PracticeUpdate Oncology May 2019

EXPERT OPINION 19

Chemotherapy for Oligometastatic Prostate Cancer Interview with Tanya B. Dorff MD by Farzanna S. Haffizulla MD, FACP, FAMWA

Dr. Dorff is Associate Clinical Professor in the Department of Medical Oncology & Therapeutics Research and she serves as the head of the Genitourinary Cancers Program at City of Hope Comprehensive Cancer Centre in Duarte, California. Dr. Haffizulla: I wanted to talk about widely metastatic prostate cancer. Can you tell us how effective chemotherapy is in this setting? Dr. Dorff: So, docetaxel has been around for a long time in prostate

cancer, particularly in the castration-resistant setting. More recently, when it was studied in the metastatic hormone-sensitive setting, the question of widely metastatic versus oligometastatic appeared to be important because there appears to be a greater benefit in men who have high-volume disease. If you'll recall, in the CHAARTED study, high volume was defined as four or more bone metastases with one outside the axial skeleton or visceral involvement. So, oligometastatic doesn't have as clear a definition and there's still some debate about what it means to be oligometastatic, but the use of chemotherapy does seem to be more beneficial, at least when we move it earlier in the more widely metastatic setting. Dr. Haffizulla: Speaking of oligometastatic disease, is there any known difference in tumor biology in these patients compared with others? Dr. Dorff: That's a great question. We don't really have an answer for that yet. Part of the problem is that we see these men as a snapshot and it might be that they have only two or three metastases visible today and are on a very aggressive course and in a month will have widespread disease, and we've just caught them at that moment. And so until we can define the biology, it will become very difficult to treat them dif- ferently on that basis, so we probably overtreat some patients who appear to have widely metastatic disease who may have more indolent behavior and conversely, we might under treat an oligomet who really needs more aggressive therapy. But there's a lot of work being done by a lot of outstanding scientists trying to come up with these kinds of molecular-based definitions that will help us understand the natural history of the disease better. Dr. Haffizulla: What is the benefit of chemotherapy in these patients? Dr. Dorff: The CHAARTED study showed fairly clearly that although the study as a whole was positive and using docetaxel upfront when starting androgen deprivation for a patient with metastatic prostate cancer is beneficial, that the low volume or what you might consider oligometastatic patients didn't appear to derive benefit. Very interest- ingly, that may be a common theme as we're seeing some longer-term data from the LATITUDE study with abiraterone. So there may really be a different biology in terms of who needs intensification and who does not, but for right now, an oligometastatic patient is not typically offered chemotherapy upfront. Dr. Haffizulla: So, what then would be the best treatment options for these patients or treatment approach rather for these patients? Dr. Dorff: That's an area of great debate. A lot of people are interested in metastasis-di- rected therapy, so using, for instance, SBRT to a couple of osseous metastases. In our institution, we're studying the use of SBRT together with androgen deprivation and radium early for bone metastases. There's also a big interest in treating the primary in some cases, restricted to oligometastatic patients, to see if treating the mothership, as it were, impacts the overall disease progression. So, there are a lot of clinical trials right now asking these very interesting and important questions for these special patients.

case. You know, they always traditionally showed worse outcomes and so women were always told well, you should termi- nate your pregnancy, a wanted pregnancy, because you’re going to do worse. However, in the several groups that I’ve been treating now for several decades, if you give standard-of-care chemotherapy in the sec- ond and third trimester, you do just as well as the breast cancer patient who’s not pregnant. And I think that that is the important aspect, to go ahead and treat in the second and third trimester. Some groups have given chemo light or maybe just one chemo. Well, you wouldn’t do that to a non-preg- nant patient and expect them to do as well, and they don’t. So standard-of-care therapy, and so far we have not seen dif- ferences as far as those children who have been exposed to the chemother- apy in utero as long as we waited until the second and third trimester. I think the overall message is this has to be a team approach. You need the surgeon, the radi- ation oncologist, the medical oncologist, and the maternal fetal medicine specialist all working together with each of the chem- otherapies and have a specific plan for that patient. Dr. Gaines is a board-certified Emergency Medicine physician as well as a 15-year news veteran. www.practiceupdate.com/c/75671 Watch Dr. Litton discuss breast cancer in young adults at www.practiceupdate.com/c/77716

Dr. Haffizulla practices general internal medicine in Davie, Florida, within her own internal medicine concierge practice. She is also the Assistant Dean of Community and Global Health at Nova Southeastern University’s College of Allopathic Medicine in Florida.

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VOL. 3 • NO. 2 • 2019