RTOG 0232 was a large clinical trial conducted to determine whether low dose rate brachytherapy (BT) alone was of equal benefit compared to external beam radiation therapy with a brachytherapy boost (EBRT+BT) in intermediate risk patients.
The study was conducted at 68 cancer centers in the US and Canada from 2003 to 2012. 588 intermediate risk men were treated. For the purposes of this study, “intermediate risk” was defined as:
- Stage T1c – T2b, and
- Either Gleason Score of 7 and PSA less than 10 ng/ml, or
- Gleason score of 6 and PSA between 10 and 20 ng/ml
They did not collect detailed data and report separately those who would now be classified as “favorable intermediate risk” by the Zumsteg definition (Gleason score 3+4, less than half the biopsy cores positive, and otherwise low risk). However, Howard Sandler, the Principal Investigator, wrote:
It was deliberately a favorable intermediate group largely. At the time (2002) we felt that combination therapy was mandatory for the more advance patients and we weren’t comfortable randomizing to brachy alone for those patients.
So it is important that we do not generalize their findings to unfavorable intermediate-risk or high-risk patients.
The patients were treated as follows:
- BT: 145 Gy of I-125 seeds or 125 Gy of Pd-103 seeds
- EBRT+BT: 45 Gy of EBRT and a boost with 110 Gy of I-125 seeds or 100 Gy of Pd-103 seeds
After 5 years of follow-up:
- Progression-free survival was 85% for EBRT+BT patients, 86% for BT patients (no difference)
- Acute grade 3 (serious) side effects were suffered by 8% in each group.
- Late-term grade 3 (serious) side effects were higher (12%) in the EBRT+BT compared to 7% in the BT group
o Urinary side effects: 7% in the EBRT+BT group vs. 3% in the BT group
o Rectal side effects: 3% in the EBRT+BT group vs. 2% in the BT group
So, the addition of external beam radiation added nothing to cancer control, at least out as long as 5 years. While side effects were low for both groups, combination therapy increased them.
We saw recently in an analysis of the patients at Cleveland Clinic who were treated exclusively with BT only (see this link, especially the section on intermediate risk), that progression-free survival was very good for “low intermediate risk” patients. Furthermore, Drs. Stone and Zelefsky agreed that the combination therapy is unnecessary for this group, especially when treated with a sufficient brachytherapy dose. Radiotherapy Clinics of Georgia has built a business out of treating even low-risk patients with the combination therapy. This is now proved to be an overtreatment that is needlessly toxic.