Androgen Deprivation Therapy in Localized Prostate Cancer

Quoc-Dien Trinh, MD

Today we are discussing the utility of primary androgen deprivation therapy, or ADT, in men with localized prostate cancer with Quoc-Dien Trinh, MD, a urologic oncologist at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston. Dr. Trinh recently wrote an editorial that accompanied a publication of a 15-year study in JAMA Internal Medicine, which showed that primary ADT has no survival benefit for those men diagnosed with localized prostate cancer. Another study, published in April in the Journal of Clinical Oncology, also showed that primary ADT had no mortality benefit.

  -Interviewed by Anna Azvolinsky  

Cancer Network: Dr. Trinh, what are the monitoring and treatment options for men that are diagnosed with localized prostate cancer that has not yet spread to other parts of the body?

Dr. Trinh: When men are diagnosed with prostate cancer, there are a couple of options that are offered to them. One option is active surveillance. The idea of active surveillance is to defer treatment until absolutely necessary, which may end up being never. That is essentially to follow the patient with re-biopsies, PSA [prostate-specific antigen] blood tests, and digital rectal exams. Another treatment that can be offered for these patients is surgery, which is radical prostatectomy, and that can be done using an open or a robotic-assisted laparoscopic approach. Other treatments that can be given are in the field of radiation therapy-external beam radiation therapy, proton therapy, and also brachytherapy, which is essentially seeds that are placed directly in the prostate.

Cancer Network: Can you tell us about the setup and the key results of this 15-year localized prostate cancer study that was published in JAMA?

Dr. Trinh: The Lu-Yao et al study is building upon evidence that was published in previous years using the same dataset. The dataset used here is called SEER-Medicare, which is a linked dataset of SEER-the Surveillance, Epidemiology, and End Results Program, a cancer registry that is linked to Medicare claims. An important thing to know here is that this is Medicare claims, so the patients that are included in this study are all 66 years of age or older. This is a large study that ranged from 1992 to 2009 and that encompassed over 66,717 patients. And what the study found is that by looking at the endpoints of interest, prostate cancer–specific survival and overall survival, it showed that primary ADT was associated with no benefit with regards to survival or prostate cancer–specific survival in men with localized prostate cancer. It is important to mention that these are men who are treated for localized prostate cancer. We know that primary ADT has a role to play in other contexts, such as metastatic prostate cancer, as an adjunct to radiation therapy in men with locally advanced prostate cancer. But in the context of simply localized prostate cancer, it seems that primary ADT does not have a role to play.

Cancer Network: You mentioned this a bit already, but what else do we know about primary ADT for localized prostate cancer from other studies? Are there any benefits and what are the potential harms of this treatment?

Dr. Trinh: I think more than anything else, there are studies demonstrating that there is harm associated with primary ADT. There is this 15-year study and also the Potosky et al study published in JCO [Journal of Clinical Oncology] that you mentioned. This was a study that used a different dataset-men that were included in multiple health systems including Henry Ford and Kaiser Permanente. And these authors also showed that there was absolutely no mortality benefit with primary ADT. There were other retrospective studies done earlier using a variety of sources, institutional and registry claims data, and none of these showed a benefit for primary ADT. If anything, there are harms. The harms of primary ADT are well known, harms with regard to bone loss, osteoporosis, risk of fracture, potential cardiovascular issues, diabetes, and others. There is a lot of compelling evidence that there are lots of harms to ADT, and in the context of primary ADT, where it does not even confer any survival benefits, I think the harms outweigh any benefit.

Cancer Network: Are these results enough to be practice-changing in your opinion? Will these results decrease the number of localized prostate cancer patients treated with primary ADT?

Dr. Trinh: I think this study and the JCO study that we mentioned are certainly compelling studies that provide more evidence for the physician to not prescribe primary ADT. I think it builds on previous work, and the rate and use of primary ADT has been decreasing over the years anyway, but these studies are certainly going to contribute and clarify to physicians that these drugs should not be used in the context of primary treatment for localized disease.

Cancer Network: You mention in your editorial that, according to statistics, as late as 2009, the use of primary ADT remains relatively high despite the indication that the therapy does not improve patient outcomes. What are the likely causes of this trend and is it now on a decline as a result of some of these studies?

Dr. Trinh: I think there are a lot of data to show that the use of primary ADT is declining. I think it is still alarming that some patients still get primary ADT. There are specifics of each clinical case and we are talking from a broad perspective but there is pretty much not much indication for primary ADT for purely localized disease. I think that there were pretty important studies that showed that, with the Medicare Modernization Act, which decreased the reimbursement of ADT by about 50%, the misuse of ADT, especially in the context of primary ADT, seems to have decreased. But there are still patients out there receiving primary ADT. It is certainly a worthwhile and important clinical question, a research question, to ask why, but it is reassuring to know that at least in the United States its use is declining and most likely because the bulk of these studies show no benefit from this therapy.

Cancer Network: Lastly, you mentioned some of the ways that patients with localized prostate cancer can be treated or monitored. What are the patient factors to consider when deciding on how and whether to treat a patient recently diagnosed with localized disease?

Dr. Trinh: There are many things to factor in. One is certainly the life expectancy of a patient and how likely it is that the patient will benefit from treatment. Prostate cancer is a disease that is slow-evolving in most cases, so you always want to factor in life expectancy with disease severity. As to which treatment to choose, the most important thing to weigh in, probably, are the side effect profiles of each treatment. The side effects of prostatectomy, prostate cancer surgery, are quite different from radiation therapy, and in the absence of any evidence showing that one is clearly better than the other, I think the side effect profile of each should guide the patient to which treatment he should be choosing, if he is a candidate to be treated because, as I mentioned earlier, there are other considerations such as life expectancy and comorbidities that play a role in the decision.

Cancer Network: Thank you so much for joining us today, Dr. Trinh.

Dr. Trinh: A pleasure, thank you.