Levine Speaks On Treatment Options for Patients With mCRPC

Richard Levine, MD

Richard Levine, MD

In an interview withTargeted Oncology, Richard Levine, MD, medical director, Moffitt International Plaza, Moffitt Cancer Center,  discussed the selection of therapies available for patients with metastatic castration-resistant prostate cancer (mCRPC) and the next steps in the field.

TARGETED ONCOLOGY:What are some of the key considerations for community oncologists when treating a patient with metastatic prostate cancer?

Levine:

There are many different options now for patients diagnosed with metastatic prostate cancer. Most of those treatments have very minimal side effects. We are trying to maintain quality of life, as well as maximize quantity of life. Once again, usually the mainstay of treatment for prostate cancer is androgen-deprivation therapy (ADT), with leuprolide acetate for depot suspension (Lupron Depot) or leuprolide acetate for injectable suspension (Eligard), for example, or degarelix (Firmagon). Patients can also receive bicalutamide (Casodex) with that, either initially with therapy or it could be held.

Patients with prostate cancer who have bone involvement, which is the majority at about 80%, often benefit from zoledronic acid (Zometa), denosumab (Xgeva), or pamidronic acid (Aredia), in order to help strengthen the bone and decrease the risk of pathologic fracture.

After first-line therapy, there are many different options, depending on the patient’s symptomatology, volume of disease, and personal wishes. There is immune therapy with sipuleucel-T (Provenge), radiation therapy for diffuse bone pain, abiraterone acetate (Zytiga), and enzalutamide (Xtandi).

For patients with aggressive cancer who are young and want to be treated with a combined modality approach, they would be given docetaxel as chemotherapy of choice, and paclitaxel/carboplatin to follow.

In patients with the small cell subtype of prostate cancer who are treated with a different chemotherapy that is platinum-based, I have seen either cisplatin or carboplatin with BP16.

There are variants of prostate cancer that one must be aware of. These are usually very advanced, rapidly growing cancers of the prostate that often have very low prostate-specific antigens (PSAs). If a patient has a low PSA as well as hyponatremia, then we are thinking about small cell cancer of the prostate.

TARGETED ONCOLOGY:What are some treatment trends in the field of prostate cancer?

Levine:

There is more examination of the role of PSA and of treatment in early prostate cancer that is low grade with a Gleason 6 score or less, watching the PSA doubling time, and perhaps [doing] a repeat biopsy. There may be some issues with overtreatment of prostate cancer. Once again, there are experts who disagree and do not support PSA screening. That is an area that is always at conferences, and [discussed in] papers and panel discussions. People study the role of radiotherapy as primary treatment, brachytherapy, and external-beam radiotherapy or combined, as well as discussion of postoperative radiotherapy after radical prostatectomy. What are the criteria? What is a benefit for progression-free survival and overall survival?

There is also proton beam therapy, which is now offered at proton beam centers. Some of the literature suggests that it may be a little less toxic. I’m not sure that it improves survival, but those papers may be coming out. The proton beam therapy is not widely available, and standard radiotherapy is minimally toxic today. Patients can feel comfortable going to a radiotherapy center that has state-of-the-art equipment, and have a very effective radiotherapy [as a] cure with very minimal impact on their quality of life.

Immuno-oncology is where the research and the excitement are going, specifically with the PD-1/PD-L1 inhibitors. There is going to be a major advance in treating prostate cancer; it will be in the field of immuno-oncology.

Moreover, response rates are excellent. It can be up to 90% and that can palliate pain, shrink tumors that are widespread, and improve performance status and quality of life. Duration is up to the cancer—whether it is going to last 3 months, 3 years, or 13 years. Usually, this is bone-only prostate cancer.

TARGETED ONCOLOGY:What are some of the biggest questions that could be answered in the next 5 or 10 years?

Levine:

There is difficulty in getting good scientific evidence—clinical trials in the field of prostate cancer. Men are not going to be randomized to radical prostatectomy versus radiotherapy. That has not been very successful, and patients have their preferences. There is a lot of literature that compares survival up to 15 years.

In my opinion, there is probably going to be a more significant role for radiotherapy in the future rather than radical prostatectomy. A lot of patients relapse. Cryosurgery is an area of active treatment—though not necessarily primary treatment, although it is offered—but usually for relapse after RT.