Dr Spratt on Sequencing Radiation Therapy and Hormone Therapy in Prostate Cancer

Daniel Spratt, MD, professor, Department of Radiation Oncology, Case Western Reserve University School of Medicine; member, Developmental Therapeutics Program, Case Comprehensive Cancer Center, discusses research findings that have delineated the optimal sequencing of radiation therapy and hormone therapy for patients with prostate cancer.

Extending as far back as the 1970s, investigations have attempted to to discern the presence of a potential synergistic effect between radiation therapy and hormone therapy, such as androgen deprivation therapy, that inhibits androgen receptor (AR) signaling, Spratt says. Several clinical trials over the past few decades have aimed to define optimal strategies for the concurrent administration of radiation therapy and hormone therapy, Spratt explains.

Some of these trials were influenced by the notion that initiating hormone therapy prior to radiation therapy may mitigate adverse effects, such as hypoxia, or disease factors believed to contribute to radioresistance, Spratt notes. However, contemporary research challenges these hypotheses, indicating that administering hormone therapy prior to radiation therapy may not yield the anticipated oncologic advantages, Spratt emphasizes. Although hormone therapy can effectively target cancer cells, it may not be the optimal treatment strategy for enhancing the effects of radiotherapy, according to Spratt. Administering adjuvant hormone therapy immediately following radiation therapy may generate superior outcomes, Spratt says.

For instance, a preclinical study conducted by Spratt and colleagues explored the effects of sequencing AR signaling inhibitors (ARSIs) with radiotherapy neoadjuvantly, concurrently, or adjuvantly in prostate cancer cell lines. This study showed that delivering adjuvant ARSIs after radiotherapy was the most effective method for killing colony-forming cells and decreasing AR target gene translation and transcription in tumors.

Additionally, research has shown that radiation therapy can impede DNA damage repair, Spratt explains. Therefore, delivering radiation therapy alongside hormone therapy for an extended period may also be a strategy using these treatments that induces favorable synergistic effects, Spratt concludes.