The American Society of Clinical Oncology’s provisional clinical opinion on the use of second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer issued by uncovered some surprising findings and issues.
The American Society of Clinical Oncology (ASCO) has issued its first provisional clinical opinion on the use of second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer.
This is an area left largely unaddressed as treatment of castration-resistant prostate cancer has rapidly evolved, according to Katherine S. Virgo, PhD, MBA, co-chair of the expert panel that developed the clinical opinion, which was published online in the Journal of Clinical Oncology (April 25, 2017).
“The last few years have seen an unprecedented number of systemic therapies reporting improvements in pre- and post-docetaxel [Taxotere] men diagnosed with castration-resistant prostate cancer. Newer systemic therapies, such as enzalutamide [XTANDI] and abiraterone acetate [ZYTIGA], are considered hormonal interventions,” said Dr. Virgo, of Emory University, Atlanta.
A companion ASCO guideline addresses the use of systemic therapy agents, such as chemotherapy and radium-223 [Xofigo], in men with radiographic or pathologic evidence of metastatic castration-resistant prostate cancer, Dr. Virgo noted, but that document does not address second-line hormonal therapy management of non-metastatic prostate cancer recurrence. It also does not directly address second-line hormonal therapy in the chemotherapy-naïve population.
Without published guidelines, physicians managing these patients faced challenges and, even today, treatment patterns for castration-resistant prostate cancer vary considerably. According to Dr. Virgo, that’s likely due to the scarcity of high-quality data on the topic, the relative efficacy and nonspecific mechanisms of action of available treatment approaches, and uncertainty among clinicians regarding optimal treatment.
The new provisional clinical opinion uncovered some surprising findings and issues. Among the recommendations:
PSA monitoring. No evidence provides guidance about the optimal frequency of PSA monitoring prior to starting second-line hormonal therapy or once treatment has begun. As a result, the expert panel used clinical experience, training, and judgment to formulate the provisional clinical opinion, according to Dr. Virgo.
“Consideration was given to the inconvenience and anxiety introduced by more frequent PSA testing, versus potential harms resulting from delayed recognition of a rapid PSA doubling time,” she said.
According to the document, PSA evaluation should be done every 4 to 6 months for low-risk men who develop castration-resistant prostate cancer and have no radiographic evidence of metastases and a slow PSA doubling time or velocity. If PSA levels are rising, consideration should be given to checking serum testosterone levels.
A PSA evaluation is recommended every 3 months for high-risk men who develop castration-resistant prostate cancer with a rapid PSA doubling time or velocity, or who already have radiographic evidence of metastases.
“[Urologists] might also be surprised by the lack of clinical trial data to support recommendations regarding which imaging modalities are appropriate for men with castration-resistant prostate cancer,” Dr. Virgo said.
Imaging. The expert panel also used their clinical experience, training, and judgment as the basis for their recommendation that, when imaging is performed for men with castration-resistant prostate cancer, a bone scan and either computed tomography or magnetic resonance imaging of the abdomen and pelvis should be offered. Dr. Virgo noted that sodium fluoride PET (18F-PET) imaging is only approved in the U.S. for the diagnosis of recurrent prostate cancer among men with elevated PSA after treatment. The use of the technique is otherwise limited to patients participating in clinical trials and prospective registries. Whole-body MRI to detect oligometastatic disease, radiotracers, and imaging agents, such as c-11 choline, prostate-specific membrane antigen and 18F-flucicovine, are considered investigational for patients with chemotherapy-naïve castration-resistant prostate cancer, she said.
Treatment for men with no evidence of metastases. When considering the use of second-line hormonal therapies for chemotherapy-naïve men with castration-resistant prostate cancer and no radiographic evidence of metastases, it is key for urologists to recognize that different recommendations apply based on risk of developing metastases. In fact, there are no data to support use of second-line hormonal therapy in men who are at low risk of developing metastases, according to Dr. Virgo.
“However, for chemotherapy-naïve men at high risk of developing metastases, second-line hormonal therapies, which lower PSA values or slow the rate of rise, may be appropriate,” she said.
It’s preferable that the second-line therapies are offered in a clinical trial setting, following a discussion with the patient about the limited scientific evidence, potential harms, benefits, cost and patient preferences, according to Dr. Virgo.
“Men at greatest risk of developing metastatic disease may, therefore, benefit from additional anti-tumor therapy. But this has not been prospectively demonstrated in studies to date,” she said. “Age and life expectancy should be taken into consideration. Older men with short life expectancies and high risk of developing metastatic disease may not be optimal candidates for second-line hormonal therapies.”
Treatment for men with evidence of metastases. Another key point for urologists: Abiraterone plus prednisone or enzalutamide alone is recommended as second-line hormonal treatment after first-line hormonal treatment failure for chemotherapy-naïve men who develop castration-resistant prostate cancer and already have radiographic evidence of metastases. However, palliative care should be offered to all chemotherapy-naïve high-risk castration-resistant prostate cancer patients who have failed first-line hormonal treatment and are showing symptoms or decreased quality of life.
Gaps in knowledge remain about how to best manage these patients. Among those: No evidence provides guidance about the optimal order of hormonal therapies after second-line hormonal therapy for high risk chemotherapy-naïve men with low-risk, castration-resistant prostate cancer. The panel was also unable to come to consensus on sequencing, Dr. Virgo said.
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