In Reply We are pleased by the interest of Schernberg and colleagues in our analysis of the association of definitive pelvic radiation therapy with survival among patients with newly diagnosed metastatic cervical cancer in the National Cancer Database (NCDB).1 This analysis was a retrospective, hypothesis-generating study.
We totally agree with Schernberg et al that this study had limitations, including the inherent bias for any retrospective study. We were unable to control for unknown selection factors and patient characteristics. For example, the NCDB does not have information on the number of metastases. However, the metastatic site (distant lymph node, distant organ, or both) was taken into account for the survival analyses. Among all 3169 patients, 1300 (41.0%) had a distant lymph node metastasis and 1067 (33.7%) had a distant organ metastasis. Involvement of para-aortic lymph nodes is considered metastatic (M1) disease in the sixth and seventh editions of the AJCC (American Joint Committee on Cancer) staging system.2 However, patients with positive para-aortic lymph nodes are routinely treated with extended field radiation and chemotherapy.3,4 Unfortunately, the NCDB does not have specific information about para-aortic irradiation. In order to minimize the potential confounding from patients with para-aortic lymph node metastases, survival analysis was done for the 1067 patients with organ-only metastases by excluding patients with any distant node metastasis. Adding pelvic radiotherapy (RT) to chemotherapy was associated with improved overall survival by univariate (HR, 0.71; 95% CI, 0.62-0.82; P < .001) and multivariate regression analysis (HR, 0.71; 95% CI, 0.62-0.82; P < .001) over chemotherapy alone. Secondary analysis by radiation type showed external beam radiotherapy plus brachytherapy had better median survival than external beam radiotherapy alone and no radiation (19.4 vs 10.9 vs 8.3 months, P < .001). These results clearly demonstrated that the benefit of definitive pelvic radiation was not compromised by the possible confounding from patients with para-aortic lymph node metastases.
Wang Y, VanderWalde N, Ballo MT. Level of Evidence and Ethical Considerations for Locoregional Treatments in Metastatic Cervical Cancer—In Reply. JAMA Oncol. 2019;5(4):575–576. doi:10.1001/jamaoncol.2019.0028
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