Ask the Experts – Adam B. Weiner, MD

Question 1. What prompted you to conduct the study?

Answer
At the VA hospital in Chicago, over and over again, I would see patients with metastatic prostate cancer who missed appointments for re-dosing of their androgen deprivation therapy. This will affect their outcomes. I would end up recommending surgical castration to those patients because even if they missed follow-up appointments, outcomes wouldn’t be quite as bad because surgery is a permanent form of androgen deprivation. However, once men start on routine injections for medical castration, they frequently want to stay on it. They might never have been offered surgery to begin with and want to avoid any surgery. Often they also don’t see the costs of the injections because they’re routinely covered by insurance.

Question 2. Were you surprised by any of your findings?

Answer
I was surprised to see that the rates of surgical castration have gone as low as they have: from 8% to 3% during the study period (2004 to 2016). The use of surgical castration has continued to plummet even though there is no evidence that one form of castration is better than another. There really is no good explanation aside from the possibility that doctors are just not counseling patients that surgical castration is an option. Plenty of data from years prior to our study period already showed declines in the use of surgical castration, with interesting correlations related to reimbursement rates for medical castration, even for different forms of medical castration.

Question 3. Why did you limit your study cohort to men with de novo metastastic prostate cancer?

Answer
We wanted to have a group of patients with clear indications for a permanent form of androgen deprivation. One limitation of our dataset is that we could not determine which patients developed metastatic disease following local therapy or a period of observation.

Question 4. Are there men for whom surgical castration would be a better option than medical castration?

Answer
Surgical castration makes a lot of sense for patients with metastatic prostate cancer and are going to be on lifelong androgen deprivation therapy or who may have difficulties or barriers to getting care and coming in for frequent medical appointments. Even though patients at the VA do not pay anything for their medical care, there is certainly a burden that goes along with their having to come into the office frequently. They may not be able to make appointments because they live far away or transportation is difficult. That is the kind of patient where it makes a lot of sense to get surgical castration. Surgical castration is a less expensive form of castration than medical castration over the long-term for patients. It is a simple outpatient procedure with relatively low complication rates, and it requires less follow-up. You can’t deny the convenience factor. The new oral therapies do require more follow-up than conventional androgen deprivation with labs and symptom checks. There is certainly a benefit to those patients getting a one-time surgery rather than frequent injections.

Question 5. How much of the decline in surgical castration, if any, do you think is related to the advent of the novel oral antiandrogens (abiraterone, enzalutamide, apalutamide)?

Answer
What’s great about those medications is that they are not injectable drugs, but they require more monitoring with labs relative to conventional androgen deprivation. These oral drugs extend patients’ lives but also adds costs. Surgical castration is a great option for reducing the costs of medical care for these patients. It’s one of the oldest forms of targeted therapy for cancer. It’s just surprising that it is so underused.

Question 6. How does survival compare between surgical and medical castration?

Answer
A lot of the previous data comparing survival between surgical and medical castration were all from old randomized controlled trials that accrued patients largely in the 80s and 90s. Once medical castration became more popular, some suggested that it was also superior. Our study showed that in a contemporary group of patients with metastatic prostate cancer there really is no difference in survival. Additionally, although our study didn’t look at this, there have been studies in the past couple years that have shown that men who got surgical castration as opposed to medical castration actually had fewer adverse effects related to treatment, including a lower incidence of peripheral arterial disease and fractures.

Question 7. Your study also looked at factors that predicted surgical castration use. What are the major ones?

Answer
We did notice in our study that the patients most likely to get the surgery are those who come from areas of low income, and typically these patients are either on Medicaid or have no insurance. This perhaps reflects provider bias to offer a permanent form of androgen deprivation. It makes a lot of sense. It could be that patients who come from areas of higher income or have better insurance are offered both castration options but quite simply want to avoid the surgery because they have insurance that will cover whatever treatment they end up getting. A prior study of a cohort limited to California also found that patients from areas of lower income tended to more often get surgical castration as well. It is unclear why. Is it that the provider wants to recommend surgical castration more often for these men because they just want to guarantee adherence to the androgen deprivation? Or is it that patients who come from areas of higher income don’t really see the cost quite as much, so their preference is just to avoid a surgery?

One thing that we were unable to look at—which could be an important factor—was the specialty of the doctor who started patients on androgen deprivation. Urologists can offer surgery, but medical oncologists do not perform surgery and may not think to offer it as an option. The dataset in our study didn’t have that granularity to answer that question. The next step would be to examine individual patient- and provider-level factors that go into making the decision about castration.