RESUMO
OBJECTIVE: To quantify the ability of two new comorbidity indices to adjust for confounding, by benchmarking a target trial emulation against the randomized controlled trial result. STUDY DESIGN AND SETTING: Observational study including 18 316 men from Prostate Cancer data Base Sweden 5.0, diagnosed with prostate cancer between 2008 and 2019 and treated with primary radical prostatectomy (n=14 379) or radiotherapy (n=3937). The effect on adjusted risk of death from any cause after adjustment for comorbidity by use of two new comorbidity indices, the Multidimensional Diagnosis-based Comorbidity Index (MDCI) and the Drug Comorbidity Index (DCI), were compared to adjustment for the Charlson Comorbidity Index (CCI). RESULTS: Risk of death was higher after radiotherapy than radical prostatectomy (HR=1.94; 95% CI: 1.70 - 2.21). The difference decreased when adjusting for age, cancer characteristics, and CCI (HR=1.32, 95% CI: 1.06 - 1.66). Adjustment for the two new comorbidity indices further attenuated the difference (HR 1.14, 95% CI 0.91 - 1.44). Emulation of a hypothetical pragmatic trial where also older men with any type of baseline comorbidity were included, largely confirmed these results (HR 1.10; 95% CI 0.95 - 1.26). CONCLUSIONS: Adjustment for comorbidity using two new indices provided comparable risk of death from any cause in line with results of a randomized controlled trial. Similar results were seen in a broader study population, more representative of clinical practice.
RESUMO
BACKGROUND: Socioeconomic inequalities in the uptake of colorectal cancer screening are well documented, but the implications on inequities in health gain remain unclear. METHODS: Sixty-year-olds were randomly recruited from the Swedish population between March 2014 and March 2020 and invited to undergo either 2 rounds of fecal immunochemical testing (FIT) 2 years apart (n = 60â137) or primary colonoscopy just once (n = 30â400). By linkage to Statistics Sweden's registries, we obtained socioeconomic data. In each defined socioeconomic group, we estimated the cumulative yield of advanced neoplasia in each screening arm (intention-to-screen analysis). In the biennial FIT arm, we predicted the probability of exceeding the yield in the primary colonoscopy arm by linear extrapolation of the cumulative yield to (hypothetical) additional rounds of FIT. RESULTS: In the lowest income group, the yield of advanced neoplasia was 1.63% (95% confidence interval [CI] = 1.35% to 1.93%) after 2 rounds of FIT vs 1.93% (95% CI = 1.49% to 2.40%) in the primary colonoscopy arm. Extrapolation to a third round of FIT implied a 86% probability of exceeding the yield in the primary colonoscopy arm. In the highest income group, we found a more pronounced yield gap between the 2 screening strategies-2.32% (95% CI = 2.15% to 2.49%) vs 3.71% (95% CI = 3.41% to 4.02%)- implying a low (2%) predicted probability of exceeding yield after a third round of FIT. CONCLUSIONS: Yield of advanced neoplasia from 2 rounds of FIT 2 years apart was poorer as compared with primary colonoscopy, but the difference was less in lower socioeconomic groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02078804.
Assuntos
Colonoscopia , Neoplasias Colorretais , Detecção Precoce de Câncer , Sangue Oculto , Humanos , Neoplasias Colorretais/diagnóstico , Colonoscopia/estatística & dados numéricos , Detecção Precoce de Câncer/métodos , Pessoa de Meia-Idade , Masculino , Feminino , Suécia , Idoso , Fatores Socioeconômicos , Fezes/química , Renda , Disparidades em Assistência à Saúde , ImunoquímicaRESUMO
BACKGROUND: We determined the impact of an increased two-stool faecal immunochemical test (FIT) cut-off on colonoscopy positivity and relative sensitivity and specificity in the randomized controlled screening trial screening of Swedish colons conducted in Sweden. METHODS: We performed a cross-sectional analysis of participants in the FIT arm that performed FIT between March 2014 and 2020 within the study registered with ClinicalTrials.gov, NCT02078804, who had a faecal haemoglobin concentration of at least 10 µg/g in at least one of two stool samples and who underwent a colonoscopy (n = 3841). For each increase in cut-off, we computed the positive predictive value (PPV), numbers needed to scope (NNS), sensitivity and specificity for finding colorectal cancer (CRC) and advanced neoplasia (AN; advanced adenoma or CRC) relative to cut-off 10 µg/g. RESULTS: The PPV for AN increased from 23.0% (95% confidence intervals [CI]: 22.3%-23.6%) at cut-off 10 µg/g to 28.8% (95% CI: 27.8%-29.7%) and 33.1% (95% CI: 31.9%-34.4%) at cut-offs 20 and 40 µg/g, respectively, whereas the NNS to find a CRC correspondingly decreased from 41 to 27 and 19. The PPV for AN was higher in men than women at each cut-off, for example 31.5% (95% CI: 30.1%-32.8%) in men and 25.6% (95% CI: 24.3%-27.0%) in women at 20 µg/g. The relative sensitivity and relative specificity were similar in men and women at each cut-off. CONCLUSION: A low cut-off of around 20-40 µg/g allows detection and removal of many AN compared to 10 µg/g while reducing the number of colonoscopies in both men and women.
Assuntos
Colonoscopia , Neoplasias Colorretais , Detecção Precoce de Câncer , Sangue Oculto , Sensibilidade e Especificidade , Humanos , Estudos Transversais , Feminino , Masculino , Neoplasias Colorretais/diagnóstico , Pessoa de Meia-Idade , Detecção Precoce de Câncer/métodos , Idoso , Suécia , Fezes/química , Hemoglobinas/análise , Valor Preditivo dos Testes , Adenoma/diagnóstico , ImunoquímicaRESUMO
BACKGROUND AND AIMS: One out of three men who undergo cystoprostatectomy for bladder cancer is diagnosed with incidental prostate cancer (PCa) at histopathological examination. Many of these men are PSA tested as part of their follow-up, but it is unclear if this is needed. The aim of this study was to assess the risk of PCa death in these men and the need of PSA-testing during follow-up. METHODS: Between 2002 and 2020, 1,554 men were diagnosed with PCa after cystoprostatectomy performed for non-metastatic bladder cancer and registered in the National Prostate Cancer Register (NPCR) of Sweden. We assessed their risk of death from PCa, bladder cancer and other causes up to 15 years after diagnosis by use of data in The Cause of Death Register. The use of androgen deprivation therapy (ADT) as a proxy for PCa progression was assessed by fillings in The Prescribed Drug Register. RESULTS: Fifteen years after diagnosis, cumulative incidence of death from PCa was 2.6% (95% CI 2.3%-2.9%), from bladder cancer 32% (95% CI: 30%-34%) and from other causes 40% (95% CI: 36%-44%). Only 35% of men with PCa recorded as primary cause of death in The Cause of Death Register had started ADT before date of death, indicating sticky-diagnosis bias with inflated risk of PCa death. CONCLUSIONS: For a large majority of men diagnosed with incidental PCa at cystoprostatectomy performed for bladder cancer, the risk of PCa death is very small so there is no rationale for PSA testing during follow-up.
Assuntos
Cistectomia , Prostatectomia , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/mortalidade , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Prostatectomia/métodos , Idoso , Suécia/epidemiologia , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Medição de Risco , Idoso de 80 Anos ou mais , Achados IncidentaisRESUMO
Assessment of comorbidity is crucial for confounding adjustment and prediction of mortality in register-based studies, but the commonly used Charlson comorbidity index is not sufficiently predictive. We aimed to develop a multidimensional diagnosis-based comorbidity index (MDCI) that captures comorbidity better than the Charlson Comorbidity index. The index was developed based on 286,688 men free of prostate cancer randomly selected from the Swedish general population, and validated in 54,539 men without and 68,357 men with prostate cancer. All ICD-10 codes from inpatient and outpatient discharges during 10 years prior to the index date were used to define variables indicating frequency of code occurrence, recency, and total duration of related hospital admissions. Penalized Cox regression was used to predict 10-year all-cause mortality. The MDCI predicted risk of death better than the Charlson comorbidity index, with a c-index of 0.756 (95% confidence interval [CI] = 0.751, 0.762) vs 0.688 (95% CI = 0.683, 0.693) in the validation cohort of men without prostate cancer. Men in the lowest vs highest MDCI quartile had distinctively different survival in the validation cohort of men with prostate cancer, with an overall hazard ratio [HR] of 5.08 (95% CI = 4.90, 5.26). This was also consistent within strata of age and Charlson comorbidity index, e.g. HR = 5.90 (95% CI = 4.65, 7.50) in men younger than 60 years with CCI 0. These results indicate that comorbidity assessment in register-based studies can be improved by use of all ICD-10 codes and taking related frequency, recency, and duration of hospital admissions into account.
Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/epidemiologia , Comorbidade , Modelos de Riscos Proporcionais , Suécia/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Data on functional and psychological side effects following curative treatment for prostate cancer are lacking from large, contemporary, unselected, population-based cohorts. OBJECTIVE: To assess urinary symptoms, bowel disturbances, erectile dysfunction (ED), and quality of life (QoL) 12 mo after robot-assisted radical prostatectomy (RARP) and radiotherapy (RT) using patient-reported outcome measures in the Swedish prostate cancer database. DESIGN, SETTING, AND PARTICIPANTS: This was a nationwide, population-based, cohort study in Sweden of men who underwent primary RARP or RT between January 1, 2018 and December 31, 2020. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Absolute proportions and odds ratios (ORs) were calculated using multivariable logistic regression, with adjustment for clinical characteristics. RESULTS AND LIMITATIONS: A total of 2557 men underwent RARP and 1741 received RT. Men who underwent RT were older (69 vs 65 yr) and had more comorbidities at baseline. After RARP, 13% of men experienced incontinence, compared to 6% after RT. The frequency of urinary bother was similar, at 18% after RARP and 18% after RT. Urgency to defecate was reported by 14% of men after RARP and 34% after RT. At 1 yr, 73% of men had ED after RARP, and 77% after RT. High QoL was reported by 85% of men after RARP and 78% of men after RT. On multivariable regression analysis, RT was associated with lower risks of urinary incontinence (OR 0.25, 95% confidence interval [CI] 0.19-0.33), urinary bother (OR 0.79, 95% CI 0.66-0.95), and ED (OR 0.54, 95% CI 0.46-0.65), but higher risk of bowel symptoms (OR 2.86, 95% CI 2.42-3.39). QoL was higher after RARP than after RT (OR 1.34, 95% CI 1.12-1.61). CONCLUSIONS: Short-term specific side effects after curative treatment for prostate cancer significantly differed between RARP and RT in this large and unselected cohort. Nevertheless, the risk of urinary bother was lower after RT, while higher QoL was common after RARP. PATIENT SUMMARY: In our study of patients treated for prostate cancer, urinary bother and overall quality of life are comparable at 1 year after surgical removal of the prostate in comparison to radiotherapy, despite substantial differences in other side effects.
Assuntos
Disfunção Erétil , Medidas de Resultados Relatados pelo Paciente , Prostatectomia , Neoplasias da Próstata , Qualidade de Vida , Sistema de Registros , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Prostatectomia/efeitos adversos , Idoso , Pessoa de Meia-Idade , Disfunção Erétil/etiologia , Disfunção Erétil/epidemiologia , Suécia/epidemiologia , Estudos de Coortes , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Radioterapia/efeitos adversos , Fatores de Tempo , Incontinência Urinária/etiologia , Incontinência Urinária/epidemiologiaRESUMO
BACKGROUND: Fewer adenomas are detected at colonoscopy in women compared to men and failure to detect adenomas and sessile serrated polyps is associated with an increased risk of post-colonoscopy colorectal cancer. The aim of this study was to investigate whether this was in part due to the greater difficulty of conducting colonoscopy in women, with the difference being more apparent in colonoscopies conducted by less skilled endoscopists. MATERIAL AND METHODS: Cross-sectional exploratory analysis of data on 16,551 individuals undergoing a primary colonoscopy (PCOL group) or colonoscopy after positive faecal immunochemical test (FIT group) within the randomized controlled trial SCREESCO. Endoscopist adenoma detection rate (ADR; low or high) was determined based on each endoscopist's colonoscopies performed in SCREESCO. In each study group, the relationship between the sex difference in colonoscopy outcome and endoscopist ADR was assessed using multiplicative interaction tests. RESULTS: Endoscopists performed equally many colonoscopies in men and women (median 52% men). There were no signs of effect modification of the risk ratio of any finding (men vs women) by endoscopist ADR in the PCOL group (p = 0.33) or the FIT group (p = 0.30). The proportion of incomplete index colonoscopies was lower in men than in women in both groups and there was no effect modification by endoscopist ADR in either the PCOL group (p = 0.41) or the FIT group (p = 0.96). CONCLUSIONS: This study provides no evidence that endoscopist skill measured by ADR underlies the sex difference in adenoma detection at colonoscopy. This study has trial number NCT02078804 and is registered with ClinicalTrials.gov.
Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Pólipos , Humanos , Feminino , Masculino , Estudos Transversais , Caracteres Sexuais , Colonoscopia , Adenoma/diagnóstico , Detecção Precoce de Câncer , Neoplasias Colorretais/diagnóstico , Pólipos do Colo/diagnósticoRESUMO
Importance: Recently, life-prolonging treatments for patients with advanced prostate cancer have been introduced in clinical practice. Objective: To investigate if the introduction of doublet therapy is associated with changes in survival on a population-basis. Design, Setting, and Participants: 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. Exposure: The proportion of men with mCSPC who received doublet therapy, ie, androgen deprivation therapy plus androgen receptor pathway inhibitor drugs or chemotherapy was assessed. Main Outcomes and Measures: Standardized overall survival, taking age, comorbidity, and cancer characteristics into consideration, was estimated by use of a parametric survival model. Results: A total of 11â¯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. Conclusions and Relevance: 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.
Assuntos
Neoplasias da Próstata , Masculino , Humanos , Idoso , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/uso terapêutico , Estudos de Coortes , Antígeno Prostático Específico , Antagonistas de Receptores de Andrógenos/uso terapêuticoRESUMO
We consider the analysis of longitudinal data of multiple types of events where some of the events are observed on a coarser level (e.g. grouped) at some time points during the follow-up, for example, when certain events, such as disease progression, are only observable during parts of follow-up for some subjects, causing gaps in the data, or when the time of death is observed but the cause of death is unknown. In this case, there is missing data in key characteristics of the event history such as onset, time in state, and number of events. We derive the likelihood function, score and observed information under independent and non-informative coarsening, and conduct a simulation study where we compare bias, empirical standard errors, and confidence interval coverage of estimators based on direct maximum likelihood, Monte Carlo Expectation Maximisation, ignoring the coarsening thus acting as if no event occurred, and artificial right censoring at the first time of coarsening. Longitudinal data on drug prescriptions and survival in men receiving palliative treatment for prostate cancer is used to estimate the parameters of one of the data-generating models. We demonstrate that the performance depends on several factors, including sample size and type of coarsening.
Assuntos
Neoplasias da Próstata , Masculino , Humanos , Funções Verossimilhança , Simulação por Computador , Progressão da Doença , Modelos Estatísticos , Método de Monte CarloRESUMO
OBJECTIVES: To study how handling missing data on M stage in a clinical cancer register affects estimates of incidence of metastatic prostate cancer. STUDY DESIGN AND SETTING: Estimates of age-standardized incidence of metastatic prostate cancer were obtained by the use of data in a population-based clinical cancer register in Sweden and using four methods for imputation of missing M stage. Adjusted survival was used to compare men with known and imputed M stage. RESULTS: The proportion of men with missing M stage was high (66%) and varied according to the risk group and over calendar time. The estimated incidence of metastatic disease varied depending on imputation method, with all methods indicating a decreasing incidence over time. A combination of deterministic imputation (DI) and multiple imputation (MI) produced adjusted survival curves for men with imputed M stage that best resembled the survival for men with known M stage. CONCLUSIONS: Plausible estimates of incidence of metastatic prostate cancer in clinical cancer registers can be obtained by the use of a combination of DI of missing M stage and MI.
Assuntos
Neoplasias da Próstata , Masculino , Humanos , Incidência , Neoplasias da Próstata/epidemiologia , Coleta de Dados , Sistema de Registros , Fatores de RiscoRESUMO
AIM: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Assuntos
Neoplasias Ósseas , Fraturas Ósseas , Neoplasias de Próstata Resistentes à Castração , Rádio (Elemento) , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Rádio (Elemento)/uso terapêutico , Suécia/epidemiologia , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/tratamento farmacológico , Estudos RetrospectivosRESUMO
The main aim of the study was to determine the impact of diagnostic activity and life expectancy on the lifetime risk of a prostate cancer diagnosis. We used a state transition simulation model based on Swedish population-based data to simulate life trajectories for 2,000,000 men from age 40 to 100 in order to estimate the lifetime risk of a prostate cancer diagnosis. Risk estimates were determined by the level of diagnostic activity and estimated life expectancy. Higher exposure to diagnostic activity resulted in more prostate cancer diagnoses. This was especially true for men diagnosed with low or intermediate grade disease. Men exposed to high diagnostic compared to low diagnostic activity had a five-fold increased lifetime risk (22% vs. 5%) of being diagnosed with a low or intermediate-risk prostate cancer and half the risk of being diagnosed with a high-risk prostate cancer (6% vs. 13%). Men with a long life expectancy had a higher lifetime risk of a prostate cancer diagnosis both overall (21% vs. 15%) and in all risk categories when compared to men with a short life expectancy. The lifetime risk of a prostate cancer diagnosis is strongly influenced by diagnostic activity and to a lesser degree by life expectancy.
Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Pelve , Expectativa de Vida , Simulação por ComputadorRESUMO
Background: Little is known about disease trajectories for men with castration-resistant prostate cancer (CRPC). Objective: To create a state transition model that estimates time spent in the CRPC state and its outcomes. Design setting and participants: The model was generated using population-based prostate-specific antigen data from 40% of the Swedish male population, which were linked to nationwide population-based databases. We compared the observed and predicted cumulative incidence of transitions to and from the CRPC state. Outcome measurements and statistical analysis: We measured time spent in the CRPC state and the proportion of men who died of prostate cancer during follow-up by CRPC risk category. Results and limitations: Time spent in the CRPC state varied from 1.1 yr for the highest risk category to 3.9 yr for the lowest risk category. The proportion of men who died from prostate cancer within 10 yr ranged from 93% for the highest risk category to 54% for the lowest. There was good agreement between the model estimates and observed data. Conclusions: There is large variation in the time spent in the CRPC state, varying from 1 yr to 4 yr according to risk category. Patient summary: It is possible to accurately estimate the disease trajectory and duration for men with castration-resistant prostate cancer.
RESUMO
BACKGROUND AND AIM: Colonoscopy quality, including lesion detectability, is variable, and factors influencing lesion detection are not fully understood. This study investigated lesion detection rates during colonoscopies and the associated factors in the SCREEning of Swedish COlons (SCREESCO) study. METHODS: In this cross-sectional analysis of data from SCREESCO, a large-scale randomized controlled trial of colorectal cancer screening in the Swedish population aged 60 years, we assessed data of first-time colonoscopies performed in both colonoscopy and fecal immunochemical test (FIT) arms. RESULTS: This study included 16 552 individuals. The adenoma detection rate was 23.9% and 37.8% in colonoscopy and FIT arms, respectively. Regarding colonoscopy procedures, a withdrawal time ≥ 6 min was associated with higher detection rates of advanced adenomas (adjusted odds ratio [AOR] 2.474, 95% confidence interval [CI] 1.295-4.723), adenomas (2.181, 1.515-3.140), and proximal serrated lesions (pSLs) (1.713, 1.007-2.915). Antispasmodic use was associated with higher detection rates of these lesions and sessile serrated lesions (SSLs) (AOR, 95% CI: 1.523, 1.295-1.791; 1.361, 1.217-1.522; 1.450, 1.247-1.687; and 1.810, 1.512-2.167, respectively). Insertion time > 20 min was related to lower detection rates of adenomas, pSLs, and SSLs (AOR, 95% CI: 0.753, 0.639-0.887; 0.640, 0.495-0.828; and 0.704, 0.518-0.955, respectively). The relationship between a recent period and higher detection rates of pSLs and SSLs was also demonstrated. CONCLUSION: Lesion detectability in SCREESCO was mostly acceptable with room for improvement. In addition to sufficient withdrawal time, antispasmodic use and acquiring skills enabling short insertion time may improve lesion detection. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02078804.
Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Humanos , Estudos Transversais , Parassimpatolíticos , Suécia/epidemiologia , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/patologia , Detecção Precoce de Câncer/métodos , Pólipos do Colo/diagnóstico , Pólipos do Colo/epidemiologia , Pólipos do Colo/patologiaRESUMO
Background: Attempts to reduce prostate cancer (PC) mortality require an understanding of temporal changes in the characteristics of men with lethal PC. Objective: To describe the diagnostic characteristics of and time trends for a nationwide population-based cohort of Swedish men who died from PC between 1992 and 2016. Design setting and participants: Men with PC as the underlying cause of death from 1992 to 2016 according to the Swedish Cause of Death Register were included in the study. Characteristics at diagnosis were collected via links to other nationwide registries using personal identity numbers. Outcome measurements and statistical analysis: Data on disease duration, age at death, and risk category were analyzed. Missing data for risk categories for men with an early date of PC diagnosis were imputed according to the method of chained equations. Results and limitations: Between 1992 and 2016, age-standardized PC mortality decreased by 25%. Median PC disease duration increased from 3.3 yr (interquartile range [IQR] 1.6-6.3) to 5.9 yr (IQR 2.5-10.3) and the median age at death from PC increased from 78.9 yr (IQR 73.3-84.2) to 82.2 yr (IQR 75.2-87.5). The proportion of men with localized disease at diagnosis who died from PC increased from 34% to 48%, while the rate of distant metastases at diagnosis decreased from 56% to 42%. The rate of distant metastases at diagnosis was highest among the youngest men. Treatment trajectories could not be described owing to the large proportion of missing data before the start of registration in the National Prostate Cancer Registry. Conclusion: Age-standardized PC mortality has decreased substantially since 1992. However, there is still a high proportion of men who die from PC who had localized disease at diagnosis, which indicates that more attention is needed to identify the underlying causes to prevent disease progression. Since the proportion of men with distant metastases at diagnosis remains high, early detection of lethal tumors is essential to further reduce PC mortality. Patient summary: We investigated the characteristics of men who died from prostate cancer in Sweden between 1992 and 2016. We found that men with lethal prostate cancer live longer and are older when they die today in comparison to men who died at the beginning of the study period. However, the proportion of men with distant metastases at diagnosis remains high, which is why early detection of lethal tumors is essential to reduce mortality.
RESUMO
Objectives: To predict castration-resistant prostate cancer (CRPC) and prostate cancer (Pca) death by use of clinical variables at Pca diagnosis and PSA levels after start of gonadotropin-releasing hormone agonists (GnRH) in men with non-metastatic castration sensitive prostate cancer (nmCSPC).Materials and Methods: PSA values for 1603 men with nmCSPC in the National Prostate Cancer Register of Sweden who received GnRH as primary treatment were retrieved from Uppsala-Örebro PSA Cohort and Stockholm PSA and Biopsy Register. All men had measured PSA before (pre-GnRH PSA) and 3-6 months after (post-GnRH PSA) date of start of GnRH. Unadjusted and adjusted Cox models were used to predict CRPC by PSA levels. PSA levels and ISUP grade were used to construct a risk score to stratify men by tertiles according to risk of CRPC and Pca death.Results: 788 (49%) men reached CRPC and 456 (28%) died of Pca during follow-up. Post-GnRH PSA predicted CRPC regardless of pre-GnRH PSA. CRPC risk increased with higher post-GnRH PSA, HR 4.7 (95% CI: 3.4-6.7) for PSA > 16 ng/mL vs 0-0.25 ng/mL and with ISUP grade, HR 3.7 (95%: 2.5-5.4) for ISUP 5 vs ISUP 1. Risk of Pca death in men above top vs bellow bottom tertile of post-GnRH PSA and ISUP grade was HR 4.1 (95% CI: 3.0-5.5).Conclusion: A risk score based on post-GnRH PSA and ISUP grade could be used for early identification of a target group for future clinical trials on additional therapy to GnRH.
Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Masculino , Orquiectomia , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológicoRESUMO
Objectives: The objective of this study is to find clinical variables that predict the prognosis for men with castration-resistant prostate cancer (CRPC) in a Swedish real-life CRPC cohort, including a risk group classification to clarify the risk of succumbing to prostate cancer. This is a natural history cohort representing the premodern drug era before the introduction of novel hormonal drug therapies. Methods: PSA tests from the clinical chemistry laboratories serving health care in six regions of Sweden were retrieved and cross-linked to the National Prostate Cancer Registry (NPCR) to identify men with a prostate cancer diagnosis. Through further cross-linking with data sources at the Swedish Board of Health and Welfare, we retrieved other relevant information such as prescribed drugs, hospitalizations, and cause of death. Men entered the CRPC cohort at the first date of doubling of their PSA nadir value with the last value being >2 ng/ml, or an absolute increase of >5 ng/ml or more, whilst on 3 months of medical castration or if they had been surgically castrated (n = 4098). By combining the two variables with the largest C-statistics, "PSA at time of CRPC" and "PSA doubling time," a risk group classification was created. Results: PSA-DT and PSA at date of CRPC are the strongest variables associated with PC specific survival. At the end of follow-up, the proportion of men who died due to PC was 57%, 71%, 81%, 86%, and 89% for risk categories one through five, respectively. The median overall survival in our cohort of men with CRPC was 1.86 years (95% CI: 1.79-1.97). Conclusion: For a man with castration-resistant prostate cancer, there is a high probability that this will be the main cause contributing to his death. However, there is a significant difference in mortality that varies in relation to tumor burden assessed as PSA doubling time and PSA at time of CRCP. This information could be used in a clinical setting when deciding when to treat more or less aggressively once entering the CRPC phase of the disease.