Commentary on Prostate Brachytherapy for Localized Prostate Cancer
Article Outline
- Definition of biochemical failure
- Importance of implant quality
- Role of supplemental external radiotherapy
- Role of androgen deprivation
- References
- Copyright
Potters et al report on 12-year outcomes after permanent prostate brachytherapy in 1,449 men treated consecutively between 1992 and 2000. The median followup was 82 months with 39 men at risk for 144 months. Followup duration was less than 12 months in only 51 men. 125Iodine was used in 22% of the implants and 103palladium was used in 78%. Of the patients 400 had received prior neoadjuvant hormonal therapy with a mean duration of 5.2 months and 301 had received supplemental external beam radiation. Risk group distribution of the population, based on intermediate risk being 1 adverse factor and high risk being 2 or more adverse factors, was 33% low, 38% intermediate and 29% high risk.
The results from this mature data set make an important contribution to the brachytherapy literature. Within the limitations of a single center experience Potters et al offer insight into several key issues concerning prostate brachytherapy, such as the definition of biochemical failure, the importance of implant quality, and the roles of external radiotherapy and hormonal therapy combined with brachytherapy.
Definition of biochemical failure
Biochemical failure after radiotherapy has been variously defined. The American Society for Therapeutic Radiology and Oncology (ASTRO) definition (3 consecutive increases 3 to 6 months apart with backdating of failure to halfway between the nadir and the first rise) and the current ASTRO-Phoenix definition (nadir + 2 ng/ml) were based on analysis of a broad experience with external radiotherapy,1 and are believed to represent the best compromise between sensitivity and specificity for this group of patients. Although meant as a guideline for uniform reporting of results, these definitions are often used as a basis for initiation of second line treatment, in which case over calling failure can have significant impact on management. The best definition of biochemical failure after brachytherapy has yet to be determined.
Potters et al analyzed their data using 4 definitions from ASTRO, ASTRO-Kattan, ASTRO last-call (no backdating) and nadir + 2 ng/ml. Although the ASTRO definition consistently yields the highest biochemical freedom from failure rates, with mature followup, as in this series, all definitions perform within a few percentage points of each other. Also, a benign prostate specific antigen bounce is often seen in the first 3 years after brachytherapy. It has been demonstrated that 15% of benign bounces will meet the nadir + 2 definition for biochemical failure.2
Importance of implant quality
Potters et al routinely obtained post-plan dosimetry for all patients after 1996, with results available for 960 of the 1,449 men (66%). They emphasize the importance of implant quality with respect to outcome. Having previously specified that D90 should be a minimum of 90% of the prescribed dose (130 Gy for a prescribed dose of 144 Gy), in this analysis they identified D90 (isodose enclosing 90% of the gland) as the strongest predictor of biochemical freedom from failure in Cox regression (p <0.0001) along with pretreatment prostate specific antigen (p=0.001), Gleason score (p=0.002) and percentage positive biopsies (p=0.037). However one of the weaknesses of D90 as an ultimate measure of implant quality is that it does not relate the dose map to the tumor location, which the authors acknowledge. Consequently, an apparently excellent D90 may actually leave a critical area of tumor bearing prostate under dosed.
Role of supplemental external radiotherapy
Although few would argue in favor of a role for combined external beam radiotherapy with brachytherapy for favorable risk prostate cancer, its use for intermediate and high risk disease is widespread. Only 20% of this series received supplemental external radiotherapy, with a trend towards more common use in higher risk patients (2.3% low risk, 11.2% intermediate and 25.6% high risk). Although the addition of external beam radiotherapy did not predict for freedom from biochemical failure in the entire group, its effect was not examined by risk group. Current randomized trials such as the Radiation Therapy Oncology Group 0232 address this issue for intermediate risk prostate cancer.
Role of androgen deprivation
The most common indication for the combination of androgen deprivation (AD) with brachytherapy is prostate size reduction to facilitate access under the pubic arch. There are no randomized studies indicating a benefit for neoadjuvant or adjuvant hormonal therapy combined with brachytherapy. The use of AD was more balanced among the risk groups in this series than was the use of supplemental external beam (22.7% favorable, 27.6% intermediate and 33% high risk). Overall, the addition of AD was not an independent predictor of freedom from biochemical failure. A caveat to indiscriminate use of AD with brachytherapy was described by Beyer et al who reported diminished overall survival for men receiving AD plus permanent prostate brachytherapy compared to those treated with brachytherapy alone.3 Until randomized trials clarify the indications, the combination of AD and brachytherapy should be used with caution.
The study by Potters et al adds to the growing body of literature affirming the long- term efficacy of permanent prostate brachytherapy. Although only 39 of the patients have actually been followed for 12 years, more than 100 have been followed for 9 years with biochemical disease-free rates of more than 90% for favorable, more than 80% for intermediate and 70% for high risk disease. These results compare favorably with those of other treatment approaches.
References
- Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys. 2006;65:965
- . PSA kinetics and PSA bounce following permanent seed prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2007;69:426
- . Impact of short course hormonal therapy on overall and cancer specific survival after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2005;61:1299
PII: S0022-5347(08)00546-6
doi:10.1016/j.juro.2008.03.004
© 2008 American Urological Association. Published by Elsevier Inc. All rights reserved.