Reliability of Alkaline Phosphatase for Differentiating Flare Phenomenon from Disease Progression with Bone Scintigraphy

Simple Summary Bone scintigraphy is the most widely used radionuclide technique to investigate bone metastasis, primarily due to its reasonable time and cost factor. However, it is important to recognize that bone scintigraphy to assess treatment response sometimes shows a "flare phenomenon", which can be misinterpreted as disease progression. Distinction between flare phenomenon and disease progression could help in the decision to continue effective treatments in patients with flare phenomenon and to cease ineffective treatments and consider other salvage treatment plans in patients with disease progression. Despite many methods having been tried to answer this question, there was still no reliable way to differentiate between flare phenomenon and progression of bone metastases. Our results suggest that ALP is a useful serologic marker to differentiate flare phenomenon from disease progression on bone scintigraphy in breast or prostate cancer patients with bone metastasis. The flare phenomenon (FP) on bone scintigraphy after the initiation of systemic treatment seriously complicates evaluations of therapeutic response in patients with bone metastases. The aim of this study was to evaluate whether serum alkaline phosphatase (ALP) can differentiate FP from disease progression on bone scintigraphy in these patients. Breast or prostate cancer patients with bone metastases who newly underwent systemic therapy were reviewed. Pretreatment baseline and follow-up data, including age, pathologic factors, type of systemic therapy, radiologic and bone scintigraphy findings, and ALP levels, were obtained. Univariate and multivariate analyses of these factors were performed to predict FP. An increased extent and/or new lesions were found in 160 patients on follow-up bone scintigraphy after therapy. Among the 160 patients, 80 (50%) had an improvement on subsequent bone scintigraphy (BS), while subsequent scintigraphy also showed an increased uptake in 80 (50%, progression). Multiple regression analysis revealed that stable or decreased ALP was an independent predictor for FP (p < 0.0001). ALP was an independent predictor for FP on subgroup analysis for breast and prostate cancer (p = 0.001 and p = 0.0223, respectively). Results of the study suggest that ALP is a useful serologic marker to differentiate FP from disease progression on bone scintigraphy in patients with bone metastasis. Clinical interpretation for scintigraphic aggravation can be further improved by the ALP data and it may prevent fruitless changes of therapeutic modality by misdiagnosis of disease progression in cases of FP.