PMC5765335_01
Peripheral blood cell counts before, during, and after Ra-223 treatment. White and red blood cell (WBC, RBC, respectively) and platelet (PLT) counts are normal before and decreased during and after Ra-223 therapy. The patient has thrombocytopenia (with PLT of 11.9x104/muL at the third injection of Ra-223 therapy) and anemia (with a hemoglobin of 9.9 g/dL four weeks after the third injection of Ra-223 therapy), which rapidly gets worse. He became transfusion-dependent, presenting with a hemoglobin of 7.7 g/dL and requiring monthly red-cell transfusions.
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F1
Before Ra-223 therapy, his hemoglobin was 14.9 g/dL, with a leukocyte count of 5900/muL and a platelet count of 24x104/muL; all were normal (Figure 1). Ra-223 therapy. PSA elevation suggested a PSA flare or relapse. Ra-223 therapy was discontinued due to thrombocytopenia (Figure 1).
Prostate-specific antigen (PSA) and serum total alkaline phosphatase (ALP, marker indicating osteoblastic activity) trends and the response to Ra-223, with concomitant use of hormonal therapy. The PSA level is 64 ng/ml before Ra-223 therapy, and it increases by twice a month, with PSA peaking at 1303 ng/ml eight weeks after the third injection of Ra-223 therapy. ALP decreases from 506 to 361 U/L during Ra-223 therapy, compatible with a favorable response to radiotherapy and concordant with the general decrease of Tc-99m HMDP uptake in bone lesions.
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F2
He had remained on androgen deprivation therapy with a novel endocrine agent, first enzalutamide and then abiraterone, with Ra-223 therapy (Figure 2).
Tc-99m HMDP bone scintigraphy: images from left to right, pretreatment (posterior and anterior views) and 2 weeks after the third injection (posterior and anterior views) of Ra-223 therapy. Ra-223 therapy has somewhat reduced abnormal uptake on right shoulder and lumbar vertebra with pain relief, and somewhat increased uptake on some parts of skull, left jaw, sternum, thoracic vertebra, and patchy and mixed of increased and decreased uptake on humeri and femur in bone metastases. Meanwhile, the serum PSA level increases from 64 ng/mL before treatment to 869 ng/mL at 4 weeks after the third injection of Ra-223 therapy.
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F3
Tc-99m HMDP bone scintigraphy (Figure 3). To evaluate for metastases, FDG PET/CT was performed four weeks after the third injection of Ra-223 therapy and showed diffuse FDG uptake in bone without osteoblastic lesions (Figure 4).
F-18 FDG PET maximum intensity projection (MIP) image (A), axial pelvic PET (B), CT (C), and fused PET/CT (D) at 4 weeks after the third injection of Ra-223 therapy. Diffuse FDG uptake in the bone without osteoblastic lesions shows active osteolytic metastases or bone marrow involvement. Osteoblastic lesions without FDG correspond to lesions with decreased HMDP uptake.
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F4
Tc-99m HMDP bone scintigraphy (Figure 3). To evaluate for metastases, FDG PET/CT was performed four weeks after the third injection of Ra-223 therapy and showed diffuse FDG uptake in bone without osteoblastic lesions (Figure 4).
The images of a bone marrow biopsy are shown. Hematoxylin and eosin stain (A), x400. Histologically, small round cells are diffusely spread in bone marrow. There is no ordinary tubular formation, as shown in adenocarcinoma of the prostate. On immunostaining, x400, androgen receptor (B) and cytokeratin AE1/3 (C) are both positive. Strong androgen receptor nuclear staining (B) indicates histological malignancy. Positive immunostaining for prostate-specific antigen is confirmed in some cells (D), which is not inconsistent with low-grade prostatic carcinoma. The microscopic examination shows bone marrow infiltration with prostate carcinoma.
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F5
Bone marrow metastasis was confirmed by pathological examination following FDG PET/CT-guided bone marrow biopsy (Figure 5).