The abstract for the presentation of the resulsts of the REDEEM trial (to be presented on Thursday at the Gentourinary Cancer Symposium in Orlando) was published this evening on the ASCO web site. The data show that dutasteride delayed progression of prostate cancer in a well-defined group of patients compared to placebo therapy.
The Reduction by Dutasteride of Clinical Progression Events in Expectant Management of Prostate Cancer (REDEEM) study was designed to investigate whether dutasteride — a 5α-reductase inhibitor or 5-ARI — could affect the progression of disease in a well-defined group of patients with pre-existing, low-risk, localized prostate cancer.
The trial enrolled a total of 302 patients, all diagnosed with prostate cancer and aged between 48 and 82 years, who met the following criteria:
- PSA < 11 ng/ml
- Gleason score ≤ 6
- Not more than 3 biopsy cores positive for cancer
- Less than 50 percent of every positive core containing cancer
The patients were randomized to receive either dutasteride (0.5 mg once daily) or a placebo for 3 years.
All patients were initially scheduled to receive repeat 12-core biopsies after 18 and 36 months. However, the patinets could also receive follow-up biopsies “for cause” (i.e., because of other indications of the posibility of disease progression) at other times during the study.
The primary endpoint for the study was time to progression. Progression was characterized by any one of several possible events:
- Pathological forms of progression evident on biopsy
- A Gleason score >6
- 4 or more positive biopsy cores on a 12-core biopsy
- More than 50 percent of any biopsy core positive for cancer
- Therapeutic forms of progression requiring treatment (by radical prostatectomy, radiation therapy, or hormonal ablation)
The abstract of the presentation to be given by Fleshner et al. provides the following results:
- 96 percent of study participants of subjects reached the primary endpoint or had at least one post-baseline biopsy.
- Dutasteride significantly reduced time to prostate progression compared to placebo (relative risk reduction = 38.9 percent; P = 0.007).
- 23 percent of men (N = 31) in the placebo group and 36 percent of men (N = 50) in the dutasteride group had no cancer detected at the time of their 36-month biopsy.
- Prostate cancer-related anxiety was reduced in the dutasteride arm compared to the placebo arm (P = 0.036).
- Drug-related adverse events were similar to those previously reported for dutasteride.
- There was no evidence of Gleason score upgrading over time among men on dutasteride therapy.
Fleshner and his colleagues conclude that, in this cohort of low-risk patients, who were effectively being managed with active surveillance with or without dutasteride therapy, “dutasteride delayed the time to [prostate cancer] progression, increased the percent of men with no detectable [prostate cancer], and improved [prostate cancer]-related anxiety.”
Can we conclude from this study that dutasteride is a safe and effective form of treatment for men with low-risk prostate cancer who are suitable candidates for active surveillance? That is going to be a much more complex question, and we are going to delay offering our answer to that question until we have heard the full presentation on Thursday.
Filed under: Diagnosis, Living with Prostate Cancer, Management, Risk, Treatment | Tagged: dutasteride, localized, low risk, REDEEM |
THE "NEW" PROSTATE CANCER INFOLINK 
I hope we are not instilling a false sense of security with another short-term study. Do you think that the results would be the same for finasteride? I look forward to your follow up.
Interesting article. I understand you are going to attend the presentation and I wonder if you could ask if they have an explanation or a suggestion regarding the reduction in prostate-cancer anxiety for the treated versus placebo arm. After all, anxiety is a psychological phenomenon and men in both arms should have been under the impression they were treated.
Hummm! I’ll also reserve comment until you are able to report on the full presentation
Good one Reuven — How blind is a blind study?
Seems to me that anxiety had to be less on those with a stable (or reduced) PSA that were on the Avodart pill even in a blind study if those men were aware of their PSA during the study period.
Bottom line is that this 5-AR inhibitor actually affects prostate cancer progression. But then we knew that Proscar did that too long time ago as reported by Rittmaster RS et al. back in 1996.
According to Dr. Fleshner, giving the presentation this morning, the PSA levels of the patients in this study were not centrally blinded or assessed, so patients on dutasteride would likely have seen that their PSA levels were well controlled (even though they would not have actually known whether they were on durasteride or placebo).
According to the published abstract, a little over half the progression difference was due to “therapeutic” progression (11 on dutasteride vs 20 on placebo). It would be interesting to know what the reasons for this were. Is it that men chose to move on to surgery/radiation because of a worsening PSA before getting (or irrespective of) the follow up biopsies? If so part of the dutasteride “benefit” would be due to the psychological effect of lowered PSA, which may not correspond to an actual therapeutic benefit. Did the researchers comment on this aspect of the study in their presentation?
Richard:
A “pathologic” progression was a documentable progression based on biopsy data at any time during the study (whether the biopsy was triggered by a scheduled biopsy at 18 or 36 months or based on on some other reason such as a significant change in PSA or DRE findings). A “therapeutic” progression was treatment for any other reason — which clearly could include the simple desire of the patient to get treated.
As noted in an earlier comment, PSA data in this study were not centrally coordinated and were not kept confidential from the patients. (The later would probably be considered unethical.) As a consequence, many of the patients would have probably been monitoring their PSA data. If one had a rising PSA (on dutasteride or on placebo), one might decide that one wanted treatment — even if there was no pathologic data to support such a decision. No one is suggesting that using dutasteride while on active surveillance is a curative strategy. It is a possible means to (a) further delay the need for invasive therapy and (b) help men to be comfortable with that decision because dutasteride therapy helps to eliminate or at least reduce the variation in some of the common fluctuations in PSA level that commonly occur among men on active surveillance. Seen from that point of view, yes, of course some of the dutasteride benefit is “psychological.” After all, even in men men who had negative biopsies at 18 and 36 months after entering the trial, we cannot say that they now don’t have prostate cancer. They had all had a prior positive biopsy. All one can say after these later results is that we cannot (currently) find evidence of cancer at the time of the most recent biopsy.
I think that one of the most significant facts in the results of this trial is that — 23% of those participants in the placebo group “had no cancer detected at the time of their 36-month biopsy.”
These are men who had positive prostate cancer biopsies at the beginning of the trial and did nothing.
Vanishing prostate cancer??
How many of these guys would have been treated needlessly by an aggressive urologist?