Prostate cancer - CRPC Flashcards
Index patient 1 - Asymptomatic non-metastatic CRPC
Asymptomatic non-metastatic CRPC
One of the first clinical presentations of CRPC occurs in a patient with a rising PSA despite medical or surgical castration. This is typically defined as a patient with a rising PSA and no radiologic evidence of metastatic prostate cancer. The Prostate Cancer Clinical Trials Working Group 2 (PCWG2) defines PSA only failure as a rising PSA that is greater than 2ng/mL higher than the nadir, the rise has to be at least 25% over nadir and the rise has to be confirmed by a second PSA at least three weeks later. In addition, the patient is required to have castrate levels of testosterone (less than 50 ng/mL) and no radiographic evidence of metastatic disease. These patients represent a relatively common clinical presentation and the earliest clinical manifestation of castration resistance, but to date, there are no randomized trials showing an overall survival benefit in this patient population from a particular form of treatment.
- Clinicians should recommend observation with continued androgen deprivation to patients with non-metastatic CRPC.
- Clinicians may offer treatment with first generation anti-androgens (flutamide, bicalutamide and nilutamide) or first generation androgen synthesis inhibitors (ketoconazole + steroid) to select patients with non-metastatic CRPC who are unwilling to accept observation.
- Clinicians should not offer systemic chemotherapy or immunotherapy to patients with non-metastatic CRPC outside the context of a clinical trial.
Index Patient 2 - Asymptomatic or minimally symptomatic, mCRPC without prior docetaxel chemotherapy
Asymptomatic or minimally symptomatic, mCRPC without prior docetaxel chemotherapy
This patient represents a common clinical presentation seen in the CRPC setting today. These patients are characterized as having a rising PSA in the setting of castrate levels of testosterone, documented metastatic disease on radiographic imaging and no prior treatment with docetaxel chemotherapy for CRPC. The key distinction between this patient and index patients 3 and 4 is symptom status. Specifically, this patient is defined as having no symptoms attributable to their prostate cancer. However, one must then consider whether the patient required regular opioid pain medications for symptoms thought to be attributable to documented metastases to achieve this level of pain control. In general, if patients require regular narcotic medications for pain relief, they are not included in this category.
- Clinicians should offer abiraterone + prednisone, enzalutamide, docetaxel, or sipuleucel-T to patients with asymptomatic or minimally symptomatic mCRPC with good performance status and no prior docetaxel chemotherapy.
- Clinicians may offer first- generation anti-androgen therapy, ketoconazole + steroid, or observation to patients with asymptomatic or minimally symptomatic mCRPC with good performance status and no prior docetaxel chemotherapy who do not want or cannot have one of the standard therapies.
Index Patient 3 - Symptomatic, mCRPC with good performance status and no prior chemotherapy
Symptomatic, mCRPC with good performance status and no prior chemotherapy
These patients have a rising PSA in the setting of castrate levels of testosterone, documented symptomatic metastatic disease on radiographic imaging, and no prior history of docetaxel chemotherapy for prostate cancer. The definition of symptomatic disease warrants additional explanation to contrast with Index Patient 2. First, the patient must have symptoms that are clearly attributable to the metastatic disease burden, not any other medical condition. Second, if having pain, the patient should require regular opiate pain medications for symptoms attributable to documented metastases in order to achieve an acceptable level of pain control. If patients require regular narcotic medications for pain relief, then they are symptomatic from their prostate cancer and should be included in this category.
- Clinicians should offer abiraterone + prednisone, enzalutamide, or docetaxel to patients with symptomatic, mCRPC with good performance status and no prior docetaxel chemotherapy.
- Clinicians may offer ketoconazole + steroid, mitoxantrone or radionuclide therapy to patients with symptomatic, mCRPC with good performance status and no prior docetaxel chemotherapy who do not want or cannot have one of the standard therapies.
- Clinicians should offer radium-223 to patients with symptoms from bony metastases from mCRPC with good performance status and no prior docetaxel chemotherapy and without known visceral disease.
- Clinicians should not offer treatment with either estramustine or sipuleucel-T to patients with symptomatic, mCRPC with good performance status and no prior docetaxel chemotherapy.
Index Patient 4 - Symptomatic, mCRPC with poor performance status and no prior docetaxel chemotherapy
Symptomatic, mCRPC with poor performance status and no prior docetaxel chemotherapy
Clinical trials have generally excluded patients with a poor performance status (ECOG 3-4) from participation. Thus, most data regarding management of such patients is extrapolated from randomized trials of eligible patients who had a better performance status, as well as from some smaller trials and registries. Even a phase III clinical trial that was presumptively designed for a population considered “unfit” for docetaxel (ALSYMPCA to evaluate radium-223) still only allowed a performance status of ECOG 0-1. However, treatments with acceptable safety profiles do exist and should be considered, even in poor performance status patients. This is especially true in those patients in whom the poor performance status may be considered to be directly related to the cancer itself, and thus whose status might improve with effective treatment. Treatments must be individually tailored in these patients, after a careful discussion of risks and benefits with particular attention to patient quality of life.
- Clinicians may offer treatment with abiraterone + prednisone or enzalutamide to patients with symptomatic, mCRPC with poor performance status and no prior docetaxel chemotherapy.
- Clinicians may offer treatment with ketoconazole+ steroid or radionuclide therapy to patients with symptomatic, mCRPC with poor performance status and no prior docetaxel chemotherapy who are unable or unwilling to receive abiraterone + prednisone or enzalutamide.
- Clinicians may offer docetaxel or mitoxantrone chemotherapy to patients with symptomatic mCRPC with poor performance status and no prior docetaxel chemotherapy in select cases, specifically when the performance status is directly related to the cancer.
- Clinicians may offer radium-223 to patients with symptoms from bony metastases from mCRPC with poor performance status and no prior docetaxel chemotherapy and without known visceral disease in select cases, specifically when the performance status is directly related to symptoms related to bone metastases.
- Clinicians should not offer sipuleucel-T to patients with symptomatic, mCRPC with poor performance status and no prior docetaxel chemotherapy
Index Patient 5 - Symptomatic, mCRPC with good performance status and prior docetaxel chemotherapy
Symptomatic, mCRPC with good performance status and prior docetaxel chemotherapy
As patients with prostate cancer receive hormonal therapy earlier in the course of the disease (frequently for non-metastatic disease), they may actually develop castrate-resistant disease (based on serologic progression) with non-metastatic or asymptomatic metastatic disease. Thus, additional agents, including docetaxel chemotherapy may be administered earlier in the course of metastatic disease. These trends have resulted in a population of mCRPC patients who have completed docetaxel and may continue to be asymptomatic or minimally symptomatic with an excellent performance status. While such patients may be healthy enough to receive a number of subsequent therapies, a focus of therapy should also be to maintain their excellent performance status without significant toxicity from additional therapy. It is in this context that providers should choose from a number of additional therapies to offer to this patient population.
- Clinicians should offer treatment with abiraterone + prednisone, cabazitaxel, or enzalutamide to patients with mCRPC with good performance status who have received prior docetaxel chemotherapy. If the patient received abiraterone + prednisone prior to docetaxel chemotherapy, they should be offered cabazitaxel or enzalutamide.
- Clinicians may offer ketoconazole + steroid to patients with mCRPC with good performance status who received prior docetaxel if abiraterone + prednisone, cabazitaxel or enzalutamide is unavailable.
- Clinicians may offer retreatment with docetaxel to patients with mCRPC with good performance status who were benefitting at the time of discontinuation (due to reversible side effects) of docetaxel chemotherapy.
- Clinicians should offer radium-223 to patients with symptoms from bony metastases from mCRPC with good performance status who received prior docetaxel chemotherapy and without known visceral disease.
Index Patient 6 - Symptomatic, mCRPC with poor performance status and prior docetaxel chemotherap
Symptomatic, mCRPC with poor performance status and prior docetaxel chemotherapy
The American Society of Clinical Oncology (ASCO) has posted recommendations regarding treatment for patients with advanced solid tumors; particularly in the last months of life. They advocate for an increasing emphasis on a patient’s quality of life and concentrate on symptom management. Treatment given in the last months of life may delay access tend of life care, increase costs and add unnecessary symptom management. Patients with poor performance status (ECOG 3 or 4) should not be offered further treatment.
- Clinicians should offer palliative care to patients with mCRPC with poor performance status who received prior docetaxel chemotherapy. Alternatively, for selected patients, clinicians may offer treatment with abiraterone + prednisone, enzalutamide, ketoconazole + steroid or radionuclide therapy.(Expert Opinion)
- Clinicians should not offer systemic chemotherapy or immunotherapy to patients with mCRPC with poor performance status who received prior docetaxel chemotherapy. (Expert Opinion)
Bone health for all index pts
Several factors conspire to place the average patient with metastatic prostate at a higher risk of bone complications. First, the median age of onset of the disease is in the late 60s, meaning that the average patient with metastatic disease may be in the 70s (or beyond), clearly a population at risk of physiologic, age-related decreases in bone mineral density. Secondly, a primary therapeutic intervention in patients with recurrent disease, androgen-deprivation therapy, is associated with progressive loss of bone mineral density, not infrequently to the point of measurable osteopenia or frank osteoporosis, increasing the patient’s fracture risk, even in patients with non-metastatic disease. Finally, in patients with advanced disease, bones are the most common site of metastatic disease, with as many as 70% of patients at some point in their course demonstrating evidence of disease in this site.
- Clinicians should offer preventative treatment (e.g. supplemental calcium, vitamin D) for fractures and skeletal related events to CRPC patients.
- Clinicians may choose either denosumab or zoledronic acid when selecting a preventative treatment for skeletal related events for mCRPC patients with bony metastases.
Ecog scoring
