Several randomized clinical trials have established the superior oncological outcomes of the combination of external beam radiotherapy with a high-dose-rate brachytherapy boost (see this link). In 2015, the results of the first randomized clinical trial of the combination of external beam radiotherapy with low-dose-rate brachytherapy, the ASCENDE-RT trial, was presented at the 2015 Genitourinary Conference (reported here). We now have the full details of the oncological outcomes. (Toxicity outcomes will be reported separately.)
Morris et al. reported on 398 intermediate-risk (31 percent) and high-risk (69 percent) patients treated at six facilities in British Columbia and Toronto. All patients received 12 months of androgen deprivation therapy (ADT), beginning 8 months before radiation therapy and continuing 4 months after the start of the radiation. ADT consisted of a LHRH agonist (Eligard or Suprefact) with an antiandrogen (bicalutamide or flutamide) given for the first 4 weeks. The radiation treatment was either of:
- EBRT only: 78 Gy in 39 fractions using 3D-CRT
- Brachy boost: 46 Gy in 23 fractions of EBRT (3D-CRT) + 115 Gy of iodine-125 seeds
It is worth noting that the brachy boost dose used in this trial is compared to an EBRT dose that is considered to be high enough to be curative by today’s standards.
With 6.5 years of median follow-up,
- The 9-year biochemical progression-free survival (bPFS) was 85 percent for the brachy boost cohort vs. 65 percent for EBRT only.
- The hazard ratio was 2.3 (i.e., those getting EBRT only were 2.3 times as likely to relapse compared to those getting the brachytherapy boost).
- Among those with high-risk prostate cancer, 9-year bPFS was 83 percent for the brachy boost cohort vs. 62 percent for EBRT only.
- Among those with intermediate-risk prostate cancer, 9-year bPFS was 94 percent for the brachy boost cohort vs. 70 percent for EBRT only.
- Among those who did not relapse, the median nadir PSA was 0.01 ng/ml (54 percent undetectable) for the brachy boost cohort vs. 0.25 for EBRT only (8 percent undetectable).
- In this length of follow-up, metastases, prostate cancer-specific mortality, and overall mortality were rare events, and were not statistically significantly different.
- Median patient age was 68 years.
This analysis did not address toxicity outcomes, but, as previously reported, the improved oncological outcomes came at the expense of toxicity:
- Late-term Grade 2 or higher genitourinary (GU) toxicity was higher for the brachy boost group.
- Late-term Grade 3 GU toxicity reached 19 percent for the brachy boost group vs. 5 percent for the EBRT only group.
- Late-term gastrointestinal (GI) toxicity was similarly mild for both groups.
The use of 3D-CRT rather than IMRT (which is now the more prevalent form of EBRT) probably affected toxicity, especially with the wider field of the brachy boost therapy.
This should establish brachy boost therapy (using either a high-dose-rate or low-dose-rate brachy boost) as the gold standard for oncological control for high-risk prostate cancer. Perhaps equivalent outcomes with less toxicity may be achievable for both high-risk and intermediate-risk patients using high-dose-rate brachy monotherapy, SBRT monotherapy, or SBRT boost therapy. But for now, those are experimental approaches in high-risk patients. The optimal duration of ADT use has yet to be defined. Patients with pre-existing urinary conditions should approach boost therapy with caution.
Sadly, a recent analysis of the National Cancer Database showed that utilization of brachy boost therapy for high-risk patients has declined precipitously from 28 percent in 2004 to 11 percent in 2013. If a patient sees anyone other than the first urologist, he often only sees a single radiation oncologist who only informs him about IMRT. In most parts of the US, there is a dearth of experienced brachytherapists.
Editorial note: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink. Allen thanks Dr. W. James Morris of the University of British Columbia and the British Columbia Cancer Agency, Vancouver, Canada, for allowing him to see the full text of this article.