Biochemical Recurrence and Late Toxicity Following External Beam Radiotherapy Combined With Permanent Source Prostate Brachytherapy: Analysis of RTOG 0019

Reviewer: Christopher Dolinsky, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 7, 2006

Presenter: W. Lee
Presenter's Affiliation: Wake Forest University School of Medicine
Type of Session: Scientific

Background

Previous clinical trials have shown the benefits of dose escalation with external beam radiation for patients with prostate cancer.
One strategy to deliver higher radiation doses to the prostate is to combine external beam radiation therapy with a seed implant (brachytherapy).
There is a chance that the combination of external radiation and brachytherapy may cause higher rates of treatment-related toxicity.
Patients were eligible for this study if they had prostate cancer, stages T1c ? T2b, Gleason 2-6 with PSA from 10 to 20, or Gleason 7 with PSA <10.
The primary goal of the trial was to estimate late toxicity; the secondary goal was to estimate efficacy.

Materials and Methods

138 patients were enrolled, and 130 were eligible for this analysis.
Patients were treated with external beam radiation to a dose of 45Gy in 1.8Gy fractions, and then received an Iodine-125 implant (108Gy) two to six weeks later.
Morbidity was scored using the RTOG/EORTC Late Radiation Morbidity Scale.
Efficacy was determined by analyzing biochemical disease-free survival using both the ASTRO definition (3 consecutive PSA rises) and the Phoenix definition (nadir plus 2).
This trial was performed at >20 institutions and accrued all patients in 1 year.
Median follow-up is 49 months.

Results

There were no treatment-related deaths.
Four patients developed grade 3 rectal toxicity (proctitis), but there were no grade 4 rectal toxicities seen.
Five patients developed grade 3 urinary toxicity, and two patients developed grade 4 urinary toxicity (bladder neck necrosis).
The biochemical failure rate was 14% by the Phoenix definition and 19% by the ASTRO definition.
No dosimetric factors were found to increase the risk of causing toxicity.

Author's Conclusions

Late grade 3 or 4 GU/GI toxicity rate was 15%.
This toxicity rate may be higher than other studies of dose escalation.
The biochemical failure rate was similar to other dose escalation trials.

Clinical/Scientific Implications

The authors presented an interesting analysis of a very important clinical trial. The combination of brachytherapy and external beam radiation has become a popular treatment strategy in North American radiation therapy centers. However, there is a lack of good data documenting the superiority of this approach as compared to monotherapy. It appears that the combination of implant and external beam radiation carries with it a significant risk of producing late toxicity. It would have been nice to see the grade 2 toxicity rates for this study, particularly the rectal toxicity rate. Grade 2 rectal toxicity is not clinically insignificant, as patients who develop rectal toxicity have greatly diminished quality of life. It will be important to see the results of the RTOG 0232 trial, which randomizes patients to either brachytherapy alone or in combination with external beam radiation. Until then, it appears that combination therapy should not replace monotherapy as the standard of care for men with intermediate risk prostate cancer.