Posted: Jul 30, 2016
Our radiation therapy discussion begins with Drs. Mack Roach and Michael Zelefsky.
Both discuss the future of radiation therapy and offer insight into escalating radiation to the prostate while minimizing dosing to surrounding normal tissue.
Two developments drive this effort. First, improved imaging provides a more detailed view of the cancer’s extent and its localization within the prostate as well as spread to adjacent structures. Dr. Zelefsky outlines MRI imaging’s impact. Dramatic advances in computer power have also allowed radiation oncologists to develop sophisticated treatment planning software. We can calculate with more precision radiation doses to be delivered to the cancer versus to surrounding normal tissue.
Radiation therapists can also focus external beam radiation with greater precision, leading to IMRT and Cyberknife. These techniques use high-energy photons.
We also developed approaches like brachytherapy and proton beam that augment or compete with photon-based treatments. Further progress in intensifying radiation dose may be limited. Drs. Roach and Zelefsky’s comments on these trends are well balanced.
Another trend is to shorten treatment duration. Current treatment plans require eight to nine weeks. Dr. W. Robert Lee outlines two randomized trials that show four to five and a half weeks of treatment is not inferior to eight to nine weeks of treatment. (Increasing daily radiation doses, a strategy called hypofractionation shortens treatment duration.) Shorter treatments are more convenient for patients. Larger doses per session may also reduce costs as radiation oncologists are paid per treatment session.
Stereotactic body radiotherapy (SBRT) is another way to shorten treatment duration. SBRT delivers five treatments over a week and a half. SBRT is at an earlier development stage; we have no randomized trials proving it is better than or equal to standard fractionation or hypofractionation. SBRT has theoretical advantages, as Dr. Zelefsky comments. Early results are promising, but SBRT’s full potential is still being explored.
Dr. Sean McBride’s clinical trial combines SBRT with cutting-edge hormonal therapy in patients with locally advanced disease at very high risk of recurrence after surgery: Gleason 8-10, a PSA >20, extracapsular spread, or cancer invasion into the seminal vesicles or lower part of the bladder.
Disappointingly, current adjuvant hormonal therapy for radiation typically uses LHRH agonists. Xtandi (enzalutimide) and Zytiga (abiraterone) have revolutionized metastatic prostate cancer treatment. Adding both to adjuvant hormonal treatment is persuasive. McBride’s trial uses an LHRH agonist with Zytiga (abitraterone) and a new drug called apalutamide (ARN 509). Apalutamide’s (ARN-509) mechanism of action is similar to Xtandi’s. This combination is frontline treatment for advanced metastatic prostate cancer, but in this trial, it is applied as adjuvant hormonal therapy for locally advanced prostate cancer. This trial promises to revolutionize treatment for locally advanced disease.
I’m very interested in metformin use for prostate cancer. In my clinic, we use metformin when we start hormonal therapy: a randomized trial shows that it reduces metabolic syndrome risk for men on hormonal therapy. Dr. Zelefsky observes that during radiation, patients on metformin have a reduction in distant metastases, risk of dying of prostate cancer, and risk of castrate resistance. This is retrospective data, though; these advantages need to be tested in a randomized controlled trial.
– Charles E. Myers, Jr., M