Radiation Therapy in Treating Patients With Stage II Prostate Cancer

Five-year rates are estimated by the Kaplan-Meier method. DFS events included local progression, distant metastatic progression, biochemical recurrence as defined by the Radiation Therapy Oncology Group (RTOG) Phoenix definition, or death from any cause. Patients who experienced second primary cancers remained under observation for DFS events.

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

Population: Eligible patients who did not withdraw consent

To examine trade-offs between the survival time and QOL, we were to combine them for each patient into two single measurements: quality adjusted live year (QALY) and quality adjusted disease-free survival year (QADFSY). We were to use Glasziou's multiple health-state (Q-TWiST) models to use the repeated measures of EQ-5D.

Time frame: From baseline to 5 years from the start of treatment

Population: This analysis was not conducted because there were no differences in EQ-5D scores. See results presented for Outcome Measure 10: Evaluation and Comparison of the Cost-utility of Each Treatment Arm Using EQ-5D.

Anxiety and depression were measured with the Hopkins Symptom Checklist (HSCL-25). It consists of 25 items: Part I of the HSCL-25 has 10 items for anxiety symptoms; Part II has 15 items for depression symptoms. The scale for each question includes four categories of response (Not at all, A little, Quite a bit, Extremely, rated 1 to 4, respectively). Two scores are calculated: the total score is the average of all 25 items and ranges from 0 to 100. A higher score indicates worse symptoms. The HSCL-25 tool was assessed at baseline, 6 months, 12 months, 24 months, and 5 years. For each patient, the change in score from baseline to the time point is calculated by subtracting the baseline value from the time point value.

Time frame: Baseline, 6 months, 12 months, 24 months, and 5 years

Population: Eligible patients with a follow-up HSCL-25 who did not withdraw consent

Prostate cancer (PC) Health-Related Quality of Life (HRQOL) outcomes as measured by change over time in the Expanded Prostate Cancer Index Composite \[EPIC\], a PC HRQOL instrument measuring a broad spectrum of urinary, bowel, and sexual symptoms related to radiotherapy, is compared between arms. The EPIC questionnaire was grouped into four domains (bowel, urinary, sexual, hormonal), each with a score ranging from 0 (worst) to 100 (best), and was assessed at baseline, 6, 12, and 24 months, and 5 years. The difference in score from baseline to each time point was calculated and the Wilcoxon test statistic was used to test the null hypothesis that responses are the same across the two treatment arms vs. the alternative hypothesis that they are different, using a 2-sided alpha of 0.05 at each timepoint, resulting in an alpha of 0.0125 for each domain. Each row refers to a separate analysis.

Time frame: Baseline, 6, 12, and 24 months, and 5 years

Population: Eligible patients with both a baseline and follow-up EPIC domain score, who did not withdraw consent

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). Health states are defined by the combination of the leveled responses to the 5 dimensions, generating 243 health states to which unconsciousness and death are added. The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Both the 5-item index score and the VAS score are transformed into a utility score between 0 -Worst health stat and 1 -Best health state. A two-sided Wilcoxon test with alpha 0.05 was used due to the skewed, thus non-normal, nature of the data.

Time frame: Baseline, 6 months, 12 months, 24 months, and 5 years

Population: Eligible patients with a baseline or follow-up EQ-5D score who did not withdraw consent

An event was death in association with any of the following conditions: * Primary cause of death certified as due to prostate cancer * Further clinical tumor progression occurring after initiation of salvage anti-tumor (e.g., (androgen suppression) therapy * A rise (that exceeds 1.0 ng/mL) in the serum prostate-specific antigen (PSA) level on at least two consecutive occasions that occurs during or after salvage androgen suppression therapy * Disease progression in the absence of any anti-tumor therapy * Death from a complication of therapy, irrespective of disease status. The arms were not statistically compared because of an insufficient number of events.

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

Population: All eligible patients

Clinical criteria for local recurrence are progression (increase in palpable abnormality) at any time, failure of regression of the palpable tumor by 2 years, and redevelopment of a palpable abnormality after complete disappearance of previous abnormalities. Histologic criteria for local recurrence are presence of prostatic carcinoma upon biopsy and positive biopsy of the palpably normal prostate more than 2 years after the start of treatment. The arms were not statistically compared because of an insufficient number of events.

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

Population: All eligible patients.

Five-year rates Kaplan-Meier estimates. Overall survival (OS) was measured from study entry until the date of death. Patients still alive at the time of analysis were censored at the date of last follow-up

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

Population: Eligible patients who did not withdraw consent.

Five-year rates are shown (cumulative incidence estimates). Note, although the protocol calls this endpoint Freedom from biochemical recurrence, it defines the endpoint as The time to PSA failure. An event for PSA, i.e. biochemical, failure was the first of the following: initiation of non-protocol (e.g., salvage) hormone therapy, or an increase in PSA of at least 2 ng/mL. Time to biochemical failure was measured from study entry until the date of failure.

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

Population: Eligible patients who did not withdraw consent.

The frequency of genitourinary (GU) and gastrointestinal (GI) adverse events as defined and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3) were compared between treatment arms. Acute toxicity was defined as any toxicity beginning within 90 days of completion of RT, and late toxicity was defined as any toxicity beginning more than 90 days after the completion of RT. Acute and late GU and GI toxicity rates were tabulated and reported in two ways: dichotomized as \< grade 2 vs ≥ grade 2, and dichotomized as \< grade 3 vs ≥ grade 3. Higher grade indicates more severity.

Time frame: Acute toxicity is measured from start of treatment to 90 days from the completion of treatment. Late toxicity is defined as toxicity occuring after 90 days from completion of treatment. Analysis occured at the time of the primary endpoint analysis.

Population: All eligible patients who started study treatment and did not withdraw consent

Time frame: Baseline biomarker collection. Analysis would occur after the primary endpoint analysis.

Population: The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from the NRG tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this outcome measure. Specimen use will require federal approval and funding separate from this trial.

The Utilization of Sexual Medications/Devices questionaire is designed to assess the use of erectile aids among patients treated for prostate cancer. This instrument is used to complement the sexual symptom domain in the EPIC. The percentage of Yes responses to the following questions are reported: Do you have a penile prosthesis, Have you used an medications or devices to aid or improve erections?.

Time frame: Baseline, 6, 12, and 24 months, and 5 years

Population: Eligible patients answering the questionaire, who did not withdraw consent

Time frame: From baseline to 5 years from the start of treatment.