Testing the external validity of ProtecT trial results in North American men with clinically localized prostate cancer (PCa)

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Conference Proceeding

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European Urology Supplements


INTRODUCTION & OBJECTIVES: Randomized controlled trials (RCTs) represent a high level of scientific evidence. However, these must be internally valid (i.e., design and conduct must eliminate the possibility of bias), and in order to be clinically useful, their result must also be relevant to a definable group of patients in a particular clinical setting (i.e., they must be externally valid). Indeed, reliable judgments about the external validity of RCTs are essential if treatments are to be used correctly in routine clinical practice. In this context, our objective was to evaluate the external validity of the ProtecT trial using the National Cancer Data Base (NCDB), which capture 70% of the newly diagnosed cancers in US. MATERIAL & METHODS: We identified patients within the NCDB 2010-2013, who met the inclusion criteria of ProtecT (i.e., age between 50-69 years, histologically confirmed PCa, no prior or concomitant malignancy, clinical stage T1c-T2 Nx-N0 M0, prostate-specific antigen <20ng/mL). We also excluded patients with Gleason score ≥8, because they represented only 2.3% of the ProtecT cohort. We focused on important measurements of external validity (namely age, racial group, tumor stage, and tumor grade), and compared these between ProtecT cohort and NCDB cohort, using the two-sample independent t test, and chi-square test as appropriate. RESULTS: Mean age was significantly lower in the NCDB cohort (61±5.2 yrs) vs. Protect cohort (62±5 yrs, Table). While PSA level and clinical stage were comparable, 46.7% of the NCDB cohort had a Gleason 7 tumor on biopsy, compared to only 20.6% in the ProtecT cohort. Moreover, 14.3% of the NCDB men were Black, compared to ≤1% in the trial (all p<.001). CONCLUSIONS: The ProtecT trial concluded that radical prostatectomy and radiotherapy did not reduce 10-year overall mortality and cancer-specific mortality compared with active monitoring in men with clinically localized PCa. Our findings show that these conclusions are not necessarily generalizable to North American patients, who are usually younger, and have more aggressive disease at the time of diagnosis. Both these factors can modify the beneficial effect of definitive treatment. Additionally, more men from African ancestry are diagnosed with PCa in US, and these individuals frequently harbor more aggressive tumors. (Table presented).





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