Arm 2: Prostate and tumor irradiation

Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV

Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy; and a reduced dose will be delivered to the entire prostate.

Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment.

Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy.

Stereotactic body radiation therapy (SBRT) will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy; and a reduced dose will be delivered to the entire prostate.

External beam radiation therapy (EBRT): Participants with locally recurrent prostate cancer after treatment with EBRT. These participants cannot have had permanent brachytherapy as part of their treatment.

The specificity of DCF-PyL for detecting locally recurrent prostate cancer (at baseline) will be reported using biopsy as the gold standard to evaluate 18F-DCFPyL imaging as a method to detect locally recurrent prostate cancer after radiation. Specificity is the number of true negatives divided by the sum of the number of true negatives and the number of false positives. Lesions that are not detected on DCF-PyL that are biopsy confirmed to have no tumor are considered true negatives. Lesions that are detected on DCF-PyL and are biopsy negative are considered false positives.

Changes of QOL scores during and after treatment of focally dose escalated prostate stereotactic body radiation therapy (SBRT) on participant reported outcomes (Sexual Health Inventory for Men (SHIM), in participants previously treated with radiotherapy. The QOL scores will be summarized at baseline and for each visit. Linear mixed effects model will be used to model quality of life scores at baseline and during and after treatment in which random intercept and random slope are used to account for participant-specific trajectory of QOL scores. The SHIM is a 5-question quiz used to identify erectile dysfunction and assess its severity. The composite score is generated by adding the score for each question. The total score can range from 1-25. Higer values represent better erectile function.

Changes of QOL scores during and after treatment of focally dose escalated prostate stereotactic body radiation therapy (SBRT) on participant reported outcomes, American Urologic Association (AUA) Symptom Index, in participants previously treated with radiotherapy. The QOL scores will be summarized at baseline and for each visit. Linear mixed effects model will be used to model quality of life scores at baseline and during and after treatment in which random intercept and random slope are used to account for participant-specific trajectory of QOL scores. The AUA Symptom Index is a 7-question quiz used to identify urinary symptoms and assess severity. Each question is scored based on the frequency of a different urinary symptoms. The composite score is generated by adding the score for each question. The total score can range from 0-35. Lower values represent less symptoms.

Changes of QOL scores during and after treatment on participant reported outcomes, EPIC-26 in participants previously treated with radiotherapy. The QOL scores will be summarized at baseline and for each visit. Linear mixed effects model will be used to model QOL scores at baseline and during and after treatment in which random intercept and random slope are used to account for participant-specific trajectory of QOL scores. The EPIC-26 is a shortened, validated questionnaire used to assess health related QOL in individuals with prostate cancer. The EPIC-26 measures sexual function, bowel function, hormone therapy side effects, urinary incontinence, and urinary irritative symptoms. The survey has 26 individual items that have 4 to 5 response options that reflect a range of function from poor to excellent. The EPIC-26 uses a Likert scale for each item, and scores are transformed to a 0-100 scale, with higher scores indicating better Health-Related Quality of Life.

bPFS, prostate-specific antigen (PSA) < 2 ng/dL above post stereotactic body radiation therapy (SBRT) nadir) at 1 and 2 years after treatment with focally dose escalated SBRT for locally recurrent prostate cancer after irradiation: bPFS will be estimated by the Kaplan-Meier survival analysis and effects of clinical variables on bPFS will be assessed by the Cox proportional hazards model. bPFS is defined as the duration of time from start of treatment to time of PSA progression or death, whichever occurs first. PSA progression (also known as biochemical failure) is defined based on elevation of PSA 2 ng/dL beyond the post-treatment nadir PSA, using the Phoenix criteria.

DLT's of image-guided, focally dose escalated prostate Stereotactic body radiation therapy (SBRT) in participants previously treated with radiotherapy. A DLT (during treatment and within the first three weeks after treatment) is defined as a Grade 3 rectal, small bowel, or urinary toxicity that does not resolve to Grade 2 or less within 4 days with appropriate medical management. Other grade 3 in-field toxicities attributable to SBRT that do not resolve to Grade 2 or less within 4 days with appropriate medical management. Delays of more than one week in completing radiation treatment due to toxicity. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 2 is moderate. Grade 3 is severe.

Define the dose-limiting toxicities and toxicity profile of image-guided, focally dose escalated prostate SBRT in patients previously treated with radiotherapy: DLTs will be reported descriptively.

Arm 1: Tumor irradiation. Cohort 1, Level 2, Arm 1 - 42.5 gray (Gy) to Tumor planning target volume (PTV);

External beam radiation therapy (EBRT): Participants with locally recurrent prostate cancer after treatment with EBRT. These participants cannot have had permanent brachytherapy as part of their treatment.

All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl} -ureido)-pentanedioic acid.

Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV

Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment.

All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl} -ureido)-pentanedioic acid.

Arm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV

Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment.

All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl} -ureido)-pentanedioic acid.

Total of all reporting groups

All participants in Arm 2. 42.5 Gy Tumor and 30 Gy Prostate irradiation who received at least one dose of stereotactic body radiation therapy (SBRT) are considered evaluable for toxicity. Only participants who have completed SBRT and have their prostate-specific antigen (PSA) measured are considered evaluable for response.

The sensitivity of DCF-PyL for detecting locally recurrent prostate cancer (at baseline) will be reported using biopsy as the gold standard to evaluate 18F-DCFPyL imaging as a method to detect locally recurrent prostate cancer after radiation. Sensitivity is the number of true positives divided by the sum of the number of true positives and false negatives. Lesions detected on DCF-PyL that are biopsy confirmed are considered true positives. Lesions that are not detected on DCFPyL and are biopsy positive are considered false negatives.

The specificity of DCF-PyL for detecting locally recurrent prostate cancer (at baseline) will be reported using biopsy as the gold standard to evaluate 18F-DCFPyL imaging as a method to detect locally recurrent prostate cancer after radiation. Specificity is the number of true negatives divided by the sum of the number of true negatives and the number of false positives. Lesions that are not detected on DCF-PyL that are biopsy confirmed to have no tumor are considered true negatives. Lesions that are detected on DCF-PyL and are biopsy negative are considered false positives.

Changes of QOL scores during and after treatment of focally dose escalated prostate stereotactic body radiation therapy (SBRT) on participant reported outcomes (Sexual Health Inventory for Men (SHIM), in participants previously treated with radiotherapy. The QOL scores will be summarized at baseline and for each visit. Linear mixed effects model will be used to model quality of life scores at baseline and during and after treatment in which random intercept and random slope are used to account for participant-specific trajectory of QOL scores. The SHIM is a 5-question quiz used to identify erectile dysfunction and assess its severity. The composite score is generated by adding the score for each question. The total score can range from 1-25. Higer values represent better erectile function.

Changes of QOL scores during and after treatment of focally dose escalated prostate stereotactic body radiation therapy (SBRT) on participant reported outcomes, American Urologic Association (AUA) Symptom Index, in participants previously treated with radiotherapy. The QOL scores will be summarized at baseline and for each visit. Linear mixed effects model will be used to model quality of life scores at baseline and during and after treatment in which random intercept and random slope are used to account for participant-specific trajectory of QOL scores. The AUA Symptom Index is a 7-question quiz used to identify urinary symptoms and assess severity. Each question is scored based on the frequency of a different urinary symptoms. The composite score is generated by adding the score for each question. The total score can range from 0-35. Lower values represent less symptoms.

Changes of QOL scores during and after treatment on participant reported outcomes, EPIC-26 in participants previously treated with radiotherapy. The QOL scores will be summarized at baseline and for each visit. Linear mixed effects model will be used to model QOL scores at baseline and during and after treatment in which random intercept and random slope are used to account for participant-specific trajectory of QOL scores. The EPIC-26 is a shortened, validated questionnaire used to assess health related QOL in individuals with prostate cancer. The EPIC-26 measures sexual function, bowel function, hormone therapy side effects, urinary incontinence, and urinary irritative symptoms. The survey has 26 individual items that have 4 to 5 response options that reflect a range of function from poor to excellent. The EPIC-26 uses a Likert scale for each item, and scores are transformed to a 0-100 scale, with higher scores indicating better Health-Related Quality of Life.

bPFS, prostate-specific antigen (PSA) < 2 ng/dL above post stereotactic body radiation therapy (SBRT) nadir) at 1 and 2 years after treatment with focally dose escalated SBRT for locally recurrent prostate cancer after irradiation: bPFS will be estimated by the Kaplan-Meier survival analysis and effects of clinical variables on bPFS will be assessed by the Cox proportional hazards model. bPFS is defined as the duration of time from start of treatment to time of PSA progression or death, whichever occurs first. PSA progression (also known as biochemical failure) is defined based on elevation of PSA 2 ng/dL beyond the post-treatment nadir PSA, using the Phoenix criteria.

DLT's of image-guided, focally dose escalated prostate Stereotactic body radiation therapy (SBRT) in participants previously treated with radiotherapy. A DLT (during treatment and within the first three weeks after treatment) is defined as a Grade 3 rectal, small bowel, or urinary toxicity that does not resolve to Grade 2 or less within 4 days with appropriate medical management. Other grade 3 in-field toxicities attributable to SBRT that do not resolve to Grade 2 or less within 4 days with appropriate medical management. Delays of more than one week in completing radiation treatment due to toxicity. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 2 is moderate. Grade 3 is severe.

Define the dose-limiting toxicities and toxicity profile of image-guided, focally dose escalated prostate SBRT in patients previously treated with radiotherapy: DLTs will be reported descriptively.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Arm 1: Tumor irradiation. Cohort 1, Level 2, Arm 1 - 42.5 gray (Gy) to Tumor planning target volume (PTV);

External beam radiation therapy (EBRT): Participants with locally recurrent prostate cancer after treatment with EBRT. These participants cannot have had permanent brachytherapy as part of their treatment.

All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl} -ureido)-pentanedioic acid.

Arm 2: Prostate and tumor irradiation Cohort 2, Level 1, Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 40Gy to Tumor PTV

Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment.

All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl} -ureido)-pentanedioic acid.

AArm 2: Prostate and tumor irradiation Arm 2 - 30 gray (Gy) planning target volume (PTV) to Prostate and 42.5 Gy to Tumor PTV

Brachytherapy: Participants with locally recurrent prostate cancer after treatment with brachytherapy +/- external beam radiation therapy (EBRT). These participants must have had brachytherapy as part of their treatment.

All participants received stereotactic body radiation therapy (SBRT) and 2-(3-{ 1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl} -ureido)-pentanedioic acid.