Flare phenomenon visualized by 99mTc-bone scintigraphy has prognostic value for patients with metastatic castration-resistant prostate cancer

Xue Zhang; Kenichi Nakajima; Atsushi Mizokami; Hiroyuki Horikoshi; Koshiro Nishimoto; Katsuyoshi Hashine; Hideyasu Matsuyama; Satoru Takahashi; Hiroshi Wakabayashi; Seigo Kinuya

doi:10.1007/s12149-024-01914-8

Flare phenomenon visualized by ^99mTc-bone scintigraphy has prognostic value for patients with metastatic castration-resistant prostate cancer

Ann Nucl Med. 2024 Mar 13. doi: 10.1007/s12149-024-01914-8. Online ahead of print.

Authors

Affiliations

¹ Department of Nuclear Medicine, Kanazawa University, Kanazawa, Japan.
² Department of Functional Imaging and Artificial Intelligence, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640, Japan. nakajima@med.kanazawa-u.ac.jp.
³ Department of Urology, Kanazawa University, Kanazawa, Japan.
⁴ Department of Diagnostic Radiology, Gunma Prefectural Cancer Center, Ota, Japan.
⁵ Department of Uro-Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
⁶ Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
⁷ Department of Urology, NHO Shikoku Cancer Center, Matsuyama, Japan.
⁸ Department of Urology, JA Yamaguchi Kouseiren Nagato General Hospital, Nagato, Japan.
⁹ Department of Urology, Nihon University School of Medicine, Tokyo, Japan.

PMID: 38478154
DOI: 10.1007/s12149-024-01914-8

Abstract

Objective: This study aimed to determine the prognostic value of the flare phenomenon in patients with metastatic castration-resistant prostate cancer (mCRPC) using the bone scan index (BSI) derived from ^99mTc-methylenediphosphonate (MDP) bone scintigraphy images.

Methods: We categorized 72 patients from the PROSTAT-BSI registry with mCRPC who were followed-up for 2 years after starting docetaxel chemotherapy to groups based on pre-chemotherapy BSI values of < 1, 1-4, and > 4. We assessed the effects of the flare phenomenon (defined as a > 10% increase in the BSI within 3 months of starting chemotherapy, followed by > 10% improvement within the next 3 months) on survival using Kaplan-Meier curves and Cox proportional hazard analyses.

Results: The flare phenomenon was found in 26 (36%) of the 72 patients. Prostate-specific antigen (PSA), alkaline phosphatase (ALP), and hemoglobin (Hb) levels steadily increased, then deteriorated in patients with and without flare, respectively. Elevated BSI and PSA values at 3 months after starting therapy and the absence of abiraterone or/and enzalutamide therapy led to poor 2-year overall survival (OS) in the group without flare. In contrast, no influence was noticeable in the group with flare. The results of multivariable analyses that included only factors associated with PSA and BSI showed that increased baseline BSI (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.04-1.86; P = 0.023) and PSA (HR, 7.15; 95% CI 2.13-24.04; P = 0.0015) values could be independent risk factors for patients with mCRPC without flare. However, these factors lost significance during flare. The risk for all-cause death was significantly higher among patients with BSI > 4 without, than with flare. The results of univariable analyses indicated that flare positively impacted survival (HR, 0.24; 95% CI 0.06‒0.91; P = 0.035). Multivariable analysis did not identify any factors that could predict outcomes.

Conclusion: Favorable prognosis, with fewer disturbances from other factors such as the use of abiraterone or/and enzalutamide, PSA changes, and BSI, was attainable in cases when the mCRPC patient demonstrated flare phenomenon. Follow-up bone scintigraphy at least every 3 months could help to determine the prognosis of patients with bone metastasis of mCRPC.

Keywords: Biomarker; Bone scan index; Chemotherapy; Multicenter study; Prognosis.