualität sprechen, führten seltener eine Selbstuntersuchung durch (p 0,05). Männliche Studierende, die in den letzten 4 Wochen vor Befragung keinen Geschlechtsverkehr hatten und weibliche Studierende, die im gleichen Zeitraum nicht masturbierten, führten seltener eine Selbstuntersuchung durch (p 0,05).Der Anteil an Medizinstudierenden, der eine regelmäßige Selbstuntersuchung durchführt, ist im Vergleich zu weniger medizinisch gebildeten jungen Erwachsenen hoch. Wissen über die Relevanz von Hoden- bzw. Brustkrebs scheint grundlegend für eine regelmäßige Selbstuntersuchung zu sein. Ein belastetes Sexualleben schränkt solch ein Gesundheitsverhalten möglicherweise ein. Eine Verbesserung der Aufklärung über Hodenkrebs und die urologische Anbindung von Jungen/junger Männer bieten daher die Möglichkeit, die Bereitschaft zur Selbstuntersuchung innerhalb dieser Altersgruppe zu steigern.

Purpose To assess whether a first-degree family history or a fatal family history of prostate cancer (PCa) are associated with postoperative upgrading and upstaging among men with low risk and favourable intermediate-risk (FIR) PCa and to provide guidance on clinical decision making for active surveillance (AS) in this patient population. Methods Participants in the German Familial Prostate Cancer database diagnosed from 1994 to 2019 with (1) low risk (clinical T1c–T2a, biopsy Gleason Grade Group (GGG) 1, PSA Results Among 4091 men who underwent RP, mean age at surgery was 64.4 (SD 6.7) years, 24.7% reported a family history, and 3.4% a fatal family history. Neither family history nor fatal family history were associated with upgrading or upstaging at low risk, Gleason 6 FIR, and Gleason 3 + 4 FIR PCa patients. Conclusion Results from the current study indicated no detrimental effect of family history on postoperative upgrading or upstaging. Therefore, a positive family history or fatal family history of PCa in FIR PCa patients should not be a reason to refrain from AS in men otherwise suitable.

Purpose The safety of active surveillance (AS) in favorable intermediate-risk (FIR) prostate cancer (PCa) remains uncertain. To provide guidance on clinical decision-making, we examined long-term and pathological outcomes of low-risk and intermediate-risk PCa patients after radical prostatectomy (RP). Methods The study involved 5693 patients diagnosed between 1994 and 2019 with low-risk, FIR, and unfavorable intermediate-risk (UIR) PCa (stratification according to the AUA guidelines) who underwent RP. Pathological outcomes were compared, and Kaplan–Meier analysis determined biochemical recurrence-free survival (BRFS) and cancer-specific survival (CSS) at 5, 10, 15, and 20 years. Multiple Cox regression was used to simultaneously control for relevant confounders. Results Those at FIR had higher rates of upgrading and upstaging (12.8% vs. 7.2%, p p p p > 0.001) compared to patients at low risk. The 20-year BRFS was 69%, 65%, and 44% and the 20-year CSS was 98%, 95%, and 89% in low-risk, FIR, and UIR patients. On multiple Cox regression, FIR was not associated with a worse BRFS (HR 1.07, CI 0.87–1.32), UIR was associated with a worse BRFS (HR 1.49, CI 1.20–1.85). Conclusion Patients at FIR had only slightly worse pathological and long-term outcomes compared to patients at low risk, whereas the difference compared to patients at UIR was large. This emphasizes AS in these patients as a possible treatment strategy in well-counseled patients.

Introduction: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic’s background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. Methods: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. Results: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. Conclusion: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

BACKGROUND: Penile rehabilitation after nerve-sparing radical prostatectomy (nsRP) improves the functional outcome, i.e., erectile function and urinary continence. Masturbation as a concept of penile rehabilitation has been practically not investigated. The aim of this observational and explorative study was to evaluate the association between masturbation and the recovery of the functional outcome in patients after nsRP. METHODS: Patients after nsRP (11/2013-3/2016) with preoperative International Erectile Function Score-Erectile Function (IIEF-EF) of ≥22 and/or Erection Hardness Score (EHS) of ≥3 without neo- or adjuvant therapy were included in this analysis. Patients were classified according to their masturbation behavior (yes: m; no: nm). Chi-square tests were used to test for association between masturbation and functional outcome. The main outcome measures were rates of erectile function, morning erections, and urinary continence 6, 12, 24, and 36 months after nsRP. RESULTS: A total of 250 preoperatively potent patients with median age of 63.8 years (1(st), 3(rd) quartile: 59.1, 69.6) at nsRP were included. After 24 months, m-patients had a numerically higher rate of moderate to good erectile function compared to nm-patients (47.5% vs. 37.5%; P=0.193) and had morning erections more often than nm-patients (54.6% vs. 34.9%; P=0.011). Urinary continence rate 12 months after nsRP was higher compared to nm-patients (12 months: 83.1% vs. 70.2%; P=0.042). CONCLUSIONS: Masturbation might be a promising approach of both erectile function and urinary continence recovery, and patients could be encouraged to masturbate after nsRP. However, due to the study design, causality cannot be concluded. Thus, masturbation as a possible concept of penile rehabilitation warrants further investigation.