LEAD: MRI-Guided Lattice Extreme Ablative Dose Radiotherapy For Prostate Cancer

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT01411319
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 25
• Location: 1
• Arm: 1
• Actual Duration (Months): 98.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The hypotheses of this study are:

1. Delivery of single fraction Lattice Extreme Ablative Dose (LEAD) radiotherapy (RT) to the dominant tumor lesion(s) in the prostate as identified by multiparametric functional Magnetic Resonance Imaging is safe and feasible when given prior to standard prostate radiotherapy.

2. Biomarker expression levels differ in the functional MRI identified suspicious tumor regions and unsuspicious tumor regions. The investigators hypothesize that a significant source of variation in biomarker levels is due to tumor heterogeneity and that it is molecular abnormalities in the dominant tumor areas that are angiogenic and determine outcome.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer; Prostate Adenocarcinoma	Radiation: Lattice Extreme Ablative Dose Radiation Therapy; Radiation: Standard IMRT	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Trial of MRI-Guided Lattice Extreme Ablative Dose Radiotherapy For Prostate Cancer
• Actual Study Start Date: Dec 27, 2011
• Actual Primary Completion Date: Dec 31, 2014
• Actual Study Completion Date: Mar 2, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LEAD Radiation Therapy Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2.	Radiation: Lattice Extreme Ablative Dose Radiation Therapy; 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1.; Other Names: LEAD RT ; Radiation: Standard IMRT; 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.; Other Names: IMRT

Outcome Measures

Primary Outcome Measures

1. Number of Study Participants Experiencing Treatment-Related Toxicity [Up to 8.5 weeks]

   Toxicity are any Grade 2 or higher treatment-related adverse events as assessed by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0.

2. Percentage of Enrolled Patients for Whom LEAD RT Dose Can be Successfully Administered Following MRI-guided Planning. [Up to 8 weeks]

   The percentage of enrolled patients for whom LEAD RT dose can be successfully administered following MRI-guided planning.

Secondary Outcome Measures

1. Number of Participants With Remaining Tumor Cells in the Prostate Post Treatment [Up to 2.5 Years]

   The number of participants with positive tumor cells left in the prostate after LEAD RT as evaluated by prostate biopsy.

2. Percentage of Participants With Positive Prostate Biopsies After Completion of Treatment [From Baseline to 2.5 Years Post Completion of Study Therapy (Approximately 3 years)]

   Preliminary indication of efficacy of treatment will be reported as the percentage of participants with positive prostate biopsies after completion of treatment.

3. Rate of Participants That Achieve Failure-Free Survival (FFS) [Up to 6 years]

   The percentage of participants achieving FFS will be reported. Failure-free is defined as no documented evidence of biochemical and/or or clinical failure or death from any cause, whichever occur first. Biochemical failure is defined is a increase of 2 or greater from nadir of Prostate Specific Antigen (PSA) levels. Clinical Failure is defined as newly identified extension outside the prostate after initial regression, or urinary obstructive symptoms with carcinoma or regional/distant failure due to radiographic evidence metastasis.

4. Overall Survival (OS) [Up to 6 years]

   Overall survival is defined as the elapsed time from study enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact.

5. HrQoL as Assessed by EPIC-SF12 Questionnaire [At Baseline (Prior to RT), at 8 weeks (Last week of RT), At 6 weeks post RT, At 3 months post RT, At 6 months post RT, At 9 months post RT, At 15 months post RT, At 27 months post RT, At 39 months post RT, At 51 months post RT, At 63 months post RT]

   Health-related Quality of Life (HRQOL) will be measured using the Expanded Prostate Cancer Index Composite and Medical Outcomes Study SF-12 (EPIC SF-12) to evaluate patient function and satisfaction after prostate cancer treatment. The questionnaire has 5 subscales (Urinary Function, Urinary Symptoms, Bowel Habits, Sexual Function and Hormonal Function). Each subscale has a total score ranging from 0-100, with higher scores representing better HRQOL.

6. HrQoL as Assessed by MAX-PC Questionnaire [At Baseline (Prior to RT), at 8 weeks (Last week of RT), At 6 weeks post RT, At 3 months post RT, At 6 months post RT, At 9 months post RT, At 15 months post RT, At 27 months post RT, At 39 months post RT, At 51 months post RT, At 63 months post RT]

   Health-related quality of life (HRQOL) will be measured using the scores on the Modified 18-item Memorial Anxiety Scale for Prostate Cancer (MAX-PC) from pre-treatment to post-treatment. The scale consists of 18 items (e.g. "I thought about prostate cancer even though I didn't mean to.") scored on a scale from 0 ("not at all") to 3 ("often"). Total scores range from 0 to 54, with higher scores indicating higher levels of anxiety.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 85 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Biopsy confirmed adenocarcinoma of the prostate.

2. T1-T3a disease based on digital rectal exam (DRE).

• T3a disease based on MRI is acceptable (no evidence of frank (clear cut) seminal vesicle (SV) involvement or invasion of bladder or rectum).

1. Gleason score 6-10.

2. Patients with Gleason score ≥8 must be offered long term androgen deprivation therapy (ADT) and refuse such treatment because only 4-6 months (+/- 2 months) (short term ADT) is permitted (not required) on this protocol. The ADT is recommended to begin after fiducial marker placement; however, ADT is permitted to have been started up to two months prior to the signing of consent. All patients in this protocol may (not required) be treated with 4-6 months (+/- 2 months) of ADT, at the discretion of the treating physician.

• Gleason ≥ 8 must have < 40% of the tissue involved with Gleason 8 in the biopsy specimen.

1. Prostate-specific antigen (PSA) ≤ 30 ng/mL within 3 months of enrollment. If PSA was above 30 and dropped to ≤ 30 with antibiotics, this is acceptable for enrollment.

2. No previous pelvic radiotherapy.

3. No previous history of radical/total prostatectomy (suprapubic prostatectomy is acceptable).

4. No concurrent, active malignancy, other than nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for ≥ 5 years then the patient is eligible.

5. Identifiable multiparametric-MRI tumor lesion or lesions, that total in volume < 33% of the prostate

• Multiparametric MRI of prostate and pelvis is required prior to protocol consideration.

• If contrast not given, the point dose on the apparent diffusion coefficient (ADC) map should be < 1000.

1. Ability to understand and the willingness to sign a written informed consent document.

2. Zubrod performance status < 2.

3. Willingness to fill out quality of life forms.

4. Bone scan negative if PSA > 15 ng/mL or Gleason ≥ 8 disease. A questionable bone scan is acceptable if other imaging tests are negative for metastasis.

5. Serum testosterone is within 40% of normal assay limits (e.g., x=0.4lower assay limit and x=.04upper assay limit + upper assay limit), and taken within 4 months of enrollment. Patients who have been started on ADT prior to signing consent are not required to have a serum testosterone at this level prior to signing consent; but, a serum testosterone prior to fiducial marker placement is recommended.

6. Serum liver function tests (LFT) are taken within 3 months of enrollment.

7. Complete blood counts are taken within 3 months of enrollment.

8. Age ≥ 35 and ≤ 85 years.

Exclusion Criteria:

1. T3a disease on digital rectal exam or >T3a disease clearly identified by MRI.

2. Gleason score < 6.

3. ≥ 40% Gleason 8-10 tumor, over the total tissue including other tumor and normal tissue. For example: (Gleason 8-10 tumor length/other biopsy tissue length)*100 = ≥ 40%.

4. Androgen deprivation therapy longer than 8 months. Androgen deprivation timing is for the Luteinizing hormone-releasing hormone (LHRH) agonist portion only and not when anti-androgen is started beforehand with the purpose of counteracting the surge in testosterone from the LHRH agonist - PSA > 30 ng/mL within 3 months of enrollment.

5. PSA > 30 ng/mL within 3 months of enrollment

6. Unable to obtain a 1.5T or 3.0T multiparametric MRI of the pelvis and prostate with contrast.

7. Unidentifiable multiparametric MRI tumor lesion.

8. Identifiable multiparametric-MRI tumor lesions, that total in volume ≥ 33% of the prostate.

9. Previous pelvic radiotherapy.

10. Previous history of radical prostatectomy.

11. Concurrent, active malignancy, which is not nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for < 5 years then the patient is not eligible.

12. Zubrod performance status ≥ 2.

13. Inability to understand or unwilling to sign a written informed consent document

14. Unwilling to fill out quality of life/psychosocial forms.

15. Bone scan is positive and other imaging tests confirm a suspicion of metastasis from prostate cancer.

16. Serum testosterone is not within 40% of normal assay limits taken within 4 months of enrollment (only applicable to patients not started on ADT prior to signing consent).

17. Serum liver function tests (LFTs) are not taken within 3 months of enrollment.

18. Complete blood counts are not taken within 3 months of enrollment.

19. Age < 35 and > 85 years.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Alan Pollack, MD, PhD, University of Miami

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 11, 2018

More Information

Publications

None provided.

• Responsible Party: Alan Pollack, MD, PhD, Professor, University of Miami
• ClinicalTrials.gov Identifier: NCT01411319
• Other Study ID Numbers: 20100389; R21CA153826
• First Posted: Aug 8, 2011
• Last Update Posted: Jul 13, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	LEAD Radiation Therapy
Arm/Group Description	Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2. Lattice Extreme Ablative Dose Radiation Therapy: 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1. Standard IMRT: 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.
Period Title: Overall Study
STARTED	25
COMPLETED	24
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	LEAD Radiation Therapy
Arm/Group Description	Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2. Lattice Extreme Ablative Dose Radiation Therapy: 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1. Standard IMRT: 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.
Overall Participants	25
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 28%
>=65 years	18 72%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	25 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	17 68%
Not Hispanic or Latino	8 32%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 4%
White	23 92%
More than one race	0 0%
Unknown or Not Reported	1 4%

Outcome Measures

1. Primary Outcome

Title	Number of Study Participants Experiencing Treatment-Related Toxicity
Description	Toxicity are any Grade 2 or higher treatment-related adverse events as assessed by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0.
Time Frame	Up to 8.5 weeks

Outcome Measure Data

Analysis Population Description

All 25 participants were evaluated up to 8.5 weeks.

Arm/Group Title	LEAD Radiation Therapy
Arm/Group Description	Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2. Lattice Extreme Ablative Dose Radiation Therapy: 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1. Standard IMRT: 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.
Measure Participants	25
Serious Adverse Events (SAEs) with Definite Relation to Study Treatment	0 0%
SAEs with Probable Relation to Study Treatment	0 0%
SAEs with Possible Relation to Study Treatment	1 4%
Adverse Events (AEs) with Definite Relation to Study Treatment	9 36%
AEs with Probable Relation to Study Treatment	10 40%
AEs with Possible Relation to Study Treatment	5 20%

2. Primary Outcome

Title	Percentage of Enrolled Patients for Whom LEAD RT Dose Can be Successfully Administered Following MRI-guided Planning.
Description	The percentage of enrolled patients for whom LEAD RT dose can be successfully administered following MRI-guided planning.
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description

All 25 enrolled participants completed the duration of study treatment (8 weeks).

Arm/Group Title	LEAD Radiation Therapy
Arm/Group Description	Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2. Lattice Extreme Ablative Dose Radiation Therapy: 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1. Standard IMRT: 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.
Measure Participants	25
Number [percentage of participants]	100 400%

3. Secondary Outcome

Title	Number of Participants With Remaining Tumor Cells in the Prostate Post Treatment
Description	The number of participants with positive tumor cells left in the prostate after LEAD RT as evaluated by prostate biopsy.
Time Frame	Up to 2.5 Years

Outcome Measure Data

Analysis Population Description

Endpoint biopsy was collected only on 12 of 25 participants.

Arm/Group Title	LEAD Radiation Therapy
Arm/Group Description	Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2. Lattice Extreme Ablative Dose Radiation Therapy: 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1. Standard IMRT: 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.
Measure Participants	12
Count of Participants [Participants]	1 4%

4. Secondary Outcome

Title	Percentage of Participants With Positive Prostate Biopsies After Completion of Treatment
Description	Preliminary indication of efficacy of treatment will be reported as the percentage of participants with positive prostate biopsies after completion of treatment.
Time Frame	From Baseline to 2.5 Years Post Completion of Study Therapy (Approximately 3 years)

Outcome Measure Data

Analysis Population Description

One participant was lost to follow-up at the follow-up period post-completion of treatment.

Arm/Group Title	LEAD Radiation Therapy
Arm/Group Description	Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2. Lattice Extreme Ablative Dose Radiation Therapy: 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1. Standard IMRT: 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.
Measure Participants	24
Number (95% Confidence Interval) [percentage of participants]	4 16%

5. Secondary Outcome

Title	Rate of Participants That Achieve Failure-Free Survival (FFS)
Description	The percentage of participants achieving FFS will be reported. Failure-free is defined as no documented evidence of biochemical and/or or clinical failure or death from any cause, whichever occur first. Biochemical failure is defined is a increase of 2 or greater from nadir of Prostate Specific Antigen (PSA) levels. Clinical Failure is defined as newly identified extension outside the prostate after initial regression, or urinary obstructive symptoms with carcinoma or regional/distant failure due to radiographic evidence metastasis.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

One participant was lost to follow-up at the follow-up period post-completion of treatment.

Arm/Group Title	LEAD Radiation Therapy
Arm/Group Description	Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2. Lattice Extreme Ablative Dose Radiation Therapy: 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1. Standard IMRT: 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.
Measure Participants	24
Number [percentage of participants]	90.5 362%

6. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is defined as the elapsed time from study enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Timeframe allows for study visit windows.

Arm/Group Title	LEAD Radiation Therapy
Arm/Group Description	Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2. Lattice Extreme Ablative Dose Radiation Therapy: 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1. Standard IMRT: 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.
Measure Participants	25
Median (Full Range) [months]	66

7. Secondary Outcome

Title	HrQoL as Assessed by EPIC-SF12 Questionnaire
Description	Health-related Quality of Life (HRQOL) will be measured using the Expanded Prostate Cancer Index Composite and Medical Outcomes Study SF-12 (EPIC SF-12) to evaluate patient function and satisfaction after prostate cancer treatment. The questionnaire has 5 subscales (Urinary Function, Urinary Symptoms, Bowel Habits, Sexual Function and Hormonal Function). Each subscale has a total score ranging from 0-100, with higher scores representing better HRQOL.
Time Frame	At Baseline (Prior to RT), at 8 weeks (Last week of RT), At 6 weeks post RT, At 3 months post RT, At 6 months post RT, At 9 months post RT, At 15 months post RT, At 27 months post RT, At 39 months post RT, At 51 months post RT, At 63 months post RT

Outcome Measure Data

Analysis Population Description

Not all participants were able to complete the questionnaires at different timepoints in the study.

Arm/Group Title	LEAD Radiation Therapy
Arm/Group Description	Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2. Lattice Extreme Ablative Dose Radiation Therapy: 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1. Standard IMRT: 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.
Measure Participants	25
Urinary Function: Prior to Radiation Therapy (RT)	94.5 (10.9)
Urinary Function: 8 Weeks (Last Week of RT)	92.5 (14.4)
Urinary Function: 6 Weeks Post-RT	92.8 (20)
Urinary Function: 3 Months Post-RT	93.1 (17.6)
Urinary Function: 9 Months Post-RT	93.5 (16.6)
Urinary Function: 15 Months Post-RT	93.2 (14.5)
Urinary Function: 27 Months Post-RT	93.6 (15.5)
Urinary Function: 39 Months Post-RT	95.8 (9.2)
Urinary Function: 51 Months Post-RT	92.8 (17)
Urinary Function: 63 Months Post-RT	94.2 (18.8)
Urinary Symptoms: Prior to RT	88.5 (13.9)
Urinary Symptoms: 8 Weeks (Last Week of RT)	79.2 (13)
Urinary Symptoms: 6 Weeks Post-RT	85.7 (11.9)
Urinary Symptoms: 3 Months Post-RT	87.5 (11.6)
Urinary Symptoms: 9 Months Post-RT	85.1 (17.9)
Urinary Symptoms: 15 Months Post-RT	87.2 (13.8)
Urinary Symptoms: 27 Months Post-RT	91.4 (7.3)
Urinary Symptoms: 39 Months Post-RT	90.8 (7.4)
Urinary Symptoms: 51 Months Post-RT	91.2 (13.6)
Urinary Symptoms: 63 Months Post-RT	90.8 (8.6)
Bowel Habits: Prior to RT	98.5 (4.5)
Bowel Habits: 8 Weeks (Last Weeks of RT)	89.7 (14.1)
Bowel Habits: 6 Weeks Post-RT	95.3 (8)
Bowel Habits: 3 Months Post-RT	93.7 (10)
Bowel Habits: 9 Months Post-RT	95.1 (8.3)
Bowel Habits: 15 Months Post-RT	95.7 (6.6)
Bowel Habits: 27 Months Post-RT	93.3 (9.6)
Bowel Habits: 39 Months Post-RT	95.8 (7.6)
Bowel Habits: 51 Months Post-RT	91.7 (13.3)
Bowel Habits: 63 Months Post-RT	93.6 (10.1)
Sexual Function: Prior to RT	55.2 (23.9)
Sexual Function: 8 Weeks (Last Week of RT)	39.5 (31.6)
Sexual Function: 6 Weeks Post-RT	38.2 (34.7)
Sexual Function: 3 Months Post-RT	42.7 (37.3)
Sexual Function: 9 Months Post-RT	44.6 (33)
Sexual Function: 15 Months Post-RT	49.2 (31.4)
Sexual Function: 27 Months Post-RT	44.5 (28.8)
Sexual Function: 39 Months Post-RT	41.8 (29.2)
Sexual Function: 51 Months Post-RT	47.7 (29)
Sexual Function: 63 Months Post-RT	36.6 (25.1)
Hormonal Function: Prior to RT	88 (15.1)
Hormonal Function: 8 Weeks (Last week of RT)	86.2 (15.1)
Hormonal Function: 6 Weeks Post-RT	86.5 (13.4)
Hormonal Function: 3 Months Post-RT	85.4 (17.1)
Hormonal Function: 9 Months Post-RT	89.8 (11.4)
Hormonal Function: 15 Months Post-RT	92.8 (9)
Hormonal Function: 27 Months Post-RT	93.8 (7.2)
Hormonal Function: 39 Months Post-RT	91.9 (10.3)
Hormonal Function: 51 Months Post-RT	87.9 (17.1)
Hormonal Function: 63 Months Post-RT	91.5 (10)

8. Secondary Outcome

Title	HrQoL as Assessed by MAX-PC Questionnaire
Description	Health-related quality of life (HRQOL) will be measured using the scores on the Modified 18-item Memorial Anxiety Scale for Prostate Cancer (MAX-PC) from pre-treatment to post-treatment. The scale consists of 18 items (e.g. "I thought about prostate cancer even though I didn't mean to.") scored on a scale from 0 ("not at all") to 3 ("often"). Total scores range from 0 to 54, with higher scores indicating higher levels of anxiety.
Time Frame	At Baseline (Prior to RT), at 8 weeks (Last week of RT), At 6 weeks post RT, At 3 months post RT, At 6 months post RT, At 9 months post RT, At 15 months post RT, At 27 months post RT, At 39 months post RT, At 51 months post RT, At 63 months post RT

Outcome Measure Data

Analysis Population Description

Not all participants were able to complete the questionnaires at different timepoints in the study.

Arm/Group Title	LEAD Radiation Therapy
Arm/Group Description	Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2. Lattice Extreme Ablative Dose Radiation Therapy: 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1. Standard IMRT: 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.
Measure Participants	25
Prior to Radiation Therapy (RT)	13.7 (6.3)
8 Weeks (Last Week of RT)	15.1 (7.2)
6 Weeks Post-RT	13.3 (7.5)
3 Months Post-RT	11.7 (7.5)
9 Months Post-RT	12.6 (7.5)
15 Months Post-RT	10 (6.9)
27 Months Post-RT	12.2 (6.1)
39 Months Post-RT	12.3 (7.2)
51 Months Post-RT	11.2 (9.1)
63 Months Post-RT	12.9 (6.2)

Adverse Events

Time Frame	Up to 6 years
Arm/Group Title	LEAD Radiation Therapy
Arm/Group Description	Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2. Lattice Extreme Ablative Dose Radiation Therapy: 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1. Standard IMRT: 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.
All Cause Mortality
	LEAD Radiation Therapy
	Affected / at Risk (%)	# Events
Total	1/25 (4%)
Serious Adverse Events
	LEAD Radiation Therapy
	Affected / at Risk (%)	# Events
Total	1/25 (4%)
Renal and urinary disorders
Urinary Tract Infection	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	LEAD Radiation Therapy
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
Anemia	1/25 (4%)	1
Low Testosterone	1/25 (4%)	1
Endocrine disorders
Low Testosterone	1/25 (4%)	1
Gastrointestinal disorders
Abdominal Pain	1/25 (4%)	1
Bloating	2/25 (8%)	2
Constipation	3/25 (12%)	4
Diarrhea	9/25 (36%)	15
Flatulence	1/25 (4%)	1
Hemorrhoidal hemorrhage	1/25 (4%)	1
Nausea	1/25 (4%)	1
Rectal hemorrhage	1/25 (4%)	1
Rectal pain	4/25 (16%)	4
General disorders
Chills	1/25 (4%)	1
Edema limbs	1/25 (4%)	1
Fatigue	10/25 (40%)	11
Fever	1/25 (4%)	1
Increased appetite	1/25 (4%)	1
Pain	1/25 (4%)	1
Investigations
Alanine aminotransferase increased	1/25 (4%)	1
Low testosterone	2/25 (8%)	2
Platelet count decreased	1/25 (4%)	1
Weight loss	1/25 (4%)	1
Metabolism and nutrition disorders
Anorexia	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	1/25 (4%)	1
Nervous system disorders
Dizziness	1/25 (4%)	1
Renal and urinary disorders
Cystitis noninfective	13/25 (52%)	17
Hematuria	3/25 (12%)	3
Urinary obstructive symptoms, urinary hesitancy, increased frequency of bowel movement (no diarrhea)	7/25 (28%)	7
Urinary frequency	19/25 (76%)	27
Urinary incontinence	4/25 (16%)	4
Urinary retention	8/25 (32%)	9
Urinary tract infection	1/25 (4%)	1
Urinary tract obstruction	4/25 (16%)	5
Urinary tract pain	1/25 (4%)	1
Urinary urgency	16/25 (64%)	25
Reproductive system and breast disorders
Ejaculation disorder	1/25 (4%)	1
Erectile dysfunction	3/25 (12%)	5
Penile pain	1/25 (4%)	1
Prostatic pain	1/25 (4%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/25 (4%)	1
Vascular disorders
Hot flashes	2/25 (8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.