Our July issue on radiation therapy debuts next week.
In the meantime, Dr. Snuffy Myers frames this month’s conversations for us.
This issue focuses on the interaction between radiation therapy and immunotherapy for prostate cancer. This interaction has been extensively documented in laboratory models where the combined treatment can show benefit even in metastatic prostate cancer.
In the laboratory models, it appears that cancer cells damaged or killed by radiation trigger an immune response. This response can be enhanced by additional agents.
The most promising situation to test this approach is in patients with oligometastatic prostate cancer. These patients have 5 or fewer metastatic lesions that can be targeted by radiation therapy. In this setting, all detectable prostate metastases receive a radiation dose sufficient to treat the cancer.
The hope is that triggering an immune response will enhance the ability of radiation to kill all cancer in the irradiated lesions. There is also a hope that this immune response might suppress the growth of cancer metastases that are present but not radiated because the lesions are too small to be detected. This would act to delay the appearance of new metastatic lesions and possibly extend survival.
There are several unresolved issues in this area of research. First and foremost, immunotherapeutic agents with activity against prostate cancer are of limited effectiveness currently. For example, while the Provenge (sipuleucel-T) vaccine is FDAapproved to treat prostate cancer, it extends survival by only months. Immune checkpoint inhibitors, such as those that target PD1/PD1L, can cause dramatic responses, but they do so in only a small proportion of patients. Nevertheless, prostate cancer immunotherapy is a very active area of investigation with a number of promising concepts at various stages of testing.
Another unresolved issue is when is the best time to administer immunotherapy with regard to radiation treatment—before, during, or after. Radiation dose may also be critical as extensive radiation can dramatically suppress immune system function.
Despite these limitations, this is a research area worthy of investigation. The ultimate goal of cancer treatment is a durable complete remission. As it is unlikely that patients with metastatic cancer will ever be cancer-free, a more reasonable goal is to place remaining cancer cells in a state of dormancy. In laboratory models, immunotherapy is one of the most successful approaches to achieve cancer dormancy.