Pain, PSA flare, and bone scan response in a patient with metastatic castration-resistant prostate cancer treated with radium-223, a case report

Our patient first presented in February 2008 with lower urinary tract symptoms and was found to have an elevated PSA at 14.8 ng/mL (Figure 1). Subsequent transrectal ultrasound-guided biopsy of the prostate showed high-grade prostate adenocarcinoma, with Gleason Score 4 + 5 = 9 and 4 + 4 = 8, in 10 of 13 cores, in all areas of the prostate. Because of the high-grade disease, staging studies were performed. Bone scan showed increased uptake in the left pubic ramus (Figure 2A). CT scan of the abdomen and pelvis did not show lymphadenopathy or intraabdominal disease but did demonstrate blastic activity in the left superior pubic ramus, corresponding to the region of increased uptake seen on bone scan. Overall, this presentation was felt to be consistent with metastatic prostate cancer with a single, asymptomatic, bone metastasis.

In June 2008, he was initiated on androgen deprivation therapy (ADT), which he has remained on, with or without additional therapies, since then. Please refer to Table 1 for full details of his treatment course prior to radium-223. Briefly, from June 2010 to June 2013, he was treated with a DHEAS inhibitor on a Phase I clinical trial, sipuleucel-T immunotherapy, a CYP17 inhibitor plus prednisone on a Phase III clinical trial, 10 cycles of docetaxel chemotherapy plus prednisone, and enzalutamide, as well as two courses of palliative radiation to painful osseous metastases. He had transient improvement in his mCRPC in response to many of these therapies, but overall his course was characterized by disease progression, with rising PSA, increasing alkaline phosphatase, and growing osseous metastases.

By July 2013, PSA had reached 653 ng/mL (Figure 1) and alkaline phosphatase was 564 U/L (Figure 3). He had also developed severe diffuse bone pain. Re-staging scans showed disease progression with increase in the size of diffuse bone metastases, some of which were now confluent (Figure 2E). There was still no evidence of visceral metastatic disease.

On August 1, 2013, he received his first dose of radium-223 50 kBq/kg. Enzalutamide (and leuprolide) were continued. Following the first dose of radium-223, he experienced a flare in his bone pain, which he described as “severe, total body pain” that caused him to be bedbound for 10 days. A concurrent flare in PSA was also observed, with PSA peaking at 996 ng/mL three weeks after the first dose of radium-223 (Figure 1). After the initial flare, bone pain and PSA steadily improved. He was able to discontinue opioids within eight weeks of start of therapy. After his fifth dose of radium-223, he developed symptomatic anemia with hemoglobin 7.5 g/dL. He was transfused two units of packed red blood cells and has remained red blood cell transfusion-dependent since then, requiring transfusions every two to four weeks. He completed his sixth dose of radium-223 in December 2013. PSA nadired at 554 ng/mL in January 2014 (Figure 1). Alkaline phosphatase dropped steadily throughout the course of radium-223 and nadired at 144 U/L in January 2014 (Figure 3). Re-staging bone scan in February 2014 showed a dramatic response to radium-223 with significant decrease in activity of all skeletal metastases (Figure 2F).

He had a sustained excellent response to radium-223, with continued pain relief, requiring only as-needed NSAIDs, and stable PSA of about 600 ng/mL until July 2014 (Figure 1), when he reported new right temporal headache and diplopia. Brain MRI at that time showed interval development of new diffuse osseous metastatic disease in the skull, not present at the time of radium, with intracranial and intraorbital mass extension, exerting mass effect on the lateral rectus and optic nerve. Bone scan confirmed the MRI findings and showed no change in the appearance of his previously existing metastatic disease. PSA had increased to 780 ng/mL (Figure 1). He was started on steroids and underwent stereotactic radio-surgery (SRS) to the skull base mass, with resolution of his headaches and diplopia.

Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Per our institutional policy, we also obtained IRB approval for this Case (IRB number Pro00059303).