Continuation of PROSTATE CANCER: LATE STAGE
There are studies to support the concern that adrenal androgen precursors can increase in the setting of PC treatment and that this increase leads to higher T levels, which in turn effects a poor clinical outcome, if unrecognized. The elevation in androstenedione and T shown below in 10 of 27 men undergoing orchiectomy for PC supports our concerns (Sciarra et al., Clin. Endocrinol., 1993).
| Take-home Lesson 1 In situations involving progressive disease as seen by a consistently rising PSA, stop and reassess the hormone status to determine whether AIPC is present. |
The Response to ADT as a Guide to the Presence of AIPC
The evaluation of the response of available bio-markers to ADT provides clues to the presence or absence of AIPC. In essence, it is an in vivo test of the tumor cell population. If the tumor cell population is predominantly that of ADPC (androgen-dependent PC), there is usually a brisk drop in PSA to very low levels that are maintained during the course of ADT. This assumes that an ARM has not developed over the course of time. The newly diagnosed patient with dramatic sensitivity to ADT, most likely has ADPC. We use an ultra-sensitive assay (3rd Generation Immulite from DPC International, Los Angeles) and define an undetectable PSA (UDPSA) as <0.05. If the patient achieves and maintains this level, it has been our experience that the development of AIPC is rare. On the other hand, if a UDPSA is not achieved or is achieved after a prolonged period of time, we are concerned about the presence of AIPC. In our experience, the biology of the tumor is manifested in its response to ADT. It therefore becomes significant to use a sensitive assay to monitor the response to ADT to confirm suspicions to the presence of AIPC.
| Take-home Lesson 2 The response to therapy using ADT is a clue to the nature of the tumor cell population. ADT and its response is an in vivo test of the tumor cell population. Understand the nature of the PC by its response to a treatment approach. If a UDPSA is not reached in a relatively short period of time, be more concerned about the presence of AIPC. |
Androgen Receptor Mutation (ARM) and
Anti-androgen Withdrawal (AAW)
We now know that an ARM can result in the antiandrogen paradoxically stimulating tumor growth. Antiandrogen withdrawal in such patients has been shown to result in tumor regression in approximately 20% of patients. This phenomenon is referred to as an anti-androgen withdrawal response (AAWR).
If androgen blockade included an anti-androgen- e.g. Eulexin, Casodex, or Nilandron-these agents must be stopped in order to monitor for a possible AAWR. Failure to recognize an AAWR is one of the problems encountered when we attempt to interpret results of studies of PC treatments published in the past. If a patient stopped anti-androgen therapy at the same time a different therapy was started, an AAWR, if it occurred, could affect the assessment of response to the second therapy. PC treatment studies should require withdrawal of anti-androgens for at least 2 to 6 weeks (the longer time in patients being withdrawn from Casodex) to assess whether or not the PSA decline is due to an AAWR.
Another reason for supporting measurement of adrenal androgen precursor levels was reported in a 1994 abstract. In that study, Herrada et al. (Proc. Am. Soc. Clin. Oncol., 1994) measured serum levels of dehydroepiandrosterone (DHEA) in 10 patients with PSA progression on ADT. After antiandrogen therapy was stopped, patients were observed for an AAWR. None of the patients with DHEA levels > 75 ng/ml had an AAWR, while 3 of 5 patients (60%) with DHEA levels < 75 ng/ml achieved an AAWR. Therefore, DHEA levels at the time of PSA progression may be used to identify patients who may or may not benefit from anti-androgen withdrawal.
Continuation of PROSTATE CANCER: LATE STAGE