Comparative Analysis of Clinical Outcomes and Procedural Costs between the Conventional Two-stage Technique and 4D Brachytherapy for Early Prostate Cancer.

AIMS: To assess long-term outcomes and resource use of 4D Brachytherapy, a one-stage real-time implant for the treatment of prostate cancer that uses stranded and loose iodine-125 seeds, and to compare with the conventional two-stage (2S) technique. MATERIALS AND METHODS: Prospectively collected data of men who underwent 2S and 4D low dose rate brachytherapy in a single institution were analysed. Survival estimates were analysed using the Kaplan-Meier method and Log-rank test. Treatment failure rates were further compared by Cox proportional hazards (Coxph) regression or by a surrogate prostate-specific antigen value cut-off of 0.4 ng/ml 48 months post-implant. Treatment toxicity outcomes were also evaluated. Comparative costs were based on published English National Health Service data. RESULTS: We compared outcomes of 690 men treated with 2S and 1031 men with 4D brachytherapy. Median follow-up times were 10.4 and 5.2 years (P < 0.001) for 2S and 4D cases, respectively. Day 0 post-implant dosimetry was improved in 4D brachytherapy patients. Five years post-implant ≥98% of cases were alive and ≥95% were free from disease relapse irrespective of technique. Coxph regression showed the risk of relapse after 4D brachytherapy was similar to the 2S technique (hazard ratio 0.67, 95% confidence interval 0.44-1.03, P = 0.065). Forty-eight months post-implant there was a significantly greater proportion of 4D brachytherapy cases with a prostate-specific antigen below 0.4 ng/ml relative to the 2S technique. Urinary and bowel symptom scores showed reduced toxicity after 4D implants and potency conservation was similar to the 2S technique. The reduction in time and resource use decreased the cost of 4D brachytherapy by 40% compared with the 2S technique. CONCLUSION: Two-stage and 4D brachytherapy are both highly effective for the control of localised prostate cancer. However, relative to the 2S technique, the 4D technique was associated with improved dosimetry, reduced treatment-related toxicity and reduced cost. Further follow-up will assess disease control superiority of 4D brachytherapy beyond 5 years post-implant.

Biochemical relapse-free survival in 400 patients treated with I-125 prostate brachytherapy: the Guildford experience.

A total of 1200 patients had undergone I-125 prostate brachytherapy (BXT) in our centre. We present prospective outcome data for the first 400 treated patients. Data were analysed from a prospective database of 400 consecutive patients treated with permanent prostate BXT between March 1999 and December 2003. Patients were stratified into low (49%), intermediate (36%) and high (15%) risk as defined by the Memorial Sloan-Kettering Prognostic Index. Patients received 145 Gy BXT alone (41%), BXT with 3 months neoadjuvant androgen deprivation (NAAD) (39%), 45 Gy external beam radiotherapy (EBRT) with 110 Gy BXT (3%) or a combination of NAAD, 45 Gy EBRT and 110 Gy BXT (17%). Biochemical relapse-free survival (bRFS) and prostate-specific antigen (PSA) nadirs were analysed for treatment received in each risk group. Median follow-up was 54 months (range, 38-96 months) with a mean patient age of 63 years. Prostate cancer-specific survival was 99.5%. Twenty-eight patients (7%) experienced biochemical failure according to the 2006 Radiation Therapy Oncology Group-American Society for Therapeutic Radiology and Oncology (RTOG-ASTRO) Phoenix Consensus definition (PSA nadir plus >or=2 ng ml(-1)): nine low-, fourteen intermediate- and five high-risk patients. When stratified by treatment group for low-, intermediate- and high-risk groups, the 5-year actuarial bRFS was 98, 89 and 100% for BXT; 91, 87 and 88% for NAAD and BXT; 100, 80 and 100% for EBRT and BXT; and 100, 92 and 88% for NAAD, EBRT and BXT, respectively. Overall 4- and 5-year PSA

Interstitial low dose rate brachytherapy for prostate cancer--a focus on intermediate- and high-risk disease.

AIMS: To investigate the role of brachytherapy in intermediate- and high-risk prostate cancer. We report our results and a review of published studies. MATERIALS AND METHODS: Between March 1999 and April 2003, 300 patients were treated with low dose rate 1-125 interstitial prostate brachytherapy and followed prospectively. The patients were stratified into low-, intermediate- and high-risk groups and received brachytherapy alone or in combination with external beam radiotherapy (EBRT) and/or neoadjuvant androgen deprivation (NAAD). One hundred and forty-six patients were classified as low risk, 111 as intermediate risk and 43 as high risk. Biochemical freedom from disease and prostate-specific antigen (PSA) nadirs were analysed for risk groups and for treatment received in each risk group. RESULTS: The median follow-up was 45 months (range 33-82 months) with a mean age of 63 years. Actuarial 5-year biochemical relapse-free survival for the low-risk group was 96%, 89% for the intermediate-risk group and 93% for the high-risk group. When stratified by treatment group, low-risk patients had a 5-year actuarial biochemical relapse-free survival of 94% for brachytherapy alone (n=77), 92% for NAAD and brachytherapy (n=66) and 100% for NAAD, EBRT and brachytherapy (n=3). In the intermediate-risk patients, biochemical relapse-free survival was 93% for brachytherapy alone (n=15), 94% for NAAD and brachytherapy (n=67), 75% for EBRT and brachytherapy (n=4) and 92% for NAAD, EBRT and brachytherapy (n=25). In the high-risk group, biochemical relapse-free survival was 100% for brachytherapy alone (n=2), 88% for NAAD and brachytherapy (n=7), 80% for EBRT and brachytherapy (n=5) and 96% for NAAD, EBRT and brachytherapy (n=29). Overall 3- and 4-year PSA = 0.5 ng/ml were achieved by 71 and 86%, respectively, and a 4-year PSA = 0.2 ng/ml was achieved by 63%. CONCLUSION: Although the role of combination treatment with pelvic EBRT and androgen therapy is not clear, our early results show that many patients with intermediate- and high-risk disease have excellent results with brachytherapy.

Biological equivalent dose assessment of the consequences of hypofractionated radiotherapy.

PURPOSE: To investigate the changes in biological effective dose (BED) that occur in high-dose regions within a target volume when radiotherapy is hypofractionated. METHODS AND MATERIALS: By comparing a standard prescription of 2 Gy per fraction that is matched to give the same BED as a hypofractionated schedule at a standard intersectional prescription point, the BED increments for late-tissue effects at a higher dose region within the planning target volume (PTV) are compared. The alternative approach of BED matching between a conventional and hypofractionated schedule at the high-dose region is also considered. The results are presented as a sequence of calculations that can be understood by practicing radiation oncologists and in graphical form. RESULTS: The BED increment at the high-dose region is marginally increased by hypofractionation, although the latter effect is relatively small: up to 5% additional BED due to hypofractionation for a 20% increase in physical dose when the prescribed fraction size is 6-7 Gy. BED matching for late effects between a conventional and hypofractionated schedule at the high-dose region produces lower BED values throughout the remaining PTV, but at the expense of a reduced tumor control BED. CONCLUSION: Clinical trials that use BED isoeffect matching for late reacting tissue effects to design a hypofractioned test schedule should include comprehensive calculations of the likely BED in high-dose regions.