Flare phenomenon in prostate cancer: recent evidence on new drugs and next generation imaging

Abstract

Over the years, an increasing proportion of metastatic prostate cancer patients has been found to experience an initial bone flare phenomenon under both standard therapies (androgen deprivation therapy, chemotherapy, radiotherapy, abiraterone, enzalutamide) and novel agents (immunotherapy, bone-targeting radioisotopes). The underlying biological mechanisms of the flare phenomenon are still elusive and need further clarification, particularly in relation to different types of treatment and their treatment response assessment. Flare phenomenon is often underestimated and, in some cases, can negatively affect clinical outcome. In cases with suspected bone flare, the treatment should be continued for a minimum of 12 more weeks before further decisions about efficacy can be taken. Physicians and patients should be aware of this effect to avoid unwarranted anxiety and inadequate early discontinuation of treatment. This review aims at highlighting new evidence on flare phenomenon arising after the introduction of new drugs extending across the biochemical, radiographic and clinical spectrum of the disease.

Flare on [18F]PSMA-1007 PET/CT after short-term androgen deprivation therapy and its correlation to FDG uptake: possible marker of tumor aggressiveness in treatment-naïve metastatic prostate cancer patients

“…Therefore, this flare phenomenon might be able to identify more aggressive Bone flare is a phenomenon that has already been observed in bone scintigraphy as either an increase in metabolic activity or the presence of new lesions within few weeks to few months of oncological treatments in PCa as well as other malignances. This phenomenon has been considered as a sign of favorable response to treatment [20]. In our study, 22/23 patients with bone metastases presented with flare of PSMA uptake after ADT in the bone.…”

“…The possible pathogenesis of the flare in bone tissue might be caused by the healing processes of new bone formation after short-term treatment. In addition, an immune response, specifically a T-cell reaction accompanied by the release of pro-inflammatory cytokines might possibly be involved in the flare phenomenon [20].…”

Bone flare after initiation of novel hormonal therapy in patients with metastatic hormone-sensitive prostate cancer: A case report

“…During treatment, the PSA level decreased significantly, and the alkaline phosphatase level did not change significantly. Vincenza et al [ 7 ] pointed out that therapy for metastatic disease may lead to healing and new bone formation, which causes an initial increase in tracer uptake (akin to callus formation). This deterioration, followed by subsequent improvement in the bone scan appearance after successful therapy, is defined as a flare response.…”

Bone Metastases Are Measurable: The Role of Whole-Body MRI and Positron Emission Tomography

“…The optimal timing of disease assessment will depend on the specific treatment type a patient is receiving, such as radiotherapy, RLT, chemotherapy, or other targeted drugs. For example, systemic cytotoxic or antihormonal treatments may elicit so called 'flare' phenomena, potentially precluding the use of PET early during treatment follow-up (147)(148)(149)(150). This can be avoided by adhering to clinical guidelines and not performing PET too soon after treatment initiation.…”