This study was approved by the institutional review board of Yokosuka City Hospital (No. 2023-9). Between May 2022 and August 2023, 22 patients with prostate cancer were implanted with a hydrogel spacer (SpaceOAR, Boston Scientific Corporation, Marlborough, MA, USA) for EBRT. The patient age was defined as the age at the time of hydrogel spacer implantation. All patients received combined androgen blockade therapy before hydrogel spacer implantation. The obesity parameter, BMI, was calculated from the weight and height at the time of hydrogel spacer implantation. eGFR was estimated using the following conversion formula for Japanese men: eGFR (mL/min/1.73 m2) = 194 × serum creatinine (SCr)−1.094 × age−0.287 [14] before hydrogel spacer implantation. VFA around the implanted hydrogel spacer was evaluated at the umbilical position, as previously described [15], and also at the femoral head position using computed tomography (CT) images obtained for RT planning. These calculations were performed using Ziostation2 version 2.9.x (Ziosoft, Tokyo, Japan).

MRI was performed before and during EBRT. Before EBRT, MRI was performed 8 days (median, range of 7 to 14 days) after hydrogel spacer implantation. During EBRT, MRI was performed on the day when the radiation dose of 48 Gy (median, range of 44 to 58 Gy) was delivered at 55 days (median, range of 49 to 64 days) after implantation. All patients underwent prostate MRI on 3.0 Tesla MR scanners (Skyra, Siemens, Erlangen, Germany) with a body coil. The main parameters of axial T2-weighted images (T2WI) and internal validation set were as follows: the echo time (TE) was 90 ms, the repetition time (TR) was 4000 ms, the spacing between slices was 0.7 mm, the slice thickness was 3.5 mm, the field of view was 220 mm × 220 mm and the voxel size was 0.4 × 0.4 × 3.5 mm3. T2WI were acquired because they have been shown to reveal the hydrogel spacer clearly [16]. MRI data were transferred as digital imaging and communications in medicine (DICOM) files to a radiation treatment planning system (Monaco version 5/6, Elekta AB, Stockholm, Sweden) to contour the hydrogel spacer and determine the spacer volume. All contours were defined jointly by the two radiation oncologists (radiation oncologist A, with experience of 20 years and radiation oncologist B, with experience of 30 years) to exclude inter-observer variability. MRI images were also used to measure the maximum and minimum distances between the prostate and anterior wall of the rectum at the middle height of the prostate before and during EBRT [10].

The clinical target volume (CTV) was defined as the prostate ± proximal seminal vesicles, and the planning target volume (PTV) of the CTV had a margin of 8 mm, with 2 mm on the posterior rectal side. EBRT was planned so that 95% of the prescribed dose covered the PTV or at least the entire CTV. All patients were treated with three-dimensional conformal radiation therapy (3D-CRT) consisting of seven tangential beams, with a prescribed dose of 70 Gy over 35 fractions. For only one patient with pelvic lymph node metastasis, irradiation started with the prophylactic pelvic irradiation field, and the boost consisted of seven tangential beams, which was delivered to the PTV of the prostate. Patients did not exhibit acute toxicity related to RT, namely grades of  ≥ 3 according to National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 [17]. Grade 2 urinary retention was observed in only one patient, in whom the hydrogel spacer partially migrated into the prostate, resulting in termination of EBRT after a total radiation dose of 64 Gy.

Data were statistically analyzed using SPSS version 21.0 (IBM, Armonk, NY, USA). Univariate analysis with Pearson’s χ2 test and multivariate analysis using logistic regression via the forced entry procedure were performed to evaluate whether patient factors (i.e., age, BMI, eGFR, VFA, and hydrogel spacer volume before EBRT) were associated with spacer volume changes. P-values < 0.05 were considered statistically significant. In addition, scattergrams were plotted to correlate the change in the spacer volume with the change in the distance between the prostate and anterior wall of the rectum. Correlation coefficients were calculated using Spearman’s rank correlation.