The use of androgen deprivation therapy (ADT) alone and in conjunction with other forms of treatment for the management of patients with relatively early stages of prostate cancer (i.e., cancer that is not definitively at least lymph node positive) has been increasingly called into question.
A new article by Fang et al. reviews currently available data on the role of ADT in the management of early stage, high-risk prostate cancer. The authors focus the majority of their attention on the value of adjuvant and neoadjuvant ADT in combination with various types of radiation therapy. They note that current clinical practice patterns seem to have been driven by inappropriate extrapolation of existing data and financial incentives.
Fang and her colleagues propose that, in the management of early stage, high-risk patients, ADT should be used selectively and limited to settings in which a clear patient benefit can be documented. They also emphasize the idea that cardiac risk factors should be carefully assessed before initiating ADT, that modifiable cardiac risk factors should be addressed pre-treatment, and that special attention should be paid to patients’ global health status. They point out that “harming patients in the pursuit of improving cure rates and other less noble causes” should not be an acceptable medical objective.
Three additional commentaries are published in conjunction with this review article.
O’Malley et al. discuss the role, the timing, and the duration of ADT. They state their opinion that, based on the available evidence, “Two or 3 years of neoadjuvant/concomitant/adjuvant ADT should be used when possible in high-risk patients undergoing potentially curative RT, and a shorter ADT course of 6 months should be considered for intermediate- or high-risk patients who are physiologically older. ADT should be used with radical prostatectomy in lymph node–negative patients only in the setting of a clinical trial.”
Leja and Yeh address the management of cardiovascular risk associated with the use of ADT. They suggest that, while decisions about when to initiate hormone therapy and for how long hormone therapy is needed, should be made between the individual patient and his doctor:
- Patients’ primary care physicians should monitor these patients closely for manageable changes in metabolism related to ADT.
- Patients receiving ADT, especially those patients with baseline cardiac disease, should likely have appropriate, aggressive management with lipid-lowering therapy, antihypertensive medications, glucose-lowering therapy, and antiplatelet therapy.
- Healthy lifestyle changes, including smoking cessation, targeting obesity reduction, and increasing exercise, should be advised in patients receiving ADT.
Buyyounouski comments specifically on the linkage between ADT and radiation therapy. He makes the interesting point that the “duration” of ADT (which may be anywhere from a month to 3 years) normally refers to the length of treatment with an LHRH agonist as opposed to the the length of time that the testosterone level is suppressed. He notes that time to recovery of serum testosterone following ADT varies greatly, and that sometimes recovery of serum testosterone does not occur. He suggests that without continuous assessment of serum testosterone levels, neither the doctor or the individual patient actually know what the “true duration” of ADT actually is, implying that regular monitoring of serum testosterone (during and after hormone therapy) is a critical component of ADT.
The bottom line for patients?
- Don’t let yourself get rushed into early hormone therapy without a clear conversation with your doctors about the appropriateness of ADT in your individual case.
- Make sure that your cardiovascular risk factors are specifically addressed before starting hormone therapy.
- Know how long you are going to be on hormone therapy before you start.
- Discuss the need for regular monitoring of your testosterone levels with your doctors as a component of your treatment.
We are still learning how best to take advantage of hormone therapy in the management of non-metastatic prostate cancer. It’s value in node-positive disease and truly metastatic disease is well established, but earlier use should be considered carefully on an individual basis.
Filed under: Management, Treatment Tagged: | ADT, androgen deprivation therapy
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A point well noted is the importance of determining cardiac risk prior to administration of ADT. We rarely see this mentioned when ADT is being considered. As to not administering ADT until metastasis is determined: there is a fine line, particularly with recurring disease, in being able to recognize whether absolute metastasis has occurred. It is my understanding that ADT is prescribed to men with recurring disease because of the possibility metastasis has occurred, though not necessarily visible in imaging.
Chuck:
I think it would perhaps be most accurate to state that ADT is currently prescribed for men with a rising PSA because it is medically defensible (because of the possibility of clinically significant micrometastasis) and legally wise (so that one doesn’t get sued later for malpractice if the patient does have metastasis).
Micrometastasis may still be clinically insignificant if a patient’s PSA doubling time is long (e.g., > 15 months), and, rightly or wrongly, some centers, including Johns Hopkins, will strongly encourage patients not to use ADT until there is definitive evidence of metastasis. The question we are trying to address here is, “What is good medical practice, and how does one make the appropriate clinical decision for the individual patient?”