Trial Outcomes & Findings for CyberKnife Radiosurgery For Low & Intermediate Risk Prostate Cancer: Emulating HDR Brachytherapy Dosimetry (NCT NCT00643617)

Last Updated: 2023-05-09

Results Overview

To estimate the rates of acute and late Grade 3-5 gastrointestinal and genitourinary toxicities (adverse events \[AE\]) observed in both low-risk and intermediate-risk cohorts during the 5 years following CyberKnife (CK) treatment for prostate cancer. Kaplan Meier estimates for 5-yr and 10-yr are reported. Adverse events occurring within 3 months of treatment were categorized as acute toxicities, and those developing after 3 months were considered late toxicities. The rates were determined using the first Grade 3 or higher adverse event per patient, reported as possibly, probably, or definitely related to CK treatment. The Common Toxicity Criteria for Adverse Events (CTCAE) Version 3.0 was used to determine the Grade or severity of adverse events in this study, with Grade 3 being severe or medically significant but not immediately life-threatening, Grade 4 being life-threatening and Grade 5 being death related to the adverse event.

Recruitment status

COMPLETED

Study phase

Target enrollment

307 participants

Primary outcome timeframe

Primary Safety Endpoint was measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years.

Results posted on

2023-05-09

Participant Flow

From October 2007 through December 2011, 307 subjects signed informed consent and were enrolled in the study at 18 centers in the United States.

Of these 307 subjects, 48 patients did not receive study treatment and were withdrawn from the study. Reasons for withdrawal included meeting exclusion criteria after central pathology review, insurance did not approve participation in a clinical study, or patient decision to withdraw prior to receiving treatment. 259 subjects were assigned to either the "Low Risk" or "Intermediate Risk" groups after central pathology review results.

Participant milestones

Participant milestones
Measure	Low Risk Patients with clinical stage (CS) Tumor (T) 1b-T2a and Gleason 2-6 and Prostate specific Antigen (PSA) ≤ 10 ng/ml	Intermediate Risk Patients with CS T2b and Gleason 2-6 and PSA ≤ 10 ng/ml or CS T1b-T2b and Gleason 2-6 and PSA ≤ 20 ng/ml or Gleason 7 and PSA ≤ 10 ng/ml
Overall Study STARTED	112	147
Overall Study 10-yr Follow up	36	33
Overall Study COMPLETED	64	87
Overall Study NOT COMPLETED	48	60

Reasons for withdrawal

Reasons for withdrawal
Measure	Low Risk Patients with clinical stage (CS) Tumor (T) 1b-T2a and Gleason 2-6 and Prostate specific Antigen (PSA) ≤ 10 ng/ml	Intermediate Risk Patients with CS T2b and Gleason 2-6 and PSA ≤ 10 ng/ml or CS T1b-T2b and Gleason 2-6 and PSA ≤ 20 ng/ml or Gleason 7 and PSA ≤ 10 ng/ml
Overall Study Death	6	9
Overall Study Lost to Follow-up	42	51

Baseline Characteristics

CyberKnife Radiosurgery For Low & Intermediate Risk Prostate Cancer: Emulating HDR Brachytherapy Dosimetry

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CyberKnife Stereotactic Radiosurgery - Low Risk n=112 Participants 38 Gy delivered in 4 fractions of 9.5 Gy per fraction with a radial margin of 2 mm around the prostate	CyberKnife Stereotactic Radiosurgery - Intermediate Risk n=147 Participants 38 Gy delivered in 4 fractions of 9.5 Gy per fraction with a radial margin of 5mm posterolaterally	Total n=259 Participants Total of all reporting groups
Age, Continuous	67.2 years n=99 Participants	68.4 years n=107 Participants	67.8 years n=206 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Sex: Female, Male Male	112 Participants n=99 Participants	147 Participants n=107 Participants	259 Participants n=206 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race/Ethnicity, Customized Asian	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Race/Ethnicity, Customized Black/African American	5 Participants n=99 Participants	3 Participants n=107 Participants	8 Participants n=206 Participants
Race/Ethnicity, Customized Hispanic/Latino	1 Participants n=99 Participants	12 Participants n=107 Participants	13 Participants n=206 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Race/Ethnicity, Customized White	105 Participants n=99 Participants	127 Participants n=107 Participants	232 Participants n=206 Participants
Region of Enrollment United States	112 Participants n=99 Participants	147 Participants n=107 Participants	259 Participants n=206 Participants
Tumor Clinical Stage (CS) T1b = Tumor incidental histological finding in >5% of tissue resected	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Tumor Clinical Stage (CS) T1c = Tumor identified by needle biopsy found in one or both sides, but not palpable	85 Participants n=99 Participants	98 Participants n=107 Participants	183 Participants n=206 Participants
Tumor Clinical Stage (CS) T2a = Tumor involves ½ of one side or less	27 Participants n=99 Participants	46 Participants n=107 Participants	73 Participants n=206 Participants
Tumor Clinical Stage (CS) T2b = Tumor involves >½ of one side but not both sides	0 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants
Total Gleason Score Gleason 2 - 6	112 Participants n=99 Participants	11 Participants n=107 Participants	123 Participants n=206 Participants
Total Gleason Score Gleason 7	0 Participants n=99 Participants	136 Participants n=107 Participants	136 Participants n=206 Participants
Prostate Specific Antigen (PSA)	4.72 ng/mL n=99 Participants	6.31 ng/mL n=107 Participants	5.6 ng/mL n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Fully active, able to carry on all pre-disease performance without restriction	109 Participants n=99 Participants	137 Participants n=107 Participants	246 Participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 = Restricted in physically strenuous activity	2 Participants n=99 Participants	9 Participants n=107 Participants	11 Participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = Capable of all selfcare but unable to carry out any work activities	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 3 = Capable of only limited selfcare	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Unreported	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
American Joint Committee on Cancer (AJCC) 6th Edition Risk Group Low: CS T1b-T2a, Gleason 2-6, PSA ≤ 10 ng/ml	112 Participants n=99 Participants	0 Participants n=107 Participants	112 Participants n=206 Participants
American Joint Committee on Cancer (AJCC) 6th Edition Risk Group Intermediate: CS T2b, Gleason 2-6, PSA ≤ 10 ng/ml	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
American Joint Committee on Cancer (AJCC) 6th Edition Risk Group Intermediate: CS T1b-T2b, and Gleason 2-6, PSA ≤ 20 ng/ml	0 Participants n=99 Participants	9 Participants n=107 Participants	9 Participants n=206 Participants
American Joint Committee on Cancer (AJCC) 6th Edition Risk Group Intermediate: CS T1b-T2b and Gleason 7, PSA ≤ 10 ng/ml	0 Participants n=99 Participants	136 Participants n=107 Participants	136 Participants n=206 Participants

PRIMARY outcome

Timeframe: Primary Safety Endpoint was measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years.

Outcome measures

Outcome measures
Measure	Low Risk n=112 Participants Patients with Clinical Stage (CS) Tumor (T)1b-T2a and Gleason 2-6 and Prostate Specific Antigen (PSA) ≤ 10 ng/ml	Intermediate Risk n=147 Participants Patients with CS T2b and Gleason 2-6 and PSA ≤ 10 ng/ml or CS T1b-T2b and Gleason 2-6 and PSA ≤ 20 ng/ml or Gleason 7 and PSA ≤ 10 ng/ml
Risk for Gastrointestinal (GI) and Genitourinary (GU) Toxicity Probability of experiencing Acute GI Grade 3+ event(s)	0 percentage of participants	0 percentage of participants
Risk for Gastrointestinal (GI) and Genitourinary (GU) Toxicity Probability of experiencing Acute GU Grade 3+ event(s)	1.8 percentage of participants	0.7 percentage of participants
Risk for Gastrointestinal (GI) and Genitourinary (GU) Toxicity Probability of experiencing Late GI Grade 3+ events 5 years post treatment	0 percentage of participants	0 percentage of participants
Risk for Gastrointestinal (GI) and Genitourinary (GU) Toxicity Probability of experiencing Late GU Grade 3+ events 5 years post treatment	1.0 percentage of participants	3.7 percentage of participants
Risk for Gastrointestinal (GI) and Genitourinary (GU) Toxicity Probability of experiencing Late GI Grade 3+ event(s) at 10 years post CK treatment	0 percentage of participants	0 percentage of participants
Risk for Gastrointestinal (GI) and Genitourinary (GU) Toxicity Probability of experiencing Late GU Grade 3+ event(s) at 10 years post CK treatment	1.0 percentage of participants	3.7 percentage of participants

PRIMARY outcome

Timeframe: Primary Efficacy Endpoint was measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years.

To determine the rate of biochemical Disease-Free Survival (bDFS), using the Phoenix definition, following CyberKnife treatment. Kaplan Meier survival curves for bDFS were created and the 5-yr and 10-yr percentages are reported. The Phoenix definition uses a Prostate Specific Antigen (PSA) value exceeding the patients lowest PSA value (nadir) + 2 ng/mL as an indicator of disease recurrence. The percentage of patients who did not have such a PSA rise or receive any interventional therapy to treat prostate cancer are reported below.

Outcome measures

Outcome measures
Measure	Low Risk n=112 Participants Patients with Clinical Stage (CS) Tumor (T)1b-T2a and Gleason 2-6 and Prostate Specific Antigen (PSA) ≤ 10 ng/ml	Intermediate Risk n=147 Participants Patients with CS T2b and Gleason 2-6 and PSA ≤ 10 ng/ml or CS T1b-T2b and Gleason 2-6 and PSA ≤ 20 ng/ml or Gleason 7 and PSA ≤ 10 ng/ml
Biochemical Disease-Free Survival (bDFS) Probability of remaining disease-free at 5 years post-CyberKnife treatment	100 percentage of participants	89.1 percentage of participants
Biochemical Disease-Free Survival (bDFS) Probability of remaining disease-free at 10 years post-CyberKnife treatment	100 percentage of participants	80 percentage of participants

SECONDARY outcome

Timeframe: Secondary outcomes were measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years.

To determine the rates of local failure, distant failure, disease-free survival, disease-specific survival, and overall survival following CyberKnife treatment in prostate cancer patients.

Outcome measures

Outcome measures
Measure	Low Risk n=112 Participants Patients with Clinical Stage (CS) Tumor (T)1b-T2a and Gleason 2-6 and Prostate Specific Antigen (PSA) ≤ 10 ng/ml	Intermediate Risk n=147 Participants Patients with CS T2b and Gleason 2-6 and PSA ≤ 10 ng/ml or CS T1b-T2b and Gleason 2-6 and PSA ≤ 20 ng/ml or Gleason 7 and PSA ≤ 10 ng/ml
Disease Control and Survival Outcomes Probability of remaining free from Local Failure at 5 years post-CyberKnife treatment	100 percentage of participants	98.3 percentage of participants
Disease Control and Survival Outcomes Probability of remaining free from Local Failure at 10 years post-CyberKnife treatment	100 percentage of participants	98.3 percentage of participants
Disease Control and Survival Outcomes Probability of remaining free from Distant Failure at 5 years post-CyberKnife treatment	100 percentage of participants	95 percentage of participants
Disease Control and Survival Outcomes Probability of remaining free from Distant Failure at 10 years post-CyberKnife treatment	100 percentage of participants	95 percentage of participants
Disease Control and Survival Outcomes Probability of remaining free from disease at 5 years post-CyberKnife treatment	100 percentage of participants	89.1 percentage of participants
Disease Control and Survival Outcomes Probability of remaining free from disease at 10 years post-CyberKnife treatment	100 percentage of participants	80 percentage of participants
Disease Control and Survival Outcomes Probability of surviving prostate cancer at 5 years post-CyberKnife treatment	100 percentage of participants	100 percentage of participants
Disease Control and Survival Outcomes Probability of surviving prostate cancer at 10 years post-CyberKnife treatment	100 percentage of participants	100 percentage of participants
Disease Control and Survival Outcomes Probability of Overall survival at 5 years post-CyberKnife treatment	95.4 percentage of participants	91.7 percentage of participants
Disease Control and Survival Outcomes Probability of Overall survival at 10 years post-CyberKnife treatment	83.8 percentage of participants	86.4 percentage of participants

SECONDARY outcome

Timeframe: AUA questionnaire was completed at Baseline, CK Treatment, and post treatment at: 1 week, 1 month, 3 months, 6 months, and then biannually up to 5 years. Sites and patients had the option of continuing follow-up through 10 years.

Population: AUA questionnaires were to be completed by patients for each follow-up visit. All questions need to be completed in order to calculate the score. During follow-up, patients may have withdrawn from the study, did not consent to continue follow-up through 10 years, were lost to follow-up, decided not to complete a questionnaire, or did not fully complete a questionnaire. Scores were calculated on fully completed questionnaires even if received/dated outside protocol specified visit window.

AUA-SI is a 7-item self-report measure used to assess urinary urgency, frequency, and voiding symptoms with scores ranging from 0 (no symptom) to 5 (symptom occurs almost always) Total score: 0-7 mild symptoms; 8-19 moderate symptoms; 20-35 severe symptoms

Outcome measures

Outcome measures
Measure	Low Risk n=111 Participants Patients with Clinical Stage (CS) Tumor (T)1b-T2a and Gleason 2-6 and Prostate Specific Antigen (PSA) ≤ 10 ng/ml	Intermediate Risk n=146 Participants Patients with CS T2b and Gleason 2-6 and PSA ≤ 10 ng/ml or CS T1b-T2b and Gleason 2-6 and PSA ≤ 20 ng/ml or Gleason 7 and PSA ≤ 10 ng/ml
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 120 Months Post Treatment	7.94 score on a scale Standard Deviation 7.41	8.69 score on a scale Standard Deviation 6.89
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) Baseline	7.05 score on a scale Standard Deviation 6.32	7.12 score on a scale Standard Deviation 5.79
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) Last Day of Treatment	9.49 score on a scale Standard Deviation 7.53	8.64 score on a scale Standard Deviation 7.14
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 1 Week Post Treatment	13.57 score on a scale Standard Deviation 9.17	14.14 score on a scale Standard Deviation 8.85
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 1 Month Post Treatment	11.00 score on a scale Standard Deviation 7.3	10.74 score on a scale Standard Deviation 6.91
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 3 Months Post Treatment	7.09 score on a scale Standard Deviation 5.55	7.26 score on a scale Standard Deviation 5.88
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 6 Months Post Treatment	7.78 score on a scale Standard Deviation 7.1	8.09 score on a scale Standard Deviation 6.51
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 12 Months Post Treatment	8.39 score on a scale Standard Deviation 6.69	10.05 score on a scale Standard Deviation 7.23
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 18 Months Post Treatment	8.39 score on a scale Standard Deviation 6.9	10.24 score on a scale Standard Deviation 8.22
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 24 Months Post Treatment	7.80 score on a scale Standard Deviation 6.88	9.47 score on a scale Standard Deviation 7.53
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 36 Months Post Treatment	7.25 score on a scale Standard Deviation 7.06	7.88 score on a scale Standard Deviation 6.62
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 48 Months Post Treatment	6.69 score on a scale Standard Deviation 6.73	7.97 score on a scale Standard Deviation 6.01
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 60 Months Post Treatment	7.23 score on a scale Standard Deviation 7.15	9.19 score on a scale Standard Deviation 7.03
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 72 Months Post Treatment	7.81 score on a scale Standard Deviation 7.04	8.16 score on a scale Standard Deviation 7.56
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 84 Months Post Treatment	7.59 score on a scale Standard Deviation 6.28	9.84 score on a scale Standard Deviation 8.53
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 96 Months Post Treatment	8.76 score on a scale Standard Deviation 8.05	8.64 score on a scale Standard Deviation 6.83
Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) 108 Months Post Treatment	8.00 score on a scale Standard Deviation 7.35	8.75 score on a scale Standard Deviation 6.6

SECONDARY outcome

Timeframe: Secondary outcomes were measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years.

Population: EPIC questionnaires were completed by patients at follow-up visits. A minimum number of questions needed to be completed within each domain in order to calculate a domain score. Domain scores obtained per instructions (if possible) and analyzed even if questionnaires were received/dated outside protocol specified visit window.

EPIC-26 is a short form version of the Expanded Prostate Cancer Index Composite, and is a validated comprehensive instrument developed to measure the health-related quality of life among men with prostate cancer. EPIC-26 consists of 26 items under 5 domains of urinary incontinence, urinary irritative/obstructive, bowel, sexual, and hormonal. Answers qualitatively measure patient's bother for each symptom and are then normalized on a scale of 0 (worst) to 100 (best) to calculate domain scores if sufficient input is provided.

Outcome measures

Outcome measures
Measure	Low Risk n=111 Participants Patients with Clinical Stage (CS) Tumor (T)1b-T2a and Gleason 2-6 and Prostate Specific Antigen (PSA) ≤ 10 ng/ml	Intermediate Risk n=146 Participants Patients with CS T2b and Gleason 2-6 and PSA ≤ 10 ng/ml or CS T1b-T2b and Gleason 2-6 and PSA ≤ 20 ng/ml or Gleason 7 and PSA ≤ 10 ng/ml
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence Baseline	95.77 score on a scale Standard Deviation 10.42	91.59 score on a scale Standard Deviation 14.39
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence 1 Month Post Treatment	90.33 score on a scale Standard Deviation 14.56	88.83 score on a scale Standard Deviation 16.85
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence 6 Months Post Treatment	92.81 score on a scale Standard Deviation 14.08	88.48 score on a scale Standard Deviation 16.51
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence 12 Months Post Treatment	90.64 score on a scale Standard Deviation 17.39	85.37 score on a scale Standard Deviation 19.23
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence 24 Months Post Treatment	87.66 score on a scale Standard Deviation 17.32	78.44 score on a scale Standard Deviation 25.72
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence 36 Months Post Treatment	90.2 score on a scale Standard Deviation 19.38	81.08 score on a scale Standard Deviation 22.8
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence 48 Months Post Treatment	88.74 score on a scale Standard Deviation 20.88	80.62 score on a scale Standard Deviation 22.11
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence 60 Months Post Treatment	89.5 score on a scale Standard Deviation 18.31	80.04 score on a scale Standard Deviation 20.8
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence 72 Months Post Treatment	87.44 score on a scale Standard Deviation 19.55	75.17 score on a scale Standard Deviation 24.86
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence 84 Months Post Treatment	86.26 score on a scale Standard Deviation 19.89	76.43 score on a scale Standard Deviation 25.68
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence 96 Months Post Treatment	86.32 score on a scale Standard Deviation 18.84	76.79 score on a scale Standard Deviation 25.46
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence 108 Months Post Treatment	84.17 score on a scale Standard Deviation 23.54	73.72 score on a scale Standard Deviation 28.88
Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence 120 Months Post Treatment	87.04 score on a scale Standard Deviation 18.55	78.12 score on a scale Standard Deviation 26.25

SECONDARY outcome

Timeframe: Secondary outcomes were measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years.

Outcome measures

Outcome measures
Measure	Low Risk n=111 Participants Patients with Clinical Stage (CS) Tumor (T)1b-T2a and Gleason 2-6 and Prostate Specific Antigen (PSA) ≤ 10 ng/ml	Intermediate Risk n=146 Participants Patients with CS T2b and Gleason 2-6 and PSA ≤ 10 ng/ml or CS T1b-T2b and Gleason 2-6 and PSA ≤ 20 ng/ml or Gleason 7 and PSA ≤ 10 ng/ml
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive Baseline	87.67 score on a scale Standard Deviation 13.96	87.59 score on a scale Standard Deviation 12.32
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive 1 Month Post Treatment	74.11 score on a scale Standard Deviation 17.49	74.03 score on a scale Standard Deviation 17.82
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive 6 Months Post Treatment	86.75 score on a scale Standard Deviation 14.69	82.91 score on a scale Standard Deviation 17.4
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive 12 Months Post Treatment	83.29 score on a scale Standard Deviation 15.45	80.1 score on a scale Standard Deviation 18.79
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive 24 Months Post Treatment	86.56 score on a scale Standard Deviation 15.09	81.05 score on a scale Standard Deviation 18.71
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive 36 Months Post Treatment	86.99 score on a scale Standard Deviation 15.09	85.77 score on a scale Standard Deviation 16.77
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive 48 Months Post Treatment	87.81 score on a scale Standard Deviation 13.03	84.03 score on a scale Standard Deviation 16.36
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive 60 Months Post Treatment	87.72 score on a scale Standard Deviation 14.9	84.15 score on a scale Standard Deviation 14.32
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive 72 Months Post Treatment	85.19 score on a scale Standard Deviation 13.84	87.95 score on a scale Standard Deviation 13.37
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive 84 Months Post Treatment	87.07 score on a scale Standard Deviation 13.84	83.13 score on a scale Standard Deviation 20.13
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive 96 Months Post Treatment	85.78 score on a scale Standard Deviation 14.22	84.58 score on a scale Standard Deviation 14.45
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive 108 Months Post Treatment	85.8 score on a scale Standard Deviation 14.43	82.09 score on a scale Standard Deviation 15.11
Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive 120 Months Post Treatment	85.0 score on a scale Standard Deviation 17.42	86.25 score on a scale Standard Deviation 11.69

SECONDARY outcome

Timeframe: Secondary outcomes were measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years.

Outcome measures

Outcome measures
Measure	Low Risk n=111 Participants Patients with Clinical Stage (CS) Tumor (T)1b-T2a and Gleason 2-6 and Prostate Specific Antigen (PSA) ≤ 10 ng/ml	Intermediate Risk n=146 Participants Patients with CS T2b and Gleason 2-6 and PSA ≤ 10 ng/ml or CS T1b-T2b and Gleason 2-6 and PSA ≤ 20 ng/ml or Gleason 7 and PSA ≤ 10 ng/ml
Quality of Life Assessments: EPIC-26 Bowel Baseline	96.25 score on a scale Standard Deviation 8.14	94.84 score on a scale Standard Deviation 9.96
Quality of Life Assessments: EPIC-26 Bowel 1 Month Post Treatment	89.32 score on a scale Standard Deviation 14.63	86.05 score on a scale Standard Deviation 16.66
Quality of Life Assessments: EPIC-26 Bowel 6 Months Post Treatment	93.45 score on a scale Standard Deviation 12.06	89.92 score on a scale Standard Deviation 15.91
Quality of Life Assessments: EPIC-26 Bowel 12 Months Post Treatment	93.51 score on a scale Standard Deviation 11.41	87.97 score on a scale Standard Deviation 17.42
Quality of Life Assessments: EPIC-26 Bowel 24 Months Post Treatment	93.68 score on a scale Standard Deviation 11.16	89.28 score on a scale Standard Deviation 17.26
Quality of Life Assessments: EPIC-26 Bowel 36 Months Post Treatment	94.82 score on a scale Standard Deviation 9.27	93.29 score on a scale Standard Deviation 12.48
Quality of Life Assessments: EPIC-26 Bowel 48 Months Post Treatment	94.65 score on a scale Standard Deviation 9.77	92.04 score on a scale Standard Deviation 12.28
Quality of Life Assessments: EPIC-26 Bowel 60 Months Post Treatment	94.49 score on a scale Standard Deviation 11.67	91.03 score on a scale Standard Deviation 15.38
Quality of Life Assessments: EPIC-26 Bowel 72 Months Post Treatment	94.3 score on a scale Standard Deviation 10.98	89.54 score on a scale Standard Deviation 17.07
Quality of Life Assessments: EPIC-26 Bowel 84 Months Post Treatment	92.42 score on a scale Standard Deviation 11.31	90.49 score on a scale Standard Deviation 16.09
Quality of Life Assessments: EPIC-26 Bowel 96 Months Post Treatment	91.67 score on a scale Standard Deviation 14.22	91.27 score on a scale Standard Deviation 13.73
Quality of Life Assessments: EPIC-26 Bowel 108 Months Post Treatment	90.07 score on a scale Standard Deviation 12.56	91.33 score on a scale Standard Deviation 12.74
Quality of Life Assessments: EPIC-26 Bowel 120 Months Post Treatment	91.17 score on a scale Standard Deviation 13.07	93.59 score on a scale Standard Deviation 11.07

SECONDARY outcome

Timeframe: Secondary outcomes were measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years.

Outcome measures

Outcome measures
Measure	Low Risk n=111 Participants Patients with Clinical Stage (CS) Tumor (T)1b-T2a and Gleason 2-6 and Prostate Specific Antigen (PSA) ≤ 10 ng/ml	Intermediate Risk n=146 Participants Patients with CS T2b and Gleason 2-6 and PSA ≤ 10 ng/ml or CS T1b-T2b and Gleason 2-6 and PSA ≤ 20 ng/ml or Gleason 7 and PSA ≤ 10 ng/ml
Quality of Life Assessments: EPIC-26 Sexual 48 Months Post Treatment	38.3 score on a scale Standard Deviation 31.56	38.95 score on a scale Standard Deviation 31.8
Quality of Life Assessments: EPIC-26 Sexual 60 Months Post Treatment	32.22 score on a scale Standard Deviation 31.16	36.89 score on a scale Standard Deviation 32.44
Quality of Life Assessments: EPIC-26 Sexual 72 Months Post Treatment	30.89 score on a scale Standard Deviation 27.26	33.13 score on a scale Standard Deviation 29.08
Quality of Life Assessments: EPIC-26 Sexual Baseline	55.27 score on a scale Standard Deviation 33.41	56.32 score on a scale Standard Deviation 32.6
Quality of Life Assessments: EPIC-26 Sexual 1 Month Post Treatment	47.46 score on a scale Standard Deviation 33.58	50.58 score on a scale Standard Deviation 31.82
Quality of Life Assessments: EPIC-26 Sexual 6 Months Post Treatment	50.06 score on a scale Standard Deviation 31.91	51.23 score on a scale Standard Deviation 33.47
Quality of Life Assessments: EPIC-26 Sexual 12 Months Post Treatment	44.86 score on a scale Standard Deviation 34.82	45.2 score on a scale Standard Deviation 32.46
Quality of Life Assessments: EPIC-26 Sexual 24 Months Post Treatment	40.77 score on a scale Standard Deviation 32.15	39.73 score on a scale Standard Deviation 30.39
Quality of Life Assessments: EPIC-26 Sexual 36 Months Post Treatment	42.5 score on a scale Standard Deviation 33.57	40.99 score on a scale Standard Deviation 31.59
Quality of Life Assessments: EPIC-26 Sexual 84 Months Post Treatment	28.15 score on a scale Standard Deviation 25.51	35.14 score on a scale Standard Deviation 29.68
Quality of Life Assessments: EPIC-26 Sexual 96 Months Post Treatment	27.55 score on a scale Standard Deviation 26.55	34.74 score on a scale Standard Deviation 30.05
Quality of Life Assessments: EPIC-26 Sexual 108 Months Post Treatment	28.8 score on a scale Standard Deviation 30.09	36.19 score on a scale Standard Deviation 29.48
Quality of Life Assessments: EPIC-26 Sexual 120 Months Post Treatment	23.88 score on a scale Standard Deviation 23.55	33.69 score on a scale Standard Deviation 30.97

Adverse Events

Low Risk

Serious events: 17 serious events

Other events: 103 other events

Deaths: 9 deaths

Intermediate Risk

Serious events: 25 serious events

Other events: 142 other events

Deaths: 14 deaths

Serious adverse events

Other adverse events

Additional Information

Director of Clinical Affairs

Accuray, Inc.

Phone: 608-824-3421

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Low Risk n=112 participants at risk Patients with CS T1b-T2a and Gleason 2-6 and PSA ≤ 10	Intermediate Risk n=147 participants at risk Patients with CS T2b and Gleason 2-6 and PSA ≤ 10 or CS T1b-T2b and Gleason 2-6 and PSA ≤ 20 ng/ml or Gleason 7 and PSA ≤ 10 ng/ml
General disorders Fatigue	32.1% 36/112 • Number of events 38 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	24.5% 36/147 • Number of events 39 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Gastrointestinal disorders Constipation	13.4% 15/112 • Number of events 15 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	12.2% 18/147 • Number of events 18 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Gastrointestinal disorders Diarrhea	34.8% 39/112 • Number of events 45 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	35.4% 52/147 • Number of events 59 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Gastrointestinal disorders Urgency	1.8% 2/112 • Number of events 2 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	5.4% 8/147 • Number of events 9 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Gastrointestinal disorders Proctitis	7.1% 8/112 • Number of events 8 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	11.6% 17/147 • Number of events 18 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Gastrointestinal disorders Hemorrhage/Bleeding - GI	8.9% 10/112 • Number of events 10 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	12.2% 18/147 • Number of events 20 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Gastrointestinal disorders GI Pain	8.9% 10/112 • Number of events 11 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	14.3% 21/147 • Number of events 24 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Renal and urinary disorders Cystitis	8.0% 9/112 • Number of events 9 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	8.2% 12/147 • Number of events 12 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Renal and urinary disorders Urinary Incontinence	10.7% 12/112 • Number of events 12 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	15.6% 23/147 • Number of events 30 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Renal and urinary disorders Urinary Frequency/Urgency	67.0% 75/112 • Number of events 118 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	74.8% 110/147 • Number of events 176 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Renal and urinary disorders Urinary Retention	30.4% 34/112 • Number of events 39 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	36.7% 54/147 • Number of events 65 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Renal and urinary disorders Hemorrhage/Bleeding - GU	14.3% 16/112 • Number of events 19 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	24.5% 36/147 • Number of events 44 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Renal and urinary disorders Urinary Tract Infection	7.1% 8/112 • Number of events 9 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	5.4% 8/147 • Number of events 9 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Renal and urinary disorders Pain - GU	52.7% 59/112 • Number of events 72 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	55.1% 81/147 • Number of events 108 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Musculoskeletal and connective tissue disorders Pain - Musculoskeletal	7.1% 8/112 • Number of events 10 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	8.2% 12/147 • Number of events 14 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Reproductive system and breast disorders Hematospermia	0.00% 0/112 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	5.4% 8/147 • Number of events 8 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Reproductive system and breast disorders Pain - Reproductive/Sexual	1.8% 2/112 • Number of events 3 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	5.4% 8/147 • Number of events 10 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Reproductive system and breast disorders Ejaculatory Dysfunction	0.89% 1/112 • Number of events 1 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	4.8% 7/147 • Number of events 7 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.
Reproductive system and breast disorders Erectile Dysfunction	23.2% 26/112 • Number of events 26 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.	21.8% 32/147 • Number of events 33 • Adverse event data collected from study enrollment through end of protocol follow-up, including fiducial placement, CyberKnife radiosurgery treatment, and scheduled follow-up visits up to 10 years post-CK treatment. All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.