Early chemotherapy in treatment of high-risk and aggressive prostate cancers?

So the results from the CHAARTED and STAMPEDE trials over the past few years have re-ignited debate over the appropriateness of early use of chemotherapy in the treatment of aggressive forms of prostate cancer.

Two recent articles in JAMA Oncology take opposing positions on this issue:

Unfortunately it is not possible for most readers to be able to see the full texts of these two articles, but one can see a good deal of them.

The “New” Prostate Cancer InfoLink tends to take a position that is nearer to that held put forward by Yu and Lin. In other words, we believe that early chemotherapy is appropriate for some patients — particularly younger patients with node-positive and other very high-risk forms of localized prostate cancer — who wish to seek aggressive, potentially curative forms of treatment, and may be able to handle such therapy without high risk for serious, long-term side effects. However, we are also very clear in our minds that early chemotherapy is just one element in the combination therapy for such patients, which may require the combination of chemotherapy with surgery, radiation therapy, and androgen deprivation therapy as well. This is not a form of treatment that should be entered into lightly.

What we need at this time is to establish consensus on ways to delineate those patients for whom early chemotherapy may be a really good option, so that they can then discuss this option with their physicians. The other thing that we need is a large, randomized trial designed to see if we can confirm whether early chemotherapy really does come with a long-term survival benefit for carefully selected subsets of patients.

It is clear to us that, just as there are likely to be men who will benefit from such aggressive forms of treatment, there are also going to be men who will absolutely not benefit, and for whom the risks are definitely going to be greater than the potential rewards. We need to make sure that we are helping such patients to understand not just when they might be good candidates for early chemotherapy, but also when there are a lot of data to suggest that they are probably poor candidates for such a form of treatment.

This is — once again — not a “black and white” dichotomy. Aggressive, high-risk prostate cancer that is not evidently metastatic on a bone scan (as Yu and Lin carefully note) encompasses a highly heterogeneous group of men. These men have the right to understand all of the options that may be appropriate for them so that they can work with their physicians to seek a form of treatment that “works for them” — with a full understanding of the potential (and consequent) risks and benefits.

One Response

  1. Yu and Lin’s commentary was apparently written before the recent update of CHAARTED. They wrote that they expected that a statistically significant benefit would be demonstrated in the low volume subgroup with longer follow-up. That turned out not to be the case — the low volume subgroup continues to show no survival benefit with docetaxel. Perhaps this might change their opinion.

    It seems to me that non-metastatic prostate cancer is potentially curable

    (1) In high-risk (radical treatment-naive) patients
    (2) In patients with a locoregional-only recurrence

    In both cases, studies have failed to demonstrate a meaningful survival benefit with docetaxel adjuvant to other therapies (radical prostatectomy, radiation therapy, or salvage radiation therapy). It is possible that there is a subgroup that might benefit — but we don’t have a clue yet as to how to identify such patients.

    This leaves a third patient setting:

    (3) In non-metastatic patients who have already failed all potentially curative salvage therapies.

    It seems to me that docetaxel + ADT may provide a benefit in some such patients (we lack data on this cohort), but again we have the problem of how to select those patients that can potentially benefit.

    We know that the prostate cancer cells eventually become resistant to taxanes. My hunch is that the prostate cancer cells must previously undergo a genetic change before docetaxel is at all useful, so there is only a window of opportunity. But this is just my guess, and I have no idea what those genetic shifts might entail.

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