ctDNA guiding adjuvant immunotherapy in urothelial carcinoma.

Minimally invasive approaches to detect residual disease after surgery are needed to identify patients with cancer who are at risk for metastatic relapse. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse1. We evaluated outcomes in 581 patients who had undergone surgery and were evaluable for ctDNA from a randomized phase III trial of adjuvant atezolizumab versus observation in operable urothelial cancer. This trial did not reach its efficacy end point in the intention-to-treat population. Here we show that ctDNA testing at the start of therapy (cycle 1 day 1) identified 214 (37%) patients who were positive for ctDNA and who had poor prognosis (observation arm hazard ratio = 6.3 (95% confidence interval: 4.45-8.92); P < 0.0001). Notably, patients who were positive for ctDNA had improved disease-free survival and overall survival in the atezolizumab arm versus the observation arm (disease-free survival hazard ratio = 0.58 (95% confidence interval: 0.43-0.79); P = 0.0024, overall survival hazard ratio = 0.59 (95% confidence interval: 0.41-0.86)). No difference in disease-free survival or overall survival between treatment arms was noted for patients who were negative for ctDNA. The rate of ctDNA clearance at week 6 was higher in the atezolizumab arm (18%) than in the observation arm (4%) (P = 0.0204). Transcriptomic analysis of tumours from patients who were positive for ctDNA revealed higher expression levels of cell-cycle and keratin genes. For patients who were positive for ctDNA and who were treated with atezolizumab, non-relapse was associated with immune response signatures and basal-squamous gene features, whereas relapse was associated with angiogenesis and fibroblast TGFß signatures. These data suggest that adjuvant atezolizumab may be associated with improved outcomes compared with observation in patients who are positive for ctDNA and who are at a high risk of relapse. These findings, if validated in other settings, would shift approaches to postoperative cancer care.

Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma.

BACKGROUND: The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. METHODS: In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. RESULTS: A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. CONCLUSIONS: In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).

Targeting Cell Cycle Facilitates E1A-Independent Adenoviral Replication.

DNA replication of E1-deleted first-generation adenoviruses (AdV) in cultured cancer cells has been reported repeatedly and it was suggested that certain cellular proteins could functionally compensate for E1A, leading to the expression of the early region 2 (E2)-encoded proteins and subsequently virus replication. Referring to this, the observation was named E1A-like activity. In this study, we investigated different cell cycle inhibitors with respect to their ability to increase viral DNA replication of dl70-3, an E1-deleted adenovirus. Our analyses of this issue revealed that in particular inhibition of cyclin-dependent kinases 4/6 (CDK4/6i) increased E1-independent adenovirus E2-expression and viral DNA replication. Detailed analysis of the E2-expression in dl70-3 infected cells by RT-qPCR showed that the increase in E2-expression originated from the E2-early promoter. Mutations of the two E2F-binding sites in the E2-early promoter (pE2early-LucM) caused a significant reduction in E2-early promoter activity in trans-activation assays. Accordingly, mutations of the E2F-binding sites in the E2-early promoter in a virus named dl70-3/E2Fm completely abolished CDK4/6i induced viral DNA replication. Thus, our data show that E2F-binding sites in the E2-early promoter are crucial for E1A independent adenoviral DNA replication of E1-deleted vectors in cancer cells. IMPORTANCE E1-deleted AdV vectors are considered replication deficient and are important tools for the study of virus biology, gene therapy, and large-scale vaccine development. However, deletion of the E1 genes does not completely abolish viral DNA replication in cancer cells. Here, we report, that the two E2F-binding sites in the adenoviral E2-early promoter contribute substantially to the so-called E1A-like activity in tumor cells. With this finding, on the one hand, the safety profile of viral vaccine vectors can be increased and, on the other hand, the oncolytic property for cancer therapy might be improved through targeted manipulation of the host cell.

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.

Development of PSMA-PET-guided CT-based radiomic signature to predict biochemical recurrence after salvage radiotherapy.

PURPOSE: To develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET). MATERIAL AND METHODS: Consecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach. RESULTS: Among 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature. CONCLUSION: This is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.

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.

Treatment of muscle-invasive urothelial cancer with nivolumab (CheckMate 274 study): a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a paper published in a medical journal that describes the results of a study called CheckMate 274. This study looked at a new treatment for muscle-invasive urothelial cancer, a type of cancer found in the urinary tract that has spread from the inner lining of the urinary tract or bladder and into the surrounding muscle wall where it can then spread to other parts of the body. The standard treatment for muscle-invasive urothelial cancer is surgery to remove affected parts of the urinary tract. However, cancer returns in more than half of people after this surgery. Adjuvant therapy is given to people after surgery with muscle-invasive urothelial cancer with a goal to reduce the risk of the cancer coming back; however, at the time this study started, there was no standard adjuvant treatment. WHAT HAPPENED IN THE STUDY?: In the CheckMate 274 study, researchers compared nivolumab with a placebo as an adjuvant treatment for people with muscle-invasive urothelial cancer. The aim of the study was to understand how well nivolumab worked to reduce the chance of the cancer returning after surgery. The study also looked at what side effects (unwanted or unexpected results or conditions that are possibly related to the use of a medication) people had with treatment. WHAT DO THE RESULTS MEAN?: The results showed that people who received nivolumab versus placebo: Survived longer before the cancer was detected again, including people who had programmed death ligand-1 (shortened to PD-L1) on their cancer cells. Survived longer before a secondary cancer outside of the urinary tract was detected. Experienced no differences in health-related quality of life (the impact of the treatment on a person's mental and physical health). Had similar side effects to the people who received nivolumab in other studies. Clinical Trial Registration: NCT02632409 (ClinicalTrials.gov).

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.

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.

Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: Despite standard curative-intent treatment with neoadjuvant cisplatin-based chemotherapy, followed by radical surgery in eligible patients, muscle-invasive urothelial carcinoma has a high recurrence rate and no level 1 evidence for adjuvant therapy. We aimed to evaluate atezolizumab as adjuvant therapy in patients with high-risk muscle-invasive urothelial carcinoma. METHOD: In the IMvigor010 study, a multicentre, open-label, randomised, phase 3 trial done in 192 hospitals, academic centres, and community oncology practices across 24 countries or regions, patients aged 18 years and older with histologically confirmed muscle-invasive urothelial carcinoma and an Eastern Cooperative Oncology Group performance status of 0, 1, or 2 were enrolled within 14 weeks after radical cystectomy or nephroureterectomy with lymph node dissection. Patients had ypT2-4a or ypN+ tumours following neoadjuvant chemotherapy or pT3-4a or pN+ tumours if no neoadjuvant chemotherapy was received. Patients not treated with neoadjuvant chemotherapy must have been ineligible for or declined cisplatin-based adjuvant chemotherapy. No post-surgical radiotherapy or previous adjuvant chemotherapy was allowed. Patients were randomly assigned (1:1) using a permuted block (block size of four) method and interactive voice-web response system to receive 1200 mg atezolizumab given intravenously every 3 weeks for 16 cycles or up to 1 year, whichever occurred first, or to observation. Randomisation was stratified by previous neoadjuvant chemotherapy use, number of lymph nodes resected, pathological nodal status, tumour stage, and PD-L1 expression on tumour-infiltrating immune cells. The primary endpoint was disease-free survival in the intention-to-treat population. Safety was assessed in patients who either received at least one dose of atezolizumab or had at least one post-baseline safety assessment. This trial is registered with ClinicalTrials.gov, NCT02450331, and is ongoing but not recruiting patients. FINDINGS: Between Oct 5, 2015, and July 30, 2018, we enrolled 809 patients, of whom 406 were assigned to the atezolizumab group and 403 were assigned to the observation group. Median follow-up was 21·9 months (IQR 13·2-29·8). Median disease-free survival was 19·4 months (95% CI 15·9-24·8) with atezolizumab and 16·6 months (11·2-24·8) with observation (stratified hazard ratio 0·89 [95% CI 0·74-1·08]; p=0·24). The most common grade 3 or 4 adverse events were urinary tract infection (31 [8%] of 390 patients in the atezolizumab group vs 20 [5%] of 397 patients in the observation group), pyelonephritis (12 [3%]) vs 14 [4%]), and anaemia (eight [2%] vs seven [2%]). Serious adverse events occurred in 122 (31%) patients who received atezolizumab and 71 (18%) who underwent observation. 63 (16%) patients who received atezolizumab had a treatment-related grade 3 or 4 adverse event. One treatment-related death, due to acute respiratory distress syndrome, occurred in the atezolizumab group. INTERPRETATION: To our knowledge, IMvigor010 is the largest, first-completed phase 3 adjuvant study to evaluate the role of a checkpoint inhibitor in muscle-invasive urothelial carcinoma. The trial did not meet its primary endpoint of improved disease-free survival in the atezolizumab group over observation. Atezolizumab was generally tolerable, with no new safety signals; however, higher frequencies of adverse events leading to discontinuation were reported than in metastatic urothelial carcinoma studies. These data do not support the use of adjuvant checkpoint inhibitor therapy in the setting evaluated in IMvigor010 at this time. FUNDING: F Hoffmann-La Roche/Genentech.

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.

Suture-Free Sealing of Tunical Defect with Collagen Fleece after Partial Plaque Excision in 319 Consecutive Patients with Peyronie's Disease: The Sealing Technique.

PURPOSE: We describe the sealing technique with collagen fleece in patients with advanced Peyronie's disease (PD) and provide the prospective long-term outcomes. MATERIALS AND METHODS: We performed a multicenter cohort study in patients with preserved erectile function and stable PD that precluded sexual intercourse. All patients underwent partial plaque excision with collagen fleece grafting. The applied technique is explained through a high-quality video accompanied by relevant animations. After hospital discharge, all patients were assessed at 1, 4 and 24 weeks after treatment. Subsequently, they presented for an additional long-term evaluation. RESULTS: From December 2004 to June 2015, 367 patients underwent surgery. Of these, 319 (86.9%) presented for the long-term evaluation and were included in the present study. At a median operative time of 79.8 minutes (range 50-130), total straightness of the penis was achieved in 299 cases (93.7%) and mean±SD penile length increased by 1.1±0.6 cm (p=0.017). After a median followup of 47.2 months (range 12-100), 291 patients (91.2%) presented with complete penile straightness. The penile glans sensation returned to the preoperative levels in 300 cases (94%). Only 11 cases of treatment-related grade 1 Clavien-Dindo complications were reported. Erectile function improved in 78 participants (24.5%) and remained unchanged in 191 (59.8%), whereas it was worsened in 50 (15.7%). Overall, the patient satisfaction rate was 87.8% and the partner satisfaction rate was 84.3%. CONCLUSIONS: Grafting with collagen fleece in patients with advanced PD is a safe and effective procedure that reduces operative time, provides an additional hemostatic effect and represents a cost-effective technique.

Functional Outcome and Complications following Ileal Neobladder Reconstruction in Male Patients without Tumor Recurrence. More than 35 Years of Experience from a Single Center.

PURPOSE: There is a lack of data on true long-term functional outcome of orthotopic bladder substitution. The primary study objective was to report our 35-year clinical experience. MATERIALS AND METHODS: Since October 1985, 259 male patients from a large single center radical cystectomy series with complete followup of more than 60 months (median 121, range 60-267) without recurrence, irradiation or undiversion that might have affected the functional outcome, were included. RESULTS: Median age at radical cystectomy and at survey was 63 (range 23-81) and 75 (range 43-92) years, respectively. Overall 87% of patients voided spontaneously and residual-free. This rate decreased with increasing age at the time of surgery (less than 50 years old 94%, 70 years old or older 82%). Overall day/nighttime continence rates were 90%/82%. These rates decreased with increasing age at the time of surgery from 100%/88% to 87%/80%. The overall pad-free rate was 71%/47%. Bicarbonate use decreased from 51% (5 years) to 19% (25 years). Patients with a followup of more than 20 years had the lowest rate of residual urine and clean intermittent catheterization (0.0%) as well as use of more than 1 pad at daytime/nighttime (6.3%/12.5%) and mucus obstruction (0.0%). Serum creatinine showed only the age related increase. The surgical complication rate was 27% and correlated inversely with functional results (chi-squared 11.227, p <0.005), even when the younger age at the time of surgery (younger than 60 years) was related to higher rates of surgical complications (chi-squared 6.80, p <0.05). CONCLUSIONS: The ileal neobladder represents an excellent long-term option for urinary diversion with an acceptable complication rate.

Patterns of care for prostate cancer radiotherapy-results from a survey among German-speaking radiation oncologists.

BACKGROUND: Emerging moderately hypofractionated and ultra-hypofractionated schemes for radiotherapy (RT) of prostate cancer (PC) have resulted in various treatment options. The aim of this survey was to evaluate recent patterns of care of German-speaking radiation oncologists for RT of PC. METHODS: We developed an online survey which we distributed via e­mail to all registered members of the German Society of Radiation Oncology (DEGRO). The survey was completed by 109 participants between March 3 and April 3, 2020. For evaluation of radiation dose, we used the equivalent dose at fractionation of 2 Gy with α/ß = 1.5 Gy, equivalent dose (EQD2 [1.5 Gy]). RESULTS: Median EQD2(1.5 Gy) for definitive RT of the prostate is 77.60 Gy (range: 64.49-84.00) with median single doses (SD) of 2.00 Gy (range: 1.80-3.00), while for postoperative RT of the prostate bed, median EQD2(1.5 Gy) is 66.00 Gy (range: 60.00-74.00) with median SD of 2.00 Gy (range: 1.80-2.00). For definitive RT, the pelvic lymph nodes (LNs) are treated in case of suspect findings in imaging (82.6%) and/or according to risk formulas/tables (78.0%). In the postoperative setting, 78.9% use imaging and 78.0% use the postoperative tumor stage for LN irradiation. In the definitive and postoperative situation, LNs are irradiated with a median EQD2(1.5 Gy) of 47.52 Gy with a range of 42.43-66.00 and 41.76-62.79, respectively. CONCLUSION: German-speaking radiation oncologists' patterns of care for patients with PC are mainly in line with the published data and treatment recommendation guidelines. However, dose prescription is highly heterogenous for RT of the prostate/prostate bed, while the dose to the pelvic LNs is mainly consistent.