What is the clinical significance of a rising PSA during Ra-223 dichloride therapy?

1277 Objectives: Radium-223 dichloride (Ra-223 Xofigo) is a treatment option for metastatic castrate-resistant prostate cancer (mCRPC) with bone metastases. It is unclear whether a rising PSA during and after Xofigo therapy is due to bone and/or soft tissue disease progression or a flare response. To answer this question, this retrospective study evaluated alkaline phosphatase (ALP) and PSA levels, along with concomitant bone scan and CT observations. Methods: A total of 30 patients diagnosed with mCRPC with bone metastases were treated with Ra-223 dichloride between July 2014 and September 2019. Twenty-four of 30 patients had PSA assessment, ALP assessment, bone scan and CT chest, abdomen and pelvis acquired before the initiation of therapy as the baseline, between injections, and after finishing Xofigo therapy. Six patients were lost to follow-up after Xofigo therapy. Results: Among the 24 patients who had follow-up, 10 patients completed all 6 treatments of Xofigo, and 14 patients completed fewer treatments (between 1 and 5 cycles). On average, the ALP decreased by 29% at the nadir and 13% at completion, and the nadir occurred between the 3rd and 4th cycles. The PSA increased on average by 44% in between each cycle, and the lowest PSA was observed between the 1st and 2nd cycles. Three out of 24 patients (12.5%) PSA levels decreased after Xofigo therapy, and their ALP levels decreased or were stable after therapy. Two of these 3 patients had PSA flare phenomenon whereby the PSA increased initially after the 1st or 2nd cycles, and then decreased below baseline after the last treatment. Twenty-one out of 24 patients (87.5%) PSA levels increased during and after Xofigo therapy. Among these 21 patients whose PSA increased, 15 patients (71.4%) ALP levels were stable or decreased after completing therapy. The majority of these patients (11 out of 15) demonstrated soft tissue disease progression on CT scan, including metastases to the adrenal gland, liver, lung, lymph nodes or brain. The bone scans performed on these 15 patients showed variable responses, for example, 1 patient demonstrated improvement, 2 patients had stable bone scan findings, 4 patients showed mixed response (with some foci showing interval improvement and other foci demonstrating interval progression), and 8 patients demonstrated bone disease progression. Among the 21 patients whose PSA increased after therapy, 6 patients (28.6%) ALP levels increased, and their bone scans demonstrated progression (n=4) or mixed response (n=2). In addition, 5 of the 6 patients demonstrated soft tissue disease progression on CT with metastases to the adrenal gland, lung, liver, or lymph nodes. Conclusions: Most mCRPC patients (87.5%) in our study demonstrated increasing PSA levels during and after Ra-223 dichloride therapy. Despite a rising PSA, however, the majority (71.4%) of patients had ALP levels that were stable or decreased, and these patients were more likely to exhibit soft tissue disease progression on CT, with a variable response on bone scan. Patients with an increase in both PSA and ALP levels after Ra-223 dichloride therapy demonstrated disease progression in both the bones and soft tissues.