Overall survival among participants in the Prostate Cancer Prevention Trial

The Prostate Cancer Prevention Trial (PCPT) showed that treatment with finasteride (a 5α-reductase inhibitor) could lower the number of prostate cancers diagnosed in the U.S. each year by about 25 percent. However, there was also an apparent risk that treatment with finasteride could increase (very slightly) the chance for diagnosis with high grade prostate cancer.

Between October 1993 and May 1997, the PCPT enrolled 18,882 (mostly white) patients, so it has now been 15 to 20 years since all these men (who had to be at least 55 years of age at time of enrollment) were originally randomized to treatment with finasteride or to a placebo.

At the Genitourinary Cancers Symposium today in Orlando, Florida, Goodman et al. will present data from a survival analysis of all PCPT participants designed to look for any evidence of an increase in risk of death for the men who were randomized to treatment with finasteride, which would be a potential indicator of a “true” increased risk of high grade (HG) disease among participants in the PCPT.

To do this, the research team carried out a search of the U.S. Social Security Death Index to determine the dates of death of all participants in the PCPT who had died. They then used these data to estimate hazard ratios (HRs) and to determine whether survival times of men randomized to finasteride and to placebo were equivalent.

Here is what Goodman and her colleagues will report today:

  • 5,128/18,882 men are reported to have died.
    • 2,584 are men randomized to treatment with finasteride.
    • 2,544 are men randomized to treatment with the placebo.
  • The 15-year survival rates for all randomized men in each arm is 78 percent.
  • The HR for overall survival on finasteride compared to placebo is 1.04 (which is not statistically significant).
  • The 10-year survival from diagnosis for all men actually diagnosed with prostate cancer during the PCPT was
    • 83 percent for men randomized to finasteride
    • 81 percent for men randomized to the placebo
  • For men diagnosed with high grade prostate cancer during the PCPT, there was no evidence of worse survival on finasteride (HR = 1.01).
  • For men diagnosed with low grade prostate cancer during the PCPT, there was statistically significant evidence of superior survival for men on finasteride (HR= 0.73).

Now Goodman and her colleagues are quick to point out that one can not conclude from their data that treatment with finasteride was necessarily the cause of extended survival of the men with low grade prostate cancer, although this is certainly possible.

What Goodman et al. do conclude is that

With follow-up of 18 years, finasteride administration for 7-years does not appear to affect mortality but significantly reduces the risk of a … diagnosis [of prostate cancer].

5 Responses

  1. What were the participating “patients” being “treated” for by taking finasteride? I take it that none had been diagnosed with prostate cancer before starting the test. Am I missing something?

  2. Anderson:

    These were otherwise healthy men who were being given finasteride or a placebo to see if treatment with finasteride would lower their risk for having a diagnosis of prostate cancer. It was a prevention trial, not a treatment trial.

  3. With reference to the relative survival rates for men diagnosed with prostate cancer, are there disease-specific mortality rates quoted?

  4. Terry:

    No. I do not think the authors were able to obtain the detailed “cause of death” records for all the men who had died, so it would not have been possible to assess disease-specific mortality rates, let alone the accuracy of the assignment of cause of death.

    Dr. Goodman was very clear with me that all they had been able to demonstrate was that there appeared to be no greater risk for overall mortality in the men treated with finasteride, suggesting that the idea that men taking finasteride were at any significantly higher risk for more aggressive forms of prostate cancer (and consequent death therefrom) appears to be invalid.

  5. Thank you so much for posting this important result.

    On Dec. 1, 2010 I watched a live webcast of the FDA Oncologic Drug Advisory Committee meeting on finasteride’s sister antiandrogen class drug, dutasteride, for prevention, and I posted my profound disappointment with the ODAC result here that evening. The elephant in the room as the committee made its decision against dutasteride (Avodart) for prevention was the high grade issue, especially the evidence in the finasteride trial, addressed in the current report.

    I am delighted to see this evidence that supports the absence of stimulating higher Gleason grade cancer in some men. I have some hope that the FDA will reconsider its label requirements for both finasteride and dutasteride that warn about that effect (based on what I view as overreaction to shaky evidence). Someday I hope the labels for both drugs will be revised to indicate potential for prevention of a proportion of low grade prostate cancer.

    Though anecdotal, my own experience with a Gleason 4 + 3 cancer at original diagnosis (per Epstein) is in line with the current research: no evidence through the 14th year point of a shift to Gleason 8 or higher cancer based on all evidence of the behavior of my cancer. While I have been convinced for some time that the high grade potential suggested by some analysis of the PCPT was an artifact, as explained by the expert trialists (such as Dr. Ian Thompson), it is also personally reassuring to see this current evidence because a 5-ARI inhibitor has been part of my cancer control regimen every day since September 17, 2000 for a challenging case of prostate cancer considered incurable until recently. Today, in fact, I got my CT planning session and target marks for upcoming TOMOtherapy radiation. I am in the fifth month of my fourth on-cycle of intermittent triple androgen deprivation therapy, and my PSA has again declined nicely from a tested high of 19.24 on September 17, 2012 (date coincident with start of finasteride, above) to 1.9 last week. (I’ve been on dutasteride for some time as my DHT clearly was lower and in the best range on dutasteride, something I could not quite accomplish on finasteride.)

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