Objective Hemoglobin (Hb) is a prognostic factor in cervical cancer, but the underlying mechanisms remain unknown. In this study, we hypothesized that low Hb level, either before or during radiotherapy (RT), is a surrogate for a more infiltrative and therefore aggressive disease, with uterine corpus invasion and nodal metastases.

Methods and Materials Prospectively collected data of patients with locally advanced cervical cancer treated with curative intent using chemoradiation at a tertiary academic center was reviewed. All eligible patients had a positron emission tomographic scan and pelvic magnetic resonance imaging. Hemoglobin levels before RT and Hb nadir during RT were collected from the medical record.

Results The median follow-up for 263 eligible patients was 38.7 months. Ninety-six patients (36.5%) had both uterine corpus invasion and positron emission tomography–positive nodal disease (C+N+). Patients with pretreatment Hb level of less than 120 g/L were more likely to have C+N+ disease (47%) compared with patients with a high pretreatment Hb level (32%; P = 0.034). The 3-year disease-free survival and overall survival (OS) were significantly lower in the C+N+ group compared with the remaining patients (40.1% vs 76.1%, P < 0.001, and 59.7% vs 83.1%, P < 0.001, respectively). Patients with low Hb nadir were more likely to have a C+N+ disease (P < 0.001), and low Hb nadir during RT was significantly an indicator of a higher recurrence rate (P = 0.002) and lower OS (P < 0.001). In multifactor analysis, statistically significant prognostic factors for OS included histology, high-echelon nodal involvement, tumor volume on magnetic resonance imaging, C+N+ status, and Hb nadir during treatment. Pretreatment Hb level was not an independent prognostic factor.

Conclusions The combination of corpus invasion and nodal metastases is associated with lower Hb level and inferior prognosis. Because C+N+ state is related to tumor growth from early invasion to the time of presentation, it is unlikely that the correction of Hb level during treatment will have a major impact on outcome.