Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Behaviors and Mental Disorders

Prostatic Neoplasms

Adenocarcinoma

Erectile Dysfunction

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

* GTV represents MR defined dominant radiographic disease, if identifiable.
* CTV encompasses the full prostate. At physician's discretion, the insertion of the seminal vesicle upon the prostate on slices containing prostate may be included.
* PTV1_30Gy will not be used or created on this arm
* PTV2_SAbR40Gy OR PTV2_SAbR45Gy will be generated by a 3mm expansion on the CTV. PTV2_SAbR will receive 8-9 Gy per fraction for 5 fractions (40-45 Gy).

* GTV represents MR defined dominant radiographic disease, if identifiable.
* CTV encompasses the full prostate. At physician's discretion, the insertion of the seminal vesicle upon the prostate on slices containing prostate may be included.
* PTV1_30Gy represents a 3mm expansion on the CTV, excluding the neurovascular structures on the side to be spared (left or right). PTV1 will receive 6 Gy per fraction for 5 fractions (30 Gy).
* PTV2_SAbR40Gy OR PTV2_SAbR45Gy will be generated by subtracting a 5mm expansion around the neurovascular elements to be spared (at least one side, left or right) from PTV1. These neurovascular structures consist of the neurovascular bundle, penile bulb, and internal pudendal arteries (see 4.1.5.2.16). PTV2 will receive 8-9 Gy per fraction for 5 fractions (40-45 Gy).

PTV1_30Gy represents a 3mm expansion on the prostate (and proximal seminal vesicle per physician discretion), excluding the neurovascular structures on the side to be spared (left or right). PTV1 will receive 6 Gy per fraction for 5 fractions (30 Gy).

30Gy (Gray) planning target volume (PTV)

Reduction of dose to or 'sparing' of neurovascular structures during stereotactic ablative body radiotherapy (SAbR) for localized prostate cancer will improve retention of sexual potency, while retaining excellent oncologic control and other secondary health-related quality of life (HRQOL) endpoints.

Primary Objectives:

• To compare the decline in patient health-related quality of life (HRQOL) instrument-defined erectile dysfunction following stereotactic ablative body radiotherapy (SAbR) with or without neurovascular sparing

Secondary Objectives:

* Assess acute (within 3 months of treatment) and chronic (\>3 months after treatment) SAbR related GU and GI toxicities, as well as serial impact on HRQOL metrics over time
* Assess biochemical progression free survival, local recurrence, distant recurrence, and survival
* Evaluate simplified 'practical' secondary HRQOL sexual potency endpoints that can be compared to prior literature.

Exploratory Objectives:

* Evaluate feasibility of MRI BOLD/TOLD to be integrated as hypoxia monitoring sequences to standard already planned diagnostic and/or treatment planning MRI on the study in five patient pilot.
* Evaluate quality of spacer placement and its effect on dose to neurovascular structures
* Evaluate rate local recurrence in the area of sparing adjacent to the neurovascular elements by biopsy in those with biochemical progression.

This is a phase II randomized, multi-institution, open-label, patient and HRQOL endpoint assessor blinded study evaluating the ability of neurovascular element sparing SAbR to decrease erectile dysfunction. The study procedure is to reduce 2-year Expanded prostate cancer index composite (EPIC) sexual domain score decline by 50% (-20 to -10), there by improving potency preservation. This reduction is usually expected to observe in patients undergoing the treatment stereotactic ablative body radiotherapy (SAbR) to 40-45 Gy with rectal spacer +/- sparing of at least one side's neurovascular structures using dose-painting.

Primary Endpoint:

• The Expanded prostate cancer index composite (EPIC) health-related quality of life (HRQOL) instrument includes a sexual function domain, which is used to produce a composite score of 0-100 from 9 questions related to ability to achieve an erection with or without aids and participate in intercourse. The primary endpoint will be the mean 24-month decline in EPIC sexual function domain composite score.

Secondary Endpoints:

* Acute Genitourinary (GU) and Gastrointestinal (GI) toxicity is defined as grade 1-5 toxicity occurring prior to 270 days from the start of protocol treatment. It is graded based on CTCAE v4.0.
* Delayed GU and GI toxicity is defined as grade 1-5 toxicity occurring prior to 270 days from the start of protocol treatment. It is graded based on CTCAE v4.0.
* Non GU and GI toxicity up to six months post treatment.
* Biochemical failure Radiation therapy oncology group-American Society for Therapeutic Radiology and Oncology (RTOG-ASTRO) definition (also known as Phoenix definition) - Thus, when the Prostate Specific Antigen (PSA) rises by more than 2 ng/ml above the lowest level (nadir) achieved after treatment, biochemical failure has occurred and the date of the failure is recorded at the time the nadir plus 2 ng/ml level is reached. Patients should be followed for a minimum of 5 years on this study to evaluate this endpoint.
* Overall survival
* Disease-specific survival
* Clinical progression including local/regional and distant relapse
* HRQOL questionnaires (EPIC and SF-12)
* Erectile function medication and device aids tracked before and after therapy longitudinally
* Feasibility of MRI BOLD/TOLD in evaluating tumor hypoxia in no more than five patient pilot

Sample Size: To enroll 120 patients (60 patients in each treatment arm).

The sample size is estimated, first, assuming that neurovascular element sparing SAbR (experimental arm intervention) will result in a mean 24 month decline in EPIC (HRQOL instrument) sexual domain composite score of -20, as compared to a decline of -10 in a standard SAbR without neurovascular element sparing. A total sample size of 102 patients (51 patients in each treatment group) achieves 80% power to detect this difference of 10 in EPIC sexual domain composite score decline at 24 months after treatment, with an equal standard deviation of 20 in both groups and at a two-sided significance level of 0.10, using a two-sample t-test (effect size 0.50).

An attrition rate of EPIC sexual domain questionnaire completion at 2-years of 15% is anticipated, based upon yields from multi-center prospective trials in prostate cancer radiotherapy with EPIC HRQOL endpoints. A total of 120 patients will be accrued to account for this 15% attrition rate.

Statistical Analysis: For the primary endpoint, a two-sided two-sample t-test will be used to compare EPIC sexual function domain score composite declines at 24 months from treatment between experimental SAbR arms with and without neurovascular sparing. Our sample size of 60 patients in each arm gives a calculated 80% power to detect a difference of 10 (considered the minimally important difference for sexual domain) at a two-sided significance level 0.10, assuming an equal standard deviation of 20 in both groups and allowing for 15% attrition in survey completion. Secondary endpoints and their analysis methodology is further specified in the protocol.

Prostate Oncologic Therapy While Ensuring Neurovascular Conservation (POTEN-C)

A Phase II Randomized Controlled Trial of Stereotactic Ablative Body Radiotherapy (SAbR) With or Without Neurovascular Sparing for Erectile Function Preservation in Localized Prostate Cancer

To compare the decline in patient health-related quality of life (HRQOL) instrument-defined erectile dysfunction following stereotactic ablative body radiotherapy (SAbR) with or without neurovascular sparing. The Expanded Prostate Cancer Index Composite (EPIC) health-related quality of life (HRQOL) instrument includes four sub-scales like urinary function, bowel habits, sexual function, and hormonal function. The primary outcome (sexual function) which has a range score of 0-100 from 9 questions related to ability to achieve an erection with or without aids and participate in intercourse. Higher the score represents the better outcome. Individual responses are summed for a total score of sexual function.

Assess acute (within 3 months of treatment) and chronic (\>3 months after treatment) SAbR related GU and GI toxicities, as well as serial impact on HRQOL metrics over time. Severity or Toxicity will be assessed according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. The consequences of gastointestinal/renal/genitourinary/sexual and reproductive toxicity should all be graded 1-5 according to the Common Terminology Criteria For Adverse Events (CTCAE), version 4.0 occurring prior to 270 days from the start of protocol treatment. Other treatment related toxicity attributed to the therapy will be captured, recorded and the consequences of should all be graded 1-5 according to the Common Terminology Criteria For Adverse Events (CTCAE). CTCAE V4.0 along with grades 1-5 is provided in the link for reference (https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf).

Assess biochemical progression free survival. Biochemical failure RTOG-ASTRO definition - when the PSA rises by more than 2 ng/ml above the lowest level (nadir) achieved after treatment, biochemical failure has occurred and the date of the failure is recorded at the time the nadir plus 2 ng/ml level is reached.

The time to progression will be measured from the date of study entry to the date of documented local progression as determined by clinical exam and/or MRI. Local progression is defined by progression within the prostate, seminal vesicles or immediately adjacent extracapsular soft tissue. Biopsy confirmation is not required but is encouraged.

The time to distant failure will be measured from the date of study entry to the date of documented regional nodal recurrence or distant disease relapse. Patients with evidence of biochemical failure, but a negative prostate biopsy, will be considered as distant failure only.

The survival time will be measured from the date of accession to the date of death. All patients will be followed for survival. Every effort should be made to document the cause of death.

Evaluate simplified 'practical' secondary HRQOL sexual potency endpoints that can be compared to prior literature. The Expanded Prostate Cancer Index Composite (EPIC) health-related quality of life (HRQOL) instrument includes four sub-scales like urinary function, bowel habits, sexual function, and hormonal function. The primary outcome (sexual function) which has a range score of 0-100 from 9 questions related to ability to achieve an erection with or without aids and participate in intercourse. Higher the score represents the better outcome. Individual responses are summed for a total score of sexual function.

Spots Global Cancer Trial Database for erectile dysfunction, neurovascular, prostate, rectal spacer, radiotherapy