A castrate state should be maintained indefinitely in men who develop castration-resistant prostate cancer despite castrate levels of testosterone, according to a provisional clinical opinion issued by ASCO.
The provisional clinical opinion focuses on the use of second-line hormonal therapy for chemotherapy-naive men who have castration-resistant prostate cancer, including those who are asymptomatic with only biochemical evidence of disease to those who have document metastases but minimal symptoms.
“We hope that this [provisional clinical opinion] will offer clinicians and patients timely direction to help inform treatment planning and shared decision-making,” Eric A. Singer, MD, MA, FACS, urologic oncologist at Rutgers Cancer Institute of New Jersey and co-chair of the ASCO expert panel that developed the recommendations, said in a press release.
The goal for the treatment of castration-resistant prostate cancer — or hormone-sensitive prostate cancer that recurs or progresses despite first-line androgen deprivation therapy — is palliation and avoidance of chemotherapy. Results from clinical trials have shown various second-line treatments — including abiraterone acetate (Zytiga, Janssen Oncology) and enzalutamide (Xtandi; Astellas, Medivation), both which are FDA approved for pre-and postdocetaxel treatment in patients with castration-resistant prostate cancer — slow cancer growth and lead to a better quality of life.
In addition, sipuleucel-T (Provenge, Dendreon), a nonhormonal agent, has also been approved in the prechemotherapy setting.
Despite the changing landscape of therapy, data are still limited and challenges remain for clinicians on how to manage and treat patients.
“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 castration-resistant prostate cancer,” Katherine S. Virgo, PhD, adjunct professor in the School of Public Health at Emory University and co-chair of the ASCO expert panel, said in the release. “However, due to a lack of guidelines on second-line hormonal therapy for chemotherapy-naive patients, there has been uncertainly regarding the optimal treatment among clinicians.”
Therefore, Singer, Virgo and colleagues conducted a systematic review of six randomized controlled clinical trials conducted between 2000 and 2014 to update ASCO guidelines.
Based on their analysis, the expert panel recommends:
- A castrate state be maintained “indefinitely” for men who develop castration-resistant prostate cancer regardless of castrate levels of testosterone;
- Second-line therapies be offered to chemotherapy-naive men with M0 castration-resistant prostate cancer at high risk for the development of metastases;
- Second-line treatment not be given to chemotherapy-naive men with M0 castration-resistant prostate cancer at low risk for the development of metastases;
- Second-line hormonal treatment — abiraterone acetate plus prednisone, or enzalutamide — should be offered, along with palliative care, to chemotherapy-naive men with castration-resistant prostate cancer and evidence of metastases;
- Men with M0 castration-resistant prostate cancer and low risk for the development of metastases should undergo PSA evaluation every 4 to 6 months, whereas men with M0 castration-resistant prostate cancer at high risk or with radiographic evidence of metastases should undergo evaluation every 3 months;
- A bone scan with CT or MRI of the abdomen and pelvis should be offered if a patient undergoes imaging. The frequency of imaging should be determined by patient symptoms;
- Radiographic imaging should not be offered to men with castration-resistant prostate cancer and a rising PSA unless radiographic findings could change treatment selection or if symptoms develop; and
- Routine surveillance radiographic restaging only be used in patients for whom PSA is not a reliable marker of the disease.
The panel noted that the primary limitation was the lack of data from the phase 3 randomized controlled trials. Because the guideline focused on second-line hormonal therapy for chemotherapy-naive patients with M0 and M1 castration-resistant prostate cancer, the panel wrote that updates are anticipated as recommendations are put into practice.
“Further studies of cost and quality-of-life implications of second-line, third-line and so forth hormonal therapies are needed to aid oncologists in discussing treatment options with patients,” the panel wrote. – by Melinda Stevens
Disclosures: Singer and Virgo report no relevant financial disclosures. Please see the full guideline for a list of all other authors’ relevant financial disclosures.