Treating mCRPC: Not a Sprint, But a Marathon

Pedro C. Barata, MD, MSc:We scan prostate cancer patients perhaps a little bit differently than we would for different solid tumors because we have a good biomarker, which is PSA, and also clinical symptoms. When PSA rises or PSA rising precedes development or new disease on the scans and development of new clinical symptoms, we usually don’t scan patients every 3 months as we usually do to monitor treatment in other cancers. Now, when we don’t use PSA or when PSA is not reliable, I would argue that we should think about scanning patients more often rather than waiting for new symptoms, for example.

The reason why I’m saying that is because from the ALSYMPCA data, we know that PSA is not the best biomarker, or even alkaline phosphatase. In other words, we shouldn’t be using a blood test to dictate whether or not we will complete treatment with radium 223. So I still scan patients on radium 223 probably while they’re on treatment once. So I get baseline scans, and then perhaps after 3 or 4 cycles with radium 223, I scan again. The reason why I do that is because I want to have an updated evaluation of that patient with scanning. If the patient is doing great and I happen not to scan him in the middle of the 6 cycles of treatment, I will do it after 6 cycles of treatment, so I have a newly updated baseline if you will.

For those of us who treat prostate cancer, we do see this every day. Metastatic prostate cancer is not a sprint; it’s a marathon. So we do have a number of systemic treatments available. That number is not unlimited, though. So our goal is to first make sure the patient does not develop symptoms from the disease, or if he does have them, that we will be able to actually improve quality of life. Second, we want to improve overall survival of these patients, and third, we want to do that by squeezing the effect of each line of treatment as much as we can. We have a number of treatments that are able to do that. We started having data available, suggesting that a combination of treatments might be helpful, but at other times it’s not that helpful. And the example of that is how radium 223 as monotherapy is a good treatment option. Abiraterone as a single therapy is a good systemic option. Combining both agents is not a good idea, and that’s based on the ERA 223 trial.

So we are starting to learn that the fact that we have ABCD, etc, treatments available doesn’t mean that A plus B is better than A or B alone. As we go further, we are excited to see how studies with novel treatments read out, as well as combination options such as enzalutamide and radium 223 read out. And the next question is, if these studies are positive, how is that going to impact how we treat patients today, and how is it going to impact the optimal sequencing that we’re going to have available for our patients?

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)