Radiogenomics: Biomarkers for Prostate Cancer Radiotherapy Outcomes

Radiogenomics is an emerging field that aims to identify and validate more specific genetic biomarkers that predict patient radio-toxicity and tumor radiosensitivity. Several candidate biomarkers show promise for prostate cancer, according to a review published in Seminars in Radiation Oncology.¹

Researchers are making progress in the search for biomarkers that can help identify which patients are most likely to benefit from radiotherapy. Current risk-stratification practices based on clinicopathologic factors can be imprecise.²

The success of cancer radiotherapy hinges on 2 things: delivery of cytotoxic radiation doses to all tumor cells in a target volume, and minimization of irradiation of healthy, non-target tissues. Technological advances like conformal radiotherapy and intensity-modulated radiotherapy (IMRT) help to reduce irradiation of non-target tissues along external-beam radiation pathways and safety (micro-metastatic tumor cell-killing) margins around tumors. Despite these advances, however, radiation toxicities remain a treatment-limiting problem and frequent cause of discontinuation before therapeutic radiation dose goals are achieved. The use of IMRT for prostate cancer is therefore a controversial practice.³

Identifying patients whose healthy tissues are likely to be particularly radiosensitive and toxicity-prone—and whose tumors are most likely to respond to radiation therapy—would be invaluable steps toward personalizing radiation oncology, identifying patients who are likely to benefit from radiation, and devising optimal radiotherapy plans for them.

Prostate-specific antigen (PSA) velocity and doubling time are believed to be prognostic biomarkers for patients undergoing prostate cancer radiotherapy, with proponents advocating treatment intensification and consideration of androgen blockade based on elevated scores. There is not, however, sufficient evidence that doing so improves survival times for patients undergoing radiotherapy. PSA nadir level and time to PSA decline are reported to be predictive of PSA progression-free survival after both external-beam radiotherapy and radiation “bead” brachytherapy.^4,5 Despite PSA’s long use as a gold standard in the detection and assessment of prostate cancer risk, however, this biomarker yielded “diminishing returns,” Dr Feng and coauthors noted.

Pretreatment levels of serum C-reactive protein (CRP) show promise as a predictive biomarker for time to biochemical therapy following radiotherapy. But more precise tools are needed.