Prospective Study of Ultrahypofractionated Proton Beam Therapy for Localized Prostate Cancer

Prospective Cohort Study for Identifying Factors Predicting Long-term Outcomes of Prostate Cancer Patients Who Received Ultrahypofractionated Proton Beam Therapy

The goal of this prospective observational cohort study is to evaluate the long-term efficacy and safety of ultrahypofractionated proton beam therapy in patients with localized prostate cancer and to identify clinical and treatment-related factors associated with oncologic outcomes and treatment-related toxicity.

The main questions it aims to answer are:

What are the long-term biochemical recurrence-free survival, clinical progression-free survival, overall survival, and acute and late treatment-related toxicity outcomes following ultrahypofractionated proton beam therapy? Which clinical characteristics, treatment planning parameters, and patient-reported outcomes are predictive of long-term oncologic outcomes and treatment-related toxicity?

Participants will:

Receive protocol-based ultrahypofractionated proton beam therapy (35-40 Gy[RBE] in 5 fractions).

Undergo routine clinical evaluation, laboratory testing including prostate-specific antigen (PSA), and imaging studies according to the institutional follow-up schedule.

Complete patient-reported outcome questionnaires (EPIC-CP and Visual Analog Scale [VAS]) before treatment and during follow-up.

Be followed prospectively to assess biochemical recurrence, clinical progression, survival outcomes, and acute and late treatment-related toxicities.

Study Overview

• Status: Recruiting
• Conditions: Prostate Neoplasm
• Intervention / Treatment: Radiation: Ultrahypofractionated Proton Beam Therapy

Detailed Description

Localized prostate cancer can be effectively treated with external beam radiotherapy (EBRT). Ultrahypofractionated radiotherapy has become an established treatment option because of its favorable radiobiological characteristics, shorter treatment duration, and improved patient convenience. Owing to the low alpha/beta ratio of prostate cancer, delivery of larger doses per fraction may provide radiobiological advantages while maintaining excellent tumor control.

Proton beam therapy (PBT) offers unique dosimetric advantages over photon radiotherapy by reducing unnecessary radiation exposure to surrounding normal tissues through the Bragg peak effect. These characteristics may be particularly beneficial for ultrahypofractionated treatment, especially in patients with intermediate- or high-risk disease who require treatment of larger target volumes, including the seminal vesicles or pelvic lymph nodes. However, prospective data regarding the long-term efficacy, safety, patient-reported outcomes, and predictive factors associated with ultrahypofractionated proton beam therapy remain limited.

This is a prospective, single-center observational cohort study conducted at the National Cancer Center, Republic of Korea. Approximately 50 adult patients with histologically confirmed localized prostate adenocarcinoma who are scheduled to undergo definitive ultrahypofractionated proton beam therapy will be prospectively enrolled after providing written informed consent.

All participants will receive protocol-based ultrahypofractionated proton beam therapy consisting of 35-40 Gy(RBE) delivered in five fractions using image-guided proton therapy. Androgen deprivation therapy will be administered according to contemporary clinical guidelines and physician discretion when indicated.

The primary objective of this study is to evaluate the long-term efficacy and safety of ultrahypofractionated proton beam therapy for localized prostate cancer. Secondary objectives include evaluation of biochemical recurrence-free survival, clinical progression-free survival, overall survival, acute and late treatment-related toxicity, and patient-reported quality of life. In addition, the study will prospectively investigate clinical characteristics, treatment planning parameters, dosimetric variables, and patient-reported outcome measures to identify factors associated with oncologic outcomes and treatment-related toxicity.

Clinical information, treatment planning data, physician-reported adverse events, laboratory findings including prostate-specific antigen (PSA), imaging studies, and patient-reported outcome measures using the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) and the Visual Analog Scale (VAS) will be prospectively collected. Patients will be followed every three months during the first two years, every six months during years three and four, and annually thereafter according to institutional follow-up practice.

The findings from this prospective cohort study are expected to provide high-quality evidence regarding the clinical effectiveness and safety of ultrahypofractionated proton beam therapy and to facilitate the development of individualized treatment strategies for patients with localized prostate cancer by identifying predictors of long-term oncologic outcomes and treatment-related toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hyuna Park Clinical Research Coordinator, BS; Phone Number: 0491 82-31-920-0491; Email: 77313@ncc.re.kr

Study Locations

• South Korea
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, South Korea, 10408
      • Recruiting
      • National Cancer Center, Korea
      • Contact: Sung Uk Lee, M.D., Ph.D.; Phone Number: 82-31-920-1720; Email: sulee126@ncc.re.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed localized adenocarcinoma of the prostate.
• No evidence of distant metastasis (M0).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Eligible to receive definitive image-guided ultrahypofractionated pencil beam scanning proton beam therapy according to the study protocol.
• Ability to complete study questionnaires and comply with scheduled follow-up assessments.
• Provision of written informed consent before study enrollment.

Exclusion Criteria:

• Residual or recurrent prostate cancer following prior radical prostatectomy.
• Previous pelvic radiotherapy.
• Evidence of distant metastatic disease.
• Active malignancy within the previous 1 year, except adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or completely resected T1N0M0 malignancies.
• Uncontrolled psychiatric illness, severe traumatic brain injury, chronic alcohol or substance dependence, or other medical conditions that, in the investigator's judgment, would preclude safe participation or adequate follow-up.
• Inability or unwillingness to provide written informed consent or comply with study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ultrahypofractionated proton beam therapy; Participants receive definitive ultrahypofractionated proton beam therapy (35-40 Gy[RBE] in 5 fractions) for localized prostate adenocarcinoma using image-guided proton therapy. Participants are prospectively followed for oncologic outcomes, treatment-related toxicity, and patient-reported quality of life.

Radiation: Ultrahypofractionated Proton Beam Therapy; Ultrahypofractionated proton beam therapy is delivered using pencil beam scanning (PBS) with image-guided proton therapy. Before treatment planning, all participants undergo placement of an absorbable rectal hydrogel spacer and two intraprostatic gold fiducial markers. Treatment planning is performed using CT simulation with MRI fusion after hydrogel stabilization. Daily cone-beam CT (CBCT) with fiducial marker matching is used for image guidance and patient positioning. A total dose of 36.25-40.0 Gy(RBE) is delivered in 5 fractions over approximately 1-2 weeks. Unlike conventional proton beam therapy using opposed right and left lateral beam arrangements, this protocol employs four oblique beam angles (right anterior oblique, right posterior oblique, left posterior oblique, and left anterior oblique) to optimize dose conformity while minimizing radiation exposure to adjacent normal tissues.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical recurrence-free survival	Biochemical recurrence is defined according to the Phoenix definition (PSA nadir + 2 ng/mL). Biochemical recurrence-free survival is measured from completion of proton beam therapy to biochemical recurrence or last follow-up.	Up to 5 years after completion of proton beam therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported quality of life	Patient-reported quality of life will be assessed using the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP). Scores range from 0 to 100, with higher scores indicating better urinary quality of life.	baseline, postRT 1 month, 4 months, 7 months and 1 year
Clinical recurrence-free survival	Time from radiotherapy completion to first occurrence of any clinical recurrence (local, regional, or distant) or death. Recurrence will be confirmed by imaging studies and/or histopathological findings when available.	Up to 5 years after completion of proton beam therapy
Overall survival	Time from completion of ultrahypofractionated proton beam therapy to death from any cause. Participants who are alive at the time of analysis will be censored at the date of the last follow-up.	From completion of proton beam therapy to 5 years after treatment
Treatment-related genitourinary toxicity	Treatment-related genitourinary (GU) toxicity will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Acute toxicity is defined as adverse events occurring within 90 days after completion of proton beam therapy, and late toxicity as events occurring more than 90 days after treatment completion.	Up to 5 years after completion of proton beam therapy
Treatment-related gastrointestinal toxicity	Treatment-related gastrointestinal (GI) toxicity will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Acute toxicity is defined as adverse events occurring within 90 days after completion of proton beam therapy, and late toxicity as events occurring more than 90 days after treatment completion.	Up to 5 years after completion of proton beam therapy

Collaborators and Investigators

• Sponsor: National Cancer Center, Korea

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2024
• Primary Completion (Estimated): December 31, 2034
• Study Completion (Estimated): December 31, 2034

Study Registration Dates

• First Submitted: July 2, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 13, 2026

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: prostate neoplasm; proton therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: NCC2024-0253

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No