Why this matters
Brachytherapy can deliver very high intraprostatic doses and has produced excellent biochemical control in prostate cancer. But whether that additional dose intensification provides meaningful benefit over modern dose-escalated external beam radiotherapy in patients with purely intermediate-risk disease has remained uncertain.
GETUG P05 directly tested that question in a randomized phase III trial without routine androgen deprivation therapy.
The result is clear: adding a brachytherapy boost did not improve 5-year biochemical progression-free survival compared with dose-escalated EBRT to 80 Gy, while urinary toxicity was more frequent.
Study design
GETUG P05 was an open-label randomized phase III trial enrolling patients with intermediate-risk prostate cancer.
Intermediate-risk disease was defined by one or more of:
- PSA 10-20 ng/mL
- Gleason score 7
- clinical stage T2b
Patients first received 46 Gy external beam radiotherapy to the prostate and proximal seminal vesicles.
They were then randomized to one of two boost strategies:
- brachytherapy boost using either Iodine-125 LDR brachytherapy at 110 Gy or HDR brachytherapy at 14 Gy
- external beam boost to a total prostate dose of 80 Gy
The choice between LDR and HDR brachytherapy was determined by the treating center.
ADT was not part of the treatment strategy.
The primary endpoint was 5-year biochemical progression-free survival according to the Phoenix definition.
Secondary endpoints included overall survival, prostate cancer-specific survival, metastasis-free survival, toxicity, and quality of life.
A total of 298 patients were randomized across 27 centers, with 296 evaluable:
- 155 in the EBRT boost arm
- 141 in the brachytherapy boost arm
Among patients receiving brachytherapy, 79 received LDR and 55 received HDR treatment.
Median follow-up for the biochemical endpoint was 61.7 months.
Key results
The primary endpoint was negative.
Five-year biochemical progression-free survival was:
- 88.0% with brachytherapy boost
- 88.2% with EBRT boost
- p=0.90
There was therefore no evidence that brachytherapy boost improved biochemical control over dose-escalated EBRT.
The type of brachytherapy boost, LDR or HDR, did not significantly affect biochemical outcomes.
No benefit from brachytherapy was identified according to Gleason subgroup, including either Gleason 3+4 or 4+3 disease.
Overall survival was also similar:
- 5-year OS: 96.0% with brachytherapy vs 92.7% with EBRT
- p=0.30
Quality of life and sexual function did not significantly differ between treatment groups.
Toxicity
The main tradeoff was urinary toxicity.
Acute urinary adverse events were more frequent after brachytherapy:
- 55% with brachytherapy
- 26% with EBRT
- p<0.0001
Late urinary adverse events were also more frequent:
- approximately 82% with brachytherapy
- 64% with EBRT
- p<0.001
The most common urinary symptoms were dysuria and pollakiuria.
However, most of the excess toxicity consisted of grade 1-2 events.
There was no significant difference in grade 3 urinary toxicity, and no grade 4 toxicity was observed.
Gastrointestinal toxicity was also similar between treatment strategies.
Interpretation
GETUG P05 addresses an important distinction in prostate radiotherapy: more dose does not necessarily mean better outcomes once external beam treatment has already been escalated to an effective dose.
Brachytherapy offers a powerful method of intraprostatic dose escalation, but in this intermediate-risk population it did not improve 5-year biochemical control compared with EBRT to 80 Gy.
The biochemical outcomes were almost identical.
This is particularly relevant when interpreting earlier trials supporting brachytherapy boost. Studies such as ASCENDE-RT included substantially higher-risk populations and different systemic treatment strategies. GETUG P05 instead focused on intermediate-risk disease and directly compared brachytherapy boost against modern dose-escalated EBRT without ADT.
The lack of biochemical benefit was accompanied by more acute and late urinary symptoms.
Importantly, this does not mean brachytherapy and EBRT have been proven equivalent. The trial failed to demonstrate superiority of brachytherapy boost. That is different from formally demonstrating equivalence or noninferiority.
It also does not imply that brachytherapy has no role in intermediate-risk prostate cancer. Treatment duration, patient preference, resource availability, anatomy, and the use of brachytherapy as monotherapy are separate questions not answered by this trial.
What GETUG P05 does challenge is the assumption that a brachytherapy boost should provide better oncologic outcomes simply because it delivers greater intraprostatic dose escalation.
Limitations
The analysis is based on approximately 5 years of biochemical follow-up, and longer observation will be useful for metastasis and prostate cancer-specific survival.
The brachytherapy arm included both LDR and HDR techniques, introducing treatment heterogeneity, although no difference in biochemical outcome was observed between the two modalities.
The trial studied intermediate-risk disease without routine ADT, so the findings should not automatically be extrapolated to high-risk prostate cancer or treatment strategies combining brachytherapy with hormonal therapy.
The trial also tested a brachytherapy boost strategy rather than brachytherapy monotherapy.