Men initially diagnosed with de novo metastatic prostate cancer are living longer


A newly published study entitled “Improved cancer-specific free survival and overall free survival in contemporary metastatic prostate cancer patients: a population-based study” is important … but needs to be interpreted with a significant degree of caution.

Bandini et al. have conducted a careful and sophisticated statistical analysis of the overall and prostate cancer-specific survival times of men diagnosed with metastatic prostate cancer in the US between 2004 and 2014. (See also this commentary on the Medscape web site.) Starting with >19,000 men identifiable in the SEER database, the authors used a technique known as “propensity score matching” to winnow down the initial 19,000+ men to a cohort of 8,596 patients with de novo metastatic prostate cancer who were “matched” to each other in a consistent manner.

Based on the median year of diagnosis of these men, they divided them into two groups:

  • Group A: Men diagnosed between 2004 and 2008 (n = 4,298)
  • Group B: Men diagnosed between 2009 and 2014 (also n = 4,298)

The 4,298 men in each group had an average (median) age of 70 years, and the majority had received no prior treatment for localized disease.

They then looked at the prostate cancer-specific and overall survival data for these two groups of patients.

Here is what they found:

  • Cancer-specific mortality-free survival from time of diagnosis was
    • 32 months for patients in Group A
    • 36 months for patients in Group B
    • This difference was highly statistically significant (p < 0.0001)
  • Overall mortality-free survival from time of diagnosis was
    • 26 months for patients in Group A
    • 29 months for patients in  Group B
    • This difference was also highly statistically significant (p < 0.0001)
  • For men in Group B compared to men in  Group A,
    • The hazard ratio for cancer-specific mortality was significantly lower (HR = 0.88)
    • The hazard ratio for overall mortality was also significantly lower (HR = 0.88)

The inescapable conclusion is that there was a small but significant average increase in cancer-specific and overall survival times of men diagnosed with de novo metastatic prostate cancer from 2004-2008 to 2009-2014 — and that probably doesn’t include any benefit from initial combination therapy of such patients using standard androgen deprivation therapy (ADT) + docetaxel-based chemotherapy or abiraterone + docetaxel-based chemotherapy shown in  recent trials like the CHAARTED, STAMPEDE, and LATITUDE trials (because the data from these trials weren’t reported until 2014 at the earliest).

As the authors carefully point out:

This population-based study provides the first evidence of improved [cancer-specific mortality] free survival and [overall mortality] free survival in patients with de novo [metastatic prostate cancer] since the introduction of several systemic agents for CRPC patients.

However … and this is a big “however” … we need to remember that back in the late 1980s and early 1990s, the oft-quoted overall survival time of a man newly diagnosed with metastatic prostate cancer was said to be 18 to 36 months (i.e., an average of about 27 months). So just how much progress have we really made with all these new drugs?

We suspect that what has really happened here is that, just as there has always been a subset of men who got extraordinary increases in cancer-specific survival times from treatment with “old-fashioned” forms of ADT, there are also small subsets of men who have been getting extraordinary increases in their cancer-specific survival times from one or more of all these new drugs in the treatment of metastatic, castration-resistant prostate cancer: docetaxel (Taxotere), cabazitaxel (Jevtana), sipuleucel-T (Provenge), abiraterone acetate (Zytiga), and enzalutamide (Xtandi). However, out in the “real world” (i.e., outside of clinical trials), it seems to The “New” Prostate Cancer InfoLink, based on this analysis at least, that we may not have made as much progress as we would sometimes like to think has been achieved. Many, many men diagnosed with de novo metastatic prostate cancer appear to still be dying within the same time frame as they were back in the late 1980s.

The progress described by Bandini et al. is good, of course. But there have to be real questions about whether the majority of men diagnosed with metastatic prostate cancer have actually been getting optimal forms of treatment. Several of these new drugs are expensive; they may be inappropriate for many patients because those patients have c o-morbid conditions; or their doctors may not have been ensuring that the right drugs were offered to the right patients early enough in the progression of their disease.

It is not enough to just have these new drugs available in theory. We need to be making sure that they are actually available — based on the medical, fiscal, and social realities — to all the patients who really could benefit from their appropriate use. And the same is true if we are to see the potentially significant increases in survival times that have been strongly suggested by the data from the CHAARTED, STAMPEDE, and LATITUDE trials over the past 3 years.

3 Responses

  1. My husband has — in his treatment of metastatic, castration-resistant prostate cancer — received all of the following: 40 Rounds of radiation; docetaxel (Taxotere), cabazitaxel (Jevtana), sipuleucel-T (Provenge), abiraterone acetate (Zytiga), and enzalutamide (Xtandi) + Firmagon injections as the first treatment — then changed to Lupron injections every 6 months. He was diagnosed 5 years ago this month, with a PSA of “well over 100”, and a Gleason score of 10. Stage IV metastatic prostate cancer at diagnosis, with lymph node and bone involvement.

    I was hoping that CAR-T would be an option, if not a cure for him, but due to other issues, he’s not a likely candidate — though at this point, I don’t see the harm in trying. I don’t think things could get much worse for him — healthwise — in this lifetime.

    Thank you for these informative reads — I read them for any ounce of earthly hope for a cure for my husband of 39 years. Nothing yet seems to be out there for my husband at this stage. Hoping that the cure will come soon for all men. Living in hope until there is no hope for my own husband.

    Thank you again!

    Ellen

  2. Dear Ellen:

    I am sure that many readers will entirely understand your message and we all have great sympathy and sorrow for your husband’s situation — and your’s too.

    Alas, real progress is often slow, but as I told Dr. June on the phone on Wednesday, I seriously expect him and some of his collaborators to get a Nobel Prize for the development of CAR-T, and hopefully we will indeed find a way to make it work in prostate cancer as well as in the hematological cancers.

  3. Good luck to you and yours @Ellen

    @Sitemaster: adding to your thesis more of the later cohort will have been detected by screening as well, biasing diagnosis earlier.

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