Integrating Prostate Cancer Trial Findings Into Practice: A Case-Based Discussion - Episode 2

Case Study: Treating High Risk CRPC

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During the discussion, moderator Raoul S. Concepcion, MD, presents the first of three case studies focused on patients with prostate cancer. In the first case scenario, a 58-year-old African American male with coronary artery disease and insulin-dependent diabetes presented to the emergency department with abdominal pain and low back pain in January 2015. While conducting laboratory testing, it was discovered that his PSA was 251.

Upon examination, the patient is very cachectic, has poor dentition, and a nodular prostate. An abdominal CT scan shows multiple blastic lesions of the lumbar spine and pelvis, but no soft tissue disease. The emergency department physician refers the patients to urology, where he undergoes a traditional TRUS biopsy, which reveals a 53 gram prostate with 12 of 12 cores positive for Gleason 4 × 5. A bone scan is positive to the thoracic and lumbar spine, pelvis, right femur, and scapula.

For this patient, in order to get rapid suppression of testosterone, Joseph F. Renzulli, II, MD, would use an antagonist and then watch for his PSA response and symptomatic response. Historically, when this type of high-risk patient has presented to the urologist, the standard has always been androgen deprivation therapy (ADT), either monotherapy or complete androgen blockade, explains Concepcion. This patient has 5 separate sites of bone metastases, but no visceral disease or soft tissue lesions, and can therefore be classified as high risk, states Daniel P. Petrylak, MD.

Based on the data presented from the CHAARTED trial, early chemotherapy should be considered for this patient, notes Petrylak. One interesting characteristic of this patient, Petrylak points out, is that he is diabetic. In the CHAARTED, there were no corticosteroids, except for premedication. With no continuous prednisone, he explains, there is no issue with a patient who has diabetes. Still, there was a significant improvement in survival, a 40% reduction in risk of death in those patients who received 6 cycles of docetaxel along with their hormone therapy versus those patients who received hormone therapy alone.

Patients in the CHAARTED trial were stratified between high-volume and low-volume disease, adds Concepcion. Mirroring the CHAARTED trial, the STAMPEDE trial, conducted predominantly in the UK, also showed that the addition of docetaxel to standard ADT in newly diagnosed patients with metastatic disease do benefit in terms of overall survival, adds Celestia S. Higano, MD.

In thinking about mutations and the complexity of the genetics, a higher volume of disease is more likely to have a greater number of genetic abnormalities, and thus more drug resistance. Adding another agent would make sense, but how docetaxel is working and why such great differences are being observed remains unclear.