Interstitial Brachytherapy With or Without External-Beam Radiation Therapy in Treating Patients With Prostate Cancer

A Freedom from Progression (FFP) failure includes biochemical failure, local failure, distant failure, or death due to any cause. Patients who are failure free with less than 5 years of follow-up or who receive any secondary salvage therapy are censored. Freedom from Progression rates are estimated using the Kaplan-Meier method.

Time frame: From randomization to 5 years

Population: All Eligible Patients

Biochemical Failure is defined as an increase of 2 ng/ml or more in PSA over the nadir PSA after 24 months from the start of treatment or the start of salvage hormones. Time to biochemical is defined as time from randomization to the date of first biochemical failure, last known follow-up (censored), or death without biochemical failure (competing risk). Biochemical failure rates are estimated using the cumulative incidence method. Five year rates are reported.

Time frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years.Maximum follow-up at time of analysis was 13.9 years.

Population: All Eligible Patients

Biochemical failure is defined as having 3 consecutive rises of post-treatment PSA or starting hormones after one or more elevations in post-treatment PSA but before 3 consecutive elevations are documented. The sum of the 3 consecutive rises must exceed 1 ng/mL above the nadir. If 3 consecutive PSA rises occur during the first 24 months followed by a subsequent non-hormonal induced PSA decrease, patients will not be considered PSA failures. Three consecutive rises with any of the 3 PSA values occurring more than 24 months after the implant procedure will constitute a failure. Time to biochemical is defined as time from randomization to the date of first biochemical failure, last known follow-up (censored), or death without biochemical failure (competing risk). Biochemical failure rates are estimated using the cumulative incidence method. Five year rates are reported.

Time frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.9 years.

Population: All Eligible Patients

The EQ5D is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The change score was calculated as the value at the follow-up timepoint minus the value at baseline. A negative change reflects a decline at the follow-up timepoint and a positive change reflects an improvement at the follow-up timepoint.

Time frame: Baseline and 24 months after start of radiation

Population: Questionnaires were not completed by all eligible participants. 210 and 212 EBRT + Brachytherapy participants had VAS and index score data, respectively, at baseline and 24 months; 212 and 226 Brachytherapy Only participants had VAS and index score data, respectively, at baseline and 24 months.

The EQ-5D is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The change score was calculated as the value at the follow-up timepoint minus the value at baseline. A negative change reflects a decline at the follow-up timepoint and a positive change reflects an improvement at the follow-up timepoint.

Time frame: Baseline and 4 months after start of radiation

Population: Questionnaires were not completed by all eligible participants. 218 and 227 EBRT + Brachytherapy participants had VAS and index score data, respectively, at baseline and 4 months; 237 and 248 Brachytherapy Only participants had VAS and index score data, respectively, at baseline and 4 months.

The EPIC form is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal function). The urinary domain summary score can be separated into 2 distinct subscales: urinary incontinence and urinary irritative. Hormonal domain was excluded as concurrent use of hormones was exclusionary and prior neoadjuvant hormone use was low. Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. The change score was calculated as the value at 24 months minus the value at baseline. A negative change reflects a decline at 24 months and a positive change reflects an improvement at 24 months.

Time frame: Baseline and 24 months after start of radiation

Population: Eligible patients with baseline and 24-month EPIC data

The EPIC form is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal function). The urinary domain summary score can be separated into 2 distinct subscales: urinary incontinence and urinary irritative. Hormonal domain was excluded as concurrent use of hormones was exclusionary and prior neoadjuvant hormone use was low. Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. The change score was calculated as the value at 4 months minus the value at baseline. A negative change reflects a decline at 4 months and a positive change reflects an improvement at 4 months.

Time frame: Baseline and 4 months after start of radiation

Population: Eligible patients with baseline and 4-month EPIC data

The AUA-SI is a validated 7-item measure used to assess urinary symptoms. A higher score indicates more severe symptoms for the individual questions and overall total. Six questions ask about frequency of symptoms over the past month with possible responses: 0= Not at all; 1 = Less than 1 time in 5; 2 = less than half the time, 3 = About half the time, 4 = More than half the time, 5 = Almost always. An additional question asks the number of times one gets up to urinate after going to bed, with response indicating the exact number of times ranging from 0 to 5. The total score is the sum of the questions and ranges from 0 to 35. Change is calculated as follow-up timepoint score - baseline score such that a negative change reflects an improvement at the follow-up timepoint and a positive change reflects a decline at the follow-up timepoint.

Time frame: Baseline and 24 months after start of radiation

Population: Eligible patients who had a total AUA-SI score at baseline and 24 months.

The AUA-SI is a validated 7-item measure used to assess urinary symptoms. A higher score indicates more severe symptoms for the individual questions and overall total. Six questions ask about frequency of symptoms over the past month with possible responses: 0= Not at all; 1 = Less than 1 time in 5; 2 = less than half the time, 3 = About half the time, 4 = More than half the time, 5 = Almost always. An additional question asks the number of times one gets up to urinate after going to bed, with response indicating the exact number of times ranging from 0 to 5. The total score is the sum of the questions and ranges from 0 to 35. Change is calculated as follow-up timepoint score - baseline score such that a negative change reflects an improvement at the follow-up timepoint and a positive change reflects a decline at the follow-up timepoint.

Time frame: Baseline and 4 months after start of radiation

Population: Eligible patients who had a total AUA-SI score at baseline and 4 months

Failure is defined as the appearance of any distant metastases. Time to distant metastases is defined as time from randomization to the date of first distant metastases, last known follow-up (censored), or death without distant metastases (competing risk). Distant metastases rates are estimated using the cumulative incidence method. Five year rates are reported.

Time frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.9 years.

Population: All Eligible Patients

Failure is defined as progression (increase in palpable abnormality) at any time, failure of regression of the palpable tumor by two years, and redevelopment of a palpable abnormality after complete disappearance of previous abnormalities. Histologic criteria for local failure are presence of prostatic carcinoma upon biopsy and positive biopsy of the palpably normal prostate more than two years after the start of treatment. Time to local failure is defined as time from randomization to the date of first local failure, last known follow-up (censored), or death without local failure (competing risk). Local failure rates are estimated using the cumulative incidence method. Five year rates are reported.

Time frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.9 years.

Population: All Eligible Patients

Failure is defined as death due to any cause. Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Survival rates are estimated using the Kaplan-Meier method. Five year rates are reported.

Time frame: From randomization to last follow-up. Analysis occurs after all patients had been on study for at least 5 years. Maximum follow-up at time of analysis was 13.9 years.

Population: All Eligible Patients

Acute toxicities are scored according to NCI Common Toxicity Criteria (CTC) version 2.0 and will be defined as the worst severity of the toxicity occurring ≤ 180 days from start of radiation. The CTC v 2.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to based.

Time frame: Zero to 180 days from the start of radiation

Population: Eligible patients who started study treatment

Prostate cancer death is defined as death due to prostate cancer or complications of treatment or death associated with any of the following: 1) further clinical tumor progression occurring after initiation of salvage androgen suppression therapy; 2) a rise that exceeds 1.0 ng/ml in the serum PSA level on at least two consecutive occasions that occurs during or after salvage androgen suppression therapy; and 3) disease progression in the absence of any anti-tumor therapy. Time to prostate cancer death is defined as time from randomization to the date of prostate cancer death, last known follow-up (censored), or death without prostate cancer (competing risk). Prostate cancer death rates are estimated using the cumulative incidence method. Five year rates are reported.

Time frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.9 years.

Population: All Eligible Patients

Late toxicities are scored according to the Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) Late Radiation Morbidity Scoring Scheme and will be defined as the worst severity of the toxicity occurring \> 180 days from radiation start. Grade 3+ GU/GI and overall were analyzed. RTOG/EORTC Late Radiation Morbidity Scoring Scheme assigns Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity. Time to late grade 3+ toxicity is defined as time from randomization to the date of first late grade 3+ toxicity, last known follow-up (censored), or death without late grade 3+ toxicity (competing risk). Late grade 3+ toxicity rates are estimated using the cumulative incidence method. Five year rates are reported.

Time frame: From 181 days after the start of radiation to last follow-up. Maximum follow-up at time of analysis was 13.9 years.

Population: Eligible patients who started study treatment and had follow-up data \> 180 days from the start of treatment

Time frame: Analysis occurs after all patients have been potentially followed for 5 years.

Population: The pilot portion of the trial determined that the data required for this analysis was not able to be obtained, and therefore, there are no results for this outcome measure.