Managing Bone Metastasis in Patients With mCRPC
Nicholas J. Vogelzang, MD, FASCO, FACP:Castration resistance is most easily measured by a rising PSA [prostate-specific antigen], in the face of a castrate level of testosterone. In this case, the patient’s testosterone was very lowless than 3—and his PSA was rising; that’s the definition of castration resistance.
Usually, we like to also see whether there’s bone metastases, and in that case this patient underwent a CT [computed tomography scan], and it did in fact show new bone lesions. There’s a lot of debate about whether you need a bone scan to prove that, because the bone scan will show variable changes. It’s not uncommon for the bone scan to become much improved such that, in some cases, the bone scan is virtually normal, and the only thing you’ll see on the CT scan is white bone areasmany of which are probably inactive. There’s a debate as to how you can image test to prove castration resistance. Some of us use the older standard of F18 [fluciclovine 18]. Some of us are using the Axumin scan. Some are using the PSMA [prostate—specific membrane antigen] scan. But a definition of a new bone lesion is sometimes required for clinical trials. A new bone lesion usually has to be seen in a bone scan. In this case, the patient exhibited obvious signs: He had a rising PSA and new bone lesions. It was no debate clinically about his state—mainly he was castration resistant with rising PSA.
Patients who are castration sensitive are typically already metastatic to bone. Some will be metastatic only to the lymph nodes and other organs such as the lungs, liver, or renal gland, but the majority of patients who present as this patient did, with de novo castration-sensitive disease, will have bone metastases. If he had them before, he will still have themthey haven’t gone away.
The incidence of bone metastases is about 70% to 90% of all patients with hormone-sensitive metastatic disease. Lymph node metastases-only patients account for about 20% to 30% of patients; they do better than patients with bone metastases. When we think about the development of castration-resistance in lymph node metastases patients, that will manifest by measurable disease: increasing lymph nodes in the chest, abdomen, or pelvis and only a small number of bone metastases. So, for example, I have a patient right now who has a PSA of 1000 and hardly any bone metastases but a large volume of lymph node metastases: These are slightly different patientsthey’re a different biology; they live longer; they are less likely to have pain. Furthermore, targeting the bone isn’t as necessary. Since about 70% of patients with castrate-resistant prostate cancer have bone metastases—some in the presence of node metastases—we think, in general, of castrate-resistant prostate cancer as being a bone disease.
Patients with bone metastases often have significant pain; it can be migratory, and they can be prone to fractures. They are prone to stress fractures, including falls and bone insufficiency. They are also prone to bone marrow failure, since the bone marrow is occupied by the prostate cancer. They also become anemic: Their alkaline phosphates rise, and their pain scores therefore rise. It becomes very challenging to care for them because they’re not immediately at risk for death from a visceral crisis. Their liver does not fail, and their lungs do not fail, but it’s fairly unpleasant for these patients.
Our patient has a rising PSA and new bone metastases; however, he did not have visceral metastases or lung, liver, or new nodal metastases. Generally, the path we follow would either be something like sipuleucel-T [Provenge], an alternative antiandrogen such as enzalutamide [Xtandi], radium-223 [dichloride; Xofigo], chemotherapy with either docetaxel or cabazitaxel [Jevtana], or a clinical trial; all of those are acceptable options. Exactly which sequence should be given is a subject for considerable debate.
Transcript edited for clarity.
Hormone Sensitive mPC progressing to mCRPC
March 2015
H&P:
- A 76-year old gentleman presented to his urologist with nocturia and lower back pain
- PMH: unremarkable
- Digital rectal examination revealed an abnormal area of hardness
Imaging:
- Transrectal ultrasound and biopsy revealed adenocarcinoma of the prostate gland with a Gleason score 8 [4+4] with 9 of 12 cores positive
- PSA, 85.3 ng/mL
- Testosterone, 300 ng/dL
- CT scan showed multiple metastases of the spine
- He was started on abiraterone + prednisone + goserelin
- PSA and testosterone level continued to decline over the next 2 years to PSA, 0.1 ng/ml; testosterone <3 ng/dL.
March 2018
- After 3 years of therapy patient reported increasing fatigue
- PSA and testosterone levels began to rise
- PSA increased from 0.5 ng/ml to 1.0 ng/ml; 2.0 ng/mg to 4.8 ng/ml at 2-3 month intervals
- Testosterone, <3 ng/dL
- CT scan shows several new bone metastasis; others improved
- Patient is diagnosed as castration resistant and abiraterone + prednisone was discontinued
- Radium-223 therapy was initiated
