Prostate Cancer Data Base Sweden Research Articles

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.

Androgen deprivation therapy and excess mortality in men with prostate cancer during the initial phase of the COVID-19 pandemic

BackgroundMen have a higher risk of death from COVID-19 than women and androgens facilitate entrance of the SARS-CoV-2 virus into respiratory epithelial cells. Thus, androgen deprivation therapy may reduce infection rates and improve outcomes for COVID-19. In the spring of 2020, Sweden was highly affected by COVID-19. The aim was to estimate the impact of androgen deprivation therapy on mortality from COVID-19 in men with prevalent prostate cancer by comparing all-cause mortality in the spring of 2020 to that in previous years.Patients and methodsUsing the Prostate Cancer data Base Sweden all men with prostate cancer on March 1 each year in 2015–2020 were followed until June 30 the same year. Exposure to androgen deprivation therapy was ascertained from filled prescriptions for bicalutamide monotherapy, gonadotropin-releasing hormone agonists (GnRH), or bilateral orchidectomy.ResultsA total of 9,822 men died in March-June in the years 2015–2020, of whom 5,034 men were on androgen deprivation therapy. There was an excess mortality in 2020 vs previous years in all men. The crude relative mortality rate ratio for 2020 vs 2015–2019 was 0.93 (95% confidence interval (CI) 0.83 to 1.04) in men on GnRH, and 0.90 (95% CI 0.78 to 1.05) in men on bicalutamide monotherapy. After multivariable adjustment these ratios were attenuated to 1.00 (95% CI 0.89 to 1.12) and 0.97 (95% CI 0.84 to 1.12), respectively. When restricting the analysis to the regions with the highest incidence of COVID-19 or to the time period between 2 April to 10 June when mortality in 2020 was increased >30% compared to previous years, the results were similar to the main analysis.ConclusionsIn this large national population-based cohort of men with prevalent prostate cancer, there was no clear evidence in support for an effect of androgen deprivation therapy on COVID-19 mortality.

Short-term ciprofloxacin prophylaxis for prostate biopsy and risk of aortic aneurysm. Nationwide, population-based cohort study

Introduction The use of quinolones has recently been questioned due to reports on side effects including an increased risk of aortic aneurysm. The aim of the study was to examine the risk of aortic aneurysm (AA) after short-term ciprofloxacin as prophylaxis for prostate biopsy. Materials and Methods We used the Prostate Cancer data Base Sweden and investigated 192,024 prostate biopsy exposures vs. 554,974 non-exposures for risk of AA. Prostate biopsy was used as a proxy for quinolone use as short-term ciprofloxacin is the recommended and documented prophylaxis in Sweden for this procedure. The outcome was the hazard ratio (HR) of AA in men who underwent a biopsy vs. those that did not. Results The absolute risk of AA was small, 39/10,000 person years for all AÁs and for ruptured AÁs 3.5/10,000 person years. In multivariate analyses, there were small, non-significant increases in risk of all AA’s (adjusted HR = 1.13, 95% CI: 0.91 to 1.39) and ruptured AÁs (adjusted HR = 1.05, 95% CI: 0.52 to 2.15) in men who underwent biopsy. A significantly increased risk of AA was observed in men diagnosed with high-risk prostate cancer on biopsy (HR = 1.50, 95% CI: 1.15–2.21). The use of prostate biopsy as a proxy for exposure to ciprofloxacin was a limitation of the study. Conclusions Short-term ciprofloxacin was not associated with an increased risk of aortic aneurysm and the increased risk in men with high-risk prostate cancer was likely due detection bias caused by imaging more commonly performed in these men.

The Value of Real-World Data in Understanding Prostate Cancer Risk and Improving Clinical Care: Examples from Swedish Registries.

Simple SummaryReal-world data (RWD), i.e., data reflecting normal clinical practice collected outside the constraints of randomised controlled trials, provide important insights into our understanding of prostate cancer and its management. Clinical cancer registries are an important source of RWD. Depending on their scope and the potential linkage to other data sources, registry-based data can be utilised to address a variety of questions including risk factors, healthcare utilisation, treatment effectiveness, adverse effects, disparities in healthcare access, quality of care and healthcare economics. This review describes the various registry-based RWD sources for prostate cancer research in Sweden (namely the National Prostate Cancer Register, the Prostate Cancer data Base Sweden (PCBaSe) and the Patient-overview Prostate Cancer) and documents their utility for better understanding prostate cancer aetiology and improving clinical care.Real-world data (RWD), that is, data from sources other than controlled clinical trials, play an increasingly important role in medical research. The development of quality clinical registers, increasing access to administrative data sources, growing computing power and data linkage capacities have contributed to greater availability of RWD. Evidence derived from RWD increases our understanding of prostate cancer (PCa) aetiology, natural history and effective management. While randomised controlled trials offer the best level of evidence for establishing the efficacy of medical interventions and making causal inferences, studies using RWD offer complementary evidence about the effectiveness, long-term outcomes and safety of interventions in real-world settings. RWD provide the only means of addressing questions about risk factors and exposures that cannot be “controlled”, or when assessing rare outcomes. This review provides examples of the value of RWD for generating evidence about PCa, focusing on studies using data from a quality clinical register, namely the National Prostate Cancer Register (NPCR) Sweden, with longitudinal data on advanced PCa in Patient-overview Prostate Cancer (PPC) and data linkages to other sources in Prostate Cancer data Base Sweden (PCBaSe).

Risk of cardiovascular events in men on abiraterone or enzalutamide combined with GnRH agonists: nation-wide, population-based cohort study in Sweden

Background Men with prostate cancer (PCa) on gonadotropin-releasing hormone agonists (GnRH) have an increased risk of cardiovascular disease (CVD) compared to men with PCa not on GnRH as well as compared with PCa-free men. Whether the addition of androgen receptor targeted (ART) drugs to GnRH further increases CVD risk, remains to be fully elucidated. Material and methods We investigated risk of CVD for men with castration resistant PCa (CRPC) on GnRH plus ART; abiraterone or enzalutamide vs 5,127 and 12,079 respective matched comparator men on GnRH in Prostate Cancer data Base Sweden (PCBaSeTraject) 4.1 between 1 June 2015 and 31 December 2018. PCBaSeTraject links National Prostate Cancer Register of Sweden to other healthcare registries and demographic databases. We conducted multivariable Cox proportional hazard models adjusting for PCa risk category, Charlson comorbidity index (CCI), insulin or statin use, civil status, level of education, history of CVD events and number of CVD drugs, with any incident or fatal CVD as the outcome. Results and conclusion 1,310 men were treated with abiraterone and 3,579 with enzalutamide. In multivariable analysis, CVD risk was increased in men on abiraterone (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.03–1.38) and in men on enzalutamide (HR: 1.10; 95% CI: 1.01–1.20). Men with a recent CVD (<12 months) including both men on ART as well as comparators had a much higher probability of a new CVD vs men with no prior CVD. CVD risk was mildly increased in men with PCa on GnRH plus abiraterone or enzalutamide vs comparator men on GnRH. Residual confounding and detection bias may at least partly explain this association.

Time spent in hormone-sensitive and castration-resistant disease states in men with advanced prostate cancer, and its health economic impact: registry-based study in Sweden

Objective To investigate time spent in hormone-sensitive and castration-resistant disease states in men with advanced prostate cancer in Sweden, and the associated health economic impact. Materials and methods Registry study (NCT03619980) of the Prostate Cancer data Base Sweden with data from the National Prostate Cancer Register, including the Patient-overview Prostate Cancer (PPC) and other national healthcare registries. The primary endpoint was time in each disease state. Secondary endpoints were co-medications, comorbidities and healthcare resource utilization (HRU) and cost in each disease state. Results In total, 1,869 men with advanced prostate cancer registered in PPC between 2014 and 2016, with data on the start of androgen deprivation therapy, were identified. Median time to progression and median survival were 4 and 11 years, respectively, for men with non-metastatic (nm) hormone-sensitive prostate cancer (HSPC); 1 and 7 years for men with metastatic (m) HSPC; and 1 and 8.5 years for men with nm castration-resistant prostate cancer (CRPC). Median survival for men with mCRPC was 4 years. Total annual mean costs for HRU per patient increased with increasing severity of disease, from 41,064 Swedish krona (SEK) for nmHSPC to 288,242 SEK for mCRPC. Conclusion Progression time from mHSPC and nmCRPC to the mCRPC state was short and survival in the mCRPC state was approximately 4 years. Survival times were longer than expected, likely due to the selection of long-term survivors among prevalent cases. Healthcare costs were high for men with mCRPC. Further studies are needed to confirm our pilot study findings.

Use of Warfarin or Direct Oral Anticoagulants and Risk of Prostate Cancer in PCBaSe: A Nationwide Case-Control Study.

Existing literature examining warfarin's association with prostate cancer (PCa) risk provides conflicting results, while the association with direct oral anticoagulants (DOACs) has not yet been studied. We investigated the association of warfarin and DOAC use on PCa risk among men within the population-based Prostate Cancer database Sweden (PCBaSe), using a case-control design. The study population included PCa cases diagnosed 2014–2016 and five age-matched PCa-free controls. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for PCa associated with warfarin and DOAC use, adjusted for marital status, education level, other drug use, and comorbidities. Among 31,591 cases and 156,802 controls, there were 18,522 (9.8%) warfarin and 4,455 (2.4%) DOAC users. Warfarin ever-use was associated with reduced risk of PCa overall (OR 0.92 95% CI 0.88–0.96) as were both past and current use. DOAC use was not associated with PCa risk. For some warfarin exposures, decreased risk was observed for unfavorable PCa (high risk/locally advanced/distant metastatic) but not with favorable PCa (low/intermediate risk). Increased risk of favorable PCa was observed for men whose initial warfarin exposure occurred in the 12 month period before diagnosis (OR 1.39; 95% CI 1.13–1.70). Our findings are consistent with previous publications reporting decreased PCa risk with warfarin exposure. Increased risk of favorable PCa suggests detection bias due to increased prostate specific antigen testing when starting on warfarin. Decreased overall PCa risk could reflect bias due to reduced biopsy rates among long-term warfarin users.

Long-Term Risk of Hip Complications After Radiation Therapy for Prostate Cancer: A Dose-Response Study

PurposeThe aim of the present study was to analyze the long-term incidence of hip complications after external beam radiation therapy compared with age-matched controls from the general population. We also investigated whether there were any dose−response associations. Methods and materialsA total of 349 patients with prostate cancer treated to curative dose with external beam radiation therapy between 1997 and 2002 were included in the study. Physical and fractionation-corrected dose-volume descriptors were derived for the femoral heads, pubic bone, and sacrum. Information on skeletal events was collected for the patients and 1661 matched controls through the Prostate Cancer database Sweden. Uni- and multivariable Cox proportional hazard regressions were used to analyze the time to event. ResultsData from 346 patients were available for analysis. The median mean physical dose and corresponding equivalent 2-Gy/fraction dose (EQD2) to the femoral heads were 35.5 Gy and 28.7 Gy, respectively. The median follow-up time was 16.0 years. During the follow up, 12 hip fractures occurred. Hip osteoarthritis was diagnosed in 36 cases, with 29 cases leading to replacement surgery. No increased risk of hip fractures was found. Hip osteoarthritis was the only event for which a statistically significant difference was found between the irradiated cohort and the controls (cause-specific hazard ratio: 1.56; 95% confidence interval, 1.07-2.26; P = .02). The cumulative incidence of osteoarthritis at 10 years was 8.1% and 4.9% in the irradiated cohort and the controls, respectively. A significant relationship between osteoarthritis and the volume of the femoral head receiving ≥40 Gy (ie, EQD2) was found. ConclusionsIn this study of 346 patients treated with conventional radiation therapy, we found no increased risk of hip fracture but an increased risk of clinically relevant osteoarthritis at long-term follow up. Our results indicate a dose–response relationship between osteoarthritis and the volume of the femoral head receiving an EQD2 dose of ≥40 Gy.

Comparative performance and external validation of the multivariable PREDICT Prostate tool for non-metastatic prostate cancer: a study in 69,206 men from Prostate Cancer data Base Sweden (PCBaSe)

BackgroundPREDICT Prostate is an endorsed prognostic model that provides individualised long-term prostate cancer-specific and overall survival estimates. The model, derived from UK data, estimates potential treatment benefit on overall survival. In this study, we externally validated the model in a large independent dataset and compared performance to existing models and within treatment groups.MethodsMen with non-metastatic prostate cancer and prostate-specific antigen (PSA) < 100 ng/ml diagnosed between 2000 and 2010 in the nationwide population-based Prostate Cancer data Base Sweden (PCBaSe) were included. Data on age, PSA, clinical stage, grade group, biopsy involvement, primary treatment and comorbidity were retrieved. Sixty-nine thousand two hundred six men were included with 13.9 years of median follow-up. Fifteen-year survival estimates were calculated using PREDICT Prostate for prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). Discrimination was assessed using Harrell’s concordance (c)-index in R. Calibration was evaluated using cumulative available follow-up in Stata (TX, USA).ResultsOverall discrimination of PREDICT Prostate was good with c-indices of 0.85 (95% CI 0.85–0.86) for PCSM and 0.79 (95% CI 0.79–0.80) for ACM. Overall calibration of the model was excellent with 25,925 deaths predicted and 25,849 deaths observed. Within the conservative management and radical treatment groups, c-indices for 15-year PCSM were 0.81 and 0.78, respectively. Calibration also remained good within treatment groups. The discrimination of PREDICT Prostate significantly outperformed the EAU, NCCN and CAPRA scores for both PCSM and ACM within this cohort overall.A key limitation is the use of retrospective cohort data.ConclusionsThis large external validation demonstrates that PREDICT Prostate is a robust and generalisable model to aid clinical decision-making.

Association of type 2 diabetes mellitus and antidiabetic medication with risk of prostate cancer: a population-based case-control study

BackgroundProstate cancer (PCa) and type 2 diabetes mellitus (T2DM) are prevalent conditions that often occur concomitantly. However, many aspects of the impact of T2DM, particularly the duration of T2DM and antidiabetic medications, on PCa risk are poorly understood.MethodsTo assess the association of duration of T2DM and antidiabetic medication with PCa risk, we designed a matched case-control study, including 31,415 men with PCa and 154,812 PCa-free men in Prostate Cancer data Base Sweden (PCBaSe) 4.1.ResultsOverall, a decreased risk of PCa was observed for men with T2DM (odds ratio (OR): 0.81, 95% confidence interval (CI): 0.78–0.84), as compared to men without T2DM. The decreased risk of PCa was consistently showed across duration of T2DM. With respect to use of antidiabetic drugs, this inverse association with duration was also found for all medications types, as compared to men without T2DM, including insulin, metformin and sulphonylurea (SU) (e.g. 3- < 5 yr insulin OR:0.69, 95%CI:0.60–0.80; 3- < 5 yr metformin OR: 0.82, 95%CI: 0.74–0.91; 3- < 5 yr SU OR: 0.72, 95%CI: 0.62–0.83). When stratifying by PCa risk categories, this decreased risk was most evident for diagnosis of low and intermediate-risk PCa (low-risk OR: 0.65, 95%CI: 0.66–0.70, intermediate-risk OR: 0.80, 95%CI: 0.75–0.85).ConclusionsThe study showed an inverse association between pre-existing T2DM and PCa across different durations of T2DM and all types of T2DM medication received. This inverse association was most evident for low- and intermediate-risk PCa, suggesting that whilst T2DM and its medication may protect some men from developing PCa, the relationship warrants further study.

Incidence of second primary malignancies in metastatic castration-resistant prostate cancer: results from observational studies in three countries.

Aim: This reports some of the first incidence rate (IR) estimates of second primary malignancies (SPMs) in men with metastatic castration-resistant prostate cancer (mCRPC) in three countries. Patients & methods: Claims data from the German Pharmacoepidemiological Research Database; registry data from the Prostate Cancer Data Base Sweden; and combined registry-claims data from the US Surveillance, Epidemiology and End Results-Medicare database were analyzed to obtain overall survival and incidence of SPMs in men with mCRPC. Results: SPMs occurred in 308 German (n = 2360), 273 Swedish (n = 2849) and 172 US (n = 2234) men with mCRPC. IRs of SPMs were 79.0 (95% CI: 70.4-88.4), 101.7 (95% CI: 90.3-114.5) and 59 (95% CI: 50-68) per 1000 person-years in German, Swedish and US cohorts, respectively. Conclusion: These studies report some of the first IR estimates of SPMs in men with mCRPC, providing a historical risk estimate of SPM in this patient population.

Changes in treatment and mortality in men with locally advanced prostate cancer between 2000 and 2016: a nationwide, population-based study in Sweden.

To evaluate whether the effects of radical treatment in men with locally advanced prostate cancer (PCa) on PCa mortality observed in randomised clinical trials are applicable on a population basis. We conducted a population-based cohort study using the Prostate Cancer data Base Sweden of 20350 men diagnosed between 2000 and 2016 with locally advanced PCa, defined as clinical local stage T3/T4, M0, Mx and a prostate-specific antigen level of <100ng/mL. Cumulative PCa mortality was examined using competing risk analysis of all men with locally advanced PCa, and also including men who did not undergo radical treatment. Multivariate regression analysis, including prognostic factors, was used to calculate hazard ratios (HRs) for all-cause and PCa-specific death. The proportion of men treated with primary radical radiotherapy (n=4174) or prostatectomy (n=1210) increased from 15% in 2000-2003, 25% in 2004-2007, 33% in 2008-2011 to 43% in 2012-2016. The corresponding 5-year PCa mortality decreased from 19%, 18%, 17%, to 15% for all men, with the steepest decrease in men aged 65-74years, from 16% to 8%. The risk of PCa mortality in men aged <80years was lower in the last period compared to the first period, with a HR of 0.65 (95% confidence interval 0.56-0.76) in multivariate analysis. The threefold increase in use of radical treatment was accompanied by a modest decrease in PCa mortality in all men with newly diagnosed locally advanced PCa. For men aged 65-74years, there was a 50% decrease in the relative risk of PCa death. This indicates that the benefits previously observed in randomised trials can also be achieved in a real-life setting.

Radical radiotherapy for prostate cancer: patterns of care in Sweden 1998–2016

Introduction: Radiotherapy is an established treatment option for prostate cancer (PCa), both as primary treatment and secondary treatment after radical prostatectomy (RP). Since 1998, detailed data on radiotherapy delivered to Swedish men with PCa (e.g. treatment modalities, absorbed doses, fractionation) have been collated within PCa data Base Sweden (PCBaSe). This study reports patterns of radical radiotherapy for PCa in Sweden over the past two decades.Materials and methods: All men with non-metastatic PCa (1998–2016) who received external beam radiotherapy (EBRT) or high or low dose-rate brachytherapy (HDR-BT/LDR-BT) were identified in PCBaSe. Analyses included: trends in radiation techniques, fractionation patterns and total doses over time; PCa-specific survival comparing treatment in 2007–2017 with 1998–2006; and regional variation in type of primary radiotherapy.Results: About 20,876 men underwent primary radiotherapy. The main treatment modalities include conventionally fractionated (2.0 Gy/fraction) EBRT (51%), EBRT with HDR-BT boost (27%) and hypofractionated (>2.4 Gy/fraction) EBRT (11%). EBRT with photon or proton boost and HDR-BT and LDR-BT monotherapies were each used minimally. Use of dose-escalated EBRT (>74 Gy) and moderate hypofractionation increased over time, while use of HDR-BT declined. Considerable regional variation in treatment modalities was apparent. Risk of PCa death following primary radiotherapy had declined for intermediate-risk (HR: 0.60; 95%CI 0.47–0.87) and high-risk PCa (HR: 0.72; 95%CI 0.61-0.86).Discussion: Increased use of dose escalation and hypofractionated EBRT has occurred in Sweden over the past two decades, reflecting current evidence and practice guidelines. Disease-specific outcomes have also improved. Data collected in PCBaSe provide an excellent resource for further research into RT use in PCa management.

Spironolactone use is associated with lower prostate cancer risk: a population-wide case-control study.

Spironolactone, a cheap effective diuretic used to manage hypertension and heart failure, also has anti-androgenic effects through its non-selective binding to steroid receptors, and hence may affect prostate cancer (PCa) risk. This study investigated the association between spironolactone use and PCa risk. For comparison, we also examined associations with thiazide diuretics which do not have anti-androgenic properties. A matched case-control study was undertaken using population-wide data from the Prostate Cancer Data Base Sweden (PCBaSe). All PCa cases diagnosed from 2014 to 2016 were matched by birth year and county with PCa-free controls selected from the general population (1:5). Multivariable conditional logistic regression was used to examine associations between spironolactone use (dose and duration) and PCa risk, and similarly for thiazides. Three percent of the 31,591 cases and 4% of the 156,802 controls had been prescribed spironolactone. Multivariable analyses indicated reduced risk of PCa among those ever exposed to spironolactone (odds ratio [OR] 0.83; 95% confidence interval [CI]: 0.76-0.89), with a stronger association for current users (OR: 0.77, 95% CI: 0.69-0.86) than past users (OR: 0.88; 95% CI: 0.79-0.97) and decreasing risk with increasing dose (p-trend < 0.001). No association was observed for thiazide exposure and PCa risk. Biases due to differences in prescribing patterns or frequency of PSA testing may have influenced these findings. PCa risk was reduced among men exposed to the diuretic spironolactone. Further investigation of spironolactone's potential chemopreventive effects is warranted.

Duration of sick leave after active surveillance, surgery or radiotherapy for localised prostate cancer: a nationwide cohort study

ObjectivesTo compare the loss of working time due to sick leave by treatment strategy for localised prostate cancer.DesignNationwide cohort study.SettingSweden.ParticipantsA total of 15 902 working-aged men with localised low or...

Overall survival and second primary malignancies in men with metastatic prostate cancer.

BackgroundAmong prostate cancer (PC) patients, over 90% of distant metastases occur in the bone. PC treatments may be associated with side effects, including second primary malignancies (SPM). There is limited information on the incidence of SPM among men with bone metastatic PC (mPC) and among men with bone metastatic castration-resistant PC (mCRPC). We estimated overall survival and the incidence of SPM in men with mPC and mCRPC.MethodsIn the Prostate Cancer data Base Sweden, the National Prostate Cancer Register was linked to other national health care registers, 15,953 men with mPC in 1999–2011 were identified. Further, 693 men with mCRPC were identified. Outcomes were evaluated using stratified incidence rates, Kaplan-Meier estimators and Cox models.ResultsThe mean age among men with mPC was 73.9 years and in men with mCRPC 70.0 years. The median respective survivals were 1.5 (13,965 deaths) and 1.14 years (599 deaths), and average times since PC diagnosis 1.8 and 4.7 years. We observed 2,669 SPMs in men with mPC and 100 SPMs in men with mCRPC. The incidence rate of SPM per 1,000 person-years was 81.8 (78.8–85.0) for mPC and 115.6 (95.1–140.7) for mCRPC. High age, prior neoplasms, urinary tract infection, congestive heart failure, diabetes and renal disease were most strongly associated with increased mortality risk. Prior neoplasms and prior use of antineoplastic agents were most strongly associated with increased SPM risk. Several factors associated with increased mortality and SPM risks were more prevalent in the mCRPC cohort.ConclusionsOur results on mortality for men with mPC and mCRPC are in line with previous studies from the same time period. Investigation of factors associated with mortality and SPM in men with mPC and mCRPC can help to further understand these outcomes in the era prior to several new treatments have come available.

Comparative Effectiveness of Different Radical Radiotherapy Treatment Regimens for Prostate Cancer: A Population-Based Cohort Study.

BackgroundIt is unclear which radiotherapy technique and dose fractionation scheme is most effective in decreasing the risk of prostate cancer death.MethodsWe conducted a population-based cohort study among 15 164 men in the Prostate Cancer database Sweden (version 4.0) treated with primary radical radiotherapy for prostate cancer in Sweden from 1998 to 2016. We calculated hazard ratios with 95% confidence intervals (CIs) of the association between the following exposure groups and outcome: conventionally fractionated external beam radiotherapy (EBRT) to 78 Gy (39 × 2 Gy), EBRT combined with high dose-rate brachytherapy (HDR-BT) (25 × 2 Gy + 2 × 10 Gy), conventionally fractionated EBRT to 70 Gy (35 × 2 Gy), and moderately hypofractionated (M-HF) dose-escalated EBRT (29 × 2.5 Gy or 22 × 3 Gy).ResultsOf the men, 7296 received conventionally fractionated EBRT to 78 Gy, 4657 EBRT combined with HDR-BT, 1672 conventionally fractionated EBRT to 70 Gy, and 1539 M-HF EBRT. Using EBRT to 78 Gy as the reference, the multivariable hazard ratios (95% CIs) of prostate cancer death was 0.64 (0.53 to 0.78) for EBRT combined with HDR-BT, 1.00 (0.80 to 1.27) for EBRT to 70 Gy, and 1.51 (0.99 to 2.32) for M-HF EBRT. The multivariable hazard ratios (95% CIs) for death from any cause were 0.79 (0.71 to 0.88), 0.99 (0.87 to 1.14), and 1.12 (0.88 to 1.42), respectively. The lower risk of prostate cancer death comparing EBRT combined with HDR-BT with conventionally fractionated EBRT to 78 Gy was more pronounced for men with high-risk or poorly differentiated tumors.ConclusionsIn this study, EBRT combined with HDR-BT was the most effective radiotherapy treatment regimen, especially for poorly differentiated tumors. Randomized trials comparing EBRT combined with HDR-BT with dose-escalated EBRT should be a priority.

Prostate cancer in kidney transplant recipients - a nationwide register study.

To investigate whether post-transplantation immunosuppression negatively affects prostate cancer outcomes in male kidney transplant recipients. We used the Swedish Renal Register and the National Prostate Cancer Register to identify all kidney transplantation recipients diagnosed with prostate cancer in Sweden 1998-2016. After linking these registers with Prostate Cancer Database Sweden (PCBaSe), a case-control study was designed to compare time period and risk category-specific probabilities of a prostate cancer diagnosis amongst kidney transplantation recipients versus the male general population. The registers did not include information about the specific immunosuppression agent used in all transplantation recipients. Data from PCBaSe were used to compare prostate cancer characteristics at diagnosis and survival for patients with prostate cancer with versus without a kidney transplant. Propensity score matching, Cox regression analysis and Fisher's exact test were used and 95% confidence intervals (CIs) calculated. Almost half of the 133 kidney transplantation recipients were transplanted before the mid-1990s, when PSA testing became common. The transplant recipients were not more likely than age-matched control men to be diagnosed with any (odds ratio [OR] 0.84, 95% CI 0.70-0.99) or high-risk or metastatic prostate cancer (OR 0.84, 95% CI 0.62-1.13). None of the ORs for the different categories of prostate cancer increased with time since transplantation. Cancer characteristics at the time of diagnosis and cancer-specific survival were similar amongst transplant recipients and the control group of 665 men diagnosed with prostate cancer without a kidney transplant. This Swedish nationwide, register-based study gave no indication that immunosuppression after kidney transplantation increases the risk of prostate cancer or adversely affects prostate cancer outcomes. The study suggests that men with untreated low-grade prostate cancer can be accepted for transplantation.

Prediction of metastatic prostate cancer by prostate-specific antigen in combination with T stage and Gleason Grade: Nationwide, population-based register study.

The objective was to investigate the proportion of men with metastatic prostate cancer in groups defined by T stage, Gleason Grade Group (GGG) and serum levels of prostate-specific antigen (PSA) and if PSA can be used to rule in metastatic prostate cancer when combined with T stage and GGG. We identified 102,076 men in Prostate Cancer data Base Sweden 4.0 who were diagnosed with prostate cancer in 2006-2016. Risk of metastases was assessed for PSA stratified on T stage and five-tiered GGG. For men who had not undergone bone imaging, we used multiple imputation to classify metastatic prostate cancer. Advanced T stage, high GGG and high PSA were related to bone metastases. For example: only 79/38 190 (0.2%) of men with T1-2 and GGG 1 had PSA above 500 ng/mL, and 29/79 (44%) of these men had metastases; whereas 1 154/7 018 (16%) of men with T3-4 and GGG 5 had PSA above 500 ng/ml and 1 088/1 154 (94%) of these men had metastases. However, no PSA cut-off could accurately identify the majority of men with metastatic prostate cancer (i.e. high sensitivity) while also correctly classifying most men without metastasis (i.e. high specificity). In conclusion, these results support the use of imaging to confirm bone metastases in men with advanced prostate cancer as no PSA level in combination with T stage and GGG could accurately rule in metastatic prostate cancer and thereby safely omit bone imaging.

Long-term adherence to GnRH agonists in men with prostate cancer. A nation-wide population-based study in prostate cancer data base Sweden

Aim: Gonadotropin-releasing hormone (GnRH) agonists are used to treat men with prostate cancer (PCa). To date, no study has fully assessed patterns of adherence to GnRH agonists. We investigated patterns of adherence to GnRH agonists using data from Prostate Cancer data Base Sweden (PCBaSe).Methods: PCBaSe links the National Prostate Cancer Register (NPCR) Sweden to other healthcare registers and demographic databases. Men on primary or secondary GnRH agonists between 2006–2013 entered the study 45 days after GnRH agonists’ initiation (run-in period) and exited at 3 years. Medication possession ratio quantified adherents (≥80%). Multivariable logistic regression models included age, injection interval, PCa risk categories, Charlson Comorbidity Index, prior PCa treatment, civil status and year of GnRH initiation. Odds ratios (OR) and 95% confidence intervals (CI) expressed odds of adherence.Results: Men on primary GnRH agonists (n = 8,105) were more adherent with increasing age (75–84 years compared to ≤65 years OR: 1.49; 95% CI: 1.23–1.81), longer injection intervals (365 days compared to 90 days OR: 3.29; 95% CI: 2.52–4.30) and higher PCa risk categories at diagnosis (distant metastasis compared to low risk PCa OR: 3.56; 95% CI: 2.54–5.00). Men on secondary GnRH agonists (n = 4,738) were more adherent with increasing age (≥85 years compared to ≤65 years OR: 1.65; 95% CI: 1.23–2.22) and prior PCa treatment (anti-androgens compared to deferred treatment OR: 1.50; 95% CI: 1.23–1.82), (radiotherapy compared to deferred treatment OR: 1.35; 95% CI: 1.11–1.64).Conclusions: Longer injection intervals could be addressed in the clinical setting to improve adherence.