Randomised trial of external-beam radiotherapy alone or with high-dose-rate brachytherapy for prostate cancer: Mature 12-year results.

BACKGROUND AND PURPOSE: A randomised phase-III trial compared external beam radiotherapy (EBRT) alone with EBRT combined with high-dose-rate brachytherapy boost (HDR-BTb) in localised prostate adenocarcinoma. Previous analysis, at median follow up of 85 months, demonstrated improved relapse free survival (RFS) with EBRT + HDR-BTb. This data has now been updated with a median follow up of 131 months. MATERIALS AND METHODS: From December 1997 to August 2005, patients were assigned either to EBRT alone delivering 55 Gy in 20 fractions over 4 weeks or EBRT followed by a temporary high-dose-rate implant delivering 2 × 8·5 Gy over 24 h. The primary endpoint was RFS defined by a PSA rise ≥2.0 µg/l above nadir, clinical progression or death. Actuarial survival rates and Hazard Ratios (HRs) were calculated using the Kaplan-Meier method and Cox's Proportional Hazard Model, respectively. Secondary endpoints were overall survival (OS), urinary and bowel toxicity. RESULTS: One hundred and six patients received EBRT alone and 110 EBRT + HDR-BTb. Median time to relapse was 137 months in the HDR-BTb arm compared to 82 months for EBRT alone (p = 0·01). A 27% risk of recurrence with EBRT alone was observed (p = 0·001), resulting in a 21% improvement in RFS at 12 years with EBRT + HDR-BTb. In multivariate analysis treatment arm, risk category and no androgen deprivation therapy were significant covariates for risk of relapse. Differences in overall survival were not significant. CONCLUSION: At 12 years there remains a significant improvement in RFS after EBRT + HDR-BTb; both treatments were equitoxic for severe late urinary and bowel events and urethral strictures.

Optimal source distribution for focal boosts using high dose rate (HDR) brachytherapy alone in prostate cancer.

PURPOSE: To investigate the optimal distribution of sources using high dose rate brachytherapy to deliver a focal boost to a dominant lesion within the whole prostate gland based on multi-parametric magnetic resonance imaging (mpMRI). METHODS: Sixteen patients with prostate cancer underwent mpMRI each of which demonstrated a dominant lesion. There were single lesions in 6 patients, two lesions in 4 and 3 lesions in 6 patients. Two dosimetric models and parameters were compared in each case. The first model used 10mm intervals between needles, and the second model used additional needles at 5 mm intervals between each needle in the boost area. RESULTS: Three of thirty-two plans did not achieve the plan objectives. These three plans were in the first model. A higher median urethral volume was seen in the 'unsuccessful' group (2.7 cc, and 1.9 cc, respectively, p-value=0.12). Conformity indices of the second model were also better than the first model (COIN index; 0.716 and 0.643, respectively). CONCLUSIONS: Focal monotherapy based on mpMRI achieves optimal dosimetry by individualizing the needle positions using 5mm spacing rather than 10mm spacing within the boost volume. A larger urethral volume may have an adverse effect on this distribution. Formal clinical evaluation of this approach is currently underway.

Dosimetric predictors of biochemical control of prostate cancer in patients randomised to external beam radiotherapy with a boost of high dose rate brachytherapy.

BACKGROUND: To correlate dose and volume dosimetric parameters (D90 and V100) with biochemical control in advanced prostate cancer treated with high-dose rate brachytherapy (HDR-BT). METHODS: One hundred and eight patients received external beam radiotherapy (EBRT) to 35.75 Gy in 13 fractions followed by HDR-BT of 2 × 8.5 Gy. Kaplan-Meier freedom-from-biochemical relapse (FFbR; nadir+2 µg/L) fits were grouped by the first (Q1), second (Q2) and third (Q3) D90 and V100 quartiles. Groups were compared with the log-rank test. Univariate and multivariate Hazard Ratios (HR) for D90 and V100 and other co-variates (PSA, androgen deprivation therapy (ADT) were obtained using Cox's proportional hazard model. RESULTS: FFbR was significantly higher in patients whose D90 and V100 were at or above the second and third quartile (log rank p ≤ 0·04). In multivariate analysis D90, V100 were significant covariates for risk of relapse. CONCLUSIONS: Dichotomising the data using 6 levels of response (above and below Q1, Q2 and Q3) showed a progressive and continuous improvement in biochemical control of disease across the entire dose (and volume) range. The data show that a minimum D90 of 108% of the prescribed dose should be the target to achieve.

Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer.

BACKGROUND: A randomised phase-III trial compared external beam radiotherapy (EBRT) alone with EBRT combined with high-dose-rate brachytherapy boost (HDR-BTb) in localised prostate adenocarcinoma. METHODS: From December 1997 to August 2005, 218 patients were assigned to EBRT alone (n=108) or EBRT followed by a temporary high-dose-rate implant (n=110). Patients were stratified according to tumour stage, PSA, Gleason score and androgen deprivation therapy (ADT). Biochemical/clinical relapse-free survival (RFS) was the primary endpoint. Secondary endpoints were overall survival (OS), urinary and bowel toxicity. RESULTS: RFS was significantly higher in patients treated with EBRT+HDR-BTb (log rank p=0.04). In multivariate analysis treatment arm, risk category and ADT were significant covariates for risk of relapse. Differences in OS were not significant. Incidence of severe late urinary and bowel morbidity was similar. CONCLUSIONS: EBRT+HDR-BTb resulted in a significant improvement in RFS compared to EBRT alone with a 31% reduction in the risk of recurrence (p=0.01) and similar incidence of severe late urinary and rectal morbidity.