For effective clinical management of patients being treated with Ra-223, there is a need for radiographic response biomarkers to minimize disease progression and to stratify patients for subsequent treatment options. The objective of this study was to evaluate automated Bone Scan Index (aBSI) as a quantitative assessment of bone scan for radiographic response in patients with metastatic castration resistant prostate cancer (mCRPC).
Methods
In a multi-center retrospective study, bone scans from patients with mCRPC treated with monthly injections of Ra-223, were collected from seven hospitals in Sweden. Patients with available bone scans prior to treatment with Ra-223 and at treatment discontinuation were eligible for the study. Using EXINI automated platform, the aBSI was generated at baseline and at treatment discontinuation. The Spearman´s rank correlation was used to correlate aBSI with the baseline covariates – alkaline phosphatase (ALP) and Prostate Specific Antigen (PSA). Cox proportional hazard model and KaplanMeier curve was used to evaluate the association of covariates at baseline and their change at treatment discontinuation with overall survival (OS). Concordance index (C-index) was used to evaluate the discriminating strength of covariates in predicting OS.
Results
Bone scan images at baseline were available from 156 patients, and 67 patients had both baseline and treatment discontinuation bone scan (median dose= 5; IQR: 3 – 6). Baseline aBSI (median=4.5; IQR: 2.4-6.5) was moderately correlated with ALP (r=0.60, p<0.0001) and with PSA (r=0.38, p=0.003). Among baseline covariates, aBSI (p=0.01) and ALP (p=0.001) were both significantly associated with OS, whereas PSA values were not (p=0.059. After treatment discontinuation, 36% (24/67), 80% (54/67), and 13% (9/67) patients demonstrated decline in aBSI, ALP and in PSA, respectively. As a continuous variable, the relative change in aBSI after treatment compared to baseline, was significantly associated with OS (p<0.0001), with a C-index of 0.67. Median OS of patients with both BSI and ALP decline (median=134 weeks) was found to be significantly longer than in patients with ALP decline only (median=77 weeks, p=0.029).
Conclusions
aBSI at baseline and its change at treatment discontinuation were both significant parameters associated with OS. The study warrants prospective validation of aBSI as a quantitative imaging response biomarker to predict OS in patients with mCRPC treated with Ra-223.
Written by: Aseem Anand,1 Elin Tragardh,2 Lars Edenbrandt,3 Lars Beckman,4 Jan-Henry Svensson,5 Camilla Thellenberg,6 Anders Widmark,6 Jon Kindblom,7 Anders Ullén,8 Anders Bjartell1
- Skane University Hospital, Dept of Translational Medicine, Division of Urological Cancers, Lund University, Malmo, Sweden
- Skane University Hospital, Clinical Physiology and Nuclear Medicine, Malmo, Sweden
- Gothenburg University, Dept. of Nuclear Medicine, Gothenburg, Sweden
- SundsvallHärnösand County Hospital, Dept. of Oncology, Sundsvall, Sweden
- Skovde Hospital, Dept. of Urology, Skövde, Sweden
- Umea University, Dept. of Radiation Sciences, Umea, Sweden
- Gothenburg University, Dept. of Oncology, Gothenburg, Sweden
- Karolinska University Hospital and Dept. of Oncology, Karolinska Institutet, Stockholm, Sweden