"Rather than receiving definitive radiation treatment for localized disease, these patients may have received treatment aimed at preventing the further spread of what was incorrectly identified as metastatic disease," says Thomas Hope, MD.
Bone scans demonstrated a significantly higher false positive rate for metastases in the initial staging of prostate cancer compared with PSMA-PET imaging, suggesting that patients deemed low-volume metastatic may actually have had localized disease, according to recent data published in The Journal of Nuclear Medicine.1
“Most research to date has focused on the increased sensitivity of PSMA PET versus conventional imaging such as bone scans and CT. In this study, my colleagues and I took the opposite approach and looked at where PSMA PET was negative when bone scans were positive,” said Thomas Hope, MD, vice chair of clinical operations and strategy in the Department of Radiology and Director of Molecular Therapy at the University of California, San Francisco, in a news release on the findings.2
The investigators found that the positive predictive value (PPV) for bone scans among all patients included in the study was 0.73 (95% CI, 0.61-0.82), compared with 0.43 (95% CI, 0.26-0.63) among patients at initial staging. Overall, 57% of positive bone scans were found to be false positives.
Further, osseous region disease was identified in 13 (17%) of patients on PSMA PET, compared with 23 (30%) on bone scan. Inter-reader agreement among 3 blinded readers for osseous lesions was moderate for bone scans (Fleiss κ, 0.51) and substantial for PSMA PET (Fleiss κ, 0.80).
Across all patients, the negative predictive value (NPV) and specificity for bone scans were both 0.82 (95% CI, 0.74-0.88). At initial stage, the NPV and specificity for bone scans was 0.94 (95% CI, 0.85-0.98) and 0.80 (95% CI, 0.68-0.88), respectively.
The authors wrote, “If one were to apply our initial staging data to the [STAMPEDE] M1 RT trial, 56% of patients with low-volume disease based on bone scanning had localized disease by PSMA PET. Therefore, there is a greater likelihood that the overall survival benefit seen in the trial is not driven by preventing further development of metastatic disease but rather by providing definitive RT to nonmetastatic disease that was incorrectly classified as M1 by bone scanning.”1
In total, the retrospective study assessed data from 167 patients with prostate cancer who were imaged with both bone scans and PSMA PET within 100 days. Among those, 77 patients were at initial staging, 60 were in the biochemical recurrence (BCR) and castration-sensitive setting prostate cancer (CSPC) settings, and 30 were in the castration-resistant prostate cancer (CRPC) setting. The median time between bone scan and PSMA PET scan was 29 days, with PSMA PET performed earlier than bone scan in 70% of patients.
Additional data in the BCR/CSPC setting showed a PPV of 0.77 (95% CI, 0.57-0.90), an NPV of 0.74 (95% CI, 0.58-0.85), and a specificity of 0.85 (95% CI, 0.69-0.93). In the CRPC setting, the PPV was 1.0 (95% CI, 0.85-1.0), the NPV was 0.56 (95% CI, 0.27-0.81), and the specificity was 1.0 (95% CI, 0.57-1.0).
Hope concluded, “Rather than receiving definitive radiation treatment for localized disease, these patients may have received treatment aimed at preventing the further spread of what was incorrectly identified as metastatic disease. These results bring into question how to apply data from clinical trials that are based on bone scans to patients who receive PSMA PET. Looking at the big picture, this study highlights the importance of understanding how test characteristics impact patient management.”2
1. Hope TA, Benz M, Jiang F, et al. Do bone scans overstage disease compared with PSMA PET at initial staging? An International Multicenter Retrospective Study with Masked Independent Readers. J Nucl Med. 2023;64(11):1744-1747. doi: 10.2967/jnumed.123.265916
2. Bone scans overstage prostate cancer at initial staging compared with PSMA PET. News release. Society of Nuclear Medicine and Molecular Imaging. November 13, 2023. Accessed November 21, 2023. https://www.eurekalert.org/news-releases/1007834