1. Introduction

Definitive treatments for clinically localized prostate cancer (PCa) traditionally included radical prostatectomy (RP) and radiation therapy (RT) [1–3]. However, the absence of randomized controlled trials directly comparing their efficacy poses a challenge for clinicians and patients in making informed treatment decisions. Additionally, the impact of acute adverse events, surgical complications, and their effects on urinary continence, sexual function, and long-term oncological outcomes remains inadequately understood. Current clinical guidelines endorse both treatment options, further complicating the selection of the optimal approach.

Given this uncertainty, a thorough evaluation of treatment outcomes is crucial. Analyzing our institutional experience with RP and RT may yield valuable insights into their respective clinical efficacies, associated adverse events, and alternative strategies for PCa management. This study aims to comprehensively assess the effectiveness of RP and RT within our patient cohort while closely examining treatment-related adverse events. Furthermore, we investigate their potential impact on key oncological endpoints, including long-term overall survival (OS) and PCa-specific survival (PCSS). The primary objective of this study is to provide a rigorous comparison of both surgical and radiological treatments, offering insights to guide clinical decision-making. Based on 25 years of experience, this study represents the longest comparative analysis of oncological outcomes between these two treatment modalities and aims to contribute meaningful evidence to daily clinical practice.

2. Patients and Methods

3. Results

3.4. Sexual Function

Figure 1 illustrates a significant decline in sexual function from baseline to 4 weeks postoperatively in the RARP group (p < 0.001).

3.5. OS

Figure 2 depicts Kaplan–Meier survival curves for OS. Cox regression analysis revealed a significant difference in OS between the RP and IMRTG cohorts in the univariate analysis, with the RP cohort demonstrating a substantially lower hazard ratio. However, this difference was not observed in the multivariate analysis, likely due to the IMRTG cohort having a higher proportion of high-risk disease at baseline.

The 10-year OS rates were 93.1% for the RP cohort and 89.0% for the IMRTG cohort, while the 15-year OS rates were 80.9% and 58.3%, respectively.

3.6. PCSS

Figure 3 illustrates the Kaplan–Meier curves for PCSS. No mortality was observed in the IMRTG cohort, rendering the data nonestimable. The 10-year PCSS rates were 98.7% for the RP cohort and 100% for the IMRTG cohort, with identical rates observed at 15 years.

4. Discussion

Recent longitudinal studies have shed light on the extended clinical outcomes of various treatment modalities for localized PCa [10]. Notably, the ProtecT trial utilized radiotherapy combined with neoadjuvant ADT for 3–6 months, employing three-dimensional conformal RT (3D-CRT) at 74 Gy in 37 fractions. In contrast, our study employed IMRTG at 78 Gy in 39 fractions, accompanied by ADT. Several treatment planning studies have consistently demonstrated the superiority of IMRT over 3D-CRT in minimizing radiation exposure to surrounding organs [11–13]. Furthermore, the integration of image-guided RT (IGRT) in our study enhanced treatment precision [4].

This study aimed to compare IMRTG and RP in patients with clinically localized or locally advanced PCa, focusing on clinical characteristics, acute adverse events, complications, urinary continence, sexual function, and long-term oncologic outcomes. Initially, the study included patients treated with 3D-CRT, brachytherapy, and heavy-ion therapy. However, to ensure a robust comparison of IMRTG and RP, we ultimately narrowed the cohort to 274 patients receiving IMRTG due to the limited number of patients in the non-IMRT treatment groups.

BCR was observed in 25% of RP patients (median time: 27 months) and 4% of IMRTG patients (median time: 82 months) (Table 1). Salvage treatments for biochemically recurrent PCa (BRPC) after RP included observation, external beam RT plus ADT, or ADT alone, depending on risk factors such as pathological Gleason score ≥ 8, PSADT at BCR ≤ 9 months, and time to BCR ≤ 12 months). In contrast, salvage treatments for BRPC after IMRTG included observation, ADT alone, or ADT combined with an androgen receptor signaling inhibitor. Distant metastases occurred in 1.8% (11/610) of RP patients (median time: 19 months) and 1.5% (4/274) of IMRTG patients (median time: 82 months) (Table 1). The management of metastatic disease followed Japanese clinical practice guidelines for metastatic castration-sensitive or castration-resistant PCa [1].

Table 2 summarizes the perioperative outcomes of the RP cohort. The median operation time was 4.11 h, and nerve sparing techniques employed in 45% of cases. Median blood loss was 310 mL, and urinary incontinence occurred in 13.0% of patients, with a median hospital stay of 14 days. In comparison, Yaxley et al. reported mean surgery times of 3.9 h for ORRP and 3.4 h for RARP, with average blood loss of 1338 mL for ORRP and 444 mL for RARP. The reported median hospital stays were 3.27 days for ORRP and 1.55 days for RARP [14]. In our study, estimated blood loss in the ORRP cohort was approximately three times higher than in the RARP cohort (p < 0.001), and the median hospital stay was significantly longer (p < 0.001). These findings are consistent with previous studies, except for hospital stay duration, which may vary due to differences in healthcare systems and insurance policies [15, 16].

Acute phase complications (Table 3) were reported in 33.3% (12/36) of ORRP patients and 26.4% (34/129) of RARP patients, including two Grade 4 adverse events. Novara et al. conducted a systematic review and reported a mean complication rate of 9%, with significantly lower blood loss and transfusion rates in RARP, although other complications were comparable between ORRP and RARP [15].

A prospective, controlled, nonrandomized trial comparing ORRP and RARP found that RARP modestly improved erectile function at 12 months postsurgery [17]. In our study, early sexual function (EPIC item 23) declined significantly 4 weeks postoperatively in the RARP cohort (p < 0.001) (Figure 1). However, due to the lack of postsurgical sexual function data for the ORRP cohort, a direct comparison was not feasible. Erectile function can improve for up to 3 years postsurgery [18], and we continue to assess this aspect. Notably, nerve-sparing technique were employed in 55.0% of RARP cases versus only 8.3% of ORRP cases. This reflects the robotic-assisted approach’s enhanced visualization and precision, leading to better functional outcomes in urinary continence and erectile function, particularly in low-and intermediate-risk patients [19].

Table 4 summarizes radiation-induced complications in the IMRTG cohort. Over 80% of patients experienced radiation-induced urological complications, with 11% reporting Grade 2 adverse effects. Radiation-induced proctitis affected approximately 20% of patients, while the incidence of radiation-induced cystitis was relatively low at 3.6%. Our proctitis incidence was higher than in previous reports, likely due to stricter diagnostic criteria. Zelefsky et al. reported acute gastrointestinal (GI) toxicity (≥ Grade 2) at 3% and genitourinary (GU) toxicity at 37%, noting that acute toxicities often predict late toxicities [20]. A review by David et al. found 60-month cumulative incidences of GU toxicity (≥ Grade 2) at 33%, hematuria at 5%, urinary incontinence at 12%, and urinary retention at 24% [21]. Overall, the incidence of ≥ Grade 2 acute phase complications was 20% in the RP cohort and 15% in the IMRTG cohort, showing comparable outcomes between the two treatments.

The overall mortality rate was 8.9%, and the PCa-specific mortality rate was 0.8% over a median follow-up of 98 months. The ProtecT trial reported 15-year all-cause mortality at 21.7% and PCa-specific mortality at 2.7% [10]. Kaplan–Meier survival analysis (Figure 2) showed significant differences in OS between the RP and IMRTG cohorts in univariate analysis, with RP showing a lower hazard ratio. However, this significance diminished in multivariate analysis, likely due to higher-risk disease in the IMRTG cohort. A systematic review comparing radical surgery and radiotherapy in localized PCa consistently reported higher mortality rates with radiotherapy [22]. Our OS rates for radiotherapy and surgery were 89.0% and 93.1% at 10 years, and 58.3% and 80.9% at 15 years, respectively. Kaplan–Meier analysis for PCSS (Figure 3) showed 100% survival in the IMRTG cohort, rendering the data nonestimable. Our PCSS rates for radiotherapy and surgery were both 100% and 98.7% at 10 and 15 years, respectively, comparable to the ProtecT trial’s PCSS rates of 97.1% and 97.8% for radiotherapy and surgery, respectively [10].

Table 5 outlines the causes of death in both cohorts. Approximately 45% of all deaths were attributed to malignant tumors, followed by heart and lung diseases, reflecting the aging nature of the patient population.

Several limitations must be acknowledged. First, this is a retrospective observational study with a moderate sample size. Second, outcomes may have been influenced by the involvement of multiple physicians and diverse treatment approaches. Third, imbalance in treatment group size, as RP was prioritized before IMRTG became widely available. Forth, the limited number of PCa-specific mortality events restricts comprehensive evaluation of PCSS. Lastly, the study does not specifically address long-term adverse effects, including radiation-induced urological or GI complications, urinary incontinence, and sexual dysfunction.

5. Conclusion

This long-term retrospective study provides comparative insights into RP and IMRTG outcomes in PCa patients. Both treatments resulted in adverse events, complications, and impacts on urinary continence and sexual function. Clinical decision-making should consider these factors, and continuous advancements in treatment techniques and post-treatment care are essential to improving patient outcomes.

Conflicts of Interest

The authors declare no conflicts of interest.

Funding

This clinical research received no specific grant from any founding agency in public, commercial, or nonprofit sectors.