The American Society of Clinical Oncology (ASCO) has issued a provisional clinical opinion (PCO) on how oncologists might rationally approach the use of second-line hormonal therapy for chemotherapy-naive men with prostate cancer whose condition progresses to castrate-resistant prostate cancer (CRPC) despite having achieved castrate levels of testosterone.
"Clinicians face many challenges when treating patients with CRPC, particularly those who are chemotherapy-naive with no evidence of radiographic metastases," write the authors.
"So to develop these recommendations, we used evidence from trials as well as a formal consensus technique that relied on clinical experience, training, and judgement, when evidence was limited," commented Eric Singer MD, co-chair of the expert panel that developed the new document.
"And we hope that this PCO will offer clinicians and patients timely direction to help inform treatment planning and share decision-making," he added.
ASCO's PCO was published online April 25 in the Journal of Clinical Oncology.
The clinical opinion document focused on two patient groups: men who have not received chemotherapy, who are asymptomatic, and for whom there is only biochemical evidence of CRPC (MO CRCP), and those who have documented metastases but minimal symptoms (M1a CRPC).
"For men who develop CRPC despite castrate levels of testosterone, patients should be maintained in a castrate state indefinitely," panel members indicate.
This should be done either surgically through orchiectomy or pharmacologically through the use of luteinizing hormone–releasing hormone agonists or antagonists or an antiandrogen.
Second-line hormonal therapies are not indicated in men who are naive to chemotherapy, who do not have MO CRPC disease, and who are felt to be at low risk for metastases by virtue of having a low prostate-specific antigen (PSA) level and a slow PSA doubling time.
Second-line hormonal therapies that lower PSA levels or slow the rate of PSA doubling may be considered in men who are naive to chemotherapy but who are at high risk of developing metastases by virtue of rapid PSA doubling times or velocity.
Alternatively, observation may also be considered for this group of patients, provided patients are maintained in a castrate state.
"Chemotherapy or immunotherapy is not suggested except in a clinical trial," ASCO panel members add.
Evidence of Metastases
Chemotherapy-naive men who develop CRPC and for whom there is radiographic evidence of metastases but who have minimal symptoms — those with M1a/M1s CRPC ― may receive either abiraterone acetate (Zytiga, Janssen) plus prednisone or enzalutamide (Xtandi, Medivation/Astellas), each of which is considered to be a hormonal therapy.
Both drugs have been shown to prolong progression-free and overall survival, and both are well tolerated.
Alternatively, immunotherapy with sipuleucel-T (Provenge, Dendreon), or chemotherapy with docetaxel and prednisone, or treatment with radium-223 (Xofigo, Bayer) may each be considered in these patients.
The antiandrogens prednisone or ketoconazole plus hydrocortisone provide only modest clinical benefit in this particular setting but may be considered if other treatment options are not available or are not well tolerated.
"Palliative care should be offered to all chemotherapy-naive men with M1 CRPC, particularly to those who exhibit symptoms or decreased quality of life," the panel members indicated.
Evidence was insufficient to determine what the optimal order might be for offering second-line hormonal therapy in either MO or M1CRPC patients, the panel members note.
PSA levels may be evaluated every 4 to 6 months in men for whom there is no radiographic evidence of metastases and for whom the PSA doubling time is slow. PSA levels may be evaluated every 3 months in men whose PSA doubling time is rapid, who have rapid PSA velocity, or in whom there is radiographic evidence of metastases.
"When imaging is considered for patients both before and while receiving treatment, a bone scan and either computed tomography or magnetic resonance imaging of the abdomen and pelvis are reasonable," the panel members write.
In contrast, imaging with 18F-labeled positron-emission tomography is not approved in the United States for this indication and is thus not recommended for CRPC patients.
Nor is routine radiographic restaging generally recommended unless a patient's PSA levels are not a reliable marker of underlying disease.
Radiographic imaging is also not indicated in men whose PSA level is rising unless imaging is expected to alter the direction of treatment or if symptoms such as bone pain that are attributable to the disease develop or worsen.
ASCO panel members addressed the cost implications of selecting one treatment option over the other, but studies were limited.
The available evidence suggests that abiraterone acetate is less expensive than enzalutamide, but that neither abiraterone acetate nor sipuleucel-T were cost-effective in an asymptomatic chemotherapy-naive population compared with prednisone, at least at usual cost thresholds of $150,000 per quality-adjusted life-year.
"Out-of-pocket (OOP) costs, the potential adverse effects of OOP costs (referred to as financial toxicity) and expected quality of life should be discussed with patients during the treatment decision-making process," panel members emphasize.
"And oncologists must continue to advocate for patient access to beneficial therapies while being responsible stewards of health care resources," they add.
All significant financial relationships of members of the expert panel are listed in the published article.
J Clin Oncol. Published online April 25, 2017.