Prostate cancer has emerged as a significant health issue in Korea, with its incidence steadily increasing over recent years [1,2]. It has become one of the most diagnosed cancers among Korean men, reflecting shifts in lifestyle, aging demographics, and advancements in diagnostic techniques. For elderly patients or those with high comorbidities, surgical interventions such as robotic-assisted radical prostatectomy may not be feasible due to elevated risks associated with surgery [3-5]. In such cases, radiotherapy serves as a crucial treatment modality, offering a noninvasive alternative to manage the disease effectively.

Carbon ion radiotherapy (CIRT) is an advanced form of radiotherapy that utilizes carbon ions to deliver highprecision treatment to cancer cells [6]. Its advantages over conventional photon-based therapies include superior dose distribution and a higher relative biological effectiveness, leading to improved tumor control [7]. It arises as an effective and safe options in elderly patients for their treatment of high-risk prostate cancer [8]. However, one of the associated risks with CIRT is gastrointestinal toxicity, particularly affecting the rectum due to its close proximity to the prostate [9]. Exposure of the rectal tissue to radiation can result in adverse effects such as rectal bleeding, pain, and incontinence, which significantly impact the patient’s quality of life [10].

To mitigate these risks, rectal spacers like the SpaceOAR hydrogel have been developed [11]. The hydrogel is injected into the space between the prostate and rectum, physically increasing the distance and thereby reducing the radiation dose received by the rectal wall. Previous studies have demonstrated the effectiveness of SpaceOAR hydrogel in reducing rectal radiation exposure and minimizing gastrointestinal toxicity in patients undergoing photon-based radiotherapy or brachytherapy [12-17]. These studies have reported not only decreased incidence of acute and late rectal side effects but also improved overall treatment tolerability and patient satisfaction.

Despite the established benefits of SpaceOAR hydrogel in reducing rectal toxicity during prostate radiotherapy, data on the placement accuracy and learning curve specific to Korean patients—particularly in the context of CIRT remain limited. Existing studies primarily focus on Western populations and do not address the unique challenges or procedural outcomes relevant to Korean patients undergoing advanced radiotherapy modalities. Additionally, the simultaneous insertion of gold fiducial markers, which is essential for precise image-guided radiotherapys [18], has not been thoroughly examined alongside SpaceOAR hydrogel placement. This gap highlights the need for procedural standardization to optimize both spacer and marker positioning for enhanced treatment precision.

This study aims to address these gaps by focusing on the periprocedural outcomes of SpaceOAR hydrogel insertion, specifically evaluating the immediate complications, technical challenges, and procedural safety rather than long-term postradiotherapy effects. By analyzing the first 104 cases performed by a single urologist without prior experience, we assess the placement accuracy and learning curve involved in the combined insertion of SpaceOAR and gold fiducial markers in Korean prostate cancer patients undergoing CIRT. The findings are intended to inform clinical practice by providing insights into the feasibility, safety, and efficiency of these techniques, with potential implications for training protocols, improved patient outcomes, and broader adoption in prostate cancer radiotherapy.

A total of 108 SpaceOAR procedures were performed during the study period. Four cases were excluded from the analysis due to prior radiotherapy, leaving 104 patients for the final analysis, with a median follow-up period of 5.0 months. The baseline characteristics of the cohort are summarized in Table 1. The mean prostate-specific antigen level was 11.0±22.2 ng/mL (range, 1.64-207.0 ng/mL). The majority of patients had Gleason grade group 2 (38.5%) and group 3 (26.9%). Grade group 4 or higher were present in 13.5% of patients. Advanced local stages (cT3a/bN0M0) accounted for 20.2% of patients. According to the NCCN risk stratification criteria, 45.2% were classified as unfavorable intermediate-risk, and 25.0% as high-risk or very-high risk group. One patient was classified as cT2bN0M1b (oligometastasis). Neoadjuvant androgen deprivation therapy (ADT) was administered to 71.2% of patients, mostly of the unfavorable intermediate or higher risk groups. The mean prostate volume was 21.6±10.6 mL (range, 6-65 mL). The small size of the prostate reflects decrease following 2-3 months of neoadjuvant ADT.

Of the total 104 procedures, 26 were performed under general anesthesia, primarily during the initial phase of the study, while 78 were conducted under local anesthesia. Notably, all procedures after case #36 were carried out under local anesthesia, with no instances of conversion from local to general anesthesia occurring throughout the study. The mean operative time for all cases was 12.70±3.40 minutes. Patients who underwent the procedure under general anesthesia had a mean operative time of 15.12±6.90 minutes, compared to 11.76±2.96 minutes for those under local anesthesia—a difference that was statistically significant (Mann-Whitney U=1,315.5, p=0.023) (Fig. 4A). Including both anesthesia types, the average operative time decreased slightly from 12.70±3.40 minutes in the first 50 cases to 12.50±5.35 minutes in the subsequent 54 cases. Linear regression analysis of operative time versus case number demonstrated a statistically significant learning curve (F[1, 102]=5.969, p=0.0163), described by the equation Y=-0.03507×X+14.44 (Fig. 4B). This indicates a reduction of approximately 0.35 minutes in operative time for every 10 additional cases, reflecting an improvement in procedural efficiency over time.

Using planning MRI obtained on postoperative days 10 to 14, we reviewed the thickness and symmetry of the injected hydrogel. Spacer thickness was measured as the distance between the prostate midgland and the rectal wall on sagittal MRI views. All cases achieved a spacer thickness of 10 mm or greater, with a median thickness of 14 mm (range, 10-22 mm). Spacer placement accuracy was assessed using a patient-level symmetry scoring method, where a score of 1 indicated gel symmetry in all 3 slices, and scores of 2 through 5 indicated increasing asymmetry. One failure case (case #75) occurred due to fibrosis resulting from a prior high-intensity focused ultrasound (HIFU) procedure, which prevented the creation of space between the prostate and rectum. Excluding this case, 89 patients (86.4%) achieved a symmetry score of 2 or less. The incidence of asymmetry (scores 3, 4, or 5) decreased from 10 cases in the first 50 procedures to 5 cases in the subsequent 53 procedures. A rolling average of symmetry scores over case numbers (using a window size of 10 cases) suggested procedural refinement over time (Fig. 5).

Procedural complications were observed in 25 patients (24.0%), including the case involving HIFU failure. The most common adverse events were constipation (9.6%), decreased urinary stream (4.8%), and perianal pain (3.8%). Grade 2 AUR occurred in 3 patients (3%).

• Case #4: an 81-year-old male, developed AUR after undergoing SpaceOAR insertion under general anesthesia, necessitating Foley catheterization for 2 weeks. His scheduled CIRT proceeded without delay; however, during the final week of treatment, he experienced recurrent retention requiring an additional 2 days of catheterization. (preprocedure International Prostate Symptom Score [IPSS] S8 L2, prostate volume was 19 g).

• Case #18: a 66-year-old male, also encountered AUR following the procedure under general anesthesia and regained normal voiding function after 11 days with a Foley catheter (preprocedure IPSS S26 L4, prostate volume was 29 g).

• Case #76: who received SpaceOAR insertion under local anesthesia, presented with AUR that required 15 days of catheterization. Notably, neither case #18 nor case #76 experienced further urinary difficulties during or after CIRT (preprocedure IPSS not surveyed, prostate volume was 32 g).

Other complications, such as urgency, nocturia, and hematuria, were rare and generally mild (grade 1), resolving without intervention. No significant differences were found between patients with complications and those without in terms of age (p=0.416), operative time (p=0.291), or prostate volume (p=0.356). The complications are summarized in Table 2.

This study evaluated the placement accuracy and learning curve associated with SpaceOAR hydrogel and gold fiducial marker insertion in Korean prostate cancer patients undergoing CIRT. Performed by a single urologist without prior experience, the procedure demonstrated high placement accuracy, a modest learning curve, and a low complication rate. Our findings suggest that SpaceOAR insertion with fiducial marker placement is a reliable and efficient procedure that can be effectively adopted in clinical practice, even by practitioners new to the technique.

With a high success rate of 103 successful hydrogel injections out of 104 cases, our findings are consistent with previous studies demonstrating the effectiveness and feaTable sibility of SpaceOAR hydrogel placement. For instance, Mariados et al. [12] reported successful spacer placement in 99% of patients scheduled for intensity-modulated radiation therapy (IMRT), highlighting the procedure’s feasibility during the initial phase of rectal hydrogel utilization. Similarly, Song et al. [14] achieved significant reductions in rectal radiation exposure through hydrogel placement in 95.7% of patients within their IMRT cohort, reinforcing the technique’s reproducibility . In the setting of high-dose brachytherapy, Wu et al. [16] reported successful hydrogel injection in all 18 consecutive patients. Moreover, Pinkawa et al. [20] successfully performed hydrogel placement even during salvage radiotherapy, injecting the gel between the local recurrence and rectal wall under TRUS guidance. These collective findings underscore the inherent ease and adaptability of the hydrogel injection procedure across various radiation therapy modalities. Our study extends these findings to a Korean population undergoing CIRT, a modality where precise targeting is crucial due to the steep dose gradients involved. Our study is significant as it is one of the few to assess SpaceOAR placement accuracy and the learning curve in the context of CIRT. By demonstrating that urologists without prior experience can achieve high placement accuracy and procedural efficiency, we support the broader adoption of this technique in centers offering advanced radiotherapy modalities.

The modest learning curve observed in our study is noteworthy. Operative time decreased significantly over the course of the study, with a reduction of approximately 0.35 minutes per every 10 additional cases. This improvement is consistent with other studies that have examined the learning curve for SpaceOAR hydrogel insertion. For instance, Pinkawa et al. [21] demonstrated that increasing experience with the procedure led to improved and more symmetrical spacer placement, greater prostate-rectum separation, decreased rectal dose, and reduced acute toxicity. The transition from general to local anesthesia after case #36 further reduced operative times, suggesting that the procedure can be comfortably and efficiently performed under local anesthesia. This shift not only enhances patient convenience by reducing anesthesia-related risks and recovery times but also optimizes resource utilization by decreasing operating room demands. Overall, these findings underscore the practicality and adaptability of SpaceOAR hydrogel insertion in various clinical settings.

In our study, complication rates were low and predominantly minor, with constipation, weak urinary stream, and perianal pain being the most common. AUR occurred in 3% of patients but did not result in delays of the scheduled CIRT. These findings are comparable to those reported in other populations, including those planned for brachytherapy or EBRT [22-27]. The absence of serious complications previously reported—such as rectal ulcers, fistulas, and infections [28,29]—underscores the safety and maturity of the procedure, which has been established over the past 10 years [21,23], as well as the preparedness of our staff. We did not use intravenous antibiotic prophylaxis; instead, we prescribed only 5 days of oral antibiotics with nonsteroidal anti-inflammatory drugs.

One notable case of spacer insertion failure occurred in a patient with prior HIFU therapy, resulting in fibrosis that impeded space creation between the prostate and rectum. This suggests that a history of prostate interventions may affect spacer placement and should be carefully considered during patient selection. However, another patient with a history of HIFU and other patients with previous prostate interventions—including irreversible electroporation, transurethral resection of the prostate, and UroLift—had no difficulties completing the procedure. Further studies could explore the impact of previous treatments on spacer insertion success rates. Further studies could explore the impact of previous treatments on spacer insertion success rates.

This study has several limitations. First, as a retrospective observational study conducted at a single institution with a single surgeon, the findings may not be generalizable to other settings or operators. Second, long-term outcomes— such as late rectal toxicity and quality of life measures— in this special population undergoing hypofractionated radiotherapy (CIRT, 12 fractions) were not assessed and should be investigated in future studies. Comparing these results with previous studies on CIRT functional outcomes (gastrointestinal/genitourinary) without rectal spacers would provide valuable insights [30]. Additionally, preprocedural IPSS scores were not included in the analysis, and uroflowmetry was not performed for most patients, limiting our ability to fully assess predictive factors for AUR or other complications. These factors should be considered in future studies to strengthen the predictive assessment of such adverse events.

n summary, our study demonstrates that rectal hydrogel and gold fiducial marker insertion is a feasible, efficient, and safe procedure that can be readily adopted by urologists without prior experience. The high placement accuracy, modest learning curve with significant reductions in operative time, and the successful shift from general to local anesthesia highlight the practicality of integrating this technique into clinical practice. Importantly, the low complication rates—predominantly minor and comparable to other radiation therapy settings—underscore the procedure’s maturity and its potential to minimize rectal toxicity in this population. We encourage fellow urologists to consider adopting SpaceOAR hydrogel insertion as it offers a valuable tool to enhance treatment precision and protect patients from rectal toxicity, ultimately improving outcomes in prostate cancer radiotherapy.