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Sexual Differences in Cancer Survival: Hormones or Stage at Diagnosis?-Reply

Hans-Olav Adami, MD; Lars Klareskog, MD; Lars Holmberg, MD; Jan Pontén, MD; Ingemar Persson, MD
JAMA. 1990;264(14):1810-1811. doi:10.1001/jama.1990.03450140030023.
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In Reply.—  Dr Lowenfels points out that differences in survival (hazard rate) that we have reported may arise not only from a more malignant behavior of cancers in young males but also from a systematically earlier diagnosis in young females, which causes a more favorable stage distribution and introduces a lead time bias. The major determinants of stage of disease at diagnosis are probably time (patient's delay and physician's delay) and biologic features of the tumor. These are interdependent, since high biologic malignancy will increase the prevalence of nodal spread and distant metastases at the time of diagnosis and thus cause a tumor to be at a more advanced stage. Stage of disease can accordingly be looked on both as a confounding variable (as suggested by Dr Lowenfels) and as an intervening variable. The latter alternative is in our view more important in the context of our study.Dr Lowenfels


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