Last June, at the annual meeting of the American Society for Clinical Oncology, Hussain and colleagues presented data from the S9346/INT-0162 trial of continuous vs. intermittent androgen deprivation therapy in men with androgen-sensitive, metastatic prostate cancer.
The finalized results of this trial have now been published in this week’s edition of The New England Journal of Medicine (NEJM), and they confirm the difficulties discussed at the ASCO meeting and subsequently about exactly how best to interpret the outcome of this 17-year-long study. (Unfortunately, the full text of the article is only available to subscribers to NEJM.)
To quote the conclusion of the published report by Hussain et al.:
Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life.
It would appear that, perhaps because of what can now (nearly 20 years later) be seen to be some flaws in the design of the study, the question of whether intermittent ADT is or is not as good as continuous ADT for specific patients with progressive prostate cancer remains unresolved.
Readers who have not previously been aware of this study and all of the surrounding issues may wish to review some of the other posts that address the study findings and related topics:
- IAD vs. CAD in men with hormone-sensitive, metastatic prostate cancer (June 3, 2012)
- Interpreting the data from the S9346/INT-0162 trial in hormone-sensitive, metastatic disease (June 4, 2012)
- IAD vs. CAD all over again: are you confused yet? (August 14, 2012)
- IADT: the still unanswered questions and choices that must be made (September 6, 2012)
Filed under: Living with Prostate Cancer, Management, Treatment | Tagged: androgen, continuous, deprivation, intermittent, metastatic |
THE "NEW" PROSTATE CANCER INFOLINK 
Am very glad the study was conducted. For those with the caution to hear and heed warnings, findings that are fuzzy and tentative are preferable to no report at all.
Two questions:
1. The quote refers to “a 20% greater risk of death with [IADT] than with continuous therapy.” Would this be (a) prostate-cancer-specific death, as might be expected? or, instead (b) death from all causes?
To my mind, 1(a) and 1(b) represent rather different findings.
2. The quote states, baldly, “Intermittent therapy resulted in small improvements in quality of life.” Is it possible to learn which of the following two very different statements is intended?
(a) “Individually, for each man on IADT, only a small QoL improvement was provided by ADT holidays, according to repeated standard questionnaire-based assessments” or, instead (b) “Aggregated over all men on both kinds of therapies, a single retroactive questionnaire-based assessment found only a small QoL improvement in cohort A (IADT) compared to cohort B (continuous therapy).”
To my mind, 2(a) and 2(b) represent totally different findings, even though each could be condensed into the quote cited.
Why is this important? For me personally, a 20% increase in prostate-cancer-specific death is a risk I’d gladly take in exchange for the vast (for me) improvement in QoL afforded by ADT holiday. If the study was reporting either result 2(a) or result 2(b), then the “question of whether intermittent ADT is or is not as good as continuous ADT” is clearly resolved (for me).
Another factor: If the men were allowed to choose between IADT and continuous therapy, it’s reasonable to guess that those choosing IADT have a miserable reaction to ADT, and thus might have an overall worse QoL than those who have very little reaction to ADT. This might significantly bias the results of interpretation 2(b), which might be refactored as a big win for IADT rather than a small loss.
If interpretation 2(a) was intended, then I am not typical. But if 2(b) and 1(a), then (for me) IADT is enormously superior to continuous therapy, even if it were to fail the specific myopic metric of being differentially better than continuous therapy at averting or postponing death specifically by prostate cancer.
Dear Paul:
First, the mortality rates reported in this study were overall mortality rates from all causes and not prostate cancer-specific mortality rates.
Second, it is my understanding that the reference to small improvements in quality of life are a reference to “average” consolidated data. While some individuals may appear to demonstrate significant quality of life benefits, these would be outliers (as would those who may have shown quality of life deficits while on intermittent androgen deprivation).