Search

We aimed to compare short term outcomes after robot assisted radical cystectomy (RARC) and open radical cystectomy (ORC) for urinary bladder cancer in a large population. We included all patients without distant metastases who underwent either RARC or ORC with ileal conduit between 2011 and 2019 registered in the Bladder cancer data Base Sweden (BladderBaSe) 2.0. Primary outcome was unplanned readmissions within 90 days, and secondary outcomes within 90 days of surgery were reoperations, Clavien 3–5 complications, total days alive and out of hospital, and mortality. The analysis was carried out using multivariate regression models. Out of 2905 patients, 832 were operated with RARC and 2073 with ORC. Robotic procedures were to a larger extent performed during later years, at high volume centers (47% vs 17%), more often for organ-confined disease (82% vs. 72%) and more frequently in patients with high socioeconomic status (26% vs. 21%). Patients operated with RARC were more commonly readmitted (29% vs. 25%). In multivariable analysis RARC was associated with decreased risk of Clavien 3–5 complications (OR 0.58, 95% CI 0.47–0.72), reoperations (OR 0.53, 95% CI 0.39–0.71) and had more days alive and out of hospital (mean difference 3.7 days, 95% CI 2.4–5.0). This study illustrates the "real-world" effects of a gradual and nation-wide introduction of RARC. Patients operated with RARC had fewer major complications and reoperations but were more frequently readmitted compared to ORC. The observed differences were largely due to more wound related complications among patients treated with ORC. [ABSTRACT FROM AUTHOR]

Prior studies regarding use of Aromatase inhibitors (AIs) and risk for cardiovascular disease (CVD) have shown conflicting results. This retrospective cohort study aimed to investigate whether AIs use affects risk for CVD events in postmenopausal breast cancer survivors. Using a retrospective cohort study design, four CVD outcomes; heart failure or cardiomyopathy, arrhythmia, acute ischemic heart disease and ischemic stroke or Transient Ischemic Attack were compared with uni- and multivariate Cox regression analyses according to exposure to endocrine therapy (use of AI, tamoxifen or AI/tamoxifen sequentially) or no endocrine therapy. In total 15815 postmenopausal women, surgically treated to early breast cancer during 2006–2012, were included. No significantly increased risk for CVD events was observed in patients with AI use in the whole cohort. However, two subgroup analyses showed increased risk for CVD events in the AI/tamoxifen sequential group; heart failure in patients older than 75 years (Hazard Ratio (HR) 2.44; 95% Confidence Interval (CI): 1.32–4.54) and arrhythmia in patients without prior CVD (HR 1.45; 95% CI: 1.01–2.10). An increased risk for arrhythmia and acute ischemic heart disease in patients with at least four years of AI treatment compared with no or short-time exposure was observed (HR 2.12; 95% CI: 1.40–3.25 for arrhythmia; HR 2.03; 95% CI: 1.15–3.58 for ischemic heart disease). Our results indicate an increased risk for ischemic heart disease and arrhythmia in patients treated for more than four years with AIs. This should be considered in the risk-benefit assessment concerning endocrine therapy. • A potential negative impact of aromatase inhibitors as adjuvant treatment on risk for cardiovascular events has been proposed. • We investigated the risk for cardiovascular events in breast cancer patients treated with aromatase inhibitors in a retrospective cohort study. • Use of aromatase inhibitors for four years or more was associated with increased risk for ischemic heart disease and arrhythmia. • Our findings support the need to include this information to the risk-benefit assessment concerning endocrine therapy. [ABSTRACT FROM AUTHOR]

Major advances in breast cancer treatment have led to a reducuction in mortality. However, there are still women who are not cured. We hypothesize there is a sub-group of women with treatment-resistant cancers causing early death. Between 1975 and 2006, 5392 women with invasive breast cancer underwent surgery at Guy's Hospital, London. Data on patient demographics, tumour characteristics, treatment regimens, local recurrence, secondary metastasis, and death were prospectively recorded. We considered four time periods (1975–1982, 1983–1990, 1991–1998, 1999–2006). Risks and time to event analysis were performed with Cox proportional hazards model and Kaplan-Meier estimation. Unadjusted hazard ratios for developing metastasis and overall mortality relative to the 1975–1982 cohort decreased steadily to 0.23 and 0.63, respectively in 1999–2006. However, metastasis-free interval shortened, with the proportion of women developing metastasis ≤5 years increasing from 73.9% to 83.0%. Furthermore, median post-metastatic survival decreased from 1.49 years to 0.94 years. Applying our risk criteria identified the presence of ±200 patients in each cohort who developed metastasis early and died within a much shorter time frame. Advances in treatment have decreased the risk of metastasis and improved survival in women with invasive breast cancer over the last 40 years. Despite this, a subpopulation with shorter metastasis-free and post-metastatic survival who are unresponsive to available treatment remains. This may be due to the ATRESS phenomenon (adjuvant therapy-related shortening of survival) secondary to preselection inherent in adjuvant therapy, successful treatment of less malignant tumour cells and treatment-induced resistance in the remaining tumour clones. • Improved survival, decreased risk of metastasis in breast cancer over last 40 years. • However, women seem to develop metastases earlier in the most recent cohort. • Women with metastatic disease also have shorter survival in the most recent cohort. • This concerns a treatment resistant subgroup of women present in each time cohort. • Has been described in literature as adjuvant therapy-related shortening of survival. [ABSTRACT FROM AUTHOR]

Numerous pretreatment risk classification tools are available for prostate cancer. Which tool is best in predicting prostate cancer death is unclear. To systematically compare the prognostic performance of the most commonly used pretreatment risk stratification tools for prostate cancer. A nationwide cohort study was conducted, including 154 811 men in Prostate Cancer data Base Sweden (PCBaSe) 4.0 diagnosed with nonmetastatic prostate cancer during 1998–2016 and followed through 2016. We compared the D'Amico, National Institute for Health and Care Excellence (NICE), European Association of Urology (EAU), Genito-Urinary Radiation Oncologists of Canada (GUROC), American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), and Cambridge Prognostic Groups (CPG) risk group systems; the Cancer of the Prostate Risk Assessment (CAPRA) score; and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting prostate cancer death by estimating the concordance index (C-index) and the observed versus predicted cumulative incidences at different follow-up times. A total of 139 515 men were included in the main analysis, of whom 15 961 died from prostate cancer during follow-up. The C-index at 10 yr of follow-up ranged from 0.73 (95% confidence interval [CI]: 0.72–0.73) to 0.81 (95% CI: 0.80–0.81) across the compared tools. The MSKCC nomogram (C-index: 0.81, 95% CI: 0.80–0.81), CAPRA score (C-index: 0.80, 95% CI: 0.79–0.81), and CPG system (C-index: 0.78, 95% CI: 0.78–0.79) performed the best. The order of performance between the tools remained in analyses stratified by primary treatment and year of diagnosis. The predicted cumulative incidences were close to the observed ones, with some underestimation at 5 yr. It is a limitation that the study was conducted solely in a Swedish setting (ie, case mix). The MSKCC nomogram, CAPRA score, and CPG risk grouping system performed better in discriminating prostate cancer death than the D'Amico and D'Amico-derived systems (NICE, GUROC, EAU, AUA, and NCCN). Use of these tools may improve clinical decision making. There are numerous pretreatment risk classification tools that can aid treatment decision for prostate cancer. We systematically compared the prognostic performance of the most commonly used tools in a large cohort of Swedish men with prostate cancer. The Memorial Sloan Kettering Cancer Center nomogram, Cancer of the Prostate Risk Assessment score, and Cambridge Prognostic Groups performed best in predicting prostate cancer death. The use of these tools may improve treatment decisions. There are numerous pretreatment risk classification tools for prostate cancer. In a head-to-head comparison, the Memorial Sloan Kettering Cancer Center nomogram, Cancer of the Prostate Risk Assessment score, and Cambridge Prognostic Groups system performed best in predicting prostate cancer death. The use of these tools may improve clinical decision making. [ABSTRACT FROM AUTHOR]

Observational studies suggest that breast conserving surgery (BCS) and radiotherapy (RT) offers superior survival compared to mastectomy. The aim was to compare patient and tumour characteristics in women with invasive breast cancer ≤30 mm treated with either BCS or mastectomy, and to explore the underlying reason for choosing mastectomy. Women registered with breast cancer ≤30 mm and ≤4 positive axillary lymph nodes in the Swedish National Breast Cancer Register 2013–2016 were included. Logistic regression analyses were performed to assess the association of tumour and patient characteristics with receiving a mastectomy vs. BCS. Of 1860 breast cancers in 1825 women, 1346 were treated by BCS and 514 by mastectomy. Adjuvant RT was given to 1309 women (97.1 %) after BCS and 146 (27.6 %) after mastectomy. Variables associated with receiving a mastectomy vs. BCS included clinical detection (Odds Ratio (OR) 4.15 (95 % Confidence Interval (CI) 3.35–5.14)) and clinical stage (T2 vs. T1 (OR 3.68 (95 % CI 2.90–4.68)), N1 vs. N0 (OR 2.02 (95 % CI 1.38–2.96)). Women receiving mastectomy more often had oestrogen receptor negative, HER2 positive tumours of higher histological grade. The most common reported reason for mastectomy was large or multifocal tumours (53.5 %), followed by patient preference (34.5 %). Choice of surgery is strongly associated with key prognostic factors among women undergoing BCS with RT compared to mastectomy. Failure to control for all relevant confounders may bias results in outcome studies in favour of BCS. • Results in observational studies comparing breast conservation to mastectomy may be influenced by a selection bias. • Choice of surgery is strongly associated with key prognostic factors. • Failure to control for relevant confounders may bias results in outcome studies in favour of breast conserving surgery. [ABSTRACT FROM AUTHOR]

Abstract Background Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias. Objective To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study. Design, setting, and participants Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT). Outcome measures and statistical methods Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses. Results and limitations Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20–1.44). Conclusions Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment. Patient summary Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy. Take Home Message The increase in overall comorbidity following androgen androgen deprivation therapy for advanced prostate cancer was significantly higher for gonadotrophin gonadotrophin-releasing hormone agonists than for anti-androgen (AA) monotherapy. More consideration should be given to AA monotherapy as an alternative first-line therapy. [ABSTRACT FROM AUTHOR]

Background Active surveillance (AS) is commonly used for men with low-risk prostate cancer (PCa). When life expectancy becomes too short for curative treatment to be beneficial, a change from AS to watchful waiting (WW) follows. Little is known about this change since it is rarely documented in medical records. Objective To model transition from AS to WW and how this is affected by age and comorbidity among men with very low-risk PCa. Design, setting, and participants National population-based healthcare registers were used for analysis. Outcome measurements and statistical analysis Using data on PCa characteristics, age, and comorbidity, a state transition model was created to estimate the probability of changes between predefined treatments to estimate transition from AS to WW. Results and limitations Our estimates indicate that 48% of men with very low-risk PCa starting AS eventually changed to WW over a life course. This proportion increased with age at time of AS initiation. Within 10 yr from start of AS, 10% of men aged 55 yr and 50% of men aged 70 yr with no comorbidity at initiation changed to WW. Our prevalence simulation suggests that the number of men on WW who were previously on AS will eventually stabilise after 30 yr. A limitation is the limited information from clinical follow-up visits (eg, repeat biopsies). Conclusions We estimated that changes from AS to WW become common among men with very low-risk PCa who are elderly. This potential change to WW should be discussed with men starting on AS. Moreover, our estimates may help in planning health care resources allocated to men on AS, as the transition to WW is associated with lower demands on outpatient resources. Patient summary Changes from active surveillance to watchful waiting will become more common among men with very low-risk prostate cancer. These observations suggest that patients need to be informed about this potential change before they start on active surveillance. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the risk of thromboembolic disease (TED) after radiation therapy (RT) with curative intent for prostate cancer (PCa).Patients and Methods: We identified all men who received RT as curative treatment (n=9410) and grouped according to external beam RT (EBRT) or brachytherapy (BT). By comparing with an age- and county-matched comparison cohort of PCa-free men (n=46,826), we investigated risk of TED after RT using Cox proportional hazard regression models. The model was adjusted for tumor characteristics, demographics, comorbidities, PCa treatments, and known risk factors of TED, such as recent surgery and disease progression.Results: Between 2006 and 2013, 6232 men with PCa received EBRT, and 3178 underwent BT. A statistically significant association was found between EBRT and BT and risk of pulmonary embolism in the crude analysis. However, upon adjusting for known TED risk factors these associations disappeared. No significant associations were found between BT or EBRT and deep venous thrombosis.Conclusion: Curative RT for prostate cancer using contemporary methodologies was not associated with an increased risk of TED. [ABSTRACT FROM AUTHOR]

Side effects from the prolonged use of gonadotropin-releasing hormone (GnRH) agonists may lead to nonadherence to the treatment in men with advanced prostate cancer (PCa). We investigated the reasons contributing to nonadherence to GnRH agonists through interviews with men with PCa and focus groups with their health care professionals. The three stages of the study were validation of themes, interviews with men on GnRH agonists, and focus groups with oncology specialists and clinical nurse specialists. An experienced oncologist validated factors contributing to nonadherence identified from the literature. A total of 10 men with PCa were recruited from a large teaching hospital and were interviewed on a one-to-one basis using a topic guide. In stage three, two separate focus groups were held with oncology specialists and clinical nurse specialists treating men with PCa. The interviews and focus groups were audio recorded and transcribed verbatim. Initial codes identified from stage three were grouped into themes and thematically analyzed. Themes identified from the interviews and focus groups influencing adherence to treatment were side effects of treatment, patient belief system, benefits outweigh harm, quality of life over quantity of life, social support, and patient-clinician relationship. Although side effects such as hot flushes and loss of libido were sometimes overwhelming for many, these men felt that treatment benefits outweighed harm. Reasons leading to nonadherence can be multifactorial and unique to each patient. Employing different strategies by health care professionals may lead to the eventual acceptance of treatment, while also acknowledging their reasons for nonadherence. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Many men diagnosed with localised prostate cancer will eventually be treated with androgen deprivation therapy (ADT). ADT is associated with adverse effects and its timing is controversial. Data on patterns of use are scarce. We describe patterns of ADT use, defined as castration (medical and surgical) or antiandrogen monotherapy initiated after primary treatment, in a population-based cohort. Methods and materials: Data were extracted from the population-based Prostate Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and 2009 with clinical stage T1–2, N0–NX, M0–MX and prostate specific antigen (PSA)<50ng/ml without primary ADT were included. Outcomes in the period 2006 through 2010 were analysed using a period analysis approach. Results: The cumulative incidence of castration at 10years after diagnosis was 11.6% (95% confidence interval (CI), 11.0–12.2%). The corresponding proportion of antiandrogen monotherapy was 10.8% (95% CI, 10.2–11.4%). Castration was the dominant therapy among men on deferred treatment. The probability of receiving castration rather than antiandrogen monotherapy increased with age. Estimated median durations of castration ranged from 4years in the deferred treatment high-risk group to 17years in the prostatectomy low-risk group. The main limitation was the lack of information on progression to metastatic disease and PSA at the time for initiation of ADT. Conclusion: When initiated early after curative treatment, the duration of castration can be decades. The findings indicate that more accurate tools are necessary to guide which men should be selected for ADT as secondary treatment. [Copyright &y& Elsevier]

Abstract: Background: Studies enumerating the dynamics of physical and emotional symptoms following prostate cancer (PCa) treatment are needed to guide therapeutic strategy. Yet, overcoming patient selection forces is a formidable challenge for observational studies comparing treatment groups. Objective: To compare patterns of symptom burden and distress in men with localized PCa randomized to radical prostatectomy (RP) or watchful waiting (WW) and followed up longitudinally. Design, setting, and participants: The three largest, Swedish, randomization centers for the Scandinavian Prostate Cancer Group-4 trial conducted a longitudinal study to assess symptoms and distress from several psychological and physical domains by mailed questionnaire every 6 mo for 2 yr and then yearly through 8 yr of follow-up. Intervention: RP compared with WW. Outcome measurements and statistical analysis: A questionnaire was mailed at baseline and then repeatedly during follow-up with questions concerning physical and mental symptoms. Each analysis of quality of life was based on a dichotomization of the outcome (yes vs no) studied in a binomial response, generalized linear mixed model. Results and limitations: Of 347 randomized men, 272 completed at least five questionnaires during an 8-yr follow-up period. Almost all men reported that PCa negatively influenced daily activities and relationships. Health-related distress, worry, feeling low, and insomnia were consistently reported by approximately 30–40% in both groups. Men in the RP group consistently reported more leakage, impaired erection and libido, and fewer obstructive voiding symptoms. For men in the WW group, distress related to erectile symptoms increased gradually over time. Symptom burden and distress at baseline was predictive of long-term outlook. Conclusions: Cancer negatively influenced daily activities among almost all men in both treatment groups; health-related distress was common. Trade-offs exist between physiologic symptoms, highlighting the importance of tailored treatment decision-making. Men who are likely to experience profound long-term distress can be identified early in disease management. [Copyright &y& Elsevier]

Abstract: Aim: Many men diagnosed with localised prostate cancer will eventually be treated with androgen deprivation therapy (ADT). ADT is associated with adverse effects and its timing is controversial. Data on patterns of use are scarce. We describe patterns of ADT use, defined as castration (medical and surgical) or antiandrogen monotherapy initiated after primary treatment, in a population-based cohort. Methods and materials: Data were extracted from the population-based Prostate Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and 2009 with clinical stage T1–2, N0–NX, M0–MX and prostate specific antigen (PSA)<50ng/ml without primary ADT were included. Outcomes in the period 2006 through 2010 were analysed using a period analysis approach. Results: The cumulative incidence of castration at 10years after diagnosis was 11.6% (95% confidence interval (CI), 11.0–12.2%). The corresponding proportion of antiandrogen monotherapy was 10.8% (95% CI, 10.2–11.4%). Castration was the dominant therapy among men on deferred treatment. The probability of receiving castration rather than antiandrogen monotherapy increased with age. Estimated median durations of castration ranged from 4years in the deferred treatment high-risk group to 17years in the prostatectomy low-risk group. The main limitation was the lack of information on progression to metastatic disease and PSA at the time for initiation of ADT. Conclusion: When initiated early after curative treatment, the duration of castration can be decades. The findings indicate that more accurate tools are necessary to guide which men should be selected for ADT as secondary treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: Prostate cancer (PCa) and surgery are both associated with increased risk of thromboembolic diseases (TED). Objective: We assessed risk of TED among men undergoing different types of urologic surgery. Design, setting, and participants: Using the Prostate Cancer Database Sweden (PCBaSe) Sweden, we identified all men (n =45 065) undergoing pelvic lymph node dissection (PLND), radical prostatectomy (RP) with or without PLND, orchiectomy due to PCa, or a transurethral resection of the prostate (TURP). We identified a comparison cohort from the population. Outcome measurements and statistical analysis: Main outcomes were deep venous thrombosis (DVT) and pulmonary embolism (PE) as primary diagnoses in the National Patient Register or Cause of Death Register (2002–2010). We calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable Cox proportional hazards models. Results and limitations: All surgical procedures were associated with increased risk of TED; laparoscopic and open RP with a PLND were the most strongly associated with TED (HR for PE: 8.1 [95% CI, 2.9–23.0] and 7.8 [95% CI, 4.9–13], respectively). For surgery including a PLND, the risk increased during the second half of the first postoperative month. The HR for PE after TURP in men with PCa was 3.0 (95% CI, 1.8–5.1). Patients with a history of TED had a strongly increased risk of TED (HR for DVT: 4.5; 95% CI, 2.6–8.0). A limitation is lack of information on TED prophylaxis, but its use was standardized during the study period for RP and PLND. Other limitations are lack of information on extent of PLND and lifestyle factors. Conclusions: Surgeries for PCa, including TURP, are associated with hospitalization for TED. Patients with a history of TED and patients undergoing a PLND were at highest risk. The largest risk was observed from days 14 to 28 postoperatively. Thus, our results suggest that prophylactic measures may be beneficial during the first 4 wk in these patients. [Copyright &y& Elsevier]

Abstract: Background: To date, adverse events of prostate cancer (PCa) treatment have only been studied as a single event, and little is known about the risk of subsequent adverse events. Objective: We assessed the frequency of multiple events (fractures, stroke, heart disease [HD], and thromboembolic disease [TED]) following PCa diagnosis. Design, setting, and participants: PCBaSe Sweden is based on the National Prostate Cancer Register (NPCR) that covers >96% of incident PCa cases in Sweden. Measurements: We evaluated the number of events (fractures, stroke, HD, and TED) leading to hospitalisation recorded in the National Hospital Discharge Registry after PCa diagnosis and conducted multivariate age-adjusted Cox proportional hazards regression to estimate the risk of developing multiple events. Results and limitations: Between 1997 and 2007, 30 642 men received primary endocrine treatment, 26 432 curative treatment, and 19 526 surveillance: 75% had no event during follow-up, 17% had one event, and 9% had more than one event. The incidence of any event was 102 in 1000 person-years. Men who already had experienced an event, particularly HD, before or after the date of PCa diagnosis were more likely to have multiple events afterwards. For example, the hazard ratio of developing a third event for those with two or more events of HD before PCa diagnosis was 1.40 (95% confidence interval, 1.28–1.52) compared with those with no events of HD before PCa diagnosis. Events treated without hospitalisation were not included, so the number of adverse events is possibly underestimated. Conclusions: A third of PCa patients with an adverse event after treatment subsequently experienced another adverse event, but apart from history of HD or stroke before PCa diagnosis, no specific characteristics were found for these men. Thus PCa management needs to take into account the risk of adverse events in all PCa patients, especially those with a history of adverse events before PCa diagnosis. [Copyright &y& Elsevier]

Abstract: Background: Outcomes for many cancer forms are associated with socioeconomic status (SES).We investigated if SES was associated with management and mortality in men with high risk prostate cancer. Material and methods: A nation-wide population-based cohort in Prostate Cancer Data Base Sweden (PCBaSe), a merged database including data on incident prostate cancer identified in the National Prostate Cancer Register (NPCR) between 1997 and 2006. High risk PCa was defined as T3 tumour, and/or Gleason score 8–10 and/or PSA 20–50ng/mL. Use of bone scan, curative treatment, and mortality in relation to SES was assessed by logistic, Cox, and competing risk regression with hazard ratios (HR), sub-distributed HR and 95% confidence intervals (CI) adjusted for co-morbidity, age, calendar period and clinical subgroups. Results: Amongst 17,522 high risk prostate cancer patients, a bone scan was more often performed in higher white-collar than in blue-collar workers (OR 1.30; 95% CI 1.21–1.40). Amongst men without metastases, the likelihood of intention to treat was higher in higher white-collar workers (OR 1.43; 95% CI 1.28–1.57). In men who received curative treatment, the likelihood was higher to undergo radical prostatectomy for higher white-collar patients (OR 1.29; 95% CI 1.10–1.47). In men without metastases, not only overall mortality was lower amongst higher white-collar workers (HR, 0.76; 95% CI 0.60–0.97), but also prostate cancer-specific mortality (sHR 0.70; 95% CI, 0.49–0.99). Conclusions: We conclude that socioeconomic disparities in the management and mortality in men with high risk prostate cancer exist also within the setting of a National Health Care System aiming to provide care on equal terms to all residents. [Copyright &y& Elsevier]

Abstract: Aim: To explore whether the self-reported psychological distress among men with prostate cancer was to the extent that it required psychiatric treatment. Methods: PCBaSe Sweden, a merged database based on the National Prostate Cancer Register including 97% of all prostate cancers registered as well as age-matched controls. We calculated relative risks and 95% confidence intervals to compare risks of psychiatric treatment due to depression, anxiety, and post-traumatic stress disorder controlling for age and socio-economic factors. We used odds ratios to compare use or no use of antidepressants. Findings: In total 72,613 men with prostate cancer and 217,839 men without prostate cancer were included for analyses. Psychiatric hospitalisation due to depression, anxiety and post-traumatic stress disorder were significantly increased (RR 1.29, (95% CI 1.14–1.45), RR 1.42 (95% CI 1.12–1.80) and RR 1.61 (95% CI 1.16–2.24), respectively). However, hospitalisations due to anxiety were only increased in men with more advanced tumours RR 2.28 (95% CI 1.45–3.57). The use of antidepressants was increased for all men with prostate cancer RR 1.65 (95% CI 1.54–1.77) and treatment strategies RR 1.93 (95% CI 1.75–2.13). Interpretation: Men diagnosed with prostate cancer had increased risk of psychiatric treatment for depression, post-traumatic stress disorder and use of antidepressants regardless of risk group and treatment strategy compared to age-matched controls, whilst more advanced prostate cancer was associated with severe anxiety disorders. [ABSTRACT FROM AUTHOR]

Abstract: Background: There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment. Objective: To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent. Design, setting, and participants: We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis. Measurements: We followed up the patient cohort in the Cause of Death Register for ≤11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics. Results and limitations: The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25–32%) for Gleason score (GS) 2–6, 41% (95% CI, 38–44%) for GS 7, 52% (95% CI, 47–57%) for GS 8, and 64% (95% CI, 59–69%) for GS 9–10. Even for men aged >85 yr at diagnosis with GS 8–10, PCa was a major cause of death: 42% (95% CI, 37–47%). Men with locally advanced disease and a PSA<4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status. Conclusions: The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors. [Copyright &y& Elsevier]

Abstract: Background: Prostate-specific antigen (PSA) measurements are increasingly used to monitor men with localised prostate cancer (PCa), but there is little consensus about the method to use. Objective: To apply age-specific predictions of PSA level (developed in men without cancer) to one cohort of men with clinically identified PCa and one cohort of men with PSA-detected PCa. We hypothesise that among men with clinically identified cancer, the annual increase in PSA level would be steeper than in men with PSA-detected cancer. Design, setting, and participants: The Scandinavian Prostate Cancer Group 4 (SPCG-4) cohort consisted of 321 men assigned to the watchful waiting arm of the SPCG-4 trial. The UK cohort consisted of 320 men with PSA-detected PCa in the Prostate testing for cancer and Treatment (ProtecT) study who opted for monitoring. Multilevel models describing changes in PSA level were fitted to the two cohorts, and average PSA level at age 50, change in PSA level with age, and predicted PSA values were derived. Measurements: PSA level. Results and limitations: In the SPCG-4 cohort, mean PSA at age 50 was similar to the cancer-free cohort but with a steeper yearly increase in PSA level (16.4% vs 4.0%). In the UK cohort, mean PSA level was higher than that in the cancer-free cohort (due to a PSA biopsy threshold of 3.0ng/ml) but with a similar yearly increase in PSA level (4.1%). Predictions were less accurate for the SPCG-4 cohort (median difference between observed and predicted PSA level: −2.0ng/ml; interquartile range [IQR]: −7.6–0.7ng/ml) than for the UK cohort (median difference between observed and predicted PSA level: −0.8ng/ml; IQR: −2.1–0.1ng/ml). Conclusions: In PSA-detected men, yearly change in PSA was similar to that in cancer-free men, whereas in men with symptomatic PCa, the yearly change in PSA level was considerably higher. Our method needs further evaluation but has promise for refining active monitoring protocols. [Copyright &y& Elsevier]

Abstract: Background: The risk of suicide is increased among cancer patients including men with prostate cancer (PCa). However, whether this increased risk applies to men diagnosed subsequent to prostate-specific antigen (PSA) testing is not known. Objective: To assess the risk of suicide among men diagnosed with PCa subsequent to PSA testing. Design, setting, and participants: The Prostate Cancer Base Sweden (PCBaSe Sweden) database, the Swedish Cause of Death Register, and the Swedish census database were used. The PCBaSe Sweden is a merged database that includes data from the Swedish National Prostate Cancer Register (NPCR) for cases diagnosed between January 1, 1997, and December 31, 2006. The number of suicides registered for cases in the PCBaSe cohort was compared with the expected number of suicides in an age-matched general male Swedish population. Measurements: Standardised mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated for different categories of cases. Results and limitations: There were 128 suicides among the 77 439 PCa cases in the NPCR compared with an expected number of 85 (SMR: 1.5; 95% CI, 1.3–1.8). The risk of suicide was not increased for the 22 405 men with PSA-detected T1c tumours (SMR: 1.0; 95% CI, 0.6–1.5), whereas the 22 929 men with locally advanced nonmetastatic tumours (SMR: 2.2; 95% CI, 1.6–2.9) and the 8350 men with distant metastases (SMR: 2.1; 95% CI, 1.2–3.6) had statistically significant increased SMRs for suicide. Potential effects of comorbid medical and psychiatric conditions could not be investigated. Conclusions: No increased risk of committing suicide was observed among men with PCa diagnosed subsequent to PSA testing, whereas the risk was twice as high among men with locally advanced or metastatic disease, compared with an age-matched male population. [Copyright &y& Elsevier]

Abstract: We studied risk of second malignancies and causes of death in 1829 cases of adenocarcinoma and 3055 cases of carcinoid tumours in the small bowel reported to the Swedish Cancer Registry from 1960 through to 2000. Data on causes of death were analysed as from 1966 whereas data on second tumours was available during the whole registry-period. Follow-up was available until 2001. Standard mortality ratio (SMR) and standard incidence ratio (SIR) were calculated. Female patients with adenocarcinoma had increased risk of acquiring cancer in the female genital organs (SIR 3.2; 95% confidence intervals (CI) 1.9–5.0) and breasts (SIR 2.7; 95% CI 1.1–5.4). Both sexes combined had increased risk of second tumours in the gastrointestinal tract (SIR 1.5; 95% CI 1.1–2.1) and skin (SIR 4.6; 95% CI 1.2–12). Men with carcinoid tumour had increased risk of prostate cancer (SIR 2.8; 95% CI 1.6–4.6). Increased risk was seen for both sexes with carcinoid for malignant melanoma (SIR 6.3; 95% CI 2.7–12), malignant skin tumours (SIR 3.6; 95% CI 1.7–6.7) and malignancies of endocrine organs (SIR 2.3 95% CI 1.3–3.8). Patients with adenocarcinoma had increased risk of dying from malignant diseases other than the primary cancer (SMR 9.5; 95% CI 8.6–10) and gastrointestinal disease (SMR 2.6 95% CI 1.6–4.2). The cohort with carcinoid had higher than expected risk of dying from malignant disease (SMR 4.3; 95% CI 4.0–4.6), gastrointestinal disease (SMR 2.8; 95% CI 2.1–3.6) and cardiovascular disease (SMR 1.1; 95% CI 1.0–1.3). The increased risk of second malignant tumours is an indication of common aetiology, or possibly, a general vulnerability to malignant disease for these patients. A detailed analysis of causes of death in a population-based cohort of small intestinal malignancies has not been presented before in the literature. [Copyright &y& Elsevier]

Invasive Breast Cancer Over Four Decades Reveals Persisting Poor Metastatic Outcomes In Treatment Resistant Subgroup - The "ATRESS" Phenomenon However, the metastasis-free interval shortened, with the proportion of women developing metastasis <=5 years increasing from 73.9% to 83.0%. Advances in treatment have decreased the risk of metastasis and improved survival in women with invasive breast cancer over the last 40 years. [Extracted from the article]

Highlights • Essential thrombocythemia (ET) has a risk of malignant transformation. • We determined transformation to acute myelogenous leukemia (AML). • Standardized incidence ratio of AML was high in ET patients on hydroxycarbamide. • No cases of AML occurred in ET patients treated with anagrelide. • Rates for non-AML cancers were similar in the two groups. Abstract EXELS, a post-marketing observational study, is the largest prospective study of high-risk essential thrombocythemia (ET) patients, with an observation time of 5 years. EXELS found higher event rates of acute leukemia transformation in patients treated with hydroxycarbamide (HC). In the current analysis, we report age-adjusted rates of malignant transformation from 3460 EXELS patients exposed to HC, anagrelide (ANA), or both. At registration, 481 patients had ANA treatment without HC exposure, 2305 had HC without ANA exposure, and 674 had been exposed to both. Standard incidence ratios (SIRs) were calculated using data from the Cancer Incidence in Five Continents database to account for differences in age-, gender-, and country-specific background rates. SIRs for acute myelogenous leukemia (AML) were high in ET patients. SIRs for AML were high in HC-treated patients, but AML was rare in ANA-treated patients; no cases of AML were found in patients only treated with ANA. No statistically significant difference was seen between SIRs for ANA and HC treatment for AML or skin cancer. SIRs for other cancers were similar in the HC and ANA groups and close to 1, indicating little difference in risk. Although statistically inconclusive, this study strengthens concerns regarding possible leukemogenic risk with HC treatment. (NCT00202644) [ABSTRACT FROM AUTHOR]

Background Symptoms of terminal cancer have previously been reported as undertreated. The aim of this study was to assess the use of palliative medications before death from prostate cancer. Methods This Swedish register study included men who died from 2009 to 2012 with prostate cancer as the underlying cause of death. We assessed the proportion who collected a prescription of androgen deprivation therapy, non-steroidal anti-inflammatory drugs, paracetamol, opioids, glucocorticoids, antidepressants, anxiolytics and sedative-hypnotics and the differences in treatment related to age, time since diagnosis, educational level, close relatives and comorbidities. Data were collected from 3 years before death from prostate cancer. Results We included 8326 men. The proportion who received opioids increased from 30% to 72% during the last year of life, and 67% received a strong opioid at the time of death. Antidepressants increased from 13% to 22%, anxiolytics from 9% to 27% and sedative-hypnotics from 21% to 33%. Men without close relatives and older men had lower probability to receive opioids (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.47–0.66 for >85 years versus <70 years) and (OR 0.78, 95% CI: 0.66–0.92 for unmarried without children versus married with children). Conclusion Our results represent robust epidemiological data from Sweden for comparison of palliative care quality between countries. The findings indicate that men without close relatives and older men are disadvantaged with respect to the treatment of cancer pain and need closer attention from health care providers and highlight the importance to identify psychological distress in terminal prostate cancer. [ABSTRACT FROM AUTHOR]

Background In observational studies, men with prostate cancer treated with gonadotropin-releasing hormone (GnRH) agonists had a higher risk of cardiovascular disease (CVD) compared to men who had undergone orchiectomy. However, selection bias may have influenced the difference in risk. Objective To investigate the association of type of androgen deprivation therapy (ADT) with risk of CVD while minimising selection bias. Design, setting, and participants Semi-ecologic study of 6556 men who received GnRH agonists and 3330 men who underwent orchiectomy as primary treatment during 1992–1999 in the Prostate Cancer Database Sweden 3.0. Outcome measurements and statistical analysis We measured the proportion of men who received GnRH agonists as primary treatment in 580 experimental units defined by healthcare provider, diagnostic time period, and age at diagnosis. Incident or fatal CVD events in units with high and units with low use of GnRH agonists were compared. Net and crude probabilities were also analysed. Results and limitations The risk of CVD was similar between units with the highest and units with the lowest proportion of GnRH agonist use (relative risk 1.01, 95% confidence interval [CI] 0.93–1.11). Accordingly, there was no difference in the net probability of CVD after GnRH agonist compared to orchiectomy (hazard ratio 1.02, 95% CI 0.96–1.09). The 10-yr crude probability of CVD was 0.56 (95% CI 0.55–0.57) for men on GnRH agonists and 0.52 (95% CI 0.50–0.54) for men treated with orchiectomy. The main limitation was the nonrandom allocation to treatment, with younger men with lower comorbidity and less advanced cancer more likely to receive GnRH agonists. Conclusion Our data do not support previous observations that GnRH agonists increase the risk of CVD in comparison to orchiectomy. Patient summary We found a similar risk of cardiovascular disease between medical and surgical treatment as androgen deprivation therapy for prostate cancer. [ABSTRACT FROM AUTHOR]

SIMULATE is the first international, multicentre, randomised controlled trial that demonstrates that surgical simulation improves the performance of residents in advanced-level procedures and significantly reduces overall surgical complications. Trainees who underwent simulation training for ureteroscopy, selected as an index procedure, scored higher overall on the Objective Structured Assessment of Technical Skill scale and encountered fewer ureteric injuries. It is hypothesised that simulation enhances progression along the initial phase of the surgical learning curve. To evaluate whether residents undergoing additional simulation, compared to conventional training, are able to achieve proficiency sooner with better patient outcomes. This international, multicentre, randomised controlled trial recruited 94 urology residents with experience of zero to ten procedures and no prior exposure to simulation in ureterorenoscopy, selected as an index procedure. Participants were randomised to simulation or conventional operating room training, as is the current standard globally, and followed for 25 procedures or over 18 mo. The number of procedures required to achieve proficiency, defined as achieving a score of ≥28 on the Objective Structured Assessment of Technical Skill (OSATS) scale over three consecutive operations, was measured. Surgical complications were evaluated as a key secondary outcome. This trial is registered at www.isrctn.com as ISCRTN 12260261. A total of 1140 cases were performed by 65 participants, with proficiency achieved by 21 simulation and 18 conventional participants over a median of eight and nine procedures, respectively (hazard ratio [HR] 1.41, 95% confidence interval [CI] 0.72–2.75). More participants reached proficiency in the simulation arm in flexible ureterorenoscopy, requiring a lower number of procedures (HR 0.89, 95% CI 0.39–2.02). Significant differences were observed in overall comparison of OSATS scores between the groups (mean difference 1.42, 95% CI 0.91–1.92; p < 0.001), with fewer total complications (15 vs 37; p = 0.003) and ureteric injuries (3 vs 9; p < 0.001) in the simulation group. Although the number of procedures required to reach proficiency was similar, simulation-based training led to higher overall proficiency scores than for conventional training. Fewer procedures were required to achieve proficiency in the complex form of the index procedure, with fewer serious complications overall. This study investigated the effect of simulation training in junior surgeons and found that it may improve performance in real operating settings and reduce surgical complications for complex procedures. [ABSTRACT FROM AUTHOR]

Abstract: Background: Genetic factors seem to be of greater importance in prostate cancer than in other forms of cancer. Studies have suggested familial concordance in survival, but the extent to which that is due to tumor characteristics is not known. Objective: We hypothesized that a brother of an index case with prostate cancer is at particularly increased risk of prostate cancer with the same tumor differentiation as the index case. Design, setting and participants: We identified 21 930 brothers of index cases with prostate cancer in the Prostate Cancer Data Base Sweden and followed them up for incidence of prostate cancer. Outcome measurements and statistical analysis: The relative risk of Gleason score–specific prostate cancer in the cohort of brothers was estimated by using the standardized incidence ratio (SIR) stratified by Gleason score of the index case. We estimated 95% confidence intervals (CIs) assuming a Poisson distribution. Results and limitations: Among brothers of index cases with Gleason score 8–10 cancer, the SIR was 2.53 (95% CI, 1.97–3.21) for a Gleason score 2–6 cancer and 4.00 (95% CI, 2.63–5.82) for a Gleason score 8–10 cancer. SIR for Gleason score 2–6 cancer among brothers decreased with time since the date of the index cases’ diagnoses, whereas the risk of Gleason 8–10 cancer increased over time for brothers of index cases with Gleason 8–10 cancer (p for trend = 0.009). Conclusions: Brothers of men with high-grade prostate cancer are at particularly increased risk of high-grade prostate cancer. Likewise, there is a concordance of less malignant prostate cancers within families. These findings may have direct clinical relevance for counseling men with a family history of prostate cancer. [Copyright &y& Elsevier]

Summary: Background: Cancer is associated with an increased risk of thromboembolic diseases, but data on the association between prostate cancer and thromboembolic diseases are scarce. We investigated the risk of thromboembolic disease in men with prostate cancer who were receiving endocrine treatment, curative treatment, or surveillance. Methods: We analysed data from PCBaSe Sweden, a database based on the National Prostate Cancer Register, which covers over 96% of prostate cancer cases in Sweden. Standardised incidence ratios (SIR) of deep-venous thrombosis (DVT), pulmonary embolism, and arterial embolism were calculated by comparing observed and expected (using the total Swedish male population) occurrences of thromboembolic disease, taking into account age, calendar-time, number of thromboembolic diseases, and time since previous thromboembolic disease. Findings: Between Jan 1, 1997, and Dec 31, 2007, 30 642 men received primary endocrine therapy, 26 432 curative treatment, and 19 526 surveillance. 1881 developed a thromboembolic disease. For men on endocrine therapy, risks for DVT (SIR 2·48, 95% CI 2·25–2·73) and pulmonary embolism (1·95, 1·81–2·15) were increased, although this was not the case for arterial embolism (1·00, 0·82–1·20). Similar patterns were seen for men who received curative treatment (DVT: 1·73, 1·47–2·01; pulmonary embolism: 2·03, 1·79–2·30; arterial embolism: 0·95, 0·69–1·27) and men who were on surveillance (DVT: 1·27, 1·08–1·47; pulmonary embolism: 1·57, 1·38–1·78; arterial embolism: 1·08, 0·87–1·33). Increased risks for thromboembolic disease were maintained when patients were stratified by age and tumour stage. Interpretation: All men with prostate cancer were at higher risk of thromboembolic diseases, with the highest risk for those on endocrine therapy. Our results indicate that prostate cancer itself, prostate cancer treatments, and selection mechanisms all contribute to increased risk of thromboembolic disease. Thromboembolic disease should be a concern when managing patients with prostate cancer. Funding: Swedish Research Council, Stockholm Cancer Society, and Cancer Research UK. [Copyright &y& Elsevier]

Abstract: Meta-analyses have shown an excess of vascular deaths in women with breast cancer given radiotherapy (RT). In women with breast cancer, RT to the supraclavicular lymph nodes gives a substantial radiation dose to the proximal carotid artery. RT is known to increase the risk of carotid stenosis and ischaemic stroke in head and neck cancer. A study base of 25,171 women with breast cancer was defined. A linkage between the study base and the Hospital Discharge Register yielded 1766 women who were diagnosed with a stroke after a breast cancer. The observed number of strokes was compared with the expected number in the background population. The Relative Risk (RR) of stroke in the study group with breast cancer was 1.12 (95% Confidence Interval (CI)=1.07–1.17). The increased risk was confined to the subtype cerebral infarction, RR=1.12 (95% CI=1.05–1.19). A statistically significant increase in the risk of stroke was seen among women with a history of breast cancer. Whether this risk is associated with the breast cancer disease per se or related to any treatment requires further study. [Copyright &y& Elsevier]

Background Current guidelines recommend androgen deprivation therapy only for men with very high-risk prostate cancer (PCa), but there is little evidence to support this stance. Objective To investigate the association between radical local treatment and mortality in men with very high-risk PCa. Design, setting, and participants Semiecologic study of men aged <80 yr within the Prostate Cancer data Base Sweden, diagnosed in 1998–2012 with very high-risk PCa (local clinical stage T4 and/or prostate-specific antigen [PSA] level 50–200 ng/ml, any N, and M0). Men with locally advanced PCa (local clinical stage T3 and PSA level <50 ng/ml, any N, and M0) were used as positive controls. Intervention Proportion of men who received prostatectomy or full-dose radiotherapy in 640 experimental units defined by county, diagnostic period, and age at diagnosis. Outcome measurements and statistical analysis PCa and all-cause mortality rate ratios (MRRs). Results and limitations Both PCa and all-cause mortality were half as high in units in the highest tertile of exposure to radical local treatment compared with units in the lowest tertile (PCa MRR: 0.51; 95% confidence interval [CI], 0.28–0.95; and all-cause MRR: 0.56; 95% CI, 0.33–0.92). The results observed for locally advanced PCa for highest versus lowest tertile of exposure were in agreement with results from randomized trials (PCa MRR: 0.75; 95% CI, 0.60–0.94; and all-cause MRR: 0.85; 95% CI, 0.72–1.00). Although the semiecologic design minimized selection bias on an individual level, the effect of high therapeutic activity could not be separated from that of high diagnostic activity. Conclusions The substantially lower mortality in units with the highest exposure to radical local treatment suggests that radical treatment decreases mortality even in men with very high-risk PCa for whom such treatment has been considered ineffective. Patient summary Men with very high-risk prostate cancer diagnosed and treated in units with the highest exposure to surgery or radiotherapy had a substantially lower mortality. [ABSTRACT FROM AUTHOR]