# Predictors of acute genitourinary toxicity in real-time image-gated spot-scanning proton beam therapy for prostate cancer

**Authors:** Sho Seri, Norihiro Aibe, Takuya Kimoto, Toshiyuki Ogata, Kanako Kawabata, Koji Masui, Shinsuke Nagasawa, Yuki Yoshino, Sho Watanabe, Akito Asato, Shoko Hirano, Satoshi Ikeda, Takumi Shiraishi, Atsuko Fujihara, Hideya Yamazaki, Osamu Ukimura, Kei Yamada, Gen Suzuki

PMC · DOI: 10.1093/jrr/rrag012 · 2026-03-16

## TL;DR

This study identifies baseline urinary symptoms and older age as key factors predicting acute genitourinary side effects in proton therapy for prostate cancer.

## Contribution

The study identifies independent predictors of acute GU toxicity in real-time image-gated proton therapy for prostate cancer.

## Key findings

- 127 out of 326 patients experienced grade 2 acute GU adverse events.
- Baseline IPSS (moderate and severe) and age ≥75 years were significant predictors of grade ≥2 GU AEs.
- Dose-volume histogram parameters were not significantly associated with GU toxicity.

## Abstract

Proton beam therapy (PBT) provides sharper dose gradients than conventional photon radiotherapy, potentially reducing radiation exposure to normal tissues. However, acute genitourinary adverse events (GU AEs) remain a clinical concern. This study aimed to evaluate the incidence and predictors of grade ≥ 2 acute GU AEs in patients with localized prostate cancer treated with real-time image-gated, spot-scanning PBT (RGPT). We analyzed the prospective study data of 326 patients who received RGPT at a dose of 63 Gy (relative biological effectiveness [RBE]) in 21 fractions between 2019 and 2021. Acute GU AEs were graded according to the Common Terminology Criteria for Adverse Events (version 5.0). Multivariable logistic regression was used to analyze potential predictive factors, including baseline International Prostate Symptom Score (IPSS), age, comorbidities, hydrogel spacer placement, use of anticoagulants or urinary symptom medications, clinical stage, National Comprehensive Cancer Network (NCCN) risk classification, prostate volume, and dose–volume histogram parameters. Grade 2 acute GU AEs occurred in 127 patients (39.0%), whereas no grade ≥ 3 events were observed. Moderate (odds ratio [OR] = 1.71; 95% confidence interval [CI]: 1.03–2.82) and severe (OR = 3.75; 95% CI: 1.49–9.46) baseline IPSS, as well as age ≥ 75 years (OR = 1.80; 95% CI: 1.10–2.95), were significant independent predictors of grade ≥ 2 GU AEs. No dose–volume histogram parameters were significantly associated with grade ≥ 2 GU AEs. Baseline urinary symptoms and older age were independent predictors of grade ≥ 2 GU AEs, emphasizing the importance of pretreatment evaluation in optimizing patient selection and management.

## Linked entities

- **Diseases:** prostate cancer (MONDO:0005159)

## Full-text entities

- **Genes:** TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, KLK3 (kallikrein related peptidase 3) [NCBI Gene 354] {aka APS, KLK2A1, PSA, hK3}
- **Diseases:** RGPT (MESH:C564543), Prostate Cancer (MESH:D011471), metastasis (MESH:D009362), urinary retention (MESH:D016055), pelvic pain (MESH:D017699), nocturia (MESH:D053158), Prostate (MESH:D011472), diabetes (MESH:D003920), dysuria (MESH:D053159), GU adverse events (MESH:D064420), GU AEs (MESH:D002318), genitourinary adverse (MESH:D000091642), Cancer (MESH:D009369), Symptom (MESH:D012816), acute genitourinary toxicity (MESH:D040701), hypertension (MESH:D006973), bladder (MESH:D001745), GU complications (MESH:D008107)
- **Chemicals:** -1 blockers (-), tamsulosin (MESH:D000077409), PS (MESH:D010758), water (MESH:D014867)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC13019134