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  • br expectancy br ACCEPTED MANUSCRIPT br Manuscript br Introd

    2019-09-16


    59 expectancy
    ACCEPTED MANUSCRIPT
    60 Manuscript
    61 Introduction
    62 In clinically localized prostate cancer (PCa), the ideal radical prostatectomy (RP) or external
    63 beam radiation therapy (EBRT) candidate should enjoy the longest possible survival without
    65 mortality reduction may be considered most valuable. According to this premise, surgeons
    66 and radiation oncologists have been striving to select patients for treatment of localized PCa
    67 according to the most favorable OCM-free survival. Indeed, several investigators showed that
    68 PCa patients treated with RP are at lower risk of mortality than the general population (4,5).
    69 This phenomenon of better survival is in general less pronounced in radiation oncology
    70 patients (5). We hypothesized that the ability of clinicians to select ideal treatment candidates
    71 for RP and radiation therapy has improved over time. According to our hypothesis, the rate of
    72 OCM should decrease in a time-dependent fashion. We tested this Meropenem in a large
    73 North-American patient cohort of individuals treated with either RP or EBRT for clinically
    74 localized PCa over the past 25 years within the Surveillance, Epidemiology and End Results
    ACCEPTED MANUSCRIPT
    77 Patients and methods
    78 Study population
    79 The SEER database samples 26% of the United States and approximates the United States in
    80 terms of demographic composition, as well as of cancer incidence (6). Within the SEER
    81 database (1987-2011), we identified patients aged ≥18 years with histologically confirmed
    82 PCa diagnosis at biopsy (International Classification of Disease for Oncology [ICD-O-3] code
    84 without lymph node or distant metastases (cN0 cM0). Moreover, only patients treated with
    85 either RP or EBRT were included. This resulted in a cohort of 367,884 clinically localized
    88 Outcomes of interest
    89 Our analyses focused on OCM which was defined as death attributable to other causes than
    90 PCa. The main outcome of interest was OCM at 5 years of follow-up, over time. Therefore,
    91 we included patients within a 25-year period, until 2011 inclusively. We relied on
    94 ethnicity (Caucasian vs. African-American vs. Hispanic vs. others), marital status (married vs.
    97 Statistical analyses
    98 Descriptive statistics included medians and interquartile ranges, as well as frequencies and
    99 proportions for continuous and categorical variables, respectively. The statistical significance
    100 of differences in medians and proportions was evaluated with the Kruskal-Wallis and chi-
    ACCEPTED MANUSCRIPT
    102 Kaplan-Meier was used to estimate the 5-year OCM rates. Annual trends were examined with
    103 linear regression models according to Kaplan-Meier and age-adjusted Cox regression-derived
    105 Furthermore, we relied on multivariable Cox regression models testing the effect of year of
    106 diagnosis strata on OCM according to treatment type (RP and EBRT), age category, ethnicity
    107 and marital status. For all statistical analyses R software environment for statistical computing
    108 and graphics (version 3.4.3) was used. All tests were two sided with a level of significance set
    ACCEPTED MANUSCRIPT
    118 patients died of OCM at 5 years of follow-up according to year of diagnosis categories 1987-
    120 In age-adjusted analyses cytokinins were further stratified according to treatment type, EBRT
    121 Meropenem patients exhibited higher 5-year OCM rates over time that ranged from 11.0% in the most
    127 years), oldest patients exhibited the highest 5-year OCM rates over time that ranged from