Changes in Osteoblastic Bone Metastasis Detected Incidentally by Cone-Beam Computed Tomography: A Case Report

Prostate cancer is the most commonly diagnosed malignancy in men worldwide. According to the National Comprehensive Cancer Network guidelines, high-risk prostate cancer is defined as the presence of one or more of the following criteria: prostate-specific antigen (PSA) levels exceeding 20 ng/mL, Gleason score of 8 or higher, or clinical stage of T3a or greater, without evidence of lymph node involvement or distant metastasis [1]. The standard treatment for localized high-risk prostate cancer generally includes prostatectomy or a combination of radical radiotherapy and androgen deprivation therapy [2]. Salvage radiotherapy to the prostate bed is recommended in cases of biochemical recurrence without lymph node or distant metastasis after surgery [3].

Intensity-modulated radiotherapy (IMRT) is commonly used for the treatment of high-risk prostate cancer [2]. IMRT delivers high doses of radiation to the prostate while minimizing radiation exposure to surrounding tissues such as the rectum and bladder, thereby reducing the risk of both acute and long-term adverse events compared to traditional three-dimensional conformal radiotherapy [4, 5]. Image-guided radiotherapy is essential for ensuring treatment precision, and cone-beam computed tomography (CT) (CBCT) is frequently used for accurate patient positioning and target localization before each radiation [6].

We present a case in which CBCT performed to guide postoperative radiotherapy for prostate cancer revealed progressive changes in osteoblastic bone metastases. This incidental finding highlights the potential of CBCT as a valuable diagnostic tool beyond its primary role in imaging guidance. The ability of CBCT to detect clinically significant changes can directly influence treatment decisions and patient management.

The patient was a 65-year-old man in whom an elevation of prostate-specific antigen (PSA) level to 13.8 ng/mL was detected during a routine medical examination. He was subsequently diagnosed with high-risk prostate cancer (cT3aN0M0) with a Gleason score of 4 + 3. The patient underwent robot-assisted radical prostatectomy, and pathological examination revealed a Gleason score of 4 + 5, pT3aN0M0, and negative resection margins. Four months postoperatively, his PSA level increased to 0.30 ng/mL, indicating biochemical recurrence. Whole-body CT and bone scintigraphy found no evidence of metastasis (shown in Fig. 1a, b), resulting in the decision to administer salvage radiation therapy.

IMRT was delivered to the postoperative prostate bed at a total radiation dose of 66 Gy in 33 fractions. The prostate floor was delineated as the clinical target volume, and a planning target volume margin of 8 mm was added in all directions, except 4 mm posteriorly, to account for setup errors. Two months after the completion of irradiation therapy, the patient’s PSA increased to 3.04 ng/mL. Subsequent imaging identified osteoblastic bone metastasis in the left acetabulum (shown in Fig. 1c, d).

Although no bone metastasis had been detected in the left acetabulum before radiation therapy, a retrospective review of the CBCT images acquired during the treatment period incidentally revealed progressive osteoblastic changes in the same region. To objectively evaluate these changes, the Hounsfield unit (HU) values were measured at the site of bone metastasis on the CBCT images. While 33 CBCT images were available, to minimize radiation exposure, three different imaging settings were used throughout the treatment. Since the reference HU values differ depending on imaging conditions, we extracted 10 CBCT images captured under identical conditions for HU measurements (shown in Fig. 2). A circular region of interest with a diameter of 2.5 mm was placed on the area of bone metastasis, ensuring no overlap with the cortical bone. The average HU value within the region of interest was recorded, and the changes in HU values over the course of treatment were plotted on a graph (shown in Fig. 3).

Consecutive CBCT images showed that the HU of the left acetabulum region increased gradually, indicating the progression of osteoblastic metastasis, whereas the HU of the right acetabulum region did not change during radiotherapy.

This case report highlights the usefulness of CBCT in monitoring progressive changes in bone metastasis during postoperative radiotherapy for prostate cancer. Generally, CBCT is used primarily for tumor localization before irradiation in image-guided radiotherapy. However, in this case, CBCT demonstrated potential for tracking subtle osteoblastic changes throughout the course of treatment, an application that is not widely documented.

Clarke et al. reported similar findings, i.e., changes in the CBCT images acquired during radiotherapy for non-small cell lung cancer, observing tumor and lung parenchymal changes in 72% of patients [7]. Similarly, Rosen et al. evaluated dynamic changes in the parotid glands using CBCT to predict the risk of chronic xerostomia 1 year after head and neck cancer radiotherapy [8]. Mushonga et al. further demonstrated that CBCT detected anatomical changes requiring replanning in 11% of stage III NSCLC patients [9]. These results suggest that CBCT may serve not only as a guide for radiation delivery but also as a means of monitoring disease progression and treatment-induced changes in various tissues.

In osteoblastic bone metastases, cancer cells stimulate excessive osteoblast activity, leading to new bone formation, which manifests as increased density on CT and X-ray. This process begins with osteoclast activation, followed by the release of transforming growth factor and insulin-like growth factor, both of which stimulate the activity of cancer cells and osteoblasts. The bone morphogenetic protein and Wnt signaling pathways abnormally accelerate bone formation [10‒12]. In prostate cancer, this interaction is further amplified through androgen receptors, enhancing osteoblastic activity [10].

In this patient, early bone metastasis prior to radiotherapy was not detected by conventional CT or 99 mTc-methylene diphosphonate bone scintigraphy. If prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT had been utilized, it could have facilitated earlier detection of bone metastases. Diagnostic and therapeutic approaches utilizing the PSMA have become increasingly critical in managing prostate cancer, especially for detecting bone metastases [13‒15]. PSMA PET/CT imaging with 68Ga-PSMA or 18F-PSMA possesses superior sensitivity (85%) and specificity (98%) in detecting bone metastases, surpassing the performance of traditional CT and bone scintigraphy [13]. Although PSMA PET/CT is not yet covered by insurance in Japan, integrating multiple imaging modalities holds promise for improving diagnostic accuracy and treatment outcomes.

In this study, we highlight the diagnostic value of CBCT in visualizing osteoblastic changes. However, the daily review of CBCT images presents a significant burden and is not practical. Although still a conceptual approach, artificial intelligence (AI)-assisted CBCT image analysis holds promise for addressing this issue by automating image interpretation. When integrated with established subtraction techniques, it could further enhance diagnostic precision [16]. These subtraction techniques, commonly utilized in digital subtraction angiography [17], enhance the visualization of blood vessels by removing overlapping structures and highlighting only the area of interest. This method can also be employed to detect subtle changes in lung lesions and fractures, thereby improving diagnostic accuracy. Implementing these AI-assisted techniques would facilitate early diagnosis and treatment planning, significantly aiding clinical decision-making.

Future research should focus on optimizing CBCT as a diagnostic tool by integrating it with other imaging modalities and AI-based analyses, culminating in more personalized management for several cancers, ultimately improving patient outcomes. The postoperative bone changes observed on CBCT in this case underscore its diagnostic value in radiation therapy, suggesting its potential as a vital tool for daily imaging evaluation and treatment monitoring.

We are grateful to the patient described in this case report. We also wish to offer special thanks to the medical team at Jichi Medical University Hospital for their support during the patient’s care and the preparation of this manuscript.

Ethics approval was obtained from the Institutional Review Board (IRB) of Jichi Medical University Hospital for this study. The study was conducted in accordance with the principles of the Declaration of Helsinki. The patient provided written informed consent to participate in this study. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

The authors have no competing interests to declare.

There were no funding sources for this study.

Conceptualization: U.H., M.E., and K.S.; data curation: U.H., M.E., K. Okada, S.T., and K. Ogawa; formal analysis: U.H., M.E., M. Nakagawa, M. Nakamura, C.S., and Y.F.; investigation: U.H., K.A., and M.K.; writing – original draft preparation: U.H.; writing – review and editing: M.E., H.M., and K.S. All authors have read and approved the final version of this case report.

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author, K.S., upon reasonable request. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000545252).