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Peer reviewed: True, Funder: NIHR Health Protection Unit in Behavioural Science and Evaluation, When comparing the risk of a post-infection binary outcome, for example, hospitalisation, for two variants of an infectious pathogen, it is important to adjust for calendar time of infection. Typically, the infection time is unknown and positive test time used as a proxy for it. Positive test time may also be used when assessing how risk of the outcome changes over calendar time. We show that if time from infection to positive test is correlated with the outcome, the risk conditional on positive test time is a function of the trajectory of infection incidence. Hence, a risk ratio adjusted for positive test time can be quite different from the risk ratio adjusted for infection time. We propose a simple sensitivity analysis that indicates how risk ratios adjusted for positive test time and infection time may differ. This involves adjusting for a shifted positive test time, shifted to make the difference between it and infection time uncorrelated with the outcome. We illustrate this method by reanalysing published results on the relative risk of hospitalisation following infection with the Alpha versus pre-existing variants of SARS-CoV-2. Results indicate the relative risk adjusted for infection time may be lower than that adjusted for positive test time.

Background: \ud The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.\ud \ud Methods: \ud This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status.\ud \ud Findings: \ud Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.\ud \ud Interpretation: \ud This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.\ud \ud Funding: \ud Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

Following publication of the original article [1], the authors identified an error in the author name of Kim Beernaert. The incorrect author name is: Kim Beenaert. The correct author name is: Kim Beernaert. The author group has been updated above and the original article [1] has been corrected.

Objective To evaluate the relation between diagnosis of covid-19 with SARS-CoV-2 variant B.1.1.7 (also known as variant of concern 202012/01) and the risk of hospital admission compared with diagnosis with wild-type SARS-CoV-2 variants. Design Retrospective cohort analysis. Setting Community based SARS-CoV-2 testing in England, individually linked with hospital admission data. Participants 839 278 patients with laboratory confirmed covid-19, of whom 36 233 had been admitted to hospital within 14 days, tested between 23 November 2020 and 31 January 2021 and analysed at a laboratory with an available TaqPath assay that enables assessment of S-gene target failure (SGTF), a proxy test for the B.1.1.7 variant. Patient data were stratified by age, sex, ethnicity, deprivation, region of residence, and date of positive test. Main outcome measures Hospital admission between one and 14 days after the first positive SARS-CoV-2 test. Results 27 710 (4.7%) of 592 409 patients with SGTF variants and 8523 (3.5%) of 246 869 patients without SGTF variants had been admitted to hospital within one to 14 days. The stratum adjusted hazard ratio of hospital admission was 1.52 (95% confidence interval 1.47 to 1.57) for patients with covid-19 infected with SGTF variants, compared with those infected with non-SGTF variants. The effect was modified by age (P Conclusions The results suggest that the risk of hospital admission is higher for people infected with the B.1.1.7 variant compared with wild-type SARS-CoV-2, likely reflecting a more severe disease. The higher severity may be specific to adults older than 30 years.

A BRCA2 prostate cancer cluster region (PCCR) was recently proposed (c.7914 to 3′) wherein pathogenic variants (PVs) are associated with higher prostate cancer (PCa) risk than PVs elsewhere in the BRCA2 gene. Using a prospective cohort study of 447 male BRCA2 PV carriers recruited in the UK and Ireland from 1998 to 2016, we estimated standardised incidence ratios (SIRs) compared with population incidences and assessed variation in risk by PV location. Carriers of PVs in the PCCR had a PCa SIR of 8.33 (95% confidence interval [CI] 4.46–15.6) and were at a higher risk of PCa than carriers of other BRCA2 PVs (SIR = 3.31, 95% CI 1.97–5.57; hazard ratio = 2.34, 95% CI 1.09–5.03). PCCR PV carriers had an estimated cumulative PCa risk of 44% (95% CI 23–72%) by the age of 75 yr and 78% (95% CI 54–94%) by the age of 85 yr. Our results corroborate the existence of a PCCR in BRCA2 in a prospective cohort. Patient summary In this report, we investigated whether the risk of prostate cancer for men with a harmful mutation in the BRCA2 gene differs based on where in the gene the mutation is located. We found that men with mutations in one region of BRCA2 had a higher risk of prostate cancer than men with mutations elsewhere in the gene., Take Home Message BRCA2 pathogenic variants located in a recently proposed prostate cancer cluster region confers higher risks of prostate cancer than other BRCA2 variants. This report corroborates the existence of this prostate cancer cluster region in a large prospective cohort study.

It is unclear whether preoperative staging using Magnetic Resonance Imaging (MRI) reduces the risk of positive margins in prostate cancer. We aimed to assess the effect on surgical margins and degree of nerve sparing of a pelvic MRI presented at a preoperative MRI conference. Single institution, observational cohort study including 1037 men that underwent robot assisted radical prostatectomy between October 2013 and June 2015. Of these, 557 underwent a preoperative MRI combined with a preoperative MRI conference and 410 did not. With whole-mount prostate specimen histopathology as gold standard we assessed the ability of MRI in finding the index tumor and the sensitivity and specificity for extra prostatic extension. We calculated relative risks for positive surgical margins and non-nerve sparing procedure, adjusting for preoperative risk factors using stabilized inverse-probability weighting. MRI detected the index tumor in 80% of the cases. Non-organ confined disease (pT3) at histology was present in the MRI and the non-MRI group in 42% and 24%, respectively. Rate of positive surgical margins comparing the MRI and non-MRI groups was 26.7% and 33.7%, respectively, relative risk 0.79 [95% CI 0.65–0.96], weighted relative risk (wRR) 0.69 [95% CI 0.55–0.86]. The wRR of extensive positive surgical margins was 0.45 [95% CI 0.31–0.67]. Undergoing MRI was also associated with an increased risk of being operated with a non-nerve sparing technique (wRR, 1.84 [95% CI 1.11–3.03]). Our study suggests that preoperative prostate MRI in combination with a preoperative MRI conference affects the degree of nerve-sparing surgery and reduces positive surgical margins.

Investigate symptoms and how they affect daily life in patients with Non-Muscle Invasive Bladder Cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) instillations.Patients treated with BCG were included. After an initial transurethral resection (TURB) followed by a second-look resection, the patients were given an induction course with BCG for 6 weeks followed by maintenance therapy for 2 years. The patients answered a questionnaire before, during and after the treatment. The questionnaire contained questions about specific symptoms combined with bother questions on how each symptom affected patients' life.In total, 113 of 116 patients responded to the first questionnaire. Thirty per cent of all patients were bothered by disease-specific symptoms before the start of BCG. Few patients reported fever, haematuria, illness or urinary tract symptoms. No difference in symptoms was found between patients with or without concomitant CIS (carcinoma in situ). Patients younger than 65 years of age reported a greater worry about the symptom burden in the future than those who were older. Patients younger than 65 years reported a decreased level of mental well-being.Patients with bladder cancer T1G2-G3 had disease-specific symptoms present already before the start of the BCG. The burden of symptoms was reduced over time and showed that the bladder might recover. BCG instillations had side-effects that negatively affected the patient's well-being. It is important to record the patients' baseline bladder and voiding status before as well as during the BCG-instillation period in order to understand symptoms caused by the treatment.

Robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) treatment has been widely adopted with limited evidence for long-term (5 yr) oncologic efficacy.To evaluate long-term oncologic outcomes following RARP.Prospective cohort study of 885 patients who underwent RARP as monotherapy for PCa between 2002 and 2006 in a single European centre and followed up until 2016.RARP as monotherapy.Biochemical recurrence (BCR)-free survival (BCRFS), salvage therapy (ST)-free survival (STFS), prostate cancer-specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method, and event-time distributions were compared using the log-rank test. Variables predictive of BCR and ST were identified using Cox proportional hazards models.We identified 167 BCRs, 110 STs, 16 PCa-related deaths, and 51 deaths from other/unknown causes. BCRFS, STFS, CSS, and OS rates were 81.8%, 87.5%, 98.5%, and 93.0%, respectively, at median follow-up of 10.5 yr. On multivariable analysis, the strongest independent predictors of both BCR and ST were preoperative Gleason score, pathological T stage, positive surgical margins (PSMs), and preoperative prostate-specific antigen. PSM3mm/multifocal but not ≤3mm independently affected the risk of both BCR and ST. Study limitations include a lack of centralised histopathologic reporting, lymph node and post-operative tumour volume data in a historical cohort, and patient-reported outcomes.RARP appears to confer effective long-term oncologic efficacy. The risk of BCR or ST is unaffected by ≤3mm PSM, but further follow-up is required to determine any impact on CSS.Robot-assisted surgery for prostate cancer is effective 10 yr after treatment. Very small (3mm) amounts of cancer at the cut edge of the prostate do not appear to impact on recurrence risk and the need for additional treatment, but it is not yet known whether this affects the risk of death from prostate cancer.

Background Whether surgeons perform better utilising a robot-assisted laparoscopic technique compared with an open approach during prostate cancer surgery is debatable. Objective To report erectile function and early oncologic outcomes for both surgical modalities, stratified by prostate cancer risk grouping. Design, setting, and participants In a prospective nonrandomised trial, we recruited 2545 men with prostate cancer from seven open ( n =753) and seven robot-assisted ( n =1792) Swedish centres (2008–2011). Outcome measurements and statistical analysis Clinometrically-validated questionnaire-based patient-reported erectile function was collected before, 3 mo, 12 mo, and 24 mo after surgery. Surgeon-reported degree of neurovascular-bundle preservation, pathologist-reported positive surgical margin (PSM) rates, and 2-yr prostate-specific antigen-relapse rates were measured. Results and limitations Among 1702 preoperatively potent men, we found enhanced erectile function recovery for low/intermediate-risk patients in the robot-assisted group at 3 mo. For patients with high-risk tumours, point estimates for erectile function recovery at 24 mo favoured the open surgery group. The degree of neurovascular bundle preservation and erectile function recovery were greater correlated for robot-assisted surgery. In pT2 tumours, 10% versus 17% PSM rates were observed for open and robot-assisted surgery, respectively; corresponding rates for pT3 tumours were 48% and 33%. These differences were associated with biochemical recurrence in pT3 but not pT2 disease. The study is limited by its nonrandomised design and relatively short follow-up. Conclusions Earlier recovery of erectile function in the robot-assisted surgery group in lower-risk patients is counterbalanced by lower PSM rates for open surgeons in organ-confined disease; thus, both open and robotic surgeons need to consider this trade-off when determining the plane of surgical dissection. Robot-assisted surgery also facilitates easier identification of nerve preservation planes during radical prostatectomy as well as wider dissection for pT3 cases. Patient summary For prostate cancer surgery, an open operation reduces erection problems in high-risk cancers but has higher relapse rates than robotic surgery. Relapse rates appear similar in low/intermediate-risk cancers and the robot appears better at preserving erections in these cases.

BACKGROUND: BRCA1 and BRCA2 mutations have been associated with prostate cancer (PCa) risk but a wide range of risk estimates have been reported that are based on retrospective studies. OBJECTIVE: To estimate relative and absolute PCa risks associated with BRCA1/2 mutations and to assess risk modification by age, family history, and mutation location. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study of male BRCA1 (n = 376) and BRCA2 carriers (n = 447) identified in clinical genetics centres in the UK and Ireland (median follow-up 5.9 and 5.3 yr, respectively). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standardised incidence/mortality ratios (SIRs/SMRs) relative to population incidences or mortality rates, absolute risks, and hazard ratios (HRs) were estimated using cohort and survival analysis methods. RESULTS AND LIMITATIONS: Sixteen BRCA1 and 26 BRCA2 carriers were diagnosed with PCa during follow-up. BRCA2 carriers had an SIR of 4.45 (95% confidence interval [CI] 2.99-6.61) and absolute PCa risk of 27% (95% CI 17-41%) and 60% (95% CI 43-78%) by ages 75 and 85 yr, respectively. For BRCA1 carriers, the overall SIR was 2.35 (95% CI 1.43-3.88); the corresponding SIR at age

Objective The aim of this study was to investigate levels of perceived family cohesion during childhood, teenage years, and young adulthood in cancer‐bereaved youths compared with non‐bereaved peers. Methods In this nationwide, population‐based study, 622 (73%) young adults (aged 18‐26) who had lost a parent to cancer 6 to 9 years previously, when they were teenagers (aged 13–16), and 330 (78%) non‐bereaved peers from a matched random sample answered a study‐specific questionnaire. Associations were assessed using multivariable logistic regression. Results Compared with non‐bereaved youths, the cancer‐bereaved participants were more likely to report poor family cohesion during teenage years (odds ratio [OR] 1.6, 95% CI, 1.0‐2.4, and 2.3, 95% CI, 1.5‐3.5, for paternally and maternally bereaved youths, respectively). This was also seen in young adulthood among maternally bereaved participants (OR 2.5; 95% CI, 1.6‐4.1), while there was no difference between paternally bereaved and non‐bereaved youths. After controlling for a number of covariates (eg, year of birth, number of siblings, and depression), the adjusted ORs for poor family cohesion remained statistically significant. In a further analysis stratified for gender, this difference in perceived poor family cohesion was only noted in females. Conclusion Teenage loss of a parent to cancer was associated with perceived poor family cohesion during teenage years. This was also noted in young adulthood among the maternally bereaved. Females were more likely to report poor family cohesion. Our results indicate a need for increased awareness of family cohesion in bereaved‐to‐be families with teenage offspring, with special attention to gender roles.

Encountering the body of a child who died by suicide at the site of death is believed to be especially harmful for bereaved parents. We investigated the association between encountering the body at the site of the suicide and psychological distress in 666 suicide-bereaved parents. Parents who had encountered their child's body at the site of the suicide (n = 147) did not have a higher risk of nightmares (relative risk [RR] 0.95, 95% confidence interval [CI] 0.67-1.35), intrusive memories (RR 0.97, 95% CI 0.84-1.13), avoidance of thoughts (RR 0.97, 95% CI 0.74-1.27), avoidance of places or things (RR 0.91, 95% CI 0.66-1.25), anxiety (RR 0.93, 95% CI 0.64-1.33), or depression (RR 0.94, 95% CI 0.63-1.42) compared with parents who had not encountered the body (n = 512). Our results suggest that losing a child by suicide is sufficiently disastrous by itself to elicit posttraumatic responses or psychiatric morbidity whether or not the parent has encountered the deceased child at the site of death.

The aim of this study was to create a preoperative prediction model predicting extraprostatic tumour growth in men with clinically organ-confined disease from a prospectively collected Swedish cohort.The study used data from 3386 men in the prospective multi-centre Laparoscopic Prostatectomy Robot Open (LAPPRO) trial, with 14 participating urological departments. External validation was performed using a cohort of 634 men from the largest study centre with patients who underwent surgery before and after the inclusion period of the LAPPRO study. External validation of the updated Partin table was used for comparison. The prediction models were created by multivariable logistic regression. Nomogram prediction performance, internal, internal-external and external validation are presented as the area under the receiver operating characteristic curve (AUC).The nomogram reached a prediction performance with an AUC of 0.741, with internal and external validation of 0.738 and 0.698, respectively. Internal-external validation showed great divergence between centres, with AUCs ranging from 0.476 to 0.892, indicating inconsistencies in pathological staging or one or more of the included variables in the regression model. When including centre as a variable in the multivariable model it was significantly associated with the outcome of pT3 (p 0.001). AUC for external validation of the Partin table was 0.694.Accurate prediction tools in prostate cancer require consistent assessment of included variables, and local validation is needed before the use of such tools in clinical practice.

To analyse oncological and functional outcomes 12 months after treatment of very-low-risk prostate cancer with radical prostatectomy in men who could have been candidates for active surveillance.We conducted a prospective study of all men with very-low-risk prostate cancer who underwent radical prostatectomy at one of 14 participating centres. Validated patient questionnaires were collected at baseline and after 12 months by independent healthcare researchers. Biochemical recurrence (BCR) was defined as prostate-specific antigen (PSA) ≥0.25 ng/mL or treatment with salvage radiotherapy or with hormones. Urinary continence was defined as1 pad changed per 24 h. Erectile function was defined as ability to achieve erection hard enough for penetration more than half of the time after sexual stimulation. Changes in tumour grade and stage were obtained from pathology reports. We report descriptive frequencies and proportions of men who had each outcome in various subgroups. Fisher's exact test was used to assess differences between the age groups.Of the 4003 men in the LAPPRO cohort, 338 men fulfilled the preoperative national criteria for very-low-risk prostate cancer. Adverse pathology outcomes included upgrading, defined as pT3 or postoperative Gleason sum ≥7, which was present in 35% of the men (115/333) and positive surgical margins, which were present in 16% of the men (54/329). Only 2.1% of the men (7/329) had a PSA concentration0.1 ng/mL 6-12 weeks postoperatively. Erectile function and urinary continence were observed in 44% (98/222) and 84% of the men (264/315), respectively, 12 months postoperatively. The proportion of men achieving the trifecta, defined as preoperative potent and continent men who remained potent and continent with no BCR, was 38% (84/221 men) at 12 months.Our prospective study of men with very-low-risk prostate cancer undergoing open or robot-assisted radical prostatectomy showed that there were favourable oncological outcomes in approximately two-thirds. Approximately 40% did not have surgically induced urinary incontinence or erectile dysfunction 12 months postoperatively. These results provide additional support for the use of active surveillance in men with very-low-risk prostate cancer; however, the number of men with risk of upgrading and upstaging is not negligible. Improved stratification is still urgently needed.

Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, 8-10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3+4=7 and 4+3=7 are often considered the same prognostic group.To verify that a new grading system accurately produces a smaller number of grades with the most significant prognostic differences, using multi-institutional and multimodal therapy data.Between 2005 and 2014, 20,845 consecutive men were treated by radical prostatectomy at five academic institutions; 5501 men were treated with radiotherapy at two academic institutions.Outcome was based on biochemical recurrence (BCR). The log-rank test assessed univariable differences in BCR by Gleason score. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores.In the surgery cohort, we found large differences in recurrence rates between both Gleason 3+4 versus 4+3 and Gleason 8 versus 9. The hazard ratios relative to Gleason score 6 were 1.9, 5.1, 8.0, and 11.7 for Gleason scores 3+4, 4+3, 8, and 9-10, respectively. These differences were attenuated in the radiotherapy cohort as a whole due to increased adjuvant or neoadjuvant hormones for patients with high-grade disease but were clearly seen in patients undergoing radiotherapy only. A five-grade group system had the highest prognostic discrimination for all cohorts on both univariable and multivariable analysis. The major limitation was the unavoidable use of prostate-specific antigen BCR as an end point as opposed to cancer-related death.The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.

Introduction Radiotherapy or radical hysterectomy with salpingo-oophorectomy (SOE) as treatment for uterine cervical cancer causes estrogen deprivation in premenopausal women. The effects on androgen production have rarely been examined but could be relevant for survivors of cervical cancer because insufficiency has been associated with low sexual function. Aim To investigate the effects of pelvic radiotherapy, hysterectomy with SOE, or surgery without SOE on androgen levels and to explore potential associations with sexual function. Methods Patients with cervical cancer (N = 60) were prospectively examined through blood sampling and questionnaires before and 1 year after treatments. Main Outcome Measures Serum testosterone (measured by liquid chromatography and tandem mass spectrometry), sex hormone-binding globulin, androstenedione, dehydroepiandrosterone sulfate, follicle-stimulating hormone, luteinizing hormone, and estradiol levels and Female Sexual Function Index scores. Results In women treated with radiotherapy (n = 38), median total and free testosterone levels were significantly decreased at 1-year follow-up compared with baseline in premenopausal women (n = 16; total testosterone −29%, P = .01; free testosterone −22%, P = .007) and postmenopausal women (n = 22; total testosterone −25%, P = .03; free testosterone −29%, P = .03). Androstenedione was decreased in premenopausal women only and dehydroepiandrosterone sulfate was decreased in postmenopausal women only after radiotherapy. In women treated with hysterectomy and SOE (n = 10), testosterone levels were lower but not significantly lower, and there was no change in those having surgery without SOE (n = 12). Female Sexual Function Index scores lower than 26.5 in sexually active women were reported by 80% 1 year after radiotherapy, by 44% after hysterectomy with SOE, and by 40% after surgery without SOE, with no significant differences compared with baseline values. No direct correlation between androgen levels and Female Sexual Function Index scores were found at 1-year follow-up. Conclusion Total and free testosterone levels decreased slightly but significantly after pelvic radiotherapy in pre- and postmenopausal women. The clinical importance of this decrease is unclear, but androgen levels were not directly related to sexual function in this pilot setting.

Background. We aimed to investigate cancer-bereaved youths’ opinions and experiences of being told about a parent's imminent death from cancer and of barriers to this communication.Material and methods. This nationwide population-based survey included 622/851 (73%) youths (aged 18–26) who at age 13–16, 6–9 years earlier had lost a parent to cancer.Results. In total 595 of 610 (98%) of the participants stated that teenage children should be informed when the parent's death was imminent (i.e. a matter of hours or days, not weeks). 59% stated that they themselves had been told this, 37% by the parents, 7% by parents and healthcare professionals together and 8% by professionals only. Frequent reasons for why the teenager and parents did not talk about imminent death before loss were that one (n = 106) or both (n = 25) of the parents together with the teenage child had pretended that the illness was not that serious, or that none of the parents had been aware that death was imminent (n = 80). Up to a couple of hours before the loss, 43% of participants had not realized that death was imminent.Conclusion. In this population-based study virtually all youth who at ages 13–16 had lost a parent to cancer afterwards stated that teenagers should be told when loss is near, i.e. a matter of hours or days, not weeks. Many stated that they had not been given this information and few were informed by professionals, with implications for future improvements in end-of-life care of patients with teenage children.

BACKGROUND: Parents who lose a child by suicide have elevated risks of depression. No clinical prediction tools exist to identify which suicide-bereaved parents will be particularly vulnerable; we aimed to create a prediction model for long-term depression for this purpose. METHOD: During 2009 and 2010 we collected data using a nationwide study-specific questionnaire among parents in Sweden who had lost a child aged 15-30 by suicide in years 2004-2007. Current depression was assessed with the Patient Health Questionnaire (PHQ-9) and a single question on antidepressant use. We considered 26 potential predictors assumed clinically assessable at the time of loss, including socio-economics, relationship status, history of psychological stress and morbidity, and suicide-related circumstances. We developed a novel prediction model using logistic regression with all subsets selection and stratified cross-validation. The model was assessed for classification performance and calibration, overall and stratified by time since loss. RESULTS: In total 666/915 (73%) participated. The model showed acceptable classification performance (adjusted area under the curve [AUC] = 0.720, 95% confidence interval [CI] 0.673-0.766), but performed classification best for those at shortest time since loss. Agreement between model-predicted and observed risks was fair, but with a tendency for underestimation and overestimation for individuals with shortest and longest time since loss, respectively. The identified predictors include female sex (odds ratio [OR] = 1.84); sick-leave (OR = 2.81) or unemployment (OR = 1.64); psychological premorbidity debuting during the last 10 years, before loss (OR = 3.64), or more than 10 years ago (OR = 4.96); suicide in biological relatives (OR = 1.54); with non-legal guardianship during the child's upbringing (OR = 0.48); and non-biological parenthood (OR = 0.22) found as protective. CONCLUSIONS: Our prediction model shows promising internal validity, but should be externally validated before application. Psychological premorbidity seems to be a prominent predictor of long-term depression among suicide-bereaved parents, and thus important for healthcare providers to assess.

Background: A majority of cancer-bereaved siblings report long-term unresolved grief, thus it is important to identify factors that may contribute to resolving their grief. Objective: To identify modifiable or avoidable family and care-related factors associated with unresolved grief among siblings two to nine years post loss. Design: This is a nationwide Swedish postal survey. Measurements: Study-specific questions and the standardized instrument Hospital Anxiety and Depression Scale. Primary outcome was unresolved grief, and family and care-related factors were used as predictors. Setting/Participants: Cancer-bereaved sibling (N = 174) who lost a brother/sister to childhood cancer during 2000–2007 in Sweden (participation rate 73%). Seventy-three were males and 101 females. The age of the siblings at time of loss was 12–25 years and at the time of the survey between 19 and 33 years. Results: Several predictors for unresolved grief were identified: siblings' perception that it was not a peaceful death [odds ratio (OR): 9.86, 95% confidence interval (CI): 2.39–40.65], limited information given to siblings the last month of life (OR: 5.96, 95% CI: 1.87–13.68), information about the impending death communicated the day before it occurred (OR: 2.73, 95% CI: 1.02–7.33), siblings' avoidance of the doctors (OR: 3.22, 95% CI: 0.75–13.76), and lack of communication with family (OR: 2.86, 95% CI: 1.01–8.04) and people outside the family about death (OR: 5.07, 95% CI: 1.64–15.70). Depressive symptoms (OR: 1.27, 95% CI: 1.12–1.45) and time since loss (two to four years: OR: 10.36, 95% CI: 2.87–37.48 and five to seven years: OR: 8.36, 95% CI: 2.36–29.57) also predicted unresolved grief. Together, these predictors explained 54% of the variance of unresolved grief. Conclusion: Siblings' perception that it was not a peaceful death and poor communication with family, friends, and healthcare increased the risk for unresolved grief among the siblings.

Background The evidence supporting the use of magnetic resonance imaging (MRI) in prostate cancer detection has been established, but its accuracy in local staging is questioned. Purpose To investigate the additional value of multi-planar radial reconstructions of a three-dimensional (3D) T2-weighted (T2W) MRI sequence, intercepting the prostate capsule perpendicularly, for improving local staging of prostate cancer. Material and Methods Preoperative, bi-parametric prostate MRI examinations in 94 patients operated between June 2014 and January 2015 where retrospectively reviewed by two experienced abdominal radiologists. Each patient was presented in two separate sets including diffusion-weighted imaging, without and with the 3D T2W set that included radial reconstructions. Each set was read at least two months apart. Extraprostatic tumor extension (EPE) was assessed according to a 5-point grading scale. Sensitivity and specificity for EPE was calculated and presented as receiver operating characteristics (ROC) with area under the curve (AUC), using histology from whole-mount prostate specimen as gold standard. Inter-rater agreement was calculated for the two different reading modes using Cohen’s kappa. Results The AUC for detection of EPE for Readers 1 and 2 in the two-dimensional (2D) set was 0.70 and 0.68, respectively, and for the 2D + 3D set 0.62 and 0.65, respectively. Inter-rater agreement (Reader 1 vs. Reader 2) on EPE using Cohen’s kappa for the 2D and 2D + 3D set, respectively, was 0.42 and 0.17 (i.e. moderate and poor agreement, respectively). Conclusion The addition of 3D T2W MRI with radial reconstructions did not improve local staging in prostate cancer.

The aim of this study was to assess the effect of introducing an enhanced recovery programme (ERP) to an established robot-assisted radical cystectomy (RARC) service.Data were prospectively collected on 221 consecutive patients undergoing totally intracorporeal RARC between December 2003 and May 2014. The ERP was specifically designed to support an evolving RARC service, where increasing proportions of patients requiring radical cystectomy underwent RARC. Patient demographics and outcomes before and after implementation of the ERP were compared. The primary endpoint was length of stay (LOS). Secondary outcomes included age, American Society of Anesthesiologists (ASA) score, preoperative staging, operative time, complications and readmissions. Differences in outcomes between patients before and after implementation of ERP were tested with the Jonckheere-Terpstra trend test and quantile regression with backward selection.Following implementation of the ERP, the demographics of the patients (n = 135) changed, with median age increasing from 66 to 70 years (p0.01), higher ASA grade (p0.001), higher preoperative stage cancer (pT ≥ 2, p0.05) and increased likelihood of undergoing an ileal conduit diversion (p0.001). Median LOS before ERP was 9 days [interquartile range (IQR) 8-13 days] and after ERP was 8 days (IQR 6-10 days) (p0.001). ASA grade and neoadjuvant chemotherapy also affected LOS (p0.05 and p0.01, respectively). There was no significant difference in 30 day complication rates, readmission rates or 90 day mortality, with 59% experiencing complications before ERP implementation and 57% after implementation. The majority of complications were low grade.Patient demographics changed as the RARC service evolved from selected patients to a general service. Despite worsening demographics, LOS decreased following ERP implementation. This evidence-based ERP safely standardized perioperative care, resulting in decreased LOS and decreased variability in LOS.

This study aims to assess use of hormone therapy (HT) after cervical cancer treatment in women of premenopause age.We identified 837 women aged 45 years or younger at diagnosis of cervical cancer in the Swedish Cancer Register from January 1, 2005 to September 30, 2009 with a minimal follow-up of 1.5 years. Information on cancer treatment (surgical operation, radiotherapy, and/or chemotherapy) was obtained through the National Patient Register. Use of HT was estimated through HT dispensing during follow-up as recorded in the Prescribed Drug Register. Percentage of recommended dose was assessed by frequency of HT dispensing at half-year intervals up to April 1, 2011 or a maximal age of 50 years.A total of 257 women (31%) received acute estrogen deprivation due to bilateral salpingo-oophorectomy and/or radiotherapy. Among these women, 171 (67%) of 257 had at least one dispensing of HT during the period 0.5 to 1 year after diagnosis, and 118 (46%) of 257 were dispensed 75% or more of the recommended dose. Proportion users decreased to 39% at 4.5 to 5 years after diagnosis (21% with ≥ 75% of the recommended dose). Women younger than 40 years had a higher prevalence of HT use at 0.5 to 1 year (79%), decreasing to 45% after 4.5 to 5 years. The results did not vary by cancer histology.Fewer than half of cervical cancer survivors with therapy-induced early menopause used HT at or close to the recommended dose, and the use decreased during follow-up. Increased awareness of the health benefits of HT for this patient group is needed among professionals and women.

Abstract. Background: Lack of trust in the health-care system after losing a child to suicide may prevent bereaved parents from seeking professional treatment when needed, thus diminishing their chances of recovery. Aims: This is the first large study to aim at evaluating the incidence of lack of trust in the health-care system and associated variables in suicide-bereaved parents. Method: This nationwide population-based survey included 569 parents who lost a child to suicide 2-5 years earlier and a matched comparison group of 326 nonbereaved parents. Using a study-specific questionnaire, we asked bereaved and nonbereaved parents if they trusted the health-care system and measured psychological and background variables. Results: Prevalence of lack of trust in the health-care system differed between the bereaved (46.5%) and the nonbereaved parents (18.3%), giving a relative risk of 2.5 (95% CI = 2.0-3.3). After multivariable modeling, high scores of depression, living in big cities, and being single were identified as variables associated with lack of trust in suicide-bereaved parents. Conclusion: Suicide-bereaved parents show lack of trust in the health-care system. We present possible effect modifiers that may be considered in professional interventions aiming at influencing suicide-bereaved parents' level of trust.

Lymph node dissection in patients with prostate cancer may increase complications. An association of lymph node dissection with thromboembolic events was suggested. We compared the incidence and investigated predictors of deep venous thrombosis and pulmonary embolism among other complications in patients who did or did not undergo lymph node dissection during open and robot-assisted laparoscopic radical prostatectomy.Included in study were 3,544 patients between 2008 and 2011. The cohort was derived from LAPPRO, a multicenter, prospective, controlled trial. Data on adverse events were extracted from patient completed questionnaires. Our primary study outcome was the prevalence of deep venous thrombosis and/or pulmonary embolism. Secondary outcomes were other types of 90-day adverse events and causes of hospital readmission.Lymph node dissection was performed in 547 patients (15.4%). It was associated with eightfold and sixfold greater risk of deep venous thrombosis and pulmonary embolism events compared to that in patients without lymph node dissection (RR 7.80, 95% CI 3.51-17.32 and 6.29, 95% CI 2.11-18.73, respectively). Factors predictive of thromboembolic events included a history of thrombosis, pT4 stage and Gleason score 8 or greater. Open radical prostatectomy and lymph node dissection carried a higher risk of deep venous thrombosis and/or pulmonary embolism than robot-assisted laparoscopic radical prostatectomy (RR 12.67, 95% CI 5.05-31.77 vs 7.52, 95% CI 2.84-19.88). In patients without lymph node dissection open radical prostatectomy increased the thromboembolic risk 3.8-fold (95% CI 1.42-9.99) compared to robot-assisted laparoscopic radical prostatectomy. Lymph node dissection induced more wound, respiratory, cardiovascular and neuromusculoskeletal events. It also caused more readmissions than no lymph node dissection (14.6% vs 6.3%).Among other adverse events we found that lymph node dissection during radical prostatectomy increased the incidence of deep venous thrombosis and pulmonary embolism. Open surgery increased the risks more than robot-assisted surgery. This was most prominent in patients who were not treated with lymph node dissection.

Background Men with prostate cancer experience adjuvant androgen deprivation therapy (ADT) differently. Objective To evaluate the effect of ADT on quality of life (QoL), patients’ experience of clinical check-ups, and differences in cancer information as explanatory factors. Design, setting, and participants A study-specific questionnaire was sent to all men randomized in the SPCG-4 trial to radical prostatectomy (RP) or watchful waiting (WW) still alive (400/695) and a control group of 281 men. Intervention ADT. Outcome measurements and statistical analysis Self-assessed QoL, worry at clinical check-ups, and amount of information received. Estimated relative risks with associated 95% confidence intervals (CI) for risk comparisons between groups using a log-binomial regression. Results and limitations The SPCG-4 men had median follow-up of 12.2 yr and median age of 77.0 yr; 26% in the RP group and 40% in the WW group received ADT treatment. High QoL for men without ADT was 36% for the RP group, 44% for the WW group, and 45% for the control group. High QoL for men with ADT was 30% for the RP group and 20% for the WW group. Among men with ADT, those in the WW group received significantly less information about the disease than men in the RP group. Receiving no or little information about prostate cancer was reported by 17% of patients in the RP group and 39% in the WW group among men receiving ADT (relative risk 0.44, 95% CI 0.22–0.89). At clinical check-ups, men treated with ADT had significantly higher levels of worry, regardless of study group, than men without ADT. Limitations include the lack of longitudinal data and a low number of men receiving ADT in the RP group. Conclusions Men on WW without ADT reported high QoL comparable to that for men without prostate cancer. ADT treatment in the WW group was associated with the lowest scores for all psychological parameters, and these men reported that they were least informed about prostate cancer and its consequences. Patient summary Good communication and information from caregivers are associated with less negative psychological effects at prostate cancer progression.

Purpose Previous research shows that the death of a parent places children at risk for a number of negative outcomes. The role of trust in health care at the end of life has been acknowledged as crucial for patients and adult family members. However, the consequences of children’s distrust in the care provided to their parents remain unknown. Therefore, we investigated the negative long-term outcomes of cancer-bereaved sons’ and daughters’ distrust in the care that was provided to a dying parent. Methods We used a population-based nationwide survey to investigate self-reported distrust in the care provided and possible negative outcomes in 622 (73%) participants who had lost a parent as a result of cancer 6 to 9 years earlier, at ages 13 to 16 years. All participants were 18 years or older at the time of the survey. Results In those who reported no or little trust (ie, distrust) in the health care provided to their dying parents, we found statistically significantly higher risks of various negative outcomes at the time of survey: bitterness toward health care professionals for not having done everything that was possible (crude risk ratio [RR], 3.5; 95% CI, 2.3 to 5.1) and for having stopped treatment (RR, 3.4; 95% CI, 2.1 to 6.0), self-destructiveness (eg, self-injury [RR, 1.7; 95% CI, 1.2 to 2.4]), and psychological problems (eg, moderate to severe depression according to the Patient Health Questionnaire–9 [RR, 2.3; 95% CI, 1.5 to 3.5]). Conclusion In cancer-bereaved former adolescents, distrust in the health care provided to the dying parent is associated with a higher risk of negative long-term outcomes. The health care professionals involved in this care might play an important role in safeguarding the trust of adolescents.

Background Surgery for prostate cancer has a large impact on quality of life (QoL). Objective To evaluate predictors for the level of self-assessed QoL at 3 mo, 12 mo, and 24 mo after robot-assisted laparoscopic (RALP) and open radical prostatectomy (ORP). Design, setting, and participants The LAParoscopic Prostatectomy Robot Open study, a prospective, controlled, nonrandomised trial of more than 4000 men who underwent radical prostatectomy at 14 centres. Here we report on QoL issues after RALP and ORP. Outcome measurements and statistical analysis The primary outcome was self-assessed QoL preoperatively and at 3 mo, 12 mo, and 24 mo postoperatively. A direct validated question of self-assessed QoL on a seven-digit visual scale was used. Differences in QoL were analysed using logistic regression, with adjustment for confounders. Results and limitations QoL did not differ between RALP and ORP postoperatively. Men undergoing ORP had a preoperatively significantly lower level of self-assessed QoL in a multivariable analysis compared with men undergoing RALP (odds ratio: 1.21, 95% confidence interval: 1.02–1.43), that disappeared when adjusted for preoperative preparedness for incontinence, erectile dysfunction, and certainty of being cured (odds ratio: 1.18, 95% confidence interval: 0.99–1.40). Incontinence and erectile dysfunction increased the risk for poor QoL at 3 mo, 12 mo, and 24 mo postoperatively. Biochemical recurrence did not affect QoL. A limitation of the study is the nonrandomised design. Conclusions QoL at 3 mo, 12 mo, and 24 mo after RALP or ORP did not differ significantly between the two techniques. Poor QoL was associated with postoperative incontinence and erectile dysfunction but not with early cancer relapse, which was related to thoughts of death and waking up at night with worry. Patient summary We did not find any difference in quality of life at 3 mo, 12 mo, and 24 mo when open and robot-assisted surgery for prostate cancer were compared. Postoperative incontinence and erectile dysfunction were associated with poor quality of life.

Objective To evaluate the role of positive surgical margin (PSM) size/focality and location in relation to risk of biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). Patients and Methods Clinicopathological data were collected from 904 patients who underwent RARP at a single European institution from 2002 to 2006. PSM status after RARP was defined as cancer cells at the inked margin, and was stratified by size/focality and location. The outcome variable was BCR, defined as a postoperative PSA level of ≥0.2 ng/mL. We modelled clinicopathological covariates including PSM size/focality and location using Cox proportional hazards regression. In subgroup analyses, we assessed the effect of PSM size and location at different pathological stages and grades of disease. Results Compared with negative SM, a PSM of >3 mm/multifocal was associated with an increased risk of BCR in the entire cohort (hazard ratio [HR] 2.84, 95% confidence interval 1.76–4.59), while unifocal PSMs of ≤3 mm were not significantly associated with BCR. In subgroup analyses, the negative impact of >3 mm/multifocal PSM appeared greatest in those with lower postoperative stage and grade of disease. The prognostic role of PSM location was unconfirmed, although data indicated that posterolateral PSMs may be of lower significance in RARP patients. The study is limited by lack of central pathology review, and lack of statistical adjustment for tumour volume, lymph node status, and surgeon volume. Conclusion We found that men with >3 mm/multifocal PSMs have a higher risk of BCR than those with unifocal PSMs of ≤3 mm or negative SMs, especially if they have lower risk disease. Posterolateral margins may be of little significance in a RARP population.

Background: Self-injury, a manifestation of severe psychological distress, is increased in cancer-bereaved youths. Little is known about the potential influence on the risk for self-injury of factors that could be clinically relevant to and modifiable by the health-care professionals involved in the care of the dying parent. Methods: In a nationwide population-based anonymous study, 622 (73.1%) youths (aged 18-26) who, 6 to 9 years earlier at ages 13 to 16, had lost a parent to cancer answered study-specific questions about self-injury and factors related to the family and parental health care. Results: Univariable analyses showed that the risk for self-injury was increased among cancer-bereaved youths who reported poor family cohesion the years before (relative risk [RR], 3.4, 95% confidence interval [CI], 2.5-4.6) and after the loss (RR, 3.3, 95% CI, 2.4-4.4), distrust in the health care provided to the dying parent (RR, 1.7, 95% CI, 1.2-2.4), perceiving poor health-care efforts to cure the parent (RR 1.5, 95% CI, 1.1-2.1) and poor efforts to prevent suffering (RR, 1.6, 95% CI, 1.1-2.4), that at least one of their parents had been depressed or had troubles in life (RR, 1.5, CI, 1.1-2.1) and believing 3 days before the loss that the treatment would probably cure the parent (RR, 1.6, CI, 1.1-2.3). In the total multivariable models, only poor family cohesion before and after the loss remained statistically significantly associated with self-injury. Conclusion: Poor family cohesion before and after the loss of a parent to cancer is associated with an increased risk of self-injury in teenage children. Copyright (C) 2014 John Wiley & Sons, Ltd. (Less)

Objective To evaluate the effect of the learning curve on operative, postoperative, and pathological outcomes of the first 67 totally intracorporeal robot-assisted radical cystectomies (RARCs) with neobladders performed by two lead surgeons at Karolinska University Hospital. Patients and Methods Between December 2003 and October 2012, 67 patients (61 men and six women) underwent RARC with orthotopic urinary diversion by two main surgeons. Data were collected prospectively on patient demographics, peri- and postoperative outcomes including operation times, conversion rates, blood loss, complication rates, pathological data and length of stay (LOS) for these 67 consecutive patients. The two surgeons operated on 47 and 20 patients, respectively. The patients were divided into sequential groups of 10 in each individual surgeon's series and assessed for effect of the learning curve. Results Patient demographics and clinical characteristics were similar in both surgeons' groups. The overall total operation times trended down in both surgeons' series from a median time of 565 min in the first group of 10 cases, to a median of 345 min in the last group for surgeon A (P < 0.001) and 413 to 385 min for surgeon B (not statistically significant). Risk of conversion to open surgery also decreased with a 30% conversion rate in the first group to zero in latter groups (P < 0.01). Overall complications decreased as the learning curve progressed from 70% in the first group to 30% in the later groups (P < 0.05), although major complications were not statistically different when compared between the groups. Patient demographics did not change over time. The mean estimated blood loss was unchanged across groups with increasing experience. The pathological staging, mean total lymph node yield and number of positive margins were also unchanged across groups. There was a decrease in LOS from a mean of 19 days in the first group to a mean (range) of 9 (4–78) days in the later groups, although the median LOS was unchanged and therefore not statistically significant. Conclusions Totally intracorporeal RARC with intracorporeal neobladder is a complex procedure, but it can be performed safely, with a structured approach, at a high-volume established robotic surgery centre without compromising perioperative and pathological outcomes during the learning curve for surgeons. An experienced robotic team and mentor can impact the learning curve of a new surgeon in the same centre resulting in decreased operation times early in their personal series, reducing conversion rates and complication rates.

Many clinicians believe that preparedness before surgery for possible post-surgery side effects reduces the level of bother experienced from urinary incontinence and decreased sexual health after surgery. There are no published studies evaluating this belief. Therefore, we aimed to study the level of preparedness before radical prostatectomy and the level of bother experienced from urinary incontinence and decreased sexual health after surgery.We prospectively collected data from a non-selected group of men undergoing radical prostatectomy in 14 centers between 2008 and 2011. Before surgery, we asked about preparedness for surgery-induced urinary problems and decreased sexual health. One year after surgery, we asked about bother caused by urinary incontinence and erectile dysfunction. As a measure of the association between preparedness and bothersomeness we modeled odds ratios (ORs) by means of logistic regression.Altogether 1372 men had urinary incontinence one year after surgery as well as had no urinary leakage or a small urinary dribble before surgery. Among these men, low preparedness was associated with bother resulting from urinary incontinence [OR 2.84; 95% confidence interval (CI) 1.59-5.10]. In a separate analysis of 1657 men we found a strong association between preparedness for decreased sexual health and experiencing bother from erectile dysfunction (OR 5.92; 95% CI 3.32-10.55).In this large-sized prospective trial, we found that preparedness before surgery for urinary problems or sexual side effects decreases bother from urinary incontinence and erectile dysfunction one year after surgery.

Recurrence following radical cystectomy often occurs early, with >80% of recurrences occurring within the first 2 yr. Debate remains as to whether robot-assisted radical cystectomy (RARC) negatively impacts early recurrence patterns because of inadequate resection or pneumoperitoneum. We report early recurrence patterns among 717 patients who underwent RARC with intracorporeal urinary diversion at nine different institutions with a minimum follow-up of 12 mo. Clinical, pathologic, radiologic, and survival data at the latest follow-up were collected. Recurrence-free survival (RFS) estimates were generated using the Kaplan-Meier method, and Cox regression models were built to assess variables associated with recurrence. RFS at 3, 12, and 24 mo was 95.9%, 80.2%, and 74.6% respectively. Distant recurrences most frequently occurred in the bones, lungs, and liver, and pelvic lymph nodes were the commonest site of local recurrence. We identified five patients (0.7%) with peritoneal carcinomatosis and two patients (0.3%) with metastasis at the port site (wound site). We conclude that unusual recurrence patterns were not identified in this multi-institutional series and that recurrence patterns appear similar to those in open radical cystectomy series. Patient summary In this multi-institutional study, bladder cancer recurrences following robotic surgery are described. Early recurrence rates and locations appear to be similar to those for open radical cystectomy series.

Introduction: The aim of this report is to describe our surgical technique of totally intracorporeal robotic assisted radical cystectomy (RARC) with neobladder formation. Materials and Methods: Between December 2003 and March 2013, a total of 147 patients (118 male, 29 female) underwent totally intracorporeal RARC for urinary bladder cancer. We also performed a systematic search of Medline, Embase and PubMed databases using the terms RARC, robotic cystectomy, robot-assisted, totally intracorporeal RARC, intracorporeal neobladder, intracorporeal urinary diversion, oncological outcomes, functional outcomes, and complication rates. Results: The mean age of our patients was 64 years (range 37-87). On surgical pathology 47% had pT1 or less disease, 27% had pT2, 16% had pT3 and 10% had pT4. The mean number of lymph nodes removed was 21 (range 0-60). 24% of patients had lymph node positive dAQ1isease. Positive surgical margins occurred in 6 cases (4%). Mean follow-up was 31 months (range 4-115 months). Two patients (1.4%) died within 90 days of their operation. Using Kaplan-Meier analysis, overall survival and cancer specific survival at 60 months was 68% and 69.6%, respectively. 80 patients (54%) received a continent diversion with totally intracorporeal neobladder formation. In the neobladder subgroup median total operating time was 420 minutes (range 265-760). Daytime continence and satisfactory sexual function or potency at 12 months ranged between 70-90% in both men and women. Conclusions: Our experience with totally intracorporeal RARC demonstrates acceptable oncological and functional outcomes that suggest this is a viable alternative to open radical cystectomy.

OBJECTIVE: To compare the survival outcomes of patients treated with surgery or radiotherapy for prostate cancer. DESIGN: Observational study. SETTING: Sweden, 1996-2010. PARTICIPANTS: 34,515 men primarily treated for prostate cancer with surgery (n=21,533) or radiotherapy (n=12,982). Patients were categorised by risk group (low, intermediate, high, and metastatic), age, and Charlson comorbidity score. MAIN OUTCOME MEASURES: Cumulative incidence of mortality from prostate cancer and other causes. Competing risks regression hazard ratios for radiotherapy versus surgery were computed without adjustment and after propensity score and traditional (multivariable) adjustments, as well as after propensity score matching. Several sensitivity analyses were performed. RESULTS: Prostate cancer mortality became a larger proportion of overall mortality as risk group increased for both the surgery and the radiotherapy cohorts. Among patients with non-metastatic prostate cancer the adjusted subdistribution hazard ratio for prostate cancer mortality favoured surgery (1.76, 95% confidence interval 1.49 to 2.08, for radiotherapy v prostatectomy), whereas there was no discernible difference in treatment effect among men with metastatic disease. Subgroup analyses indicated more clear benefits of surgery among younger and fitter men with intermediate and high risk disease. Sensitivity analyses confirmed the main findings. CONCLUSIONS: This large observational study with follow-up to 15 years suggests that for most men with non-metastatic prostate cancer, surgery leads to better survival than does radiotherapy. Younger men and those with less comorbidity who have intermediate or high risk localised prostate cancer might have a greater benefit from surgery.

Background: Robot-assisted radical prostatectomy (RARP) is an increasingly commonly used surgical treatment option for prostate cancer (PCa); however, its longer-term oncologic results remain uncertain. Objective: To report biochemical recurrence–free survival (BRFS) outcomes for men who underwent RARP � 5 yr ago at a single European centre. Design, setting, and participants: A total of 944 patients underwent RARP as monotherapy for PCa from January 2002 to December 2006 at Karolinska University Hospital, Stockholm, Sweden. Standard clinicopathologic variables were recorded and entered into a secure, ethics-approved database made up of those men with registered domiciles in Stockholm. The median follow-up time was 6.3 yr (interquartile range: 5.6–7.2). Outcome measurements and statistical analysis: The outcome of this study was biochemical recurrence (BCR), defined as a confirmed prostate-specific antigen (PSA) of � 0.2 ng/ml. Kaplan-Meier survival plots with log-rank tests, as well as Cox univariable and multivariable regression analyses, were used to determine BRFS estimates and determine predictors of PSA relapse, respectively. Results and limitations: The BRFS for the entire cohort at median follow-up was 84.8% (95% confidence interval [CI], 82.2–87.1); estimates at 5, 7, and 9 yr were 87.1% (95% CI, 84.8–89.2), 84.5% (95% CI, 81.8–86.8), and 82.6% (95% CI, 79.0–85.6), respectively. Nine and 19 patients died of PCa and other causes, respectively, giving end– of–follow-up Kaplan-Meier survival estimates of 98.0% (95% CI, 95.5–99.1) and 94.1% (95% CI, 90.4–96.4), respectively. Preoperative PSA >10, postoperative Gleason sum � 4+ 3, pathologic T3 disease, positive surgical margin status, and lower surgeon volume were associated with increased risk of BCR on multivariable analysis. This study is limited by a lack of nodal status and tumour volume, which may have confounded our findings. Conclusions: This case series from a single, high-volume, European centre demonstrates that RARP has satisfactory medium-term BRFS. Further follow-up is necessary to determine how this finding will translate into cancer-specific and overall survival outcomes.

To analyze the relationship between mean radiation dose to the bowels and the anal-sphincter and occurrence of 'defecation into clothing without forewarning', a specific and serious fecal incontinence symptom after gynecological radiotherapy. Additional potential risk factors associated with the symptom are explored.Data were collected for 519 eligible gynecological cancer survivors, treated with pelvic radiotherapy, with a median follow-up of 5.8 years, using a study-specific questionnaire and medical records. Correlations between defecation into clothing without forewarning and mean dose to organs at risk; the anal-sphincter region, the rectum, the sigmoid and the small intestines were investigated, also taking other risk factors into account.Twelve percent reported having had the symptom at least once in the preceding six months. Mean doses 50 Gy to the anal-sphincter region, the rectum, the sigmoid and the small intestines were related to the occurrence of the symptom. Significantly associated risk factors were deliveries with high birth weight, heart failure and lactose and/or gluten intolerance. After adjusting for these factors, mean doses 50 Gy to the anal-sphincter region, the sigmoid and the small intestines remained related to the occurrence of the symptom.Mean doses to the bowels and anal-sphincter region are related to the risk of defecation into clothing without forewarning in long-term gynecological cancer survivors treated with pelvic radiotherapy. Further radiobiological modeling may distinguish which organ(s) contribute most to development of the symptom.

There is increasing low-quality evidence rationalizing the use of radical therapy for men at high risk of disseminated prostate cancer.To investigate, using high-quality epidemiologic data, whether initial radical therapy in men at high risk of disseminated prostate cancer improves survival.An observational population-based Swedish study from 1996 to 2010 of men at high risk of disseminated prostate cancer (prostate-specific antigen [PSA]50) initially treated by radical therapy (radiation therapy [n=630] or radical prostatectomy [n=120]) or androgen deprivation therapy (n=17 602), and followed for up to 15 yr.Prostate-cancer and other-cause mortality was estimated for the treatment groups. We also matched the two cohorts for grade, T stage, M stage, Charlson score, year of diagnosis, age, and PSA, and found androgen deprivation therapy patient matches for 575 of the radical therapy patients, and then repeated comparative effectiveness analyses.Prostate-cancer mortality was substantially greater in the androgen deprivation therapy group compared with the radically treated one, in unmatched (9062/17 602 vs 86/750) and matched (177/575 vs 71/575) cohorts. Among matched cohorts, initial androgen deprivation therapy was associated with nearly three-fold higher hazard of prostate-cancer death compared with initial radical therapy (2.87; 95% confidence interval 2.16-3.82). Multiple sensitivity analyses suggested that the findings were robust, although the general limitations of nonrandomized studies remain. Further, the study cohort may have included men with both systemic and nonsystemic disease, as a sole eligibility criterion of PSA50 was used.This large and comprehensive population-based study suggests that initial radical therapy in men at high risk of disseminated prostate cancer improves survival.This large Swedish study suggests that men with prostate cancer that has spread beyond the prostate benefit from treating the prostate itself with radiation therapy or surgery rather than treating the disease with hormones alone.

Background Current trials are investigating radical intervention in men with metastatic prostate cancer. However, there is a lack of safety data for radical prostatectomy as therapy in this setting. Objective To examine perioperative outcomes and short-term complications after radical prostatectomy for locally resectable, distant metastatic prostate cancer. Design, setting, and participants A retrospective case series from 2007 to 2014 comprising 106 patients with newly diagnosed metastatic (M1) prostate cancer from the USA, Germany, Italy, and Sweden. Intervention Radical prostatectomy and extended pelvic lymphadenectomy. Outcome measurements and statistical analysis Descriptive statistics were used to present margin status, continence, and readmission, reoperation, and overall complication rates at 90 d, as well as for 21 specific complications. Kaplan-Meier plots were used to estimate survival function. Intercenter variability and M1a/ M1b subgroups were examined. Results and limitations Some 79.2% of patients did not suffer any complications; positive-margin (53.8%), lymphocele (8.5%), and wound infection (4.7%) rates were higher in our cohort than in a meta-analysis of open radical prostatectomy performed for standard indications. At a median follow-up of 22.8 mo, 94/106 (88.7%) men were still alive. The study is limited by its retrospective design, differing selection criteria, and short follow-up. Conclusions Radical prostatectomy for men with locally resectable, distant metastatic prostate cancer appears safe in expert hands for meticulously selected patients. Overall and specific complication rates related to the surgical extirpation are not more frequent than when radical prostatectomy is performed for standard indications, and the use of extended pelvic lymphadenectomy in all of this cohort compared to its selective use in localized/locally advanced prostate cancer accounts for any extra morbidity. Patient summary Men presenting with advanced prostate cancer that has spread beyond the prostate are increasingly being considered for treatments directed at the prostate itself. On the basis of results for our international series of 106 men, surgery appears reasonably safe in this setting for certain patients.

The aim of this study was to investigate what bowel organ and delivered dose levels are most relevant for the development of 'emptying of all stools into clothing without forewarning' so that the related dose-responses could be derived as an aid in avoiding this distressing symptom in the future.Of the 77 gynecological cancer survivors treated with radiotherapy (RT) for gynecological cancer, 13 developed the symptom. The survivors were treated between 1991 and 2003. The anal-sphincter region, the rectum, the sigmoid and the small intestines were all delineated and the dose-volume histograms were exported for each patient. The dose-volume parameters were estimated fitting the data to the Relative Seriality (RS), the Lyman and the generalized Equivalent Uniform Dose (gEUD) model.The dose-response parameters for all three models and four organs at risk (OARs) were estimated. The data from the sigmoid fits the studied models best: D50 was 58.8 and 59.5 Gy (RS, Lyman), γ50 was 1.60 and 1.57 (RS, Lyman), s was 0.32, n was 0.13 and a was 7.7 (RS, Lyman, gEUD). The estimated volume parameters indicate that the investigated OARs behave serially for this endpoint. Our results for the three models studied indicate that they have the same predictive power (similar LL values) for the symptom as a function of the dose for all investigated OARs.In our study, the anal-sphincter region and sigmoid fit our data best, but all OARs were found to have steep dose-responses for 'emptying of all stools into clothing without forewarning' and thus, the outcome can be predicted with an NTCP model. In addition, the dose to the four studied OARs may be considered when minimizing the risk of the symptom.

BACKGROUND: The objective of this study was to assess long-term psychological distress in siblings who lost a brother or sister to cancer 2 to 9 years earlier, as compared with a control group of n ...

Summary Background For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years. Methods All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint. Findings 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7–17) and a median age of 77·0 years (range 61–88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07–1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life. Interpretation For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information. Funding US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linner.

OBJECTIVE To identify predictors for long-term urinary leakage after radical prostatectomy. PATIENTS AND METHODS A consecutive series of 1411 patients who underwent radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital between 2002 and 2006 were invited to complete a study-specific questionnaire. Urinary leakage was defined as use of two or more pads per day. RESULTS Questionnaires were received from 1288 (91%) patients with a median follow-up of 2.2 years. Age at surgery predicts in an exponential manner long-term urinary incontinence at follow-up with an estimated relative increase of 6% per year. Among the oldest patients, 19% had urinary incontinence compared with 6% in the youngest age group, translating to a prevalence ratio of 2.4 (95% confidence interval [CI], 1.5-8.1). Low educational level, as compared with high, yielded an increased age-adjusted prevalence ratio of 2.5 (95% CI, 1.7-3.9). Patients who had undergone salvage radiation therapy had an increased prevalence of urinary incontinence (2.5; 95% CI, 1.6-3.8), as did those with respiratory disease (2.4; 95% CI, 1.3-4.4). Body mass index, prostate weight, presence of diabetes or previous transurethral resection did not appear to influence the prevalence of urinary incontinence. CONCLUSIONS In this series, a patient's age at radical prostatectomy influenced, in an exponential manner, his risk of long-term urinary incontinence. Other predictors are low educational level, salvage radiation therapy and respiratory disease. Intervention studies are needed to understand if these data are relevant to the prevalence of urinary leakage if a radical prostatectomy is postponed in an active monitoring programme.

Objectives To assess the surgery-related complications at robot-assisted radical cystectomy with total intracorporeal urinary diversion during our learning curve in treating 45 patients with bladder cancer. Methods A total of 45 patients were pooled in 3 consecutive groups of 15 cases each to evaluate the complications according to the Clavien classification. As a surrogate for our learning curve, the following parameters were assessed: operative time, blood loss, urinary diversion type, lymph node yield, surgical margin status, and length of hospital stay. Results Early surgery-related complications were noted in 40% of the patients and late complications in 30%. The early Clavien grade III complications remained significant (27%) and did not decline with time. Overall, fewer complications were observed between the groups over time, with a significant decrease in late versus early complications ( P = .005 and P = .058). The mean operative times declined from the first group to the second and third groups ( P = .005) and the hospital stays shortened ( P = .006). No significant difference was observed between groups regarding the lymph node yield at cystectomy ( P = .108), with a mean of 22.5 nodes (range 10-52) removed. More patients received an orthotopic bladder substitute (Studer) in each of the latter 2 groups than in the first. Conclusions Although robot-assisted radical cystectomy with total intracorporeal urinary diversion is a complex procedure, we observed decreased surgery-related complications and improved outcomes over time in the present series. Our results need to be confirmed by others before robot-assisted radical cystectomy with totally intracorporeal urinary diversion can be accepted as a treatment option for patients with bladder cancer.

We analyzed whether the NOS2 promoter microsatellite (CCTTT)n polymorphism influences bladder cancer pathogenesis.We genotyped 359 patients with bladder cancer in a population based cohort and 164 population controls by DNA fragment analysis and sequencing. Genotypes were combined with information on tumor stage, grade and stage, grade progression and cancer specific death. Clinical followup was 5 years.We divided (CCTTT)n alleles into short-10 or fewer, intermediate-11 or 12 and long-13 or greater repeats. Patients homozygous for 13 or longer (CCTTT)n repeats were at decreased odds ratio for bladder cancer (p = 0.010). However, after illness developed they were at 3-fold increased hazard ratio for stage progression (p = 0.062) and 4-fold increased hazard ratio for death from bladder cancer (p = 0.056). We discovered what is to our knowledge a previously undescribed polymorphism at position 23105343 (C/T). There was no difference in frequency between bladder cancer cases and population controls for this polymorphism. No associations were found between tumor stage, grade or stage and grade progression. However, patients with bladder cancer with the heterozygous CT genotype were at 3-fold increased hazard ratio of death from cancer (p = 0.011).Nitric oxide can induce proliferation or apoptosis depending on the cellular context. Results suggest that the (CCTTT)n NOS2 microsatellite may influence bladder cancer risk and aggressiveness. This polymorphism may have an impact on disease pathogenesis, possibly by affecting intracellular nitric oxide levels.