Urologists Treatment Armory Expands With New Novel Agents and Immunotherapies

Greg Kennelty

With a renewed armory of treatments consisting heavily of immunotherapies, urologists can employ new paradigms of treatment for patients with metastatic castration-resistant prostate cancer (mCRPC).

Raoul S. Concepcion, MD, FACS

With a renewed armory of treatments consisting heavily of immunotherapies, urologists can employ new paradigms of treatment for patients with metastatic castration-resistant prostate cancer (mCRPC).

"We have had five or six new agents that have been specifically approved for this very difficult population of patients with mCRPC. The beauty about that is that all of these therapeutics have a survival benefit and the delivery of these therapeutics actually can be done by the urologist. However, it does take a well-motivated urologist or urology group to go ahead and adopt and adapt that treatment paradigm," said Raoul S. Concepcion, MD, FACS, director of Advanced Therapeutics at Urology Associates, PC, in an interview withTargeted Oncology.

The FDA has approved numerous therapies to treat patients with mCRPC since 2010. These treatments include the immunotherapy sipuleucel-T (Provenge), cabazitaxel (Jevtana), the androgen axis modulators abiraterone acetate (Zytiga) and enzalutamide (Xtandi), as well as two bone-targeting therapies, those being denosumab (Xgeva) and radium-223 (Xofigo).

Denosumab was approved for the prevention of skeletal-related events, and radium-223 was approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in men with symptomatic bony metastases with limited soft tissue involvement.

Concepcion said prior to the approval of these treatments, urologists had historically tended not to manage patients post-failure of androgen deprivation therapy. He said this non-treatment stemmed from the fact that the only treatment available then was cytotoxic chemotherapy, a treatment not delivered by most urologists throughout the country.

"With all the new therapeutics, it is incumbent upon the urologist to identify [mCRPC] patients early. If they want to start therapy, which I believe we should as a specialty, then we need to identify these patients early and institute treatment," said Concepcion.

"If, as an individual or as a group, you don’t want to treat because you feel like it’s not within your wheelhouse, then at least identify the patients and then get them to a medical oncologist so that the patient can be treated. It is incumbent, again, upon us. We are taking care of these patients, and it would be unconscionable to not offer these patients some types of therapies."

Concepcion said most urologists decide the appropriate sequence of treatment going by tional Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) guidelines. He added that while these guidelines are helpful, most treatments are currently employed as single-agent therapies.

"All the studies have been done, essentially, not in combination with other drugs. They’re all monotherapy trials, single-agent trials, and no one really knows the best combination. Most of the time, we believe that if the patient starts to get symptomatic, there are many factors that come into play. Was there progression on imaging? Does the patient have more bony metastases? Does the patient have visceral metastases, lung, liver, or soft tissue? How rapid is the PSA going up? You have to take all of that into consideration and it’s not just PSA," he said.

Concepcion elaborated on that by adding that if a patient has more symptomatic bone pain, a urologist might consider the addition of radium-223. If patients experience progression, more soft tissue disease, worsening bone disease, and becomes resistant to traditional cytotoxic chemotherapy some oral agents such as abiraterone acetate, an androgen synthesis inhibitor, as well as enzalutamide, an androgen receptor blocker, both can be used.

Looking toward the future, Concepcion said there is a "tremendous" amount of work going on in the furthering of treatments for mCRPC.

"We have two or three global trials that are looking at the M0 space in those patients with mCRPC who do not have demonstrable radiographic evidence of spread. That’s a very difficult patient to treat because none of the therapies that are currently approved that have a survival benefit in the M1 space are approved in the M0 space. So that’s index patient 1 in the AUA guidelines, and that’s the M0 space in NCCN, and all we can offer them are clinical trials versus observation," he said.