Flare phenomenon

The flare phenomenon (bone flare or scintigraphic flare) is an apparent early worsening on a bone scan, PET or PSMA-PET scan that reflects a reparative or reactive process rather than true disease progression, and is followed by genuine improvement on later imaging if the underlying treatment is actually working. On technetium-99m bone scintigraphy it appears as new or more intense uptake at existing or previously inconspicuous lesions, driven by reparative osteoblastic mineralisation around healing metastases as bone lesions respond to hormone therapy, chemotherapy or bone-seeking radiopharmaceuticals; it typically appears between two weeks and three months after starting treatment, occasionally as late as six months. Reported incidence varies widely: series in patients starting first-line hormone therapy for metastatic prostate cancer describe flare in roughly 6-41% of patients depending on definition and timing of the repeat scan, and around 10% of patients receiving bone-seeking radiopharmaceutical therapy (strontium-89, samarium-153, rhenium-186, and radium-223) show a comparable flare pattern.

Because flare can be mistaken for progression, standard practice (reflected in the MD Anderson bone response criteria) is to continue therapy for a minimum of roughly 12 additional weeks before concluding a scan reflects true progression, and to confirm any apparent worsening with a repeat scan 2-3 months later showing subsequent improvement, rather than acting on a single early scan. A parallel phenomenon, PSA flare (a transient early rise in prostate-specific antigen after starting androgen deprivation therapy or antiandrogens, from an initial agonist effect before suppression takes hold), is a distinct biochemical marker that does not always occur together with bone flare; in one series both bone and PSA flare co-occurred in only about one in four patients showing either.

On PSMA-PET, flare has been studied less consistently: one cohort study found no clear PSMA expression flare after starting androgen-receptor-pathway inhibitors, while retaining the possibility that a short-duration or very early flare could have been missed, so PSMA-PET response assessment guidance generally still recommends confirmatory follow-up imaging before calling early progression, particularly close to treatment initiation.