New Guidance Issued on Second-Line Hormonal Therapy in Prostate Cancer

Katherine S. Virgo, PhD

Katherine S. Virgo, PhD

Informed by new clinical evidence, ASCO has issued updated guidance on the use of second-line hormonal therapy for chemotherapy-naïve patients with castration-resistant prostate cancer (CRPC). The provisional clinical opinion (PCO) addresses patients who are asymptomatic, with only biochemical evidence of CRPC, as well as those who have documented metastases and minimal symptoms.

Many patients with hormone-sensitive prostate cancer experience recurrence or progression despite first-line androgen deprivation therapy, but prior guidelines have not addressed second-line hormonal therapy for patients with nonmetastatic CRPC or for those who are chemotherapy-naïve, ASCO said. The new PCO reflects the findings of several recent clinical trials, which have shown that second-line hormonal treatments such as abiraterone acetate (Zytiga) and enzalutamide (Xtandi) impede cancer growth, extend survival, and provide meaningful improvement in quality of life for patients with CRPC.

"In the last few years we have seen an unprecedented number of new systemic therapies showing improvements in survival and quality of life for men with CRPC," Katherine S. Virgo, PhD, co-chair of the expert panel that developed the PCO, said in a release. "However, due to lack of guidelines on second-line hormone therapy for chemotherapy-naïve patients, there has been uncertainty regarding optimal treatment among clinicians."

An expert panel considered 6 phase III randomized controlled trials to inform the recommendations expressed in the PCO. The guidance also incorporates a systematic review of literature published from 1985 through October 2016, consensus opinions, and observed and reported clinical experiences.

The recommendations are as follows:

For patients who develop CRPC despite receiving castrate levels of testosterone, a castrate state should be maintained indefinitely, ASCO said.

Prostate-specific antigen (PSA) levels should be key to determining second-line treatment, ASCO said. The PCO defines patients at high risk for developing metastases as those who have rapid PSA doubling time or velocity, and patients who are at low risk as having low PSA and slow PSA doubling time.

The PCO recommends that for chemotherapy-naïve patients with M0 (no radiographic evidence of metastases) CRPC who have high risk of developing metastases, second-line hormonal therapies may be offered, “following discussion with the patient about the limited scientific evidence, potential harms, benefits, cost, and patient preferences.” These therapies can include antiandrogens or CYP17 inhibitors.

For chemotherapy-naïve patients with M0 CRPC who are at a low risk of developing metastases, second-line hormonal therapy is not suggested.

ASCO said second-line hormonal treatment (abiraterone acetate plus prednisone, or enzalutamide) should be offered for chemotherapy-naïve men who develop CRPC and have radiographic evidence of metastases, because these agents significantly increase radiographic progression-free survival and overall survival. Palliative care also should be offered.

The recommendations call for a PSA test every 4 to 6 months for men with MO CRPC whose risk of developing metastases is low, and every 3 months for men with MO CRPC who are at high risk of developing metastases or already have radiographic evidence of metastases.

When imaging is done for patients with CRPC, a bone scan should be offered, as well as either a CT scan or MRI of the abdomen and pelvis. “The appropriate frequency of imaging is variable and largely dependent on symptoms,” ASCO said.

Radiographic imaging is not suggested for patients with CRPC and a rising PSA, unless treatment selection would be altered based on radiographic findings, or if symptoms attributable to the disease develop or worsen (such as bone pain). Radiographic restaging as routine surveillance also is not recommended, except for patients for whom PSA level is not a reliable marker of disease, ASCO said.

For chemotherapy-naïve patients with CRPC who have radiographic evidence of metastases (M1a/M1s) and minimal symptoms, enzalutamide, radium-223, sipuleucel-T, or abiraterone acetate plus prednisone should be offered, because these agents significantly increase radiographic progression-free survival and overall survival. Palliative care also should be offered for this patient population, according to the PCO.

The PCO states that no evidence exists for optimal order of hormonal therapies for CRPC beyond second-line treatment. In addition to the evidence from clinical trials, the expert panel relied on a consensus technique that drew upon clinical experience, training, and judgement “when evidence was limited,” Eric A. Singer, MD, MA, a co-chair of the panel, said in the release. “We hope that this PCO will offer clinicians and patients timely direction to help inform treatment planning and shared decision making."

Virgo KS, Basch E, Loblaw DA, et al. Second-line hormonal therapy for men with chemotherapy-naïve castration-resistant prostate cancer PCO [published online April 25, 2017]. J Clin Oncol. doi:10.1200/JCO.2017.72.8030.