Daniel P. Petrylak, MD: Sequencing Therapies in mCRPC


Daniel P. Petrylak, MD, Professor of Medicine (Medical Oncology) and of Urology, Professor and Co-Director, Signal Transduction Research Program, Yale Cancer Center, notes that this patient has symptomatic metastatic castration-resistant prostate cancer (CRPC).

First, bicalutamide should be discontinued. Approximately 20% to 30% of patients will respond to antiandrogen withdrawal, as evidenced by PSA declines and, in some patients, improvement in symptoms. This generally occurs 4 to 6 weeks after treatment. It takes approximately 6 weeks for this effect to be noted.

It is important to know whether or not the patient is on narcotic analgesics, as well as whether the patient has visceral disease, Petrylak notes. This is an important decision point for subsequent treatments. A CT scan of the chest/abdomen/pelvis would be appropriate for restaging, Petrylak adds.

If the patient is not on narcotic analgesics or has no evidence of visceral disease on CT scan, immunotherapy would be appropriate. Of course, if the patient has rapidly progressing disease or bone pain it may not be appropriate to wait for anti-androgen withdrawal. There’s been no evidence that this strategy has any effect on survival, Petrylak adds.

For symptomatic patients with bone metastases, first-line treatment options would include chemotherapy with docetaxel, other treatment options would include isotope therapy with radium-223, as well as other hormonal manipulations with abiraterone/prednisone or enzalutamide. This patient also should be on a bone-targeting agent, such as denosumab or zoledronic acid.

CASE 1: Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Robert C. is a 63-year-old physical education teacher and high school wrestling coach from Savannah, Georgia

In May 2007, patient presented to his PCP and received routine screening for prostate cancer.

Patient’s PSA level was 6.2 ng/mL

Digital rectal examination and subsequent CT scan revealed the presence of prostate adenocarcinoma T2bN0M0, Gleason 6 (2+4), classified as intermediate risk

Patient underwent radical prostatectomy and adjuvant radiotherapy in June 2007

Patient’s prior medical history is notable for abdominal aortic aneurysm surgery in 2002 and hypertension (well controlled on current therapy)

His liver function tests were unremarkable

In July 2010, after approximately 3 years, the patient returned to his PCP for a routine physical, and an increase in PSA to 9.7 ng/mL was detected; he was asymptomatic.

Bone scan in August 2010 was negative

Androgen deprivation therapy (ADT) was initiated in August 2010 with goserelin; the patient’s PSA subsequently decreased to 0.5 ng/mL

In September 2012, after approximately 2 years, the patient’s PSA began to rise to 2.0 ng/mL; testosterone level was 19 ng/dL

Oral bicalutamide was added to his ADT; he continued to be asymptomatic

In April 2013, the patient presented to his PCP complaining of lower back pain and moderate to severe fatigue; his PSA had increased to 3.7 ng/mL

Bone scan revealed the presence of diffuse bone lesions in the lumbar and sacral vertebral bodies

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