Biological predictors of cervical cancer response to radiation therapy

The addition of cisplatin-based chemotherapy to standard radiation therapy reduces the risk of recurrence and disease-related death rates from locally advanced cervical cancers by as much as 50%. However, the absolute gains are relatively small for patients with early tumors, many of whom would have been cured with radiation alone, and recurrence rates are still high for patients who have very large or advanced-stage tumors. As a result, there is a pressing need for more accurate predictors of radiocurability. A variety of types of biomarkers have been shown to correlate with cervical cancer response to radiation therapy. These include traditional clinical and morphologic predictors, non-molecular biomarkers, including hypoxia and fluorodeoxyglucose-positron emission tomography (FDG-PET) avidity, as well as molecular biomarkers, which include single-gene markers or array-based multigene predictors. Multi-gene predictors of response remain immature in cervical cancer, but studies thus far have paved the way for future studies to validate these findings. Methods will need to be standardized and markers will need to be validated on homogeneous patient populations and treatment approaches before they can become useful tools for clinical decision making. In addition, new biomarkers will be of major value only if they add to the predictive value of traditional clinical and morphologic predictors. Ultimately, the most useful biomarkers will identify patients who will benefit from specific molecularly targeted agents in addition to radiation therapy or perhaps identify patient who are at low risk for recurrence, for whom the dose of radiation or chemotherapy can be reduced.