Primary and Secondary Outcome Measures in a Study of Prostate-specific Antigen (PSA) Doubling Time and Disease Progression

Primary Outcome Measures : Time to Prostate-specific Antigen (PSA) Doubling From Baseline (in Days) [ Time Frame: up to 28 months ] Time to PSA doubling is defined as the number of days between the baseline date and the study day of the first post-baseline PSA evaluation date (within treatment period, typically up to 24-month evaluations) on which the PSA value was at least twice as much as the baseline PSA value, and the immediate subsequent value, if available, was at least 85% of two times the baseline value. Participants who never achieved PSA doubling were censored at the last post-baseline, non-missing PSA evaluation. Number of Participants With PSA Doubling From Baseline [ Time Frame: up to 28 months ] PSA doubling is defined as the first post-baseline PSA value (within treatment period, typically up to 24-month evaluations) that was at least twice as much as the baseline PSA value and was confirmed as such (at least 85% of two times the baseline PSA value) in the immediate subsequent PSA value if one is available. Time to PSA Doubling From Baseline (in Days) Within Year 1 [ Time Frame: up to 16 months ] Time to PSA doubling is defined as the number of days between the baseline date and the study day of the first post-baseline PSA evaluation date within Year 1 (Y1; within treatment period, typically up to 12-month evaluations) on which the PSA value was at least twice as much as the baseline PSA value, and the immediate subsequent value, if available, was at least 85% of two times the baseline value. Number of Participants With PSA Doubling From Baseline During Year 1 [ Time Frame: up to 16 months ] PSA doubling is defined as the first post-baseline PSA value (within treatment period, typically up to 12-month evaluations) that was at least twice as much as the baseline PSA value and was confirmed as such (at least 85% of two times the baseline PSA value) in the immediate subsequent PSA value if one is available. Secondary Outcome Measures : Time to Disease Progression From Baseline (in Days) [ Time Frame: up to 28 months ] Time to disease progression is defined as the number of days between baseline and the first occurrence of any of the following: PSA doubling time (PSADT)<=91 days, PSA value is at least 50% more than baseline value (>20 nanogram/milliliter [ng/ml] for primary radiotherapy group or >10 ng/ml for radical prostatectomy group), rescue treatment, cancer-positive biopsy, cancer-positive bone scan. (Confirmation of PSA criteria is required in an immediate subsequent PSA, if available, and PSA values for consideration are restricted to treatment period, typically up to 24-month evaluations.) Number of Participants With Disease Progression [ Time Frame: up to 28 months ] Disease progression is defined as the first occurrence of any of the following: PSADT<=91 days, PSA value is at least 50% more than baseline value (>20 ng/ml for primary radiotherapy group or >10 ng/ml for radical prostatectomy group), rescue treatment, cancer-positive biopsy, cancer-positive bone scan. If one of the PSA criteria is qualifying (within treatment period, typically up to 24-month evaluations), an immediate subsequent PSA, if available, must confirm either criterion (or at least 85% of the qualifying value). Number of Participants Classified as Treatment Responders at Months 3, 6, 9, 12, 15, 18, 21, and 24 [ Time Frame: Months 3, 6, 9, 12, 15, 18, 21, and 24 ] Treatment responders at Month X were defined as participants (par.) with either a PSA decrease or an increase <=15% from baseline to Month X confirmed in all PSA measurements between baseline (BL) and Month X. Time to PSA Rise From Baseline (in Days) [ Time Frame: up to 28 months ] A participant was designated as having a PSA rise if there existed a post-baseline PSA value (within treatment period, typically up to 24-month evaluations) that was >1.15 times the baseline PSA value, and all subsequent PSA values were >1.15 times the baseline PSA value. The study day for the first PSA evaluation that qualified for analysis of PSA rise was used for time to PSA rise. If none of the post-baseline PSA values qualified for analysis of PSA rise during the study, time to PSA rise was censored at the last post-baseline PSA evaluation. Number of Participants With a PSA Rise From Baseline [ Time Frame: up to 28 months ] A participant was designated as having a PSA rise if there existed a post-baseline PSA value (within treatment period, typically up to 24-month evluations) that was >1.15 times the baseline PSA value, and all subsequent PSA values were >1.15 times the baseline PSA value. Time to PSA Progression (in Days) [ Time Frame: up to 28 months ] A participant was designated as having PSA progression if there existed a post-baseline PSA value (within treatment period, typically up to 24-month evaluations) that was >10 ng/ml if radical prostatectomy or >20 ng/ml if primary radiotherapy and PSA >=1.5 times the baseline PSA value, or 0<PSADT<=91 days, and all subsequent PSA values satisfied these criteria. The study day for the first PSA qualifying for progression was used for time to PSA progression. If none of the PSA values qualified for PSA progression, time to PSA progression was censored at the last post-baseline PSA evaluation. Number of Participants With PSA Progression [ Time Frame: up to 28 months ] A participant was designated as having a PSA progression if there existed a post-baseline PSA value (within treatment period, typically up to 24-month evaluations) that was (>10 ng/ml if radical prostatectomy or >20 ng/ml if primary radiotherapy) and PSA >=1.5 times the baseline PSA value), or 0<PSADT<=91 days, and all subsequent PSA values satisfied either of these criteria. Change in Total PSA From Baseline at Months 12 and 24 [ Time Frame: Baseline; Months 12 and 24 ] Change in PSA from baseline at Month X = Month X PSA - Baseline PSA. The missing PSA value for scheduled visits could have been replaced by non-missing PSA values within 30 days after the clinic visit date. If such replacement was not possible, the latest non-missing post-baseline PSA before the scheduled visit was used for the scheduled visit PSA (Last Observation Carried Forward). Percent Change in Total PSA From Baseline at Months 12 and 24 [ Time Frame: Baseline; Months 12 and 24 ] Percent change in PSA from baseline at Month X = 100*(Month X PSA - Baseline PSA)/Baseline PSA. The missing PSA value for scheduled visits could have been replaced by non-missing PSA values within 30 days after the clinic visit date. If such replacement was not possible, the latest non-missing post-baseline PSA before the scheduled visit was used for the scheduled visit PSA (Last Observation Carried Forward). Change in PSA From Nadir PSA at Months 12 and 24 [ Time Frame: Baseline; Months 12 and 24 ] Change from nadir PSA at Month X = Month X PSA - nadir PSA. Nadir PSA was reported by the site as the lowest historical PSA value after the radical therapy. A nadir value below the detection level was captured as 0.0. The missing PSA value for scheduled visits could have been replaced by non-missing PSA values within 30 days after the clinic visit date. If such replacement was not possible, the latest non-missing post-baseline PSA before the scheduled visit was used for the scheduled visit PSA (Last Observation Carried Forward). Percent Change in PSA From Nadir PSA at Months 12 and 24 [ Time Frame: Baseline; Months 12 and 24 ] Percent change from nadir PSA at Month X = 100*(Month X PSA - nadir PSA)/Nadir PSA. Nadir PSA was reported by the site as the lowest historical PSA value after the radical therapy. A nadir value below the detection level was captured as 0.0. The missing PSA value for scheduled visits could have been replaced by non-missing PSA values within 30 days after the clinic visit date. If such replacement was not possible, the latest non-missing post-baseline PSA before the scheduled visit was used for the scheduled visit PSA (Last Observation Carried Forward). Number of Participants With the Indicated Change in PSA Doubling Time (PSADT) From Baseline at Month 12, Month 24, and End-of-treatment (up to 28 Months) [ Time Frame: Baseline; Month 12, Month 24, End-of-Treatment (up to 28 months) ] Participants with improvement included those whose PSADT at a specified visit was positive but more than the baseline PSADT, whose PSA at the visit was the same as the baseline PSA, or whose PSA at the visit was less than the baseline PSA. Participants with worsening included those whose PSADT at the visit was positive but less than the baseline PSADT. Changes From Baseline in Disease-related Anxiety Measured by the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) [ Time Frame: Baseline; Months 3, 6, 12, 18, and 24 ] MAX-PC is an 18-item, self-reported measure that evaluates prostate cancer-related anxiety. The score ranges from 0 to 54, and an increase in the score indicates a worsened anxiety level. Change from Baseline at Month X = Month X MAX-PC score - Baseline MAX-PC score. A missing post-baseline value is replaced by the last available post-baseline value (Last Observation Carried Forward(LOCF)). A general linear model controls for previous therapy, site cluster, and baseline MAX-PC score. Number of Participants With a Shift From Normal at Baseline to at Least One Abnormal Laboratory Value for Any Parameter Any Time During the Study [ Time Frame: Baseline; up to 28 months ] A participant has a normal value for a laboratory parameter if the value is within the low and high range of normal provided by the laboratory. Each laboratory parameter is evaluated for shift from normal at baseline to abnormal any time post-baseline. A participant with any laboratory parameter showing this shift is counted. A participant is counted only once even if he had such a shift in more than one laboratory parameter or more than once among all post-baseline evaluations. Number of Participants With a Threshold Laboratory Value for Any Parameter at Baseline (BL) and Any Time Post-baseline [ Time Frame: Baseline; up to 28 months ] Threshold laboratory values are defined in terms of a multiplicative factor of the testing laboratory's normal range, pre-specified in the analysis plan. A laboratory value that is above the upper limit factor multiplied by the upper limit of the normal range is considered a high threshold value. A laboratory value that is below the lower limit factor multiplied by the lower limit of the normal range is considered a low threshold value. Number of Participants With Palpable Breast Tissue (PBT) at Baseline (BL) and Any Time Post-baseline [ Time Frame: Baseline; up to 28 months ] Participants underwent clinical examination of the breasts, to evaluate for palpable breast tissue. Clinical significance of the results was determined by subjective judgment of the clinical personnel performing the examination. Number of Participants With Nipple Tenderness (NT) at Baseline (BL) and Any Time Post-baseline [ Time Frame: Baseline; up to 28 months ] Participants underwent clinical examination of the breasts, to evaluate for nipple tenderness. Clinical significance of the results was determined by subjective judgment of the clinical personnel performing the examination. Number of Participants With a Digital Rectal Examination (DRE) Evaluation Changing From Normal/Diffusely Enlarged at Baseline to Focal Abnormality at Any Time Post-baseline [ Time Frame: Baseline; up to 28 months ] Participants underwent a digital rectal examination to evaluate for focal abnormality of the prostate. Number of Participants With Threshold Vital Signs at Baseline and Any Time Post-baseline [ Time Frame: Baseline; up to 28 months ] Threshold vital signs are defined as follows: < 80 mmHg or > 165 mmHg for systolic blood pressure; < 40 mmHg or > 105 mm Hg for diastolic blood pressure, < 40 beats per minute (bpm) or > 100 bpm for heart rate.