New ASCO Guideline for Castration-Resistant Prostate Cancer

Alexander M. Castellino, PhD

September 11, 2014

With the approval of several new agents over the past few years, systemic treatment for men with metastatic castration-resistant prostate cancer (PC) has evolved significantly. Now the American Society of Clinical Oncology (ASCO) has partnered with the Cancer Care Ontario (CCO) to provide a guideline on treating men with metastatic PC in whom androgen-deprivation therapies have failed.

The guideline was published online September 8 in Journal of Clinical Oncology.

"The guideline was prompted primarily from the host of new drugs approved for men with metastatic castration-resistant PC," said guideline lead author Ethan Basch, MD, associate professor of medicine at the Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, in an interview with Medscape Medical News.

The new guidance is similar to and complements the guideline issued by the American Urology Association (AUA), which was published last year and updated this year.

Benefits Demonstrated or Not

The guideline contextualizes the drugs with respect to their survival benefit, toxicity, and affect on quality of life (QOL). The various agents should be given in addition to indefinite treatment with continuous androgen deprivation (pharmaceutical or surgical). In addition, the new guidance indicates that bevacizumab, estramustine, and sunitinib should not be offered because survival benefits with these agents have not been demonstrated and the agents are harmful to patients.

Table. ASCO/CCO Guidelines per Survival, Quality of Life, and Toxicity

Therapies with Demonstrated... Guideline
Survival and QOL benefits
  • Abiraterone acetate and prednisone should be offered

  • Enzalutamide should be offered

  • Radium-223 should be offered to men with bone metastases

Therapies with survival benefit but unclear QOL benefit
  • Sipuleucel-T may be offered to men who are asymptomatic or minimally symptomatic

  • Cabazitaxel and prednisone may be offered to men who experience progression with docetaxel

Therapy with QOL benefit but no survival benefit
  • Mitoxantrone and prednisone may be offered

Therapies with unknown survival or QOL benefit
  • Antiandrogens (eg, bicalutamide, flutamide, nilutamide)

  • Ketoconazole

  • Low-dose corticosteroid monotherapy

 

Dr. Basch indicated that "the recommendations were developed based on systematic reviews of the scientific literature and expert panel consensus, based on the best available evidence and clinical experience as a guide. They are evidence based and informed by RCT [randomized clinical trial] data."

How the ASCO/CCO Guideline Differs From the AUA Guideline

The ASCO/CCO guideline differs from but also complements other guidelines, including the AUA guideline, in several ways: It does not differentiate treatment options on the basis of prechemotherapy and postchemotherapy or between asymptomatic and symptomatic patients. In addition, the ASCO/CCO guide provides QOL benefits for each agent.

The new guide does not indicate which agents should be used first and which should be used later, said Stephen Freedland, MD, associate professor of urology and pathology at the Duke University Medical Center and a member of the panel that formulated the AUA guideline.

The ASCO/CCO guideline builds on the same literature as the AUA guideline, but what's not addressed here is what to do next, he told Medscape Medical News. For Dr. Basch, the ASCO/CCO guideline was not meant to take all the information and provide a summary score. Every patient is different, he said. Survival, toxicity from treatment, and QOL may weigh differently for each patient. He stressed several qualifying statements from the guideline.

First, according to the guideline, patients may place a higher importance on QOL rather than length of life. Thus, clinicians need to understand individual patient values and preferences for appropriate treatment decision making. Many patients with incurable metastatic disease misperceive the goals of care to be curative, the new guideline also states. Clear communication about goals as well as potential benefits and harms of care should be prioritized, says the ASCO/CCO guideline authors.

Second, cost and availability considerations may reasonably influence treatment decisions. The financial burden that individual patients face for various therapies varies widely. This potential barrier or hardship should be openly discussed with patients, advise the ASCO/CCO guideline authors.

Dr. Freedland told Medscape Medical News: "With the many options now available for these men [with castration-resistant PC], treatment is becoming more complex. That is why it is important to have guidelines." He also said that while there are subtle differences between the AUA and ASCO/CCO guidelines, these differences relate to the level of evidence required to make a recommendation. Ultimately, it is the clinician's choice as to which guideline to follow, Dr. Freedland added.

Multiple authors have financial ties to industry.

J Clin Oncol. Published online September 8, 2014. Abstract

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