Robert B. Den, MD, associate professor of radiation oncology, Thomas Jefferson University Hospital, discusses the future of prostate cancer research.

The field of prostate cancer has gone through an explosion within the last 5 to 10 years with the FDA approvals of multiple agents. These agents have shown activity in late-stage disease, and subsequent trials have begun to show activity in earlier-stage disease, Den says. This has garnered a lot of hope for the treatment of patients with prostate cancer, as these agents are now proven to be active earlier in the disease state, and may increase survival.

Den says that these advances have led more people to become actively involved in prostate cancer research. DNA-damaging agents, such as PARP inhibitors and DNA-PK inhibitors, are being investigated, and phase II trials have shown that selecting patients by mutation may ensure benefit. This is a new area of prostate cancer research that will soon be manifested in clinical benefit for patients, Den concludes.

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Robert B. Den, MD, associate professor of radiation oncology, Thomas Jefferson University Hospital, discusses the future of prostate cancer research.
 

Dr. Den Discusses the Future of Prostate Cancer Research

Robert B. Den, MD, associate professor of radiation oncology, Thomas Jefferson University Hospital, discusses bone metastases in prostate cancer.

Prostate cancer is a unique malignancy, as it tends to have a preponderance of metastases to the bone. Bone metastases can impact a patient’s quality of life by causing severe bone pain, which is an area where investigators have been looking into targeting the bone microenvironment specifically.

Commonly used bone-targeted agents for the treatment of patients with metastatic castration-resistant prostate cancer include zoledronic acid (Zometa), denosumab (Xgeva), and radium-223 dichloride (Xofigo). These agents are designed to target the makeup of the bone, Den explains.

Robert B. Den, MD, associate professor of radiation oncology, Thomas Jefferson University Hospital, discusses bone metastases in prostate cancer.
 

Dr. Den Discusses Bone Metastases in Prostate Cancer

Robert B. Den, MD, associate professor of radiation oncology, Thomas Jefferson University Hospital, discusses bone-targeting agents in prostate cancer.

About 90% of patients with prostate cancer who develop metastases will develop bone metastases. Zoledronic acid (Zometa), radium-223 dichloride (Xofigo), and denosumab (Xgeva) are agents designed to target the makeup of the bone. The bone is generally made up of calcium and phosphatase; zoledronic acid works through the phosphatase side, radium-223 works through the calcium side, and denosumab decreases the osteoclastic activity of the bone.

The bone is constantly on a balance beam, says Den, both building and destroying bone. This balance is based on the production of bone based on the osteoblasts, and the reduction of bone by the osteoclasts. While denosumab decreases the osteoclasts, radium-223 works as a calcium mimetic to cause uptake up radium into the bone, says Den. Thus, radium gets targeted toward areas of increased prostate cancer, he adds.

Robert B. Den, MD, associate professor of radiation oncology, Thomas Jefferson University Hospital, discusses bone-targeting agents in prostate cancer.
 

Dr. Den Discusses Bone-Targeting Agents in Prostate Cancer

Robert B. Den, MD, associate professor of Radiation Oncology, Thomas Jefferson University Hospital, discusses the use of radiation therapy as a treatment for patients with prostate cancer.

Currently in the field of prostate cancer, there is quite a lot of uncertainty as to which patients derive the most benefit from post-prostatectomy radiation, according to Den. Oncologists are also a bit unsure about the ideal timing for administering radiation. There is concern about initiating radiation therapy too early, as the treatment is associated with increased toxicity.

On the other hand, some researchers are worried that, by waiting too long to administer radiation, they could be missing a window of opportunity for potential benefit for a patient, as they are allowing the disease to spread too far before such aggressive therapy can provide the right benefit.

Three randomized clinical trials addressed some of these issues in the adjuvant radiation setting. While all 3 studies showed improvement in biochemical survival, only 1 of the trials demonstrated improvement in overall survival. Moreover, in the control arm of that study, approximately 50% of patients did not develop prostate-specific antigen (PSA) recurrence at 5 years. Thus, there is a lack of understanding as to which patients will develop recurrence, who will develop recurrence despite aggressive radiation therapy, and which patients will never develop recurrence. The biggest question there, says Den, is differentiating these groups of patients.

A more recent retrospective, multicenter study sought to determine if a genomic classifier could predict the development of metastatic disease in patients who received salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. The data suggest that the genomic classifier is a strong predictor of metastases among this specific patient, accurately identifying men who are excellent candidates for systemic therapy due to their high risk of metastases.

Robert B. Den, MD, associate professor of Radiation Oncology, Jefferson Health, discusses the use of radiation therapy as a treatment for patients with prostate cancer.

Robert B. Den, MD

Articles

Dr. Den Discusses the Future of Prostate Cancer Research

Dr. Den Discusses Bone Metastases in Prostate Cancer

Dr. Den Discusses Bone-Targeting Agents in Prostate Cancer

Dr. Den on Radiation Therapy in Prostate Cancer