Predicting clinically significant prostate cancer following suspicious mpMRI: analyses from a high-volume center.

PURPOSE: mpMRI is routinely used to stratify the risk of clinically significant prostate cancer (csPCa) in men with elevated PSA values before biopsy. This study aimed to calculate a multivariable risk model incorporating standard risk factors and mpMRI findings for predicting csPCa on subsequent prostate biopsy. METHODS: Data from 677 patients undergoing mpMRI ultrasound fusion biopsy of the prostate at the TUM University Hospital tertiary urological center between 2019 and 2023 were analyzed. Patient age at biopsy (67 (median); 33-88 (range) (years)), PSA (7.2; 0.3-439 (ng/ml)), prostate volume (45; 10-300 (ml)), PSA density (0.15; 0.01-8.4), PI-RADS (V.2.0 protocol) score of index lesion (92.2% ≥3), prior negative biopsy (12.9%), suspicious digital rectal examination (31.2%), biopsy cores taken (12; 2-22), and pathological biopsy outcome were analyzed with multivariable logistic regression for independent associations with the detection of csPCa defined as ISUP ≥ 3 (n = 212 (35.2%)) and ISUP ≥ 2 (n = 459 (67.8%) performed on 603 patients with complete information. RESULTS: Older age (OR: 1.64 for a 10-year increase; p < 0.001), higher PSA density (OR: 1.60 for a doubling; p < 0.001), higher PI-RADS score of the index lesion (OR: 2.35 for an increase of 1; p < 0.001), and a prior negative biopsy (OR: 0.43; p = 0.01) were associated with csPCa. CONCLUSION: mpMRI findings are the dominant predictor for csPCa on follow-up prostate biopsy. However, PSA density, age, and prior negative biopsy history are independent predictors. They must be considered when discussing the individual risk for csPCa following suspicious mpMRI and may help facilitate the further diagnostical approach.

Cotrimoxazole and targeted antibiotic prophylaxis for transrectal prostate biopsy: a single-center study.

PURPOSE: The recent restriction on the use of fluoroquinolones for prophylaxis by the European Commission has left a gap in clear recommendations for practical antibiotic prophylaxis (PAP) for transrectal prostate biopsy (TRPB). This analysis investigated the viability of cotrimoxazole for PAP in TRPB. METHODS: This analysis included n = 697 patients who underwent TRPB for suspected prostate cancer (PCa). All patients received either empiric PAP with four doses of cotrimoxazole 960 mg or targeted antibiotic prophylaxis in case of a positive rectal or urine screening for multiresistant gram-negatives. Infectious complications after TRPB, microbiological findings, and clinical characteristics were evaluated. A multivariable logistic regression model was calculated to identify variables associated with infectious complications. RESULTS: Of the cohort, 86% (600/697) received PAP with cotrimoxazole, 1% (8/697) received cotrimoxazole plus an additional antibiotic, 4% (28/697) received amoxicillin + clavulanic acid, 4% (28/697) received fluoroquinolones, and 5% (33/697) received a single shot intravenous antibiotic prophylaxis with meropenem or piperacillin + tazobactam due to multiresistant microbiological findings in either pre-interventional urine culture or rectal swab. Infectious complications occurred in 2.6% (18/697) of patients. Fever was noted in 89% (16/18) of cases. Inpatient treatment was given to 67% (12/18) of affected patients, with 38% (7/18) having positive blood cultures, identifying cotrimoxazole-resistant E. coli strains in six out of seven cases. Multivariable logistic regression analysis revealed no clinically significant variables, including PAP with cotrimoxazole, as independent risk factors for an infectious complication. CONCLUSIONS: Using cotrimoxazole as PAP for TRPB in cases without multiresistant gram-negatives in pre-interventional urine cultures or rectal swabs seems feasible and practical.

Adherence to a risk-adapted screening strategy for prostate cancer: First results of the PROBASE trial.

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 (<1.5 ng/ml, 5-yearly screening), intermediate-risk (1.5-2.99 ng/ml, 2 yearly), and high 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.

Benefit finding in men affected by prostate cancer prior to and following radical prostatectomy - a cross-sectional study with a stratified sample.

BACKGROUND: Benefit finding (BF) - the occurrence of positive life-changes in the aftermath of traumatic live events - has been repeatedly reported in prostate cancer (PCa) survivors, but it remains unclear in which way BF might vary over time. The current study aimed to investigate the extent of BF and associated factors in different phases of the survivorship continuum. METHODS: In this cross-sectional study, men affected by PCa who were either already treated with radical prostatectomy or going to be treated with radical prostatectomy at a large German PCa center were included. These men were stratified into four groups (prior to surgery, up to 12 months after surgery, 2-5 years and ≥ 6-10 years after surgery). BF was assessed using the German version of the 17-item Benefit Finding Scale (BFS). The items are rated on a five-point Likert scale ranging from 1 to 5. A total mean score ≥ 3 was considered as moderate-to-high BF. Associations with clinical and psychological factors were assessed in men presenting before and in those who participated after surgery. Multiple linear regression was applied to identify intendent determinants of BF. RESULTS: 2,298 men affected by PCa (mean age at survey: 69.5,SD = 8.2; median follow-up: 3 years (25th -75th percentile 0.5-7)) were included. 49.6% of men reported moderate-to-high BF. The mean BF score was 2.91 (SD = 0.92). BF reported by men before surgery did not differ significantly from BF reported by men in the years after surgery (p = 0.56). Higher BF prior to and following radical prostatectomy was associated with higher perceived severity of the disease (pre-surgery: ß = 0.188, p = 0.008; post-surgery: ß = 0.161, p = < 0.0001) and higher cancer-related distress (pre-surgery: ß ? 0.155, p = 0.03; post-surgery: ß = 0.089, p < 0.0001). Post radical prostatectomy BF was also associated with biochemical recurrence during follow-up (ß = 0.089, p = 0.001), and higher quality of life (ß = 0.124, p < 0.001). CONCLUSIONS: Many men affected by PCa perceive BF already soon after diagnosis. The subjective perception of threat or severity associated with the diagnosis of PCa is an essential factor for higher levels of BF, probably more important than objective indicators of the severity of the disease. The early onset of BF and the high degree of similarity of BF reported across the different phases of survivorship suggests that BF is, to a large extent, a dispositional personal characteristic and a cognitive strategy of positively coping with cancer.

Treatment decision regret in long-term survivors after radical prostatectomy: a longitudinal study.

OBJECTIVES: To investigate prevalence, course, and predictors of longitudinal decision regret in long-term prostate cancer (PCa) survivors treated by radical prostatectomy (RP). PATIENTS AND METHODS: A total of 1003 PCa survivors from the multicentre German Familial PCa Database completed questionnaires on average 7 years after RP in 2007 and at follow-up 13 years later in 2020. Patients completed standardised patient-reported outcome measures on decision regret, decision-making, health-related quality of life, and psychosocial factors. Hierarchical multivariable logistic regression was used to assess predictors of longitudinal decision regret. RESULTS: 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 localised PCa (odds ratio [OR] 1.97, 95% confidence interval [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. CONCLUSION: The findings of the present study underline the perseverance of decision regret in long-term PCa survivors and the definitive need for involving patients in the decision-making process to mitigate regret over the long term.

Changing nationwide trends away from overtreatment among patients undergoing radical prostatectomy over the past 25 years.

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 < 0.001). The proportion of high-risk cases increased from 13.1% in 2005 to 23.1% in 2010 and 36.7% in 2015, and 40.4% in 2019 (p < 0.001). After 2005, the proportion of cases with favorable localized PCa decreased from 37.3% to 24.9% in 2010 and decreased further to 13.9% in 2015, and 1.6% in 2019 (p < 0.001). The overall 10 years OCM was 7.7%. 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.

Does experience change the role of systematic biopsy during MRI-fusion biopsy of the prostate?

PURPOSE: To determine the role of biopsy experience regarding a potential benefit of additional systematic biopsies and fusion failures during MRI-targeted biopsy of the prostate. SUBJECTS/PATIENTS AND METHODS: We retrospectively evaluated 576 men undergoing transrectal (MRI)-targeted biopsy of the prostate by seven residents in urology between November 2019 and March 2022. Benefit of systematic biopsies (detection of ISUP ≥ 2 PCa (clinically significant PCa (csPCa)) solely in systematic biopsies) and fusion failure (detection of csPCa during systematic biopsies in the area of a reported MRI-lesion and no detection of csPCa in targeted biopsy) were compared by growing biopsy experience levels. Multivariable regression analyses were calculated to investigate the association with benefit of systematic biopsies and fusion failure. RESULTS: The overall PCa detection rate was 72% (413/576). A benefit of systematic biopsies was observed in 11% (63/576); of those, fusion failure was seen in 76% (48/63). Benefit of systematic biopsies and fusion failure were more common among residents with very low experience compared to highly experienced residents (18% versus 4%, p = 0.026; 13% versus 3%, p = 0.015, respectively). Increasing biopsy experience was associated with less benefit from systematic biopsies (OR: 0.98, 95% CI 0.97-0.99) and less fusion failure (OR: 0.98, 95% CI 0.97-0.99). CONCLUSIONS: The benefit of systematic biopsies following targeted biopsy decreases with growing biopsy experience. The higher risk of fusion failure among inexperienced residents necessitates systematic biopsies to ensure the detection of csPCa. Further prospective trials are warranted before a targeted only approach can be recommended in routine clinical practice.

Prevalence and determinants of decision regret in long-term prostate cancer survivors following radical prostatectomy.

BACKGROUND: Patients with localized prostate cancer (PC) are faced with a wide spectrum of therapeutic options at initial diagnosis. Following radical prostatectomy (RP), PC patients may experience regret regarding their initial choice of treatment, especially when oncological and functional outcomes are poor. Impacts of psychosocial factors on decision regret, especially after long-term follow-up, are not well understood. This study aimed to investigate the prevalence and determinants of decision regret in long-term PC survivors following RP. METHODS: 3408 PC survivors (mean age 78.8 years, SD = 6.5) from the multicenter German Familial PC Database returned questionnaires after an average of 16.5 (SD = 3.8) years following RP. The outcome of decision regret concerning the initial choice of RP was assessed with one item from the Decision Regret Scale. Health-related quality of life (HRQoL), PC-anxiety, PSA-anxiety, as well as anxiety and depressive symptoms were considered for independent association with decision regret via multivariable logistic regression. RESULTS: 10.9% (373/3408) of PC survivors reported decision regret. Organ-confined disease at RP (OR 1.39, 95%CI 1.02-1.91), biochemical recurrence (OR 1.34, 1.00-1.80), low HRQoL (OR 1.69,1.28-2.24), depressive symptoms (OR 2.32, 1.52-3.53), and prevalent PSA anxiety (OR 1.88,1.17-3.01) were significantly associated with increased risk of decision regret. Shared decision-making reduced the odds of decision regret by 40% (OR 0.59, 0.41-0.86). CONCLUSIONS: PC survivors may experience decision regret even after 16 years following RP. Promoting shared decision-making in light of both established and novel, potentially less invasive treatments at initial diagnosis may help mitigate long-term regret. Awareness regarding patients showing depressive symptoms or PSA anxiety should be encouraged to identify patients at risk of decision regret in need of additional psychological support.

A randomized trial of risk-adapted screening for prostate cancer in young men-Results of the first screening round of the PROBASE trial.

There is no generally accepted screening strategy for prostate cancer (PCa). From February 2014 to December 2019 a randomized trial (PROBASE) recruited 46 642 men at age 45 to determine the efficacy of risk-adapted prostate-specific antigen-based (PSA) screening, starting at either 45 or 50 years. PSA tests are used to classify participants into a low (<1.5 ng/mL), intermediate (1.5-2.99 ng/mL) or high (≥3 ng/mL) risk group. In cases of confirmed PSA values ≥3 ng/mL participants are recommended a prostate biopsy with multiparametric magnetic resonance imaging (mpMRI). Half of the participants (N = 23 341) were offered PSA screening immediately at age 45; the other half (N = 23 301) were offered digital rectal examination (DRE) with delayed PSA screening at age 50. Of 23 301 participants who accepted baseline PSA testing in the immediate screening arm, 89.2% fell into the low, 9.3% into intermediate, and 1.5% (N = 344) into the high risk group. Repeat PSA measurement confirmed high-risk status for 186 men (0.8%), of whom 120 (64.5%) underwent a biopsy. A total of 48 PCas was detected (overall prevalence 0.2%), of which 15 had International Society of Uropathology (ISUP) grade 1, 29 had ISUP 2 and only 4 had ISUP ≥3 cancers. In the delayed screening arm, 23 194 participants were enrolled and 6537 underwent a DRE with 57 suspicious findings, two of which showed PCa (both ISUP 1; detection rate 0.03%). In conclusion, the prevalence of screen-detected aggressive (ISUP ≥3) PCa in 45-year-old men is very low. DRE did not turn out effective for early detection of PCa.

Distress in hospitalized cancer patients: Associations with personality traits, clinical and psychosocial characteristics.

OBJECTIVE: To improve allocation of psychosocial care and to provide patient-oriented support offers, identification of determinants of elevated distress is needed. So far, there is a lack of evidence investigating the interplay between individual disposition and current clinical and psychosocial determinants of distress in the inpatient setting. METHODS: In this cross-sectional study, we investigated 879 inpatients with different cancer sites treated in a German Comprehensive Cancer Center. Assessment of determinants of elevated distress included sociodemographic, clinical and psychosocial characteristics as well as dimensions of personality. Multiple linear regression was applied to identify determinants of psychosocial distress. RESULTS: Mean age of the patients was M = 61.9 (SD = 11.8), 48.1% were women. In the multiple linear regression model younger age (ß = -0.061, p = 0.033), higher neuroticism (ß = 0.178, p = <0.001), having metastases (ß = 0.091, p = 0.002), being in a worse physical condition (ß = 0.380, p = <0.001), depressive symptoms (ß = 0.270, p = <0.001), not feeling well informed about psychological support (ß = 0.054, p = 0.046) and previous uptake of psychological treatment (ß = 0.067, p = 0.020) showed significant associations with higher psychosocial distress. The adjusted R2 of the overall model was 0.464. CONCLUSION: Controlling for sociodemographic characteristics and dispositional vulnerability, that is neuroticism, current clinical and psychosocial characteristics were still associated with hospitalized patients' psychosocial distress. Psycho-oncologists should address both, the more transient emotional responses, such as depressive symptoms, as well as more enduring patient characteristics, like neuroticism.

Accommodating heterogeneous missing data patterns for prostate cancer risk prediction.

BACKGROUND: We compared six commonly used logistic regression methods for accommodating missing risk factor data from multiple heterogeneous cohorts, in which some cohorts do not collect some risk factors at all, and developed an online risk prediction tool that accommodates missing risk factors from the end-user. METHODS: Ten North American and European cohorts from the Prostate Biopsy Collaborative Group (PBCG) were used for fitting a risk prediction tool for clinically significant prostate cancer, defined as Gleason grade group ≥ 2 on standard TRUS prostate biopsy. One 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.

The role of pornography in the sex life of young adults-a cross-sectional cohort study on female and male German medical students.

BACKGROUND: Due to easy online accessibility of pornography its consumption is popular among adolescents and young adults. Considering recently developed frameworks on the effects of sexual media, we assessed how increased consumption of pornography is associated with the experience of certain aspects of offline and online sexual activity in German medical students. METHODS: Between April 2018 and March 2020 medical students from the Technical University of Munich in Germany were anonymously surveyed with regards to their sexual behavior, consumption of pornography, and use of social media. 468 students (female: n = 293; male: n = 175) were included in the current analysis. Data was analyzed using simple and multiple Poisson regression analysis. RESULTS: Only 7.3% of female students but the majority of male students (79.1%) consumed pornography more than 4 times in the last 4 weeks. Female and male students who reported to be inspired by pornography (female: 52.0%, male: 74.6%) and who have enjoyed the experience of anal intercourse in their life (female: 17.1%, male: 32.2%) consumed pornography more frequently. Female students who have experienced a "threesome" (9.0%), have sent erotic pictures of themselves (33.5%), or use social media in their dating life (27.6%) consumed pornography more frequently. Male students who did not experience a sexual transmitted disease (82.9%) and did not cheat on their partner (68.0%) consumed pornography more frequently (results of multiple Poisson regression analysis; all p < 0.05). CONCLUSIONS: Many students consider pornography as inspiration for their sex life and frequent consumption of pornography seems to be associated with gender specific characteristics congruent with short-term sexual quality. The desire of adolescents and young adults for practical information about sexual intercourse should be addressed openly and a proper understanding of the sexuality shown in pornography should be taught.

Fear of cancer recurrence and disease progression in long-term prostate cancer survivors after radical prostatectomy: A longitudinal study.

BACKGROUND: Although fear of cancer recurrence (FCR) or disease progression is among the most endorsed unmet needs and concerns of cancer survivors, research on the course of FCR in long-term survivors is scarce. The objective of this study was to assess longitudinally the prevalence and predictors of FCR in long-term prostate cancer (PCa) survivors. METHODS: In all, 2417 survivors from the multicenter German Familial Prostate Cancer Database completed the Fear of Progression Questionnaire-Short Form on average 7 years (T1 in 2010) after radical prostatectomy and at follow-up 9 years later (T2 in 2019). Hierarchical multivariable logistic regression was used to assess predictors of FCR at follow-up. RESULTS: The mean age at the initial assessment was 69.5 years (standard deviation, 5.9 years); 6.5% and 8.4% of patients reported clinical FCR at the initial assessment (T1) and at the follow-up (T2), respectively. In a multivariable analysis controlling for concurrent associations, longitudinal predictors of FCR 9 years later included a lower level of education (odds ratio [OR], 4.35; 95% confidence interval [CI], 2.33-8.33), years since radical prostatectomy (OR, 1.10; 95% CI, 1.03-1.18), biochemical recurrence (OR, 1.67; 95% CI, 1.02-2.72), no current adjuvant therapy (OR, 2.38; 95% CI, 1.19-4.76), FCR (OR, 10.75; 95% CI, 6.18-18.72), and anxiety (OR, 1.35; 95% CI, 1.06-1.72). CONCLUSIONS: FCR remains a burden to certain PCa survivors even many years after their diagnosis and treatment. Health care professionals should monitor for FCR and identify patients at risk to provide appropriate psychosocial care because FCR is leading to limitations in quality of life and psychological well-being.

Diversity of cancer-related identities in long-term prostate cancer survivors after radical prostatectomy.

BACKGROUND: Individuals affected by cancer need to integrate this experience into their personal biography as their life continues after primary therapy, leading to substantial changes in self-perception. This study identified factors uniquely associated with 5 different cancer-related identities in order to improve the understanding of how self-perception in men affected by prostate cancer is associated with certain clinical and psychosocial characteristics. METHODS: In this cross-sectional study, long-term prostate cancer survivors after radical prostatectomy were asked to choose one of 5 cancer-related identities that described them best. Associations with sociodemographic, clinical, and psychological variables were investigated using multivariable logistic regression. RESULTS: Three thousand three hundred forty-seven men (mean age 78.1 years) surveyed on average 15.6 years after prostatectomy were included. Most men favored the terms "someone who has had cancer" (43.9%) which was associated with a mild disease course, and "patient" (26.3%) which was associated with ongoing therapy and biochemical disease recurrence. The self-descriptions "cancer survivor" (16.8%), "cancer conqueror" (10.9%) and "victim" (2.1%) were less common. "Cancer survivor" was associated with high perceived disease severity (OR: 1.86 [1.44-2.40]). "Cancer survivor" and "cancer conqueror" were related to high benefit finding (OR: 1.89 [1.48-2.40], OR: 1.46 [1.12-1.89] respectively), and only "cancer conqueror" was associated with high well-being (OR: 1.84 [1.35-2.50]). Identification as "victim" was associated with a positive depression screening and low well-being (OR: 2.22 [1.15-4.31], OR: 0.38 [0.20-0.72] respectively) (all p < 0.05). CONCLUSIONS: Although long-term survival is common among men affected by PCa, they display a large diversity in cancer-related identities, which are associated with unique clinical and psychological characteristics. These cancer-related identities and their distinctive properties are associated with psychological well-being even after a long follow-up.

Long-term and pathological outcomes of low- and intermediate-risk prostate cancer after radical prostatectomy: implications for active surveillance.

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 < 0.001; 19.8% vs. 12.0%, p < 0.001) as well as pathological tumor and node stage (≥ pT3a: 18.8% vs. 11.6%, p < 0.001; pN1: 2.7% vs. 0.8%, 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.

No detrimental effect of a positive family history on postoperative upgrading and upstaging in men with low risk and favourable intermediate-risk prostate cancer: implications for active surveillance.

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 < 10 ng/ml), (2) Gleason 6 FIR (clinical T1c-T2a, GGG 1, PSA 10-20 ng/ml), and (3) Gleason 3 + 4 FIR (clinical T1c-T2a, GGG 2, PSA < 10 ng/ml) PCa who were subsequently treated with radical prostatectomy (RP) were analysed for upgrading, defined as postoperative GGG 3 tumour or upstaging, defined as pT3-pT4 or pN1 disease at RP. Logistic regression analysis was used to assess whether PCa family history was associated with postoperative upgrading or upstaging. 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.

Benefit finding in long-term prostate cancer survivors.

PURPOSE: Benefit 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. METHODS: BF 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. RESULTS: Mean 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. CONCLUSIONS: BF 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 SURVIVORS: PCa survivors may express BF regardless of clinical disease severity. Treating urologists should consider inquiring BF to enrich a patient's cancer narrative.

Management of Germ Cell Tumours of the Testes in Adult Patients: German Clinical Practice Guideline, PART II - Recommendations for the Treatment of Advanced, Recurrent, and Refractory Disease and Extragonadal and Sex Cord/Stromal Tumours and for the Management of Follow-Up, Toxicity, Quality of Life, Palliative Care, and Supportive Therapy.

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.

Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

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.

The role of fatal family history and mode of inheritance in prostate cancer for long-term outcomes following radical prostatectomy.

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.