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Joint Clinical Practice Guideline from ASCO & Cancer Care Ontario on Systemic Therapy for Metastatic Castration-Resistant Prostate Cancer

DiGiulio, Sarah

doi: 10.1097/01.COT.0000455785.33540.15


The American Society of Clinical Oncology and Cancer Care Ontario (CCO) have issued a joint clinical practice guideline on treating men with metastatic castration-resistant prostate cancer. The guideline includes recommendations on systemic therapies that are indicated for use alongside androgen deprivation.

“The key recommendation in the guideline is that for men with castration-resistant metastatic prostate cancer, androgen-deprivation therapy should be continued; and second, the guideline offers recommendations for the drugs that should be offered,” Ethan Basch, MD, MSc, Co-Chair of the ASCO/CCO Expert Panel that developed the guideline, said in a phone interview.



“We have seen unprecedented progress against advanced prostate cancer recently, with six new treatments approved in the last couple of years. We hope this guideline will help doctors and patients make informed treatment decisions.”

Basch, who is Director of the Cancer Outcomes Research Program and Associate Professor of Medicine and Public Health in Lineberger Comprehensive Cancer Center at the University of North Carolina-Chapel Hill, explained that there have been previous guidelines for treatment for these patients from other organizations, but this guideline is the first for this subset of patients from ASCO, and it also includes recommendations for several drugs that until recently were not available.

“The guideline lists which drugs have advantageous survival, quality of life, and low toxicity profiles—and then sequentially those that have lesser quality-of-life data or those that have greater toxicities so that patients and providers can make informed decisions about treatment,” he said.

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Key Recommendations

The first recommendation states that androgen deprivation (either pharmaceutical or surgical) should be continued indefinitely regardless of additional therapies.

The recommendation is that these drugs be offered because of their beneficial impact on both survival and quality of life:

  • Abiraterone acetate and prednisone should be offered;
  • Enzalutamide should be offered;
  • Radium-223 should be offered to men with bone metastases; and
  • Docetaxel and prednisone should be offered (with the acknowledgment that there are likely more toxicities with docetaxel than with the other products, and that those side effects risks should be discussed with the patient).

The guideline recommends that the following drugs may be offered, which have demonstrated a survival benefit but unclear quality of life benefit:

  • Sipuleucel-T may be offered to men who are asymptomatic or minimally symptomatic; and
  • Cabazitaxel and prednisone may be offered to men who experience progression with docetaxel.

The guideline also notes that mitoxantrone plus prednisone may be offered, though it is not likely to offer a survival benefit, and can bring toxicities: “There's no evidence currently comparing these drugs to each other, making it very challenging to recommend one over another—because there is no head-to-head data yet,” Basch said.



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Quality of Life and Palliative Care

Another key recommendation is that palliative care services should be offered to all men in this disease context. “Quality of life is very important in this population and in all patients with advanced cancer. Although many agents do prolong survival, that survival is often counted on the order of weeks or months—the drugs are often toxic—and therefore treatment in this context is by definition palliative, and therefore must speak to quality of life.”

And the key recommendations the guideline considered is whether drugs have a demonstrated quality-of-life benefit, Basch added. “Some drugs do not have quality-of-life data available, and in the absence of such data, we can't necessarily tell if the benefits on the patient experience outweigh the harms. We hope that one of the outcomes of this guideline is that product developers will integrate patient-reported outcomes or quality-of-life data into trials moving forward, so that information will become available.”

Quality-of-life information is also a prominent part of the discussion sections for each drug. “In prostate cancer, one of the most important symptoms is pain—and we go to lengths to discuss pain in this guideline.”

The guideline also notes in the Qualifying Statements section that there should be clear communication between patient and provider about the goals of care. “There is evidence that patients sometimes don't understand that the goal of treatment is palliative rather than curative; and when treatment is understood to be palliative people may be less enthusiastic about a more toxic regimen. Therefore, clear communication about the goals of care and prognosis is very important when selecting therapies with patients,” Basch said.

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Other Recommendations

The guideline also notes for which products there is still limited evidence available regarding survival and quality-of-life benefits. The recommendations note that antiandrogens (e.g., bicalutamide, flutamide, and nilutamide), ketoconazole, and low-dose corticosteroid monotherapy may be offered (as they have shown biologic activity), but the drugs still have unknown survival or quality-of-life benefit.

And the guideline recommends that bevacizumab, estramustine, and sunitinib should not be offered, since they have not demonstrated survival or quality-of-life benefits (the strength of that evidence being moderate, and the strength of those recommendations being strong).

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Unanswered Questions

The guideline also includes qualifying statements that note there is insufficient evidence yet on using the aforementioned drugs in combination or in sequence, and therefore this guideline does not make specific recommendations regarding those questions.

Still, there are unanswered questions: “We need to understand the mechanisms of resistance better—to understand why various treatments may be more or less effective in particular patients or in sequence or in combination, Basch said.

The guideline builds upon prior recommendations from ASCO and CCO that were based on a systematic review of 28 randomized clinical trials published between 1979 and 2004. An additional 28 randomized clinical trials on systemic therapies were identified since 2004, including on targeted therapies and immunotherapies. These additional randomized trials inform the current recommendations.

The guideline is now available online ahead of print in the Journal of Clinical Oncology (doi: 10.1200/JCO.2013.54.8404). Individuals can make comments or suggestions on this and other ASCO guidelines on the Society's new guideline wiki site:

© 2014 by Lippincott Williams & Wilkins, Inc.
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