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- Westerberg, Marcus
(författare)
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Modelling short and long term consequences of changes in diagnostic activity and treatment
- 2020
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Since the late 90’s the diagnostic activity for prostate cancer has increased in Sweden, primarily due to increased use of PSA testing, and this has led to a large increase in diagnoses. Simultaneously, there have been changes in treatment strategies, and more effective treatments have been introduced. This thesis aims to increase the understanding of short and long term consequences of these changes by use of high quality data on virtually all men diagnosed with prostate cancer in Sweden.In paper I, the survival of men with metastatic prostate cancer at diagnosis was investigatedby use of survival models, including Kaplan-Meier analyses and Cox proportional hazards regression.The median survival from diagnosis increased with 6 months when comparing mendiagnosed 1998-2001 with men diagnosed 2010-2015, and the risk of death decreased with 13%, while median levels of prostate specific antigen at diagnosis dropped with up to 50%.In paper II, the interplay between diagnostic activity, incidence and risk of death by prostate cancer was modelled using a discrete time model. Data on diagnostic activity, e.g. in termsof testing frequencies, was not available and therefore a proxy for the diagnostic activity wasused. The hazards were estimated within the framework of generalized additive models. Two simulations were performed, assuming low and high diagnostic activity respectively, to compare incidence and mortality from 2017-2060. Higher diagnostic activity, compared to lower, led to more men being diagnosed, primarily with lower risk prostate cancer, but in the long run it led to fewer men diagnosed with metastatic disease and fewer prostate cancer deaths.
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| 2. |
- Orrason, Andri Wilberg, 1988-
(författare)
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Trends in Prostate Cancer Mortality
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the early 20th century, cancer of the prostate was considered a rare and deadly disease with little to no possibility of cure. Since then, prostate cancer management has improved substantially with earlier detection, hormonal therapy, surgery and radiotherapy of the prostate. Nevertheless, prostate cancer remains the leading cause of cancer death in men in Western countries. The purpose of this thesis was to study trends in prostate cancer mortality including investigations of adjudication and measures of prostate cancer death. In paper I, we studied whether increased use of radical treatment in men with locally advanced prostate cancer diagnosed between 2000-2016 has affected prostate cancer mortality in the Swedish population. The use of radical treatment almost tripled and 5-year cumulative incidence of prostate cancer death declined from 17% to 10% for all men below age 80 with locally advanced prostate cancer. In paper II, we compared relative and cause-specific survival in all men with prostate cancer, according to age at death and risk category at diagnosis. Older men with low-risk prostate cancer at diagnosis had a substantially higher relative survival compared to cause-specific survival, 116% vs. 96% at five years after diagnosis. Despite efforts to increase comparability of expected survival, relative survival remained above 100% in these men due to healthy selection bias. In paper III, we assessed the amount of evidence in support of prostate cancer as the cause of death by review of health care records for 495 men who between 2011-2018 died of prostate cancer according to the Cause of Death Register. Older men and men with low-risk prostate cancer at diagnosis had considerably less evidence in support of prostate cancer death compared with younger men and men with high-risk disease. In paper IV, we applied a simulation model to estimate the lifetime risk of prostate cancer for different levels of diagnostic activity and life expectancy. Men exposed to high diagnostic activity had five-fold life-time risk of low or intermediate-risk prostate cancer and half the lifetime risk of high-risk or metastatic prostate cancer compared to men exposed to low diagnostic activity. Long life expectancy moderately increased the lifetime risk of prostate cancer in all risk categories, especially high-risk disease.
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| 3. |
- Ventimiglia, Eugenio, 1988-
(författare)
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How to model temporal changes in epidemiological data : Treatment trajectories in men with prostate cancer
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Owing to the improvements in detection, diagnostics, and treatment, many men currently diagnosed with prostate cancer (PCa) have a low risk of PCa death. For many men PCa has become a chronic disease with a small risk of progression that remains even decades after date of diag-nosis. In this thesis PCa was used as an example of a chronic disease, since it holds all the main characteristics required by the WHO definition of a chronic disease. Against this background, the aim of this PhD thesis was to create models that can be used to quantify the probability of dif-ferent treatment trajectories and to assess the duration of certain disease states, while accounting for patient characteristics, disease severity, and primary treatment.In Paper I a state transition model was developed for prediction of dis-ease trajectories. The developed state transition model showed good consistency with a follow-up spanning up to 30 years.In Paper II a state transition model was developed and validated using age, Charlson comorbidity index, and a drug comorbidity index (DCI) based on filled drug prescriptions collected at a population-based level to estimate life expectancy.In Paper III the state transition model proposed in Paper I was used to assess 30-year PCa trajectories in men managed with active surveillance, in order to identify the ideal candidates for this management strategy.In Paper IV the state transition model from Paper I was updated includ-ing the castration resistant PCa (CRPC) state as an additional state and estimating the duration of the CRPC state as well as its outcomes.In Paper V, the updated state transition model from Paper IV was used to model long term outcomes for men with PCa managed with watchful waiting (WW). Since WW is currently recommended for men with PCa and life expectancy less than 10 years, the state transition model from Paper II was used to estimate life expectancy.
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| 4. |
- Westerberg, Marcus, 1990-
(författare)
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Prostate cancer incidence, treatment and mortality : Empirical longitudinal register-based studies and methods for handling missing data
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The diagnostic activity for prostate cancer has increased substantially in Sweden, primarily due to increased use of prostate-specific antigen (PSA) testing in asymptomatic men, and this has led to a large increase in diagnoses. There have also been changes in the diagnostic workup, guidelines, treatment strategies, and more effective treatments have been introduced in different phases of the disease. This thesis aims to increase the understanding of consequences of changes in diagnostic activity and treatment, with a focus on empirical studies, methodological development, and handling of missing data.In paper I, the survival of men with metastatic prostate cancer was investigated across calendar time periods by use of Kaplan-Meier analyses and Cox regression. The median survival from diagnosis increased with six months comparing men diagnosed 1998-2001 with men diagnosed 2010-2015, while median PSA decreased.In paper II, a discrete time multivariate longitudinal model was combined with a proxy for the unobserved level of diagnostic activity to produce prognoses of incidence and mortality. Simulations indicated that a higher diagnostic activity was associated with fewer men diagnosed with metastatic disease and fewer prostate cancer deaths.In paper III, we looked for clinical variables predictive of the survival of men with castration-resistant prostate cancer (CRPC). A new data base was created including longitudinal data on prescriptions of hormonal treatment, PSA, and cause of death. We found that PSA doubling time and PSA at time of CRCP were highly predictive and could be used for treatment decision.In paper IV, we estimated annual incidence of metastatic prostate cancer using different methods for handling missing data in metastatic status (M stage). Missing data in M stage was high and varied over calendar time and risk groups, yet each method indicated a downward trend in incidence. Although men with unknown metastatic status cannot be assumed to have nonmetastatic disease in general, this may be reasonable among those with tumour characteristics that indicate a low risk of metastases.In paper V, the estimation of multivariate longitudinal models was considered in a context where some events are observed on a coarser level (e.g. grouped) at some time points, causing gaps in the data. The likelihood function, score and observed information were derived under an independent coarsening mechanism. A simulation study was conducted comparing properties of several estimators including direct maximum likelihood and Monte Carlo Expectation Maximisation.
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