Guidelines and the current treatment of mCRPC


The December 1 issue of The ASCO Post contains two articles that will be of interest to many patients with progressive disease and their family members.

The first article, by Matthew Stenger, is a summary of the recently released ASCO/CCO guideline on the systemic treatment of men with metastatic, castration-resistant prostate cancer (mCRPC) with drugs intended to manage their cancer. We have already mentioned this new guidance, and  we don’t plan to revisit this article here in detail. It offers some relatively straightforward advice about what forms of anti-cancer drug therapy can be used in the management of mCRPC and when.

The second article, by Maha Hussain, MD, is perhaps going to be of greater interest to many readers of this web site.

Dr. Hussain, a highly-regarded opinion-leader in the management of late-stage, progressive forms of prostate cancer, makes two key points in her article. First:

The authors [of the guideline] should be congratulated on their effort and a very balanced discussion. As a practicing oncologist, however, I am not clear that the content and the guidance change what we are currently doing in practice. It is also important that we streamline the different practice and consensus guidelines through collaboration between representative societies and groups (e.g., ASCO, American Urological Association, National Comprehensive Cancer Network) to create one unified guideline … that is practical to use.

She goes on to state that:

Finally, we must raise the bar for future trials by requiring greater therapeutic efficacy, minimizing use of placebo, avoiding artificial disease contexts, developing multitargeted treatment strategies aiming at a maximum cytotoxic impact, and evaluating and maximizing cost-effectiveness.

We have multiple approved drugs that can now be used on- and off-label in the management of mCRPC:

  • The older, standard forms of androgen deprivation therapy (ADT), including the LHRH agonists, the LHRH antagonist degarelix, and the antiandrogens (bicalutamide, flutamide, etc.)
  • Older, standard forms of chemotherapy — basically docetaxel + prednisone and mitoxantrone + prednisone
  • Older forms of systemic radiotherapy — strontium-89 chloride and samarium-153 lexidronam
  • Newer forms of ADT, including abiraterone acetate + prednisone and enzalutamide
  • Newer forms of chemotherapy — cabazitaxel + prednisone
  • A single form of immunotherapy — sipuleucel-T
  • A single new form of systemic radiotherapy — radium-223 dichloride

The basic problem with the new ASCO/CCO guideline is that while it nicely summarizes the known facts about all of these drugs, it is unable to offer us clear guidance about their optimal use. Why? Because we just don’t have the necessary or the relevant data that would allow us to determine how best to use these drugs — alone, in combination, or in sequence — in any particular patient. Even the one really clear directive in the new guideline (that all patients with mCRPC should continue to receive continuous standard ADT for life, regardless of other forms of treatment) has been questioned by some members of the professional and the patient community! We don’t, after all, have any data suggesting that stopping ADT when you start a man on (say) abiraterone acetate is either beneficial or problematic compared to maintaining him on the ADT.

We believe that Dr. Hussain is right on  target in her comments about the new guideline. It offers guidance to medical oncologists who aren’t highly familiar with the treatment of mCRPC  about what they can and should not reasonably do. It offers no really useful guidance about what is best for the patient.

One Response

  1. AMEN to Sitemaster’s conclusions

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