Radical Prostatectomy or Watchful Waiting in Prostate Cancer - 29-Year Follow-up.

BACKGROUND: Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term follow-up is sparse. METHODS: We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model. RESULTS: By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer). CONCLUSIONS: Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer. (Funded by the Swedish Cancer Society and others.).

Prostate cancer mortality and metastasis under different biopsy frequencies in North American active surveillance cohorts.

BACKGROUND: Active surveillance (AS) is an accepted means of managing low-risk prostate cancer. Because of the rarity of downstream events, data from existing AS cohorts cannot yet address how differences in surveillance intensity affect metastasis and mortality. This study projected the comparative benefits of different AS schedules in men diagnosed with prostate cancer who had Gleason score (GS) ≤6 disease and risk profiles similar to those in North American AS cohorts. METHODS: Times of GS upgrading were simulated based on AS data from the University of Toronto, Johns Hopkins University, the University of California at San Francisco, and the Canary Pass Active Surveillance Cohort. Times to metastasis and prostate cancer death, informed by models from the Scandinavian Prostate Cancer Group 4 trial, were projected under biopsy surveillance schedules ranging from watchful waiting to annual biopsies. Outcomes included the risk of metastasis, the risk of death, remaining life-years (LYs), and quality-adjusted LYs. RESULTS: Compared with watchful waiting, AS biopsies reduced the risk of prostate cancer metastasis and prostate cancer death at 20 years by 1.4% to 3.3% and 1.0% to 2.4%, respectively; and 5-year biopsies reduced the risk of metastasis and prostate cancer death by 1.0% to 2.4% and 0.6% to 1.6%, respectively. There was little difference between annual and 5-year biopsy schedules in terms of LYs (range of differences, 0.04-0.16 LYs) and quality-adjusted LYs (range of differences, -0.02 to 0.09 quality-adjusted LYs). CONCLUSIONS: Among men diagnosed with GS ≤6 prostate cancer, obtaining a biopsy every 3 or 4 years appears to be an acceptable alternative to more frequent biopsies. Reducing surveillance intensity for those who have a low risk of progression reduces the number of biopsies while preserving the benefit of more frequent schedules.

Changes in lifestyle among prostate cancer survivors: A nationwide population-based study.

OBJECTIVE: Long-term information on lifestyle changes among prostate survivors is lacking. In this nationwide, population-based study we investigated the prevalence of lifestyle changes, factors associated with lifestyle changes and associations between lifestyle changes and general quality of life. METHODS: All men registered in the National Prostate Cancer Register of Sweden diagnosed in 2008 with low-risk prostate cancer at age 70 years or younger were sent a questionnaire. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals for factors potentially associated with lifestyle change. RESULTS: Out of 1288, 1720 men (75%) were responded. A total of 279 (22%) reported a positive lifestyle change regarding diet or exercise. Poor functional outcomes after treatment was associated with exercising less (OR 1.6, 95% CI 1.2-2.1) and less interest in social activities and relationships (OR 1.8, 95% CI 1.5-2.1). Men who exercised more (OR 7.9, 95% CI 4.4-14) and men who had an increased interest in relationships and social activities (OR 5.2, 95% CI 2.1-13) reported higher general quality of life. CONCLUSIONS: A considerable proportion of men reported making positive lifestyle changes after the prostate cancer diagnosis. The time after diagnosis may be a teachable moment that facilitates lifestyle interventions. Poor functional outcomes after treatment may reduce the willingness to engage in positive lifestyle change, which need be considered when supporting men after treatment. Men who made a positive lifestyle change, regardless of whether it was exercise or regarding relationships and social activities more often reported a high level of general quality of life.

Cocreated internet-based stepped care for individuals with cancer and concurrent symptoms of anxiety and depression: Results from the U-CARE AdultCan randomized controlled trial.

OBJECTIVE: The aim was to evaluate the effects of cocreated internet-based stepped care (iCAN-DO) on anxiety, depression, posttraumatic stress, and health-related quality of life (HRQoL) in individuals with cancer and self-reported anxiety and/or depression symptoms, compared with standard care. METHODS: Clinically recruited individuals with breast, colorectal, or prostate cancer underwent online screening with the Hospital Anxiety and Depression Scale (HADS). Those with anxiety and/or depression symptoms (>7 on any of the HADS subscales) were randomized to iCAN-DO or standard care. iCAN-DO comprised psychoeducation and self-care strategies (step 1) and internet-based cognitive behavioral therapy (iCBT, step 2). Data were collected before randomization and at 1, 4, 7, and 10 months and analyzed with intention-to-treat regression analysis and randomization tests. RESULTS: Online screening identified 245 (27%) of 909 individuals who reported anxiety and/or depression symptoms. They were randomized to iCAN-DO (n = 124) or standard care (n = 121). Of them 49% completed the 10-month assessment, and in the iCAN-DO group 85% accessed step 1 and 13% underwent iCBT. iCAN-DO decreased the levels of symptoms of depression (-0.54, 95% confidence interval: -1.08 to -0.01, P < .05) and the proportion of individuals with symptoms of depression (P < .01) at 10 months, compared with standard care, according to HADS. There were no significant effects on anxiety, posttraumatic stress, or HRQoL. CONCLUSION: Internet-based stepped care improves symptoms of depression in individuals with cancer. Further studies are needed to gain knowledge on how to optimize and implement internet-based support in oncology care.

Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study.

OBJECTIVE: To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision-making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG-4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s. PATIENTS AND METHODS: A propensity score-matched analysis of prostate cancer mortality and all-cause mortality in the SPCG-4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998-2006 was conducted. Cumulative incidence of prostate cancer mortality and all-cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR. RESULTS: Matched men in the NPCR treated in 2005-2006 had half the risk of prostate cancer mortality compared to men in the SPCG-4 (HR 0.46, 95% CI 0.19-1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36-1.47). CONCLUSIONS: Outcomes after RP for men in the SPCG-4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG-4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for.

U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.

BACKGROUND: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population. MATERIAL AND METHODS: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data. RESULTS: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort. CONCLUSIONS: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

Radical prostatectomy or watchful waiting in early prostate cancer.

BACKGROUND: Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. METHODS: Between 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy. RESULTS: During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04). CONCLUSIONS: Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.).

Prostate-specific antigen patterns in US and European populations: comparison of six diverse cohorts.

OBJECTIVE: To determine whether there are differences in prostate-specific antigen (PSA) levels at diagnosis or changes in PSA levels between US and European populations of men with and without prostate cancer (PCa). SUBJECTS AND METHODS: We analysed repeated measures of PSA from six clinically and geographically diverse cohorts of men: two cohorts with PSA-detected PCa, two cohorts with clinically detected PCa and two cohorts without PCa. Using multilevel models, average PSA at diagnosis and PSA change over time were compared among study populations. RESULTS: The annual percentage PSA change of 4-5% was similar between men without cancer and men with PSA-detected cancer. PSA at diagnosis was 1.7 ng/mL lower in a US cohort of men with PSA-detected PCa (95% confidence interval 1.3-2.0 ng/mL), compared with a UK cohort of men with PSA-detected PCa, but there was no evidence of a different rate of PSA change between these populations. CONCLUSION: We found that PSA changes over time are similar in UK and US men diagnosed through PSA testing and even in men without PCa. Further development of PSA models to monitor men on active surveillance should be undertaken in order to take advantage of these similarities. We found no evidence that guidelines for using PSA to monitor men cannot be passed between US and European studies.

Radical prostatectomy versus watchful waiting in early prostate cancer.

BACKGROUND: In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results. METHODS: From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model. RESULTS: During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4). CONCLUSIONS: Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment. (Funded by the Swedish Cancer Society and the National Institutes of Health.).

Nationwide population based study of infections after transrectal ultrasound guided prostate biopsy.

PURPOSE: Transrectal ultrasound guided biopsy is the gold standard for detecting prostate cancer but international reports suggest that increasing risks are associated with the procedure. We estimated incidence and risk factors for infection after prostate biopsy as well as 90-day mortality using a nationwide Swedish sample. MATERIAL AND METHODS: We performed a population based study of 51,321 men from PCBaSe between 2006 and 2011. Primary outcome measures were dispensed prescriptions of antibiotics for urinary tract infection and hospitalization with a discharge diagnosis of urinary tract infection. Multivariable logistic regression was used to examine risk factors for infection in men who underwent prostate biopsy. RESULTS: During the 6 months before biopsy the background incidence of urinary tract infection was approximately 2%. Within 30 days after biopsy 6% of the men had a dispensed prescription for urinary tract antibiotics and 1% were hospitalized with infection. The strongest risk factors for an antibiotic prescription were prior infection (OR 1.59, 95% CI 1.45-1.73), high Charlson comorbidity index (OR 1.25, 95% CI 1.11-1.41) and diabetes (OR 1.32, 95% CI 1.17-1.49). Risk of an antibiotic prescription after biopsy decreased from 2006 to 2011 (OR 0.79, 95% CI 0.70-0.90) but the risk of hospital admission increased (OR 2.14, 95% CI 1.58-2.94). No significant increase was observed in 90-day mortality. CONCLUSIONS: Severe infections with hospitalization after prostate biopsy are increasing in Sweden. The risk of post-biopsy infection is highest in men with a history of urinary tract infection and those with significant comorbidities.

Rehospitalization after radical prostatectomy in a nationwide, population based study.

PURPOSE: We investigated hospital readmission frequency during the 90 days after radical prostatectomy and assessed the readmission risk associated with potentially related variables. MATERIALS AND METHODS: Using the population based, nationwide PCBaSe (Prostate Cancer data Base Sweden) we identified men diagnosed with incident prostate cancer between 2000 and 2011 who underwent radical prostatectomy as primary treatment. We used logistic regression analysis to examine the association of the risk of 90-day postoperative readmission with surgical method, calendar period, tumor risk category, hospital case load and patient characteristics. RESULTS: During 90 postoperative days 2,317 of the 24,122 men (10%) identified were nonelectively readmitted, specifically 10% after retropubic, 9% after robot-assisted and 11% after laparoscopic radical prostatectomy. The range in readmission frequency among hospitals was 0% to 35%. Higher readmission risk was associated with the early calendar period (2009 to 2011 vs 2000 to 2002 OR 0.71, 95% CI 0.61-0.83), greater age (70 or greater vs less than 60 years OR 1.17, 95% CI 1.00-1.36), higher risk category (high vs low OR 1.78, 95% CI 1.57-2.03), high comorbidity (Charlson comorbidity index 3 or greater vs 0 OR 1.77, 95% CI 1.29-2.44) and low hospital surgical volume (150 or greater vs fewer than 30 radical prostatectomies per year OR 0.70, 95% CI 0.60-0.81). CONCLUSIONS: Readmission rates after different radical prostatectomy methods were similar, ranging from 9% to 11%, with wide variation among hospitals. Readmission rates can be used as an indicator of perioperative care quality but potential confounders must be adjusted to avoid bias.

Dietary patterns and prostate cancer risk: report from the population based ULSAM cohort study of Swedish men.

Dietary pattern analyses have increased the possibilities to detect associations between diet and disease. However, studies on dietary pattern and prostate cancer are scarce. Food intake data in the Uppsala Longitudinal Study of Adult Men cohort was determined by 7-day food records. Adherence to a modified Mediterranean Diet Score (mMDS) and a low carbohydrate-high protein (LCHP) score were grouped as low, medium, or high in the whole study population (n = 1,044) and in those identified as adequate reporters of energy intake (n = 566), respectively. Prostate cancer risk was analyzed with Cox proportional hazard regression (median follow-up 13 years) and competing risk of death was considered. There were no associations between dietary patterns and prostate cancer (n = 133) in the whole study population. Among adequate reporters the mMDS was not associated with prostate cancer (n = 72). The LCHP score was inversely related to prostate cancer in adequate reporters, adjusted hazard ratios; 0.55 (0.32-0.96) for medium and 0.47 (0.21-1.04) for high compared to low adherent participants (P-for-trend 0.04). Risk relations were not attributable to competing risk of death. In this study, a LCHP diet was associated with lower prostate cancer incidence. Relations emerged in adequate reporters, underscoring the importance of high-quality dietary data.

Triggers for transition from active surveillance to radical treatment of prostate cancer 2008-2020 - a case-control study.

OBJECTIVE: To examine associations between objective signs of progression (triggers) and transition from active surveillance (AS) to radical treatment for prostate cancer (PC). PATIENTS AND METHODS: This case-control study included men with low- or favourable intermediate-risk PC in the region of Halland, with data from The National Prostate Cancer Register (NPCR), Sweden, starting AS between 2008 and 2020. Cases were men who transitioned to radical treatment. For each case, 10 controls who remained in AS were selected without further matching. Triggers for transition to treatment were histopathological progression, magnetic resonance imaging (MRI) progression and increases in prostate-specific antigen (PSA) levels. We compared the probabilities for triggers between cases and controls, in 2008-2014 and 2015-2020, using logistic regression. RESULTS: Amongst 846 men, we identified 98 cases in 2008-2014 and 172 cases in 2015-2020. Histopathological progression was associated with transition, most strongly in the later period (2008-2014: odds ratios [OR] 6.88, 95% confidence interval [CI] 3.69-12.80; and 2015-2020: OR 75.29, 95% CI 39.60-143.17). MRI progression was associated with transition in 2015-2020 (OR 6.38, 95% CI 2.70-15.06), whereas an increase in PSA was weakly associated with transition in the early period. The absence of triggers was associated with no transition (2008-2014: OR 0.24, 95% CI 0.15-0.40, and 2015-2020: OR 0.09, 95% CI 0.06-0.14). The probability of no trigger was 27% in cases 2015-2020. CONCLUSION: The increase in association between histopathological trigger and transition to treatment indicates increased quality of AS. Still, amongst men treated from 2015 to 2020, 27% transitioned without any trigger.

Intraoperative cavernous nerve stimulation and Laser-Doppler flowmetry during radical prostatectomy.

INTRODUCTION: Erectile dysfunction is a common side effect following radical prostatectomy mainly due to damage of the pelvic autonomic nerve fibers (cavernous nerves). Intraoperative electrical stimulation of the cavernous nerves while measuring changes in penile girth has previously been shown to provide the surgeon with feedback of nerve integrity. AIM: To test the feasibility of recording changes in glans penis blood flow by Laser Doppler flowmetry from cavernous nerve stimulation. METHODS: Fifteen patients with localized prostate cancer undergoing radical prostatectomy had electrical stimulation of the proximal and distal parts of the neurovascular bundles after prostate removal. The stimulation consisted of 30-40 seconds biphasic constant current (10-30 mA) with 0.5 millisecond pulse duration. MAIN OUTCOME MEASURES: Stimulus induced changes in penile blood flow was recorded from a Laser Doppler probe attached to the glans penis. Changes in penile girth were simultaneously recorded from a mercury-in rubber strain gauge. Erectile function was evaluated three months after surgery. RESULTS: Ten patients had stimulus induced increase in Laser Doppler flow unilaterally (N=7) or bilaterally (N=3). Out of 10 patients, 6 reported some preserved erectile function postoperatively at 3 months follow-up (indicating 6 true and 4 false positives). Three patients had no Doppler response from stimulation and had no postoperative erectile function postoperatively (indicating three true negatives). Two patients were excluded from the study due to bad signal quality in the Laser Doppler signal. In the majority of patients, stimulation produced increase in penile girth sensed by the strain gauge. CONCLUSION: This preliminary report provides evidence that Laser Doppler Flowmetry is able to detect increased penile blood flow from intraoperative electrical stimulation of the neurovascular bundles. However, further improvement in the recording technique is required. Laser Doppler Flowmetry may also be feasible to confirm autonomic nerve sparing in women undergoing pelvic surgery.

Variations in the Uptake of Active Surveillance for Prostate Cancer and Its Impact on Outcomes.

Background: Regional differences in active surveillance (AS) uptake for prostate cancer (PC) illustrate an inequality in treatment strategies. Objective: To examine the association between regional differences in AS uptake and transition to radical treatment, start of androgen deprivation therapy (ADT), watchful waiting, or death. Design setting and participants: A Swedish population-based cohort study was conducted including men in the National Prostate Cancer Register in Sweden with low-risk or favorable intermediate-risk PC, starting AS from January 1, 2007 and continuing till December 31, 2019. Intervention: Regional tradition of low, intermediate, or high proportions of immediate radical treatment. Outcomes measurements and statistical analysis: Probabilities of transition from AS to radical treatment, start of ADT, watchful waiting, or death from other causes were assessed. Results and limitations: We included 13 679 men. The median age was 66 yr, median PSA 5.1 ng/ml, and median follow-up 5.7 yr. Men from regions with a high AS uptake had a lower probability of transition to radical treatment (36%) than men from regions with a low AS uptake (40%; absolute difference 4.1%; 95% confidence interval [CI] 1.0-7.2), but not a higher probability of AS failure defined as the start of ADT (absolute difference 0.4%; 95% CI -0.7 to 1.4). There were no statistically significant differences in the probability of transition to watchful waiting or death from other causes. Limitations include uncertainty in the estimation of remaining lifetime and transition to watchful waiting. Conclusions: A regional tradition of a high AS uptake is associated with a lower probability of transition to radical treatment, but not with AS failure. A low AS uptake suggests overtreatment. Patient summary: There are considerable regional differences in active surveillance (AS) uptake for prostate cancer. This study compared the outcomes of AS in different regions and found no association between AS uptake and failure of AS; it suggests that a low AS uptake indicates overtreatment.

Long-term Risks of Depression and Suicide Among Men with Prostate Cancer: A National Cohort Study.

BACKGROUND: A diagnosis of prostate cancer (PC) may cause psychosocial distress that worsens quality of life; however, long-term mental health outcomes are unclear. OBJECTIVE: To determine the long-term risks of major depression and death by suicide in a large population-based cohort. DESIGN, SETTING, AND PARTICIPANTS: This was a national cohort study of 180 189 men diagnosed with PC during 1998-2017 and 1 801 890 age-matched, population-based, control men in Sweden. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Major depression and death by suicide were ascertained from nationwide outpatient, inpatient, and death records up to 2018. Cox regression was used to compute hazard ratios (HRs) adjusted for sociodemographic factors and comorbidities. Subanalyses assessed differences by PC treatment during 2005-2017. RESULTS AND LIMITATIONS: Men diagnosed with high-risk PC had higher relative rates of major depression (adjusted HR [aHR] 1.82, 95% confidence interval [CI] 1.75-1.89) and death by suicide (aHR 2.43, 95% CI 2.01-2.95). These associations persisted for ≥10 yr after PC diagnosis. The relative increase in major depression was lower among those treated with radiation (aHR 1.44, 95% CI 1.31-1.57) or surgery (aHR 1.60, 95% CI 1.31-1.95) in comparison to androgen deprivation therapy (ADT) alone (aHR 2.02, 95% CI 1.89-2.16), whereas the relative rate of suicide death was higher only among those treated solely with ADT (aHR 2.83, 95% CI 1.80-4.43). By contrast, men with low- or intermediate-risk PC had a modestly higher relative rate of major depression (aHR 1.19, 95% CI 1.16-1.23) and higher relative rate of suicide death at 3-12 mo after PC diagnosis (aHR 1.88, 95% CI 1.11-3.18) but not across the entire follow-up period (aHR 1.02, 95% CI 0.84-1.25). This study was limited to Sweden and will need replication in other populations. CONCLUSIONS: In this large cohort, high-risk PC was associated with substantially higher relative rates of major depression and death by suicide, which persisted for ≥10 yr after PC diagnosis. PC survivors need close follow-up for timely detection and treatment of psychosocial distress. PATIENT SUMMARY: In a large Swedish population, men with aggressive prostate cancer had higher long-term relative rates of depression and suicide.

Short term outcomes after robot assisted and open cystectomy - A nation-wide population-based study.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial.

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 Linnér.