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Short read · Oncology

Bone Scan Flare or Progression: How Do You Approach the Difference?

Oncology · 3 min read

Brighter bones can mean healing. Timing, tumor markers and a second scan tell you which.

Weeks into a new treatment for any cancer with bone metastases, the bone scan looks worse — brighter lesions, perhaps new ones. That can be tumour growing, or bone healing around tumour that is dying. Call it wrong and you stop a treatment that is working.

What flare is

  • Definition: more or brighter lesions during treatment, which fade on a later scan.
  • Why: the tracer marks osteoblastic activity. When treatment works, bone repairs around the dying tumour and takes up tracer avidly — lytic lesions turn sclerotic.
  • After: hormone therapy, chemotherapy, targeted drugs and radiotherapy — in breast, lung, prostate and other cancers.
  • When: usually within the first 3 months; settles by about 6 months.
Cancer and treatmentFlare
Breast, systemic therapy (Coleman 1988)12 of 16 whose lytic disease healed
Breast, hormones or chemotherapy (Janicek 1994)12%; seen at 3.2 ± 1.4 months, settled by 6.2 ± 3.0 months
Breast, first-line hormone therapy (Vogel 1995)Possible flare in 29% by week 16
Lung (NSCLC), gefitinib (Chao 2009)7 of 33 (21%); median day 34
Prostate, abiraterone (Ryan 2011)11 of 23 (48%)
  • Flare is good news: flare marks a response to treatment — after successful therapy it is common, not rare.

Flare vs progression

CheckFlareProgression
TimingFirst ~3 months of a new treatmentAny time; new lesions after ~6 months mean progression
Tumour markersFalling (e.g. PSA, CA 15-3, CEA)Rising
Bone painSettlingWorsening
X-ray / CTLytic lesions turning sclerotic (healing)New lytic lesions or soft-tissue mass
Disease elsewhereResponding — nodes, liver, lungProgressing
Next scanLesions fading, nothing newStill more new lesions
Remember

“Markers fall, bones flare; markers rise, beware.” Lytic turning sclerotic is healing, not spread.

What to do

Flare or progression. New or brighter bone lesions in the first 3 months of treatment are not yet progression. A scan 6 to 12 weeks later decides: further new lesions with rising markers mean progression; otherwise it was flare and treatment continues.keep treatingBaselinestart therapyScan 1first ~3 monthsScan 26–12 weeks laterYesNoNew or brighter lesions:not progression yetFurther new lesions,markers rising?Progression— changetreatmentFlare —continuetreatment
Figure 1. An early worse-looking scan waits for a second scan before it is called progression.
  • Don’t call it on one scan: in the first 3 months, brighter lesions alone are not progression.
  • Correlate at once: markers, symptoms, CT of the lesions, and disease outside bone.
  • Report it neutrally: “increased activity, may represent flare; suggest follow-up scan in 6–12 weeks.”
  • The second scan decides: further new lesions on the next scan mean progression; fading lesions mean flare.
Prostate example: the 2+2 rule

Prostate trials formalise this (PCWG): ≥2 new lesions on the first on-treatment scan count as progression only if a scan ≥6 weeks later shows ≥2 more.

Pitfalls
  • Stopping a working drug. In one breast cancer trial, over a third of patients with a possible flare were taken off therapy; of those kept on it, 72% benefited.
  • Not only bone scan. 18F-NaF PET and even FDG PET can show a bone flare.
  • G-CSF mimic. Growth factors cause diffuse marrow and juxta-articular uptake — not metastases.
  • Flare needs a working treatment. Rising markers with new lesions, or progression elsewhere, is progression whatever the timing.
Take home
  • Flare is healing bone lighting up after effective treatment in any cancer — usually in the first 3 months, settling by about 6.
  • Read the scan with timing, tumour markers, pain, CT and disease elsewhere; lytic lesions turning sclerotic mean healing.
  • Never call progression on the first on-treatment scan alone — confirm on a later scan (in prostate cancer, the 2+2 rule).
Sources
  1. Coleman RE, Mashiter G, Whitaker KB, et al. Bone scan flare predicts successful systemic therapy for bone metastases. J Nucl Med. 1988;29(8):1354-9.
  2. Janicek MJ, Hayes DF, Kaplan WD. Healing flare in skeletal metastases from breast cancer. Radiology. 1994;192(1):201-4.
  3. Vogel CL, Schoenfelder J, Shemano I, et al. Worsening bone scan in the evaluation of antitumor response during hormonal therapy of breast cancer. J Clin Oncol. 1995;13(5):1123-8.
  4. Chao HS, Chang CP, Chiu CH, et al. Bone scan flare phenomenon in non-small-cell lung cancer patients treated with gefitinib. Clin Nucl Med. 2009;34(6):346-9.
  5. Ryan CJ, Shah S, Efstathiou E, et al. Phase II study of abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer displaying bone flare discordant with serologic response. Clin Cancer Res. 2011;17(14):4854-61.
  6. Scher HI, Morris MJ, Stadler WM, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34(12):1402-18.
  7. Weisman AJ, Harmon SA, Perk TG, et al. Quantification of bone flare on 18F-NaF PET/CT in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2019;22(2):324-30.
  8. Krupitskaya Y, Eslamy HK, Nguyen DD, et al. Osteoblastic bone flare on F18-FDG PET in non-small cell lung cancer (NSCLC) patients receiving bevacizumab in addition to standard chemotherapy. J Thorac Oncol. 2009;4(3):429-31.
  9. Stokkel MP, Valdés Olmos RA, Hoefnagel CA, Richel DJ. Tumor and therapy associated abnormal changes on bone scintigraphy. Old and new phenomena. Clin Nucl Med. 1993;18(10):821-8.
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