Prostate Cancer Data Base Sweden Research Articles

Prognosis of Gleason score 8 prostatic adenocarcinoma in needle biopsies: a nationwide population-based study.

A 5-tier grouping of Gleason scores has recently been proposed. Studies have indicated prognostic heterogeneity within these groups. We assessed prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) for men diagnosed with Gleason score 3 + 5 = 8, 4 + 4 = 8 and 5 + 3 = 8 acinar adenocarcinoma on needle biopsy in a population-based national cohort. The Prostate Cancer data Base Sweden 5.0 was used for survival analysis with PCSM and ACM at 5 and 10years as endpoints. Multivariable Cox regression models controlling for socioeconomic factors, stage and primary treatment type were used for PCSM and ACM. Among 199,620 men reported with prostate cancer in 2000-2020, 172,112 were diagnosed on needle biopsy. In 18,281 (11%), there was a Gleason score of 8 in needle biopsies, including a Gleason score of 3 + 5, 4 + 4 and 5 + 3 in 11%, 86% and 2.3%, respectively. The primary treatment was androgen deprivation therapy (55%), deferred treatment (8%), radical prostatectomy (16%) or radical radiotherapy (21%). PCSM in men with Gleason scores of 3 + 5, 4 + 4 and 5 + 3 at 5years of follow-up was 0.10 (95% CI 0.09-0.12), 0.22 (0.22-0.23) and 0.32 (0.27-0.36), respectively, and at 10years 0.19 (0.17-0.22), 0.34 (0.33-0.35) and 0.44 (0.39-0.49), respectively. There was a significantly higher PCSM after 5 and 10years in men with Gleason score 5 + 3 cancers than in those with 4 + 4 and in Gleason score 4 + 4 cancers than in those with 3 + 5. Grouping of Gleason scores will eliminate the prognostic granularity of Gleason scoring, thus diminishing the prognostic significance of this proposed grading system.

Population-based study of disease trajectory after radical treatment for high-risk prostate cancer.

To investigate long-term disease trajectories among men with high-risk localized or locally advanced prostate cancer (HRLPC) treated with radical radiotherapy (RT) or radical prostatectomy (RP). Men diagnosed with HRLPC in 2006-2020, who received primary RT or RP, were identified from the Prostate Cancer data Base Sweden (PCBaSe) 5.0. Follow-up ended on 30 June 2021. Treatment trajectories and risk of death from prostate cancer (PCa) or other causes were assessed by competing risk analyses using cumulative incidence for each event. In total, 8317 men received RT and 4923 men underwent RP. The median (interquartile range) follow-up was 6.2 (3.6-9.5) years. After RT, the 10-year risk of PCa-related death was 0.13 (95% confidence interval [CI] 0.12-0.14) and the risk of death from all causes was 0.32 (95% CI 0.31-0.34). After RP, the 10-year risk of PCa-related death was 0.09 (95% CI 0.08-0.10) and the risk of death from all causes was 0.19 (95% CI 0.18-0.21). The 10-year risks of androgen deprivation therapy (ADT) as secondary treatment were 0.42 (95% CI 0.41-0.44) and 0.21 (95% CI 0.20-0.23) after RT and RP, respectively. Among men who received ADT as secondary treatment, the risk of PCa-related death at 10 years after initiation of ADT was 0.33 (95% CI 030-0.36) after RT and 0.27 (95% CI 0.24-0.30) after RP. Approximately one in 10 men with HRLPC who received primary RT or RP had died from PCa 10 years after diagnosis. Approximately one in three men who received secondary ADT, an indication of PCa progression, died from PCa 10 years after the start of ADT. Early identification and aggressive treatment of men with high risk of progression after radical treatment are warranted.

Socioeconomic inequality in prostate cancer diagnostics, primary treatment, rehabilitation, and mortality in Sweden.

We designed a nationwide study to investigate the association between socioeconomic factors (household income and education) and different aspects of prostate cancer care, considering both individual- and neighbourhood-level variables. Data were obtained from Prostate Cancer data Base Sweden (PCBaSe), a research database with data from several national health care registers including clinical characteristics and treatments for nearly all men diagnosed with prostate cancer in Sweden. Four outcomes were analysed: use of pre-biopsy magnetic resonance imaging (MRI) in 2018-2020 (n = 11,843), primary treatment of high-risk non-metastatic disease in 2016-2020 (n = 6633), rehabilitation (≥2 dispensed prescriptions for erectile dysfunction within 1 year from surgery in 2016-2020, n = 6505), and prostate cancer death in 7770 men with high-risk non-metastatic disease diagnosed in 2010-2016. Unadjusted and adjusted odds and hazard ratios (OR/HRs) with 95% confidence intervals (CIs) were calculated. Adjusted odds ratio (ORs) comparing low versus high individual education were 0.74 (95% CI 0.66-0.83) for pre-biopsy MRI, 0.66 (0.54-0.81) for primary treatment, and 0.82 (0.69-0.97) for rehabilitation. HR gradients for prostate cancer death were significant on unadjusted analysis only (low vs. high individual education HR 1.41, 95% CI 1.17-1.70); co-variate adjustments markedly attenuated the gradients (low vs. high individual education HR 1.10, 95% CI 0.90-1.35). Generally, neighbourhood-level analyses showed weaker gradients over the socioeconomic strata, except for pre-biopsy MRI. Socioeconomic factors influenced how men were diagnosed with prostate cancer in Sweden but had less influence on subsequent specialist care. Neighbourhood-level socioeconomic data are more useful for evaluating inequality in diagnostics than in later specialist care.

Prognosis of Gleason Score 9–10 Prostatic Adenocarcinoma in Needle Biopsies: A Nationwide Population-based Study

BackgroundSince 2014, prostate cancer is reported using five-tier grouping of Gleason scores. Studies have suggested prognostic heterogeneity within the groups. ObjectiveWe assessed the risk of prostate cancer death for men diagnosed with Gleason scores 4 + 5, 5 + 4, and 5 + 5 on needle biopsy in a population-based cohort. Design, setting, and participantsWe used the data from Prostate Cancer data Base Sweden (PCBaSe) 4.0 for a survival analysis. Among 199 620 men reported to have prostate cancer in 2000–2020, 172 112 were diagnosed on needle biopsy. The primary treatment was classified as androgen deprivation therapy (66%), deferred treatment (5%), radical prostatectomy (7%), or radical radiotherapy (21%). Outcome measurements and statistical analysisThe risks of death from prostate cancer in men with Gleason score 9–10 at 5 and 10 yr were used as endpoints. Multivariable Cox regression models controlling for socioeconomic factors and primary treatment were used for time-to-event analyses of death from prostate cancer and death from any causes. Results and limitationsA total of 20 419 (12%) men had a Gleason score of 9–10, including Gleason scores of 4 + 5, 5 + 4, and 5 + 5 in 14 333 (70%), 4223 (21%), and 1863 (9%) men, respectively. The risks of prostate cancer death for men with Gleason scores 4 + 5, 5 + 4, and 5 + 5 at 10 yr of follow-up were 0.45 (confidence interval [CI] 0.44–0.46), 0.56 (0.55–0.58), and 0.66 (0.63–0.68), respectively. The risks of death of any cause for men with Gleason scores 4 + 5, 5 + 4, and 5 + 5 at 10 yr were 0.73 (CI 0.72–0.74), 0.81 (0.80–0.83), and 0.87 (0.85–0.89), respectively. ConclusionsWe demonstrate in the largest and most complete cohort analyzed to date that collapsing the Gleason scores by grouping results in loss of prognostic information in men with Gleason score 9–10 cancer. Patient summarySurvival of prostate cancer patients with the highest tumor grades varies depending on grade composition.

Risk of prostate cancer death after radical radiotherapy with neoadjuvant and adjuvant therapy with bicalutamide or gonadotropin-releasing hormone agonists

Background Oncological outcome after radical radiotherapy (RRT) combined with neoadjuvant and adjuvant androgen suppression therapy (AST) may differ according to type of AST. The aim of this nationwide register-based study was to investigate risk of prostate cancer (Pca) death after different neoadjuvant and adjuvant ASTs; (i) bicalutamide, (ii) gonadotropin-releasing hormone agonists (GnRH) or (iii) combined bicalutamide and GnRH (CAB), together with RRT. Materials and Methods Data for 6882 men diagnosed with high-risk Pca between 2007 and 2020 and treated with primary RRT was retrieved from Prostate Cancer data Base Sweden (PCBaSe) 5.0. Time to Pca death according to type of neoadjuvant and adjuvant AST was assessed by use of Kaplan–Meier plots and Cox proportional hazard models adjusted for putative confounders. Results Data were stratified by RRT type since the effect of AST in risk of Pca death differed according to type of RRT. Compared with the reference RRT combined with neoadjuvant CAB/adjuvant GnRH, risk of Pca death for men treated with CAB/bicalutamide and conventionally fractionated external beam radiotherapy (CF-EBRT) was hazard ratio (HR) 0.73 (95% CI: 0.50–1.04), hypofractionated EBRT (HF-EBRT), HR 1.35 (95% CI: 0.65–2.81) and EBRT with high dose rate brachytherapy (EBRT-HDRBT), HR 0.85 (95% CI: 0.37–1.95). Risk of Pca death for men treated with bicalutamide/bicalutamide and: (i) CF-EBRT was HR 2.35 (95% CI: 1.42–3.90), (ii) HF-EBRT, HR 0.70 (95% CI: 0.26–1.85), (iii) HF-EBRT, HR 4.07 (95% CI: 1.88–8.77) vs the reference. Conclusion In this observational study, risk of Pca death between men receiving different combinations of AST varied according to RRT type. No difference was found in risk of Pca death for men treated with bicalutamide or GnRH as adjuvant therapy to RRT following neoadjuvant CAB. Risk of Pca death was increased for men with monotherapy neo-/adjuvant bicalutamide in combination with CF-EBRT or EBRT-HDRBT.

Survival Trend in Individuals With De Novo Metastatic Prostate Cancer After the Introduction of Doublet Therapy

Recently, life-prolonging treatments for patients with advanced prostate cancer have been introduced in clinical practice. To investigate if the introduction of doublet therapy is associated with changes in survival on a population-basis. This nationwide population-based cohort study used data from the Prostate Cancer data Base Sweden from 2008 to 2020. Men registered with de novo metastatic castration-sensitive prostate cancer (mCSPC) were included. The proportion of men with mCSPC who received doublet therapy, ie, androgen deprivation therapy plus androgen receptor pathway inhibitor drugs or chemotherapy was assessed. Standardized overall survival, taking age, comorbidity, and cancer characteristics into consideration, was estimated by use of a parametric survival model. A total of 11 382 men were included in this study (median [IQR] age, 74.0 [68-81] years). There was a shift toward less advanced prostate cancer during the study period with a decrease in median (IQR) prostate-specific antigen at diagnosis in men with mCSPC from 145 (39-571) ng/mL to 107 (27-426) ng/mL. Upfront treatment with doublet therapy in these men simultaneously increased from 1% (7 of 991) in 2016 to 44% (402 of 922) in 2020. The adjusted 5-year overall survival increased from 26% (95% CI, 25%-28%) from 2008 to 2012 to 35% (95% CI, 31%-40%) from 2017 to 2020. During the first 5 years after diagnosis, there was an increase in mean survival of 6 months, from 2.7 (95% CI, 2.6-2.8) years from 2008 to 2012 to 3.2 (95% CI, 3.1-3.1) years from 2017 to 2020. In parallel with improvements in treatment of advanced prostate cancer, a clinically meaningful increase in mean survival was observed in men with de novo mCSPC in Sweden between 2008 and 2020 in this study.

Risk of colorectal adenocarcinoma in men receiving androgen deprivation therapy for prostate cancer; a nationwide cohort study

PurposeTo assess whether androgens play a role in explaining the sex related differences in the incidence of colorectal cancer (CRC).MethodsA nationwide matched cohort study was conducted employing the Prostate Cancer data Base Sweden (PCBaSe) 4.0 during the study period 2006–2016. Prostate cancer (PC) patients receiving androgen deprivation therapy (ADT) were treated as exposed. Prostate cancer-free men from the general population were randomly selected and matched to the index case by birth year and county of residence, forming the unexposed group. All were followed until a diagnosis of CRC, death, emigration, or end of the study period. The risk of CRC among ADT exposed PC patients compared to unexposed cancer-free men was calculated using a flexible parametric survival model and expressed as hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsThere was an increased risk of CRC among ADT exposed PC patients compared to unexposed cancer-free men (HR 1.27 [95% CI 1.15–1.41]), in particular an increased risk of adenocarcinoma of the colon (HR 1.33 [95% CI 1.17–1.51]) and more specifically an increased risk of adenocarcinoma of the distal colon (HR 1.53 [95% CI 1.26–1.85]). Examination of latency effects yielded significantly decreased HRs over time for CRC (p = 0.049 for trend).ConclusionsThis population-based study found an increased risk of CRC among PC patients exposed to ADT, specifically adenocarcinoma of the distal colon, which indicates an increased association between ADT (PC + ADT) and CRC but not a positive dose-response trend questioning a true causal effect.

PD27-09 PATIENT REPORTED OUTCOMES AFTER RADICAL PROSTATECTOMY OR RADIOTHERAPY FOR PROSTATE CANCER, A REGISTER-BASED NATIONWIDE STUDY

You have accessJournal of UrologyCME1 Apr 2023PD27-09 PATIENT REPORTED OUTCOMES AFTER RADICAL PROSTATECTOMY OR RADIOTHERAPY FOR PROSTATE CANCER, A REGISTER-BASED NATIONWIDE STUDY Oskar Bergengren, Christian Corsini, Stefan Carlsson, Ingela Franck-Lissbrant, Hans Garmo, Marie Hjelm-Eriksson, Per Fransson, Jon Kindblom, David Robinson, Marcus Westerberg, Pär Stattin, and Sigrid Carlsson Oskar BergengrenOskar Bergengren More articles by this author , Christian CorsiniChristian Corsini More articles by this author , Stefan CarlssonStefan Carlsson More articles by this author , Ingela Franck-LissbrantIngela Franck-Lissbrant More articles by this author , Hans GarmoHans Garmo More articles by this author , Marie Hjelm-ErikssonMarie Hjelm-Eriksson More articles by this author , Per FranssonPer Fransson More articles by this author , Jon KindblomJon Kindblom More articles by this author , David RobinsonDavid Robinson More articles by this author , Marcus WesterbergMarcus Westerberg More articles by this author , Pär StattinPär Stattin More articles by this author , and Sigrid CarlssonSigrid Carlsson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003305.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The two main alternatives for curative treatment of prostate cancer (PCa) are robot assisted radical prostatectomy (RARP) and radiotherapy (RT). We assessed outcomes after RARP and RT by use of Patient Reported Outcomes Measures (PROM) in a large, contemporary population. METHODS: The National Prostate Cancer Register of Sweden (NPCR) includes information on almost all Swedish men with PCa. The PCa Data Base Sweden (PCBaSe) links data to multiple national population-based registries. PROM are distributed to all men scheduled for curative treatment. 12 month PROM were used to evaluate the outcomes erectile dysfunction, urinary symptoms, bowel dysfunction, and quality of life (QoL). Data for all men who completed 12 month PROM in PCBaSe 5.0 aged <75 years, with clinical T1c-T3 or Tx, any Gleason score, preoperative PSA levels <l00 ng/mL, no metastases (N0, Nx. M0 or Mx) who underwent RARP or RT between 1 January 2018 and 31 December 2020 were analyzed (n=4298). Comorbidities were assessed by Charlson Comorbidity Index and a Drug Comorbidity Index. Adjusted odds ratios (OR) for each outcome comparing RT vs RARP (reference) were obtained using logistic regression, adjusting for confounders at date of treatment (age, comorbidities, educational level, civil status, PSA, prostate volume, biopsies with cancer, cT-stage and Gleason score). RESULTS: 2557 men underwent RARP and 1741 men received RT. On average, men who had undergone RT were 4 years older and had more comorbidities. The prevalence of erectile dysfunction was 80% among men who underwent RARP and 82% among RT. 13% of the men were incontinent one year after RARP while only 5% reported incontinence after RT. 17% of men treated with RT and 18% with RARP reported high urinary bother. 34% of men who underwent RT reported urgency to defecate compared to 14% of men treated with RARP. High QoL was reported by 85% of men who underwent RARP and 79% who underwent RT. RT was associated with lower risk of erectile dysfunction (OR 0.57, 95% CI 0.48-0.67), lower risk of urine incontinence (OR 0.24, 95% CI 0.19-0.32), lower urinary bother (OR 0.74, 95% CI 0.61-0.89) but higher risk of bowel related symptoms (OR 2.84 95%, CI: 2.40-3.37). RARP was associated with higher QoL (OR 1.33, 95% CI: 1.11-1.60). CONCLUSIONS: Results from this large, contemporary, and unselected population confirms previous reports on common side-effects after curative treatment for PCa. However, QoL is high regardless of treatment suggesting that factors other than side-effects are the main drivers of QoL. Source of Funding: National Institutes of Health/National Cancer Institute (K22 CA234400) to Dr. Carlsson and Hillevi Fries Research Foudation, Johanna Hagstrand and Sigfrid Linnérs Research Foundation, Nyströms America Scholarship, and the Swedish Society of Medicine to Dr. Bergengren © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e745 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Oskar Bergengren More articles by this author Christian Corsini More articles by this author Stefan Carlsson More articles by this author Ingela Franck-Lissbrant More articles by this author Hans Garmo More articles by this author Marie Hjelm-Eriksson More articles by this author Per Fransson More articles by this author Jon Kindblom More articles by this author David Robinson More articles by this author Marcus Westerberg More articles by this author Pär Stattin More articles by this author Sigrid Carlsson More articles by this author Expand All Advertisement PDF downloadLoading ...

PD21-03 THIRTY-YEAR OUTCOMES FOR MEN WITH PROSTATE CANCER ON WATCHFUL WAITING. NATION-WIDE POPULATION-BASED STUDY

You have accessJournal of UrologyCME1 Apr 2023PD21-03 THIRTY-YEAR OUTCOMES FOR MEN WITH PROSTATE CANCER ON WATCHFUL WAITING. NATION-WIDE POPULATION-BASED STUDY Eugenio Ventimiglia, Christian Corsini, Pär Stattin, and Hans Garmo Eugenio VentimigliaEugenio Ventimiglia More articles by this author , Christian CorsiniChristian Corsini More articles by this author , Pär StattinPär Stattin More articles by this author , and Hans GarmoHans Garmo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003287.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To model long-term outcomes for men with prostate cancer (PCa) on watchful waiting. METHODS: We developed and applied a state transition model based on data from 11,648 men with PCa managed with watchful waiting (WW) and registered in Prostate Cancer data Base Sweden (PCBaSe). For each man, we calculated the estimated remaining lifetime (ERL) at PCa diagnosis using a previously validated model including both Charlson Comorbidity Index (CCI) and a novel drug comorbidity index (DCI). We analysed the incidence of transition from WW to next treatment state; androgen deprivation therapy, castration resistant PCa, and death from PCa or other causes, stratified according to ERL. We then estimated the duration of time spent in the WW state and the proportion of wen who transitioned to CRPC or PCa death for each combination of PCa baseline risk category and ERL RESULTS: Median (IQR) age at diagnosis was 76 (72-81) years. A majority of men (62%) had no comorbidities (CCI=0, n=7246). Low-risk PCa was diagnosed in 3328 (28%) men, whereas higher-risk PCa (Gleason ≥3+4 or PSA>20 ng/ml or local stage T3) in 40% men. Median ERL was 10.5 years (IQR 7.9-13.5). Men in the low-risk PCa risk category managed with WW had shorter ERL (43 % below the median ERL value) vs. men with higher-risk PCa (61% below the median ERL value). Among men with ERL above median, 58% of men with low-risk PCa were still in the WW state 10 years after diagnosis vs 38% in the higher-risk PCa. At 30 years after diagnosis among men with ERL above median, the proportion of PCa death was 17% for low-risk PCa death and 23% for higher-risk PCa. CONCLUSIONS: One out of two men on watchful waiting had an ERL of at least 10 years, and ten years after diagnosis more than half of these men were still on watchful waiting. Death from other causes was the most common outcome for these men, even for men with higher-risk disease at diagnosis. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e590 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eugenio Ventimiglia More articles by this author Christian Corsini More articles by this author Pär Stattin More articles by this author Hans Garmo More articles by this author Expand All Advertisement PDF downloadLoading ...

Use of Antiepileptic Drugs and Risk of Prostate Cancer: A Nationwide Case-Control Study in Prostate Cancer Data Base Sweden.

An inverse association between use of antiepileptic drugs (AEDs) and prostate cancer (PCa) has been suggested, putatively due to the histone deacetylases inhibitory (HDACi) properties of the AEDs. In a case-control study in Prostate Cancer data Base Sweden (PCBaSe), PCa cases diagnosed between 2014 and 2016 were matched to five controls by year of birth and county of residence. AED prescriptions were identified in the Prescribed Drug Registry. Odds ratios (ORs) and 95% confidence intervals for risk of PCa were estimated using multivariable conditional logistic regression, adjusted for civil status, education level, Charlson comorbidity index, number of outpatient visits, and cumulative duration of hospital stay. Dose responses in different PCa risk categories and HDACi properties of specific AED substances were further explored. 1738/31591 (5.5%) cases and 9674/156802 (6.2%) controls had been exposed to AED. Overall, users of any AED had a reduced risk of PCa as compared to nonusers (OR: 0.92; 95% CI: 0.87-0.97) which was attenuated by adjustment to healthcare utilisation. A reduced risk was also observed in all models for high-risk or metastatic PCa in AED users compared to nonusers (OR: 0.89; 95% CI: 0.81-0.97). No significant findings were observed for dose response or HDACi analyses. Our findings suggest a weak inverse association between AED use and PCa risk, which was attenuated by adjustment for healthcare utilisation. Moreover, our study showed no consistent dose-response pattern and no support for a stronger reduction related to HDAC inhibition. Further studies focusing on advanced PCa and PCa treatments are needed to better analyse the association between use of AED and risk of PCa.

Real World Outcomes in Patients With Metastatic, Castration-Resistant Prostate Cancer Treated With Radium-223 in Routine Clinical Practice in Sweden.

Estimate the effect of Radium-223 (Ra-223) on the incidence of bone fractures, prostate cancer death, and all-cause death compared with other standard treatments for metastatic, castration-resistant prostate cancer (mCRPC). Using a cohort design, we estimated the effect of Ra-223 on the risk of bone fractures, all-cause and prostate cancer-specific mortality across different lines of treatment for mCRPC using Prostate Cancer data Base Sweden (2013-2018). The comparator group comprised other standard treatments for mCRPC. We used 36-month risk differences and hazard ratios (HRs) as effect estimates. The number of eligible individuals was 635, 453, 262, and 84 for the first-, second-, third-, and fourth-line cohorts, respectively. When compared Ra-223 to other standard treatments, the difference in the 36-month risk of fracture was 6% (95% confidence interval [CI], -7% to 18%) in the first-line cohort (n=635) and 8% (95% CI, -7% to 18%) in the second-line cohort (n=453). The number of fractures in the third-/fourth-line cohorts was too small for an adjusted comparison. The difference in 36-month mortality was higher in the first-line cohort 13% (95% CI, -3% to 31%), but lower in the second- and third-/fourth-line cohorts-8% (95% CI, -23% to 7%) and -14% (95% CI, -21% to 16%) respectively. Most deaths were due to prostate cancer. Results suggest that the difference in the risk of fractures is small, if any. A difference in the risk of mortality may be present in first-line treatment, but a decreased risk of mortality was observed in second and later lines of treatment. The results on mortality need to be considered in the context of potential unmeasured or residual confounding.

Long-term Outcomes Among Men Undergoing Active Surveillance for Prostate Cancer in Sweden

The long-term outcomes among men with prostate cancer (PC) whose disease is managed with active surveillance (AS) remains unknown. To develop a simulation model with a 30-year follow-up for men with PC managed with AS. In this cohort study, a state transition model was created using data from Prostate Cancer data Base Sweden (PCBaSe) on 23 655 men diagnosed with PC and managed with deferred treatment to estimate treatment trajectories. A simulation was performed with 100 000 men in each combination of age at diagnosis, Charlson Comorbidity Index, and PC risk with a follow-up of 30 years. Death from PC and death from other causes were estimated, and the proportion of time without active PC treatment was assessed until date of death or age 85 years. This study included 23 655 men from PCBaSe with a median age at diagnosis of 69 years (IQR, 64-74 years). Of these, 16 177 men underwent active surveillance for PC and 7478 underwent watchful waiting. The proportion of men who were diagnosed at age 55 years and died of PC before age 85 years was 9% for very low-risk PC, 13% for low-risk PC, and 15% for intermediate-risk PC. Among men with a Charlson Comorbidity Index of 0 who were diagnosed at age 70 years, the corresponding percentages were 3%, 6%, and 7%, respectively. The mean proportion of remaining life-years without active PC treatment for men diagnosed at age 55 years was 12 of 25 years (48%) for very low-risk PC, 9 of 25 years (36%) for low-risk PC, and 7 of 25 (29%) for intermediate-risk PC. For men aged 70 years, the corresponding numbers were 10 of 13 years (77%), 9 of 13 years (66%), and 8 of 13 years (60%), respectively. Men with intermediate-risk PC who were younger than 60 years at diagnosis had a high risk of PC death (12%-15%) and fewer remaining life-years without active PC treatment (29%-33%). In contrast, men with low-risk PC who were older than 65 years at diagnosis had a lower risk of PC death (3%-5%) and more remaining life-years without active PC treatment (62%-77%). The findings of this Swedish cohort study suggest that active surveillance may be a safe strategy for disease management among men with PC who were older than 65 years at diagnosis.

Association of Gonadotropin-Releasing Hormone Agonists for Prostate Cancer With Cardiovascular Disease Risk and Hypertension in Men With Diabetes

Men with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Meanwhile, gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer (PCa) are associated with increased risk of CVD. To evaluate the association between GnRH agonist use, PCa diagnosis per se, and CVD risk in men with type 2 diabetes. This nationwide population-based cohort study identified men with type 2 diabetes by use of data in the Prostate Cancer Data Base Sweden version 4.1 and the Swedish National Diabetes Register, with longitudinal data from 2006 to 2016. These data were used to create 2 cohorts, 1 including men with and without PCa and the other including men with PCa who received and did not receive GnRH agonists. Data analysis was conducted from January 2006 to December 2016. Treatment with GnRH agonists and PCa diagnosis were the primary exposures. Primary outcome was a 10% increase in predicted 5-year CVD risk score. Secondary outcome was worsening hypertension as defined by the European Society of Hypertension Guidelines. Cox proportional hazards regression models were used to analyze the association. The PCa exposure cohort included 5714 men (median [IQR] age, 72.0 [11.0]), and the non-PCa cohort included 28 445 men without PCa (median [IQR] age, 72.0 [11.0]). The GnRH agonist-exposure cohort included 692 men with PCa who received a GnRH agonist, compared with 3460 men with PCa who did not receive a GnRH agonist. Men with PCa receiving GnRH agonists had an increased estimated 5-year CVD risk score compared with men without PCa (hazard ratio [HR], 1.25; 95% CI, 1.16-1.36) and compared with men with PCa not receiving GnRH agonists (HR, 1.53; 95% CI, 1.35-1.74). Men receiving GnRH agonists had decreased blood pressure compared with men without PCa (HR, 0.70; 95% CI, 0.61-0.80) and compared with men with PCa not receiving GnRH agonists (HR, 0.68; 95% CI, 0.56-0.82). In this population-based cohort study, there was an increased risk of CVD in men with type 2 diabetes who received a GnRH agonist for PCa. These findings highlight the need to closely control CVD risk factors in men with type 2 diabetes treated with GnRH agonists. The association between GnRH agonist use and decreased blood pressure levels warrants further study.

Susceptibility to SARS-Cov-2 infection and risk for severe COVID-19 in patients with prostate cancer on androgen deprivation therapy.

Androgen deprivation therapy (ADT) has been hypothesized to protect against COVID‐19, but previous observational studies of men with prostate cancer on ADT have been inconsistent regarding mortality risk from coronavirus disease 2019 (COVID‐19). Using data from the Prostate Cancer data Base Sweden (PCBaSe), we identified a cohort of 114 547 men with prevalent prostate cancer on the start of follow‐up in February 2020, and followed them until 16 December 2020 to evaluate the association between ADT and time to test positive for COVID‐19. Among men testing positive for COVID‐19, we used regression analyses to estimate the association between ADT and risk of COVID‐19‐related hospital admission/death from any cause within 30 days of the positive test. In total, 1695 men with prostate cancer tested positive for COVID‐19. In crude analyses, exposure to ADT was associated with a 3‐fold increased risk of both testing positive for COVID‐19 infection and subsequent hospital admission/death. Adjustment for age, comorbidity and prostate cancer risk category substantially attenuated the associations: HR 1.3 (95% CI: 1.1‐1.5) for testing positive for COVID‐19, and OR 1.4 (95% CI: 1.0‐1.9) for risk of subsequent hospital admission/death. In conclusion, although these results suggest increased risks of a positive COVID‐19 test, and COVID‐19‐related hospital admission/death in men on ADT, these findings are likely explained by confounding by old age, cancer‐associated morbidity and other comorbidities being more prevalent in men on ADT, rather than a direct effect of the therapy.

Risk of severe late toxicity after radiotherapy following radical prostatectomy - a nationwide study.

To estimate the long-term risks of severe late toxicities for radiation therapy (RT) following radical prostatectomy (RP) in an unselected nationwide cohort, as severe side-effects are rare but may occur years later. The study population comprised all men undergoing RP between 1997 and 2016 in the Prostate Cancer database Sweden (PCBaSe) (n = 40 962). By (1:2) matching, two cohorts were created: 2789 men exposed to postoperative RT and 5578 unexposed men with comparable age, comorbidities, and year of surgery. Cumulative incidences and rate ratios were calculated for the following outcomes: symptoms and interventions of the urinary or intestinal tract demanding inpatient care, secondary malignancies, and non-prostate cancer mortality. The largest differences were seen for late toxicities affecting the urinary tract. The 10-year cumulative incidences among those exposed to postoperative RT vs the RP-only group were: 17.8% vs 10.5% for procedures of the urinary tract (difference 7.3%, 95% confidence interval [CI] 4.4 to 10.3; relative risk [RR] 1.74, 95% CI 1.47 to 2.05); 6.0% vs 1.2% for haematuria (difference 4.8%, 95% CI 3.1 to 6.5; RR 6.50, 95% CI 4.31 to 10.10); and 2.4% vs 1.1% for bladder cancer (difference 1.4%, 95% CI 0.4 to 2.3; RR 2.71, 95% CI 1.72 to 4.33). The groups were similar regarding intestinal toxicity, other secondary malignancies, and non-prostate cancer mortality. Adjustments for preoperative tumour risk factors did not importantly affect the rate ratios. Severe late toxicity after postoperative RT following RP predominately affects the bladder and can appear many years after RT.

Risk of venous thromboembolism in men with prostate cancer compared with men in the general population: a nationwide population-based cohort study in Sweden.

ObjectiveTo estimate the additional risk of venous thromboembolism (VTE) in men with prostate cancer compared with men without prostate cancer in Sweden.DesignNationwide cohort study following 92 105 men with prostate cancer and 466 241 men without prostate cancer (comparison cohort) matched 5:1 by birth year and residential region.SettingThe male general population of Sweden (using the Nationwide Prostate Cancer data Base Sweden).Primary and secondary outcome measuresCrude incidence proportion ratios (IPRs) comparing the incidence of VTE in men with prostate cancer and men in the comparison cohort. Cox regression was used to calculate HRs for VTE adjusted for confounders.Results2955 men with prostate cancer and 9774 men in the comparison cohort experienced a first VTE during a median of 4.5 years’ follow-up. Deep vein thrombosis (DVT) accounted for 52% of VTE cases in both cohorts. Median time from start of follow-up to VTE was 2.5 years (IQR 0.9–4.7) in the prostate cancer cohort and 2.9 years (IQR 1.3–5.0) in the comparison cohort. Crude incidence rates of VTE per 1000 person-years were 6.54 (95% CI 6.31 to 6.78) in the prostate cancer cohort (n=2955 events) and 4.27 (95% CI 4.18 to 4.35) in the comparison cohort (n=9774 events). The IPR decreased from 2.53 (95% CI 2.26 to 2.83) at 6 months to 1.59 (95% CI 1.52 to 1.67) at 5 years’ follow-up. Adjusted HRs were 1.48 (95% CI 1.39 to 1.57) for DVT and 1.47 (95% CI 1.39 to 1.56) for pulmonary embolism after adjustment for patient characteristics.ConclusionsSwedish men with prostate cancer had a mean 50% increased risk of VTE during the 5 years following their cancer diagnosis compared with matched men free of prostate cancer. Physicians should be mindful of this marked increase in VTE risk in men with prostate cancer to help ensure timely diagnosis.

Androgen deprivation therapy, comorbidity, cancer stage and mortality from COVID-19 in men with prostate cancer

Background Androgens facilitate entrance of the severe acute respiratory syndrome coronavirus 2 into respiratory epithelial cells, and male sex is associated with a higher risk of death from corona virus disease (COVID-19). Androgen deprivation therapy (ADT) could possibly improve COVID-19 outcomes. Methods In a case–control study nested in the Prostate Cancer data Base Sweden (PCBaSe) RAPID 2019, we evaluated the association between ADT and COVID-19 as registered cause of death in men with prostate cancer. Each case was matched to 50 controls by region. We used conditional logistic regression to adjust for confounders and also evaluated potential impact of residual confounding. Results We identified 474 men who died from COVID-19 in March–December 2020. In crude analyses, ADT exposure was associated with an increased risk of COVID-19 death (odds ratio [OR] 5.05, 95% CI: 4.18–6.10); however, the OR was substantially attenuated after adjustment for age, comorbidity, prostate cancer characteristics at diagnosis, recent healthcare use, and indicators of advanced cancer (adjusted OR 1.25, 95% CI: 0.95–1.65). If adjustment has accounted for at least 85% of confounding, then the true effect could be no more than a 5% reduction of the odds for COVID-19 death. Conclusions The increased mortality from COVID-19 in men with prostate cancer treated with ADT was mainly related to high age, comorbidity, and more advanced prostate cancer. There was no evidence to support the hypothesis that ADT is associated with improved COVID-19 outcomes.

O22 ANDROGEN DEPRIVATION THERAPY AND THE RISK FOR INGUINAL HERNIA

Abstract Aim To investigate whether androgen deprivation therapy (ADT) for prostate cancer increases the risk for inguinal hernia. Material and Methods A population-based nested case-control study based on data from the Prostate Cancer Database Sweden. The cohort included men with prostate cancer who had not received curative treatment. Men who had been diagnosed with inguinal hernia or had undergone inguinal hernia repair (n = 1324) were cases and controls were men, not diagnosed, nor operated on for inguinal hernia, matched on birth year (n = 13 240). Conditional multivariate logistic regression models were used to assess any temporal association between ADT and inguinal hernia, adjusting for confounders. Results Odds Ratio [OR] for repair of inguinal hernia 0-1 years from start of ADT was 0.5 (95% confidence Interval (CI)) 0.38-0.68), between 1 and 3 years after, the OR was 0.35 (95% CI 0.26-0.47), 3-5 years after, the OR was 0.39 (95% CI 0.26-0.56), 5-7 years after, the OR was 0.6, (95% CI: 0.41-0.97), and &amp;gt; 9 years after, the OR was 3.68 (95% CI 2.45-5.53). Conclusions The marked increase in OR for inguinal hernia after 9 years of ADT supports the hypothesis that low testosterone levels increase the risk for inguinal hernia. The low risk for inguinal hernia during the first eight years on ADT is likely caused by selection of men with advanced cancer unlikely to be diagnosed or treated for inguinal hernia. This finding may support the hypothesis that sex hormones plays a crucial role in inguinal hernia development.

Exploring the association between use of gonadotropin releasing hormones agonists and prostate cancer diagnosis per se and diabetes control in men with type 2 diabetes mellitus: a nationwide, population-based cohort study

BackgroundGonadotropin Releasing Hormones agonists (GnRH), which are first line treatment for metastatic prostate cancer (PCa), increase risk of type 2 diabetes mellitus (T2DM). This study aims to quantify the association of use of GnRH with diabetes control in PCa men with T2DM.MethodsNationwide population-based cohort study in the Swedish National Diabetes Register and Prostate Cancer data Base Sweden 4.1, on the association between GnRH and diabetes control in T2DM men with PCa by comparing T2DM men with PCa vs. without PCa, as well as comparing T2DM men with PCa on or not on GnRH. The primary exposure was use of GnRH. Worsening diabetes control was the primary outcome, defined as: 1) HbA1c rose to 58 mmol/mol or higher; 2) HbA1c increase by 10 mmol/mol or more; 3) Start of antidiabetic drugs or switch to insulin. We also combined all above definitions. Cox proportional hazards regression was used to analyze the association.ResultsThere were 5714 T2DM men with PCa of whom 692 were on GnRH and 28,445 PCa-free men with T2DM with similar baseline characteristics. Diabetes control was worse in men with GnRH vs. PCa-free men (HR: 1.24, 95% CI: 1.13–1.34) as well as compared with PCa men without GnRH (HR:1.58, 95% CI: 1.39–1.80), when we defined the worsening control of diabetes by combining all definitions above.ConclusionUse of GnRH in T2DM men with PCa was associated with worse glycemic control. The findings highlight the need to closely monitor diabetes control in men with T2DM and PCa starting GnRH.

Androgen Deprivation Therapy and the Risk for Inguinal Hernia: An Observational Nested Case Control Study

It has been suggested that hypogonadism increases the risk for inguinal hernia (IH). The aim of this study was to investigate any association between androgen deprivation therapy (ADT) for prostate cancer and increased risk for IH. The study population in this population-based nested case-control study was based on data from the Prostate Cancer Database Sweden. The cohort included all men with prostate cancer who had not received curative treatment. Men who had been diagnosed or had undergone IH repair (n = 1,324) were cases and controls, where not diagnosed, nor operated on for IH, matched only on birth year (n = 13,240). Conditional multivariate logistic regression models were used to assess any temporal association between ADT and IH, adjusting for marital status, education level, prostate cancer risk category, Charlson Comorbidity Index, ADT, time since prostate cancer diagnosis, and primary prostate cancer treatment. Odds ratio (OR) for diagnosis/repair of IH 0 to 1 year from start of ADT was 0.5 (95% confidence interval [CI] = [0.38, 0.68]); between 1 and 3 years after, the OR was 0.35 (95% CI = [0.26, 0.47]); between 3 and 5 years after, the OR was 0.39 (95% CI = [0.26, 0.56]); between 5 and 7 years after, the OR was 0.6 (95% CI = [0.41, 0.97]); and >9 years after, the OR was 3.68 (95% CI = [2.45, 5.53]). The marked increase in OR for IH after 9 years of ADT supports the hypothesis that low testosterone levels increase the risk for IH. The low risk for IH during the first 8 years on ADT is likely caused by selection of men with advanced cancer unlikely to be diagnosed or treated for IH.