Impact of Bone Metastases in mCRPC

Pedro C. Barata, MD, MSc:Symptoms for metastatic prostate cancer can vary, depending on where you develop metastases, basically. So I would argue that most patients will present with bone metastasis, which is the most common site of disease, followed by nodal involvement, and then soft tissue and visceral disease. If I have a patient with bone metastasis, 1 of the most common symptoms that occurs is actually bone pain. And so for all patients, we should think of bone pain and fatigue when we are suspicious of metastasis. But for example, if you develop metastasis in other sites—such as nodal involvement or the pelvic region, for instance—you can develop other types of symptoms, such as obstructive symptoms, edema, etc. So I would argue that the presenting symptoms depend on where you have metastatic disease. But bone pain is 1 of the most common symptoms.

Bone metastasis is the most common site of metastases in patients with metastatic prostate cancer. It can occur alone, meaning the patient might present with bone-only disease, which occurs in maybe half or even more than half of the patients we see in clinic. Or patients can present with bone metastases plus other sites of disease, and that can go as high as 90% or so. And then you can also have patients who also present with nodal involvement only or nodes plus visceral disease with no bone metastases, but that group of patients is probably a minority.

The biology of prostate cancer is extremely important and does have prognostic and therapeutic implications. Patients with predominantly bone disease are different from patients with visceral disease, for example. And I’m thinking of patients who have straightforward adenocarcinoma of the prostate without neuroendocrine features. Compared with patients who develop visceral disease, they usually have poor differentiation of clones of the tumor, where neuroendocrine features can arise. Again, it does help to know the characteristics of the tumor and the biology of the tumor. It does have predictive prognostic implications. So it’s important for us, for treating physicians, to know what type of prostate cancer this patient has.

Historically, we have been using conventional scans, including bone scans and CT [computed tomography] scans, to diagnose men with metastatic prostate cancer. In trials, we have still been including conventional scanning as part of the protocols. But I would argue that novel imaging, using PET [positron emission tomography] scans with prostate-specific tracers, is being increasingly used. We now have a number of options that are either FDA approved or soon to be FDA approved, and I’m thinking about PSMA [prostate-specific membrane antigen], Axumin or fluciclovine [F 18], choline, and fluoride PET. The advantage of these PET scans or the use of these tracers is that they increase our ability to diagnose metastatic disease much sooner compared with the use of CT and bone scans. In the future, as we tend to use more and more PET scans for prostate cancer, we’ll very likely diagnose prostate cancer at advanced stages much earlier.

PSA has historically been a biomarker that we all use. There are some conflicting data about the absolute number and the value of that number. But it’s true that we all use it to monitor response to treatments, right? So we usually say that symptoms are relevant, and then scans are relevant, and then numbers—meaning PSA—are relevant too. What happens is as we treat, as we expose different treatments for patients who develop progressive metastatic CRPC [castrate-resistant protate cancer], we are basically selecting poorly differentiated or undifferentiated clones of this prostate cancer. In other words, we are selecting clones that are less likely to respond to androgen-directed therapies, and it might be [that] their growth is being driven by other mechanism and pathways. And so when that happens, PSA is less important. In other words, in clinical practice, it is very possible that we see a patient who is progressing despite low levels of PSA or even no PSA at all.

When we have a patient with bone metastases and we know we have adenocarcinoma of the prostate, regardless of the Gleason score, we can consider all treatments available for this patient, including androgen receptor targeted therapies, chemotherapy, bone-targeted therapy such as radium 223, or even dendritic cell vaccine, Provenge. When we have patients with soft tissue or visceral disease, we usually consider chemotherapy as a stronger option. Although we do have data showing that androgen receptor targeted therapies are options as well, such as enzalutamide or abiraterone. But other therapies, such as radium 223, become less valuable because they don’t work for patients who have disease outside the bone.

Transcript edited for clarity.

Case: A 69-Year-Old Man With mCRPC Progressing on Therapy

July 2016

H&P:

• A 69-year old gentleman presented with nocturia
• PMH: unremarkable
• DRE, enlarged prostate
• PSA, 50.3 ng/mL
• TRUS and biopsy showed adenocarcinoma of the prostate gland; Gleason score 8 [4+4]
• CT scan showed minimal nodal involvement

Treatment:

• Started on ADT with initial PSA response - 15 ng/ml — August 2016

March 2017

8 months later, patient complained of fatigue and mild back discomfort

• Imaging with CT and bone scan showed two metastatic bone lesions (1 spine, 1 pelvis)
• PSA, 25 ng/mL
• Hb, 9.0 g/dL
• ANC, 1.7

Treatment:Enzalutamide

• Initial PSA response — 10 mg/ml but rising over one year later continued

March 2018

• PSA 30 ng/ml
• CT showed 4 bone metastases (2 spine, 2 pelvis) and diffuse liver lesions

April 2018

• Radium-223 initiated, patient received 6 injections

April 2019

One year later patient presented with increased lower back discomfort causing disruption in daily activity.

• CT showed new lymphadenopathy and diffuse liver lesions
• PSA 45 ng/mL
• Hb, 9.0 g/dL
• ANC, 1.6
• Treatment: Patient started on docetaxel, 6 cycles completed; achieved stable disease (Hb, 14.1 g/dL)