A Case of Metastatic Castration-Resistant Prostate Cancer

Pedro C. Barata, MD, MSc:This is a 69-year-old man who presented in the summer of 2016 with nocturia. And that triggered a PSA, which happened to be elevated, around 50 [ng/mL] or so, and an enlarged prostate detected on a digital rectal exam. He underwent prostate biopsy, which confirmed adenocarcinoma of the prostate and a Gleason score of 8. He also got restaging scans with a bone scan and CT [computed tomography] scan, which revealed some nodal involvement and no bone metastasis.

In the context of nodal involvement and a diagnosis of metastatic prostate cancer, this patient was started on androgen deprivation therapy in August of the same year. He initially got very nice serological response. His PSA dropped beautifully, but after several months, his PSA started to go up again. And a few months later, he developed some fatigue and some mild back discomfort, which triggered restaging scans. The scans at that time revealed 2 new bone metastases, and so this patient was considered for enzalutamide.

Enzalutamide is an androgen receptor targeted therapy. The way it works is that it basically blocks the androgen receptor, and it is 1 of the life-prolonging therapies available that we commonly use. Basically, its approval is based on 2 large phase III trials in the metastatic setting with PREVAIL and AFFIRM data, both with survival benefit. So we can use enzalutamide in the metastatic castration-resistant setting pre- and post-chemotherapy with taxanes. So when we have a patient who progresses despite androgen deprivation therapy—he develops metastatic castration-resistant prostate cancer [CRPC]—enzalutamide is 1 of my favorite options because it’s an oral therapy, it improves survival, it leads to serological response, and it delays time to new disease in the scans.

PSA at the time of enzalutamide initiation was 25 [ng/mL]. The patient got a PSA response on treatment with enzalutamide, but then PSA started to rise again. So response lasted for approximately a year or so. And then restaging scans done a year later revealed further bone metastasis. So he was failing enzalutamide therapy and was considered for treatment with radium 223, Xofigo.

The patient was started on radium 223 and completed 6 cycles of therapy for 6 months in total, 1 treatment per month basically. He was doing quite well with overall PSA stabilization, but approximately a year later, he developed new clinical symptoms, mainly with fatigue. He felt beaten up, and restaging scans revealed lymphadenopathy that was new, as well as new liver metastasis. At this time, the decision was to offer him chemotherapy with docetaxel, which he has started with good clinical and serological response so far.

When we have a patient with metastatic castration-resistant prostate cancer, we have a few things that we take into consideration when we select a treatment among all the available treatments. One of the points is actually improved survival. We have 6 life-prolonging therapies, in which chemotherapy with docetaxel is included, as well as radium 223, enzalutamide, etc. So when we pick a treatment in this patient, when we considered him for docetaxel, the goal was mainly to control his symptoms. We have to regain control of the disease that’s clearly progressing, despite androgen-deprivation therapy after radium 223. The second goal is trying to improve his survival. We know disease is progressing, despite how he has seen androgen-deprivation therapy, enzalutamide, and radium 223, so 2 life-prolonging therapies for CRPC disease. And so the hope is that with chemotherapy, we can regain control of the disease and make him live longer and keep his quality of life as best as possible.

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)