Raoul Concepcion, MD
A great deal of progress has been made on the diagnosis and treatment of genitourinary cancers. For castration-resistant prostate cancer (CRPC), initiating therapy can begin prior to bone metastases.
There are now a variety of therapeutic agents available to treat advanced prostate cancer; however, how to sequence them remains somewhat unclear. For bladder cancer, enhanced immune therapies are approved in refractory disease, while genetic profiling is coming into play.
However, even as our understanding of the biology of prostate and bladder cancers improves and treatment protocols are refined, there remain many clinical scenarios in which no clear-cut answers are available.
Peer Exchange® roundtable discussion, titled “Clinical Challenges in Genitourinary Cancers,” focuses on some of the more challenging scenarios facing oncologists and urologists in the genitourinary field, using a case-based approach to emphasize important discussion points.
In Case 1, a patient with metastatic CRPC has progressed despite aggressive definitive therapy, including therapy with the immunotherapy sipuleucel- T. The treatment strategy would depend upon whether the patient has minimal symptoms or is asymptomatic, or, if he is symptomatic despite the absence of visceral metastases, explained Michael S. Cookson, MD, MMHC. If he is minimally symptomatic or asymptomatic, active agents including enzalutamide, abiraterone, docetaxel, and sipuleucel-T would be appropriate. If the patient progressed to a more symptomatic stage, those agents would still be considered; however, the presence of bone lesions and absence of visceral metastases would suggest radium-223 as another option.
The panel then discussed symptoms, which encompass discomfort and quality of life, and not just pain. They noted that some patients will hide symptoms and that nurses and the patient’s spouse or caregiver may prove good sources of information about the extent of these symptoms. Early on, Daniel P. Petrylak, MD, recommended obtaining a standard computed tomography (CT) of the chest, abdomen, and pelvis with contrast “to be sure he does not have liver metastases or something else that we are missing.” If the patient is older or frail, enzalutamide might not be appropriate because its profile includes CNS effects.
The panel also addressed taking advantage of the opportunity to treat with immunotherapy and to avoid complacency, said Cookson. If the patient clearly has visceral disease, consider the addition of chemotherapy. If he presents with bone-only disease or nodal disease, Cookson recommends enzalutamide or abiraterone. If the patient is experiencing pain that is related to bone and he does not have visceral metastases, there is an opportunity to administer radium-223. If radium-223 is not given at this time, and a year later the patient develops visceral metastases, the agent is not indicated for this setting. In the current case, for example, there is an opportunity to use radium-223 and the decision should be dependent upon results of a CT scan, said David I. Quinn, MBBS, PhD.
The addition of chemotherapy would be reserved for a patient who either is experiencing major pain and requires opioid agents to manage it, or, visceral metastases, said Quinn. With radium-223 therapy, Quinn says he has a low threshold for adding enzalutamide or abiraterone. For patients not taking these agents, he would conduct an additional scan between the third and fourth radium treatments. Should the identification of small liver metastases lead him to add docetaxel to the radium-223, he would not give a full dose of either.
Michael S. Cookson, MD, MMHC
However, a recent study by Neal D. Shore, MD, and colleagues, concluded that “combining abiraterone and radium-223 does not change the safety profile or the toxicity events.” Thus, Shore has become more aggressive in his treatment strategy by combining the therapies. In his experience, Shore tries to get in the full 6 cycles, as well as to give chemotherapy when appropriate.
Petrylak concurred that completing the full cycle of radium-223 treatment usually results in a survival benefit. In the patient who develops visceral disease, Petrylak would consider adding chemotherapy. If the patient has a positive response, he would consider adding radium-223 later.